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Johansson, C.; Hunt, H.; Signorelli, M.; Edfors, F.; Hober, A.; Svensson, A.S.; ... ; Szigyarto, C.A. 2023

Orthogonal proteomics methods warrant the development of Duchenne muscular dystrophy biomarkers

Article / Letter to editor

open access

BackgroundMolecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While... Show moreBackgroundMolecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, their translation to clinical use is difficult due to the lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy was developed and used to assess the reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD). DMD is a monogenic incurable disease characterized by progressive muscle damage that currently lacks reliable and specific disease monitoring tools.MethodsTwo technological platforms are used to detect and quantify the biomarkers in 72 longitudinally collected serum samples from DMD patients at 3 to 5 timepoints. Quantification of the biomarkers is achieved by detection of the same biomarker fragment either through interaction with validated antibodies in immuno-assays or through quantification of peptides by Parallel Reaction Monitoring Mass Spectrometry assay (PRM-MS).ResultsFive, out of ten biomarkers previously identified by affinity-based proteomics methods, were confirmed to be associated with DMD using the mass spectrometry-based method. Two biomarkers, carbonic anhydrase III and lactate dehydrogenase B, were quantified with two independent methods, sandwich immunoassays and PRM-MS, with Pearson correlations of 0.92 and 0.946 respectively. The median concentrations of CA3 and LDHB in DMD patients was elevated in comparison to those in healthy individuals by 35- and 3-fold, respectively. Levels of CA3 vary between 10.26 and 0.36 ng/ml in DMD patients whereas those of LDHB vary between 15.1 and 0.8 ng/ml.ConclusionsThese results demonstrate that orthogonal assays can be used to assess the analytical reliability of biomarker quantification assays, providing a means to facilitate the translation of biomarkers to clinical practice. This strategy also warrants the development of the most relevant biomarkers, markers that can be reliably quantified with different proteomics methods. Show less

Tol, L.S. van; Smaling, H.J.A.; Janus, S.I.M.; Caljouw, M.A.A.; Achterberg, W.P. 2023

Priority measures to prevent infections and maintain residents' well-being during COVID-19 outbreaks in nursing homes: consensus among staff and resident representatives determined in an online nominal group technique study

Article / Letter to editor

open access

Background: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and... Show moreBackground: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and residents' well-being, and about nursing home residents' autonomy in COVID-19 policymaking.Objective: This study explores consensus among nursing home staff about which measures they found to be most important in contributing to preventing infections and to maintaining well-being of residents during COVID-19 outbreaks. In addition, this study explores the decision-making processes regarding COVID-19 measures and the involvement of residents or their representatives.Design: Mixed methods based on an online nominal group technique. Setting(s): Dutch nursing homes, June-November 2020.Participants: Managers, policy advisors, elderly care physicians, psychologists, a spiritual coun-selor, nurses, care assistants, and resident representatives (N = 35).Methods: Four panels from the viewpoint of infection prevention, and four panels from the viewpoint of well-being were performed with 3 to 7 participants per panel. Participants indi-vidually selected the measure they found most important, discussed these measures together in an online conversation, and rated the importance and urgency of these measures during COVID-19 outbreaks on a 5-point Likert scale. The measures that were rated as (very) important and (very) urgent by all members of that panel were defined as 'prioritized in consensus'. Panels also dis-cussed the decision-making process regarding COVID-19 measures and the involvement of resi-dents or their representatives. These conversations were transcribed verbatim and thematically coded using an inductive approach.Results: The infection prevention panels prioritized isolation measures; testing measures; testing and isolation combinations; use of personal protective equipment around (suspected) infected Show less

Brust, M.; Gebhardt, W.A.; Bruggen, S. van; Janssen, V.; Numans, M.E.; Jong, J.C.K.D. 2023

Making sense of a myocardial infarction in relation to changing lifestyle in the five months following the event: an interpretative phenomenological analysis

Article / Letter to editor

open access

ObjectivePrevious research has shown that experiencing an acute cardiac event, such as a myocardial infarction (MI), can lead to lifestyle changes. This study aimed to explore the potential of a MI as a ‘teachable moment’ (TM) for positive lifestyle changes and to identify psychosocial sensemaking processes that facilitate or hinder the presence of a TM.MethodWe conducted semi-structured interviews with 14 patients who suffered their first MI and were hospitalized in a larger Dutch city. Participants were interviewed twice, respectively one and five months after their hospitalization. They were encouraged to explain how they experienced their MI and how this had affected their lifestyle. We used an Interpretative Phenomenological Analysis approach to the data collection and analysis.FindingsThe participants varied in their willingness to adopt a healthy lifestyle due to their MI. Most participants experienced their event as a TM for changing specific health behaviors, for example facilitated by reflecting on self-concept or social roles and by constructing and comprehending a personal narrative of their MI. Some participants struggled to follow through on their intentions to change their behavior, for example because of a negative attitude towards a healthy behavior or because they perceived it as incongruent to their identity. Only three participants maintained most former health behaviors, for example because they failed to acknowledge their MI as severe or because of earlier life events that elicited more blunted cognitive responses.ConclusionCardiac patients may experience a TM, which is the consequence of interrelated processes of psychosocial sensemaking. As this does not occur at a singular time point, we suggest using the term ‘teachable window’ rather than ‘moment’. Given these findings, there is a window of opportunity to provide continuous psychosocial and lifestyle support during and after hospitalization for acute cardiac events.

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Swets, M.C.; Termorshuizen, F.; Keizer, N.F. de; Paassen, J. van; Palmen, M.; Visser, L.G.; ... ; Groeneveld, G.H. 2023

Influenza season and outcome after elective cardiac surgery: an observational cohort study

Article / Letter to editor

open access

BackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral... Show moreBackgroundAn asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients.MethodsCardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pao2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality.ResultsA total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pao2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46).ConclusionsPatients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications. Show less

Steur, W.O. de 2023

Quality assessment and multimodality in gastric cancer treatment

Doctoral Thesis

metadata only

Kopland, M.C.G.; Vrabel, K.; Landt, M.S.O.; Hoffart, A.; Johnson, S.U.; Giltay, E.J. 2023

Breaking the cycle: Identifying key symptom pathways of eating disorders and the influence of childhood maltreatment

Article / Letter to editor

open access

BackgroundMost network analyses on central symptoms in eating disorders (EDs) have been cross-sectional. Longitudinal within-person analyses of therapy processes are scarce. Our aim was to... Show moreBackgroundMost network analyses on central symptoms in eating disorders (EDs) have been cross-sectional. Longitudinal within-person analyses of therapy processes are scarce. Our aim was to investigate central change processes in therapy in a transdiagnostic sample, considering the influence of childhood maltreatment.MethodWe employed dynamic time warping analyses to identify clusters of symptoms that tended to change similarly across therapy on a within-person level. Symptoms were measured by a 28-item Eating Disorder Examination Questionnaire (EDE-Q). Furthermore, we examined the temporal direction of symptom change to identify symptoms that tended to precede and predict other symptoms. Finally, we estimated two directed, temporal networks in patients with and without a history of childhood maltreatment.ResultsOur analysis included 122 ED patients (mean age = 30.9, SD = 9.7; illness duration = 14.2 years, SD = 8.9; prior treatment = 5.6 years, SD = 5.1). The initial network revealed three robust clusters of symptoms over time: (1) ED behavior, (2) inhibition, and (3) cognitions and feelings about body and weight. Overvaluation of shape had the highest out-strength preceding and predicting other symptoms. Dissatisfaction with weight preceded and predicted other symptoms in the maltreatment network. The non-maltreatment network showed a similar structure to the transdiagnostic network.ConclusionTargeting and monitoring feelings and cognitions related to shape may be crucial for achieving lasting symptom improvement in a transdiagnostic sample. Furthermore, our findings highlight the need for further investigation into the different processes driving EDs based on maltreatment status. Show less

Groeneveldt, P.C. 2023

Harnessing the immunostimulatory properties of oncolytic reovirus for anticancer immunotherapy

Doctoral Thesis

some documents under embargo until 2024-11-23

In this thesis, we unraveled the immunostimulatory potential of oncolytic reovirus and investigated how these immunostimulatory characteristics could be exploited for effective anticancer... Show moreIn this thesis, we unraveled the immunostimulatory potential of oncolytic reovirus and investigated how these immunostimulatory characteristics could be exploited for effective anticancer immunotherapy. We demonstrated that administration of oncolytic reovirus does not lead to strong oncolytic effects in tumors, but instead unleashes a very potent immune response, including the priming of reovirus-specific CD8 T cells. We showed that these reovirus-specific CD8 T cells can be effectively employed for anticancer immunotherapy, by either bypassing their specificity (with CD3-bsAbs) or by exploiting their specificity (via installing a preinduced pool using SLP vaccination). Besides the induction of reovirus-specific CD8 T cells, reovirus administration also leads to very fast B-cell responses. We demonstrated that the presence of neutralizing antibodies (NAbs) restricts the use of reovirus as an oncolytic agent, but that the reovirus-induced influx of CD8 T cells is retained and the use of reovirus in combination with T-cell-based immunotherapy can still result in potent antitumor responses. Lastly, we showed that blockade of Transforming Growth Factor-β (TGF-β) does not impair reovirus infection and reovirus-induced ISG expression or the reovirus-induced attraction and activation of T cells, but that intrinsic differences between preclinical tumor models can determine if TGF-β blockade is a beneficial addition to combined reovirus and T-cell-based immunotherapy. Show less

Does, F.H.S. van der; Nagamine, M.; Wee, N.J.A. van der; Chiba, T.; Edo, N.; Kitano, M.; ... ; Giltay, E.J. 2023

PTSD Symptom dynamics after the great east japan earthquake: mapping the temporal structure using Dynamic Time Warping

Article / Letter to editor

open access

Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The... Show moreBackground: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system. Show less

Sluckin, T.C. 2023

Lateral lymph nodes in rectal cancer

Doctoral Thesis

some documents under embargo until 2027-11-21

There is a lack of knowledge regarding the definition, classification and appropriate treatment of malignant lateral lymph nodes in patients with (locally advanced) rectal cancer. This thesis aimed... Show moreThere is a lack of knowledge regarding the definition, classification and appropriate treatment of malignant lateral lymph nodes in patients with (locally advanced) rectal cancer. This thesis aimed to increase this knowledge and improve treatment practices for this population. Show less

Meeuwsen, E.G.; Kleijn, M.J.J. de; Boer, E.M. de; Koçak, A.F.; Chavannes, N.H.; Meijer, E. 2023

"Boy, what are we all doing? We are crazy, really crazy" a qualitative study of psychosocial processes around an atypical one-time smoking cessation course

Article / Letter to editor

open access

BackgroundSmoking prevalence is still high, which requires effective interventions that help many people who smoke at once in addition to time-consuming individual interventions. ‘I Quit’ is a... Show moreBackgroundSmoking prevalence is still high, which requires effective interventions that help many people who smoke at once in addition to time-consuming individual interventions. ‘I Quit’ is a large-scale smoking cessation course in The Netherlands. This qualitative study explored I Quit participants’ experiences during and after the course, and perceptions of whether and how the course may have altered their smoking behavior.MethodsWe performed individual semi-structured interviews with course participants (N = 21) who had either quit successfully, attempted to quit but relapsed, or had continued to smoke after ‘I Quit’. Shortly after qualitative data collection was completed, Foundation I Quit was accused in the media of a number of misbehaviors. Although unplanned, this provided a unique opportunity to explore participants’ views on alleged fraud in a second round of interviews (N = 16). Data were collected from 2016 to 2018.ResultsQualitative findings showed two psychosocial processes that may explain smoking cessation after course attendance. First, the confrontation with a large group of people who smoke, of whom some had already developed smoking-related complaints, triggered identity processes both towards and away from quitting smoking. Unorthodox methods used in the course appeared to trigger identity processes. Second, social support after the course from participants’ own social network facilitated maintenance of successful quitting. The study also found that interview participants’ opinions on I Quit did not change much after allegations of fraud in the media.ConclusionsFindings suggest that a one-time course might initiate psychosocial processes that could help certain smokers to gain motivation to quit, requiring a minimum of resources. Identity processes triggered by the course seem tricky as people have different ways of dealing with identity threat, some of which can be counterproductive and even result in more difficulty quitting. More research is needed to examine who can benefit from a one-time course, and who needs more support in order to quit successfully. Show less

Amaruddin, A.I. 2023

Gut environment and socioeconomic status: a study of children in urban area of Makassar

Doctoral Thesis

open access

Although urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas... Show moreAlthough urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas including health. In particular, urban areas in low and middle incomecountries (LMIC), often see a widening gap in economic growth which contributes to healthdisparities between wealthy and underprivileged children. Several studies have establishedthe association between socioeconomic status (SES) and child health, showing that childrenof low-income parents had poorer health status. The rise of non-communicable diseases,the persistence of communicable disease, and the challenge of re-emerging diseases arecurrently a burden in developing countries. Given the rapid increases of urbanization andurban poverty in several developing countries including Indonesia, it is important to elaborateto what extent SES affects child health. We have done so, in relation to outcome of BCGvaccination, atopic sensitization, and intestinal barrier function. We have also investigatedthe interaction between intestinal parasitic infections and bacterial gut microbiota in orderto be able to delineate the contribution of this interaction on the function of intestinal barrier. Show less

Muyselaar-Jellema, J.Z.; Querido, S.J. 2023

Twelve tips for having more meaningful conversations with medical students on specialty career choice

Article / Letter to editor

open access

Making a career choice is a multifaceted process and support for medical students on career choice is pivotal. Not all medical schools have programs or guidelines to support having meaningful... Show moreMaking a career choice is a multifaceted process and support for medical students on career choice is pivotal. Not all medical schools have programs or guidelines to support having meaningful conversations with medical students. However, medical students have questions and are seeking answers. This article presents twelve tips for having meaningful conversations with medical students for educators, mentors and internship tutors. The twelve tips have been grouped into three categories: the conversation, the reflection and the actions students can take in the process of their specialty career choice. Show less

Scheefhals, Z.T.M.; Vries, E.F. de; Struijs, J.N.; Numans, M.E.; Exel, J. van 2023

Stakeholder perspectives on payment reform in maternity care in the Netherlands: a Q-methodology study

Article / Letter to editor

open access

Based on theoretical notions, there is consensus that alternative payment models to the common fee-for-service model have the potential to improve healthcare quality through increased collaboration... Show moreBased on theoretical notions, there is consensus that alternative payment models to the common fee-for-service model have the potential to improve healthcare quality through increased collaboration and reduced under- and overuse. This is particularly relevant for maternity care in the Netherlands because perinatal mortality rates are relatively high in comparison to other Western countries. Therefore, an experiment with bundled payments for maternity care was initiated in 2017. However, the uptake of this alternative payment model remains low, as also seen in other countries, and fee-for-service models prevail. A deeper understanding of stakeholders' perspectives on payment reform in maternity care is necessary to inform policy makers about the obstacles to implementing alternative payment models and potential ways forward. We conducted a Q-methodology study to explore perspectives of stakeholders (postpartum care managers, midwives, gynecologists, managers, health insurers) in maternity care in the Netherlands on payment reform. Participants were asked to rank a set of statements relevant to payment reform in maternity care and explain their ranking during an interview. Factor analysis was used to identify patterns in the rankings of statements. We identified three distinct perspectives on payment reform in maternity care. One general perspective, broadly supported within the sector, focusing mainly on outcomes, and two complementary perspectives, one focusing more on equality and one focusing more on collaboration. This study shows there is consensus among stakeholders in maternity care in the Netherlands that payment reform is required. However, stakeholders have different views on the purpose and desired design of the payment reform and set different conditions. Working towards payment reform in co-creation with all involved parties may improve the general attitude towards payment reform, may enhance the level of trust among stakeholders, and may contribute to a higher uptake in practice. Show less

Caspers, I.A.; Biesma, H.D.; Wiklund, K.; Pontén, F.; Lind, P.; Nordsmark, M.; ... ; Grieken, N.C.T. van 2023

Effect of preoperative chemotherapy on the histopathological classification of gastric cancer

Article / Letter to editor

open access

BackgroundIn the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative... Show moreBackgroundIn the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment.MethodsHistological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and “other” subtypes of GC were analyzed.ResultsIn total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and “other” subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the “other” subtypes, respectively.ConclusionOur results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible. Show less

Hondelink, L.M. 2023

Diagnostic challenges of today's lung cancer pathology: personalizing therapy by immunohistochemical and molecular biomarkers

Doctoral Thesis

open access

How to screen for molecular and immunotherapy targets in non-small cell lung cancer.

Carvalho, P.C.G.D.; Hirata, T.D.C.; Alves, L.Y.M.; Moscardini, I.F.; Nascimento, A.P.B. do; Costa-Martins, A.G.; ... ; VSV-EBOPLUS Consortia 2023

Baseline gene signatures of reactogenicity to Ebola vaccination: a machine learning approach across multiple cohorts

Article / Letter to editor

open access

Introduction: The rVSVDG-ZEBOV-GP (Ervebo®) vaccine is both immunogenic and protective against Ebola. However, the vaccine can cause a broad range of transient adverse reactions, from headache to... Show moreIntroduction: The rVSVDG-ZEBOV-GP (Ervebo®) vaccine is both immunogenic and protective against Ebola. However, the vaccine can cause a broad range of transient adverse reactions, from headache to arthritis. Identifying baseline reactogenicity signatures can advance personalized vaccinology and increase our understanding of the molecular factors associated with such adverse events.Methods: In this study, we developed a machine learning approach to integrate prevaccination gene expression data with adverse events that occurred within 14 days post-vaccination.Results and Discussion: We analyzed the expression of 144 genes across 343 blood samples collected from participants of 4 phase I clinical trial cohorts: Switzerland, USA, Gabon, and Kenya. Our machine learning approach revealed 22 key genes associated with adverse events such as local reactions, fatigue, headache, myalgia, fever, chills, arthralgia, nausea, and arthritis, providing insights into potential biological mechanisms linked to vaccine reactogenicity. Show less

Ge, Y.; Roon, L. van; Chen, H.S.; Methorst, R.; Paton, M.; DeRuiter, M.C.; ... ; Jongbloed, M.R.M. 2023

Low-input nucleus isolation and multiplexing with barcoded antibodies of mouse sympathetic ganglia for single-nucleus RNA sequencing

Article / Letter to editor

metadata only

The cardiac autonomic nervous system is crucial in controlling cardiac function, such as heart rate and cardiac contractility, and is divided into sympathetic and parasympathetic branches. Normally... Show moreThe cardiac autonomic nervous system is crucial in controlling cardiac function, such as heart rate and cardiac contractility, and is divided into sympathetic and parasympathetic branches. Normally, there is a balance between these two branches to maintain homeostasis. However, cardiac disease states such as myocardial infarction, heart failure, and hypertension can induce the remodeling of cells involved in cardiac innervation, which is associated with an adverse clinical outcome.Although there are vast amounts of data for the histological structure and function of the cardiac autonomic nervous system, its molecular biological architecture in health and disease is still enigmatic in many aspects. Novel technologies such as single-cell RNA sequencing (scRNA-seq) hold promise for the genetic characterization of tissues at single-cell resolution. However, the relatively large size of neurons may impede the standardized use of these techniques. Here, this protocol exploits droplet-based single-nucleus RNA sequencing (snRNA-seq), a method to characterize the biological architecture of cardiac sympathetic neurons in health and disease. A stepwise approach is demonstrated to perform snRNA-seq of the bilateral superior cervical (SCG) and stellate ganglia (StG) dissected from adult mice.This method enables long-term sample preservation, maintaining an adequate RNA quality when samples from multiple individuals/experiments cannot be collected all at once within a short period of time. Barcoding the nuclei with hashtag oligos (HTOs) enables demultiplexing and the trace-back of distinct ganglionic samples post sequencing. Subsequent analyses revealed successful nuclei capture of neuronal, satellite glial, and endothelial cells of the sympathetic ganglia, as validated by snRNA-seq. In summary, this protocol provides a stepwise approach for snRNA-seq of sympathetic extrinsic cardiac ganglia, a method that has the potential for broader application in studies of the innervation of other organs and tissues. Show less

Meer, P.B. van der 2023

Optimizing antiseizure medication treatment in glioma patients with epilepsy

Doctoral Thesis

open access

The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less

Korne, C.M. de 2023

To IMAGE or to IMAGINE: visualization of parasite migration as a means to support (malaria) parasite vaccine development

Doctoral Thesis

some documents under embargo until 2025-05-02

This thesis presents the development of quantitative imaging tools to study parasite migration. Since migration is crucial for malaria parasites to continue their life cycle, factors influencing... Show moreThis thesis presents the development of quantitative imaging tools to study parasite migration. Since migration is crucial for malaria parasites to continue their life cycle, factors influencing their migration capability may also impact the efficacy of malaria vaccine candidates. Here, imaging of parasite migration was used to gain insights that can support the development of antiparasitic vaccines. SMOOT (Sporozoite Motility Orienting and Organizing Tool) was developed and established as a quantitative software analysis tool for tracking the migration of malaria sporozoites in vitro and in human skin explant. This tool provides a readout with high kinematic detail, enabling the quantitative characterization of novel factors influencing the migration capability of malaria sporozoites. Subsequently, the study of sporozoite migration was expanded beyond in vitro and ex vivo models. A hybrid tracer labeling approach for malaria sporozoites was developed and used to reveal the in vivo dissemination of malaria sporozoites in a murine model. This multimodal imaging approach was also applied to investigate human skin invasion by helminth larvae. This thesis concludes with a review of the broader potential for imaging technology to advance the development of new diagnostic methods, therapeutic interventions and vaccines for combating parasitic infections. Show less

Olthof, P.B.; Franssen, S.; Keulen, A.M. van; Geest, L.G. van der; Hoogwater, F.J.H.; Coenraad, M.; ... ; DHCG 2023

Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma

Article / Letter to editor

open access

BackgroundMost data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients... Show moreBackgroundMost data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort.MethodsData on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry.ResultsIn total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001).DiscussionHalf of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers. Show less

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