Search Results (2)

The vulnerability of atoll countries to sea level rise underscores the pivotal connection between climate change and migration. This study examines the multifaceted challenges faced by such countries, including land loss, economic disruption, water contamination, and increased vulnerability to extreme weather events, and potential adaptation strategies, such as migration to developed countries and other islands, land reclamation, and floating platform development. The situation of the Maldives, particularly the creation of the artificial island of Hulhumalé, is explored as a case study. Hulhumalé is designed to alleviate congestion while addressing concerns about rising sea levels. This study employed a questionnaire survey and analyzed the data using importance analysis of permutation features and structural equation modeling following the Wilcoxon–Mann–Whitney tests. The results revealed that the key factors influencing resident satisfaction after migration were clean housing, resilience to natural disasters, sports facilities, and environmental quality. Adaptation strategies must be tailored to each country’s unique circumstances, considering the interconnectedness of environmental and socioeconomic factors in addressing climate-induced migration. Considering Hulhumalé as a model for climate change adaptation, concerted global action is necessary to mitigate the impacts of climate change and ensure the security and well-being of vulnerable populations. Full article

Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination with other treatment modalities such as intrathecal therapy, radiotherapy and other targeted agents is missing. We report on our clinical experience of entrectinib therapy in two CSF disseminated ROS1/NTRK-fusion-positive pHGG cases. Combination of entrectinib with radiotherapy or intrathecal chemotherapy appears to be safe and has the potential to act synergistically with entrectinib treatment. In addition, we demonstrate CSF penetrance of entrectinib for the first time in patient samples suggesting target engagement even upon CSF dissemination. Moreover, in vitro analyses of two novel cell models derived from one case with NTRK-fusion revealed that combination therapy with either a MEK (trametinib) or a CDK4/6 (abemaciclib) inhibitor synergistically enhances entrectinib anticancer effects. In summary, our comprehensive study, including clinical experience, CSF penetrance and in vitro data on entrectinib therapy of NTRK/ROS1-fusion-positive pHGG, provides essential clinical and preclinical insights into the multimodal treatment of these highly aggressive tumors. Our data suggest that combined inhibition of NTRK/ROS1 and other therapeutic vulnerabilities enhances the antitumor effect, which should be followed-up in further preclinical and clinical studies. Full article