Archivio Istituzionale della Ricerca- Università degli Studi di Foggia
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The Y58D mutation in rpsJ gene is correlated with tigecycline and eravacycline combined resistance in ST80 vancomycin-resistant Enterococcus faecium isolates
No full textObjectives: To describe the phenotypic and genetic features of vancomycin-resistant Enterococcus faecium (VREfm) isolates exhibiting resistance to tetracycline (TET), tigecycline (TGC) and eravacycline (ERV). Methods: Between December 2023 and September 2024, 32 vancomycin-resistant Enterococci (VRE) were collected from clinical samples at the Policlinico Foggia, Italy. Bacterial identification was carried out by mass spectrometry analysis (MALDI-TOF). Antimicrobial susceptibility testing for vancomycin (VA), TET, TGC and ERV was performed by reference broth microdilution method. Whole-genome sequencing (WGS) was carried out to explore the content of tetracyclines resistance determinants, and the phylogenetic relationship between isolates (in silico MLST and SNPs analysis). Results: Among studied isolates, thirty and two were E. faecium and Enterococcus faecalis (Efs), respectively. Overall, eight isolates, six VREfm and two VREfs, were resistant to TET (8/32, 25%), with four (all VREfm) being resistant to TGC and ERV (4/32, 12.5%), also. The two TET-resistant VREfs strains belonged to ST6 and carried the tet(M) gene only. All the TET-resistant VREfm were ST80 and carried tet(L) and tet(M) genes. Among these, the four TGC-resistant and ERV-resistant strains showed an uncommon Y58D substitution in the ribosomal S10 protein (rpsJ gene). SNPs analysis revealed that Y58D-carrying strains formed a separate cluster, within ST80 VREfm. Conclusions: In this study we correlated the presence of the Y58D mutation in the rpsJ gene with resistance to TGC and ERV in a cluster of VREfm ST80 clinical strains. The Y58D mutation was invariably found in co-presence with tet(L) and tet(M) genes
I segni del comando. Dallo “sceneggiato” al romanzo di Loredana Lipperini
No full textRecensione del Romanzo di Loredana Lipperini, Il segno del comando, Rai edizioni, 202
Changing metastatic patterns associate with dynamics of circulating tumor DNA in metastatic castration-resistant prostate cancer
No full textBackground: Circulating tumor DNA (ctDNA) acts as an early biomarker of the efficacy of androgen receptor signaling inhibitor (ARSI) therapy. In this study, we aimed to reveal if ctDNA can supplement imaging to better predict metastasis burden and radiographic progression disease (PD) in metastatic castration-resistant prostate cancer (mCRPC). Methods: Targeted next-generation sequencing was performed to assess ctDNA fraction. Radiographic evidence was documented by conventional imaging according to Prostate Cancer Working Group 3 criteria. Results: We prospectively collected plasma samples from 112 mCRPC with bone (n = 77), lymph nodal (n = 31), and visceral (n = 4) metastases. Only bone metastatic patterns were significantly associated with median ctDNA at baseline, during treatment and at PD (P <.0001). At first radiographic restaging, 24 (31.2%) men with a progressive worsening of bone disease had early ctDNA rise with a % ctDNA variation of 150.6% (interquartile range [IQR] = 104.9-210.7] compared with 11.1% (IQR = 0-36.6), P <.0001, in men with no change in bone disease. Univariate analysis showed that early ctDNA rise was significantly associated with progression free/overall survival (PFS/OS). In multivariable analysis including ctDNA change from baseline to 3-month treatment, variation of bone metastatic patterns (from oligometastatic to polymetastatic and/or to widespread disease), presence of visceral metastasis, age, PSA, performance status and prior docetaxel therapy, the transition from low- to high-ctDNA within 3 months of starting ARSI therapy was a significant predictor of OS (HR = 2.50, 90% CI, 1.06-5.88, P =.035) and persistent high level of ctDNA was a predictor of PFS (HR = 2.53, 95% CI, 1.10-5.81, P =.028). Metastatic involvement demonstrated that the transition from bone polymetastatic to widespread disease and the presence of visceral metastases were both associated with worse OS (HR = 2.43, 95% CI, 1.10-5.35, P =.028, and HR = 3.40, 95% CI, 1.50-7.66, P =.003, respectively). Prior therapy with docetaxel represented an independent predictor of both PFS and OS (HR = 2.47, 95% CI, 1.40-4.35, P =.002, and HR = 1.78, 95% CI, 1.00-3.15, P =.049, respectively). Conclusions: Early ctDNA variation might reflect changes in metastatic burden and, likely, in bone metastatic patterns on ARSI therapy allowing to track pattern of disease progression and to predict outcome
La «corsa» alla regolamentazione dell’intelligenza artificiale: una riflessione in chiave comparata
No full textBrewing of craft beer
No full textThis book provides a comprehensive picture of the main aspects of craft beer, an innovative product that is attracting growing interest from researchers and consumers worldwide. This book is aimed to collect the scientific knowledge available until now on craft beer, by including different issues concerning the history and legal definition, description of raw materials, and aspects related to the production process of the main beer styles, with emphasis on traditional and innovative microbial resources involved in the fermentative process, other than issues related to organoleptic quality, critical points and nutritional concerns, but also an issue related to the emerging problems, such as the sustainability of the production process
Intelligenza Artificiale e trattamento dei dati tra diritto internazionale e ordinamenti interni
No full textThis article examines the legal implications of using both personal and non-personal data
in the training of artificial intelligence (AI) systems, focusing in particular on the role of international
law and its interaction with domestic legal systems. While legal frameworks have traditionally
centred on the protection of personal data, the author highlights the inadequacy of this paradigm
in the context of machine learning, which primarily relies on non-personal data and inferential
techniques targeting indistinct groups of individuals. The article stresses the growing need
to recognize collective forms of protection, moving beyond the individual-centric approach of data
regulation. After surveying recent unilateral regulatory developments – especially in the European
Union, the United States, China, Japan, and Canada – as well as multilateral initiatives
promoted by the United Nations, G7, and the Council of Europe, the author underscores the importance
of interpretive strategies and the principle of technological neutrality. These tools are
seen as essential for adapting existing legal categories to the new challenges posed by AI. The
central thesis is that specific new rules are not always required; rather, a dynamic and technologically
agnostic application of existing legal frameworks may suffice
Adenosine A3 receptor antagonists as anti-tumor treatment in human prostate cancer: an in vitro study
No full text: Prostate cancer (PCa) is one of the most common cancers in men, and for patients with PCa that cannot be surgically resected or treated, androgen suppression therapy often results in significant adverse effects. Recent studies have shown that A3 adenosine receptors (A3ARs) are overexpressed in prostate cancer (PCa), and several A3AR agonists and antagonists have been investigated as potential anticancer drugs. In this study, we investigated the potential therapeutic effects of the A3AR antagonists AR 292 and AR 357 in human PCa cell lines. LNCaP, DU-145, and PC3 cell lines were treated with AR 292 and AR 357 compounds, and their cytotoxic effects were determined using viability assays, flow cytometry, and western blotting. Moreover, the drug transporter gene profile was evaluated using RT-PCR in untreated and A3AR antagonist-treated PCa cells. Both AR 292 and AR 357 showed antiproliferative effects with significant cell cycle arrest and induced DNA damage leading to cell death. AR 292 and especially AR 357 modulated the expression of drug transporter genes involved in chemoresistance, ferroptosis, and the hypoxia response. Ferroptosis was induced in DU-145 cells treated with both compounds as well as in PC3 cells treated with AR 357. However, the treatment of PC3 cells with AR 292 and the treatment of LNCaP cells with both AR 292 and AR 357 resulted in necrotic cell death. In conclusion, our study showed that A3AR ligands exert anticancer effects via different mechanisms on PCa cell lines through the activation of multiple molecular pathways
