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Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death, and survival outcomes vary across countries and regions. To improve survival, the European Resuscitation Council Guidelines encourage the implementation of technologies like smartphone applications to alert voluntary first responders (VFRs) who are near a suspected OHCA. VFRs are of great importance in the ´chain of survival´, but there is still a lack of knowledge about their experiences; especially of those operating in rural areas. Understanding those experiences is crucial in developing appropriate interventions to train, encourage, and safeguard VFRs in their mission. Therefore, the aim of this study was to describe VFRs´ experiences of being dispatched to suspected OHCA in rural areas., Methods: The study used an inductive design. The data were collected using individual interviews with 16 VFRs and analysed using qualitative content analysis., Results: The results are presented in terms of six generic categories ''Being motivated and prepared'', ''Having strategies to undertake the mission'', ''Collaborating with others'', ''Being ethically aware'', ''Supporting the family members'', and ''Coping with the mission'', which formed the basis of the main category 'Desire to save lives and help others'. The findings showed that VFRs had a genuine desire to contribute to save lives in this rural area. Regardless of the circumstances, they were prepared to leave everything and act to the best for the victim and their family members. In theirs' missions they collaborated with others at the scene and were guided by ethics while they acted in complex circumstances., Conclusions: VFRs dispatched in rural areas express a desire to save lives. In their missions, they acted in complex situations and experienced both emotional and ethical challenges. The design, implementation, and evaluation of support interventions directed at VFRs should be prioritised, especially in rural areas, as it can contribute to more people becoming and remaining VFRs, which in turn could contribute to sustainable development., (© 2024. The Author(s).)

The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche-related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

FLT3 tyrosine kinase inhibitor (TKI) therapy evolved into a standard therapy in FLT3-mutated AML. TKI resistance, however, develops frequently with poor outcomes. We analyzed acquired TKI resistance in AML cell lines by multilayered proteome analyses. Leupaxin (LPXN), a regulator of cell migration and adhesion, was induced during early resistance development, alongside the tyrosine kinase PTK2B which phosphorylated LPXN. Resistant cells differed in cell adhesion and migration, indicating altered niche interactions. PTK2B and LPXN were highly expressed in leukemic stem cells in FLT3-ITD patients. PTK2B/FAK inhibition abrogated resistance-associated phenotypes, such as enhanced cell migration. Altered pathways in resistant cells, assessed by nascent proteomics, were largely reverted upon PTK2B/FAK inhibition. PTK2B/FAK inhibitors PF-431396 and defactinib synergized with different TKIs or daunorubicin in FLT3-mutated AML. Midostaurin-resistant and AML cells co-cultured with mesenchymal stroma cells responded particularly well to PTK2B/FAK inhibitor addition. Xenograft mouse models showed significant longer time to leukemia symptom-related endpoint upon gilteritinib/defactinib combination treatment in comparison to treatment with either drug alone. Our data suggest that the leupaxin-PTK2B axis plays an important role in acquired TKI resistance in AML. PTK2B/FAK inhibitors act synergistically with currently used therapeutics and may overcome emerging TKI resistance in FLT3-mutated AML at an early timepoint., (© 2022. The Author(s).)

Aim: To explore nursing students' experiences of applying problem-based learning to train the core competence teamwork and collaboration., Design: The study used a qualitative descriptive design., Method: The data were collected using individual interviews with a purposive sample of 11 students and analysed using inductive qualitative content analysis., Results: The students' experiences of applying problem-based learning to train the core competence teamwork and collaboration were described in two generic categories: prerequisites to train teamwork and collaboration and abilities practised in the base group. The generic category "prerequisites to train teamwork and collaboration" includes three subcategories: previous experience and education, composition of the base group, and common goals and values in the base group. The generic category "abilities practised in the base group" includes four subcategories: taking personal responsibility, practising role distribution and leadership, developing communication skills and creating togetherness in the base group., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)