PurposeAdolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In... Show morePurposeAdolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors' interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs.MethodsThis population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed.ResultsIn total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations.ConclusionThis study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs. Show less
Shin, W.; Kutmon, M.; Mina, E.; Amelsvoort, T. van; Evelo, C.T.; Ehrhart, F. 2023
Background22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of... Show moreBackground22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood.ResultsUsing previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different.ConclusionsUsing the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity. Show less
This thesis had four main objectives:Predictors of Bipolar disorder (BD): Chapters 2 and 3 explored factors contributing to Bipolar Disorder's development and progression, considering both internal... Show moreThis thesis had four main objectives:Predictors of Bipolar disorder (BD): Chapters 2 and 3 explored factors contributing to Bipolar Disorder's development and progression, considering both internal and external influences.External Stressors: Chapter 4 investigated how external stressors, particularly the COVID-19 pandemic, impacted the stability of BD symptoms, highlighting the role of environmental factors.Symptom Interactions: Chapter 5 analyzed the complex interplay of mania and depressive symptoms in BD over time, enhancing our understanding of their evolution.Neurocognition and Brain Functioning: Chapter 6 reviewed long-term cognitive (dys)function and brain activity in BD patients, offering insights into the disorder's neural mechanisms.Overall, the thesis aimed to expand knowledge of BD, encompassing its predictors, the influence of external stressors, symptom dynamics, and neurocognitive aspects. This research contributes to better diagnosis and treatment strategies for individuals affected by BD. Show less
Purpose: Most of the network approaches in eating disorders found the highest degree of centrality for symptoms related to weight and shape concerns. However, longitudinal analyses are scarce and... Show morePurpose: Most of the network approaches in eating disorders found the highest degree of centrality for symptoms related to weight and shape concerns. However, longitudinal analyses are scarce and may increase our insight of the complex characteristics and dynamics over time. In the current study, an alternative non-linear method to perform longitudinal network analyses, the dynamic time warp approach, was used to examine whether robust dimensions of eating disorder psychopathology symptoms could be found based on the individual dynamic interplay of eating disorder symptoms co-occurrence patterns in time. Methods: The study sample included a naturalistic cohort of patients (N = 255) with all eating disorder subtypes who were assessed with the eating disorder examination questionnaire (EDE-Q) at a minimum of four times during treatment. Dynamic time warp analyses yielded distance matrices within each individual patient, which were subsequently aggregated into symptom networks and dimensions at the group level. Results: Aggregation of the individual distance matrices at the group level yielded four robust symptom dimensions: 1. restraint/rules, 2. secret eating/fasting, 3. worries/preoccupation, and 4. weight and shape concern. The items 'fear of weight gain' and 'guilt' were bridge symptoms between the dimensions 1, 3 and 4. Conclusion: Dynamic time warp could capture the within-person dynamics of eating disorder symptoms. Sumscores of the four dimensions could be used to follow patients over time. This approach could be applied in the future to visualize eating disorder symptom dynamics and signal the central symptoms within an individual and groups of patients. Show less
Kuijper, E.C.; Toonen, L.J.A.; Overzier, M.; Tsonaka, R.; Hettne, K.; Roos, M.; ... ; Mina, E. 2022
While the genetic cause of Huntington disease (HD) is known since 1993, still no cure exists. Therapeutic development would benefit from a method to monitor disease progression and treatment... Show moreWhile the genetic cause of Huntington disease (HD) is known since 1993, still no cure exists. Therapeutic development would benefit from a method to monitor disease progression and treatment efficacy, ideally using blood biomarkers. Previously, HD-specific signatures were identified in human blood representing signatures in human brain, showing biomarker potential. Since drug candidates are generally first screened in rodent models, we aimed to identify HD signatures in blood and brain of YAC128 HD mice and compare these with previously identified human signatures. RNA sequencing was performed on blood withdrawn at two time points and four brain regions from YAC128 and control mice. Weighted gene co-expression network analysis was used to identify clusters of co-expressed genes (modules) associated with the HD genotype. These HD-associated modules were annotated via text-mining to determine the biological processes they represented. Subsequently, the processes from mouse blood were compared with mouse brain, showing substantial overlap, including protein modification, cell cycle, RNA splicing, nuclear transport, and vesicle-mediated transport. Moreover, the disease-associated processes shared between mouse blood and brain were highly comparable to those previously identified in human blood and brain. In addition, we identified HD blood-specific pathology, confirming previous findings for peripheral pathology in blood. Finally, we identified hub genes for HD-associated blood modules and proposed a strategy for gene selection for development of a disease progression monitoring panel. Show less
In Bronze Age Europe, an enormous amount of metalwork was buried in the ground and never retrieved. Patterns in these finds show that this was a deliberate practice: people systematically deposited... Show moreIn Bronze Age Europe, an enormous amount of metalwork was buried in the ground and never retrieved. Patterns in these finds show that this was a deliberate practice: people systematically deposited valuable metal objects in specific places in the landscape, even in non-metalliferous regions. Although this practice seems puzzling from our modern perspective, these patterns demonstrate that this is not simply a matter of irrational human behaviour. Instead, there were supra-regionally shared ideas and conventions behind this practice.This book aims to acquire a better understanding of these ideas and conventions. By systematically investigating the objects and places that people selected for metalwork depositions, the logic behind the practice of selective metalwork deposition is unravelled.This book focuses specifically on the emergence of the practice in Denmark, northern Germany, and the Netherlands, a non-metalliferous region that has not been studied as a whole before, despite striking similarities in the archaeological record. Starting from the first introduction of metal, the emergence and development of selective metalwork depositions is examined and followed over time. In addition to a new chronological and geographical depth to research on metalwork depositions, this book provides a detailed catalogue of the metalwork from the research area. Show less
During the Second Intermediate Period (ca. 1775-1550 BC) period, Egypt was politically and culturally divided into regions, and it was characterized by the presence of groups from modern-day Syria... Show moreDuring the Second Intermediate Period (ca. 1775-1550 BC) period, Egypt was politically and culturally divided into regions, and it was characterized by the presence of groups from modern-day Syria-Palestine and Sudan. To better understand the relationships between the Egyptian sites during this period, I have analysed the objects (beads, stone vessels, scarabs and seals, metal weapons, and two particular types of pottery) that the relevant sites have in common, through network analysis. This quantitative and statistical methodology, which makes use of digital tools, is ideal to examine the relations, as well as the flow and circulation of objects, resources, information, or knowledge between different entities, based on what these entities have in common (or not). During the Second Intermediate Period, contacts can still be detected between different areas, even though they were weaker and happened mostly through desert routes. Two phenomena can be detected: the growing importance of Tell el-Dab’a/Avaris in circulation of objects and resources, and the role played by the communities of Pan-grave culture, known only form archaeological remains and featuring connections with Nubia (modern-day Sudan). Show less
Background Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms... Show moreBackground Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms shared by both disorders, with overlapping symptoms acting as so-calledbridges, funneling symptom activation between symptom clusters of each disorder. This study investigated this hypothesis by testing whether (i) twooverlappingmental states "worrying" and "feeling irritated" functioned as bridges in dynamic mental state networks of individuals with both depression and anxiety as compared to individuals with either disorder alone, and (ii) overlapping or non-overlapping mental states functioned as stronger bridges. Methods Data come from the Netherlands Study of Depression and Anxiety (NESDA). A total of 143 participants met criteria for comorbid depression and anxiety (65%), 40 participants for depression-only (18.2%), and 37 for anxiety-only (16.8%) during any NESDA wave. Participants completed momentary assessments of symptoms (i.e., mental states) of depression and anxiety, five times a day, for 2 weeks (14,185 assessments). First, dynamics between mental states were modeled with a multilevel vector autoregressive model, using Bayesian estimation. Summed average lagged indirect effects through the hypothesized bridge mental states were compared between groups. Second, we evaluated the role of all mental states as potential bridge mental states. Results While the summed indirect effect for the bridge mental state "worrying" was larger in the comorbid group compared to the single disorder groups, differences between groups were not statistically significant. The difference between groups became more pronounced when only examining individuals with recent diagnoses (< 6 months). However, the credible intervals of the difference scores remained wide. In the second analysis, a non-overlapping item ("feeling down") acted as the strongest bridge mental state in both the comorbid and anxiety-only groups. Conclusions This study empirically examined a prominent network-approach hypothesis for the first time using longitudinal data. No support was found for overlapping mental states "worrying" and "feeling irritable" functioning as bridge mental states in individuals vulnerable for comorbid depression and anxiety. Potentially, bridge mental state activity can only be observed during acute symptomatology. If so, these may present as interesting targets in treatment, but not prevention. This requires further investigation. Show less
Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG)... Show morePrematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9-10 years of age.Fifty-five children born < 32 weeks' of gestation underwent EEG at 9-10 years of age and were assessed for motor development and cognitive outcome. Relative frequency power and functional connectivity, as measured by the Phase Lag Index (PLI), were calculated for all frequency bands. Per subject, power spectrum and functional connectivity results were averaged over all channels and pairwise PLI values to explore differences in global frequency power and functional connectivity between EP and VP children. Brain networks were constructed for the upper alpha frequency band using the Minimum Spanning Tree method and were compared between EP and VP children. In addition, the relationships between upper alpha quantitative EEG results and cognitive and motor outcomes were investigated.Relative power and functional connectivity were significantly higher in VP than EP children in the upper alpha frequency band, and VP children had more integrated networks. A strong positive correlation was found between relative upper alpha power and motor outcome whilst controlling for gestational age, age during EEG recording, and gender (p = 0.493, p = 0.004).These results suggest that 9-10 years after birth, the effects of the degree of prematurity can be observed in terms of alterations in functional brain activity and that motor deficits are associated with decreases in relative upper alpha power. Show less
Adolescence is characterized by considerable changes in cognitive and socio-emotional skills. There are considerable differences between adolescents with regards to the development of these skills.... Show moreAdolescence is characterized by considerable changes in cognitive and socio-emotional skills. There are considerable differences between adolescents with regards to the development of these skills. However, most studies examine adolescents’ average functioning, without taking into account this heterogeneity. The current study applies network analysis in order to examine heterogeneity of cognitive and socio-emotional functioning in adolescents on-track or delayed in their school progression. Data was collected at two time-points for on-track (n = 320) and delayed (n = 69) adolescents (Mage = 13.30 years, SDage = 0.77). Repeated measures ANOVA showed no significant differences between the groups in cognitive and socio-emotional functioning (p’s > 0.05). Network analysis revealed that executive functions play a key role in the network of cognitive, social, and emotional functioning. This is especially the case in the delayed group where executive functions are even more central, both at T1 (inhibition and shifting) and T2 (shifting). Subsequent community analysis revealed three profiles in both groups: a well-adapted and well-balanced group, a group with high levels of need for arousal and risk-taking, and a group with regulation problems. Compared to on-track adolescents, delayed adolescents showed even higher levels of risk-taking in the second profile and higher levels of executive function problems in the third profile at T1. These differences were leveled out at T2, indicating adolescents in the delayed group catch up with their peers. This study highlights the intricate balance between cognitive, social and emotional functioning in adolescents in relation to school performance and provides preliminary evidence of the importance of taking individual differences within groups into account. Show less
The research described in this thesis aims to establish the use of detailed collaboration and citation analysis combined with other forms of bibliometric analysis as a tool enabling a better... Show moreThe research described in this thesis aims to establish the use of detailed collaboration and citation analysis combined with other forms of bibliometric analysis as a tool enabling a better understanding of the organization of scientific communities and the way knowledge is spread inside scientific communities. In the study of collaboration networks the main goal is to identify existing research groups, potential research groups, and patterns of collaboration. The analysis of citations networks through specific measures and metrics, on the other hand, makes it possible to identify main lines of research through the years. Thus, such analyses improve our understanding of the growth and decline of fields, including phenomena such as paradigm shifts and emerging research themes. Network measures and metrics also allow for the identification of important nodes (e.g., journals, articles) embedded in the citation network. Show less
