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Extracellular vesicles (EVs) appear to play an important role in intercellular communication in various physiological processes and pathological conditions such as cancer. Like enveloped viruses, EVs can transport their contents into the nucleus of recipient cells, and a new intracellular pathway has been described to explain the nuclear shuttling of EV cargoes. It involves a tripartite protein complex consisting of vesicle-associated membrane protein-associated protein A (VAP-A), oxysterol-binding protein (OSBP)-related protein-3 (ORP3) and late endosome-associated Rab7 allowing late endosome entry into the nucleoplasmic reticulum. Rab7 binding to ORP3-VAP-A complex can be blocked by the FDA-approved antifungal drug itraconazole. Here, we design a new series of smaller triazole derivatives, which lack the dioxolane moiety responsible for the antifungal function, acting on the hydrophobic sterol-binding pocket of ORP3 and evaluate their structure-activity relationship through inhibition of VOR interactions and nuclear transfer of EV and HIV-1 cargoes. Our investigation reveals that the most effective compounds that prevent nuclear transfer of EV cargo and productive infection by VSV-G-pseudotyped HIV-1 are those with a side chain between 1 and 4 carbons, linear or branched (methyl) on the triazolone region. These potent chemical drugs could find clinical applications either for nuclear transfer of cancer-derived EVs that impact metastasis or viral infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The United Kingdom patent application GB2598624A (applicants: M.F.S., G.R., P.D., G.C., A.L. and Technische Universität Dresden (TUD); inventors: M.F.S., G.R., P.D., G.C., D.C. and A.L.), European patent application EP3864409A1 (applicants: M.F.S., G.R., A.L. and TUD; inventors; M.F.S., G.R., D.C. and A.L.) and United States provisional patent number US20210353616A1 (applicants: M.F.S., G.R., A.L. and TUD; inventors: M.F.S., G.R., D.C. and A.L.) are pending. The authors declare no other competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: In recent years, the scientific community focused on developing Computer-Aided Diagnosis (CAD) tools that could improve clinicians' bone fractures diagnosis, primarily based on Convolutional Neural Networks (CNNs). However, the discerning accuracy of fractures' subtypes was far from optimal. The aim of the study was 1) to evaluate a new CAD system based on Vision Transformers (ViT), a very recent and powerful deep learning technique, and 2) to assess whether clinicians' diagnostic accuracy could be improved using this system., Materials and Methods: 4207 manually annotated images were used and distributed, by following the AO/OTA classification, in different fracture types. The ViT architecture was used and compared with a classic CNN and a multistage architecture composed of successive CNNs. To demonstrate the reliability of this approach, (1) the attention maps were used to visualize the most relevant areas of the images, (2) the performance of a generic CNN and ViT was compared through unsupervised learning techniques, and (3) 11 clinicians were asked to evaluate and classify 150 proximal femur fractures' images with and without the help of the ViT, then results were compared for potential improvement., Results: The ViT was able to predict 83% of the test images correctly. Precision, recall and F1-score were 0.77 (CI 0.64-0.90), 0.76 (CI 0.62-0.91) and 0.77 (CI 0.64-0.89), respectively. The clinicians' diagnostic improvement was 29% (accuracy 97%; p 0.003) when supported by ViT's predictions, outperforming the algorithm alone., Conclusions: This paper showed the potential of Vision Transformers in bone fracture classification. For the first time, good results were obtained in sub-fractures classification, outperforming the state of the art. Accordingly, the assisted diagnosis yielded the best results, proving the effectiveness of collaborative work between neural networks and clinicians., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI)., Methods: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure., Results: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors., Conclusions: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Congenital anomalies of the coronary arteries, although uncommon, have the potential to cause serious myocardial damage, ischemic cardiomyopathy, and sudden cardiac death. We report a rare case of origin of all three coronaries from the right sinus of Valsalva., (Copyright © 2016. Published by Elsevier B.V.)

Detection and identification of induction machine faults through the stator current signal using higher order spectra analysis is presented. This technique is known as motor current signature analysis (MCSA). This paper proposes two higher order spectra techniques, namely the power spectrum and the slices of bi-spectrum used for the analysis of induction machine stator current leading to the detection of electrical failures within the rotor cage. The method has been tested by using both healthy and broken rotor bars cases for an 18.5 kW-220 V/380 V-50 Hz-2 pair of poles induction motor under different load conditions. Experimental signals have been analyzed highlighting that bi-spectrum results show their superiority in the accurate detection of rotor broken bars. Even when the induction machine is rotating at a low level of shaft load (no-load condition), the rotor fault detection is efficient. We will also demonstrate through the analysis and experimental verification, that our proposed proposed-method has better detection performance in terms of receiver operation characteristics (ROC) curves and precision-recall graph., (Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.)

2-Diazoindoles were prepared by diazotization of the corresponding 2-aminoindoles followed by neutralisation. 2-Diazoindoles were utilised for the synthesis of 2-triazenoindoles, indolo[2,1-d][1,2,3,5]tetrazines and indolo[2,1-c][1,2,4]triazines. Most of these compounds exhibited in vitro antiproliferative activity.

The title compounds, that hold the deaza skeleton of temozolomide, exhibited potent in vitro antiproliferative activity. An evaluation of such a biological activity indicates that the mode of action of these compounds differs from that of temozolomide and is also mechanistically unrelated to that of any known antitumor drug.

The new of 1-(2-hydroxyethoxy)methylindole derivatives 3a-i were prepared in good yields. None of them showed any significant anti-HIV activity and therefore the benzocondensation between the 2 and 3 positions of the pyrrole ring definitely reduced the weak activity found in the analogues 1a-c.

The title compounds were synthesised in preparative yields by diazotization of the corresponding 2-aminopyrroles. In preliminary screening tests as antileukemic agents they showed modest activity against the murine and human leukemic cell lines FLC and K562S and their multidrug-resistant daunorubicin selected sublines.

3-Diazopyrroles, a class of compounds particularly interesting from a chemical and biological point of view, were assayed for their ability to induce gene mutations employing back mutation (his+ reversion) test in the philamentous bacterium Streptomyces coelicolor at various time during life cycle. Our results suggest that in evaluating the mutagenicity and toxicity of chemicals in Streptomyces system it is important to consider factors such as growth phase. Furthermore in this series of diazopyrroles a relationship between toxicity, mutagenicity and chemical structure was found. The observed mutagenic activity can be the molecular basis for the appearance of antitumor activity.

Indolo[3,2-c]cinnolines of type 5, variously substituted either in the indole and in the cinnoline moieties, were prepared in good overall yields, by intramolecular cyclization of indolo derivatives 4. Compounds 5a-d showed a good cytotoxic activity against FLC and K562 leukemic cell lines, both sensitive and multi-drug resistant.

Pyrrolo-, pyrazolo- and triazolo-phenanthridines were synthetized by using a Pschorrtype cyclization reaction or an intramolecular cyclization of arylnitrenium ions. By using these synthetic methods several azolo-phenanthridines, variously functionalized either in the azolo ring and in the phenanthridine moiety, were prepared. The title compounds, tested against murine leukemia cell lines, sensible and multidrug resistant, showed moderate activity with IC50 in the range 5-50 microM.

Some 3-triazenopyrroles were prepared by coupling 3-diazopyrroles and secondary amines. In preliminary in vitro screening tests derivatives 3 showed to be cytotoxic and exhibited mutagenic effects.

3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.