Potentialities and critical issues of liquid biopsy in clinical practice: An umbrella review

Background: Liquid biopsy (LB) is a laboratory test performed on a fluid sample aiming at analyzing molecular data derived from circulating cells and related entities, or from nucleic acids. This umbrella review aims to map and evaluate the evidence supporting the use of LB in medicine across different medical specialities and conditions. Methods: We searched three repositories from database inception up to October 1, 2023 and we included meta-analyses of observational studies reporting data on the use of LB, compared to gold standard, and its accuracy (area under the curve, AUC). Results: Among 726 articles initially screened, 42 systematic reviews were included. Most of the outcomes explored (202/211) were related to cancer. We found that 75/211 had an excellent accuracy (AUC >0.90), with one comparison with an AUC equal to 1, i.e., Cell-Free Human Papillomavirus DNA (cfHPV-DNA) for HPV-positive oropharyngeal squamous cell carcinoma. However, considering published meta-analyses, all the outcomes were graded as very low on the GRADE criteria, and the heterogeneity was never reported. Discussion: The literature about LB is rapidly increasing and some promising data about precision oncology are now available. However, this umbrella review on existing meta-analyses highlighted some critical issues for providing quantitative estimations on the different roles of LB

Immunohistochemical Expression of PAX8 in Central Nervous System Hemangioblastomas: A Potential Diagnostic Pitfall for Neuropathologists

: The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak. We would like to emphasize that the possibility of a PAX8-positive intracranial HB does exist and must be taken into account by neuropathologists to avoid misdiagnoses; in this regard, a broader immunohistochemical panel also including CD10, Inhibin-α, PAX2, S100, and anti-Renal cell carcinoma (RCC) antibody is highly recommended

Increasing HbA1c in children and youth with a first-degree relative with type 1 diabetes predicts progression to diabetes: a single-centre 10-year screening experience

In recent years, screening for Type 1 Diabetes (T1D) has been increasingly enhanced thanks to its demonstrated benefits in preventing diabetic ketoacidosis (DKA) at T1D onset and the availability of emerging disease-modifying therapy that can delay disease progression. Most screening programs have been performed as part of research trials and specific programs involving individuals with a family history of T1D, high-risk HLA genotype or the general population [1]. Evidence from these programs supports the increasing inclusion of screening in the national health system, as recently done in Italy thanks to the approval of a law introducing a nationwide screening for T1D and coeliac disease in the general pediatric population, with the pilot phase currently ongoing. The 15-fold increased risk of developing T1D in individuals with a first-degree relative who has T1D suggests screening family members as part of clinical care in pediatric diabetes centers. This has also been suggested as an intermediate step towards general population screening. The aim of this study was to assess the prevalence and predictors of T1D stages among children and youth who, over the last ten years, attended the T1D screening program of the Regional Center of Pediatric Diabetes of Verona (Italy)

La trasparenza societaria per lo sviluppo sostenibile. Il decreto legislativo n. 125/2024 sul rendiconto di sostenibilità

Il volume raccoglie 14 contributi in materia di trasparenza societaria sulla sostenibilità e di comunicazione d'impresa sui fattori ESG. I contributi vertono sul decreto legislativo n. 125 del 2024 e sulle normative collegate. L'Introduzione è di Anna Genovese. La prefazione è di Mario Libertini

Chapter 8: Interhemispheric differences in visual attention

The chapter explores the difference between the cerebral hemispheres in the three categories of attention described in the fundamental classification of Posner and Petersen: Alerting, Orienting, and Executive Functions. The first section is concerned with the brain localization of visuospatial attention as studied in brain-damaged patients, mainly hemineglect and callosum-sectioned patients. Other important results have been provided more recently by means of brain imaging studies of cortical and subcortical attention networks. Most of these studies have shown a clear dominance of the right hemisphere (RH) in visuospatial attention, but there are some exceptions. Accordingly, the second section concerns the role of the left hemisphere (LH) in visuospatial attention. A third section describes the contribution of attention to interhemispheric communication. A fourth section is focused on a discussion of the existence of hemispheric asymmetries not only in conscious but also in unconscious attention. Further, a fifth section concerns the effects of emotion on hemispheric differences in visuospatial attention. Finally, the last section briefly discusses the controversial evidence concerning laterality in executive functions

Intorno al 2025. Origini, caratteri e ragioni dell'Art Déco

Il saggio e il catalogo sono legati alla mostra aperta a Milano in palazzo Reale il 27 febbraio 2025 e in chiusura il 29 giugno dedicata al centenario dell'esposizione di Parigi e all'analisi del fenomeno Déco sia in Italia sia in Francia e in Austria, nei quali si riflette sulle origini e i caratteri dell'Art Déco limitandone il fenomeno agli anni 1919-192

Development and enhancement of plant pathogens diagnostic protocols based on Nanopore sequencing

In recent times, we have witnessed a concerning rise in the accidental introduction of harmful organisms into both floriculture and agricultural production. This trend poses significant threats, particularly when it comes to quarantine pathogens, many of which are notoriously difficult to diagnose. The presence of quarantine phytopathogens in floricultural plants not only jeopardizes crop health but also inflicts severe damage on the floriculture and broader agricultural sectors. Phytopathogen detection requires rapid and sensitive assays to reach effective management of crop diseases. The main limitation of current diagnostic testing is the inability to combine broad and sensitive pathogen detection with the identification of key strains, pathovars, and subspecies. This thesis work has its base in the GARDING project (Bando 2018 d.d.s. n. 4403 del 28/03/2018), sponsored by the Lombardy region and born from the collaboration between the University of Milan, the University of Verona and VIVAI NORD Snc for the protection of the territory from the invasion of potentially harmful pathogen species. The project aims to build barcoding protocols for the identification of phytopathogens directly at customs, thus eliminating the need for sample transfers to external laboratories to perform rapidly multiple pathogens tests with less time required compared to present methods. One promising solution is implementing Nanopore Third Generation Sequencing technology for pathogen detection. This technology is portable, and it allows the detection of microorganisms even at low concentrations. It validates results from existing molecular methods and extends diagnostic capabilities beyond laboratory settings. The results presented in this thesis show the development of an innovative diagnostic method based on Nanopore third-generation sequencing technology capable of identifying several quarantine pathogens in simulated infected plants, even discerning among pathogens subspecies. These outcomes prove the potential of this technology to facilitate the advancement of next-generation diagnostic assays for efficiently monitoring other plant pathogens

Botany and Diplomacy: Pietro Andrea Mattioli and his Flemish Correspondents in Constantinople (1557-1568)

The relations between the Flemish humanist and diplomat Augier Ghiselin de Busbecq and several of his fellow countrymen such as Carolus Clusius are well known in connection with the introduction of various plants such as the tulip into the gardens of Europe. Less well known but nonetheless significant is Busbecq’s role as a contributor to Pietro Andrea Mattioli’s botanical investigations during and after his mission to Constantinople. The main purpose of this chapter is to understand how the interplay between Mattioli’s position in the Habsburg court and his participation in various Venetian information networks was strategic to adding to the botanical knowledge of his time

Corporate sustainability e prevenzione delle frodi aziendali: Il contributo dei sistemi ERP

I sistemi informativi integrati di tipo Enterprise Resource Planning (ERP) sono stati un driver di valore aziendale, attraverso la gestione integrata delle informazioni ed il miglioramento dell'efficienza e dell’efficacia dei processi. Gli ERP hanno trovato ampia diffusione sia nelle aziende di grandi dimensioni che nelle PMI, divenendo un componente fondamentale del loro sistema di controllo interno (SCI). Tuttavia, data questa loro importanza e centralità, è fondamentale che il loro utilizzo avvenga con il disegno di un sistema di controllo interno adeguato al contesto considerato, pena l’insorgere di gravi vulnerabilità, fra cui quella alle frodi aziendali. Questo articolo analizza l'importanza dei controlli interni inclusi negli ERP a mitigazione del rischio frode, attraverso una review della letteratura e l'analisi di un caso di studio emblematico, riguardante la frode compiuta da Jérôme Kerviel nel 2008 ai danni Société Générale. Con il supporto di altri esempi tratti dal contesto delle PMI e delle organizzazioni non lucrative italiane si intende riflettere sui rischi e gli effetti di un sistema di controllo interno inefficace sul tema della prevenzione delle frodi aziendali, con impatti negativi sulla corporate governance e la gestione sostenibile del business. L'articolo si conclude con alcune raccomandazioni utili al rafforzamento dei controlli interni inclusi nei sistemi ERP.Integrated Enterprise Resource Planning (ERP) information systems have been a driver of corporate value, through the integrated management of information and the mprovement of the efficiency and effectiveness of processes. ERPs have become widely used in both large companies and SMEs, becoming a fundamental component of their internal control system (ICS). However, given their importance and centrality, it is essential that their use takes place with the design of an internal control system appropriate to the context considered, otherwise serious vulnerabilities will arise, including that of corporate fraud. This article analyzes the importance of internal controls included in ERPs to mitigate fraud risk, through a review of the literature and the analysis of an emblematic case study, concerning the fraud committed by Jérôme Kerviel in 2008 against Société Générale. With the support of other examples taken from the context of Italian SMEs and non-profit organizations, we intend to reflect on the risks and effects of an ineffective internal control system on the issue of corporate fraud prevention, with negative impacts on corporate governance and sustainable business management. The article concludes with some useful recommendations for strengthening the internal controls included in ERP systems

Natura e progresso morale in Nietzsche

Questo contributo mira a ricostruire la singolare teoria del progresso morale proposta da Nietzsche nel periodo maturo della sua filosofia (1883-1888), interrogandosi su opportunità e problematiche