318 research outputs found
Determining the core content of a digital survivorship care plan for melanoma survivors:A multi-stakeholder Delphi-consensus study
Increasing melanoma incidence and improved survival emphasize the importance of survivorship care plans (SCPs). We conducted a multistakeholder Delphi study to achieve consensus on core melanoma SCP content. Of the 44 potential elements, 24 (55%) reached consensus for inclusion. Notably, melanoma survivors and healthcare providers differed in their preferences, with survivors prioritizing coordination improvements and healthcare providers emphasizing psychosocial care. Exploring and overcoming these differences in opinions and including the consented elements as a basis in the design of the SCP can facilitate its implementation in practice and lead to survivorship care tailored to stakeholders' needs
Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish
BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5 days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5 μM) and TBT (1 nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p
Orchestrating a smart circular economy: Guiding principles for digital product passports
In order for firms to implement the Circular Economy, and close all material and energy cycles, connections are needed not only within but also between multiple Industrial Ecosystems. To enable such complex interconnections, the European Union is preparing legislation to enforce the use of digital product passports (DPPs). These are verifiable collections of data about products’ composition, environmental footprint and opportunities for preventing waste. The notion of the DPP relies heavily on a suitable digital infrastructure, and it opens the possibility of using the power of artificial intelligence (AI), to optimize circular production within and between Industrial Ecosystems. The benefits of DPPs will only be attained if their design, knowledge engineering, and implementation is well-orchestrated. The purpose of this paper is to develop a set of guiding principles for the orchestration of DPPs, based upon a trans-disciplinary analysis, that form a theoretical basis upon which future research can build
NGO Legitimacy: Four Models
The aim of this paper is to examine NGOs’ legitimacy in the context of global politics. In order to yield a better understanding of NGOs’ legitimacy at the international level it is important to examine how their legitimacy claims are evaluated. This paper proposes dividing the literature into four models based on the theoretical and analytical approaches to their legitimacy claims: the market model, social change model, new institutionalism model and the critical model. The legitimacy criteria generated by the models are significantly different in their analytical scope of how one is to assess the role of NGOs operating as political actors contributing to democracy. The paper argues that the models present incomplete, and sometimes conflicting, views of NGOs’ legitimacy and that this poses a legitimacy dilemma for those assessing the political agency of NGOs in world politics. The paper concludes that only by approaching their legitimacy holistically can the democratic role of NGOs be explored and analysed in the context of world politics
Caregiver education in Parkinson’s disease: formative evaluation of a standardized program in seven European countries
The formative evaluation of a standardized psychosocial education program for patients with Parkinson's disease (PD) and their caregivers. The results of the participation of the caregivers are presented next to the data of the patients. Caregivers (n = 137) and patients with PD (n = 151) participated in the 8-week program in separate groups. Measurements were performed on psychosocial problems (BELA-P/A-k), health state (EQ-5D VAS), quality of life (PDQ-39) and depression (SDS) 1 week before and 1 week after the program. Participants rated their mood on a visual analogue scale before and after each session, and they filled in an evaluation questionnaire after the last session. Scores on the BELA-P/A-k improved significantly on the 'bothered by scale' as well as the 'need for help scale'. No improvements were found on EQ-5D VAS, PDQ-39 and SDS. Mood ratings improved significantly after each session. Most participants evaluated the program as positive. Feedback led to improvements in the program, which are incorporated in a final manual. The program was feasible to run in the different countries. This exploratory study led to improvements in the program and recommendations for further research. A study on the effectiveness of the program is the next step.Pathophysiology of paroxysmal and chronic degenerative progressive disorder of the central and periferal nervous syste
From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting
BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p
From decision to reflection:understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting
BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory.METHODS:Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted.RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported.CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.</p
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