74 research outputs found

    Towards Parsimonious Generative Modeling of RNA Families

    Full text link
    Generative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the characteristics of RNA sequences, with a strong emphasis on simplicity, efficiency, and interpretability. eaDCA explicitly constructs sparse coevolutionary models for RNA families, achieving performance levels comparable to more complex methods while utilizing a significantly lower number of parameters. Our approach demonstrates efficiency in generating artificial RNA sequences that closely resemble their natural counterparts in both statistical analyses and SHAPE-MaP experiments, and in predicting the effect of mutations. Notably, eaDCA provides a unique feature: estimating the number of potential functional sequences within a given RNA family. For example, in the case of cyclic di-AMP riboswitches (RF00379), our analysis suggests the existence of approximately 1039\mathbf{10^{39}} functional nucleotide sequences. While huge compared to the known <4,000< \mathbf{4,000} natural sequences, this number represents only a tiny fraction of the vast pool of nearly 1082\mathbf{10^{82}} possible nucleotide sequences of the same length (136 nucleotides). These results underscore the promise of sparse and interpretable generative models, such as eaDCA, in enhancing our understanding of the expansive RNA sequence space.Comment: 33 pages (including SI

    Chronic NSAIDs Therapy and Upper Gastrointestinal Tract – Mechanism of Injury, Mucosal Defense, Risk Factors for Complication Development and Clinical Management

    Get PDF
    Non steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed medications worldwide because of their analgesic and anti-inflammatory properties. In fact, NSAIDs are generally prescribed for pain management in musculoskeletal or osteoarticolar pathologies and for rheumatic diseases, very common diseases in the general population. About twenty million US patients were prescribed NSAIDs every year. Although NSAIDs are generally well tolerated, chronic therapy is responsible for a significant morbidity and mortality rate; in fact, the incidence of GI events is significantly higher (about four fold) in patients receiving NSAIDs chronic therapy. Adverse gastrointestinal events related to NSAIDs therapy occur in a little but significant amount of patients, resulting in an important morbidity and mortality. In the US more than 150 per 100.000 patients were admitted every year for NSAIDs related adverse events, resulting in about 15000 deaths. The chapter covers the mechanism of NSAIDs related injury, mucosal defense, risk factors for complication development and the clinical management

    Goal-oriented Communications for the IoT: System Design and Adaptive Resource Optimization

    Full text link
    Internet of Things (IoT) applications combine sensing, wireless communication, intelligence, and actuation, enabling the interaction among heterogeneous devices that collect and process considerable amounts of data. However, the effectiveness of IoT applications needs to face the limitation of available resources, including spectrum, energy, computing, learning and inference capabilities. This paper challenges the prevailing approach to IoT communication, which prioritizes the usage of resources in order to guarantee perfect recovery, at the bit level, of the data transmitted by the sensors to the central unit. We propose a novel approach, called goal-oriented (GO) IoT system design, that transcends traditional bit-related metrics and focuses directly on the fulfillment of the goal motivating the exchange of data. The improvement is then achieved through a comprehensive system optimization, integrating sensing, communication, computation, learning, and control. We provide numerical results demonstrating the practical applications of our methodology in compelling use cases such as edge inference, cooperative sensing, and federated learning. These examples highlight the effectiveness and real-world implications of our proposed approach, with the potential to revolutionize IoT systems.Comment: Accepted for publication on IEEE Internet of Things Magazine, special issue on "Task-Oriented Communications and Networking for the Internet of Things

    COVID-19 in the tonsillectomised population

    Get PDF
    Objective: Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. Methods: Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. Results: Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. Conclusions: A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models

    Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation

    Get PDF
    Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients

    Migranti in campania

    No full text
    • …
    corecore