2,615 research outputs found

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    How social media brand community development impacts consumer engagement and value formation; perspectives from the cosmetics industry

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    Social media and social media brand communities (SMBCs) are powerful tools for long-term consumer-brand relationship building. As a result, SMBCs are becoming significant marketing channels. Despite the wide use and adoption of SMBCs, further research is called for, as both practitioners and academics lack an understanding of the processes taking place within SMBCs. This study aims to contribute to knowledge of: (1) consumer engagement, (2) value formation in SMBCs, and (3) establishing the relationship between consumer engagement and value formation within the SMBC environment. This thesis adopts netnography, a method commonly employed to explore online communities in the social media environment. Three cosmetics brands were selected for this study. The selection was driven by geographical location, posting frequency and user activity. Data were retrospectively collected from Facebook SMBCs between 1st December 2019 and 31st January 2020. The data analysis employed thematic analysis techniques and was further guided by netnographic procedural steps, encompassing 25 distinct data operations. In total, 87 conversation threads were examined, which included 6,401 consumer comments. The findings present a typology of brand posts consisting of five overarching themes: presentation of offerings, belongingness building, engagement building, value-led, and educational. The research also identified a consumer comment typology consisting of four overarching themes brand-centred communication, cognitive-centred communication, conversation-centred communication, and personal experience-centred communication. Additionally, the thesis explores value formation processes within SMBCs, and the value types formed through consumer-to-consumer value formation interaction, brand-to-consumer value formation interaction, consumer-to-brand value formation interaction, as well as individual value formation processes, i.e., customer independent value formation and brand independent value facilitation. Through the findings, thesis broadens knowledge of the implication of SMBC development on consumer engagement. Additionally, this study extends the scope of value formation beyond service marketing, providing valuable insights into how value is created and perceived in the context of SMBCs. This research is also of significance for practice as it offers guidance and insight into how different brand posts can facilitate SMBC development, and, in turn, consumer engagement and value formation. The research provides a link between SMBC development and consumer engagement, highlighting the importance of SMBCs in the successful facilitation of consumer engagement. In particular, it provides evidence that the development of an SMBC has a significant impact on consumer engagement. The typology of brand posts that this study generates highlights the link between the types of posts published by the brand and SMBC development. In addition, the typology of consumer posts also suggests that there is a link between the types of comments published by consumers and the degree of SMBC development. As a result, the findings indicate significant growth in the variety of topics discussed within more developed SMBCs alongside a shift within the topics discussed. The study also investigates value formation within SMBCs, thereby enhancing the understanding of how SMBCs can facilitate value formation. By doing so, this research successfully extends the value formation lens predominantly applied in service marketing. In particular, the findings highlight the role of different actors in enabling the formation of different value types. Furthermore, the research emphasises the value of SMBCs as knowledge repositories as important virtual spaces for both brands and consumers. The findings facilitate understanding of the importance of SMBCs in value formation processes, contributing to advancing knowledge of the role of SMBCs in the development of consumer engagement and value formation. The thesis presents a contextualised conceptual framework of value formation within SMBCs, that captures different interactions taking place in the SMBC environment but also draws attention to the different value types generated through interaction between different actors. Finally, the thesis offers a conceptual framework of SMBCs, consumer engagement and value formation, which captures the correlation between the three researched concepts

    Information actors beyond modernity and coloniality in times of climate change:A comparative design ethnography on the making of monitors for sustainable futures in Curaçao and Amsterdam, between 2019-2022

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    In his dissertation, Mr. Goilo developed a cutting-edge theoretical framework for an Anthropology of Information. This study compares information in the context of modernity in Amsterdam and coloniality in Curaçao through the making process of monitors and develops five ways to understand how information can act towards sustainable futures. The research also discusses how the two contexts, that is modernity and coloniality, have been in informational symbiosis for centuries which is producing negative informational side effects within the age of the Anthropocene. By exploring the modernity-coloniality symbiosis of information, the author explains how scholars, policymakers, and data-analysts can act through historical and structural roots of contemporary global inequities related to the production and distribution of information. Ultimately, the five theses propose conditions towards the collective production of knowledge towards a more sustainable planet

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Primary liver cancer, consisting primarily of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a heterogeneous malignancy with a dismal prognosis, resulting in the third leading cause of cancer mortality worldwide [1, 2]. It is characterized by unique histological features, late-stage diagnosis, a highly variable mutational landscape, and high levels of heterogeneity in biology and etiology [3-5]. Treatment options are limited, with surgical intervention the main curative option, although not available for the majority of patients which are diagnosed in an advanced stage. Major contributing factors to the complexity and limited treatment options are the interactions between primary tumor cells, non-neoplastic stromal and immune cells, and the extracellular matrix (ECM). ECM dysregulation plays a prominent role in multiple facets of liver cancer, including initiation and progression [6, 7]. HCC often develops in already damaged environments containing large areas of inflammation and fibrosis, while CCA is commonly characterized by significant desmoplasia, extensive formation of connective tissue surrounding the tumor [8, 9]. Thus, to gain a better understanding of liver cancer biology, sophisticated in vitro tumor models need to incorporate comprehensively the various aspects that together dictate liver cancer progression. Therefore, the aim of this thesis is to create in vitro liver cancer models through organoid technology approaches, allowing for novel insights into liver cancer biology and, in turn, providing potential avenues for therapeutic testing. To model primary epithelial liver cancer cells, organoid technology is employed in part I. To study and characterize the role of ECM in liver cancer, decellularization of tumor tissue, adjacent liver tissue, and distant metastatic organs (i.e. lung and lymph node) is described, characterized, and combined with organoid technology to create improved tissue engineered models for liver cancer in part II of this thesis. Chapter 1 provides a brief introduction into the concepts of liver cancer, cellular heterogeneity, decellularization and organoid technology. It also explains the rationale behind the work presented in this thesis. In-depth analysis of organoid technology and contrasting it to different in vitro cell culture systems employed for liver cancer modeling is done in chapter 2. Reliable establishment of liver cancer organoids is crucial for advancing translational applications of organoids, such as personalized medicine. Therefore, as described in chapter 3, a multi-center analysis was performed on establishment of liver cancer organoids. This revealed a global establishment efficiency rate of 28.2% (19.3% for hepatocellular carcinoma organoids (HCCO) and 36% for cholangiocarcinoma organoids (CCAO)). Additionally, potential solutions and future perspectives for increasing establishment are provided. Liver cancer organoids consist of solely primary epithelial tumor cells. To engineer an in vitro tumor model with the possibility of immunotherapy testing, CCAO were combined with immune cells in chapter 4. Co-culture of CCAO with peripheral blood mononuclear cells and/or allogenic T cells revealed an effective anti-tumor immune response, with distinct interpatient heterogeneity. These cytotoxic effects were mediated by cell-cell contact and release of soluble factors, albeit indirect killing through soluble factors was only observed in one organoid line. Thus, this model provided a first step towards developing immunotherapy for CCA on an individual patient level. Personalized medicine success is dependent on an organoids ability to recapitulate patient tissue faithfully. Therefore, in chapter 5 a novel organoid system was created in which branching morphogenesis was induced in cholangiocyte and CCA organoids. Branching cholangiocyte organoids self-organized into tubular structures, with high similarity to primary cholangiocytes, based on single-cell sequencing and functionality. Similarly, branching CCAO obtain a different morphology in vitro more similar to primary tumors. Moreover, these branching CCAO have a higher correlation to the transcriptomic profile of patient-paired tumor tissue and an increased drug resistance to gemcitabine and cisplatin, the standard chemotherapy regimen for CCA patients in the clinic. As discussed, CCAO represent the epithelial compartment of CCA. Proliferation, invasion, and metastasis of epithelial tumor cells is highly influenced by the interaction with their cellular and extracellular environment. The remodeling of various properties of the extracellular matrix (ECM), including stiffness, composition, alignment, and integrity, influences tumor progression. In chapter 6 the alterations of the ECM in solid tumors and the translational impact of our increased understanding of these alterations is discussed. The success of ECM-related cancer therapy development requires an intimate understanding of the malignancy-induced changes to the ECM. This principle was applied to liver cancer in chapter 7, whereby through a integrative molecular and mechanical approach the dysregulation of liver cancer ECM was characterized. An optimized agitation-based decellularization protocol was established for primary liver cancer (HCC and CCA) and paired adjacent tissue (HCC-ADJ and CCA-ADJ). Novel malignancy-related ECM protein signatures were found, which were previously overlooked in liver cancer transcriptomic data. Additionally, the mechanical characteristics were probed, which revealed divergent macro- and micro-scale mechanical properties and a higher alignment of collagen in CCA. This study provided a better understanding of ECM alterations during liver cancer as well as a potential scaffold for culture of organoids. This was applied to CCA in chapter 8 by combining decellularized CCA tumor ECM and tumor-free liver ECM with CCAO to study cell-matrix interactions. Culture of CCAO in tumor ECM resulted in a transcriptome closely resembling in vivo patient tumor tissue, and was accompanied by an increase in chemo resistance. In tumor-free liver ECM, devoid of desmoplasia, CCAO initiated a desmoplastic reaction through increased collagen production. If desmoplasia was already present, distinct ECM proteins were produced by the organoids. These were tumor-related proteins associated with poor patient survival. To extend this method of studying cell-matrix interactions to a metastatic setting, lung and lymph node tissue was decellularized and recellularized with CCAO in chapter 9, as these are common locations of metastasis in CCA. Decellularization resulted in removal of cells while preserving ECM structure and protein composition, linked to tissue-specific functioning hallmarks. Recellularization revealed that lung and lymph node ECM induced different gene expression profiles in the organoids, related to cancer stem cell phenotype, cell-ECM integrin binding, and epithelial-to-mesenchymal transition. Furthermore, the metabolic activity of CCAO in lung and lymph node was significantly influenced by the metastatic location, the original characteristics of the patient tumor, and the donor of the target organ. The previously described in vitro tumor models utilized decellularized scaffolds with native structure. Decellularized ECM can also be used for creation of tissue-specific hydrogels through digestion and gelation procedures. These hydrogels were created from both porcine and human livers in chapter 10. The liver ECM-based hydrogels were used to initiate and culture healthy cholangiocyte organoids, which maintained cholangiocyte marker expression, thus providing an alternative for initiation of organoids in BME. Building upon this, in chapter 11 human liver ECM-based extracts were used in combination with a one-step microfluidic encapsulation method to produce size standardized CCAO. The established system can facilitate the reduction of size variability conventionally seen in organoid culture by providing uniform scaffolding. Encapsulated CCAO retained their stem cell phenotype and were amendable to drug screening, showing the feasibility of scalable production of CCAO for throughput drug screening approaches. Lastly, Chapter 12 provides a global discussion and future outlook on tumor tissue engineering strategies for liver cancer, using organoid technology and decellularization. Combining multiple aspects of liver cancer, both cellular and extracellular, with tissue engineering strategies provides advanced tumor models that can delineate fundamental mechanistic insights as well as provide a platform for drug screening approaches.<br/

    It doesn't end with closure:Optimizing health care throughout life after esophageal atresia repair

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    Intestinal innervation and its role in mucosal damage and inflammation

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    The regulatory role of the autonomic nervous system (ANS) in intestinal inflammation and immunity is widely acknowledged. In this thesis, we investigated mediating pathways and demonstrated a pivotal role for the spleen. We studied the effect of electrical splenic nerve bundle stimulation (SpNS) in a mouse model of experimental colitis induced by dextran sulfate sodium and showed that SpNS reduced colitis. Further, we elucidated effects of sympathetic activity on intestinal mucosal homeostasis. Chemical sympathetic denervation through 6-hydroxydopamine led to enhanced intestinal inflammation, and impaired barrier integrity. In contrast, adrenergic receptor stimulation through UK 14,304, a specific receptor agonist, led to increased proliferation and stem cell function. Adrenergic receptor α2A was found to act as molecular delegate of intestinal epithelial sympathetic activity controlling cell proliferation, differentiation, and host defense. The ANS is a complex network activating numerous pathways and therefore effects can be ambiguous and are often challenging to interpret. Our studies increased the understanding of effects of autonomic neuronal activity on intestinal processes, and future studies should continue investigations with not only experimental, but also clinical research. Ultimately, a role for bioelectronic medicine in intestinal immunity and mucosal healing can be allocated and neuromodulatory techniques are to be examined as a plausible treatment modality

    It doesn't end with closure:Optimizing health care throughout life after esophageal atresia repair

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    Conversations on Empathy

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    In the aftermath of a global pandemic, amidst new and ongoing wars, genocide, inequality, and staggering ecological collapse, some in the public and political arena have argued that we are in desperate need of greater empathy — be this with our neighbours, refugees, war victims, the vulnerable or disappearing animal and plant species. This interdisciplinary volume asks the crucial questions: How does a better understanding of empathy contribute, if at all, to our understanding of others? How is it implicated in the ways we perceive, understand and constitute others as subjects? Conversations on Empathy examines how empathy might be enacted and experienced either as a way to highlight forms of otherness or, instead, to overcome what might otherwise appear to be irreducible differences. It explores the ways in which empathy enables us to understand, imagine and create sameness and otherness in our everyday intersubjective encounters focusing on a varied range of "radical others" – others who are perceived as being dramatically different from oneself. With a focus on the importance of empathy to understand difference, the book contends that the role of empathy is critical, now more than ever, for thinking about local and global challenges of interconnectedness, care and justice

    NEMISA Digital Skills Conference (Colloquium) 2023

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    The purpose of the colloquium and events centred around the central role that data plays today as a desirable commodity that must become an important part of massifying digital skilling efforts. Governments amass even more critical data that, if leveraged, could change the way public services are delivered, and even change the social and economic fortunes of any country. Therefore, smart governments and organisations increasingly require data skills to gain insights and foresight, to secure themselves, and for improved decision making and efficiency. However, data skills are scarce, and even more challenging is the inconsistency of the associated training programs with most curated for the Science, Technology, Engineering, and Mathematics (STEM) disciplines. Nonetheless, the interdisciplinary yet agnostic nature of data means that there is opportunity to expand data skills into the non-STEM disciplines as well.College of Engineering, Science and Technolog
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