Geographical scattering in Italian inner areas, politics and COVID-19

In recent months, the COVID-19 pandemic has been fervently considered from the perspective of various disciplines in the scientific community. Many of the proposed approaches are tied to reflections on the imminent and future effects of the pandemic. This contribution begins with a study of the recent past in Italy, analyzing the hurdles in politics that came to light due to the wave of COVID-19 infections worldwide. Particularly, the research considers the criticality of the geographical scale of reference in Italy‘s political actions. COVID-19 induced a need for the government to interact with people locally, especially through small municipalities in geographically central, inner areas, is emphasized. The main aim of this research is to attribute to this specific COVID-19 disaster the instrumental role of turning on the lights on the need to intervene in the inner areas of Italy, often very neglected. So the focus of the work is on inner areas and the probable catalysis of the political management dynamics that concern them, as an effect of the COVID's impacts. The pandemic is, therefore, only the contingent phenomenon which, in this case, can perhaps accelerate political interventions in inner areas. To explain the reason for this, we show how the vulnerability of inner areas, already generally risky, has become one of the weak links in the chain of protection from COVID-19 in terms of a geographical scattering phenomenon

Remote sensing based on time variance control in configurable area partitioning

Abstract. In this paper a sensor data fusion approach for characteristics field monitoring, based on time variance control model, is proposed. Distributed sensing and remote processing are the basic features of the employed architecture. In fact, in order to obtain meaningful information about the temporal and spatial variations, which characterize the field levels of some characteristics (electromagnetic, air pollution, seismic, etc), a distributed network of wireless and mobile smart-sensors has been designed.Starting from the partitioned configuration of a monitored geographic areas, this model allows to take into account the different levels of degradation over time in the sensors' performances associated with the different geographic partitions, progressively increasing the severity of the control. To this end, through the introduction of a reliability curve, a revised traditional control chart for variables is proposed.The proposed approach, further constituting an element of the scientific debate, aims to be a useful operational tool for professionals and managers employed in the environment control

The Iconographic Exploitation of the Urban Space for the Amplification of the Symbols of the Camorra. The Case of Spanish Quarters, Naples, Italy

This contribution is inspired by a current scenario regarding the city of Naples, Italy, where a strong popular uprising is underway against local institutions that are destroying the Camorra murals celebrating its “heroes” died in “war”. These events are very interesting to analyse the theme of the iconographic exploitation of urban space by the criminal part of society in order to amplify the identity symbols of a tribal structure such as the Camorra. While on the one hand the analysis aims to show the positive response of civil society and institutions in eradicating these celebra tory icons of evil, on the other hand the research intends to emphasise the profound and worrying systemic modification of public space according to subjective and nega tive canons that, however, are also shared by some intellectuals and even an adminis trative cour

The Iconographic Exploitation of the Urban Space for the Amplification of the Symbols of the Camorra. The Case of Spanish Quarters, Naples, Italy

This contribution is inspired by a current scenario regarding the city of Naples, Italy, where a strong popular uprising is underway against local institutions that are destroying the Camorra murals celebrating its “heroes” died in “war”. These events are very interesting to analyse the theme of the iconographic exploitation of urban space by the criminal part of society in order to amplify the identity symbols of a tribal structure such as the Camorra. While on the one hand the analysis aims to show the positive response of civil society and institutions in eradicating these celebra-tory icons of evil, on the other hand the research intends to emphasise the profound and worrying systemic modification of public space according to subjective and nega-tive canons that, however, are also shared by some intellectuals and even an adminis-trative court

Un’analisi geografica delle dinamiche del lavoro pre- e post-pandemia negli Stati Uniti

Il presente contributo, partendo dai dati del Bureau of Labor Statistics (BLS), il principale database delle agenzie investigative del governo statunitense, analizza da un punto di vista geografico le dinamiche relative all’andamento dei posti di lavoro nei diversi settori produttivi pre- e post-pandemia.L’approccio metodologico proposto si basa su un test di ipotesi bivalente. Una prima ipotesi è relativa alla possibile differenziazione geografica tra gli Stati, in relazione alle variazioni nel numero dei posti di lavoro persi e recuperati. Una seconda ipotesi attiene alla possibile differenziazione tra i vari settori produttivi a cui i dati si riferiscono.I risultati hanno mostrato tre particolari evidenze, una forte omogeneità delle variazioni analizzate tra tutti gli Stati, una particolare autocorrelazione spaziale riconoscibile sia negli Stati caratterizzati da perdite maggiori, sia in quelli a minore e media intensità di perdite, e infine, un’assenza di differenziali settoriali

How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions.

RUNX3 is the oldest known gene in the RUNX family. Data have demonstrated its function to be thoroughly involved the neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. As a TGF-beta target, RUNX3 protein is believed to be involved in TGF-beta-mediated tumor suppressor pathway; however, little is known about its role in apoptosis. According to recent data reported by Yamamura et al., (J Biol Chem 2006; 281:5267-76), RUNX3 interacts with FoxO3a/FKHRL1 expressed in gastric cancer cells to activate Bim and induce apoptosis. The cooperation between RUNX3 and the PI3K/Akt signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in the homoeostasis of gastric cells and in stomach cancer control. Here we discuss recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric malignancy and comment on possible future trends and perspectives

Triple blockade of EGFR, MEK and PD-L1 has antitumor activity in colorectal cancer models with constitutive activation of MAPK signaling and PD-L1 overexpression

Càncer colorectal; Resistència a inhibidors de MEK; Inhibidors de PD-L1Cáncer colorrectal; Resistencia a inhibidores de MEK; Inhibidores de PD-L1Colorectal cancer; MEK inhibitor resistance; PD-L1 inhibitorsBackground Molecular mechanisms driving acquired resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) are complex but generally involve the activation of the downstream RAS-RAF-MEK-MAPK pathway. Nevertheless, even if inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance, its use is limited by the development of MEK inhibitor (MEKi) resistance. Methods We have generated in vitro and in vivo different CRC models in order to underline the mechanisms of MEKi resistance. Results The three different in vitro MEKi resistant models, two generated by human CRC cells quadruple wild type for KRAS, NRAS, BRAF, PI3KCA genes (SW48-MR and LIM1215-MR) and one by human CRC cells harboring KRAS mutation (HCT116-MR) showed features related to the gene signature of colorectal cancer CMS4 with up-regulation of immune pathway as confirmed by microarray and western blot analysis. In particular, the MEKi phenotype was associated with the loss of epithelial features and acquisition of mesenchymal markers and morphology. The change in morphology was accompanied by up-regulation of PD-L1 expression and activation of EGFR and its downstream pathway, independently to RAS mutation status. To extend these in vitro findings, we have obtained mouse colon cancer MC38- and CT26-MEKi resistant syngeneic models (MC38-MR and CT26-MR). Combined treatment with MEKi, EGFR inhibitor (EGFRi) and PD-L1 inhibitor (PD-L1i) resulted in a marked inhibition of tumor growth in both models. Conclusions These results suggest a strategy to potentially improve the efficacy of MEK inhibition by co-treatment with EGFR and PD-L1 inhibitors via modulation of host immune responses.This research has been supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC) to FC (AIRC IG 18972) and and Regione Campania Cancer Research Campaign I-CURE grant to FC

Alteration of microRNAs regulated by c-Myc in burkitt lymphoma

Background: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14) and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs), whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs. Principal Findings: Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression. Conclusions: Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker

Antitumor Efficacy of Dual Blockade with Encorafenib + Cetuximab in Combination with Chemotherapy in Human BRAFV600E-Mutant Colorectal Cancer

Antitumor efficacy; Chemotherapy; Colorectal cancerEficàcia antitumoral; Quimioteràpia; Càncer colorectalEficacia antitumoral; Quimioterapia; Cáncer colorrectalPurpose: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC. Experimental Design: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts. Mice were randomized to receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin regimens (FOLFIRI or FOLFOX), (E+C) or the combination. Patients received long-term treatment until disease progression, with deescalation strategies used to mimic maintenance therapy. Transcriptomic changes after progression on cytotoxic chemotherapy or targeted therapy were assessed. Results: Antitumor activity of either FOLFIRI or E+C was better as first-line treatment as compared with second-line, with partial cross-resistance seen between a cytotoxic regimen and targeted therapy with an average 62% loss of efficacy for FOLFIRI after E+C and a 45% loss of efficacy of E+C after FOLFIRI (P < 0.001 for both). FOLFIRI-treated models had upregulation of epithelial–mesenchymal transition (EMT) and MAPK pathway activation, where E+C treated models had suppressed MAPK signaling. In contrast, with chemotherapy with E+C, EMT and MAPK signaling remained suppressed. FOLFOX or FOLFIRI, each in combination with E+C, were the most active first-line treatments as compared with E+C or to chemotherapy alone. Furthermore, FOLFOX in combination with E+C as first-line induction therapy, followed by E+C ± 5-FU as maintenance therapy, was the most effective strategy for long-term disease control. Conclusions: These results support the combination of cytotoxic chemotherapy and molecular-targeted therapy as a promising therapeutic approach in the first-line treatment of BRAFV600E mCRC.A research grant that partially covered the costs of the study was provided by Regione Campania (I-Cure Research Project, grant number: Cup 21C17000030007, to F. Ciardiello and L. Altucci). This work was also supported by Cancer Center Support Grant – Gastrointestinal Program (Project Number: 5P30 CA016672–46). O.E. Villarreal was supported by the CPRIT Training Program (RP210028)

Early Denosumab for the prevention of osteoporotic fractures in breast cancer women undergoing aromatase inhibitors: A case-control retrospective study

BACKGROUND:Aromatase inhibitors (AIs) might have a detrimental impact on bone health in breast cancer (BC) women.Denosumab has been shown to reduce the risk of fractures, but the appropriate time for starting is yet to be clearly defined.OBJECTIVE:To evaluate the effects of early treatment with Denosumab (612 months after starting AIs) compared to a delayedtreatment in BC women.METHODS:In this retrospective case-control study, we included medical records of BC post-menopausal women, treated withAIs therapy; they were divided as: study group (starting Denosumab612 months after AIs) and control group (&gt;12 months). Atthe baseline (T0) and at 18 months (T1), we evaluated the lumbar spine (LS) Tscore and femoral neck (FN) Tscore. Furthermore,at T1 we assessed the incident fragility fractures.RESULTS:Fifty-nine BC survivors (mean age: 61.5±11.5 years) were included: 28 with Early Denosumab and 31 with LateDenosumab. At T1, the study group did not show any incident hip or vertebral fragility fracture, whereas the Late Denosumabgroup showed 2 incident hip fractures (6.5%) and 4 (12.9%) vertebral fragility fractures. Early Denosumab showed a significantpositive effect on both LS (p=0.044) and FN (p=0.024) Tscore variations.CONCLUSION:Taken together, our findings suggest that an early start of Denosumab might be considered for the osteoporosismanagement in BC women undergoing AIs