42 research outputs found
MET is a new confirmed gene responsible for familial distal arthrogryposis
No full textIn this Correspondence, F. Mari and colleagues report a second two-generation family with distal arthrogryposis caused by a mutation in MET tyrosine kinase. (Figure presented.). © The Author(s) 2024
Pareto's Chronicles: Liberty and the Left
No full textThe ‘second series’ of the Giornale degli Economisti commenced in 1890. It revealed a notable change in editorial direction from the earlier series, which was a direct result of Alberto Zorli being joined by leading liberal intellectuals, Ugo Mazzola, Antonio de Viti de Marco and Maffeo Pantaleoni, as the Journal’s proprietary directors. In regard to economic science, the second series saw the Journal establish itself as the leading Italian distributor of the new marginalism. In regard to politics, it became a leading advocate for liberal policy. To that end, the Journal published a special feature from 1891 entitled ‘cronaca’, which critically chronicled practical developments in Italian public policy, public finances and the state of the economy. In 1893 Pareto took over from Ugo Mazzola as author of the chronicles, a role he continued to perform until 1897. His contributions were, overwhelmingly, critical of interventionist and militaristic actions of the Italian Government. The purpose of this paper is to place Pareto’s chronicles in their historical context and search for comments that hint at the subsequent development of sociological theory. This will be achieved by: interpreting Pareto’s ‘cronaca’ with reference to political developments in Italy from the 1880s to 1897; identifying practical illustrations in the ‘cronaca’ concerning liberty and the extreme left in Italian society; and identifying three broad consistencies between Pareto’s ‘non-scientific’ ‘Cronaca’ and his scientific ‘General Sociology’.Cronaca, Chronicle, Vilfredo Pareto, General Sociology
Blood circulating miRNAs as pancreatic cancer biomarkers: An evidence from pooled analysis and bioinformatics study
No full textPancreatic cancer (PC) is one of the deadliest cancers, characterized by a poor prognosis. Currently, there are no screening programs for the early detection of PC, and existing diagnostic methods are primarily limited to high-risk individuals. Biomarkers such as CA19–9 have not significantly improved early diagnosis, making the identification of new potential biomarkers crucial for routine clinical practice. Among the candidate biomarkers, miRNAs have been most extensively studied due to their role in regulating gene expression (either as oncomiRs or tumor suppressor miRNAs) and their potential for minimally invasive analysis through liquid biopsy techniques. This review aims to summarize the current literature on blood-circulating miRNAs and their diagnostic value in PC detection, considering the context of CA19–9 and benign pancreatic diseases. The data from the collected studies were curated through both statistical and bioinformatics analyses to identify the most promising miRNAs with optimal diagnostic accuracy for PC detection and to assess their role in the molecular processes leading to tumor development
MAFFEO PANTALEONI: FOMENTOR OF THE ANTI-SEMITIC PRESS CAMPAIGN
No full textThe author reconstructs the anti-Semitic press campaign led by Maffeo
Pantaleoni, one of the major Italian economists, between 1915 and 1924.
A declared supporter of Nationalism and Fascism, co-editor of the magazine
La Vita italiana, the economist moreover promoted the publication
of the Protocols of the Elders of Zion in 1921 plus the publication of
lists of Jews who had prominent roles in Italy. Pantaleoni’s work is particularly
important from the idealogical point of view because it supports
that of the founder of La Vita italiana, Giovanni Preziosi, who was destined
to hold, after the death of his ‘master’, a primary role in the Fascist
culture and policy of anti-Semitism during the Republic of Salo`
(19431945) which promoted the systematic extermination of Italian
Jews.
Keywords: Italian marginalism; anti-Semitism; fascism
JEL classifications: B13; J15; Z1
Economics and Anti-Semitism: the Case of Maffeo Pantaleoni
No full textThe relationship between economics and anti-Semitism has always been a controversial subject. The question is complex by nature: to describe an author as an anti-Semite means to cast a shadow over his thought, with consequences that are much more serious when there is a limited amount of documentation and firsthand accounts. In this article we examine the case of Maffeo Pantaleoni, one of the most influential Italian economists of the nineteenth century and at the same time an intellectual who was among those most closely involved in anti-Semitic propaganda. In the case of Pantaleoni, it is not necessary to ask the question of whether and to what extent his anti-Semitism could be defined as “mild” or “ambivalent” and therefore in line with that expressed by a large part of Western culture during the first half of the twentieth century. In this study we document a clear and open anti-Semitic attitude that, however, has remained ignored up to now by economic historiography. In this article we discuss the possible relationship between Pantaleoni’s anti-Semitism and his work as a theoretical economist, within a methodological framework inspired by Pierre Bourdieu’s philosophy and sociology of science
La comparatio di Lorenzo Valla tra le orazioni di Cicerone e le declamazioni di Quintiliano in una lettera di Maffeo Vallaresso
No full textNella fitta trama dell’epistolario Barb. lat. 1809 del prelato veneziano Maffeo Vallaresso l’articolo richiama l’attenzione su alcuni riferimenti a Lorenzo Valla. Il più importante tra questi rivela l’esistenza, e la notorietà all’inizio degli anni Cinquanta del Quattrocento, di uno scritto valliano dedicato alle orazioni ciceroniane e alle declamazioni pseudoquintilianee; e conferma come l’umanista, dopo il giovanile Quintiliani Tulliique examen, avesse mantenuto la promessa di pubblicare una più estesa comparatio tra le opere oratorio-declamatorie dei due scrittori antichi. Un altro consente di precisare meglio l’identità, piuttosto evanescente, di Girolamo Cinna, allievo del VallaIn the voluminous correspondence Barb. lat. 1809 of the venetian prelate Maffeo Vallaresso, the article draws attention to some references to Lorenzo Valla. The most important reveals the existence, and notoriety at the beginning of the 1450s, of a writing by Valla entirely devoted to Cicero’s orations and Quintilian’s (as he thought the author) declamations; and confirms how far the humanist, after the youthful Quintiliani Tulliique examen, had kept his promise to publish a more extensive comparatio between the oratory-declamatory works of the two ancient writers. Another hint allows us to better characterize the rather evanescent identity of Girolamo Cinna, a pupil of Vall
The Personalized Inherited Signature Predisposing to Non-Small-Cell Lung Cancer in Non-Smokers
No full textSimple Summary Building on the idea of a germline oligogenic origin of lung cancer, we performed WES of DNA from patients' peripheral blood and their unaffected sibs. Filtering for rare variants and potentially damaging effects, we identified 40 deleterious variants mapping in genes previously associated with cancer exclusively identified in patients. Transcriptome profiling on both tumor and normal lung tissues revealed that, among the selected mutated genes, 16 variants mapping in 16 genes were either down- or upregulated in cancer specimens. Among the downregulated genes, 9 variants in 9 genes carried the mutated allele suggesting a loss of heterozygosity. Notably, the group of mutated genes was unique for each patient, pinpointing to a "private" oligogenic germline signature. In the era of precision medicine, this report emphasizes the importance of an "omic" approach to uncover an oligogenic germline signature underlying cancer development and identify suitable therapeutic targets.Abstract Lung cancer (LC) continues to be an important public health problem, being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never-smoker early-onset LC patients, which does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer-predisposing genes in non-smokers patients, giving experimental support to a model of a "private genetic epidemiology". Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib's model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bioinformatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer-predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: (i) downregulation in LC tissue (indicating a "second hit" in tumor suppressor genes); (ii) upregulation in cancer tissue (likely oncogene); and (iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with a functional effect in tumor-predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of the familial clustering of non-small-cell lung cancer. In conclusion, these findings indicate that each patient has his/her own "predisposing signature" to cancer development and suggest the use of personalized therapeutic strategies in lung cancer
The Evidence Base for Circulating Tumor DNA-Methylation in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
No full textBackground: Non-Small Cell Lung Cancer (NSCLC) remains a challenging disease to manage with effectiveness. Early detection and precise monitoring are crucial for improving patient outcomes. Circulating tumor DNA (ctDNA) offers a non-invasive cancer detection and monitoring method. Emerging biomarkers, such as ctDNA methylation, have shown promise in enhancing diagnostic accuracy and prognostic assessment in NSCLC. In this review, we examined the current evidence regarding ctDNA methylation’s role in NSCLC detection through a systematic review of the existing literature and meta-analysis. Methods: We systematically searched PubMed, Medline, Embase, and Web of Science databases up to 26 June 2024 for studies on the role of ctDNA methylation analysis in NSCLC patients. We included studies from 2010 to 2024 on NSCLC patients. We excluded case reports, non-English articles, studies on cell lines or artificial samples, those without cfDNA detection, prognostic studies, and studies with non-extractable data or mixed cancer types. Funnel plots were visually examined for potential publication bias, with a p value < 0.05 indicating bias. Meta-analysis was conducted using R packages (meta, forestplot, and mada). Combined sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), positive and negative predictive values, diagnostic odds ratio (DOR), and 95% confidence intervals (95% CI) were calculated. A summary receiver operating characteristic curve (SROC) and area under the curve (AUC) with related Standard Error (SE) were used to evaluate the overall diagnostic performance. Additionally, RASSF1A, APC, SOX17, SEPT9, and RARβ2 were analyzed, since their methylation was assessed in two or more studies. Results: From 38 candidate papers, we finally identified 12 studies, including 472 NSCLC patients. The pooled sensitivity was 0.62 (0.47–0.77) and the specificity was 0.90 (0.85–0.94). The diagnostic odds ratio was 15.6 (95% CI 9.36–26.09) and the area under the curve was 0.249 (SE = 0.138). The positive and negative predictive values were 5.38 (95% CI 3.89–7.44) and 0.34 (95% CI 0.22–0.54), respectively. For single genes, the specificity reached 0.83~0.96, except for RARβ2, but the sensitivity was relatively low for each gene. Significant heterogeneity across the included studies, the potential publication bias for specificity (p = 0.0231), and the need to validate the clinical utility of ctDNA methylation for monitoring treatment response and predicting outcomes in NSCLC patients represent the main limitations of this study. Conclusions: These results provide evidence of the significant potential of ctDNA methylation as a valuable biomarker for improving the diagnosis of NSCLC, advocating for its integration into clinical practice to enhance patient management
A DNA turbine powered by a transmembrane potential across a nanopore
No full textRotary motors play key roles in energy transduction, from macroscale
windmills to nanoscale turbines such as ATP synthase in cells. Despite our
capabilities to construct engines at many scales, developing functional
synthetic turbines at the nanoscale has remained challenging. Here, we
experimentally demonstrate rationally designed nanoscale DNA-origami turbines
with three chiral blades. These DNA nanoturbines are 24-27 nm in height and
diameter and can utilise transmembrane electrochemical potentials across
nanopores to drive DNA bundles into sustained unidirectional rotations of up to
10 revolutions/s. The rotation direction is set by the designed chirality of
the turbine. All-atom molecular dynamics simulations show how hydrodynamic
flows drive this turbine. At high salt concentrations, the rotation direction
of turbines with the same chirality is reversed, which is explained by a change
in the anisotropy of the electrophoretic mobility. Our artificial turbines
operate autonomously in physiological conditions, converting energy from
naturally abundant electrochemical potentials into mechanical work. The results
open new possibilities for engineering active robotics at the nanoscale
The Genetic Analysis and Clinical Therapy in Lung Cancer: Current Advances and Future Directions
No full textLung cancer, including both non-small cell lung cancer and small cell lung cancer, remains the leading cause of cancer-related mortality worldwide, representing 18% of the total cancer deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease and have a worsening prognosis. Recent advances in the genetic understanding of lung cancer have opened new avenues for personalized treatments and targeted therapies. This review examines the latest discoveries in the genetics of lung cancer, discusses key biomarkers, and analyzes current clinical therapies based on this genetic information. It will conclude with a discussion of future prospects and potential research directions
