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Discourses of global education, citizenship and competence have been characterising the higher education literature in recent years. The COVID-19 pandemic has both heightened the relevance of global citizenship education and presented new challenges as educators and students continue to grapple with the lasting impact and implications. This paper presents the findings of a research study which looked at the perceived learning outcomes of a "virtual exchange" project which addressed issues relevant to global citizenship, involving students in European and Southern Mediterranean countries in online dialogue programmes. The study used quantitative and qualitative approaches to the analysis of responses to open survey questions using the quantitative tool IRAMUTEQ (Sbalchiero & Tuzzi, 2016) and focus groups. Participants perceived that their learning was happening above all through their encounters and discussions with people from different backgrounds. They reported learning to listen actively and carefully, to accept and/or respect different opinions and experiences. The findings open up possibilities for how higher education institutions might engage students in online transnational and global learning experiences--which can contribute to thinking about renewing education and societies in a post-pandemic world.

Abstract Breast cancer (BC) is a leading cause of global cancer-related mortality in women, necessitating accurate tumor classification for timely intervention. Molecular and histological factors, including PAM50 classification, estrogen receptor α (ERα), breast cancer type 1 susceptibility protein (BRCA1), progesterone receptor (PR), and HER2 expression, contribute to intricate BC subtyping. In this work, through a combination of bioinformatic and wet lab screenings, followed by classical signal transduction and cell proliferation methods, and employing multiple BC cell lines, we identified enhanced sensitivity of ERα-positive BC cell lines to ALK and MELK inhibitors, inducing ERα degradation and diminishing proliferation in specific BC subtypes. MELK inhibition attenuated ERα transcriptional activity, impeding E2-induced gene expression, and hampering proliferation in MCF-7 cells. Synergies between MELK inhibition with 4OH-tamoxifen (Tam) and ALK inhibition with HER2 inhibitors revealed potential therapeutic avenues for ERα-positive/PR-positive/HER2-negative and ERα-positive/PR-negative/HER2-positive tumors, respectively. Our findings propose MELK as a promising target for ERα-positive/PR-positive/HER2-negative BC and highlight ALK as a potential focus for ERα-positive/PR-negative/HER2-positive BC. The synergistic anti-proliferative effects of MELK with Tam and ALK with HER2 inhibitors underscore kinase inhibitors’ potential for selective treatment in diverse BC subtypes, paving the way for personalized and effective therapeutic strategies in BC management.

Se reporta por primera vez a Agonosoma trilineatum (Fabricius) alimentándose de Croton conduplicatus Kunth (Euphorbiaceae), además, se confirma la condición dimórfica en los machos en cuanto al patrón de color exhibido en un sistema sucesional de bosque estacionalmente seco en Bosque Mérida, Venezuela.

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD.

Previously, we found that telaprevir (Tel), the inhibitor of hepatitis C virus NS3/4A serine protease, reduces estrogen receptor α (ERα) content at the transcriptional level without binding to the receptor, prevents ERα transcriptional activity, and inhibits basal and 17β‐estradiol (E2)‐dependent cell proliferation in different breast cancer (BC) cell lines. Here, we further characterize the Tel action mechanisms on ERα levels and function, identify a possible molecular target of Tel in BC cells, and evaluate Tel as an antiproliferative agent for BC treatment. Tel‐dependent reduction in ERα levels and function depends on a Tel‐dependent decrease in FOXA1 levels and activity. The effect of Tel is transduced by the IGF1‐R/AKT/FOXA1 pathway, with the antiviral compound interacting with IGF1‐R. Tel prevents the proliferation of several BC cell lines, while it does not affect the proliferation of normal nontransformed cell lines, and its antiproliferative effect is correlated with the ratio of FOXA1/IGF1‐R expression. In conclusion, Tel interferes with the IGF1‐R/AKT/FOXA1 pathway and induces cell death in ERα‐expressing BC cells. Thus, we propose that this antiviral could be repurposed for the treatment of ERα‐expressing BC.

Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.

Abstract Background Challenges exist in the clinical treatment of luminal estrogen receptor α (ERα)-positive breast cancers (BCs) both to prevent resistance to endocrine therapy (ET) and to treat ET-resistant metastatic BCs (MBC). Therefore, we evaluated if kinases could be new targets for the treatment of luminal primary and MBCs. Methods ~ 170 kinase inhibitors were applied to MCF-7 cells either with adaptative or genetic resistance to ET drugs and both ERα levels and cell proliferation were measured. Robust-Z-score calculation identified AZD7762 (CHK1/CHK2 inhibitor) as a positive hit. Subsequently, Kaplan–Meier analyses of CHK1 and CHK2 impact on ERα-positive BC patients relapse-free-survival (RFS), bioinformatic evaluations of CHK1 and CHK2 expression and activation status as a function of ERα activation status as well as drug sensitivity studies in ERα-positive BC cell lines, validation of the impact of the ATR:CHK1 and ATM:CHK2 pathways on the control of ERα stability and BC cell proliferation via inhibitor- and siRNA-based approaches, identification of the molecular mechanism required for inhibitor-dependent ERα degradation in BC and the impact of CHK1 and CHK2 inhibition on the 17β-estradiol (E2):ERα signaling, synergy proliferation studies between ET-drugs and clinically relevant CHK1 inhibitors in different luminal BC cell lines, were performed. Results A reduced CHK1 expression correlates with a longer RFS in women with ERα-positive BCs. Interestingly, women carrying luminal A BC display an extended RFS when expressing low CHK1 levels. Accordingly, CHK1 and ERα activations are correlated in ERα-positive BC cell lines, and the ATR:CHK1 pathway controls ERα stability and cell proliferation in luminal A BC cells. Mechanistically, the generation of DNA replication stress rather than DNA damage induced by ATR:CHK1 pathway inhibition is a prerequisite for ERα degradation. Furthermore, CHK1 inhibition interferes with E2:ERα signaling to cell proliferation, and drugs approved for clinical treatment of primary and MBC (4OH-tamoxifen and the CDK4/CDK6 inhibitors abemaciclib and palbociclib) exert synergic effects with the CHK1 inhibitors in clinical trials for the treatment of solid tumors (AZD7762, MK8776, prexasertib) in preventing the proliferation of cells modeling primary and MBC. Conclusions CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs.

Time-correlated single-photon counting (TCSPC) is a powerful technique for time-resolved measurement of fast and weak light signals used in a variety of scientific fields, including biology, medicine, and quantum cryptography. Unfortunately, given its repetitive nature, TCSPC is recognized as a relatively slow technique. In the last ten years, attempts have been made to speed it up by developing multichannel integrated architectures. Yet, for the solutions proposed thus far, the measurement speed has not increased proportionally to the number of channels, reducing the benefits of a multichannel approach. Recent theoretical studies and prototypes have shown that it is possible to implement a new multichannel architecture, so-called router-based architecture, capable of optimizing the efficiency of data transfer from the integrated chip to the data processor, increasing the overall measurement speed. However, the first implementations failed to achieve the theoretical results due to implementation flaws. In this paper, we present a new logic for the router-based architecture that can operate at the same laser frequency and solve the issues of the previous implementation. Alongside the new logic, we present a new integrated low-jitter delay line combined with a new method for timing-signal distribution that allows the proper management of the pixel timing information. The new implementation is a step closer to realizing a router-based architecture that achieves the expected theoretical results. Simulations and bench tests support the results here reported.

Convolutional neural networks (CNNs), initially developed for image processing applications, have recently received significant attention within the field of medical ultrasound imaging. In this study, passive cavitation imaging/mapping (PCI/PAM), which is used to map cavitation sources based on the correlation of signals across an array of receivers, is evaluated. Traditional reconstruction techniques in PCI, such as delay-and-sum, yield high spatial resolution at the cost of a substantial computational time. This results from the resource-intensive process of determining sensor weights for individual pixels in these methodologies. Consequently, the use of conventional algorithms for image reconstruction does not meet the speed requirements that are essential for real-time monitoring. Here, we show that a three-dimensional (3D) convolutional network can learn the image reconstruction algorithm for a 16×16 element matrix probe with a receive frequency ranging from 256 kHz up to 1.0 MHz. The network was trained and evaluated using simulated data representing point sources, resulting in the successful reconstruction of volumetric images with high sensitivity, especially for single isolated sources (100% in the test set). As the number of simultaneous sources increased, the network’s ability to detect weaker intensity sources diminished, although it always correctly identified the main lobe. Notably, however, network inference was remarkably fast, completing the task in approximately 178 s for a dataset comprising 650 frames of 413 volume images with signal duration of 20μs. This processing speed is roughly thirty times faster than a parallelized implementation of the traditional time exposure acoustics algorithm on the same GPU device. This would open a new door for PCI application in the real-time monitoring of ultrasound ablation.

Abstract Background Despite the growing interest in addiction research, which demonstrates the potential predictive role of adverse childhood experiences (ACEs), little is known about their impact on the psychological symptoms of craving. Methods After reviewing the relevant diagnostic criteria for addiction and comorbid mental disorders along with routinely collected clinical and service-use data, 208 outpatients were assessed on the study protocol. Following the recruitment phase, nominal and ordinal data were analyzed using nonparametric methods. Results Most of the outpatients reported ACEs (89.1%) and experienced cravings (73.4–95.7%). A positive association between ACEs and either intention and preplanning (r = .14, p