Does Experience Matter? Unraveling the Drivers of Expert and Non-Expert Mobile Consumers

The surge in mobile shopping faces a challenge as not all potential consumers are comfortable with this mode. Retailers need a deeper understanding of factors influencing user experience to enhance marketing strategies. Despite extensive research, a gap remains in comprehending this aspect. Using a statistical PLS-SEM-ANN approach, this research aims to explore the psychological dimensions of expert and non-expert mobile shoppers for establishing better targeted marketing strategies in m-commerce settings. Analyzing experience levels in mobile commerce (m-commerce), key drivers like enjoyment, usefulness, subjective norms, and trust were scrutinized as interaction settings for consumers using mobile technologies. The findings reveal that, for less experienced m-shoppers, trust is the most significant driver of attitude and satisfaction, while, for experienced users, trust and usefulness are the primary antecedents. This research provides novel insights, aiding mobile marketers in refining targeting strategies based on consumer experience levels, emphasizing the importance of usefulness and trustworthiness for a seamless m-shopping experience

DNMT3B in vitro knocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS

Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition

BACKGROUND: Rhabdomyosarcoma (RMS) is the most commonly diagnosed malignant soft tissue tumour in children and adolescents. Aberrant expression of Anaplastic Lymphoma Kinase (ALK) and MET gene has been implicated in the malignant progression of RMS, especially in the alveolar subtype. This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied. METHODS: RH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays. Multiple approaches, including flow cytometry, immunofluorescence, western blotting and siRNA-based knock-down, were used in order to investigate possible molecular mechanisms linked to crizotinib activity. RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival. Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2. Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively. The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells. Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential. CONCLUSIONS: These results provide a further insight into the molecular mechanisms affected by crizotinib in ARMS cells inferring that it could be a useful therapeutic tool in ARMS cancer treatment

New Challenges for Sustainable Organizations in Light of Agenda 2030 for Sustainability

Sustainability is one of humanity’s most daunting issues at present. Increasing popula- tion, escalation of anthropogenic activities, industrialization, modern agricultural practices that pollute water, air, and soil around the world, and ever-increasing greenhouse gas emissions mean that sustainability is now in doubt [1]. In response to these critical concerns, the world has come up with several initiatives including Agenda 2030. Agenda 2030 is a commitment to eradicate poverty and achieve sustainable development worldwide, ensuring that no one is left behind by 2030. Its adoption was a landmark achievement, providing a shared vision towards sustainable development for all. Its 17 Sustainable Development Goals (SDGs) and 169 targets aim to end the plethora of development problems and deliver a better univers

Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype, induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells

EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines

Management of PALB2-associated breast cancer: A literature review and case report

Key Clinical Message Germline pathogenic variants (PV) of the PALB2 tumor suppressor gene are associated with an increased risk of breast, pancreatic, and ovarian cancer. In previous research, PALB2-associated breast cancer showed aggressive clinicopathological phenotypes, particularly triple-negative subtype, and higher mortality regardless of tumor stage, type of chemotherapy nor hormone receptor status. The identification of this germline alteration may have an impact on clinical management of breast cancer (BC) from the surgical approach to the systemic treatment choice. We herein report the case of a patient with a germline PV of PALB2, diagnosed with locally advanced PD-L1 positive triple-negative BC, who progressed after an immune checkpoint inhibitor (ICI)-containing regimen and then experienced a pathologic complete response after platinum-based chemotherapy. This case report hints a major role of the germline PALB2 alteration compared to the PD-L1 expression as cancer driver and gives us the opportunity to extensively review and discuss the available literature on the optimal management of PALB2-associated BC. Overall, our case report and review of the literature provide additional evidence that the germline analysis of PALB2 gene should be included in routine genetic testing for predictive purposes and to refine treatment algorithms

Back to the Past. The paleogeography as key to understand the Middle Palaeolithic peopling at Grotta dei Santi (Mt Argentario – Tuscany)

The mobility of hunter-gatherer groups is crucial in understanding Palaeolithic settlement dynamics. The concept of mobility cannot be separated from the space in which it occurs, including landscape components, localization of critical resources and of other sites, and routes between them. Nevertheless, the landscape is not constant in time due to the geomorphological changes that occurred in the long timescale of Prehistory. Here we present a paleogeographic reconstruction of the coastal area around Grotta dei Santi during the Neandertal occupation. A GIS-based approach, combining geological, bathymetric, and sea-level fluctuations data, allows us to reconstruct the landscape around the cave at about 45 ky BP. The cave today opens onto a cliff facing the sea. The Neandertal occupation occurred with a sea-level 74 m lower than present-day. Consequently, the cave faced a vast coastal plain, playing a strategic role due to its position, allowing both proximity and control of essential resources

Paleogeographic reconstruction of the Tuscan coastal area nearby Grotta dei Santi (Monte Argentario, Italy) during the Neandertal occupation

The mobility of hunter-gatherer groups is crucial in understanding Palaeolithic settlement dynamics. The concept of mobility cannot be separated from the space in which it occurs, including landscape components, localization of critical resources and of other sites, and routes between them. Nevertheless, the landscape is not constant in time due to the geomorphological changes that occurred in the long timescale of Prehistory. Here we present a paleogeographic reconstruction of the coastal area around Grotta dei Santi during the Neandertal occupation. A GIS-based approach, combining geological, bathymetric, and sea-level fluctuations data, allows us to reconstruct the landscape around the cave at about 45 ky BP. The cave today opens onto a cliff facing the sea. The Neandertal occupation occurred with a sea-level 74 m lower than present-day. Consequently, the cave faced a vast coastal plain, playing a strategic role due to its position, allowing both proximity and control of essential resources. © 2022 IMEKO TC-4 International Conference on Metrology for Archaeology and Cultural Heritage, MetroArchaeo 2022.All rights reserved

A sketch of known and novel MYCN-associated miRNA networks in neuroblastoma

Neuroblastoma (NB) originates from neural crest-derived precursors and represents the most common childhood extracranial solid tumour. MicroRNAs (miRNAs), a class of small non-coding RNAs that participate in a wide variety of biological processes by regulating gene expression, appear to play an essential role within the NB context. High-throughput next generation sequencing (NGS) was applied to study the miRNA transcriptome in a cohort of NB tumours with and without MYCN-amplification (MNA and MNnA, respectively) and in dorsal root ganglia (DRG), as a control. Out of the 128 miRNAs differentially expressed in the NB vs. DRG comparison, 47 were expressed at higher levels, while 81 were expressed at lower levels in the NB tumours. We also found that 23 miRNAs were differentially expressed in NB with or without MYCN-amplification, with 17 miRNAs being upregulated and 6 being downregulated in the MNA subtypes. Functional annotation analysis of the target genes of these differentially expressed miRNAs demonstrated that many mRNAs were involved in cancer-related pathways, such as DNA-repair and apoptosis as well as FGFR and EGFR signalling. In particular, we found that miR-628-3p negatively affects MYCN gene expression. Furthermore, we identified a novel miRNA candidate with variable expression in MNA vs. MNnA tumours, whose putative target genes are implicated in the mTOR pathway. The present study provides further insight into the molecular mechanisms that correlate miRNA dysregulation to NB development and progression

Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34+ Cells

Abstract BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs), have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs) is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+) were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+) cells with enhanced self renewal and cardioprotection