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    Revisiting the structure of Diagnostic and Statistical Manual of Mental Disorders, fifth edition, Section II personality disorder criteria using individual participant data meta-analysis

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    The factor structure of personality disorder (PD) criteria has long been debated, but due to previous heterogeneous findings, a common structure to represent covariation among the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)/DSM-5 Section II PD criteria remains an open question. This study integrated individual participant data from 25 samples ( N = 30,545) to conduct factor analyses of PD criteria. Measurement invariance tests across gender, clinical status, and assessment method indicated substantial structural differences between interview-based and self-report measures. In interviews, a confirmatory 10-factor model with factors representing specific DSM-5 PDs showed a major misfit, with results from exploratory factor analyses suggesting that this was due to a relatively small number of substantial secondary loadings. In self-reports, a confirmatory 10-factor model showed greater misfit than in interviews, and exploratory solutions were more complex. When five factors were extracted, the factors showed some similarity to maladaptive trait domains such as Negative Affectivity and Disinhibition, but there were substantial differences in factor content between interviews and self-reports. In bifactor models, a general factor explained more common variance in self-reports, whereas the content of general factors was similar in both assessment methods. Our findings suggest that interview and self-report measures of PD criteria are not structurally equivalent. To advance research on the structure of PD, it may be useful to consequently focus on the shared variance of multiple methods. For this purpose, future multimethod studies should combine interviews and self-reports with other assessment methods such as informant reports. (PsycInfo Database Record (c) 2025 APA, all rights reserved). </p

    Evolution-assisted engineering of formate assimilation via the formyl phosphate route in Escherichia coli

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    The transition towards a sustainable bioeconomy requires the use of alternative feedstocks, with CO 2-derived formate emerging as a promising candidate for industrial biotechnology. Despite its beneficial characteristics as a feedstock, microbial assimilation of formate is limited by the inefficiency of naturally evolved formate-fixing pathways. To overcome this limitation, synthetic formate reduction cascades could enable formate assimilation via formaldehyde, a key intermediate of several existing one carbon assimilation pathways. Recently, the formyl phosphate route, combining ATP-dependent activation of formate to formyl phosphate, followed by its reduction to formaldehyde, was developed through enzyme engineering and characterized in vitro. In this work, we successfully established the formyl phosphate route in vivo by developing a selection strategy that couples formate reduction to growth in a threonine/methionine auxotrophic Escherichia coli. Through adaptive laboratory evolution, we achieved formate-dependent growth via this novel pathway. Evolved strains were capable of growing robustly with formate concentrations between 20 mM and 100 mM with glucose in the co-feed. Genomic and proteomic analyses together with activity assays uncovered that formate activation was limiting in vivo. This discovery guided the rational engineering of a strain capable of efficient formate assimilation through the formyl phosphate route. By demonstrating that novel enzyme activities can link formate reduction to cell growth, our study shows how synthetic metabolic routes can be functionally established inside the cell, paving the way for the engineering of more complex synthetic pathways. </p

    Towards trustworthy artificial intelligence for decision-making:A lifecycle perspective on knowledge- and data-driven artificial intelligence systems

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    Organisations increasingly use data-driven artificial intelligence (AI) systems in their decision-making processes. These AI systems may operate autonomously, support human decision-makers or increasingly act as collaborative team members. However, data-driven AI systems often function as black boxes, lacking interpretability. This poses a challenge in decision-making, as stakeholders involved in or impacted by the decision-making process frequently need to understand the rationale behind decisions. Moreover, data-driven AI systems operate without leveraging structured domain knowledge. As a result, data-driven AI systems may generate outputs that are misaligned with the decision context, objectives, or constraints, potentially leading to poor decisions or reduced trust in AI systems among users. Consequently, recent years have seen an increasing interest in integrating domain knowledge with data-driven AI. This is evident in neuro-symbolic AI, a subfield of AI that combines neural networks with symbolic AI. While this approach shows promise for enhancing the trustworthiness of AI systems in decision-making, the specific mechanisms by which domain knowledge integration contributes to dimensions of trustworthiness remain insufficiently explored. Therefore, this study reviews and integrates recent knowledge- and data-driven AI literature, along with relevant concepts for decision-making. Building on this foundation, it proposes a lifecycle framework for integrated knowledge- and data-driven AI systems for decision-making, and demonstrates its application through a healthcare application example. It further analyses the dimensions of trustworthiness for knowledge- and data-driven AI systems using the proposed lifecycle framework and application example. In doing so, this study advances the discourse on trustworthy AI for decision-making

    Capturing a person’s daily context:integrating experience sampling and personal social network methodology

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    Recently, technological advances have enabled researching peoples’ experiences in daily life by sending them multiple short questionnaires per day on their smartphones. This ‘experience sampling methodology’(ESM) is increasingly used for mental health related research and clinical practice. Often, ESM questionnaires focus primarily on a person’s mood, thoughts, or feelings. Other, so-called ‘contextual’ factors, such as someone’s social interactions and relationships or what someone does during their day, also play a significant role in daily life and impact mental health. These factors have, however, received relatively little attention in ESM thus far. The goal of this thesis is to focus on these contextual factors and introduce new methods for both research and clinical practice. Specifically, it combines ESM with personal social network data collection (PSN) – a method mapping out a person’s social relationships. The thesis outlines the importance of someone’s (social) context and explains the potential of combining ESM and PSN. Further, it presents software for the implementation of this combination and describes its use in two studies with students and one case study in clinical practice. The ESM questionnaires used in the presented research contain open-ended questions to obtain richer, more personally meaningful descriptions of daily activities. This thesis demonstrates how such data can be analyzed with natural language processing or qualitative approaches.In sum, this thesis provides a methodological basis for researchers and practitioners to examine a person’s daily life ‘context’ – their social relationships, social interactions, and daily activities – and how it relates to symptoms or feelings

    Insights into the diversity of the endophytic community in potatoes and factors affecting this diversity

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    Plant-microbiome interactions have become a critical focus in sustainable agricultural management due to their significant impact on plant health and growth. The role of the plant microbiome in promoting plant vitality is well established. Using results from controlled greenhouse experiments, this thesis investigates the influence of environmental and host-related factors on the diversity of endophytes. Our study provides new insights for breeders seeking to incorporate microbiome-related traits into breeding programmes. This thesis starts by highlighting the concept of holobiont and emphasises the importance of plant-microbe interactions in Chapter 1. Chapter 2 provides a concise review of the strategies that have recently been employed to fully leverage the plant-microbiome interaction in agricultural practices. To delve deeper into the effect of biotic and abiotic conditions on the plant endophytic diversity, Chapter 3 highlights the significant role of soil in determining the composition of bacterial and fungal endophytes. This chapter further emphasises the stronger role of cultivars in shaping the fungal endophytes in potatoes.Chapter 4 of this thesis offers a deeper insight into plant microbiome interaction by studying the recruitment of endophytes from the rhizosphere. Source tracking analysis using FEAST package explains the discrepancies in the recruitment pattern of bacterial and fungal communities. Chapter 5 reveals that the soil microbiome inoculation effect is not limited to the rhizosphere but extends up to the endophytic compartment of the plant. Chapter 6 emphasises the importance of considering the local soil microbiome before applying microbiome-based strategies

    Natural polyphenol-based metal nanomaterials for the treatment of antibiotic-resistant bacterial infections

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    Bacterial infections represent a major global health challenge, particularly with the emergence of drug-resistant strains that cause a wide range of clinical conditions, from skin infections to internal diseases such as peritonitis, pneumonia, and sepsis. Metal nanomaterials have recently gained attention as promising antibacterial agents owing to their unique physicochemical properties, which endow them with potent antibacterial activity and broad-spectrum efficacy against drug-resistant bacteria. Unlike conventional antibiotics, metal nanomaterials rarely induce bacterial resistance due to their diverse antibacterial mechanisms, which include direct disruption of bacterial cell structures and the generation of oxidative stress. However, traditional chemical synthesis of metal nanomaterials often involves toxic organic solvents, raising safety and environmental concerns. In contrast, biosynthetic approaches, particularly those employing plant extracts as reducing agents or stabilizing ligands, offer environmentally friendly and biocompatible alternatives for nanoparticle fabrication. In this thesis, two novel antibacterial agents, ellagic acid–modified gold nanoparticles (EA-AuNPs) and a bimetal–phenolic framework (Que-Fe-CeMPF), were developed as potential alternatives to antibiotics for combating drug-resistant bacterial infections both in vitro and in vivo, using a simple green synthesis method. Both metal nanomaterials exhibited highly effective antibacterial activity without inducing bacterial resistance, which is attributed to their multimodal antibacterial mechanisms. In mouse models with bacterial infections, both EA-AuNPs and Que-Fe-CeMPF demonstrated superior therapeutic efficacy compared with traditional antibiotics. For future clinical translation, comprehensive evaluations of therapeutic efficacy and long-term biosafety in vivo are essential, ideally employing animal models with immune systems that more closely resemble those of humans

    Rising to advanced gait rehabilitation:assessment of body weight supported gait training after neurological injury

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    Robotic technology is increasingly being used in rehabilitation for people recovering from a stroke or spinal cord injury. An important innovation is body weight support: systems that support the body during standing and walking. This allows patients to start gait training early and safely, when independent walking is not yet possible. One of the latest systems is the RYSEN (Motek Medical). This system consists of a harness around the trunk, connected to a ceiling-mounted rail via a yoke and four cables. Using pulleys and smart actuators, patients can walk while their body weight is supported. Support is provided not only vertically, but also forward, backwards and sideways. Moreover, the system features augmented reality, projecting interactive games onto the floor. The versatility of such a system also raises questions. How does it fit within existing rehabilitation programs? How should appropriate settings be selected? And which settings are best for specific training goals? This thesis examines the current use of the RYSEN at Heliomare Rehabilitation Centre and explores its potential applications. The focus is on how therapists use the system and how its settings can be applied for specific training goals. Initial findings are encouraging; the RYSEN is well-accepted among patients and therapists. The system enhances confidence in balance and offers opportunities for targeted gait training. However, guidelines for structured application within rehabilitation programs are limited. Further collaboration between researchers, engineers, clinicians and patients is therefore essential to establish clinical guidelines and fully exploit the potential of the RYSEN in rehabilitation

    Symptom Burden and Patient-Reported Outcomes in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Studies

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    Rationale &amp; Objective: A multitude of symptoms may contribute to low health-related quality of life (HRQoL) in kidney transplant recipients (KTR). We aimed to identify the most occurring and distressing symptoms, to explore potential determinants of symptom burden, and to examine associations with patient-reported outcomes in KTR. Study Design: A cross-sectional retrospective patient-reported outcome measures study. Setting &amp; Participants: Stable KTR ≥1 year after transplantation participating in the TransplantLines Biobank and Cohort Studies. Predictors: Clinical variables, including sex, age, and time after transplantation. Outcomes: Symptom occurrence/distress/burden, medication adherence, symptoms of depression/anxiety, societal participation, and HRQoL. Analytical Approach: Symptoms were evaluated using ridit analyses. A burden score was calculated to explore determinants of symptom burden and its associations with other patient-reported outcomes. Results: We included 936 KTR (38.8% female; mean ± SD age, 55.6 ± 13.0 years) at a median [IQR] of 2.0 [1.0-9.0] years after transplantation. Based on ridit scores, most occurring symptoms were tiredness [0.724], bruises [0.718], and lack of energy [0.688]; most distressful symptoms were menstrual problems [0.679], impotence [0.654], and joint pain [0.611]. Worse nutritional status (P &lt; 0.001), being female (P &lt; 0.001), cyclosporine use (P = 0.005), and proton pomp inhibitor use (P &lt; 0.001) were associated with higher symptom burden. Higher symptom burden was associated with medication nonadherence, symptoms of depression and anxiety, lower societal participation, and lower physical and mental HRQoL (st.β = –0.53, 95% CI –0.59 to –0.47, P &lt;0.001 and st.β=-0.53, 95% CI –0.60 to –0.46, P &lt; 0.001, respectively). Limitations: No causality can be established because of the cross-sectional design. Conclusions: The most occurring symptoms were tiredness, bruises, and lack of energy, and the most distressing symptoms were menstrual problems, impotence, and joint pain. The strongest determinants of symptom burden were female sex, malnutrition, cyclosporine use, and proton pump inhibitor use. The associations of symptom burden with patient-related outcomes underline the importance of addressing symptom status after transplant. Plain-language Summary: Symptom burden of immunosuppressive medication may cause lower health-related quality of life (HRQoL) in kidney transplant recipients (KTR). Therefore, we aimed to assess (1) symptom occurrence and distress, (2) determinants of symptom burden, and (3) associations of symptom burden with HRQoL and other patient-reported outcomes. In 936 KTR, the most occurring symptoms were tiredness, bruises, and lack of energy, and the most distressing symptoms were menstrual problems, impotence, and joint pain. Being female, having malnutrition, using cyclosporine, and using proton pump inhibitors were determinants of high symptom burden. Furthermore, a higher symptom burden was associated with more medication nonadherence, more symptoms of anxiety/depression, lower societal participation, and lower physical and mental HRQoL. These findings may help improve patient-centered health care.</p

    Peat reclamations of the Pre-Roman Iron Age and Roman Iron Age in Friesland (The Netherlands):habitation, drainage and agriculture in a dynamic landscape

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    Archaeological observations have shown that some centuries before the beginning of the Common Era, parts of the Frisian peatlands were reclaimed by terp-dwelling communities from the salt marshes. However, small-scale excavations had made it clear that little could be stated with certainty about this phenomenon. The aim of this PhD research was therefore to gain a deeper understanding of these earliest Frisian peat reclamations. Therefore, results from earlier studies were combined with new investigations conducted within the PHD project, including various forms of field surveys, GIS analyses, and three excavations of settlements associated with these reclamations.This research provides many important new insights into these early reclamations, which now appear to have begun already in the 4th century BC. One of the principal findings is that the primary motive behind these efforts was the creation of an agricultural landscape; other activities, such as peat extraction, played only a secondary role. Another significant insight is that these reclamations were anything but sustainable. Artificial drainage caused subsidence, making the reclaimed lands wetter. Over time, this forced inhabitants to reclaim new stretches of peatland and to relocate their settlements. Interestingly, the abandoned lands gradually rose again, largely through the deposition of marine clay. This process restored the balance to some degree and, over time, made these areas suitable for habitation again, which is what happened. The study further shows that the cessation of these reclamations corresponds with the general population decline in the terp region during the 3rd and early 4th centuries AD

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