[SIC Position paper: Treat to prevent the first event - intensive LDL cholesterol lowering in patients at very high cardiovascular risk without a previous cardiovascular event. From ESC guidelines to clinical practice].

Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.

[How to interpret subgroup analyses in cardiovascular trials?].

Clinical trials provide the best evidence on the effect of a treatment, but they evaluate this effect on the total population of the study as if the effect of the randomized treatment was identical in all possible subgroups of patients (young, elderly, male, female, etc.). Subgroup analyses are an important tool to evaluate the presence of any diversity of the treatment effect concerning specific patient characteristics, if there are practical questions about who to treat and when, or if there are doubts about the benefit/risk profile of a therapy in a specific subpopulation.

[Total artificial heart: past, present, and future].

Every year, approximately 5 out of 1000 patients receive a diagnosis of advanced heart failure, with a prevalence of 1-2% in the adult population. This figure is likely underestimated, considering undiagnosed cases. Despite significant progress in medical therapy for heart failure, mortality rates persist around 20% within the first year, reaching 50-60% at 5 years from the initial diagnosis.

[Endovascular devices for severely calcified peripheral lesion preparation: state of the art].

Over the last few decades, endovascular revascularization techniques have revolutionized the treatment of peripheral artery disease, offering a less invasive alternative to surgery. However, the successful treatment of heavily calcified lesions is often compromised by various vascular complications, including recoils, dissections, and the need for target vessel reinterventions. This has prompted the development of several tools for lesion preparation, with the aim of achieving better procedural outcomes.

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer.

KLHL14 is a substrate-binding subunit of Cullin-RING ligase 3 ubiquitin ligase complex, highly enriched in thyroid since early embryonic development, together with its antisense RNA KLHL14-AS. We have previously demonstrated that Klhl14-AS is a competing endogenous RNA regulating several differentiation and survival factors in thyroid cancer, acting as tumor suppressor. Recently, also KLHL14 has been shown to function as tumor suppressor in diffuse large B-cell lymphoma and in malignant mesothelioma.

Explainable artificial intelligence and microbiome data for food geographical origin: the Mozzarella di Bufala Campana PDO Case of Study.

Identifying the origin of a food product holds paramount importance in ensuring food safety, quality, and authenticity. Knowing where a food item comes from provides crucial information about its production methods, handling practices, and potential exposure to contaminants. Machine learning techniques play a pivotal role in this process by enabling the analysis of complex data sets to uncover patterns and associations that can reveal the geographical source of a food item.

Replacing maize silage with hydroponic barley forage in lactating water buffalo diet: Impact on milk yield and composition, water and energy footprint, and economics.

This study investigated the feasibility of integrating hydroponic barley forage (HBF) production into dairy ruminant production, focusing on its effect on milk yield and components, energy and water footprints, and economic implications. Maize silage (MSil) was used as a benchmark for comparison. The research was conducted on a water buffalo dairy farm equipped with a fully automated hydroponic system producing approximately 6,000 kg/d of HBF as fed (up 1,000 kg/d on DM basis).

Endoscopic transorbital approach to the petrous apex: is orbital rim removal worthwhile for the exposure? An anatomical study with illustrative case.

Objective: The endoscopic transorbital approach (ETOA) has been demonstrated to be a feasible ventral route to the petrous apex. Yet, it has been pointed to as a deep and narrow corridor for anterior petrosectomy; particularly, medialization of the instruments can become an issue when targeting the petroclival area. To overcome this limitation, an ETOA with orbital rim removal (ETOA-OR) has been suggested, but not de facto compared, with a transorbital approach without removal of the rim.

An integrated design strategy coupling additive manufacturing and matrix-assisted pulsed laser evaporation (MAPLE) towards the development of a new concept 3D scaffold with improved properties for tissue regeneration.

Bioinspired strategies for scaffold design and optimization were improved by the introduction of Additive Manufacturing (AM), thus allowing for replicating and reproducing complex shapes and structures in a reliable manner, adopting different kinds of polymeric and nanocomposite materials properly combined according to the features of the natural host tissues. Benefiting from recent findings in AM, a Matrix-Assisted Pulsed Laser Evaporation (MAPLE) technique was employed for obtaining graphene-like material (GL) uniform coatings on 3D scaffolds for tissue repair strategies, towards the development of a new concept 3D scaffold with controlled morphological/architectural and surface features and mechanical and biological properties. The effect of the material-design combination through an integrated technological approach (, MAPLE deposition of GL on 3D AM PCL scaffolds) was assessed through scanning electron microscopy, atomic force microscopy, contact angle measurements, mechanical measurements and biological analyses (cell viability assay and alkaline phosphatase activity) in conjunction with confocal laser scanning microscopy.

A chemical modification of a peroxisome proliferator-activated receptor pan agonist produced a shift to a new dual alpha/gamma partial agonist endowed with mitochondrial pyruvate carrier inhibition and antidiabetic properties.

New analogs of the PPAR pan agonist AL29-26 encompassed ligand (S)-7 showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that (S)-7 induced anti-steatotic effects and enhancement of the glucose uptake.

Interlobar pulmonary sequestration with celiac aberrant artery in an elderly patient treated with combined endovascular and video-assisted thoracoscopic approach.

Pulmonary sequestration is a rare congenital pulmonary anomaly where a portion of the lung parenchyma is supplied by an anomalous systemic artery, usually originating from the thoracic or abdominal aorta. Traditionally surgical resection and ligation of the aberrant feeding vessel are the gold standard treatments of this disease. Hybrid operations consisting in endovascular arterial embolization and surgical resection is a promising treatment option.

Integrating system biology and intratumor gene therapy by trans-complementing the appropriate co-stimulatory molecule as payload in oncolytic herpes virus.

Systems biology has been applied at the multi-scale level within the cancer field, improving cancer prevention, diagnosis and enabling precision medicine approaches. While systems biology can expand the knowledge and skills for oncological treatment, it also represents a challenging expedition due to cancer complexity, heterogeneity and diversity not only between different cancer indications, but also in its evolution process through space and time. Here, by characterizing the transcriptional perturbations of the tumor microenvironment induced by oncolytic, we aimed to rationally design a novel armed oncolytic herpes virus.

Metabolic Plasticity of Regulatory T Cells in Health and Autoimmunity.

Immunometabolism has been demonstrated to control immune tolerance and the pathogenic events leading to autoimmunity. Compelling experimental evidence also suggests that intracellular metabolic programs influence differentiation, phenotype, proliferation, and effector functions of anti-inflammatory CD4+CD25+Foxp3+ regulatory T (Treg) cells. Indeed, alterations in intracellular metabolism associate with quantitative and qualitative impairments of Treg cells in several pathological conditions.

Single mixed refrigerant biomethane liquefaction plant integrated with solar energy: Dynamic simulation for the decarbonization of the heavy road transport sector.

This works proposes a dynamic thermoeconomic analysis of a liquefied biomethane production plant to meet the fuel demand of a fleet of heavy duty trucks in the south of Italy. The biomethane is obtained from the upgrading of the biogas produced by means of anaerobic digestion through a plug flow reactor fed by organic fraction of municipal solid waste. The upgrading of the biogas is realized using a three-stage membrane compression process, producing a 96 % pure biomethane.

MicroLOCK: Highly stable microgel biosensor using locked nucleic acids as bioreceptors for sensitive and selective detection of let-7a.

Chemically modified oligonucleotides can solve biosensing issues for the development of capture probes, antisense, CRISPR/Cas, and siRNA, by enhancing their duplex-forming ability, their stability against enzymatic degradation, and their specificity for targets with high sequence similarity as microRNA families. However, the use of modified oligonucleotides such as locked nucleic acids (LNA) for biosensors is still limited by hurdles in design and from performances on the material interface. Here we developed a fluorogenic biosensor for non-coding RNAs, represented by polymeric PEG microgels conjugated with molecular beacons (MB) modified with locked nucleic acids (MicroLOCK).

Clinical Studies Using Topical Melatonin.

Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities.

Cryptic hybridization between the ancient lineages of Natterer's bat (Myotis nattereri).

Studying hybrid zones that form between morphologically cryptic taxa offers valuable insights into the mechanisms of cryptic speciation and the evolution of reproductive barriers. Although hybrid zones have long been the focus of evolutionary studies, the awareness of cryptic hybrid zones increased recently due to rapidly growing evidence of biological diversity lacking obvious phenotypic differentiation. The characterization of cryptic hybrid zones with genome-wide analysis is in its early stages and offers new perspectives for studying population admixture and thus the impact of gene flow.

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-Ocean as a Talented Producer of Specialized Metabolites.

While the ecological role that sp. play in nitrogen fixation has been widely studied, little information is available on potential specialized metabolites that are associated with blooms and standing stock colonies. While a collection of biological material from a bloom event from North Padre Island, Texas, in 2014 indicated that this species was a prolific producer of chlorinated specialized metabolites, additional spatial and temporal resolution was needed.

Monitoring Density Redistribution at the Excited State in a Dual Emitting Molecule: An Analysis Based on Real-Time Density Functional Theory and Density Descriptors.

In this work, we computed and analyzed, by means of density-based descriptors, the real-time evolution of both the locally excited (LE) and charge-transfer (CT) excited states for the planar and twisted conformations of the DMABN (4-(,-dimethylamino)benzonitrile) molecule using real-time time-dependent density functional theory (DFT) and three different exchange-correlation energy functionals (EXC) belonging to the same family (the PBE one). Our results based on the analysis of density-based descriptors show that the underlying EXC modifies the evolution in time of the density. In particular, comparing the frequency of density reorganization computed with the three functionals (PBE, PBE0, and LC-PBE), we found that the frequency of electronic interconversion of the individual determinants involved during the dynamics increases from PBE to PBE0 and to LC-PBE.

Task-oriented machine learning surrogates for tipping points of agent-based models.

We present a machine learning framework bridging manifold learning, neural networks, Gaussian processes, and Equation-Free multiscale approach, for the construction of different types of effective reduced order models from detailed agent-based simulators and the systematic multiscale numerical analysis of their emergent dynamics. The specific tasks of interest here include the detection of tipping points, and the uncertainty quantification of rare events near them. Our illustrative examples are an event-driven, stochastic financial market model describing the mimetic behavior of traders, and a compartmental stochastic epidemic model on an Erdös-Rényi network.