The Reverse Transcriptase Encoded by LINE-1 Retrotransposons in the Genesis, Progression, and Therapy of Cancer

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity

Adaptation of an i-voting scheme to Italian Elections for Citizens Abroad

We adapt the Ara´ujo-Traor´e protocol to Italian elections, with emphasis on anti-coercion measures. In this short paper we focus on a new method for managing anti-coercion credentials for each voter

Amun: Securing E-Voting Against Over-the-Shoulder Coercion

In an election where each voter may express $P$ preferences among $M$ possible choices, the Amun protocol allows to secure vote casting against over-the-shoulder adversaries, retaining privacy, fairness, end-to-end verifiability, and correctness. Before the election, each voter receives a ballot containing valid and decoy tokens: only valid tokens contribute in the final tally, but they remain indistinguishable from the decoys. Since the voter is the only one who knows which tokens are valid (without being able to prove it to a coercer), over-the-shoulder attacks are thwarted. We prove the security of the construction under the standard Decisional Diffie Hellman assumption in the random oracle model

Coercion-Resistant Blockchain-Based E-Voting Protocol

Coercion resistance is one of the most important features of a secure voting procedure. Because of the properties such as transparency, decentralization, and non-repudiation, blockchain is a fundamental technology of great interest in its own right, and it also has large potential when integrated into many other areas. Here we propose a decentralized e-voting protocol that is coercion-resistant and vote-selling resistant, while being also completely transparent and not receipt-free. We prove the security of the protocol under the standard DDH assumption

Clinical Review of Mucosal Melanoma: The 11-Year Experience of a Referral Center

Introduction: Mucosal melanoma is a rare neoplasm. Late diagnosis is caused by occult anatomic sites and scarcity of symptoms. Novel biological therapies have now become available. Demographic, therapeutical and survival records on mucosal melanoma are scarce. Objectives: To provide an 11-year retrospective clinical review of real-world data on mucosal melanomas managed in a tertiary referral center in Italy. Methods: We included patients with histopathological mucosal melanoma diagnoses from January 2011 to December 2021. Data were collected until the last known follow-up or death. Survival analysis was performed. Results: Among 33 patients, we found 9 sinonasal, 13 anorectal and 11 urogenital mucosal melanomas (median age 82, females 66.7%). Eighteen cases (54.5%) presented with metastasis (p<0.05). In the urogenital subgroup, only 4 patients (36.4%) had metastasis at diagnosis, all in regional lymph nodes. Sinonasal melanomas were surgically managed with a debulking procedure (44.4%); every case of anorectal and urogenital melanomas underwent radical surgery (30.8% and 45.5%). Fifteen patients were treated with biological therapy (p<0.05). Radiation therapy was used in all melanomas of the sinonasal region (p<0.05). Overall survival was longer for urogenital melanomas (26 months). Univariate analysis showed an increased hazard ratio for death in patients with metastasis. A negative prognostic value of metastatic status was reported by the multivariate model, while administration of first-line immunotherapy demonstrated a protective role. Conclusions: At diagnosis, the absence of metastatic disease is the most relevant factor that influences the survival of mucosal melanomas. Moreover, the use of immunotherapy might prolong the survival of metastatic mucosal melanoma patients

Approach to leg edema

Edema is defined as a palpable swelling caused by an increase in interstitial fluid volume. Leg edema is a common problem with a wide range of possible causes and is the result of an imbalance in the filtration system between the capillary and interstitial spaces. Major causes of edema include venous obstruction, increased capillary permeability and increased plasma volume secondary to sodium and water retention. In both hospital and general practice, the patient with a swollen leg presents a common dilemma in diagnosis and treatment. The cause may be trivial or life-threatening and it is often difficult to determine the clinical pathway. The diagnosis can be narrowed by categorizing the edema according to its duration, distribution (unilateral or bilateral) and accompanying symptoms. This work provides clinically oriented recommendations for the management of leg edema in adults

Antonio Gramsci e le interazioni con il pragmatismo europeo e statunitense

Dottorato di ricerca in Modelli di formazione, analisi teorica e comparazione, XXI ciclo, A.a. 2007-2008Università della Calabria, Dipartimento di scienze dell'educazion