80 results on '"de Wit, F"'
Search Results
2. University students and HIV in Namibia: an HIV prevalence survey and a knowledge and attitude survey
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Beer, Ingrid H., Gelderblom, Huub C., Schellekens, Onno, Gaeb, Esegiel, Rooy, Gert, Mcnally, Alta, Wit, Ferdinand W., and Tobias, Rinke De Wit F.
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College students -- Beliefs, opinions and attitudes -- Health aspects ,HIV infection -- Risk factors -- Public opinion -- Demographic aspects ,Health - Abstract
Background: With an overall adult HIV prevalence of 15.3%, Namibia is facing one of the largest HIV epidemics in Africa. Young people aged 20 to 34 years constitute one of the groups at highest risk of HIV infection in Namibia. However, little is known about the impact of HIV on this group and its access to healthcare. The purpose of this study was to estimate HIV prevalence, to assess the knowledge of and attitudes towards HIV/AIDS, and to assess access to healthcare among university students in Namibia. Methods: We assessed HIV/AIDS knowledge and attitudes, HIV prevalence and access to healthcare among students at the Polytechnic of Namibia and the University of Namibia. HIV prevalence was tested through anonymous oral fluid‐based tests. Results: Half (n = 2790/5568) of the university students and 45% (n = 2807/6302) of the Polytechnic students participated in the knowledge and attitudes surveys. HIV/AIDS knowledge was reasonable, except for misperceptions about transmission. Awareness of one's own HIV status and risks was low. In all, 55% (n = 3055/5568) of university students and 58% (n = 3680/6302) of Polytechnic students participated in the HIV prevalence survey; 54 (1.8%) university students and 103 (2.8%) Polytechnic students tested HIV positive. Campus clinics were not the major providers of healthcare to the students. Conclusions: Meaningful strategies addressing the gap between knowledge, attitude and young people's perception of risk of HIV acquisition should be implemented. HIV prevalence among Namibian university students appears relatively low. Voluntary counselling and testing should be stimulated. Efforts should be made to increase access to healthcare through the campus clinics., Background Namibia in southern Africa has approximately 2.2 million inhabitants and is classified as a middle‐income country. The Namibian health system has both a public health service through the Ministry [...] more...
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- 2012
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Catalog
3. Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial
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Smits, FJ, Henry, AC, van Eijck, Casper, Besselink, MGH, Busch, ORC, Arntz, M, Bollen, TL, van Delden, OM, van den Heuvel, DAF, van der Leij, C, van Lienden, KP, Moelker, Adriaan, Bonsing, BA, Rinkes, I, Bosscha, K, van Dam, RM, Festen, S, Groot Koerkamp, B, Harst, E, de Hingh, IHJT, Kazemier, G, Liem, M, van der Kolk, BM, Meijer, VE, Patijn, GA, Roos, D, Schreinemakers, JM, de Wit, F, van Werkhoven, CH, Molenaar, IQ, van Santvoort, HC, Smits, FJ, Henry, AC, van Eijck, Casper, Besselink, MGH, Busch, ORC, Arntz, M, Bollen, TL, van Delden, OM, van den Heuvel, DAF, van der Leij, C, van Lienden, KP, Moelker, Adriaan, Bonsing, BA, Rinkes, I, Bosscha, K, van Dam, RM, Festen, S, Groot Koerkamp, B, Harst, E, de Hingh, IHJT, Kazemier, G, Liem, M, van der Kolk, BM, Meijer, VE, Patijn, GA, Roos, D, Schreinemakers, JM, de Wit, F, van Werkhoven, CH, Molenaar, IQ, and van Santvoort, HC more...
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- 2020
4. Textbook Outcome Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery
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van Roessel, S, Mackay, TM, van Dieren, S, van der Schelling, GP, Nieuwenhutjs, VB, Bosscha, K, Harst, E, van Dam, RM, Liem, MS, Festen, S, Stommel, MWJ, Roos, D, de Wit, F, Molenaar, IQ, Meijer, VE, Kazemier, G, de Hingh, I, van Santvoort, HC, Bonsing, BA, Busch, ORC, Groot Koerkamp, B, Besselink, MGH, van Roessel, S, Mackay, TM, van Dieren, S, van der Schelling, GP, Nieuwenhutjs, VB, Bosscha, K, Harst, E, van Dam, RM, Liem, MS, Festen, S, Stommel, MWJ, Roos, D, de Wit, F, Molenaar, IQ, Meijer, VE, Kazemier, G, de Hingh, I, van Santvoort, HC, Bonsing, BA, Busch, ORC, Groot Koerkamp, B, and Besselink, MGH more...
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- 2020
5. The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection
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Rodríguez-Mora S, De Wit F, García-Perez J, Bermejo M, López-Huertas MR, Mateos E, Martí P, Rocha S, Vigón L, Christ F, Debyser Z, Vílchez JJ, Coiras M, and Alcamí J
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The causative mutation responsible for limb girdle muscular dystrophy 1F (LGMD1F) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene (TNPO3). This mutation causes a carboxy-terminal extension of 15 amino acids, producing a protein of unknown function (TNPO3_mut) that is co-expressed with wild-type TNPO3 (TNPO3_wt). TNPO3 has been involved in the nuclear transport of serine/arginine-rich proteins such as splicing factors and also in HIV-1 infection through interaction with the viral integrase and capsid. We analyzed the effect of TNPO3_mut on HIV-1 infection using PBMCs from patients with LGMD1F infected ex vivo. HIV-1 infection was drastically impaired in these cells and viral integration was reduced 16-fold. No significant effects on viral reverse transcription and episomal 2-LTR circles were observed suggesting that the integration of HIV-1 genome was restricted. This is the second genetic defect described after CCR5 32 that shows strong resistance against HIV-1 infection. more...
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- 2019
6. The Burden of Power: Construing Power as Responsibility (Rather Than as Opportunity) Alters Threat-Challenge Responses
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Scholl, Annika, De Wit, F, Ellemers, N., Fetterman, AK, Sassenberg, K., Scheepers, D.T., Leerstoel Ellemers, Social identity: Morality and diversity, Leerstoel Ellemers, and Social identity: Morality and diversity more...
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Adult ,Male ,Adolescent ,Social Psychology ,Decision Making ,050109 social psychology ,050105 experimental psychology ,Power (social and political) ,Young Adult ,biopsychosocial model ,Taverne ,Humans ,0501 psychology and cognitive sciences ,Cardiovascular stress ,Aged ,Social Responsibility ,cardiovascular stress ,threat challenge ,05 social sciences ,construal of power ,Social power ,Middle Aged ,social power, construal of power, threat challenge, biopsychosocial model, cardiovascular stress ,social power ,Position (finance) ,Female ,Power, Psychological ,Comprehension ,Psychology ,Social psychology ,Stress, Psychological - Abstract
Power usually lowers stress responses. In stressful situations, having high (vs. low) power heightens challenge and lowers threat. Yet, even power-holders may experience threat when becoming aware of the responsibility that accompanies their power. Power-holders can construe (i.e., understand) a high-power position primarily as opportunity to “make things happen” or as responsibility to “take care of things.” Power-holders construing power as responsibility (rather than opportunity) may be more likely to experience demands—such as taking care of important decisions under their control—as outweighing their resources, resulting in less challenge and more threat. Four experiments with subjective and cardiovascular threat-challenge indicators support this. Going beyond prior work on structural aspects (e.g., power instability) that induce stress, we show that merely the way how power-holders construe their power can evoke stress. Specifically, we find that power construed as responsibility (vs. opportunity) is more likely to imply a “burden” for the power-holder. more...
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- 2018
7. OBSERVATIONS AND NUMERICAL MODEL RESULTS OF MORPHODYNAMIC FEEDBACK OWING TO WAVE-CURRENT INTERACTION
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HOPKINS, J., primary, DE SCHIPPER, M.A., additional, WENGROVE, M., additional, DE WIT, F., additional, and CASTELLE, B., additional
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- 2019
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8. The burden of power: Construing power as responsibility (rather than as opportunity) alters threat-challenge responses
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Leerstoel Ellemers, Social identity: Morality and diversity, Scholl, Annika, De Wit, F, Ellemers, N., Fetterman, AK, Sassenberg, K., Scheepers, D.T., Leerstoel Ellemers, Social identity: Morality and diversity, Scholl, Annika, De Wit, F, Ellemers, N., Fetterman, AK, Sassenberg, K., and Scheepers, D.T. more...
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- 2018
9. Highly identified power-holders feel responsible: The interplay between social identification and social power within groups
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Scholl, A, Sassenberg, K, Ellemers, N, Scheepers, D, de Wit, F, Scholl, A, Sassenberg, K, Ellemers, N, Scheepers, D, and de Wit, F
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Power relations affect dynamics within groups. Power-holders' decisions not only determine their personal outcomes, but also the outcomes of others in the group that they control. Yet, power-holders often tend to overlook this responsibility to take care of collective interests. The present research investigated how social identification - with the group to which both the powerful and the powerless belong - alters perceived responsibility among power-holders (and the powerless). Combining research on social power and social identity, we argue that power-holders perceive more responsibility than the powerless when strongly (rather than when weakly) identifying with the group. A study among leaders and an experiment supported this, highlighting that although power-holders are often primarily concerned about personal outcomes, they do feel responsible for considering others' interests when these others are included in the (social) self. more...
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- 2018
10. A matter of focus: Power-holders feel more responsible after adopting a cognitive other-focus, rather than a self-focus
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Scholl, A, Sassenberg, K, Scheepers, D, Ellemers, N, de Wit, F, Scholl, A, Sassenberg, K, Scheepers, D, Ellemers, N, and de Wit, F
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Social power implies responsibility. Yet, power-holders often follow only their own interests and overlook this responsibility. The present research illuminates how a previously adopted cognitive focus guides perceived responsibility when a person receives high (vs. low) power. In three experiments, adopting a cognitive focus on another person (vs. on the self or taking over another person's perspective) promoted perceived responsibility among individuals receiving high (but not low) power in a subsequent context. This effect was specific for perceived responsibility - a cognitive focus on another person did not change the perceived opportunity to pursue goals or the perceived relationship to an interaction partner (e.g., interpersonal closeness). While prior research examined how social values (i.e., chronically caring about others) guide responsibility among those holding power, the current findings highlight that mere cognitive processes (i.e., situationally focusing attention on others) alter perceived responsibility among those just about to receive power. more...
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- 2017
11. Non-invasive continuous arterial pressure and pulse pressure variation measured with Nexfin®in patients following major upper abdominal surgery: a comparative study
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de Wilde, R. B. P., primary, de Wit, F., additional, Geerts, B. F., additional, van Vliet, A. L., additional, Aarts, L. P. H. J., additional, Vuyk, J., additional, and Jansen, J. R. C., additional
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- 2016
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12. Handleiding kwaliteitsverbetering ziekenhuiszorg vanuit de ervaring van patienten
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Vennik, FD, van de Bovenkamp, Hester, Raats, I, de Wit, F, Visserman, E, Grit, Kor, and Health Care Governance (HCG)
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- 2013
13. Quantum efficiency performances of the NIR European Large Format Array detectors tested at ESTEC
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Crouzet, P.-E., additional, Duvet, L., additional, de Wit, F., additional, Beaufort, T., additional, Blommaert, S., additional, Butler, B., additional, Van Duinkerken, G., additional, ter Haar, J., additional, Heijnen, J., additional, van der Luijt, K., additional, and Smit, H., additional more...
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- 2015
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14. Leren van patiënten
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de Wit, F., Mul, M., Bal, R., and Patient Care Support
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- 2008
15. Lineaire IgA-dermatose, zowel klinisch als immunologisch een heterogene blaarziekte
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van der Meij, N., Mekkes, J. R., de Wit, F. S., Leguit, R. J., Bos, J. D., Amsterdam institute for Infection and Immunity, and Dermatology
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- 2006
16. Project Veracruz: An assessment for the eroding beach south of Veracruz
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Heineke, D. (author), Volbeda, E. (author), De Weerdt, B. (author), De Wit, F. (author), Heineke, D. (author), Volbeda, E. (author), De Weerdt, B. (author), and De Wit, F. (author)
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Due to frequently occurring storms, like hurricanes and cold fronts, the coasts around the Mexican port city Veracruz suffer from erosion. This is most severe at the beaches of Boca del Rio just south of the city of Veracruz. Here, small beaches can be found between large groynes. These groynes block the southward littoral drift significantly but proved not to provide protection against episodic storm erosion. The cause of the erosional problem is in cross-shore direction, therefore solutions should be considered which act in this direction as well. Eventually a nourishment, a dune, an offshore submerged breakwater and a beach toe were designed as possible solutions. Firstly the impact on the current situation is simulated which is referred to as the do-nothing situation. Afterwards, runs were done with an XBeach model to check the storm impact on the beach profile for several combinations of the solutions mentioned above. To evaluate the simulations above six criteria were taken into account with different importance. The extent to which the erosion is counteracted and the costs are the most important criteria, besides values for the sustainability, durability, recreational value and hindrance contribute as well to the total score of a considered solution. Finally two combinations showed interesting results. On the one hand a nourishment and on the other hand an uninterrupted submerged breakwater in combination with a nourishment. Both can additionally be combined with a dune resulting in a slightly higher value due to better performance and higher recreational value. A nourishment is initially a cheap solution, but has to be maintained every few years by additional nourishments, resulting in increasing costs and hindrance for beach recreation. A large benefit of only performing beach nourishment is that abundance of sand will be available due to extension works at the port of Veracruz. The combination of a breakwater and a nourishment requires a high initial i, Hydraulic Engineering, Civil Engineering and Geosciences more...
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- 2014
17. Quantum efficiency test set up performances for NIR detector characterization at ESTEC
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Crouzet, P.-E., additional, Duvet, L., additional, De Wit, F., additional, Beaufort, T., additional, Blommaert, S., additional, Butler, B., additional, Van Duinkerken, G., additional, ter Haar, J., additional, Heijnen, J., additional, van der Luijt, K., additional, Smit, H., additional, and Viale, T., additional more...
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- 2014
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18. Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality Improvement Cardiovascular care Kwara-I (QUICK-I)
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Hendriks, M, Brewster, L, de Wit, F, Bolarinwa, OA, Odusola, AO, Redekop, Ken, Bindraban, N, Vollaard, BA, Alli, S, Adenusi, P, Agbede, K, Akande, T, Lange, Johan, Schultsz, C, Hendriks, M, Brewster, L, de Wit, F, Bolarinwa, OA, Odusola, AO, Redekop, Ken, Bindraban, N, Vollaard, BA, Alli, S, Adenusi, P, Agbede, K, Akande, T, Lange, Johan, and Schultsz, C more...
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- 2011
19. A double-station meteor camera set-up in the Canary Islands – CILBO
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Koschny, D., primary, Bettonvil, F., additional, Licandro, J., additional, Luijt, C. v. d., additional, Mc Auliffe, J., additional, Smit, H., additional, Svedhem, H., additional, de Wit, F., additional, Witasse, O., additional, and Zender, J., additional more...
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- 2013
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20. A double-station meteor camera setup in the Canary Islands – CILBO
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Koschny, D., primary, Bettonvil, F., additional, Licandro, J., additional, Luijt, C. v. d., additional, Mc Auliffe, J., additional, Smit, H., additional, Svedhem, H., additional, de Wit, F., additional, Witasse, O., additional, and Zender, J., additional more...
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- 2013
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21. Non-invasive continuous arterial pressure and pulse pressure variation measured with Nexfin(®) in patients following major upper abdominal surgery: a comparative study.
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Wilde, R. B. P., Wit, F., Geerts, B. F., Vliet, A. L., Aarts, L. P. H. J., Vuyk, J., Jansen, J. R. C., de Wilde, R B P, de Wit, F, and van Vliet, A L
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BLOOD pressure ,RADIAL artery ,CARDIAC catheterization ,ABDOMINAL surgery ,BLAND-Altman plot ,HEMODYNAMICS ,ARTERIAL physiology ,BLOOD pressure measurement ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,POSTOPERATIVE care ,RESEARCH ,RESEARCH evaluation ,PRODUCT design ,EVALUATION research ,BLOOD pressure testing machines ,EQUIPMENT & supplies - Abstract
We compared the accuracy and precision of the non-invasive Nexfin(®) device for determining systolic, diastolic, mean arterial pressure and pulse pressure variation, with arterial blood pressure values measured from a radial artery catheter in 19 patients following upper abdominal surgery. Measurements were taken at baseline and following fluid loading. Pooled data results of the arterial blood pressures showed no difference between the two measurement modalities. Bland-Altman analysis of pulse pressure variation showed significant differences between values obtained from the radial artery catheter and Nexfin finger cuff technology (mean (SD) 1.49 (2.09)%, p < 0.001, coefficient of variation 24%, limits of agreement -2.71% to 5.69%). The effect of volume expansion on pulse pressure variation was identical between methods (concordance correlation coefficient 0.848). We consider the Nexfin monitor system to be acceptable for use in patients after major upper abdominal surgery without major cardiovascular compromise or haemodynamic support. [ABSTRACT FROM AUTHOR] more...
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- 2016
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22. Characterization of HAWAII-2RG detector and SIDECAR ASIC for the Euclid mission at ESA
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Crouzet, P-E., primary, ter Haar, J., additional, de Wit, F., additional, Beaufort, T., additional, Butler, B., additional, Smit, H., additional, van der Luijt, C., additional, and Martin, D., additional more...
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- 2012
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23. Test set up description and performances for HAWAII-2RG detector characterization at ESTEC
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Crouzet, P-E., primary, ter Haar, J., additional, de Wit, F., additional, Beaufort, T., additional, Butler, B., additional, Smit, H., additional, van der Luijt, C., additional, and Martin, D., additional more...
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- 2012
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24. University students and HIV in Namibia: an HIV prevalence survey and a knowledge and attitude survey
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de Beer, Ingrid H, primary, Gelderblom, Huub C, additional, Schellekens, Onno, additional, Gaeb, Esegiel, additional, van Rooy, Gert, additional, McNally, Alta, additional, Wit, Ferdinand W, additional, and Tobias, Rinke de Wit F, additional more...
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- 2012
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25. Traditie, vernieuwing en wederzijdse be?nvloeding/Antara tradisi, pembaharuan dan pengarum Indonesia-Belanda
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Heins, E.L., de Wit, F., and Faculteit der Letteren
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- 1995
26. The influence of pre-treatments of aluminium alloys on bonding of PET coatings
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De Wit, F. M., primary, Özkanat, Ö., additional, Mol, J. M. C., additional, Terryn, H., additional, and De Wit, J. H. W., additional
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- 2010
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27. The Influence of Chemical Pre-treatment and Magnesium Surface Enrichment on Bonding of Succinic Acid Molecules to Aluminium Alloy
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de Wit, F. M., primary, Mol, J. M. C., additional, Terryn, H., additional, and de Wit, J. H. W., additional
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- 2008
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28. User perception of computerised maintenance information system implementations.
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Amadi-Echendu, J E and de Wit, F C P
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- 2014
29. Quantum efficiency performances of the NIR European Large Format Array detectors tested at ESTEC
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Meynart, Roland, Neeck, Steven P., Shimoda, Haruhisa, Crouzet, P.-E., Duvet, L., de Wit, F., Beaufort, T., Blommaert, S., Butler, B., Van Duinkerken, G., ter Haar, J., Heijnen, J., van der Luijt, K., and Smit, H. more...
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- 2015
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30. Production of ethylene by gravistimulation: a potential problem with the interpretation of data from some experimental techniques
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DE WIT, F. L., primary, LIU, J.‐H., additional, and REID, D. M., additional
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- 1990
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31. Quantum efficiency test set up performances for NIR detector characterization at ESTEC
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Holland, Andrew D., Beletic, James, Crouzet, P.-E., Duvet, L., De Wit, F., Beaufort, T., Blommaert, S., Butler, B., Van Duinkerken, G., ter Haar, J., Heijnen, J., van der Luijt, K., Smit, H., and Viale, T. more...
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- 2013
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32. Risk factors for respiratory syncytial virus-associated acute lower respiratory infection in children under 5 years: An updated systematic review and meta-analysis.
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Deng S, Cong B, Edgoose M, De Wit F, Nair H, and Li Y
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- Humans, Risk Factors, Infant, Child, Preschool, Hospitalization statistics & numerical data, Female, Infant, Newborn, Male, Air Pollution, Indoor adverse effects, Acute Disease, Pregnancy, Respiratory Syncytial Virus Infections epidemiology, Respiratory Tract Infections epidemiology, Respiratory Tract Infections virology, Respiratory Syncytial Virus, Human
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Objectives: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed to conduct an updated systematic review of risk factors for RSV-ALRI in children under 5 years., Methods: We updated our previously published literature search to November 2022 among three English databases and additionally searched three Chinese databases (from January 1995) to identify all relevant publications. We performed random-effects meta-analyses to estimate the pooled odds ratio (OR) and 95% confidence interval (CI) for each risk factor and each outcome (RSV-ALRI in the community and RSV-ALRI hospitalization)., Results: A total of 47 studies were included (26 from the updated search). Indoor air pollution was identified as a possible risk factor for RSV-ALRI in the community (OR 1.45, 95% CI: 1.10-1.90). The identified risk factors for RSV-ALRI hospitalization fall into four categories: demographic (male sex, Māori and Pacific ethnicities vs European or other ethnicities), pre- and post-neonatal (prematurity, low birth weight, small for gestational age, maternal smoking during pregnancy or lactation, maternal age <30 years vs 30-34 years, multiparity, caesarean section vs vaginal), household and environmental (having siblings, passive smoking, maternal asthma, daycare centre attendance) and health and medical conditions (any chronic diseases, bronchopulmonary dysplasia, HIV infections, congenital heart disease, Down syndrome, cystic fibrosis, previous asthma). The pooled ORs ranged from 1.14 to 4.55., Conclusion: Our findings on the risk factors for RSV-ALRI help identify RSV high-risk groups, which has important implications for RSV prevention at both individual and population levels., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YL reports grants from WHO, GSK and Wellcome Trust; and personal fees from WHO and Pfizer, outside the submitted work. HN reports grants from the Innovative Medicines Initiative, WHO, the National Institute for Health Research, Pfizer and Icosavax; and personal fees from the Bill & Melinda Gates Foundation, Pfizer, GSK, Merck, Abbvie, Janssen, Icosavax, Sanofi, Novavax, outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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33. Prevalence of opioid dependence in Scotland 2015-2020: A multi-parameter estimation of prevalence (MPEP) study.
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Markoulidakis A, Hickman M, McAuley A, Barnsdale LR, Welton NJ, Glancy M, Shivaji T, Collins C, Lang J, de Wit F, Hunt G, Wilkinson L, Fraser R, Yeung A, Horsburgh K, Priyadarshi S, Hutchinson SJ, and Jones HE more...
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- Humans, Scotland epidemiology, Adult, Prevalence, Male, Middle Aged, Female, Young Adult, Adolescent, Opiate Substitution Treatment, Hospitalization statistics & numerical data, Analgesics, Opioid therapeutic use, Opioid-Related Disorders epidemiology, Bayes Theorem
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Background and Aims: Drug-related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15-64 from 2014/15 to 2019/20., Design: We fitted a Bayesian multi-parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid-related mortality and hospital admissions data. Estimates are stratified by age group, sex and year., Setting: Scotland, 2014/15 to 2019/20., Participants: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid-related deaths and hospital admissions (whether among or outside of this cohort)., Measurements: Rates of each adverse event type and (unobserved) prevalence were jointly modelled., Findings: The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change -0.07%, 95% CrI -0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15-34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50-64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20., Conclusions: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid-related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.) more...
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- 2024
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34. Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score-matched analysis.
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Driessen J, de Wit F, Herrera AF, Zinzani PL, LaCasce AS, Cole PD, Moskowitz CH, García-Sanz R, Fuchs M, Müller H, Borchmann P, Santoro A, Schöder H, Zijlstra JM, Hutten BA, Moskowitz AJ, and Kersten MJ more...
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- Humans, Male, Female, Adult, Middle Aged, Salvage Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Recurrence, Young Adult, Adolescent, Treatment Outcome, Aged, Neoplasm Recurrence, Local drug therapy, Drug Resistance, Neoplasm, Hodgkin Disease drug therapy, Hodgkin Disease mortality, Hodgkin Disease therapy, Brentuximab Vedotin therapeutic use, Propensity Score
- Abstract
Abstract: Several single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score-matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL. We included 768 patients, of whom 386 were treated with BV with or without chemotherapy (BV cohort), whereas 382 received chemotherapy alone (chemotherapy cohort). Propensity score matching resulted in balanced cohorts of 240 patients each. No significant differences were observed in pre-ASCT complete metabolic response (CMR) rates (P = .69) or progression free survival (PFS; P = .14) between the BV and chemotherapy cohorts. However, in the BV vs chemotherapy cohort, patients with relapsed disease had a significantly better 3-year PFS of 80% vs 70%, respectively (P = .02), whereas there was no difference for patients with primary refractory disease (56% vs 62%, respectively; P = .67). Patients with stage IV disease achieved a significantly better 3-year PFS in the BV cohort (P = .015). Post-ASCT PFS was comparable for patients achieving a CMR after BV monotherapy and those receiving BV followed by sequential chemotherapy (P = .24). Although 3-year overall survival was higher in the BV cohort (92% vs 80%, respectively; P < .001), this is likely attributed to the use of other novel therapies in later lines for patients experiencing progression, given that studies in the BV cohort were conducted more recently. In conclusion, BV with or without salvage chemotherapy appears to enhance PFS in patients with relapsed disease but not in those with primary refractory cHL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.) more...
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- 2024
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35. Single-Cell Imaging Shows That the Transcriptional State of the HIV-1 Provirus and Its Reactivation Potential Depend on the Integration Site.
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Janssens J, De Wit F, Parveen N, and Debyser Z
- Subjects
- Chromatin genetics, Humans, Proviruses genetics, Virus Integration, Virus Replication, HIV Integrase Inhibitors pharmacology, HIV Seropositivity, HIV-1 physiology
- Abstract
Current antiretroviral treatment fails to cure HIV-1 infection since latent provirus resides in long-lived cellular reservoirs, rebounding whenever therapy is discontinued. The molecular mechanisms underlying HIV-1 latency are complex where the possible link between integration and transcription is poorly understood. HIV-1 integration is targeted toward active chromatin by the direct interaction with a host protein, lens epithelium-derived growth factor (LEDGF/p75). LEDGINs are small-molecule inhibitors of the LEDGF/p75-integrase (IN) interaction that effectively inhibit and retarget HIV-1 integration out of preferred integration sites, resulting in residual provirus that is more latent. Here, we describe a single-cell branched DNA imaging method for simultaneous detection of viral DNA and RNA. We investigated how treatment with LEDGINs affects the location, transcription, and reactivation of HIV-1 in both cell lines and primary cells. This approach demonstrated that LEDGIN-mediated retargeting hampered the baseline transcriptional state and the transcriptional reactivation of the provirus, evidenced by the reduction in viral RNA expression per residual copy. Moreover, treatment of primary cells with LEDGINs induced an enrichment of provirus in deep latency. These results corroborate the impact of integration site selection for the HIV-1 transcriptional state and support block-and-lock functional cure strategies in which the latent reservoir is permanently silenced after retargeting. IMPORTANCE A longstanding question exists on the impact of the HIV-1 integration site on viral gene expression. This unsolved question has significant implications for the search toward an HIV-1 cure, as eradication strategies set up to reactivate and eliminate HIV-1 depend on the site where the provirus is integrated. The main determinant for integration site selection is the interaction of the HIV-1 integrase (IN) and the host chromatin targeting factor, LEDGF/p75. LEDGINs are small-molecule inhibitors of the LEDGF/p75-IN interaction that inhibit and retarget HIV-1 integration out of preferred integration sites. Using both LEDGINs and branched DNA (bDNA) imaging, we now investigated, in much detail, the impact of integration site selection on the three-dimensional location of the provirus, HIV-1 transcription, and reactivation. Our results provide evidence for a "block-and-lock" functional cure strategy that aims to permanently silence HIV-1 by LEDGIN-mediated retargeting to sites that are less susceptible to reactivation after treatment interruption. more...
- Published
- 2022
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36. The impact of the 2009 influenza pandemic on the seasonality of human respiratory syncytial virus: A systematic analysis.
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Li Y, Wang X, Msosa T, de Wit F, Murdock J, and Nair H
- Subjects
- Humans, Infant, Pandemics, SARS-CoV-2, Seasons, COVID-19, Influenza, Human epidemiology, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus, Human
- Abstract
Background: Several local studies showed that the 2009 influenza pandemic delayed the RSV season. However, no global-level analyses are available on the possible impact of the 2009 influenza pandemic on the RSV season., Objectives: We aim to understand the impact of the 2009 influenza pandemic on the RSV season., Methods: We compiled data from published literature (through a systematic review), online reports/datasets and previously published data on global RSV seasonality and conducted a global-level systematic analysis on the impact of the 2009 influenza pandemic on RSV seasonality., Results: We included 354 seasons of 45 unique sites, from 26 countries. Globally, the influenza pandemic delayed the onset of the first RSV season by 0.58 months on average (95% CI: 0.42, 0.73; maximum delay: 2.5 months) and the onset of the second RSV season by a lesser extent (0.25 months; 95% CI: 0.12, 0.39; maximum delay: 3.4 months); no delayed onset was observed for the third RSV season. The delayed onset was most pronounced in the northern temperate, followed by the southern temperate, and was least pronounced in the tropics., Conclusions: The 2009 influenza pandemic delayed the RSV onset on average by 0.58 months and up to 2.5 months. This suggests evidence of viral interference as well as the impact of public health measures and has important implications for preparedness for RSV season during the ongoing COVID-19 pandemic and future pandemics., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.) more...
- Published
- 2021
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37. CRISPR/Cas9-Induced Mutagenesis Corroborates the Role of Transportin-SR2 in HIV-1 Nuclear Import.
- Author
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Janssens J, Blokken J, Lampi Y, De Wit F, Zurnic Bonisch I, Nombela I, Van de Velde P, Van Remoortel B, Gijsbers R, Christ F, and Debyser Z
- Subjects
- Active Transport, Cell Nucleus, CRISPR-Cas Systems, Cell Nucleus metabolism, HIV Infections genetics, HIV Infections virology, HIV Integrase genetics, HIV Integrase metabolism, HIV-1 genetics, Humans, Protein Binding, Serine-Arginine Splicing Factors genetics, Serine-Arginine Splicing Factors metabolism, beta Karyopherins genetics, mRNA Cleavage and Polyadenylation Factors genetics, mRNA Cleavage and Polyadenylation Factors metabolism, Cell Nucleus virology, HIV-1 metabolism, beta Karyopherins metabolism
- Abstract
To infect nondividing cells, HIV-1 needs to cross the nuclear membrane. The importin transportin-SR2 (TRN-SR2 or transportin-3) has been proposed to mediate HIV-1 nuclear import, but the detailed mechanism remains unresolved. The direct interaction of TRN-SR2 with HIV-1 integrase (IN) has been proposed to drive HIV-1 nuclear import. Alternatively, TRN-SR2 may play an indirect role by mediating nuclear import of cleavage and polyadenylation specificity factor 6 (CPSF6). To unravel the role of TRN-SR2, we designed CRISPR/Cas9 guide RNAs targeting different exons of TNPO3 . Although this approach failed to generate full knockouts, monoallelic knockout clones were generated with indel mutations. HIV-1 replication was hampered in those clones at the level of HIV-1 nuclear import without an effect on the cellular distribution of the TRN-SR2 cargoes CPSF6 or alternative splicing factor1/pre-mRNA splicing factor SF2 (ASF/SF2). Recombinant ΔV
105 TRN-SR2 expressed in clone 15.15 was 2-fold impaired for interaction with HIV-1 IN and classified as an interaction mutant. Our data support a model whereby TRN-SR2 acts as a cofactor of HIV-1 nuclear import without compromising the nuclear import of cellular cargoes. CRISPR/Cas9-induced mutagenesis can be used as a method to generate interface mutants to characterize host factors of human pathogens. IMPORTANCE Combination antiretroviral therapy (cART) effectively controls HIV-1 by reducing viral loads, but it does not cure the infection. Lifelong treatment with cART is a prerequisite for sustained viral suppression. The rapid emergence of drug-resistant viral strains drives the necessity to discover new therapeutic targets. The nuclear import of HIV-1 is crucial in the HIV-1 replication cycle, but the detailed mechanism remains incompletely understood. This study provides evidence that TRN-SR2 directly mediates HIV-1 nuclear import via the interaction with HIV-1 integrase. The interaction between those proteins is therefore a promising target toward a rational drug design which could lead to new therapeutic strategies due to the bottleneck nature of HIV-1 nuclear import. more...- Published
- 2021
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38. Correction: Y-box-binding protein 1 supports the early and late steps of HIV replication.
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Weydert C, van Heertum B, Dirix L, De Houwer S, De Wit F, Mast J, Husson SJ, Busschots K, König R, Gijsbers R, De Rijck J, and Debyser Z
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0200080.].
- Published
- 2020
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39. CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis.
- Author
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van der Kroef M, Carvalheiro T, Rossato M, de Wit F, Cossu M, Chouri E, Wichers CGK, Bekker CPJ, Beretta L, Vazirpanah N, Trombetta E, Radstake TRDJ, and Angiolilli C
- Subjects
- Adult, Aged, Benzimidazoles pharmacology, Cells, Cultured, Cytokines metabolism, Female, Humans, Male, Middle Aged, Piperidines pharmacology, Receptors, Platelet-Derived Growth Factor antagonists & inhibitors, Becaplermin metabolism, Fibroblasts immunology, Inflammation immunology, Macrophages immunology, Monocytes immunology, Platelet Factor 4 metabolism, Scleroderma, Systemic immunology
- Abstract
Objective: To analyze how monocyte and macrophage exposure to CXCL4 induces inflammatory and fibrotic processes observed in Systemic sclerosis (SSc) patients., Methods: In six independent experiments, monocytes of healthy controls (HC) and SSc patients were stimulated with CXCL4, TLR-ligands, IFNɑ or TGFβ and the secretion of cytokines in the supernatant was assessed by multiplex immunoassays. PDGF-BB production by monocyte-derived macrophages was quantified using immunoassays. The number of monocytes and PDGF-BB in circulation was quantified in HC and SSc patients with the Sysmex XT-1800i haematology counter and immunoassays. Intracellular PDGF-BB was quantified in monocytes by Western blot. PDGF-receptor inhibition was achieved using siRNA-mediated knockdown or treatment with Crenolanib. The production of inflammatory mediators and extracellular matrix (ECM) components by dermal fibroblasts was analyzed by qPCR, ELISA and ECM deposition assays., Results: SSc and HC monocytes released PDGF-BB upon stimulation with CXCL4. Conversely, TLR ligands, IFNɑ or TGFβ did not induce PDGF-bb release. PDGF-BB plasma levels were significantly (P = 0.009) higher in diffuse SSc patients (n = 19), compared with HC (n = 21). In healthy dermal fibroblasts, PDGF-BB enhanced TNFɑ-induced expression of inflammatory cytokines and increased ECM production. Comparable results were observed in fibroblasts cultured in supernatant taken from macrophages stimulated with CXCL4. This effect was almost completely abrogated by inhibition of the PDGF-receptor using Crenolanib., Conclusion: Our findings demonstrate that CXCL4 can drive fibroblast activation indirectly via PDGF-BB production by myeloid cells. Hence, targeting PDGF-BB or CXCL4-induced PDGF-BB release could be clinically beneficial for patients with SSc., Competing Interests: Declarations of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2020
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40. Capsid-Labelled HIV To Investigate the Role of Capsid during Nuclear Import and Integration.
- Author
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Zurnic Bönisch I, Dirix L, Lemmens V, Borrenberghs D, De Wit F, Vernaillen F, Rocha S, Christ F, Hendrix J, Hofkens J, and Debyser Z
- Subjects
- Cell Nucleus virology, Cytoplasm metabolism, DNA, Viral genetics, Green Fluorescent Proteins metabolism, HEK293 Cells, HeLa Cells, Humans, Nuclear Envelope metabolism, RNA, Viral metabolism, Virus Replication, Virus Uncoating, Active Transport, Cell Nucleus, Capsid metabolism, Capsid Proteins metabolism, HIV-1 physiology, Virus Integration
- Abstract
The HIV-1 capsid protein performs multiple roles in virus replication both during assembly and particle release and during virus trafficking into the nucleus. In order to decipher the roles of capsid protein during early replication, a reliable method to follow its intracellular distribution is required. To complement existing approaches to track HIV-1 capsid during early infection, we developed an HIV-1 imaging strategy, relying on viruses incorporating enhanced green fluorescent protein (eGFP)-tagged capsid (CA-eGFP) protein and mCherry-tagged integrase (IN-mCherry). Wild-type infectivity and sensitivity to inhibition by PF74 point to the functionality of CA-eGFP-containing complexes. Low numbers of CA-eGFP molecules were located inside the viral core and imported into the nucleus without significant loss in intensity. Less than 5% of particles carrying both CA-eGFP and IN-mCherry retained both labelled proteins after nuclear entry, implying a major uncoating event at the nuclear envelope dissociating IN and CA. Still, 20% of all CA-eGFP-containing complexes were detected in the nucleus. Unlike for IN-mCherry complexes, addition of the integrase inhibitor raltegravir had no effect on CA-eGFP-containing complexes, suggesting that these may be not (yet) competent for integration. Our imaging strategy offers alternative visualization of viral capsid trafficking and helps clarify its potential role during integration. IMPORTANCE HIV-1 capsid protein (CA) builds a conical shell protecting viral genomic RNA inside the virus particles. Upon entry into host cells, this shell disassembles in a process of uncoating, which is coordinated with reverse transcription of viral RNA into DNA. After uncoating, a portion of CA remains associated with the viral DNA and mediates its nuclear import and, potentially, integration into host DNA. In this study, we tagged CA with eGFP to follow its trafficking in host cells and address potential CA roles in the nucleus. We found that while functional viruses import the tagged CA into the nucleus, this capsid protein is not part of integration-competent complexes. The roles of nuclear CA thus remain to be established., (Copyright © 2020 American Society for Microbiology.) more...
- Published
- 2020
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41. Design of reverse transcriptase-specific nucleosides to visualize early steps of HIV-1 replication by click labeling.
- Author
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De Wit F, Pillalamarri SR, Sebastián-Martín A, Venkatesham A, Van Aerschot A, and Debyser Z
- Subjects
- Alkynes chemistry, Cell Line, Cell Survival drug effects, DNA Primers metabolism, Deoxyuridine metabolism, Deoxyuridine toxicity, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 genetics, Humans, Kinetics, Microscopy, Confocal, RNA, Viral chemistry, RNA, Viral metabolism, Click Chemistry, Deoxyuridine analogs & derivatives, HIV Reverse Transcriptase metabolism, HIV-1 physiology, Virus Replication
- Abstract
Only a small portion of human immunodeficiency virus type 1 (HIV-1) particles entering the host cell results in productive infection, emphasizing the importance of identifying the functional virus population. Because integration of viral DNA (vDNA) is required for productive infection, efficient vDNA detection is crucial. Here, we use click chemistry to label viruses with integrase coupled to eGFP (HIV
IN-eGFP ) and visualize vDNA. Because click labeling with 5-ethynyl-2'-deoxyuridine is hampered by intense background staining of the host nucleus, we opted for developing HIV-1 reverse transcriptase (RT)-specific 2'-deoxynucleoside analogs that contain a clickable triple bond. We synthesized seven propargylated 2'-deoxynucleosides and tested them for lack of cytotoxicity and viral replication inhibition, RT-specific primer extension and incorporation kinetics in vitro , and the capacity to stain HIV-1 DNA. The triphosphate of analog A5 was specifically incorporated by HIV-1 RT, but no vDNA staining was detected during infection. Analog A3 was incorporated in vitro by HIV-1 RT and human DNA polymerase γ and did enable specific HIV-1 DNA labeling. Additionally, A3 supported mitochondria-specific DNA labeling, in line with the in vitro findings. After obtaining proof-of-principle of RT-specific DNA labeling reported here, further chemical refinement is necessary to develop even more efficient HIV-1 DNA labels without background staining of the nucleus or mitochondria., (© 2019 De Wit et al.) more...- Published
- 2019
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42. Effectiveness of a skin care programme for the prevention of contact dermatitis in healthcare workers (the Healthy Hands Project): A single-centre, cluster randomized controlled trial.
- Author
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Soltanipoor M, Kezic S, Sluiter JK, de Wit F, Bosma AL, van Asperen R, and Rustemeyer T
- Subjects
- Female, Humans, Male, Severity of Illness Index, Dermatitis, Allergic Contact prevention & control, Dermatitis, Occupational prevention & control, Hand Dermatoses prevention & control, Health Personnel, Skin Cream administration & dosage
- Abstract
Background: Healthcare workers (HCWs) are at risk of developing hand dermatitis (HD). Guidelines recommend moisturizers to prevent HD, but in practice their effectiveness has been poorly investigated., Objectives: To assess whether an intervention aimed at improving skin care leads to a reduction in HD severity., Methods: In this 1-year randomized controlled trial, 9 wards (285 HCWs) were allocated to an intervention group (IG), and 10 wards (216 HCWs) were allocated to the control group (CG). The intervention included provision of cream dispensers with electronic monitoring of use, regularly communicated to the HCWs. The primary and secondary outcomes were change from baseline in Hand Eczema Severity Index (HECSI) score (ΔHECSI) and change in natural moisturizing factor (NMF) level (ΔNMF)., Results: At 12 months, the rates of loss to follow-up were 41% and 39% in the IG and the CG, respectively. The HECSI score was reduced in the IG by -6.2 points (95%CI: -7.7 to -4.7) and in the CG by -4.2 points (95%CI: -6.0 to -2.4). There was no significant difference in ΔHECSI or ΔNMF between the groups. Relative improvement in the HECSI score was significantly higher in the IG than in the CG (56% vs 44%). In a subgroup of HCWs with mild HD, the IG showed a larger HECSI score decrease than the CG (P < 0.001)., Conclusion: Although there was no significant effect on the primary outcomes, the intervention showed overall positive effects on the HECSI score., (© 2019 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.) more...
- Published
- 2019
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43. Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration.
- Author
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Borrenberghs D, Zurnic I, De Wit F, Acke A, Dirix L, Cereseto A, Debyser Z, and Hendrix J
- Subjects
- Cell Cycle, Cell Nucleus virology, Cytoplasm virology, Genetic Vectors, HEK293 Cells, HeLa Cells, Humans, Mitosis, Protein Structure, Quaternary, Proteins antagonists & inhibitors, Proteins metabolism, Integrases chemistry, Moloney murine leukemia virus enzymology, Moloney murine leukemia virus genetics, Virus Integration
- Abstract
The Moloney murine leukemia virus (MLV) is a prototype gammaretrovirus requiring nuclear disassembly before DNA integration. In the nucleus, integration site selection towards promoter/enhancer elements is mediated by the host factor bromo- and extraterminal domain (BET) proteins (bromodomain (Brd) proteins 2, 3 and 4). MLV-based retroviral vectors are used in gene therapy trials. In some trials leukemia occurred through integration of the MLV vector in close proximity to cellular oncogenes. BET-mediated integration is poorly understood and the nature of integrase oligomers heavily debated. Here, we created wild-type infectious MLV vectors natively incorporating fluorescent labeled IN and performed single-molecule intensity and Förster resonance energy transfer experiments. The nuclear localization of the MLV pre-integration complex neither altered the IN content, nor its quaternary structure. Instead, BET-mediated interaction of the MLV intasome with chromatin in the post-mitotic nucleus reshaped its quaternary structure., (© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.) more...
- Published
- 2019
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44. Propargylated Purine Deoxynucleosides: New Tools for Fluorescence Imaging Strategies.
- Author
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Venkatesham A, Pillalamarri SR, De Wit F, Lescrinier E, Debyser Z, and Van Aerschot A
- Subjects
- Cell Line, Cell Survival, Click Chemistry, Gene Expression, Genes, Reporter, HIV-1 drug effects, HIV-1 physiology, Humans, Molecular Structure, Virus Replication drug effects, Fluorescent Dyes chemistry, Optical Imaging methods, Purine Nucleosides chemistry
- Abstract
In vivo imaging of biological processes is an important asset of modern cell biology. Selectively reacting fluorophores herein are an important tool and click chemistry reactions take a large share in these events. 5-Ethynyl-2'-deoxyuridine (EdU) is well known for visualizing DNA replication, but does not show any selectivity for incorporation into DNA. Striving for specific visualization of virus replication, in particular HIV replication, a series of propargylated purine deoxynucleosides were prepared aiming for selective incorporation by HIV reverse transcriptase (RT). We here report on the synthesis and preliminary biological effects (cellular toxicity, HIV inhibitory effects, and feasibility of the click reaction) of these nucleoside analogues., Competing Interests: The authors declare no conflict of interest. more...
- Published
- 2019
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45. Y-box-binding protein 1 supports the early and late steps of HIV replication.
- Author
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Weydert C, van Heertum B, Dirix L, De Houwer S, De Wit F, Mast J, Husson SJ, Busschots K, König R, Gijsbers R, De Rijck J, and Debyser Z
- Subjects
- Active Transport, Cell Nucleus, HIV Integrase metabolism, HIV-1 enzymology, HIV-1 genetics, HeLa Cells, Humans, RNA, Viral metabolism, Reverse Transcription, Time Factors, HIV-1 physiology, Virus Replication, Y-Box-Binding Protein 1 metabolism
- Abstract
The human immunodeficiency virus (HIV) depends on cellular proteins, so-called cofactors, to complete its replication cycle. In search for new therapeutic targets we identified the DNA and RNA binding protein Y-box-binding Protein 1 (YB-1) as a cofactor supporting early and late steps of HIV replication. YB-1 depletion resulted in a 10-fold decrease in HIV-1 replication in different cell lines. Dissection of the replication defects revealed that knockdown of YB-1 is associated with a 2- to 5-fold decrease in virion production due to interference with the viral RNA metabolism. Using single-round virus infection experiments we demonstrated that early HIV-1 replication also depends on the cellular YB-1 levels. More precisely, using quantitative PCR and an in vivo nuclear import assay with fluorescently labeled viral particles, we showed that YB-1 knockdown leads to a block between reverse transcription and nuclear import of HIV-1. Interaction studies revealed that YB-1 associates with integrase, although a direct interaction with HIV integrase could not be unambiguously proven. In conclusion, our results indicate that YB-1 affects multiple stages of HIV replication. Future research on the interaction between YB-1 and the virus will reveal whether this protein qualifies as a new antiviral target., Competing Interests: The authors have declared that no competing interests exist. more...
- Published
- 2018
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46. The Burden of Power: Construing Power as Responsibility (Rather Than as Opportunity) Alters Threat-Challenge Responses.
- Author
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Scholl A, de Wit F, Ellemers N, Fetterman AK, Sassenberg K, and Scheepers D
- Subjects
- Adolescent, Adult, Aged, Decision Making, Female, Humans, Male, Middle Aged, Young Adult, Comprehension, Power, Psychological, Social Responsibility, Stress, Psychological psychology
- Abstract
Power usually lowers stress responses. In stressful situations, having high (vs. low) power heightens challenge and lowers threat. Yet, even power-holders may experience threat when becoming aware of the responsibility that accompanies their power. Power-holders can construe (i.e., understand) a high-power position primarily as opportunity to "make things happen" or as responsibility to "take care of things." Power-holders construing power as responsibility (rather than opportunity) may be more likely to experience demands-such as taking care of important decisions under their control-as outweighing their resources, resulting in less challenge and more threat. Four experiments with subjective and cardiovascular threat-challenge indicators support this. Going beyond prior work on structural aspects (e.g., power instability) that induce stress, we show that merely the way how power-holders construe their power can evoke stress. Specifically, we find that power construed as responsibility (vs. opportunity) is more likely to imply a "burden" for the power-holder. more...
- Published
- 2018
- Full Text
- View/download PDF
47. Highly identified power-holders feel responsible: The interplay between social identification and social power within groups.
- Author
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Scholl A, Sassenberg K, Ellemers N, Scheepers D, and de Wit F
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Group Processes, Leadership, Power, Psychological, Social Identification
- Abstract
Power relations affect dynamics within groups. Power-holders' decisions not only determine their personal outcomes, but also the outcomes of others in the group that they control. Yet, power-holders often tend to overlook this responsibility to take care of collective interests. The present research investigated how social identification - with the group to which both the powerful and the powerless belong - alters perceived responsibility among power-holders (and the powerless). Combining research on social power and social identity, we argue that power-holders perceive more responsibility than the powerless when strongly (rather than when weakly) identifying with the group. A study among leaders and an experiment supported this, highlighting that although power-holders are often primarily concerned about personal outcomes, they do feel responsible for considering others' interests when these others are included in the (social) self., (© 2017 The British Psychological Society.) more...
- Published
- 2018
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48. N-terminal half of transportin SR2 interacts with HIV integrase.
- Author
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Tsirkone VG, Blokken J, De Wit F, Breemans J, De Houwer S, Debyser Z, Christ F, and Strelkov SV
- Subjects
- Active Transport, Cell Nucleus genetics, Anti-HIV Agents chemistry, Cell Nucleus chemistry, Cell Nucleus genetics, Cell Nucleus metabolism, Drug Design, HIV Integrase genetics, HIV Integrase metabolism, HIV-1 genetics, HIV-1 metabolism, Humans, Protein Domains, Repetitive Sequences, Amino Acid, X-Ray Diffraction, beta Karyopherins genetics, beta Karyopherins metabolism, HIV Infections, HIV Integrase chemistry, HIV-1 chemistry, Models, Molecular, beta Karyopherins chemistry
- Abstract
The karyopherin transportin SR2 (TRN-SR2, TNPO3) is responsible for shuttling specific cargoes such as serine/arginine-rich splicing factors from the cytoplasm to the nucleus. This protein plays a key role in HIV infection by facilitating the nuclear import of the pre-integration complex (PIC) that contains the viral DNA as well as several cellular and HIV proteins, including the integrase. The process of nuclear import is considered to be the bottleneck of the viral replication cycle and therefore represents a promising target for anti-HIV drug design. Previous studies have demonstrated that the direct interaction between TRN-SR2 and HIV integrase predominantly involves the catalytic core domain (CCD) and the C-terminal domain (CTD) of the integrase. We aimed at providing a detailed molecular view of this interaction through a biochemical characterization of the respective protein complex. Size-exclusion chromatography was used to characterize the interaction of TRN-SR2 with a truncated variant of the HIV-1 integrase, including both the CCD and CTD. These experiments indicate that one TRN-SR2 molecule can specifically bind one CCD-CTD dimer. Next, the regions of the solenoid-like TRN-SR2 molecule that are involved in the interaction with integrase were identified using AlphaScreen binding assays, revealing that the integrase interacts with the N-terminal half of TRN-SR2 principally through the HEAT repeats 4, 10, and 11. Combining these results with small-angle X-ray scattering data for the complex of TRN-SR2 with truncated integrase, we propose a molecular model of the complex. We speculate that nuclear import of the PIC may proceed concurrently with the normal nuclear transport., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.) more...
- Published
- 2017
- Full Text
- View/download PDF
49. A matter of focus: Power-holders feel more responsible after adopting a cognitive other-focus, rather than a self-focus.
- Author
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Scholl A, Sassenberg K, Scheepers D, Ellemers N, and de Wit F
- Subjects
- Adolescent, Adult, Female, Humans, Male, Young Adult, Interpersonal Relations, Power, Psychological, Social Behavior
- Abstract
Social power implies responsibility. Yet, power-holders often follow only their own interests and overlook this responsibility. The present research illuminates how a previously adopted cognitive focus guides perceived responsibility when a person receives high (vs. low) power. In three experiments, adopting a cognitive focus on another person (vs. on the self or taking over another person's perspective) promoted perceived responsibility among individuals receiving high (but not low) power in a subsequent context. This effect was specific for perceived responsibility - a cognitive focus on another person did not change the perceived opportunity to pursue goals or the perceived relationship to an interaction partner (e.g., interpersonal closeness). While prior research examined how social values (i.e., chronically caring about others) guide responsibility among those holding power, the current findings highlight that mere cognitive processes (i.e., situationally focusing attention on others) alter perceived responsibility among those just about to receive power., (© 2016 The British Psychological Society.) more...
- Published
- 2017
- Full Text
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50. Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.
- Author
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Borrenberghs D, Dirix L, De Wit F, Rocha S, Blokken J, De Houwer S, Gijsbers R, Christ F, Hofkens J, Hendrix J, and Debyser Z
- Subjects
- Active Transport, Cell Nucleus physiology, Cell Line, Cell Nucleus metabolism, Chromatin metabolism, Fluorescence Resonance Energy Transfer, HIV Integrase chemistry, HIV Integrase genetics, HIV-1 enzymology, HeLa Cells, Humans, Intercellular Signaling Peptides and Proteins metabolism, Microscopy, Confocal, Nuclear Pore metabolism, Protein Multimerization, HIV Integrase metabolism, HIV-1 physiology
- Abstract
Nuclear entry is a selective, dynamic process granting the HIV-1 pre-integration complex (PIC) access to the chromatin. Classical analysis of nuclear entry of heterogeneous viral particles only yields averaged information. We now have employed single-virus fluorescence methods to follow the fate of single viral pre-integration complexes (PICs) during infection by visualizing HIV-1 integrase (IN). Nuclear entry is associated with a reduction in the number of IN molecules in the complexes while the interaction with LEDGF/p75 enhances IN oligomerization in the nucleus. Addition of LEDGINs, small molecule inhibitors of the IN-LEDGF/p75 interaction, during virus production, prematurely stabilizes a higher-order IN multimeric state, resulting in stable IN multimers resistant to a reduction in IN content and defective for nuclear entry. This suggests that a stringent size restriction determines nuclear pore entry. Taken together, this work demonstrates the power of single-virus imaging providing crucial insights in HIV replication and enabling mechanism-of-action studies., Competing Interests: The authors declare competing financial interests: Z.D. and F.C. are patent holders on patents related to LEDGF/p75 and LEDGINs. The other authors declare no competing financial interests. more...
- Published
- 2016
- Full Text
- View/download PDF
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