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Os sistemas de saúde dos países industrializados enfrentam múltiplos desafios que tornam cada vez mais complexo garantir o direito à saúde de forma equitativa para toda a população. Neste contexto enquadram-se os processos de inovação tecnológica e, em particular, os ligados à introdução de tecnologias de informação e comunicação nos cuidados de saúde. À luz disto, analisar a interação entre o direito à saúde e os serviços digitais de saúde torna-se uma necessidade cada vez mais concreta, tanto quanto é compreender se, em que medida e através de que ferramentas, tal interação pode gerar uma reivindicação legal em nível individual, tentativa com a qual nos mediremos na continuação deste trabalho.

Le società contemporanee si affidano in misura crescente alle opportunità create dalle tecnologie che rendono possibile la produzione, raccolta, elaborazione e riutilizzo di enormi dataset per ricavare inferenze spendibili negli ambiti più disparati. Fra questi vi è anche quello medico-sanitario, che ha visto un’accelerazione inusitata dei processi di digitalizzazione in coincidenza con l’avvento della pandemia di COVID-19. Tali processi hanno contribuito al consolidamento di quella che può essere definita come informational medicine, ovvero un paradigma che si basa in misura progressivamente crescente sulla raccolta e l’analisi di dati tratti dal corpo umano. In questo contesto va inquadrata l’emersione del digital phenotyping, ovvero la quantificazione di caratteristiche fenotipiche umane attraverso l’analisi dei dati offerti dai dispositivi digitali. Come evidenziato dalla letteratura specializzata in materia, il digital phenotyping può rivoluzionare il processo diagnostico-terapeutico, soprattutto nell’ambito della salute mentale, garantendo maggiore accuratezza e tempestività d’intervento. Tuttavia, l’emersione di questa innovativa dimensione rischia di sfumare i confini tra prevenzione e sorveglianza, rappresentando una minaccia concreta non solo per la sfera personale, ma anche, più in generale, sul piano della cybersecurity. All’interno di questo lavoro si descrivono in maniera più dettagliata i rischi che possono derivare dalla diffusione del digital phenotyping attraverso un raffronto costante tra i riscontri offerti dalla letteratura e il contesto giuridico di riferimento tra cui, in particolare, la disciplina offerta dal Regolamento UE 2016/679.

Motivation Single-cell profiling has become a common practice to investigate the complexity of tissues, organs, and organisms. Recent technological advances are expanding our capabilities to profile various molecular layers beyond the transcriptome such as, but not limited to, the genome, the epigenome, and the proteome. Depending on the experimental procedure, these data can be obtained from separate assays or the very same cells. Yet, integration of more than two assays is currently not supported by the majority of the computational frameworks avaiable. Results We here propose a Multi-Omic data integration framework based on Wasserstein Generative Adversarial Networks suitable for the analysis of paired or unpaired data with a high number of modalities (>2). At the core of our strategy is a single network trained on all modalities together, limiting the computational burden when many molecular layers are evaluated. Availability and implementation Source code of our framework is available at https://github.com/vgiansanti/MOWGAN [ABSTRACT FROM AUTHOR]

Although toxin may have some advantages compared to chemotherapeutic drugs in cancer therapy, e.g. a potent cytotoxic activity and a reduced risk of resistance, their successful application in the treatments to solid tumors still remains to be fully demonstrated. In this study, we genetically modified the structure of the plant-derived single-chain ribosome inactivating protein saporin (SAP) by fusing its N-terminus to the ACDCRGDCFCG peptide (RGD-4C), an αv-integrin ligand, and explored the anti-tumor activity of the resulting protein (called RGD-SAP) in vitro and in vivo, using a model of muscle invasive bladder cancer. We found that the RGD-4C targeting domain enhances the cytotoxic activity of SAP against various tumor cell lines, in a manner dependent on αv-integrin expression levels. In a subcutaneous syngeneic model of bladder cancer, RGD-SAP significantly reduced tumor growth in a dose-dependent manner. Furthermore, systemic administration of RGD-SAP in combination with mitomycin C, a chemotherapeutic drug currently used to treat patients with bladder cancer, increased the survival of mice bearing orthotopic bladder cancer with no evidence of systemic toxicity. Overall, the results suggest that RGD-SAP represents an efficient drug that could be exploited, either alone or in combination with the state-of-the-art therapies, for the treatment of bladder cancer and, potentially, of other solid tumors.

Therapeutic strategies designed to tinker with cancer cell DNA damage response have led to the widespread use of PARP inhibitors for BRCA1/2-mutated cancers. In the haematological cancer multiple myeloma, we sought to identify analogous synthetic lethality mechanisms that could be leveraged upon established cancer treatments. The combination of ATR inhibition using the compound VX-970 with a drug eliciting interstrand cross-links, melphalan, was tested in in vitro, ex vivo, and most notably in vivo models. Cell proliferation, induction of apoptosis, tumor growth and animal survival were assessed. The combination of ATM inhibition with a drug triggering double strand breaks, doxorucibin, was also probed. We found that ATR inhibition is strongly synergistic with melphalan, even in resistant cells. The combination was dramatically effective in targeting myeloma primary patient cells and cell lines reducing cell proliferation and inducing apoptosis. The combination therapy significantly reduced tumor burden and prolonged survival in animal models. Conversely, ATM inhibition only marginally impacted on myeloma cell survival, even in combination with doxorucibin at high doses. These results indicate that myeloma cells extensively rely on ATR, but not on ATM, for DNA repair. Our findings posit that adding an ATR inhibitor such as VX-970 to established therapeutic regimens may provide a remarkably broad benefit to myeloma patients.

Multiple Myeloma (MM) is a genetically complex and heterogeneous hematological cancer that remains incurable despite the introduction of novel therapies in the clinic. Sadly, despite efforts spanning several decades, genomic analysis has failed to identify shared genetic aberrations that could be targeted in this disease. Seeking alternative strategies, various efforts have attempted to target and exploit non-oncogene addictions of MM cells, including, for example, proteasome inhibitors. The surprising finding that MM cells present rampant genomic instability has ignited concerted efforts to understand its origin and exploit it for therapeutic purposes. A credible hypothesis, supported by several lines of evidence, suggests that at the root of this phenotype there is intense replicative stress. Here, we review the current understanding of the role of replicative stress in eliciting genomic instability in MM and how MM cells rely on a single protein, Ataxia Telangiectasia-mutated and Rad3-related protein, ATR, to control and survive the ensuing, potentially fatal DNA damage. From this perspective, replicative stress per se represents not only an opportunity for MM cells to increase their evolutionary pool by increasing their genomic heterogeneity, but also a vulnerability that could be leveraged for therapeutic purposes to selectively target MM tumor cells.

Abstract Background Oral health and frailty might be linked through several pathways, but previous studies are scarce. This study examined the association between oral health and components of Fried’s frailty phenotype. Methods This cross-sectional analysis was based on a sample of 992 community-dwelling persons aged 73 to 77 years observed in the 2011 follow-up of the Lausanne 65+ cohort (Lc65+) study. Data were collected through annual mailed questionnaires, interview and physical examination. Oral health was assessed according to self-reported oral pain and masticatory ability. Frailty was defined as meeting at least one criterion of the Fried’s phenotype. Results Oral pain was reported by 14.8% and chewing problems by 9.7%. Impaired masticatory ability (IMA) was more frequent in subjects with missing teeth or removable dentures (13.5%) than among those with full dentition or fixed dental prostheses (3.2%). In logistic regression analyses adjusting for demographics, alcohol consumption, smoking, comorbidity and financial difficulties, persons with oral pain and those with chewing problems had significantly higher odds of being frail (adjusted ORpain = 1.72; 95% CI 1.17–2.53 and adjORIMA1.70; 1.07–2.72, respectively). Lack of endurance was associated with both oral pain (adjOR = 3.61; 1.92–6.76) and impaired masticatory ability (adjOR = 2.20; 1.03–4.72). The latter was additionally linked to low physical activity (adjOR = 2.35; 1.29–4.28) and low gait speed (adjOR = 3.12; 1.41–6.90), whereas oral pain was associated with weight loss (adjOR = 1.80; 1.09–2.96) and low handgrip strength (adjOR = 1.80; 1.17–2.77). Conclusion Self-reported oral pain and chewing impairment had a significant relation with frailty and its components, not only through a nutritional pathway of involuntary weight loss. Longitudinal analyses are needed to examine whether a poor oral condition might be a risk factor for the onset of frailty.