Archivio istituzionale della Ricerca - Università degli Studi di Parma
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Harnessing Vinylogy with Radicals: Photoinduced γ-Benzylation Reactions of 2-Silyloxyfurans
No full text2-Silyloxyfurans are among the most exploited Mukaiyama-type vinylogous nucleophiles from which a myriad of bioactive γ-butyrolactones have been accessed. Although a plethora of “polar” reactions featuring this scaffold as a key player have been developed so far, its behavior in radical chemistry is still in its infancy. Herein, the development of two complementary vinylogous, radical-mediated benzylations of 2-silyloxyfurans, promoted by visible light and suitable photoredox catalysts, is described. Common to both photocatalytic cycles is the reduction of a suitable redox active ester forging a key benzyl radical intermediate, which undergoes two different fates. First, the photoinduced oxidation of the silyloxyfuran generates an unprecedented silyl-radical cation species able to trap the nucleophilic benzyl radical. Alternatively, with specific electron-rich substrates, the benzyl radical can be converted to the corresponding benzyl carbocation intermediate via a net-neutral radical-polar crossover pathway, enabling a vinylogous, polar benzylation reaction. A broad scope of chiral, γ-benzyl butenolides is obtained in one step, some of which are used as strategic precursors to access bioactive phenyl-γ-valerolactone metabolites
Artificial Intelligence for Wireless Communications: The InSecTT perspective
No full textThis article presents an overview of how Artificial Intelligence (AI) and edge technology have been used to improve wireless connectivity in multiple industrial Use Cases (UCs) of the EU project “Intelligent Secure Trustable Things” (InSecTT). We present a brief introduction of the InSecTT framework for cross-domain architecture design, which targets UCs assisted by reusable and/or interoperable technical Building Blocks (BBs). These BBs constitute the “bricks” containing AI and supporting components that were used to build different UCs. The framework consists of multiple stages based on the processing of UC/BB requirements (RQs). These stages include collection, harmonization, refinement, classification, architecture alignment, and functionality modeling of RQs. The most relevant results of these stages are discussed here, with emphasis on the need for a refined granularity of technical components with common functionalities named Sub-Building blocks (SBBs), where collaboration and cross-domain reusability were optimized. The design process shed light on how AI and SBBs were implemented across different layers and entities of our reference architecture for the Internet-of-Things (IoT), including the interfaces used for information exchange. This detailed interface analysis is expected to reveal issues such as bottlenecks, constraints, vulnerabilities, scalability problems, security threats, etc. This will, in turn, contribute to identifying design gaps of AI-enabled IoT systems. The article summarizes the SBBs related to wireless connectivity, including a general description, implementation issues, a comparison of results, adopted interfaces, and conclusions across domains
Radiofrequency Echographic Multi-Spectrometry for Early Bone Health: The REMS-Bone Study Protocol (Trial Acronym: REMS-Bone)
No full textRouMBLE: A Sink-Oriented Routing Protocol for BLE Mesh Networks
No full textIn Internet of Things (IoT)-like contexts, there is often the need to leverage traffic routing mechanisms among heterogeneous devices, especially when classical (and well-known) addressing paradigms cannot be adopted or supported by constrained IoT devices deployed on the field (e.g., due to memory footprint, internal limitations, etc.). This is even more true (and necessary) when nodes interact in unstructured networks (e.g., mesh-like) lacking a specific topology (e.g., exploiting flooding approaches to transfer information) and external "smart"devices should be allowed to interact with these networks. To this end, in this paper a multi-sink routing protocol, denoted as Routing on Mesh Bluetooth Low Energy (), is proposed. Our implementation relies on BLE advertisement channels and allows sink nodes to control topology formation and data collection (with both unicast and broadcast communications), with nodes identified with compressed addresses. A relevant experimental application to environmental lighting management is presented
Cytokines from Macrophages Activated by Spike S1 of SARS-CoV-2 Cause eNOS/Arginase Imbalance in Endothelial Cells
No full textMultiple lines of evidence suggest that endothelial dysfunction is a key player in the pathogenesis of COVID-19, with cytokine storm as one of the main primary causes. Among the mechanisms underlying endothelial damage, clinical findings identify alterations in arginine metabolism, as patients with severe COVID-19 exhibit lower levels of nitric oxide synthase (eNOS) and upregulated arginase. In this study, we investigated, in human endothelial cells (HUVECs), the effect of conditioned medium from macrophages activated with SARS-CoV-2 Spike protein (CM_S1) on arginine metabolism. The results indicate that CM_S1 causes a marked decrease in eNOS and an increase in arginase, along with a greater intracellular arginine content and the induction of the CAT2 transporter. These effects are ascribable to the inflammatory mediators released by macrophages in CM_S1, mainly TNFα and IL-1β. Since infliximab, an antibody targeting TNFα, and baricitinib, an inhibitor of the JAK/STAT pathway, correct the observed imbalance between eNOS and arginase, our findings suggest the potential efficacy of a combined therapy to counteract endothelial dysfunction in COVID-19
How to Write Effective Prompts for Screening Biomedical Literature Using Large Language Models
No full textLarge language models (LLMs) have emerged as powerful tools for (semi-)automating the initial screening of abstracts in systematic reviews, offering the potential to significantly reduce the manual burden on research teams. This paper provides a broad overview of prompt engineering principles and highlights how traditional PICO (Population, Intervention, Comparison, Outcome) criteria can be converted into actionable instructions for LLMs. We analyze the trade-offs between “soft” prompts, which maximize recall by accepting articles unless they explicitly fail an inclusion requirement, and “strict” prompts, which demand explicit evidence for every criterion. Using a periodontics case study, we illustrate how prompt design affects recall, precision, and overall screening efficiency and discuss metrics (accuracy, precision, recall, F1 score) to evaluate performance. We also examine common pitfalls, such as overly lengthy prompts or ambiguous instructions, and underscore the continuing need for expert oversight to mitigate hallucinations and biases inherent in LLM outputs. Finally, we explore emerging trends, including multi-stage screening pipelines and fine-tuning, while noting ethical considerations related to data privacy and transparency. By applying systematic prompt engineering and rigorous evaluation, researchers can optimize LLM-based screening processes, allowing for faster and more comprehensive evidence synthesis across biomedical disciplines
Per «una vita politica veramente umana». Il Concilio e la responsabilità civile dei credenti
No full textNovel drug discovery strategies for chronic obstructive pulmonary disease: the latest developments
No full textIntroduction: The journey from initial drug discovery to approval for respiratory diseases typically spans approximately 10.4 years and cost over $2.8 billion. This intricate process involves five stages: target identification, therapeutic molecule discovery, preclinical testing, clinical trials, and regulatory approval. Areas covered: This review examines novel drug discovery strategies for chronic obstructive pulmonary disease (COPD), focusing on advanced in vitro models that replicate human lung conditions for accurate drug testing according to the following search string: discovery AND strategy AND COPD. It explores targeted molecular therapies, structure-based drug design, and drug repurposing approaches facilitated by computational analysis. The significance of personalized medicine in tailoring treatments for diverse COPDs is emphasized, highlighting the complexity of the disease and the necessity of these innovative methodologies to improve therapeutic outcomes. Expert opinion: COPD remains a challenging area, with a significant unmet medical need. Despite previous efforts, few effective therapies exist. Innovative in vitro models, targeted molecular therapies, and drug repurposing strategies are showing promise. Emphasizing advanced preclinical models and repurposing existing drugs could transform treatment paradigms, promoting more effective therapies for complex diseases like COPD. These innovations hold potential for enhancing drug discovery efficiency, leading to personalized and precision medicine approaches
Longitudinal transcriptomic analysis of the hyperoxia-exposed preterm rabbit as a model of BPD
No full textBronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease of premature neonates. BPD development depends on prenatal and postnatal factors that induce inflammation, altering alveolar growth and pulmonary vascular development. Animal models are essential to investigate the precise molecular pathways leading to BPD. The preterm rabbit combines many advantages of small (e.g., rodents) and large BPD models (e.g., preterm lambs and baboons). Preterm rabbits display mild-to-moderate respiratory distress at delivery, which, along with continuous exposure to hyperoxia (95% O2), leads to functional and morphological lung changes resembling a BPD-like phenotype. Nevertheless, the molecular pathways leading to the BPD-like phenotype remain poorly understood. Here, we aimed to characterize the longitudinal gene expression in the lungs of preterm rabbits exposed to 95% O2, on postnatal days 3, 5, and 7. Histological analyses confirmed extensive lung injury and reduced lung development after 7 days of hyperoxia. Longitudinal transcriptomic analysis revealed different expression patterns for several genes and pathways. Over time, extracellular matrix organization and angiogenesis were increasingly downregulated. Apoptosis, RNA processing, and inflammation showed the opposite trend. We also investigated the expression of representative genes of these pathways, whose signatures could aid in developing pharmacological treatments in the context of BPD