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Dr. Dasja Pajkrt
Amsterdam UMC, location AMC

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Journal article
Published: 29 May 2021 in Viruses
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Non-polio enteroviruses (NPEV) and parechoviruses (PeV) are widespread pathogens that cause significant morbidity. Surveillance is based on culturing or genotyping of virus strains found in clinical samples. Sero-surveillance, by measuring neutralising antibodies (nAb) through virus neutralisation assays (VNA), could provide additional information as it offers a more comprehensive overview of exposure to circulating types in the general population. In our study we evaluated Intravenous immunoglobulins (IVIG) to generate sero-surveillance data. We performed VNA of nineteen NPEV and PeV with Dutch IVIG batches from two different time points (2010 and 2017) and an IVIG batch from Vietnam (2011). We compared our findings with geno- and sero-surveillance data and evaluated changes over time and between the two countries. Our findings show a good correlation with what is known from geno-surveillance data. The highest nAb titres were found against strains from Enterovirus B, while we did not observe nAb titres against strains belonging to Enterovirus C. In conclusion, we demonstrated that sero-surveillance by means of IVIG can be used to obtain insight into circulation of EV and PeV genotypes. This is of particular interest for public health, to evaluate changes over time and population susceptibility to emerging genotypes.

ACS Style

Karen Couderé; Karlijn van der Straten; Lieke Brouwer; Gerrit Koen; Hetty van Eijk; Dasja Pajkrt; Jean-Luc Murk; Katja Wolthers. Neutralising Antibodies against Enterovirus and Parechovirus in IVIG Reflect General Circulation: A Tool for Sero-Surveillance. Viruses 2021, 13, 1028 .

AMA Style

Karen Couderé, Karlijn van der Straten, Lieke Brouwer, Gerrit Koen, Hetty van Eijk, Dasja Pajkrt, Jean-Luc Murk, Katja Wolthers. Neutralising Antibodies against Enterovirus and Parechovirus in IVIG Reflect General Circulation: A Tool for Sero-Surveillance. Viruses. 2021; 13 (6):1028.

Chicago/Turabian Style

Karen Couderé; Karlijn van der Straten; Lieke Brouwer; Gerrit Koen; Hetty van Eijk; Dasja Pajkrt; Jean-Luc Murk; Katja Wolthers. 2021. "Neutralising Antibodies against Enterovirus and Parechovirus in IVIG Reflect General Circulation: A Tool for Sero-Surveillance." Viruses 13, no. 6: 1028.

Journal article
Published: 13 May 2021 in Nutrients
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Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many put their hopes in the rapid availability of effective immunizations. Human milk, containing antibodies against syndrome coronavirus 2 (SARS-CoV-2), may serve as means of protection through passive immunization. We aimed to determine the presence and pseudovirus neutralization capacity of SARS-CoV-2 specific IgA in human milk of mothers who recovered from COVID-19, and the effect of pasteurization on these antibodies. Methods: This prospective case control study included lactating mothers, recovered from (suspected) COVID-19 and healthy controls. Human milk and serum samples were collected. To assess the presence of SARS-CoV-2 antibodies we used multiple complementary assays, namely ELISA with the SARS-CoV-2 spike protein (specific for IgA and IgG), receptor binding domain (RBD) and nucleocapsid (N) protein for IgG in serum, and bridging ELISA with the SARS-CoV-2 RBD and N protein for specific Ig (IgG, IgM and IgA in human milk and serum). To assess the effect of pasteurization, human milk was exposed to Holder (HoP) and High Pressure Pasteurization (HPP). Results: Human milk contained abundant SARS-CoV-2 antibodies in 83% of the proven cases and in 67% of the suspected cases. Unpasteurized milk with and without these antibodies was found to be capable of neutralizing a pseudovirus of SARS-CoV-2 in (97% and 85% of the samples respectively). After pasteurization, total IgA antibody levels were affected by HoP, while SARS-CoV-2 specific antibody levels were affected by HPP. Pseudovirus neutralizing capacity of the human milk samples was only retained with the HPP approach. No correlation was observed between milk antibody levels and neutralization capacity. Conclusions: Human milk from recovered COVID-19-infected mothers contains SARS-CoV-2 specific antibodies which maintained neutralization capacity after HPP. All together this may represent a safe and effective immunization strategy after HPP.

ACS Style

Britt van Keulen; Michelle Romijn; Albert Bondt; Kelly Dingess; Eva Kontopodi; Karlijn van der Straten; Maurits Den Boer; Judith Burger; Meliawati Poniman; Berend Bosch; Philip Brouwer; Christianne de Groot; Max Hoek; Wentao Li; Dasja Pajkrt; Rogier Sanders; Anne Schoonderwoerd; Sem Tamara; Rian Timmermans; Gestur Vidarsson; Koert Stittelaar; Theo Rispens; Kasper Hettinga; Marit van Gils; Albert Heck; Johannes van Goudoever. Human Milk from Previously COVID-19-Infected Mothers: The Effect of Pasteurization on Specific Antibodies and Neutralization Capacity. Nutrients 2021, 13, 1645 .

AMA Style

Britt van Keulen, Michelle Romijn, Albert Bondt, Kelly Dingess, Eva Kontopodi, Karlijn van der Straten, Maurits Den Boer, Judith Burger, Meliawati Poniman, Berend Bosch, Philip Brouwer, Christianne de Groot, Max Hoek, Wentao Li, Dasja Pajkrt, Rogier Sanders, Anne Schoonderwoerd, Sem Tamara, Rian Timmermans, Gestur Vidarsson, Koert Stittelaar, Theo Rispens, Kasper Hettinga, Marit van Gils, Albert Heck, Johannes van Goudoever. Human Milk from Previously COVID-19-Infected Mothers: The Effect of Pasteurization on Specific Antibodies and Neutralization Capacity. Nutrients. 2021; 13 (5):1645.

Chicago/Turabian Style

Britt van Keulen; Michelle Romijn; Albert Bondt; Kelly Dingess; Eva Kontopodi; Karlijn van der Straten; Maurits Den Boer; Judith Burger; Meliawati Poniman; Berend Bosch; Philip Brouwer; Christianne de Groot; Max Hoek; Wentao Li; Dasja Pajkrt; Rogier Sanders; Anne Schoonderwoerd; Sem Tamara; Rian Timmermans; Gestur Vidarsson; Koert Stittelaar; Theo Rispens; Kasper Hettinga; Marit van Gils; Albert Heck; Johannes van Goudoever. 2021. "Human Milk from Previously COVID-19-Infected Mothers: The Effect of Pasteurization on Specific Antibodies and Neutralization Capacity." Nutrients 13, no. 5: 1645.

Review
Published: 08 March 2021 in Viruses
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Enteroviruses (EVs) are highly prevalent viruses world-wide, causing a wide range of diseases in both children and adults. Insight in the global prevalence of EVs is important to define their clinical significance and total disease burden, and assists in making therapeutic decisions. While many studies have been conducted to describe epidemiology of EVs in specific (sub)populations and patient cohorts, little effort has been made to aggregate the available evidence. In the current study, we conducted a search in the PubMed and Embase (Ovid) databases to identify articles reporting EV prevalence and type distribution. We summarized the findings of 153 included studies. We found that EVs are highly prevalent viruses in all continents. Enterovirus B was the most detected species worldwide, while the other species showed continent-specific differences, with Enterovirus C more detected in Africa and Enterovirus A more detected in Asia. Echovirus 30 was by far the most detected type, especially in studies conducted in Europe. EV types in species Enterovirus B—including echovirus 30—were often detected in patient groups with neurological infections and in cerebrospinal fluid, while Enterovirus C types were often found in stool samples.

ACS Style

Lieke Brouwer; Giulia Moreni; Katja Wolthers; Dasja Pajkrt. World-Wide Prevalence and Genotype Distribution of Enteroviruses. Viruses 2021, 13, 434 .

AMA Style

Lieke Brouwer, Giulia Moreni, Katja Wolthers, Dasja Pajkrt. World-Wide Prevalence and Genotype Distribution of Enteroviruses. Viruses. 2021; 13 (3):434.

Chicago/Turabian Style

Lieke Brouwer; Giulia Moreni; Katja Wolthers; Dasja Pajkrt. 2021. "World-Wide Prevalence and Genotype Distribution of Enteroviruses." Viruses 13, no. 3: 434.

Opinion
Published: 23 November 2020 in Viruses
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Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to study viral infections in the human context. This perspective explores the potential of these organotypic cultures, also known as organoids, for virology research, antiviral testing, and shaping the virology landscape.

ACS Style

Adithya Sridhar; Salvatore Simmini; Carla M. S. Ribeiro; Caroline Tapparel; Melvin M. Evers; Dasja Pajkrt; Katja Wolthers. A Perspective on Organoids for Virology Research. Viruses 2020, 12, 1341 .

AMA Style

Adithya Sridhar, Salvatore Simmini, Carla M. S. Ribeiro, Caroline Tapparel, Melvin M. Evers, Dasja Pajkrt, Katja Wolthers. A Perspective on Organoids for Virology Research. Viruses. 2020; 12 (11):1341.

Chicago/Turabian Style

Adithya Sridhar; Salvatore Simmini; Carla M. S. Ribeiro; Caroline Tapparel; Melvin M. Evers; Dasja Pajkrt; Katja Wolthers. 2020. "A Perspective on Organoids for Virology Research." Viruses 12, no. 11: 1341.

Review
Published: 11 November 2020 in Viruses
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The knowledge about enteric viral infection has vastly increased over the last eight years due to the development of intestinal organoids and enteroids that suppose a step forward from conventional studies using cell lines. Intestinal organoids and enteroids are three-dimensional (3D) models that closely mimic intestinal cellular heterogeneity and organization. The barrier function within these models has been adapted to facilitate viral studies. In this review, several adaptations (such as organoid-derived two-dimensional (2D) monolayers) and original intestinal 3D models are discussed. The specific advantages and applications, as well as improvements of each model are analyzed and an insight into the possible path for the field is given.

ACS Style

Inés García-Rodríguez; Adithya Sridhar; Dasja Pajkrt; Katja C. Wolthers. Put Some Guts into It: Intestinal Organoid Models to Study Viral Infection. Viruses 2020, 12, 1288 .

AMA Style

Inés García-Rodríguez, Adithya Sridhar, Dasja Pajkrt, Katja C. Wolthers. Put Some Guts into It: Intestinal Organoid Models to Study Viral Infection. Viruses. 2020; 12 (11):1288.

Chicago/Turabian Style

Inés García-Rodríguez; Adithya Sridhar; Dasja Pajkrt; Katja C. Wolthers. 2020. "Put Some Guts into It: Intestinal Organoid Models to Study Viral Infection." Viruses 12, no. 11: 1288.

Research article
Published: 28 October 2020 in PLOS ONE
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Cerebral white matter hyperintensities (WMH) persist in children and adults living with HIV, despite effective combination antiretroviral therapy (cART). As age and principal routes of transmission differ between children (perinatally) and adults (behaviorally), comparing the characteristics and determinants of WMH between these populations may increase our understanding of the pathophysiology of WMH. From separate cohorts of 31 children (NOVICE) and 74 adults (AGEhIV), we cross-sectionally assessed total WMH volume and number of WMH per location (periventricular vs. deep) using fluid-attenuated inversion recovery (FLAIR) MRI images. WMH were either periventricular when within 10mm of the lateral ventricles, or deep otherwise. We assessed patient- or HIV-related determinants of total WMH volume (adjusted for intracranial volume) and location of WMH using logistic regression, while stratifying on children and adults. At enrollment, median age of participants was 13.8 years (IQR 11.4–15.9) for children and 53.4 years (IQR 48.3–60.8) for adults and 27/31 children (87%) and 74/74 adults (100%) had an HIV RNA viral load <200 copies/mL. WMH were present in 16/27 (52%) children and 74/74 adults (100%). The prevalence of deep WMH was not different between groups, (16/16 [100%] in children vs. 71/74 [96%] in adults, p = 0,999), yet periventricular WMH were more prevalent in adults (74/74 [100%]) compared to children (9/16; 56%) (p<0.001). Median WMH volume was higher in adults compared to children (1182 mm3 [425–2617] vs. 109 mm3 [61.7–625], p<0.001). In children, boys were more likely to have deep WMH compared to girls. In adults, older age was associated with higher total WMH volume, and age, hypertension and lower CD4+ T-lymphocyte nadir with a higher number of periventricular WMH. Our findings suggest that the location of WMH differs between children and adults living with HIV, hinting at a different underlying pathogenesis.

ACS Style

Jason G. Van Genderen; Malon Van Den Hof; Anders C. Boyd; Matthan W. A. Caan; Ferdinand W. N. M. Wit; Peter Reiss; Dasja Pajkrt. Differences in location of cerebral white matter hyperintensities in children and adults living with a treated HIV infection: A retrospective cohort comparison. PLOS ONE 2020, 15, e0241438 .

AMA Style

Jason G. Van Genderen, Malon Van Den Hof, Anders C. Boyd, Matthan W. A. Caan, Ferdinand W. N. M. Wit, Peter Reiss, Dasja Pajkrt. Differences in location of cerebral white matter hyperintensities in children and adults living with a treated HIV infection: A retrospective cohort comparison. PLOS ONE. 2020; 15 (10):e0241438.

Chicago/Turabian Style

Jason G. Van Genderen; Malon Van Den Hof; Anders C. Boyd; Matthan W. A. Caan; Ferdinand W. N. M. Wit; Peter Reiss; Dasja Pajkrt. 2020. "Differences in location of cerebral white matter hyperintensities in children and adults living with a treated HIV infection: A retrospective cohort comparison." PLOS ONE 15, no. 10: e0241438.

Other
Published: 21 August 2020
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Background Since the outbreak of COVID-19, many put their hopes in the rapid development of effective immunizations. For now patient isolation, physical distancing and good hygiene are the sole measures for prevention. Processed breast milk with antibodies against SaRS-CoV-2 may serve as additional protection. We aimed to determine the presence and neutralization capacity of antibodies against SaRS-CoV-2 in breastmilk of mothers who have recovered from COVID-19. Methods This prospective case control study included lactating mothers, recovered from (suspected) COVID-19 and healthy controls. Serum and breastmilk was collected. To assess the presence of antibodies in breastmilk and serum, we used multiple complementary assays, namely ELISA with the SARS-CoV-2 spike protein, SARS-CoV-2 receptor binding domain (RBD) and with the SARS-CoV-2 nucleocapsid (N) protein for IgG and bridging ELISA with the SARS-CoV-2 RBD and N protein for total Ig. To assess the effect of pasteurization breastmilk was exposed to Holder Pasteurization and High Pressure Pasteurization. Results Breastmilk contained antibodies against SARS-CoV-2 using any of the assays in 24 out of 29 (83%) proven cases, in six out of nine (67%) suspected cases and in none of the 13 controls.In vitroneutralization of SARS-CoV-2 clinical isolate virus strain was successful in a subset of serum (13%) and milk samples (26%). Although after pasteurization of the milk SARS-CoV-2 antibodies were detected with both methods of pasteurization, virus neutralizing capacity of those antibodies was only retained with the HPP approach. Conclusion Breastmilk of mothers who recovered from COVID-19 contains significant amounts of IgA against SARS-CoV-2, both before and after pasteurization. Key Points Question Does breastmilk of mothers who have recovered from coronavirus disease 2019 (COVID-19) contain antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Findings We provide multiple lines of evidence on the presence of a variety of antibodies against SARS-CoV-2, with no such antibodies present in the controls. These antibodies are capable of neutralizing a clinical isolate of SARS-CoV-2in vitro. We furthermore show that high pressure pasteurization hardly affects antibody levels and efficacy. Meaning Breastmilk, obtained from mothers who have recovered from COVID-19, may serve as a safe and widely applicable preventive strategy for vulnerable high risk populations

ACS Style

Britt J. Van Keulen; Michelle Romijn; Albert Bondt; Kelly A. Dingess; Eva Kontopodi; Karlijn Van Der Straten; Maurits A. Den Boer; Berend J. Bosch; Philip J.M. Brouwer; Christianne J.M. De Groot; Max Hoek; Wentao Li; Dasja Pajkrt; Rogier W. Sanders; Anne Schoonderwoerd; Sem Tamara; Rian A.H. Timmermans; Gestur Vidarsson; Koert J. Stittelaar; Theo T. Rispens; Kasper A. Hettinga; Marit J. Van Gils; Albert J.R. Heck; Johannes B. Van Goudoever. Breastmilk; a source of SARS-CoV-2 specific IgA antibodies. 2020, 1 .

AMA Style

Britt J. Van Keulen, Michelle Romijn, Albert Bondt, Kelly A. Dingess, Eva Kontopodi, Karlijn Van Der Straten, Maurits A. Den Boer, Berend J. Bosch, Philip J.M. Brouwer, Christianne J.M. De Groot, Max Hoek, Wentao Li, Dasja Pajkrt, Rogier W. Sanders, Anne Schoonderwoerd, Sem Tamara, Rian A.H. Timmermans, Gestur Vidarsson, Koert J. Stittelaar, Theo T. Rispens, Kasper A. Hettinga, Marit J. Van Gils, Albert J.R. Heck, Johannes B. Van Goudoever. Breastmilk; a source of SARS-CoV-2 specific IgA antibodies. . 2020; ():1.

Chicago/Turabian Style

Britt J. Van Keulen; Michelle Romijn; Albert Bondt; Kelly A. Dingess; Eva Kontopodi; Karlijn Van Der Straten; Maurits A. Den Boer; Berend J. Bosch; Philip J.M. Brouwer; Christianne J.M. De Groot; Max Hoek; Wentao Li; Dasja Pajkrt; Rogier W. Sanders; Anne Schoonderwoerd; Sem Tamara; Rian A.H. Timmermans; Gestur Vidarsson; Koert J. Stittelaar; Theo T. Rispens; Kasper A. Hettinga; Marit J. Van Gils; Albert J.R. Heck; Johannes B. Van Goudoever. 2020. "Breastmilk; a source of SARS-CoV-2 specific IgA antibodies." , no. : 1.

Journal article
Published: 30 June 2020 in Viruses
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Enteroviruses (EVs) are highly prevalent viruses worldwide. Recombination is known to occur frequently in EVs belonging to species Enterovirus A, Enterovirus B, and Enterovirus C. Although many recombinant vaccine-derived poliovirus (VDPV) strains have been reported, our knowledge on recombination in non-polio EVs in the species Enterovirus C is limited. Here, we combined a dataset consisting of 11 newly generated full-length Enterovirus C sequences and 180 publicly available sequences to study recombination dynamics in non-polio EVs. To identify recombination patterns, maximum likelihood phylogenetic trees of different genomic regions were constructed, and segregation analyses were performed. Recombination was observed between members of the same 3DPol cluster, but was rarely observed between members of different clusters. We hypothesize that this restriction may have arisen through their different compartmentalization in respiratory and enteric tracts related to differences in cellular tropisms so that the opportunity to recombine may not be available.

ACS Style

Lieke Brouwer; Kimberley S.M. Benschop; Dung Nguyen; Everlyn Kamau; Dasja Pajkrt; Peter Simmonds; Katja C. Wolthers. Recombination Analysis of Non-Poliovirus Members of the Enterovirus C Species; Restriction of Recombination Events to Members of the Same 3DPol Cluster. Viruses 2020, 12, 706 .

AMA Style

Lieke Brouwer, Kimberley S.M. Benschop, Dung Nguyen, Everlyn Kamau, Dasja Pajkrt, Peter Simmonds, Katja C. Wolthers. Recombination Analysis of Non-Poliovirus Members of the Enterovirus C Species; Restriction of Recombination Events to Members of the Same 3DPol Cluster. Viruses. 2020; 12 (7):706.

Chicago/Turabian Style

Lieke Brouwer; Kimberley S.M. Benschop; Dung Nguyen; Everlyn Kamau; Dasja Pajkrt; Peter Simmonds; Katja C. Wolthers. 2020. "Recombination Analysis of Non-Poliovirus Members of the Enterovirus C Species; Restriction of Recombination Events to Members of the Same 3DPol Cluster." Viruses 12, no. 7: 706.

Journal article
Published: 08 June 2020 in NeuroImage
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Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

ACS Style

Henk J.M.M. Mutsaerts; Jan Petr; Paul Groot; Pieter Vandemaele; Silvia Ingala; Andrew D. Robertson; Lena Václavů; Inge Groote; Hugo Kuijf; Fernando Zelaya; Owen O’Daly; Saima Hilal; Alle Meije Wink; Ilse Kant; Matthan W.A. Caan; Catherine Morgan; Jeroen de Bresser; Elisabeth Lysvik; Anouk Schrantee; Astrid Bjørnebekk; Patricia Clement; Zahra Shirzadi; Joost P.A. Kuijer; Viktor Wottschel; Udunna C. Anazodo; Dasja Pajkrt; Edo Richard; Reinoud P.H. Bokkers; Liesbeth Reneman; Mario Masellis; Matthias Günther; Bradley J. MacIntosh; Eric Achten; Michael A. Chappell; Matthias J.P. van Osch; Xavier Golay; David L. Thomas; Enrico De Vita; Atle Bjørnerud; Aart Nederveen; Jeroen Hendrikse; Iris Asllani; Frederik Barkhof. ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies. NeuroImage 2020, 219, 117031 .

AMA Style

Henk J.M.M. Mutsaerts, Jan Petr, Paul Groot, Pieter Vandemaele, Silvia Ingala, Andrew D. Robertson, Lena Václavů, Inge Groote, Hugo Kuijf, Fernando Zelaya, Owen O’Daly, Saima Hilal, Alle Meije Wink, Ilse Kant, Matthan W.A. Caan, Catherine Morgan, Jeroen de Bresser, Elisabeth Lysvik, Anouk Schrantee, Astrid Bjørnebekk, Patricia Clement, Zahra Shirzadi, Joost P.A. Kuijer, Viktor Wottschel, Udunna C. Anazodo, Dasja Pajkrt, Edo Richard, Reinoud P.H. Bokkers, Liesbeth Reneman, Mario Masellis, Matthias Günther, Bradley J. MacIntosh, Eric Achten, Michael A. Chappell, Matthias J.P. van Osch, Xavier Golay, David L. Thomas, Enrico De Vita, Atle Bjørnerud, Aart Nederveen, Jeroen Hendrikse, Iris Asllani, Frederik Barkhof. ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies. NeuroImage. 2020; 219 ():117031.

Chicago/Turabian Style

Henk J.M.M. Mutsaerts; Jan Petr; Paul Groot; Pieter Vandemaele; Silvia Ingala; Andrew D. Robertson; Lena Václavů; Inge Groote; Hugo Kuijf; Fernando Zelaya; Owen O’Daly; Saima Hilal; Alle Meije Wink; Ilse Kant; Matthan W.A. Caan; Catherine Morgan; Jeroen de Bresser; Elisabeth Lysvik; Anouk Schrantee; Astrid Bjørnebekk; Patricia Clement; Zahra Shirzadi; Joost P.A. Kuijer; Viktor Wottschel; Udunna C. Anazodo; Dasja Pajkrt; Edo Richard; Reinoud P.H. Bokkers; Liesbeth Reneman; Mario Masellis; Matthias Günther; Bradley J. MacIntosh; Eric Achten; Michael A. Chappell; Matthias J.P. van Osch; Xavier Golay; David L. Thomas; Enrico De Vita; Atle Bjørnerud; Aart Nederveen; Jeroen Hendrikse; Iris Asllani; Frederik Barkhof. 2020. "ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies." NeuroImage 219, no. : 117031.

Observational study
Published: 05 December 2019 in PLOS ONE
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HIV-associated cognitive deficiency in perinatally HIV-infected (PHIV) children has been studied in Western countries in a population of which an increasing proportion has been internationally adopted. Studies often lack an appropriate internationally adopted HIV-uninfected control group, potentially confounding the relationship between HIV and cognitive functioning. This study aims to further elucidate the association between treated HIV infection and cognitive development by addressing the background of international adoption. We cross-sectionally studied the impact of HIV on cognition by comparing PHIV children and HIV- uninfected controls, matched for age-, sex-, ethnicity-, socioeconomic status (SES)- and adoption status. We used a standardized neuropsychological test battery to measure intelligence (IQ), and the cognitive domains of processing speed, working memory, executive function, learning ability and visual-motor function and compared outcomes using lineair regression models, adjusted for IQ. We determined cognitive profiles and cognitive impairment by using multivariate normative comparison (MNC) and explored associations with HIV disease- and treatment-related factors. We enrolled fourteen PHIV children (mean age 10.45 years [1.73 SD], 93% adopted from sub-Saharan Africa at a median age of 3.3 years [IQR 2.1–4.2]) and fifteen HIV- uninfected controls. Groups did not clinically nor statistically differ in age, sex, ethnicity, SES, region of birth, adoption status and age at adoption. PHIV scored consistently lower on all cognitive domains and MNC outcomes. Compared to controls, PHIV children had a significant lower IQ (mean 81 [SD 11] versus mean 97 [SD 15], p = 0.005), and a poorer cognitive profile by MNC (Hotelling’s T2 mean -4.36 [SD 5.6] versus mean 0.16 [SD 4.5], p = 0.021), not associated with HIV disease- and treatment-related factors. Two PHIV (14%) and one control (7%) were classified as cognitively impaired (p = 0.598). Findings indicate treated HIV-infection to be independently associated with lower IQ and poorer cognitive profiles in PHIV children, irrespective of a background of international adoption.

ACS Style

M. Van Den Hof; A. M. Ter Haar; H. J. Scherpbier; P. Reiss; F. W. N. M. Wit; K. J. Oostrom; D. Pajkrt. Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption. PLOS ONE 2019, 14, e0224930 .

AMA Style

M. Van Den Hof, A. M. Ter Haar, H. J. Scherpbier, P. Reiss, F. W. N. M. Wit, K. J. Oostrom, D. Pajkrt. Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption. PLOS ONE. 2019; 14 (12):e0224930.

Chicago/Turabian Style

M. Van Den Hof; A. M. Ter Haar; H. J. Scherpbier; P. Reiss; F. W. N. M. Wit; K. J. Oostrom; D. Pajkrt. 2019. "Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption." PLOS ONE 14, no. 12: e0224930.

Preprint content
Published: 17 November 2019
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Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners.The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. The toolbox adheres to previously defined international standards for data structure, provenance, and best analysis practice.ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow.ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts to increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

ACS Style

Henk Jmm Mutsaerts; Jan Honza Petr; Paul Fc Groot; Pieter Van De Maele; Silvia Ingala; Andrew D Robertson; Lena Václavů; Inge Groote; Hugo Kuijf; Fernando Zelaya; Owen O’Daly; Saima Hilal; Alle Meije Wink; Ilse Kant; Matthan W.A. Caan; Catherine Morgan; Jeroen De Bresser; Elisabeth Lysvik; Anouk Schrantee; Astrid Bjørnebekk; Patricia Clement; Zahra Shirzadi; Joost P.A. Kuijer; Udunna C. Anazodo; Dasja Pajkrt; Edo Richard; Reinoud P.H. Bokkers; Liesbeth Reneman; Mario Masellis; Matthias Guenther; Bradley J. MacIntosh; Eric Achten; Michael A. Chappell; Matthias J.P. Van Osch; Xavier Golay; David L. Thomas; Enrico De Vita; Atle Bjørnerud; Aart Nederveen; Jeroen Hendrikse; Iris Asllani; Frederik Barkhof. ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies. 2019, 845842 .

AMA Style

Henk Jmm Mutsaerts, Jan Honza Petr, Paul Fc Groot, Pieter Van De Maele, Silvia Ingala, Andrew D Robertson, Lena Václavů, Inge Groote, Hugo Kuijf, Fernando Zelaya, Owen O’Daly, Saima Hilal, Alle Meije Wink, Ilse Kant, Matthan W.A. Caan, Catherine Morgan, Jeroen De Bresser, Elisabeth Lysvik, Anouk Schrantee, Astrid Bjørnebekk, Patricia Clement, Zahra Shirzadi, Joost P.A. Kuijer, Udunna C. Anazodo, Dasja Pajkrt, Edo Richard, Reinoud P.H. Bokkers, Liesbeth Reneman, Mario Masellis, Matthias Guenther, Bradley J. MacIntosh, Eric Achten, Michael A. Chappell, Matthias J.P. Van Osch, Xavier Golay, David L. Thomas, Enrico De Vita, Atle Bjørnerud, Aart Nederveen, Jeroen Hendrikse, Iris Asllani, Frederik Barkhof. ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies. . 2019; ():845842.

Chicago/Turabian Style

Henk Jmm Mutsaerts; Jan Honza Petr; Paul Fc Groot; Pieter Van De Maele; Silvia Ingala; Andrew D Robertson; Lena Václavů; Inge Groote; Hugo Kuijf; Fernando Zelaya; Owen O’Daly; Saima Hilal; Alle Meije Wink; Ilse Kant; Matthan W.A. Caan; Catherine Morgan; Jeroen De Bresser; Elisabeth Lysvik; Anouk Schrantee; Astrid Bjørnebekk; Patricia Clement; Zahra Shirzadi; Joost P.A. Kuijer; Udunna C. Anazodo; Dasja Pajkrt; Edo Richard; Reinoud P.H. Bokkers; Liesbeth Reneman; Mario Masellis; Matthias Guenther; Bradley J. MacIntosh; Eric Achten; Michael A. Chappell; Matthias J.P. Van Osch; Xavier Golay; David L. Thomas; Enrico De Vita; Atle Bjørnerud; Aart Nederveen; Jeroen Hendrikse; Iris Asllani; Frederik Barkhof. 2019. "ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies." , no. : 845842.

Review
Published: 14 November 2019 in Viruses
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Parechovirus A is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on Parechovirus A epidemiology and pathogenesis. This review aims to explore the Parechovirus A literature and highlight the differences between Parechovirus A genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on Parechovirus A research is provided.

ACS Style

Adithya Sridhar; Eveliina Karelehto; Lieke Brouwer; Dasja Pajkrt; Katja C. Wolthers. Parechovirus A Pathogenesis and the Enigma of Genotype A-3. Viruses 2019, 11, 1062 .

AMA Style

Adithya Sridhar, Eveliina Karelehto, Lieke Brouwer, Dasja Pajkrt, Katja C. Wolthers. Parechovirus A Pathogenesis and the Enigma of Genotype A-3. Viruses. 2019; 11 (11):1062.

Chicago/Turabian Style

Adithya Sridhar; Eveliina Karelehto; Lieke Brouwer; Dasja Pajkrt; Katja C. Wolthers. 2019. "Parechovirus A Pathogenesis and the Enigma of Genotype A-3." Viruses 11, no. 11: 1062.

Journal article
Published: 29 May 2019 in Scientific Reports
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Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8-18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.

ACS Style

C. Blokhuis; C. F. W. Peeters; S. Cohen; H. J. Scherpbier; T. W. Kuijpers; P. Reiss; N. A. Kootstra; C. E. Teunissen; D. Pajkrt. Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV. Scientific Reports 2019, 9, 8004 .

AMA Style

C. Blokhuis, C. F. W. Peeters, S. Cohen, H. J. Scherpbier, T. W. Kuijpers, P. Reiss, N. A. Kootstra, C. E. Teunissen, D. Pajkrt. Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV. Scientific Reports. 2019; 9 (1):8004.

Chicago/Turabian Style

C. Blokhuis; C. F. W. Peeters; S. Cohen; H. J. Scherpbier; T. W. Kuijpers; P. Reiss; N. A. Kootstra; C. E. Teunissen; D. Pajkrt. 2019. "Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV." Scientific Reports 9, no. 1: 8004.

Research article
Published: 30 January 2018 in PLOS Medicine
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Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. Children with perinatal HIV aged 6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4–9.3) years; 35% of children aged 400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

ACS Style

The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord; Ali Judd; Elizabeth Chappell; Anna Turkova; Sophie Le Coeur; Antoni Noguera-Julian; Tessa Goetghebuer; Katja Doerholt; Luisa Galli; Dasja Pajkrt; Laura Marques; Intira Jeannie Collins; Diana M. Gibb; Maria Isabel González Tome; Marisa Navarro; Josiane Warszawski; Christoph Königs; Vana Spoulou; Filipa Prata; Elena Chiappini; Lars Naver; Carlo Giaquinto; Claire Thorne; Magdalena Marczyńska; Liubov Okhonskaia; Klara Posfay-Barbe; Pradthana Ounchanum; Pornchai Techakunakorn; Galina Kiseleva; Ruslan Malyuta; Alla Volokha; Luminita Ene; Ruth Goodall. Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study. PLOS Medicine 2018, 15, e1002491 .

AMA Style

The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord, Ali Judd, Elizabeth Chappell, Anna Turkova, Sophie Le Coeur, Antoni Noguera-Julian, Tessa Goetghebuer, Katja Doerholt, Luisa Galli, Dasja Pajkrt, Laura Marques, Intira Jeannie Collins, Diana M. Gibb, Maria Isabel González Tome, Marisa Navarro, Josiane Warszawski, Christoph Königs, Vana Spoulou, Filipa Prata, Elena Chiappini, Lars Naver, Carlo Giaquinto, Claire Thorne, Magdalena Marczyńska, Liubov Okhonskaia, Klara Posfay-Barbe, Pradthana Ounchanum, Pornchai Techakunakorn, Galina Kiseleva, Ruslan Malyuta, Alla Volokha, Luminita Ene, Ruth Goodall. Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study. PLOS Medicine. 2018; 15 (1):e1002491.

Chicago/Turabian Style

The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord; Ali Judd; Elizabeth Chappell; Anna Turkova; Sophie Le Coeur; Antoni Noguera-Julian; Tessa Goetghebuer; Katja Doerholt; Luisa Galli; Dasja Pajkrt; Laura Marques; Intira Jeannie Collins; Diana M. Gibb; Maria Isabel González Tome; Marisa Navarro; Josiane Warszawski; Christoph Königs; Vana Spoulou; Filipa Prata; Elena Chiappini; Lars Naver; Carlo Giaquinto; Claire Thorne; Magdalena Marczyńska; Liubov Okhonskaia; Klara Posfay-Barbe; Pradthana Ounchanum; Pornchai Techakunakorn; Galina Kiseleva; Ruslan Malyuta; Alla Volokha; Luminita Ene; Ruth Goodall. 2018. "Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study." PLOS Medicine 15, no. 1: e1002491.

Journal article
Published: 21 September 2017 in Scientific Reports
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Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015. The rabbit antiserum neutralized all HPeV3 isolates whereas the neutralization capacity of the IVIG batches varied, and the mAb exclusively neutralized the A308/99 strain. Mapping of the amino acid variation among a subset of the HPeV3 strains on an HPeV3 capsid structure revealed that the majority of the surface-exposed amino acid variation was located in the VP1. Furthermore, amino acid mutations in a mAb AT12-015-resistant HPeV3 A308/99 variant indicated the location for potential antigenic determinants. Virus aggregation and the observed antigenic diversity in HPeV3 can explain the varying levels of nAb seropositivity reported in previous studies.

ACS Style

Eveliina Karelehto; Sabine Van Der Sanden; James A. Geraets; Aušra Domanska; Lonneke Van Der Linden; Dionne Hoogendoorn; Gerrit Koen; Hetty Van Eijk; Shabih Shakeel; Tim Beaumont; Menno De Jong; Dasja Pajkrt; Sarah J. Butcher; Katja C. Wolthers. Strain-dependent neutralization reveals antigenic variation of human parechovirus 3. Scientific Reports 2017, 7, 1 -10.

AMA Style

Eveliina Karelehto, Sabine Van Der Sanden, James A. Geraets, Aušra Domanska, Lonneke Van Der Linden, Dionne Hoogendoorn, Gerrit Koen, Hetty Van Eijk, Shabih Shakeel, Tim Beaumont, Menno De Jong, Dasja Pajkrt, Sarah J. Butcher, Katja C. Wolthers. Strain-dependent neutralization reveals antigenic variation of human parechovirus 3. Scientific Reports. 2017; 7 (1):1-10.

Chicago/Turabian Style

Eveliina Karelehto; Sabine Van Der Sanden; James A. Geraets; Aušra Domanska; Lonneke Van Der Linden; Dionne Hoogendoorn; Gerrit Koen; Hetty Van Eijk; Shabih Shakeel; Tim Beaumont; Menno De Jong; Dasja Pajkrt; Sarah J. Butcher; Katja C. Wolthers. 2017. "Strain-dependent neutralization reveals antigenic variation of human parechovirus 3." Scientific Reports 7, no. 1: 1-10.