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Circulating, Extracellular Vesicle-Associated Tissue Factor in Cancer Patients with and Without Venous Thromboembolism
Get PDFCancer is characterized by chronic inflammation and hypercoagulability, with an excess of venous thromboembolism (VTE). Tissue factor, the initiator of blood coagulation, circulates associated with extracellular vesicles (EV-TF). Studies investigating EV-TF between cancer-associated and non-cancer-associated VTE are lacking. We therefore compared EV-TF in unprovoked VTE (U-VTE), cancer-associated VTE (C-VTE), and cancer without VTE (C-w/o VTE). We also investigated interleukin-6 (IL-6) levels between the same groups. The final population included 68 patients (U-VTE: n = 15; C-VTE: n = 24; C-w/o VTE: n = 29). All patients with VTE were enrolled within 48 h of diagnosis; non-VTE patients were recruited in the oncologic outpatient services. EV were isolated by differential centrifugation from 4 mL of peripheral blood; the final EV pellet (16,000x g for 45 min) was resuspended in 100 mu L saline and tested for TF using a one-step clotting assay. There was a statistically significant difference for higher EV-TF in C-VTE and C-w/o VTE compared to U-VTE (p = 0.024; Kruskal-Wallis test). There was no significant difference between C-VTE and C-w/o VTE. Moreover, we did not find any difference in IL-6 levels. These preliminary data suggest that cancer represents, per se, a strong driver of EV-TF generation
Safe-CLIP: Removing NSFW Concepts from Vision-and-Language Models
No full textLarge-scale vision-and-language models, such as CLIP, are typically trained on web-scale data, which can introduce inappropriate content and lead to the development of unsafe and biased behavior. This, in turn, hampers their applicability in sensitive and trustworthy contexts and could raise significant concerns in their adoption. Our research introduces a novel approach to enhancing the safety of vision-and-language models by diminishing their sensitivity to NSFW (not safe for work) inputs. In particular, our methodology seeks to sever “toxic” linguistic and visual concepts, unlearning the linkage between unsafe linguistic or visual items and unsafe regions of the embedding space. We show how this can be done by fine-tuning a CLIP model on synthetic data obtained from a large language model trained to convert between safe and unsafe sentences, and a text-to-image generator. We conduct extensive experiments on the resulting embedding space for cross-modal retrieval, text-to-image, and image-to-text generation, where we show that our model can be remarkably employed with pre-trained generative models. Our source code and trained models are available at: https://github.com/aimagelab/safe-clip
Studying the trimethylsilylation of alkylcatechols in Asian lacquers by analytical pyrolysis coupled with online micro-reaction sampler
No full textAsian lacquers are natural polymers obtained from the sap of trees of the Anacardiaceae family. Their main chemical components are long-chain alkylcatechols that form a complex polymeric network upon curing. Analytical pyrolysis is the most powerful tool to study these polymers from a chemical point of view. However, derivatisation of polar pyrolysis products, especially alkylcatechols, is needed to ensure their detection by gas chromatographic techniques. In this study, in situ trimethylsilylation using hexamethyldisilazane (HMDS) applied to the pyrolysis of urushi (Toxicodendron vernicifluum) and thitsi (Gluta usitata) lacquers was investigated to address the issue of partial derivatisation of alkylcatechols in flash pyrolysis conditions. By using an online micro-reaction sampler (MRS) coupled to pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), the derivatisation reaction was studied under controlled conditions. The reaction time between HMDS and lacquer pyrolysis products generated at 400 °C was investigated, proving that 12 s is sufficient for the complete trimethylsilylation of alkylcatechols. This information is crucial to understand the factors affecting in situ derivatisation, showing that slightly extending the contact time between the derivatising agent and the pyrolysis products is a relatively easy solution to partial derivatisation deriving from steric hindrance. This optimised procedure yields simpler chromatograms compared to flash pyrolysis and has high potential for the enhanced characterisation of these materials and the detection of lacquer molecular markers in samples containing complex mixtures of organic materials
Usurpation of (and Corruption involving) the Right of Roman Citizenship in the Republic
No full textIn the essay the author examines how the right of Roman citizenship in the republican age was usurped, beginning with the evidence of fraudulent attempts of inclusion in Roman colonies and on Roman census lists that were tried by Latins, before analyzing episodes of falsification of tabulae in both central and local archives, and finally
considering the adscriptio of several (Eastern) Greeks in Southern Italian towns
Human-AI coevolution
No full textHuman-AI coevolution, defined as a process in which humans and AI algorithms continuously influence each other, increasingly characterises our society, but is understudied in artificial intelligence and complexity science literature. Recommender systems and assistants play a prominent role in human-AI coevolution, as they permeate many facets of daily life and influence human choices through online platforms. The interaction between users and AI results in a potentially endless feedback loop, wherein users' choices generate data to train AI models, which, in turn, shape subsequent user preferences. This human-AI feedback loop has peculiar characteristics compared to traditional human-machine interaction and gives rise to complex and often “unintended” systemic outcomes. This paper introduces human-AI coevolution as the cornerstone for a new field of study at the intersection between AI and complexity science focused on the theoretical, empirical, and mathematical investigation of the human-AI feedback loop. In doing so, we: (i) outline the pros and cons of existing methodologies and highlight shortcomings and potential ways for capturing feedback loop mechanisms; (ii) propose a reflection at the intersection between complexity science, AI and society; (iii) provide real-world examples for different human-AI ecosystems; and (iv) illustrate challenges to the creation of such a field of study, conceptualising them at increasing levels of abstraction, i.e., scientific, legal and socio-political
JG26 attenuates ADAM17 metalloproteinase-mediated ACE2 receptor processing and SARS-CoV-2 infection in vitro
No full textBackground: ADAM17 is a metalloprotease implicated in the proteolysis of angiotensin-converting enzyme 2 (ACE2), known to play a critical role in the entry and spread of SARS-CoV-2. In this context, ADAM17 results as a potential novel target for controlling SARS-CoV-2 infection. Methods: In this study, we investigated the impact on ACE2 surface expression and the antiviral efficacy against SARS-CoV-2 infection of the selective ADAM17 inhibitor JG26 and its dimeric (compound 1) and glycoconjugate (compound 2) derivatives using Calu-3 human lung cells. Results: None of the compounds exhibited cytotoxic effects on Calu-3 cells up to a concentration of 25 μM. Treatment with JG26 resulted in partial inhibition of both ACE2 receptor shedding and SARS-CoV-2 infection, followed by compound 1. Conclusion: JG26, an ADAM17 inhibitor, demonstrated promising antiviral activity against SARS-CoV-2 infection, likely attributed to reduced sACE2 availability, thus limiting viral dissemination
Water utility regulatory models for energy procurement in Europe: An empirical investigation
No full textSince the latter half of 2021, energy prices have risen owing to gas and fuel shortages following the rapid economic recovery after the restrictive measures due to the COVID-19 pandemic, with the 2022 Russian invasion of Ukraine exacerbating this stress. As energy prices rose, procurement became a strategic process even in regulated natural monopolies. To give the right impetus to water utilities, entrusting public bodies in several countries with setting rules for cost recovery, tariff methodology, and ensuring quality standards is essential. These bodies must also recognise that incentive-based regulation will influence energy procurement, especially through tariff methodologies applied by water regulators to recover the costs incurred. Therefore, this study provides an overview of the regulatory models adopted in Europe by National Regulatory Authorities (NRAs) to determine allowed energy costs, along with a detailed examination of the diverse national approaches adopted before the energy crisis. It further highlights instances where certain NRAs demonstrated limited awareness of the importance of incentive schemes associated with energy procurement. Building upon existing models, this study developed a framework to identify alternatives and incentives for regulating energy purchasing prices in the water sector. This framework benefits NRAs seeking to update their methodology for cost recovery of water utilities
Postprandial hypoglycaemia after gastric bypass in type 2 diabetes: pathophysiological mechanisms and clinical implications
No full textFactors affecting the mean electrical axis of the heart in trained Thoroughbreds
No full textBackground: Assuming that the ventricular myocardium of horses is subjected to exercise-induced hypertrophy, we hypothesised that the mean electrical axis (MEA) of the heart would change. Objectives: To define a longitudinal study to detect any changes in the direction of the MEA in Thoroughbred horses using ECG. Study design: ECGs were recorded on each horse in each training group at day 0 (T0), 1 month (T1) and 2 months (T2) of training. Methods: A total of 43 Thoroughbred horses in training in Italy were recruited. The horses were divided into three groups according to age. The ECGs were recorded by positioning the electrodes according to Dubois's method for measuring MEA in the frontal plane. Intervals with artefact-free QRS complexes in both bipolar DI and augmented unipolar aVF leads were selected, and the vector obtained was identified as the MEA. The statistical analysis was performed via generalised linear mixed model (GLMM) and principal component analysis (PCA). Results: A statistically significant effect of time passing between T0 and T2 (p < 0.001) and an interaction between time and sex on the MEA was found (p = 0.04). PCA revealed that the population studied had different patterns, with three horses showing higher variability in the MEA direction. Main limitations: There was no good sex balance in the age groups of the population studied, and there was no control group. The 1-month sampling intervals of ECGs may have been too short. Confirmatory studies are needed. Conclusions: We believe that our results are the first to suggest that training may lead to changes in MEA orientation in horses. Sex and individuality were found to influence MEA orientation and may have contributed to the difficulty in detecting training-dependent changes in MEA to date
Cold induces increased ad libitum energy intake independent of changes in energy expenditure: a controlled crossover trial in adults
No full textBackground: Measures of energy metabolism [energy expenditure (EE), respiratory exchange ratio (RER)] have been associated with ad libitum energy intake (EI) and weight gain in previous observational studies, suggesting that energy-sensing mechanisms drive EI to meet metabolic energy demands. Objective: We aimed to employ mild cold exposure as an intervention to alter energy metabolism and evaluate its causal effects on concurrent and next day ad libitum EI. Methods: In a controlled crossover study, 47 volunteers (16 female; age 37.2±10.7 years; BMI 32.4±8.6 kg/m2) completed four 24-h EE measurements in a respiratory chamber. Participants ate ad libitum for 24-h using an objective vending machine paradigm while in the chamber during both cold exposure (19°C) and thermoneutral conditions (23.5°C) and after two eucaloric chamber stays with exposure to each temperature. Energy metabolism changes were calculated from eucaloric conditions (cold vs. thermoneutral). Results: Compared to thermoneutral conditions, participants consumed 13% more while residing in the chamber during cold (mean difference: 411±987 kcal/day, p=0.006), but not the day after cold exposure. Neither eucaloric EE, RER, nor carbohydrate oxidation (CARBOX) were significantly changed by cold exposure. However, greater increases in RER and CARBOX during cold exposure were associated with greater ad libitum EI on the day after cold exposure (r=0.29, p=0.049 and r=0.33, p=0.02), but not with EI during cold exposure. Cold-induced changes in 24-h EE were not associated with changes in ad libitum EI during or after cold exposure. Conclusion: Ad libitum EI increased during but not following mild cold exposure. There was an effect of 24-h RER and CARBOX during cold exposure that was related to greater ad libitum EI following cold. These results indicate an acute effect of cold on concurrent EI independent of changes in metabolic rate, but also a residual influence of cold on subsequent EI via fuel preference. CLINICAL TRIAL REGISTRATION NUMBER (FROM CLINICALTRIALS.GOV): NCT02939404