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Abstract Background Anthracyclines can cause left ventricular (LV) dysfunction. There is little data about right ventricular (RV) damage during chemotherapy. Aim This study aimed to investigate the toxic effects of chemotherapy, analyzing its impact on right ventricular function. Material and Methods A prospective study was conducted, enrolling 83 female patients (55 ± 11 years old) affected by breast cancer treated with anthracyclines. Cardiological evaluation, HFA risk score assessment and comprehensive echocardiogram, including speckle tracking analysis and 3D analysis, were performed before starting chemotherapy (T0) and at 3 (T1), 6 (T2) and 12 months (T3) after beginning treatment. RV function was assessed with tricuspid annular plane excursion (TAPSE), S’ wave of the tricuspid annulus, fractional area change (FAC), RV global longitudinal strain (RV-GLS), free wall strain (RV-FWLS) and RV 3D ejection fraction (RV-3DEF). Subclinical LV CTRCD was defined as a reduction of GLS > 15% compared to baseline. Subclinical RV cardiotoxicity was defined as the co-presence of a relative decrease of 10% from baseline in RV-3DEF and a relative reduction of 15% from baseline RV-FWLS. Results After chemotherapy, we found a significant reduction in 2D-LVEF (p =

Abstract Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.

Liquid electrolytes are currently state-of-the-art for commercial Li-ion batteries. However, their use implicates inherent challenges, including safety concerns associated with flammability, limited thermal stability, and susceptibility to dendrite formation on the lithium metal anode, that can compromise the battery lifespan. Solid-state polymer electrolytes offer an alternative to conventional liquid electrolytes, aiming to mitigate safety, stability, and performance drawbacks. This study investigates the preparation and the comprehensive characterization of polyethylene oxide (PEO) and polycarbonate (PC) blends obtained through extrusion process. The process is solvent-free and easily scalable at the industrial level; it grants the efficient dispersion and mixing of PEO and PC. Blends at different ratios of PEO (Mw of 4 × 105 and 4 × 106 g mol˗1) and two types of PCs (namely, polyethylene and polypropylene carbonate) including lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) are prepared. Optimization and investigation of the relative effects between the application of different PCs and the variable ratios of PEO/PCs on the mechanical, morphologic and electrochemical properties of the final polymeric membranes is carried out for future applications of these systems, as efficient electrolytes in all-solid-state lithium batteries.

Background'Nebbiolo' is a grapevine cultivar typical of north-western Italy, appreciated for producing high-quality red wines. Grapevine cultivars are characterized by possessing highly heterozygous genomes, including a great incidence of genomic rearrangements larger than 50 bp, so called structural variations (SVs). Even though abundant, SVs are an under-explored source of genetic variation mainly due to methodological limitations at their detection.ResultsWe employed a multiple platform approach to produce long-range genomic data for two different 'Nebbiolo' clones, namely: optical mapping, long-reads and linked-reads. We performed a haplotype-resolved de novo assembly for cultivar 'Nebbiolo' (clone CVT 71) and used an ab-initio strategy to annotate it. The annotated assembly enhanced our ability to detect SVs, enabling the study of genomic regions not present in the grapevines' reference genome and accounting for their functional implications. We performed variant calling analyses at three different organizational levels: i) between haplotypes of clone CVT 71 (primary assembly vs haplotigs), ii) between 'Nebbiolo' and 'Cabernet Sauvignon' assemblies and iii) between clones CVT 71 and CVT 185, representing different 'Nebbiolo' biotypes. The cumulative size of non-redundant merged SVs indicated a total of 79.6 Mbp for the first comparison and 136.1 Mbp for the second one, while no SVs were detected for the third comparison. Interestingly, SVs differentiating cultivars and haplotypes affected similar numbers of coding genes.ConclusionsOur results suggest that SVs accumulation rate and their functional implications in 'Nebbiolo' genome are highly-dependent on the organizational level under study. SVs are abundant when comparing 'Nebbiolo' to a different cultivar or the two haplotypes of the same individual, while they turned absent between the two analysed clones.

Multifunctional productive systems based on native species management, a new paradigm that counters colonial worldviews, offer sustainable sources of food and materials while preserving biodiversity. Despite extensive discussions in herbaceous and agricultural systems, applying this concept to native forests in Northern Patagonia remains unclear. Multifunctional system implementation can be approached from a fractal perspective, with evaluations at the stand level being essential for understanding ecological processes across scales. Here, we exemplify research and management for multiple native species, integrating results from 10 years of field experiments on the impacts of biomass harvesting intensity (HI) on nine Nature's Contributions to People (NCPs), including habitat creation, pollination, soil formation, hazard regulation, prevention of invasions, and provision of energy, food, materials, and options. Our findings reveal that some regulating NCPs peak with null HI, while certain material and regulating NCPs maximize at the highest HI. Low to intermediate HI (30–50%) show a more balanced provision of all NCPs. Our results suggest that some biomass extraction is necessary to enhance most NCPs, emphasizing the importance of balancing material provisioning and biodiversity conservation in management schemes. We propose future directions for designing multifunctional forest systems, advocating for low-density plantation of native tree species with high wood quality within the natural forest matrix. This approach may yield higher NCPs levels over time compared to the current cattle breeding and wood extraction system, with implications beyond Patagonia, considering historical associations of such practices with colonial worldviews globally.

Introduction: Since the beginning of the COronaVIrus Disease 2019 (COVID-19) pandemic, poor attention has been paid to the indirect effects of the pandemia on cardiovascular health system, in particular in patients with Acute Coronary Syndrome (ACS). The aims of this study is to compare possible epidemiological, clinical and management differences between the four epidemic waves in groups of patients hospitalized for ACS with a view to highlighting the burden of the pandemic on the management of this syndrome. Materials and methods: In this retrospective observational study we included 98 patients admitted to Coronary Intensive Care Unit (CICU) for ACS between March 2020 and March 2022, who underwent revascularization procedure using percutaneous coronary angioplasty (PCI). The patients examined were divided into four groups representative of the four epidemic waves that affected our country. Results: The rate of hospitalization for ACS increased progressively to a 178 % increase in the third wave compared to the first (p = 0.003), with an increase of 900 % if we consider only Non-ST-Elevation Myocardial Infarction (NSTEMI) (representing 54 % of the ACS diagnoses of the third group against 14.3 % in the first). Longer door-to-balloon times were recorded in the third wave for the increased presence of NSTEMI. The average hospital stay was lower in the third wave with 5 ± 2 days (p = 0.007) as well as mortality (5.1 % in the third wave; the highest in the fourth wave with 9.5 %). Conclusions: The study show that the management of ACS suffered most from the indirect effects of the pandemic during the first wave, both because of the unpreparedness of hospital facilities and because of the fear of infection that has dissuaded people from asking for help.

Background: A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus. Methods: Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels. Results: Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling. Discussion: This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies.

Introduction: Glioblastoma is a brain cancer difficult to treat but recently mixed-ligand vanadium(V) Schiff base/catecholato complexes have exhibited high in vitro anti-proliferative activity. Hence, we explored the activity of [VVOL1L2], which contains two iron chelating ligands, 2-hydroxy-1-naphthylaldehyde iso-nicotinoyhydrazone (L1H2) and clioquinol (L2H). This complex was previously reported to be very effective against Trypanosoma cruzi, the causative agent of Chagas disease. These studies explored the possibility that a compound with efficacy against Trypanosoma cruzi also has efficacy against human glioblastoma cancer cells. Since [VVOL1L2] was poorly soluble in water and the clioquinol ligand dissociated from the complex upon addition to an aqueous environment, an understanding of the speciation was very important to interpret its biological activity.Methods: Stability studies in cell media were followed by UV/Vis spectroscopy to determine speciation of relevance to the in vitro anti-proliferative activity of the complex with T98G glioblastoma cells, which was also measured in the absence and presence of Fe(III).Results and Discussion: The current work demonstrated that the mixed-ligand vanadium coordination complex had high in vitro anti-proliferative activity against the human glioblastoma (T98G) cell line. The enhanced anti-proliferative effects of the mixed-ligand vanadium complex against T98G cells could be due to either hydrolysis of complex and release of the toxic clioquinol, or the rapid uptake of the lipophilic complex prior to hydrolysis. The speciation studies showed that at least part of the potent toxicity of the mixed-ligand coordination complex stemmed from release of the bioactive clioquinol ligand from the complex, which depended on whether Fe(III) was present. The studies also showed that the [VV(O)2 (L1H)] coordination complex was the most potent complex that remained intact and, hence, the complex that is the most biological active. Thus, future development of complexes should focus on the one-ligand intact complexes or making any mixed-ligand complex more water soluble, stable in aqueous solution, or designed to be rapidly taken up by diseased cells prior to hydrolysis.

Poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) is a soft and conjugated polymer whose conductive properties can be properly tuned through doping with various additives or solvents, preserving its excellent processability. In this work PEDOT:PSS was combined with a cost-effective graphite derivative named Edge Oxidized Graphite (EOG) for developing a nanocomposite with improved electrical conductivity, with respect to the pristine PEDOT:PSS, through an easy and environmentally friendly doping process. Firstly, the EOG powders, produced by a green oxidation process of graphite, were deeply characterized through Fourier transform infrared (FT-IR), Thermogravimetric (TGA), and Wide-angle X-ray scattering (WAXD) analysis, showing that this nanofiller has oxygenated functional groups on the sheet edges. The quality and the stability of the EOG dispersions within PEDOT:PSS were investigated at different carbon-filler concentrations, up to high loading of 25 %wt/V of EOG through rheological analyses, demonstrating pseudo-plastic behavior and excellent long-term stability of the inks due to the absence of inhomogeneities and aggregates over time; in fact, the same inks were tested under the same rheological conditions after 21 days, showing the same viscosity trend for all EOG concentrations (%wt/V). Transmission electron microscopy (TEM) and (Scanning Electron microscopy) SEM investigation of spin-coated samples onto glass substrates were performed to morphologically evaluate the nanocomposites and estimate the average size of the sheets, particularly the mean length of 1.2 μm and an approximated thickness of 26 nm of the EOG sheets dispersed into the polymer matrix (PEDOT:PSS) was determined, while WAXD analysis allowed to identify the average layer number of the EOG sheets, obtaining thus, a direct measurement of the EOG sheets aspect ratio equal to 45. Finally, sheet resistance tests showed that the increasing concentration of EOG leads to a significant improvement in the electrical conductivity of the nanocomposites, from 1.1 S/cm for pristine PEDOT:PSS to 21.9 S/cm for nanocomposites with the highest EOG content (25 %wt/V). This work demonstrates the successful development of nanocomposite based on PEDOT:PSS doped with carbon-based filler synthesized through a green and cost-effective process, promoting their use in the production of bio/electrochemical sensors or optoelectronic devices.

Abstract We compute the first moments of the q 2 distribution in inclusive semileptonic B decays as functions of the lower cut on q 2, confirming a number of results given in the literature and adding the O α s 2 β 0 $$ O\left({\alpha}_s^2{\beta}_0\right) $$ BLM contributions. We then include the q 2-moments recently measured by Belle and Belle II in a global fit to the moments. The new data are compatible with the other measurements and slightly decrease the uncertainty on the nonperturbative parameters and on |V cb |. Our updated value is |V cb | = (41.97 ± 0.48) × 10 −3.

Abstract QUIN database integrates and organizes structural-geological information from published and unpublished sources to constrain deformation in seismotectonic studies. The initial release, QUIN1.0, comprised 3,339 Fault Striation Pairs, mapped on 445 sites exposed along the Quaternary faults of central Italy. The present Data Descriptor introduces the QUIN 2.0 release, which includes 4,297 Fault Striation Pairs on 738 Structural Sites from southern Italy. The newly investigated faults span ~500 km along the Apennines chain, with strikes transitioning from ~SE to ~SW and comprehensively details Fault Striation Pairs’ location, attitude, kinematics, and deformation axes. Additionally, it offers a shapefile of the fault traces hosting the data. The QUIN 2.0 release offers a significant geographic extension to the QUIN 1.0, with comprehensive description of local geometric-kinematic complexities of the regional pattern. The QUIN data may be especially relevant for constraining intra-Apennine potential seismogenic deformation patterns, where earthquake data only offer scattered or incomplete information. QUIN’s data will support studies aimed at enhancing geological understanding, hazard assessment and comprehension of fault rupture propagation and barriers.

Abstract Background Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0–5 years. Methods This observational study involved a sample of 483 children aged 0–5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak. Results A substantial prevalence of R-URTIs was found, estimating it at 5–10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between. Conclusions The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study’s stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.

Abstract Reduction of post-weaning diarrhoea caused by ETEC is a principal objective in pig farming in terms of welfare benefits. This study determined the effects of genetic susceptibility and dietary strategies targeting inflammation and fimbriae adherence on F4-ETEC shedding and diarrhoea in weaned piglets in an experimental challenge model. A DNA marker test targeting single nucleotide polymorphism 2 (SNP2) identified piglets as heterozygous (SNP2+, susceptible) or homozygous (SNP2-, resistant) to developing F4ac-ETEC diarrhoea. A total of 50 piglets, 25 SNP2+ and 25 SNP2-, were weaned at 30 days of age and equally distributed to different treatments (n = 10): Positive control (PC): piglets fed with a negative control diet and provided with colistin via drinking water; Negative control (NC): piglets fed with a negative control diet; Tall oil fatty acids (TOFA): piglets fed with a negative control diet + 1.0 g TOFA/kg feed; Yeast hydrolysate (YH): piglets fed with a negative control diet + 1.5 g YH/kg feed derived from Saccharomyces cerevisiae; and Combination (COM): piglets fed with a negative control diet + 1.0 g TOFA and 1.5 g YH/kg feed. On day 10 post-weaning, all piglets were infected with F4-ETEC by oral administration. Piglets fed with PC, TOFA, YH or COM had a lower faecal shedding of F4-ETEC than NC piglets (P

Abstract Quantum Chromodynamics, the theory of quarks and gluons, whose interactions can be described by a local SU(3) gauge symmetry with charges called “color quantum numbers”, is reviewed; the goal of this review is to provide advanced Ph.D. students a comprehensive handbook, helpful for their research. When QCD was “discovered” 50 years ago, the idea that quarks could exist, but not be observed, left most physicists unconvinced. Then, with the discovery of charmonium in 1974 and the explanation of its excited states using the Cornell potential, consisting of the sum of a Coulomb-like attraction and a long range linear confining potential, the theory was suddenly widely accepted. This paradigm shift is now referred to as the November revolution. It had been anticipated by the observation of scaling in deep inelastic scattering, and was followed by the discovery of gluons in three-jet events. The parameters of QCD include the running coupling constant, $$\alpha _s(Q^2)$$ α s ( Q 2 ) , that varies with the energy scale $$Q^2$$ Q 2 characterising the interaction, and six quark masses. QCD cannot be solved analytically, at least not yet, and the large value of $$\alpha _s$$ α s at low momentum transfers limits perturbative calculations to the high-energy region where $$Q^2\gg \varLambda _{{\textrm{QCD}}} ^2\simeq $$ Q 2 ≫ Λ QCD 2 ≃ (250 MeV) $$^2$$ 2 . Lattice QCD (LQCD), numerical calculations on a discretized space-time lattice, is discussed in detail, the dynamics of the QCD vacuum is visualized, and the expected spectra of mesons and baryons are displayed. Progress in lattice calculations of the structure of nucleons and of quantities related to the phase diagram of dense and hot (or cold) hadronic matter are reviewed. Methods and examples of how to calculate hadronic corrections to weak matrix elements on a lattice are outlined. The wide variety of analytical approximations currently in use, and the accuracy of these approximations, are reviewed. These methods range from the Bethe–Salpeter, Dyson–Schwinger coupled relativistic equations, which are formulated in both Minkowski or Euclidean spaces, to expansions of multi-quark states in a set of basis functions using light-front coordinates, to the AdS/QCD method that imbeds 4-dimensional QCD in a 5-dimensional deSitter space, allowing confinement and spontaneous chiral symmetry breaking to be described in a novel way. Models that assume the number of colors is very large, i.e. make use of the large $$N_c$$ N c -limit, give unique insights. Many other techniques that are tailored to specific problems, such as perturbative expansions for high energy scattering or approximate calculations using the operator product expansion are discussed. The very powerful effective field theory techniques that are successful for low energy nuclear systems (chiral effective theory), or for non-relativistic systems involving heavy quarks, or the treatment of gluon exchanges between energetic, collinear partons encountered in jets, are discussed. The spectroscopy of mesons and baryons has played an important historical role in the development of QCD. The famous X,Y,Z states – and the discovery of pentaquarks – have revolutionized hadron spectroscopy; their status and interpretation are reviewed as well as recent progress in the identification of glueballs and hybrids in light-meson spectroscopy. These exotic states add to the spectrum of expected $$q{{\bar{q}}}$$ q q ¯ mesons and qqq baryons. The progress in understanding excitations of light and heavy baryons is discussed. The nucleon as the lightest baryon is discussed extensively, its form factors, its partonic structure and the status of the attempt to determine a three-dimensional picture of the parton distribution. An experimental program to study the phase diagram of QCD at high temperature and density started with fixed target experiments in various laboratories in the second half of the 1980s, and then, in this century, with colliders. QCD thermodynamics at high temperature became accessible to LQCD, and numerical results on chiral and deconfinement transitions and properties of the deconfined and chirally restored form of strongly interacting matter, called the Quark–Gluon Plasma (QGP), have become very precise by now. These results can now be confronted with experimental data that are sensitive to the nature of the phase transition. There is clear evidence that the QGP phase is created. This phase of QCD matter can already be characterized by some properties that indicate, within a temperature range of a few times the pseudocritical temperature, the medium behaves like a near ideal liquid. Experimental observables are presented that demonstrate deconfinement. High and ultrahigh density QCD matter at moderate and low temperatures shows interesting features and new phases that are of astrophysical relevance. They are reviewed here and some of the astrophysical implications are discussed. Perturbative QCD and methods to describe the different aspects of scattering processes are discussed. The primary parton–parton scattering in a collision is calculated in perturbative QCD with increasing complexity. The radiation of soft gluons can spoil the perturbative convergence, this can be cured by resummation techniques, which are also described here. Realistic descriptions of QCD scattering events need to model the cascade of quark and gluon splittings until hadron formation sets in, which is done by parton showers. The full event simulation can be performed with Monte Carlo event generators, which simulate the full chain from the hard interaction to the hadronic final states, including the modelling of non-perturbative components. The contribution of the LEP experiments (and of earlier collider experiments) to the study of jets is reviewed. Correlations between jets and the shape of jets had allowed the collaborations to determine the “color factors” – invariants of the SU(3) color group governing the strength of quark–gluon and gluon–gluon interactions. The calculated jet production rates (using perturbative QCD) are shown to agree precisely with data, for jet energies spanning more than five orders of magnitude. The production of jets recoiling against a vector boson, $$W^\pm $$ W ± or Z, is shown to be well understood. The discovery of the Higgs boson was certainly an important milestone in the development of high-energy physics. The couplings of the Higgs boson to massive vector bosons and fermions that have been measured so far support its interpretation as mass-generating boson as predicted by the Standard Model. The study of the Higgs boson recoiling against hadronic jets (without or with heavy flavors) or against vector bosons is also highlighted. Apart from the description of hard interactions taking place at high energies, the understanding of “soft QCD” is also very important. In this respect, Pomeron – and Odderon – exchange, soft and hard diffraction are discussed. Weak decays of quarks and leptons, the quark mixing matrix and the anomalous magnetic moment of the muon are processes which are governed by weak interactions. However, corrections by strong interactions are important, and these are reviewed. As the measured values are incompatible with (most of) the predictions, the question arises: are these discrepancies first hints for New Physics beyond the Standard Model? This volume concludes with a description of future facilities or important upgrades of existing facilities which improve their luminosity by orders of magnitude. The best is yet to come!

Objectives: To assess the number of new cases of Medication-Related Osteonecrosis of the Jaw (MRONJ) among patients with osteoporosis and other non-malignant bone diseases in Northwestern Italy between 2007 and 2022. Methods: MRONJ cases were collected from referral centers in a population of 4.5 million. We analysed the number of new MRONJ cases per year, type of disease, administered drugs, duration of therapy (when available), and onset time of disease. Results: We analysed 198 cases (out of 1071 total MRONJ cases); diseases included osteoporosis (87%), rheumatoid arthritis (5%), their association (4%), Paget’s disease, and other various diseases (4%). Patients received bisphosphonates alone (74%), or denosumab alone (6%), or a sequence of different drugs (20%). The number of new cases increased over five years from 2 (2003–2007) to 51 (2008–2012), 65 (2013–2017), and 79 (2018–2022), and the percentage increased from 1% to 14%, 20%, and 29% of the total cases. Conclusions: The number of new MRONJ cases per year among patients with non-malignant diseases is rapidly increasing all around the world, though underestimation cannot be excluded. In this study, we describe epidemiological and clinical characteristics of patients, and the drug most frequently involved in MRONJ cases in our region over a long period, allowing a comprehensive view of the progression of the disease. Greater collaboration among specialists is needed for correct and early diagnosis to improve measures potentially reducing disease incidence and to limit quality of life deterioration in patients with osteoporosis and other non-malignant diseases.