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    Phytochemical profiling by UPLC\u2010ESI\u2010QTOF\u2010MS of Kalaharia uncinata (Schinz) Moldenke, widely used in traditional medicine in DR Congo

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    Abstract: Kalaharia uncinata(Schinz) Moldenke, is a tropical erect bushy shrub or subshrub of the Lamiaceae family. It is an endemic plant species of Southern Africa, widely used in the pharmacopoeia against upper respiratory tract infections. A previously conducted ethnobotanical survey revealed that it is believed to contain bioactive substances. However, no relevant phytochemical information was available. This study aimed to perform a phytochemical characterization of K. uncinata and also to discuss the potential bioactivity of the identified phytochemical constituents based on documented data. Ultra\u2010performance liquid chromatography with electrospray ionization quadrupole time\u2010of\u2010flight mass spectrometry (UPLC\u2010ESI\u2010QTOF\u2010MS) was used for profiling and identification of the main phytochemical constituents from leaf extracts (MeOH 90\u2009%, DCM, AcOEt, BuOH, hexane and residue) of K. uncinata. Twenty\u2010four constituents, representing mainly flavonoids (14), followed by phenylethanoid glycosides (7), phenolic acids (2), and an iridoid glycoside (1) were tentatively identified. Most of the identified compounds are documented to have antiviral and anti\u2010inflammatory properties, which could possibly be the rationale behind the use of K. uncinata against upper respiratory tract infections

    Towards a better understanding of pain after surgery for breast cancer : a biopsychosocial perspective

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    Abstract: Pain is one of the most common and long-lasting side effects reported by women surgically treated for breast cancer. The neurophysiology of pain shows that a pain experience is determined not only by the stimulation from tissues such as muscles or nerves (biological level), but also by how a person feels and thinks about pain (psychological level), as well as one\u2019s personal environment and how one feels supported in it (social level). In turn, pain will also have an impact on an individual\u2019s physical and psychosocial functioning. Adequate evaluation and management of pain is necessary to prevent pain and improve biopsychosocial functioning, both in the short and long term after surgery for breast cancer. The aim of this doctoral thesis was twofold. The first aim of this doctoral thesis was to contribute to the understanding and biopsychosocial evaluation of the neurophysiological processes of pain and sensory disturbances in women after surgery for breast cancer. Therefore, three different studies were conducted. First, a systematic review of the existing literature regarding quantitative sensory testing (QST) methods and results in women after surgery for breast cancer, was conducted. QST is the umbrella term for non-invasive assessment techniques evaluating the functioning of the somatosensory nervous system. QST results were summarized using a narrative synthesis. Second, a reliability study evaluated both within- and between-rater reliability of a comprehensive QST protocol including static as well as dynamic QST methods in women treated for breast cancer. Third, a cross-sectional study examined whether questionnaires can be used for the evaluation of the neurophysiological processes of somatosensory functioning after surgery for breast cancer in clinical practice. The second aim of this doctoral thesis was to contribute to the prevention and treatment of pain and pain-related disability after surgery for breast cancer in the long term. Therefore, two studies were conducted. In a double-blinded randomized controlled trial the effectiveness and moderators of PNE after surgery for breast cancer were investigated on pain intensity, somatosensory and psychosocial functioning. By means of a prospective cohort study the perioperative biopsychosocial risk factors for pain and pain-related disability one year after surgery for breast cancer were investigated. The findings of this doctoral thesis are an important step forward in future research into the biopsychosocial evaluation and management of pain and sensory disturbances following breast cancer surgery. In addition to important research suggestions, deeper insights and recommendations for the biopsychosocial evaluation and management of pain in clinical practice were provided

    Predicting patient deterioration by nurse intuition : the development and validation of the nurse intuition patient deterioration scale

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    Abstract: Introduction Early warning scores based on vital signs are used in hospitals to estimate patient deterioration and to initiate an adequate and timely response when necessary. These scores show acceptable performance in predicting patient outcomes. However, they tend to generate many false positives leading to an increased workload in clinical practice. Additionally, nurses feel a tension between the application of an early warning score and their own clinical judgement. Nurse intuition is often included as an extra call criterion next to an early warning score. It is therefore important to investigate its predictive value. The aim of this study was to develop and validate a Nurse Intuition Patient Deterioration Scale (NIPDS). Methods The NIPDS was developed using the latest evidence after which relevant items were selected by an expert panel. The scale was tested in a prospective observational study in 2 surgical and 2 medical wards in a Belgian hospital. Data were collected from December 1st, 2019 until March 31st, 2020. A NIPDS registration was done at each patient admission and whenever the attending nurse felt worried. The studied outcomes were urgent physician assistance call, resuscitation team call, patient death, and unplanned transfer to intensive/medium care. Psychometric analyses and scale optimisation were carried out using Rasch modelling techniques. Finally, the scale's accuracy and an optimal threshold were determined. Results The scale item content validity index is 0.88 indicating that the selected items should be included in the instrument according to the expert panel. Item-total score correlation coefficients range between 0.573 (item 9 \u2013 pain) and 0.874 (item 6 \u2013 behaviour). The Person Separation Index is 0.814 indicating satisfactory discriminatory power. An overall fit of the NIPDS data to the Rasch model was confirmed. Rasch modelling showed that the item \u2018pain\u2019 signalled misfit. Furthermore, the person-item map showed disordered items which were corrected in the final model. The AUROC to predict an event within 24\u202fh after registration was 0.957 (95% CI 0.932\u20130.982; p\u202f<\u202f0.001) indicating excellent model performance. Discussion The results showed that the NIPDS is a valid and accurate instrument to predict events in surgical and medical patients. It showed better performance compared to an existing score estimating nurse intuition. In practice, the NIPDS could be used by nurses to estimate clinical deterioration in addition to an early warning score. It remains unclear if the combination of NIPDS with an early warning score could reduce workload without losing accuracy and this should be explored in future research

    Rationally designed drug combination screen in more physiologically relevant in vitro organoid models : can we improve personalized therapy for pancreatic cancer?

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    Abstract: Cancer remains one of the leading causes of morbidity and mortality worldwide, with pancreatic ductal adenocarcinoma (PDAC) ranking among the most lethal and treatment-resistant malignancies. Despite advances in surgery, chemotherapy, radiotherapy, and immuno-oncology, clinical outcomes remain dismal. This highlights the urgent need for predictive preclinical models that can capture tumor heterogeneity and enable personalized treatment strategies. Traditional two-dimensional cancer cell lines, although cost- effective and widely used, fail to reproduce the complex interactions and diversity of real tumors. Patient- derived xenografts (PDX) partly address this issue, but their cost, lengthy establishment, and limited success rates restrict their clinical value. In this context, patient-derived organoids (PDOs) have emerged as a powerful alternative. PDOs are three-dimensional, self-organizing structures that preserve the histology, genetics, and heterogeneity of their tumors of origin, while remaining scalable, affordable, and compatible with high-throughput testing. This thesis investigates the applications of PDOs in oncology, with particular focus on gastrointestinal cancers and PDAC. The first part reviews organoid development, culture methods, and their implementation in basic research, drug discovery, and translational medicine, while also outlining limitations such as variability in culture conditions and the absence of stromal and immune components. Subsequent chapters explore PDOs as predictive models of chemoradiation response in rectal and esophageal cancer, demonstrating their potential to guide organ-sparing strategies and individualized treatment, while also discussing challenges related to reproducibility, assay design, and clinical turnaround time. The central chapters present the development of an advanced, multiparametric PDO assay for PDAC. Moving beyond simple viability endpoints, this platform incorporates functional and phenotypic readouts, including clonal dynamics and therapy-induced adaptations. Retrospective clinical validation confirmed its predictive accuracy, and the assay was successfully applied to therapeutic discovery, identifying novel drug combinations that enhance the activity of KRAS G12D inhibitors and other emerging agents. Taken together, this thesis positions PDOs as a future technology for precision oncology. PDOs preserve the biological memory of tumors while serving as personalized \u2018avatars\u2019 for therapy selection, with the potential to accelerate drug discovery, reduce attrition in clinical trials, and improve clinical outcomes. Yet beyond their scientific value, PDOs also carry a human dimension: each culture is a living fragment of a patient\u2019s disease, a contribution that endures as a legacy of hope, even when the patients themselves are no longer with us

    Fishing in the data lake : tax audits on (digital) information: exploring the legitimacy and limits in light of the prohibition of fishing expeditions

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    Abstract: This dissertation analyses the legitimacy of tax administrations\u2019 information-gathering methods in light of the prohibition of fishing expeditions. In carrying out their control activities, tax administrations have traditionally relied on non-digital methods of information gathering. The arrival of digital technologies and the ongoing digitalisation, however, has increased data availability, strengthening tax control but raising concerns about data collection and taxpayer rights. The research finds that the aforementioned prohibition is interpreted as a \u201cspeculative and/or excessive expedition.\u201d It rests on three clusters of legal grounds: fundamental rights, principles of good administration and the tax relevance criterion. Traditional information-gathering methods are legitimate only when not speculative, nor excessive. Other methods like database consultation or web scraping can be assessed by analogy. The prohibition of fishing expeditions is not applicable on methods such as reporting obligations and data mining. The dissertation recommends legislative reform, specific legal frameworks and more transparency by tax administrations

    Bioconversion of waste lipids into long-chain dicarboxylic acids : process insights and optimisation

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    Abstract: A shift towards renewable materials and a circular economy is slowly becoming a necessity for the industry. Supply chains must reduce reliance on fossil resources while simultaneously revalorising waste streams. Within this context, long-chain dicarboxylic acids (LCDAs) are important components used in a wide variety of applications, yet their production still relies almost exclusively on non-renewable materials. To meet demand for these LCDAs in a sustainable way, alternative routes using renewable, non-food materials are essential. This thesis evaluates a biotechnological alternative, specifically the production of LCDAs from used cooking oil (UCO) and grease trap waste (GTW). Specifically, the conversion of these waste streams using Candida tropicalis ATCC 20962 and Starmerella bombicola \u394pox1\u394ugta1\u394faa1, two yeasts that are naturally capable of producing these LCDAs, is investigated. Before the bioconversion could start, the waste streams were first subjected to a detailed compositional analysis to determine their lipid class distribution, fatty acid profile and level of non-lipid contaminants. Based on this characterisation, the effect of the GTW and its components on the growth of C. tropicalis was investigated, followed by the development of a bioconversion process for the production of LCDAs. This production process was subsequently optimised, primarily by adjusting feed rates. To further improve the process and mitigate the inhibition of the contaminants, a membrane ultrafiltration pretreatment of the GTW was then performed. Finally, S. bombicola was used for the bioconversion of both UCO and GTW, enabling an assessment of its suitability as an alternative production host. This yeast was chosen due to its higher lipase activity, which is required for the triglyceride-rich UCO. Using this yeast, the effect of oxygen availability on the conversion process, as well as the effect of lipids on oxygen transfer, was determined. Compositional analysis revealed that GTW mainly contained free fatty acids, whereas UCO was predominantly composed of triglycerides. In addition, the GTW contained high levels of contaminants such as surfactants and heavy metals. Evaluation of the effect of the GTW on C. tropicalis revealed that it considerably reduced cell growth. Subsequently, this reduction in growth was found to be mostly attributable to the anionic surfactants in the GTW. Despite the inhibition, a bioconversion process was developed, and the feeding rates of both GTW and glucose were optimised. This revealed that the optimal glucose feed rate was 0.38 g/(L.h), with higher feed rates favouring biomass with little LCDA formation, while lower feed rates limited cell viability and production. GTW feed rate optimisation revealed that high feed rates suppressed LCDA production, likely due to the contaminants in the GTW, limiting the feed rate to 0.5 g/(L.h). Under these conditions, a titre of 34.7 g/L of LCDA was achieved, with a 76% yield and a productivity of 0.42 g/(L.h). Pretreating the GTW using ultrafiltration with a C1-grafted 3 nm ZrO2 membrane effectively removed the surfactants and heavy metals. During bioconversion, this pretreated GTW resulted in a 25% increase in LCDA production, with a titre of 43.5 g/L and a productivity of 0.46 g/(L.h). This clearly showed the great potential of GTW as a feedstock for LCDA production. It was found that when using S. bombicola, oxygen mainly affected lipase activity and had only minor effects on conversion rates. However, production with S. bombicola remained limited compared to C. tropicalis, with titres being only 5.13 g/L when using GTW and 1.36 g/L for UCO. This difference is likely due to the need for lipase when using UCO. Overall, the work demonstrates that lipid wastes, especially GTW, could be economically viable feedstocks for LCDA production. A suitable bioconversion process was developed and optimised, reaching economically relevant production rates

    How the Nutri-Score affects consumers and manufacturers : a focus on consumers\u2019 choices and manufacturers\u2019 reformulation efforts

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    Abstract: Imagine you are standing in the supermarket. As you gaze at the rack of breakfast cereals, you might feel overwhelmed by the numerous alternatives presented to you. How do you choose what to buy? The Nutri-Score was developed to simplify this decision by aiding consumers to compare products\u2019 healthiness. As previous research demonstrates its understandability, attention-grabbing properties, and mostly positive effects on purchase intention and choice, the European Union has considered adopting it as the official European label as part of their Farm to Fork strategy. Nevertheless, not all countries are unequivocally in favour of this label; the same holds true for companies, and even experts and researchers, who cite mixed findings and several evidence gaps. This has complicated the decision of the European Commission and led to postponing their harmonized labelling efforts. Against this backdrop, this dissertation focusses on strengthening the available evidence by addressing five key gaps. It explores the Nutri-Score\u2019s effect outside of controlled environments, its impact on multi-attribute product choices, the heterogeneity in consumers\u2019 preferences for the label, its implementation in online supermarkets, and the efforts undertaken by food manufacturers to engage in Nutri-Score-driven product reformulations. Employing a range of methodologies \u2013 including a naturalistic field experiment, discrete choice modelling, a randomized controlled trial, and retrospective observational study \u2013 this work provides fresh insights into the Nutri-Score\u2019s effectiveness. By extending our knowledge and insights on the multifaceted puzzle that surrounds the Nutri-Score, this thesis contributes to a robust evidence base that will eventually enable the European Commission to make well-informed and evidence-driven decisions on harmonized labelling efforts

    Aspects of hemorrhage & hemostasis in neurosurgery

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    Abstract: Doctoral thesis on some aspects of postoperative hemorrhage and intraoperative hemostasis in neurosurgery

    Microvascular dysfunction in adults with congenital heart disease and the effect of exercise training

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    Abstract: Congenital heart diseases (CHDs) represent a complex and heterogeneous group of cardiac malformations associated with significant morbidity and mortality, affecting approximately 1% of live births worldwide. Advances in early management and surgical techniques have increased survival rates, leading to a continuously growing population of adults with CHD. However, these patients continue to face challenges, including reduced physical fitness, lower quality of life and poorer prognoses compared to healthy individuals of similar age. Consequently, the lifelong management of these patients has become increasingly important. Advancing therapeutic strategies, risk stratification and preventive measures requires a deeper understanding of the underlying pathophysiological mechanisms. This thesis investigates microvascular dysfunction (MVD) in adults with CHD and evaluates the effects of a 16-week home-based aerobic and strength exercise program. Our findings indicate substantial evidence for the presence of MVD in a significant proportion of adults with CHD. While existing literature suggests indications of both coronary and peripheral MVD in CHD, findings remain inconsistent. In our cohort of 55 adults with various CHD subtypes, a multimodal vascular assessment revealed a higher prevalence of peripheral MVD, increased large artery stiffness and elevated carotid arterial wall thickness compared to healthy reference populations. Notably, microvascular function in the finger correlated with inflammation, whereas no significant association was observed with superoxide anion radical levels, a measure of oxidative stress. Although prior research has reported elevated oxidative stress in CHD patients and suggested an association with disease severity, we were unable to confirm these findings in our study group. Vitamin D levels were also not significantly different in our heterogeneous CHD cohort compared to controls without cardiac disease. Nevertheless, vitamin D levels correlated with exercise capacity, even after adjusting for seasonal variation as a confounding factor. Further analysis revealed that right ventricular function, assessed using two-dimensional multi-plane echocardiography, was similarly correlated with exercise capacity in CHD. Additionally, our data demonstrated a significant association between arterial stiffness and exercise capacity, suggesting that reduced arterial stiffness is linked to higher peak oxygen consumption. Finally, our 16-week home-based aerobic and strength exercise program resulted in improved exercise capacity, muscle strength and quality of life, with no reported adverse events. These results suggest that the vasculature and right ventricular function should be a key area of focus in CHD management and that structured home-based exercise interventions can be both safe and effective in promoting better health outcomes for adults with CHD

    ICH safeguarding actions : Jingdezhen porcelain industry skills in the context of UNESCO

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    Abstract: Jingdezhen has a long history of porcelain making, a complex industrial structure, and extensive skill systems. The objectives of this dissertation focus on: in such a pan-systemic craft industry city, what actions for ICH safeguarding have been taken by multiple actors, how these actions have impacted the city's social and physical structures, what adaptive changes have occurred in the skills and craftspeople of the porcelain industry during ICH safeguarding, and how the safeguarding rules have undergone responsive adjustment in practice. This dissertation selected ICH safeguarding of porcelain industry skills in Jingdezhen as the research object, primarily employing interviews and participant observation to conduct a qualitative study on the ICH safeguarding actions of multiple actors. As an urban case, Jingdezhen exhibits striking characteristics. During the activation phase of action nets, the government played a dominant role; after the foundational construction phase was completed, it granted greater autonomy to other actors through policy support, platform establishment, and power delegation, and subsequently withdrew from its leading position. The advancement of ICH safeguarding in Jingdezhen benefits from two boundary objects: inventory systems and nomination texts. The pluralized inventory systems create multiple pathways for actor participation, while the broad nomination texts provide ample space for actions. In Jingdezhen, the ICH safeguarding center manifests not as a single fixed institution but instead presents as a dispersed state. Relevant institutions, safeguarding carriers, Representative Inheritors, other actors already integrated into or proposing to join action nets, and even enthusiastic individuals actively interpret ICH, formulate safeguarding plans, and influence safeguarding actions. Some safeguarding concepts within these dispersed centers dominate for various reasons, and ultimately influence the ICH safeguarding framework, government policymaking, and heritage narrative. The activation, construction, and operation of ICH safeguarding action nets require cross-field collaboration, with boundary spanners playing a crucial role. In selecting and revitalizing cultural practices, Jingdezhen's ICH safeguarding actions follow "narrative rationality." Once a fulcrum is identified in the porcelain industry historical narrative sequence, inscribing these skills in the Representative Inventory of Intangible Cultural Heritage Elements is justified. In this process, the existence of history and the continuity of transmission are even potentially disregarded. Subsequently, through continuous modification and investment, the logical connections between elements and their relationship with Jingdezhen porcelain industry history are continuously strengthened; the narrative rationality is sustainably reinforced. In the coexisting market of handmade and mechanized porcelain, ICH safeguarding continually generates "rational narratives" that validate the price differentials between them. Jingdezhen's ICH safeguarding demonstrates a strong "textual constraint": the preparation of application/recommendation files determines the outcome of identification, with factors such as boundary spanners' assistance and actors' first-mover advantages explicitly reflected in the documentation. As the identification of Representative Inheritors progresses, an "annex book" derived from the application/recommendation forms has emerged and shows a trend toward refinement. Due to the "transmission lineage" requirements in the forms, craftspeople strategically adjust and present their social relations. Some proactively establish connections with craftspeople possessing the same skill type to embed themselves in a specific transmission lineage for application. This process has formed new social networks, "tabular relationships," among craftspeople. After inscription, the nomination texts for elements, Representative Inheritors, and safeguarding carriers are widely reproduced by media, which then in turn shapes CGIs' perception of ICH. These texts, especially those for element nomination, serve as the blueprints and templates for other plans, programs, and forms. Each semantic unit within them may be selected and translated by actors to guide or explain their actions, with element names exerting particularly significant influence as their most concise and direct part. The ambiguity of nomination texts has triggered "reconstruction of tangible carriers," while their breadth has given rise to the "pre-established inventory" mechanism, facilitating the "classification identification" model. The "pre-established inventory" refers to compiling an inventory based on the overall status of ICH prior to element nomination. This mechanism serves to safeguard complex comprehensive elements and establish regional inventories, while also providing adjustment strategies for elements whose practical existence is disconnected from the inscription. Under this mechanism, if an element has a broad scope, making its safeguarding challenging to focus or implement, it can be treated as a parent element and divided into sub-elements to refine safeguarding content. Conversely, if an element has a narrow scope, resulting in insufficient safeguarding coverage or failing to encompass the complete practice system, it can be incorporated into a broader parent element to integrate and expand safeguarding content. The national-level element Jingdezhen Handmade Porcelain Skills encompasses all skills of the porcelain industry, requiring group collaboration. Simultaneously, China conducts individual identification for Representative Inheritors. To address the disconnect between safeguarding rules and the existence of elements, multiple actors eventually confirmed the "classification identification" model. This model takes the integrity of the parent element's core content as a prerequisite. It first divides the parent element into sub-elements using specific criteria, forming a "pre-established inventory." Then, it conducts applications and recommendations for Representative Inheritors of sub-elements, ultimately jointly identifying qualified craftspeople as representative inheritors. This approach not only facilitates the identification of Representative Inheritors for group collaborative elements but also provides a systematic safeguarding framework for elements where a broad scope and complex internal structure has caused a disconnect between Representative Inheritor identification and transmission practices. This model achieves organic integration between the dynamic adjustment of the inventory system and transmission practices

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