Background The aim of this systematic review was to evaluate current inter-modality agreement of noninvasive clinical intraventricular flow (IVF) assessment with 3 emerging imaging modalities:... Show moreBackground The aim of this systematic review was to evaluate current inter-modality agreement of noninvasive clinical intraventricular flow (IVF) assessment with 3 emerging imaging modalities: echocardiographic particle image velocimetry (EPIV), vector flow mapping (VFM), and 4-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR). Methods We performed a systematic literature review in the databases EMBASE, Medline OVID and Cochrane Central for identification of studies evaluating left ventricular (LV) flow patterns using one of these flow visualization modalities. Of the 2224 initially retrieved records, 10 EPIV, 23 VFM, and 25 4D flow CMR studies were included in the final analysis. Results Vortex parameters were more extensively studied with EPIV, while LV energetics and LV transport mechanics were mainly studied with 4D flow CMR, and LV energy loss and vortex circulation were implemented by VFM studies. Pooled normative values are provided for these parameters. The meta- analysis for the values of two vortex morphology parameters, vortex length and vortex depth, failed to reveal a significant change between heart failure patients and healthy controls. Conclusion Agreement between the different modalities studying intraventricular flow is low and different methods of measurement and reporting were used among studies. A multimodality framework with a standardized set of flow parameters is necessary for implementation of noninvasive flow visualization in daily clinical practice. The full potential of noninvasive flow visualization in addition to diagnostics could also include guiding medical or interventional treatment. Show less
Dou, Y.Y.; Jansen, D.T.S.L.; Bosch, A. van den; Man, R.A. de; Montfoort, N. van; Araman, C.; ... ; Buschow, S.I. 2020
Synthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core... Show moreSynthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core protein derived SLP was capable of boosting CD4(+ )and CD8(+) T cell responses in the presence of a TLR2-ligand in chronic HBV patients ex vivo. For optimal efficacy of a therapeutic vaccine in vivo, adjuvants can be conjugated to the SLP to ensure delivery of both the antigen and the co-stimulatory signal to the same antigen-presenting cell (APC). Dendritic cells (DCs) express the receptor for the adjuvant and are optimally equipped to efficiently process and present the SLP-contained epitopes to T cells. Here, we investigated TLR2-ligand conjugation of the prototype HBV-core SLP. Results indicated that TLR2-ligand conjugation reduced cross-presentation efficiency of the SLP-contained epitope by both monocyte-derived and naturally occurring DC subsets. Importantly, cross-presentation was improved after optimization of the conjugate by either shortening the SLP or by placing a valine-citrulline linker between the TLR2-ligand and the long SLP, to facilitate endosomal dissociation of SLP and TLR2-ligand after uptake. HBV-core SLP conjugates also triggered functional patient T cell responses ex vivo. These results provide an import step forward in the design of a therapeutic SLP-based vaccine to cure chronic HBV. Show less
Dou, Y.; Jansen, D.T.S.L.; Bosch, A. van den; Man, R.A. de; Montfoort, N. van; Araman, C.; ... ; Buschow, S.I. 2020
Synthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core... Show moreSynthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core protein derived SLP was capable of boosting CD4+ and CD8+ T cell responses in the presence of a TLR2-ligand in chronic HBV patients ex vivo. For optimal efficacy of a therapeutic vaccine in vivo, adjuvants can be conjugated to the SLP to ensure delivery of both the antigen and the co-stimulatory signal to the same antigen-presenting cell (APC). Dendritic cells (DCs) express the receptor for the adjuvant and are optimally equipped to efficiently process and present the SLP-contained epitopes to T cells. Here, we investigated TLR2-ligand conjugation of the prototype HBV-core SLP. Results indicated that TLR2-ligand conjugation reduced cross-presentation efficiency of the SLP-contained epitope by both monocyte-derived and naturally occurring DC subsets. Importantly, cross-presentation was improved after optimization of the conjugate by either shortening the SLP or by placing a valine-citrulline linker between the TLR2-ligand and the long SLP, to facilitate endosomal dissociation of SLP and TLR2-ligand after uptake. HBV-core SLP conjugates also triggered functional patient T cell responses ex vivo. These results provide an import step forward in the design of a therapeutic SLP-based vaccine to cure chronic HBV. Show less
Dou, Y.Y.; Montfoort, N. van; Bosch, A. van den; Janssen, H.L.A.; Man, R.A. de; Buschow, S.I.; Woltman, A.M. 2019
In this paper, we address query-based summarization of discussion threads. New users can profit from the information shared in the forum, Please check if the inserted city and country names in the... Show moreIn this paper, we address query-based summarization of discussion threads. New users can profit from the information shared in the forum, Please check if the inserted city and country names in the affiliations are correct. if they can find back the previously posted information. However, discussion threads on a single topic can easily comprise dozens or hundreds of individual posts. Our aim is to summarize forum threads given real web search queries. We created a data set with search queries from a discussion forum’s search engine log and the discussion threads that were clicked by the user who entered the query. For 120 thread–query combinations, a reference summary was made by five different human raters. We compared two methods for automatic summarization of the threads: a query-independent method based on post features, and Maximum Marginal Relevance (MMR), a method that takes the query into account. We also compared four different word embeddings representations as alternative for standard word vectors in extractive summarization. We find (1) that the agreement between human summarizers does not improve when a query is provided that: (2) the query-independent post features as well as a centroid-based baseline outperform MMR by a large margin; (3) combining the post features with query similarity gives a small improvement over the use of post features alone; and (4) for the word embeddings, a match in domain appears to be more important than corpus size and dimensionality. However, the differences between the models were not reflected by differences in quality of the summaries created with help of these models. We conclude that query-based summarization with web queries is challenging because the queries are short, and a click on a result is not a direct indicator for the relevance of the result. Show less
Beeksma, M.; Verberne, S.; Bosch, A. van den; Hendrickx, I.; Das, E.; Groenewoud, S. 2019
{ extcopyright} 2017 The Author(s) In this paper we address extractive summarization of long threads in online discussion fora. We present an elaborate user evaluation study to determine human... Show more{ extcopyright} 2017 The Author(s) In this paper we address extractive summarization of long threads in online discussion fora. We present an elaborate user evaluation study to determine human preferences in forum summarization and to create a reference data set. We showed long threads to ten different raters and asked them to create a summary by selecting the posts that they considered to be the most important for the thread. We study the agreement between human raters on the summarization task, and we show how multiple reference summaries can be combined to develop a successful model for automatic summarization. We found that although the inter-rater agreement for the summarization task was slight to fair, the automatic summarizer obtained reasonable results in terms of precision, recall, and ROUGE. Moreover, when human raters were asked to choose between the summary created by another human and the summary created by our model in a blind side-by-side comparison, they judged the model's summary equal to or better than the human summary in over half of the cases. This shows that even for a summarization task with low inter-rater agreement, a model can be trained that generates sensible summaries. In addition, we investigated the potential for personalized summarization. However, the results for the three raters involved in this experiment were inconclusive. We release the reference summaries as a publicly available dataset. Show less
Laar, L. van de; Bosch, A. van den; Kooij, S.W. van der; Janssen, H.L.A.; Coffer, P.J.; Kooten, C. van; Woltman, A.M. 2010
The plastic role of dendritic cells (DCs) in the regulation of immune responses has made them interesting targets for immunotherapy, but also for pathogens or tumors to evade immunity. Functional... Show moreThe plastic role of dendritic cells (DCs) in the regulation of immune responses has made them interesting targets for immunotherapy, but also for pathogens or tumors to evade immunity. Functional alterations of DCs are often ascribed to manipulation of canonical NF-kappa B activity. However, though this pathway has been linked to murine myeloid DC biology, a detailed analysis of its importance in human myeloid DC differentiation, survival, maturation, and function is lacking. The myeloid DC subsets include interstitial DCs and Langerhans cells. In this study, we investigated the role of canonical NF-kappa B in human myeloid DCs generated from monocytes (monocyte-derived DCs [mo-DCs]) or CD34(+) progenitors (CD34-derived myeloid DCs [CD34-mDCs]). Inhibition of NF-kappa B activation during and after mo-DC, CD34-interstitial DC, or CD34-Langerhans cell differentiation resulted in apoptosis induction associated with caspase 3 activation and loss of mitochondrial transmembrane potential. Besides regulating survival, canonical NF-kappa B activity was required for the acquisition of a DC phenotype. Despite phenotypic differences, however, Ag uptake, costimulatory molecule and CCR7 expression, as well as T cell stimulatory capacity of cells generated under NF-kappa B inhibition were comparable to control DCs, indicating that canonical NF-kappa B activity during differentiation is redundant for the development of functional APCs. However, both mo-DC and CD34-mDC functionality were reduced by NF-kappa B inhibition during activation. In conclusion, canonical NF-kappa B activity is essential for the development and function of mo-DCs as well as CD34-mDCs. Insight into the role of this pathway may help in understanding how pathogens and tumors escape immunity and aid in developing novel treatment strategies aiming to interfere with human immune responses. The Journal of Immunology, 2010, 185: 7252-7261. Show less
