New Perspectives of Residents’ Perceptions in a Mature Seaside Destination

This research examines the relationship between residents of a mature tourist destination and tourism. To do this, the place attachment and rootedness shown by the residents towards the place where they live are assessed, as are their attitudes and level of satisfaction towards tourism. To carry out the research, 770 surveys were completed in the city of Benalmádena (Costa del Sol, Spain). Unlike other previous studies on place attachment, the level of place attachment and rootedness are assessed separately, using a specific indicator for rootedness. The results show that place attachment and rootedness behave differently in relation to the attitude towards tourism. Another significant result is that residents’ attitudes towards tourism in this destination are positive, being more favourable among native residents. Finally, residents show a clear level of place attachment and satisfaction with tourism development, which seems to be related to remarkable social resilience. Despite the strong vulnerability of the mass tourism model, Benalmádena displays significant resilience due to its social structure.The research was supported by the research projects: “Transformations of the historical urban landscape induced by tourism: contradictions and controversies, government and local governance” (CSO2016- 75470-R); “Over-tourism in Spanish coastal Destinations. Tourism de- growth strategies. An approach from the social dimension” (RTI2018- 094844-B-C33), Spanish Ministry of Science, Innovation and Universities (National Plan for R+D+i)

ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

Safety and efficacy of asciminib treatment in chronic myeloid leukemia patients in real-life clinical practice

Chronic myeloid leukemia; Asciminib; TreatmentLeucemia mieloide crónica; Asciminib; TratamientoLeucèmia mieloide crònica; Asciminib; TractamentDespite the excellent overall survival (OS) of chronic myeloid leukemia (CML) patients, a significant proportion will fail currently available tyrosine-kinase inhibitors (TKIs) due to resistance or intolerance. Intolerant patients are usually managed successfully with alternative second-generation tyrosine-kinase inhibitors (2GTKIs). However, more than half of the patients will eventually discontinue second-line treatment due to loss of response or toxicity. Ponatinib is an effective drug in the setting of resistance to 2GTKIs, however with life-threatening side effects and varying responses. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that potently and specifically inhibits BCR-ABL1 via binding to a pocket distinct from the ATP binding site of the kinase. Asciminib has the potential to overcome resistance to prior TKIs, and also offers the possibility of dual inhibition of BCR-ABL1 in combination with ATP-binding TKIs. Asciminib has been evaluated in a phase I study in patients with Ph-positive leukemia failing prior TKIs, with promising results. Our aim is to share the first data on the use of asciminib in CML patients in clinical practice, allowed by Novartis under a managed-access program (MAP)

The phylogenetically distinct early human embryo

The phylogenetic singularity of the human embryo remains unresolved as cell types of the human blastocyst have resisted classification. Combining clustering of single cellular transcriptomes and dynamically expressed genes we resolve the cell types. This unveils the missing inner cell mass (ICM) and reveals classical step-wise development. Conversely, numerous features render our blastocyst phylogenetically distinct: unlike mice, our epiblast is self-renewing and we have blastocyst non-committed cells (NCCs), part of an apoptosis-mediated quality control/purging process. At the transcriptome-level all primate embryos are distinct as the pluripotent cell types are uniquely fast evolving. A substantial fraction of gene expression gain and loss events between human and new-world monkeys involve endogenous retrovirus H (ERVH). Human pluripotent cells are unique in which (H)ERVH's are active, the extent to which these modulate neighbour gene expression and their ability to suppress mutagenic transposable elements. Current naive cultures are heterogeneous and both developmentally and phylogenetically "confused"

Combination of linear classifiers using score function -- analysis of possible combination strategies

In this work, we addressed the issue of combining linear classifiers using their score functions. The value of the scoring function depends on the distance from the decision boundary. Two score functions have been tested and four different combination strategies were investigated. During the experimental study, the proposed approach was applied to the heterogeneous ensemble and it was compared to two reference methods -- majority voting and model averaging respectively. The comparison was made in terms of seven different quality criteria. The result shows that combination strategies based on simple average, and trimmed average are the best combination strategies of the geometrical combination