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Background: Patients with head and neck cancer often experience impaired sleep. Moreover, the treatment may negatively affect sleep quality. The aim of this observational study was to evaluate the sleep quality after treatment for head and neck cancer, and its relationship with quality of life and psychological distress. Methods: A total of 151 patients who underwent treatment for head and neck cancer at our department were included in the study. Quality of life, sleep quality, risk of sleep apnea, sleepiness, pain, and psychological distress were assessed by means of specific questionnaires. Results: The median follow-up was 30 months. Poor sleep quality was observed in 55.6% of the cases. An association between PSQI global sleep quality and EORTC global health status was found. The DT, HADS anxiety, and HADS depression scores were associated to PSQI global score, sleep quality, sleep latency, sleep disturbances, and daytime dysfunction. Conclusions: Sleep disturbances, particularly OSA and insomnia, are frequent in HNC patients, and significantly impact their quality of life and psychological well-being. Given the effect of sleep on overall well-being, addressing sleep disorders should be a priority in the care of HNC patients.

Aims: The accurate prediction of blood glucose (BG) levels is critical for managing Type-1 Diabetes (T1D) in pediatric patients, where variability due to factors like physical activity and developmental changes presents significant challenges. Methods: This work explores the application of foundational models, particularly the encoder–decoder model TimeGPT, for BG forecasting in T1D pediatric patients. Methods: The performance of TimeGPT is compared against state-of-the-art models, including ARIMAX and LSTM, and multilayer perceptron (MLP) architectures such as TiDE and TSMixer. The models were evaluated using continuous glucose monitoring (CGM) data and exogenous variables, such as insulin intake. Results: TimeGPT outperforms or achieves comparable accuracy to the state of the art and MLP models in short-term predictions (15 and 30 min), with most predictions falling within the clinically safe zones of the Clarke Error Grid. Conclusions: The findings suggest that foundational models like TimeGPT offer promising generalization capabilities for medical applications and can serve as valuable tools to enhance diabetes management in pediatric T1D patients.

The approaching legalisation and associated increasing demand for medicinal and recreational Cannabis sativa L. will lead to a growing relevance for lighting systems designed for Cannabis sativa L. The interplay between plant density, light spectrum, light distribution, yield, and secondary metabolite distribution within the plant has not yet been studied. To fill this knowledge gap, a CBD-dominant Cannabis sativa L. strain was grown in a greenhouse experiment with two plant densities (2.66 and 12 plants −1 m−2) under two different light spectra. The chosen light spectra were two LED fixtures, Solray385 (SOL) and AP67, with an R: FR ratio of 12.9 and 3.7, respectively. The results indicated that light-induced effects on individual plants can be transferred to the plant stock. A low R: FR ratio induced a 16% increase in dry flower yield in the last ten days of flowering, while a change in the light spectrum could increase the potential maximum plant density per square metre. The two spectra did not affect (CBD + CBDA) yield, as a lower flower yield compensated for a higher concentration. CBDA concentration was not significantly affected by plant density. In contrast, the higher density led to an increased total cannabidiol concentration (CBD + CBDA) and altered the distribution of terpenes. Here, the light distribution over the plant stock is particularly decisive, as a more homogenous illumination led to an increased terpene concentration of up to 41%. A Photon Conversion Efficacy (PCE) of 0.05 g mol−1 under SOL and 0.06 g mol−1 under AP67 was achieved. Plants in the centre under the highest light intensity of 1200 PAR showed up to 48% reduced efficacy. These results strongly suggest that light intensity needs to be fine-tuned to the cultivation system to prevent a reduction in efficacy, resulting in yield and quality losses.

This article focuses on the effectiveness of the Swiss policy mix promoting sustainable permanent grassland (PG) management in the country. We used the Cascade Framework and stakeholder’s sentiment analysis to qualitatively assess propagation pathways for generating policy effectiveness in terms of PGs’ deliverance of ecosystem services (ESs), to ultimately enable sustainable PG management. We employed a mixed-method approach combining a review of governmental documents, formal policies and policy evaluations with semi-structured interviews with Swiss stakeholders. Through this analysis, we identified 16 policy instruments influencing PG management, including 3 regulatory instruments, 11 incentive instruments, and 2 informational instruments. Results showed that these instruments primarily aim to promote sustainable PG management by employing measures targeting the very structure and composition of the landscape. As such, we found gaps in the types of instruments employed, particularly in terms of demand-side policies, which can explain the poor policy outcomes in relation to a number of environmental quality objectives. In parallel, we found that most of the interviewed stakeholders considered Swiss grassland policy as generally effective, mainly because it was perceived as democratic. While this study focuses on Switzerland, its novel conceptual and methodological approach of using the cascade-framework for policy analysis can be applied to other biogeographical regions and socio-economic contexts. Our findings can improve the calibration of future policy instruments to enable land managers and grassland landscape users to restore or maintain PGs in good ecological condition, by targeting mechanisms that can ensure achieving environmental quality objectives while remaining democratically legitimate.

With global warming, the cultivation area of bermudagrass is moving northwards in the Mediterranean area despite its winter dormancy and loss of green color. The most common solution is overseeding with perennial ryegrass, which can be complicated to remove in spring. DLF breeders have released a new cultivar of annual ryegrass that is stress tolerant and easy to transition in spring. A trial was carried out on a sod farm in Pisa, Italy. Twenty-nine varieties of cool-season grasses, encompassing both forage and turf species, were overseeded on a hybrid bermudagrass variety ‘Tifway’ (Cynodon dactylon x transvaalensis). The aim of this trial was to compare the overseeding potential of various cool-season turfgrass species and cultivars and to identify which ones perform best in terms of cleanness of cut when overseeded on hybrid bermudagrass in autumn and maintained at a mowing height of 25 mm. Moreover, the following parameters were also assessed: actual turf height (cm); cumulated height (cm); turf visual color and quality (1–9 scale); and visual ground cover (%). Plots were managed with an autonomous mower, which adopted a daily mowing frequency and was set to work with systematic trajectories. The results showed differences between cultivars, and the annual ryegrass showed the best spring transition (scoring a mean value of 96% green cover in July 2023) compared to the other entries. The best result of CoC was measured for rough-stalked meadow grass ‘Sabrena 1’ and tall fescue ‘Turfway’ with 0.9 mm.

The quality of sports facilities, especially football pitches, has gained significant attention due to the growing importance of sports globally. This study examines the effect of two different cutting systems, a traditional ride-on mower and an autonomous mower, on the quality and functional parameters of a municipal football field. The analysis includes visual assessments, measurements of grass height, and evaluations of surface hardness, comparing the performance of the two cutting systems. Additionally, studies of turfgrass composition and machine learning techniques, particularly with YOLOv8s and YOLOv8n, are conducted to test the capability of assessing weed and turfgrass species distribution. The results indicate significant differences in grass color based on the position (5.36 in the corners and 3.69 in the central area) and surface hardness between areas managed with a traditional ride-on mower (15.25 Gmax) and an autonomous mower (10.15 Gmax) in the central region. Higher height values are recorded in the area managed with the ride-on mower (2.94 cm) than with the autonomous mower (2.61 cm). Weed presence varies significantly between the two cutting systems, with the autonomous mower demonstrating higher weed coverage in the corners (17.5%). Higher overall performance metrics were obtained through YOLOv8s. This study underscores the importance of innovative management practices and monitoring techniques in optimizing the quality and playability of a football field while minimizing environmental impact and management efforts.

In data science and machine learning, efficient and scalable algorithms are paramount for handling large datasets and complex tasks. Classification algorithms, in particular, play a crucial role in a wide range of applications, from image recognition and natural language processing to fraud detection and medical diagnosis. Traditional classification methods, while effective, often struggle with scalability and efficiency when applied to massive datasets. This challenge has driven the development of innovative approaches that leverage modern computational frameworks and parallel processing capabilities. This paper presents the Bison Algorithm, applied to classification problems. The algorithm, inspired by the social behavior of bison, aims to enhance the accuracy of classification tasks. The Bison Algorithm is implemented using PySpark, leveraging the distributed computing power to handle large datasets efficiently. This study compares the performance of the Bison Algorithm on several dataset sizes using speedup and scaleup as the performance measure.

Supernumerary teats (SNTs) or nipples often emerge around the mammary line. This study performed a genome-wide selective sweep analysis (GWS) at the copy number variant (CNV) level using two selected signal calculation methods (VST and FST) to identify candidate genes associated with SNTs in goats. A total of 12,310 CNVs were identified from 37 animals and 123 CNVs, with the top 1% VST values including 84 candidate genes (CDGs). Of these CDGs, minichromosome maintenance complex component 3, ectodysplasin A receptor associated via death domain, and cullin 5 demonstrated functions closely related to mammary gland development. In addition, 123 CNVs with the top 1% FST values were annotated to 97 CDGs. 5-Hydroxytryptamine receptor 2A, CCAAT/enhancer-binding protein alpha, and the polymeric immunoglobulin receptor affect colostrum secretion through multiple signaling pathways. Two genes, namely, RNA-binding motif protein 46 and β-1,3-galactosyltransferase 5, showed a close relation to mammary gland development. Six CNVs were identified and annotated to five genes by intersecting the top 1% of candidate CNVs with both parameters. These genes include LOC102185621, LOC102190481, and UDP-glucose pyrophosphorylase 2, which potentially affect the occurrence of BC through multiple biological processes, such as cell detoxification, glycogen synthesis, and phospholipid metabolism. In conclusion, we discovered numerous genes related to mammary development and breast cancer (BC) through a GWS, which suggests the mechanism of SNTs in goats and a certain association between mammary cancer and SNTs.

Mature and immature female swordfish show different gonadal expression patterns of melatonin synthesis-related and opsin genes, indicating that seasonality affects gonadal circadian genes, especially through opsin modulation. The high energy demands of reproduction may cause mature female swordfish to become more susceptible to environmental stressors/changes, potentially affecting their health post-reproduction. The modulation of melatonin and opsin expression may also influence swordfish biology, impacting basal metabolism and stress responses. This study aimed to investigate the hepatic expression patterns of genes involved in melatonin and opsins activity after the reproductive period, comparing mature and immature females. Liver samples of swordfish females, collected from the Central Adriatic Sea, were analyzed to evaluate the expression of a melatonin receptor (mel1b), acetylserotonin O-methyltransferase (asmt), opsins (sws, VA opsin and opsin4), and stress response (sod1, sod2 and hsp4b) genes, while histological analysis focused on hepatic melanomacrophages, melanomacrophage centers, and lipid content. The expression of all genes analyzed did not differ between mature and immature females except for sws, which was significantly downregulated in mature females. The overall health conditions of mature and immature females appeared comparable, as suggested by the histological analysis and the absence of significant differences in the expression of stress response genes. Although the study used a limited number of samples and lacked a comparison between the reproductive and non-reproductive periods, the preliminary results suggest that opsins may play a role in modulating physiological processes beyond reproduction.

Background/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a–k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 μg/mL and 0.619 μg/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 μg/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 μg/mL and 1.23 μg/mL, MIC of ciprofloxacin = 31.49 and 125.99 μg/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14α-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.

Chromatin organization, which is under the control of histone deacetylases (HDACs), is frequently deregulated in cancer cells. Amongst HDACs, HDAC8 plays an oncogenic role in different neoplasias by acting on both histone and non-histone substrates. Promising anti-cancer strategies have exploited dual-targeting drugs that inhibit both HDAC8 and tubulin. These drugs have shown the potential to enhance the outcome of anti-cancer treatments by simultaneously targeting multiple pathways critical to disease onset and progression. In this study, a structure-based virtual screening (SBVS) of 96403 natural compounds was performed towards the four Class I HDAC isoforms and tubulin. Using molecular docking and molecular dynamics simulations (MDs), we identified two molecules that could selectively interact with HDAC8 and tubulin. CNP0112925 (arundinin), bearing a polyphenolic structure, was confirmed to inhibit HDAC8 activity and tubulin organization, affecting breast cancer cell viability and triggering mitochondrial superoxide production and apoptosis.

This paper investigates the interrelated effects of thermomechanical treatments and chemical composition on the phase transformation capabilities of thin sheets made from Cu-Al-Mn shape memory alloys. The transformation capacity and transition temperatures were determined using DSC and DMA testing, while composition measurements were performed using SEM/EDX analysis. The results demonstrate that applying hot-rolling treatments to alloys of reduced thickness leads to manganese oxidation and modifications in chemical composition, adversely impacting the phase transformation performance. This effect can be mitigated by the use of cold rolling. Additionally, the presence of phosphorus impurities can create inclusions that bind manganese, preventing it from remaining in the solid solution and further affecting phase transformation capabilities.

Attentional deficits have tragic consequences on road safety. These deficits are not solely caused by distraction, since they can also arise from other mental impairments such as, most frequently, mental fatigue. Fatigue is among the most prevalent impairing conditions while driving, degrading drivers’ cognitive and physical abilities. This issue is particularly relevant for professional drivers, who spend most of their time behind the wheel. While scientific literature already documented the behavioral effects of driving fatigue, most studies have focused on drivers under sleep deprivation or anyhow at severe fatigue degrees, since it is difficult to recognize the onset of fatigue. The present study employed an EEG-driven approach to detect early signs of fatigue in professional drivers during a simulated task, with the aim of studying visual attention as fatigue begins to set in. Short-range and long-range professional drivers were recruited to take part in a 45-min-long simulated driving experiment. Questionnaires were used to validate the experimental protocol. A previously validated EEG index, the MDrow, was adopted as the benchmark measure for identifying the “fatigued” spans. Results of the eye-tracking analysis showed that, when fatigued, professional drivers tended to focus on non-informative portions of the driving environment. This paper presents evidence that an EEG-driven approach can be used to detect the onset of fatigue while driving and to study the related visual attention patterns. It was found that the onset of fatigue did not differentially impact drivers depending on their professional activity (short- vs. long-range delivery).

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance. Methods: In this work, we present a new algorithm for the genetic interpretation of the remaining rare variants in order to shed light on their potential clinical implications and reduce the burden of unknown significance. Results: Our study illustrates the potential utility of our individualized comprehensive stepwise analyses focused on the rare variants associated with IAS, which are currently classified as ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions: We advocate for personalized disease-focused population frequency data and family segregation analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity should not influence medical decisions, but a potential deleterious role would suggest a closer clinical follow-up and frequent genetic data review for a more personalized clinical approach.

Background/Objectives: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are significant public health issues, with cardiovascular morbidity and mortality being the leading causes of death in hemodialysis patients. Osteopontin (OPN), a multifunctional glycoprotein, has emerged as a potential biomarker for vascular disease in CKD due to its role in inflammation, tissue remodeling, and calcification. Methods: This cohort study included 1124 hemodialysis patients from the PROGREDIRE study, a registry involving 35 dialysis units in Southern Italy. Serum osteopontin levels were measured using enzyme-linked immunosorbent assay (ELISA). The primary endpoints were all-cause and cardiovascular mortality. Multivariate Cox regression analyses were performed to assess the association between osteopontin levels and mortality, adjusting for traditional risk factors, biomarkers of inflammation, nutritional status, and ESKD-related factors. Results: During a mean follow-up of 2.8 years, 478 patients died, 271 from cardiovascular causes. Independent correlates of osteopontin included alkaline phosphatase and parathyroid hormone. Elevated osteopontin levels were significantly associated with increased all-cause mortality (HR 1.19, 95% CI 1.09–1.31, p < 0.001) and cardiovascular mortality (HR 1.22, 95% CI 1.08–1.38, p = 0.001) after adjusting for confounders. Conclusions: Elevated osteopontin levels are associated with increased all-cause and cardiovascular mortality in hemodialysis patients. These findings implicate osteopontin in the high risk for death and cardiovascular disease in the hemodialysis population. Intervention studies are needed to definitively test this hypothesis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder whose complex immunopathogenesis has yet to be fully elucidated. Endotype-2 CRSwNP is the most common form of disease where eosinophils are the main drivers of inflammation. Traditional treatments for CRSwNP have centered around intranasal or systemic corticosteroids and endoscopic sinus surgery (ESS). However, recent advancements in targeted therapies have introduced novel biological agents that specifically target key inflammatory mediators such as IL-4, IL-5, and IL-13. These biologics offer promising options for patients with CRSwNP, particularly those who do not respond adequately to conventional treatments. Nonetheless, some patients do not satisfactorily respond to these drugs because of an insufficient blockade of the inflammatory process. The mast cell (MC) is another important (and somehow neglected) actor in the pathogenesis of CRSwNP, and the latest clinical and translational evidence in this field has been reviewed in the present paper.

Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity. Regular monitoring of hormonal responses in athletes could be a potential tool to design individual training programs and prevent overtraining syndrome.

The growing emergence of resistance mechanisms and side effects associated with antifungal agents highlight the need for alternative therapies. This study aims to investigate the antifungal potential of ozonated extra-virgin olive oil (EOO) against Candida albicans, with the goal of developing eco-friendly and highly effective treatments based on natural products. Antifungal activity was evaluated via cell viability and biofilm formation assays using Crystal Violet and Sytox green staining. The results showed that EOO reduced C. albicans viability in a dose-dependent manner, achieving over 90% cell death at a 3% (v/v) concentration. Transmission Electron Microscopy (TEM) revealed cell wall structural damage, and ROS levels increased by approximately 60% compared to untreated controls within 10 min of treatment. Additionally, the expression of autophagy-related genes atg-7 and atg-13was upregulated by 2- and 3.5-fold, respectively, after 15 min, suggesting a stress-induced cell death response. EOO also significantly inhibited hyphal formation and biofilm development, thus reducing C. albicans pathogenicity while preserving cell biocompatibility. EOO antifungal activity was also observed in the case of Candida glabrata. In conclusion, ozonated olive oil demonstrates potent antifungal activity against C. albicans by reducing cell viability, inhibiting hyphal and biofilm formation, and triggering oxidative stress and autophagy pathways. These findings position EOO as a promising alternative therapy for fungal infections.

The most common trigger of sepsis and septic shock is bacterial lipopolysaccharide (LPS). Endothelial cells are among the first to encounter LPS directly. Generally, their function is closely linked to active endothelial NO Synthase (eNOS), which is significantly reduced under septic conditions. LPS treatment of endothelial cells leads to their activation and apoptosis, resulting in loss of integrity and vascular leakage, a hallmark of septic shock. Hence, therapies that prevent endothelial leakage or restore the endothelial barrier would be invaluable for patients. Adhesion GPCRs (aGPCRs) have been largely overlooked in this context, although particularly one of them, ADGRL2/LPHN2, has been implicated in endothelial barrier function. Our study shows that overexpression of ADGRL2 protects endothelial cells from LPS-induced activation, apoptosis, and impaired migration. Mechanistically, ADGRL2 preserves eNOS activity by shifting its binding from Caveolin-1 to Heat Shock Protein 90. Furthermore, ADGRL2 enhances antioxidative responses by increasing NRF2 activity. Notably, we found that this function may be evolutionarily conserved. In the absence of lat-2, a homolog of ADGRL2 in Caenorhabditis elegans, worms show higher ROS levels and altered stress response gene expression. Additionally, lat-2 mutants have a significantly reduced lifespan, altogether indicating a protective role of ADGRL2 against oxidative stress across species.

Machine learning tools represent a key methodology for the shape optimization of complex geometries in the turbomachinery field. One of the current challenges is to redesign High-Pressure Turbine (HPT) stages to couple them with innovative combustion technologies. In fact, recent developments in the gas turbine field have led to the introduction of pioneering solutions such as Rotating Detonation Combustors (RDCs) aimed at improving the overall efficiency of the thermodynamic cycle at low overall pressure ratios. In this study, a HPT vane equipped with diffusive endwalls is optimized to allow for ingesting a high-subsonic flow (Ma=0.6) delivered by a RDC. The main purpose of this paper is to investigate the prediction ability of machine learning tools in case of multiple input parameters and different objective functions. Moreover, the model predictions are used to identify the optimal solutions in terms of vane efficiency and operating conditions. A new solution that combines optimal vane efficiency with target values for both the exit flow angle and the inlet Mach number is also presented. The impact of the newly designed geometrical features on the development of secondary flows is analyzed through numerical simulations. The optimized geometry achieved strong mitigation of the intensity of the secondary flows induced by the main flow separation from the diffusive endwalls. As a consequence, the overall vane aerodynamic efficiency increased with respect to the baseline design.

The link between the gut environment and the prostate has recently been proposed as a potential therapeutic approach for treating benign prostatic hyperplasia (BPH). Therefore, this study examined the advantages of a novel oral probiotic supplement to improve intestinal health and treat BPH. A 3D intestinal barrier model that simulated oral intake was used to analyse the combined regulative abilities of Bifidobacterium longum and Bifidobacterium psychaerophilum. Then, a co-culture prostatic model was used to investigate the biological consequences of the combination under conditions mimicking BPH. The results show the connection between the gut microbiome and prostate disease since the probiotics successfully modulate the primary mechanism involved in the pathogenesis of BPH. Indeed, after the intestinal passage, the mediators released from B. longum and B. psychaerophilum induced a substantial decrease in reactive oxidative species of about 6 times and inflammation (about 5 times regarding interleukine-6 and 10) and a sharp increase in testosterone and serotonin levels (about 95%). Further, proliferation and BPH principal mediators (such as androgen and dihydrotestosterone) were highly affected and nearly restored to physiological levels. Thus, BPH can be directly affected by probiotic supplementation; specifically, B. longum and B. psychaerophilum, in combination, seem able to promote the mitigation of this disease.

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, accounting for over 9 million deaths annually. The prevalence of CAD continues to rise, driven by ageing and the increasing prevalence of risk factors such as hypertension, diabetes, and obesity. Current clinical guidelines emphasize the importance of functional tests in the diagnostic pathway, particularly for assessing the presence and severity of ischemia. While recommended tests are valuable, they may not fully capture the complex physiological responses to exercise or provide the necessary detail to tailor personalized treatment plans. Cardiopulmonary exercise testing (CPET) offers a comprehensive assessment of the cardiovascular, pulmonary, and muscular systems under stress, potentially addressing these gaps and providing a more precise understanding of CAD, particularly in settings where traditional diagnostics may be insufficient. By enabling more personalized and precise treatment strategies, CPET could play a central role in the future of CAD management. This narrative review examines the current evidence supporting the use of CPET in CAD diagnosis and management and explores the potential for integrating CPET into existing clinical guidelines, considering its diagnostic and prognostic capabilities, cost-effectiveness, and the challenges associated with its adoption.

Background: Heart transplantation and left ventricular assist device (LVAD) implementation are effective treatments for advanced heart failure (HF), although their use is limited by organ availability and the high incidence of adverse events. The efficacy of mitral transcatheter edge-to-edge repair (TEER) as a bridge to transplantation or as a destination therapy in advanced HF is still debated. Methods: A total of 63 patients with INTERMACS class 3 or 4 with contraindications for LVAD and severe functional mitral regurgitation (FMR) were evaluated for TEER implantation eligibility. The primary endpoint was a composite of death, urgent heart transplantation and LVAD implantation at 12 months. Results: A total of 36 patients underwent TEER, while 27 patients received optimal medical therapy (MT) alone. In the intervention group, 35 patients (97%) were discharged alive. In the MT group, two in-hospital deaths occurred, two patients underwent urgent heart transplantation, and three patients were discharged on inotropes. At the 12-month follow-up, the incidence of the primary endpoint occurring was lower in the TEER group (25% vs. 70%, HR 0.25, 95% CI 0.11–0.60, p < 0.01) and the tolerance to neurohormonal therapy was higher (53% vs. 30%, p = 0.03). Conclusions: In advanced HF patients with INTERMACS profile 3 or 4 and severe FMR, TEER on top of optimal MT was associated with a lower incidence of death, urgent heart transplantation or LVAD implantation at 12 months compared to optimal MT alone.

In order to characterize a novel restorative material, knowledge about the toxicological effect on human cells and the physical behavior of a glass ionomer cement (GIC) containing flavonoids was established. The flavonoids apigenin, naringenin, quercetin, and liquiritigenin were manually incorporated into a GIC. In the control group, no incorporation was performed. Two cell culture assays evaluated the toxicity of GICs: SRB and MTT. For both assays, the keratinocyte cell line (HaCaT) was exposed to GIC (n = 3/group) for 24 h. The physical properties of the GICs were evaluated by compressive strength (n = 10), surface roughness (n = 10), and hardness (n = 10) tests. Cell viability by SRB ranged from 103% to 97%. The control revealed a significant decrease in the metabolism of cells (61%) by MTT, while the GIC+apigenin slightly increased the succinic dehydrogenase activity (105%; p > 0.05), also confirmed microscopically. The compressive strength and roughness values were similar among groups, but the hardness increased after the incorporation of naringenin and quercetin into GIC (p < 0.05). The incorporation of flavonoids positively altered the biological and physical properties of the GICs.

The well-known “click chemistry” reaction copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) was used to transform under very mild conditions hyaluronan-based graft copolymers HA(270)-FA-Pg into the crosslinked derivatives HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL. In particular, medium molecular weight (i.e., 270 kDa) hyaluronic acid (HA) grafted at various extents (i.e., 10, 20, and 40%) with fluorogenic ferulic acid (FA) residue bonding propargyl groups were used in the CuAAC reaction with novel azido-terminated crosslinking agents Tri(Ethylene Glycol) Ethyl Resorcinol Acrylate (TEGERA) and Hexa(Ethylene Glycol) Ethyl Resorcinol Acrylate (HEGERA). The resulting HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL materials were characterized from the point of view of their structure by performing NMR studies. Moreover, the swelling behavior and rheological features were assessed employing TGA and DSC analysis to evaluate the potential gel-like properties of the resulting crosslinked materials. Despite the 3D crosslinked structure, HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL frameworks showed adequate swelling performance, the required shear thinning behavior, and coefficient of friction values close to those of the main commercial HA solutions used as viscosupplements (i.e., 0.20 at 10 mm/s). Furthermore, the presence of a crosslinked structure guaranteed a longer residence time. Indeed, HA(270)-FA-TEGERA-CL-40 and HA(270)-FA-HEGERA-CL-40 after 48 h showed a four times greater enzymatic resistance than the commercial viscosupplements. Based on the promising obtained results, the crosslinked materials are proposed for their potential applicability as novel viscosupplements.

Background: Small bowel dysbiosis (SBD) is a frequent finding in subjects with irritable bowel syndrome (IBS). The sunflower lecithin (phytosome) formulation of Curcuma longa and Boswellia serrata demonstrated beneficial effects on intestinal microbiota. This study aimed to evaluate the impact of a lecithin-based delivery formulation of Curcuma longa and Boswellia serrata extracts (CUBO) on SBD in IBS subjects. Subjects: Forty-nine adult subjects with IBS and SBD were randomly supplemented for 30 days with CUBO and a low-FODMAP diet (LFD) (intervention) or with LFD and placebo (control group). Results: The intervention group showed a significant reduction in urinary indican (p < 0.001), which was the marker of SBD, and of abdominal bloating (p < 0.001) and abdominal pain (p < 0.001). The pre–post control group analysis did not evidence significant differences. The comparison between the two groups (net effect in intervention minus control subjects) showed that the changes differ significantly for urinary indican p < 0.001 (−42.88; 95% CI: −62.04 to −23.72), abdominal bloating p < 0.001 (−1.50; 95% CI: −1.93 to −1.07), and abdominal pain p < 0.001 (−2.37; 95% CI: −3.61 to −1.13) and for the global assessment of efficacy (p < 0.001). The efficacy was 20% greater in males than in females. Conclusions: In IBS subjects, the intervention with CUBO and LFD shows a significantly higher reduction in SBD, abdominal pain, and bloating compared to LFD and placebo. Additional research is needed to confirm these data.

Adsorption has emerged as a promising method for removing polyphenols in water remediation. This work explores chlorogenic acid (CGA) adsorption on zeolite-based magnetic nanocomposites synthesized from rice husk waste. In particular, enhanced adsorbing materials were attained using a hydrothermal zeolite precursor (Z18) synthesized from rice husk and possessing a remarkable specific surface area (217.69 m2 g−1). A composite material was prepared by immobilizing magnetic copper ferrite on Z18 (Z18:CuFe2O4) to recover the zeolite adsorbent. In addition, Z18 was modified (Z18 M) with a mixture of 3-aminopropyltriethoxysilane (APTES) and trimethylchlorosilane (TMCS) to improve the affinity towards organic compounds in the final nanocomposite system (Z18 M:CuFe2O4). While the unmodified composite demonstrated inconsequential CGA removal rates, Z18 M:CuFe2O4 could adsorb 89.35% of CGA within the first hour of operation. Z18 M:CuFe2O4 showed no toxicity for seed germination and achieved a mass recovery of 85% (due to a saturation magnetization of 4.1 emu g−1) when an external magnetic field was applied. These results suggest that adsorbing magnetic nanocomposites are amenable to CGA polyphenol removal from wastewater. Furthermore, the reuse, revalorization, and conversion into value-added materials of agro-industrial waste may allow the opportunity to implement sustainability and work towards a circular economy.

Idioms are figurative multiword expressions that need to be learned as part of the native phrasal vocabulary. While it has been shown that non-figurative multiword expressions are acquired with language exposure, the learning process for idioms may be different because the figurative meaning adds complexity to the learning task. Idiom vocabulary overall develops relatively late, but it is unknown to what extent children are exposed to idioms, and what kinds of idioms they encounter. Here, we investigated children’s idiom exposure and its effect on the development of idiom vocabulary in three studies: we explore the frequency of a well-tested set of Dutch idioms in a corpus of child literature, test idiom familiarity in a controlled setting in primary school children, and compare those findings to a set of online familiarity ratings. We find that children’s idiom exposure differs from adult idiom exposure, when comparing idiom frequencies based on children’s books and a corpus with resources for adults. Idiom decomposability and idiom frequencies from the children’s books, but not frequencies from the adult corpus, influenced the familiarity ratings of older children, suggesting that language exposure and idiom characteristics, such as decomposability, both play a role in idiom acquisition.

Approximately 30 distinct Mycoplasma species have been isolated from cattle, but only a few are pathogenic and can cause serious respiratory diseases. Consequently, this study aimed to identify Mycoplasma spp. infections in cattle with bovine respiratory disease (BRD), considering factors such as animal demographics, concurrent infections with other pathogens, post-mortem clinical findings and histological examinations, and seasonality. A total of 326 samples were collected from 322 cattle that had died from BRD in Northwestern Italy. A total of 54 animals (16.8%) tested positive for Mycoplasma spp., and Mycoplasma bovis (n = 22, 40.7%) and Mycoplasma dispar (n = 13, 24.1%) were the most frequently detected species among the examined cattle. Among positive cattle, those aged five months or younger were approximately five times more likely to be infected by Mycoplasma dispar than by Mycoplasma bovis compared to those older than five months (proportional incidence ratio: 5.1, 95% CI 1.2–21.2). The main bacterial pathogens identified in cattle exhibiting co-infection was Pasteurella multocida, whereas the main viral pathogens were BRSV and BoHV-1. Histopathological investigations predominantly revealed catarrhal bronchopneumonia or purulent catarrhal bronchopneumonia among the examined cattle. Finally, Mycoplasma hyopharyngis, a species isolated from the pharyngeal and nasal cavities of pigs so far, was detected for the first time in the pneumonic lung of a bovine infected with BRD. Further investigations are necessary to thoroughly characterize its host range and pathogenic potential.

In recent years, the advent of computational techniques to predict the potential activity of a drug interacting with a receptor or to predict the structure of unidentified proteins with aberrant characteristics has significantly impacted the field of drug design. We provide a comprehensive review of the current state of in silico approaches and software for investigating the effects of receptor mutations associated with human diseases, focusing on both frequent and rare mutations. The reported techniques include virtual screening, homology modeling, threading, docking, and molecular dynamics. This review clearly shows that it is common for successful studies to integrate different techniques in drug design, with docking and molecular dynamics being the most frequently used techniques. This trend reflects the current emphasis on developing novel therapies for diseases resulting from receptor mutations with the recently discovered AlphaFold algorithm as the driving force.

The rapid and accurate detection of SARS-CoV-2 in environmental settings is crucial for effective public health management during the COVID-19 pandemic. This study compares the performance of the Reverse Transcription quantitative polymerase chain reaction (RT-qPCR) and the Reverse Transcription loop-mediated isothermal amplification (RT-LAMP) for SARS-CoV-2 detection from 100 surface samples collected in healthcare environments. The reference method, RT-qPCR, identified a percentage of 25% of positive samples, while RT-LAMP detected a percentage of 27% of positive surfaces. Our findings reveal a sensitivity of 32% and specificity of 75% for RT-LAMP, with a positive predictive value of 30% and a negative predictive value of 77%. The overall accuracy and concordance with RT-qPCR was 64% for both methods. Despite its lower sensitivity compared to RT-qPCR, RT-LAMP had an advantage due to its rapid screening and environmental surveillance, which is particularly useful for confirming negative results. These results underscore the potential of RT-LAMP not only as a valuable method in the environmental monitoring of SARS-CoV-2 but also as a system to control the sanitation process in ordinary and emergency conditions, providing further optimization and validation for its reliability in routine surveillance and outbreak response efforts.

This research aimed to identify the effects of increased temperature and decreased ultraviolet (UV) exposure on berry characteristics and quality parameters of cv Nebbiolo, identifying the potential risks associated with climate change for the quality of grapes and the identity of Barolo wine. This two-year research (2022 and 2023) was performed in three vineyards, located at different elevations in La Morra (Piedmont, northwestern Italy), monitored from the beginning of veraison to harvest. A split-plot design was set up, applying a passive greenhouse amplifying temperature in the bunch zone (‘T’ = increased temperature; ‘C’ = control temperature) and UV-blocking plastics over individual bunches (‘1’ = full UV exposure; ‘0’ = UV-blocked). Berry weight, skin weight, and juice total soluble solids were measured. Grape skin anthocyanins, flavonols, and hydroxycinnamic acid tartaric esters were analyzed by HPLC-DAD. Both treatments negatively influenced the berry weight but not the skin weight; the increased T had a negative impact on the sugar per berry content. Limited UV and increased temperature negatively impacted total anthocyanins at harvest and on di-hydroxylated anthocyanins. Limited UV-depressed flavonol concentration and high temperature decreased their synthesis. Increased UV promoted cis-p-coumaroyl tartaric acid and decreased trans-p-coumaroyl tartaric acid. The results of this research are valuable for improving the quality production of Nebbiolo through understanding the impacts of increased temperature and alterations to UV exposure expected by climate change.

The Internet of Things (IoT) is set to play a significant role in the future development of smart cities, which are designed to be environmentally friendly. However, the proliferation of these devices, along with their frequent replacements and the energy required to power them, contributes to a significant environmental footprint. In this paper we provide scientific evidences on the advantages of using an energy design pattern named ‘Batch Operations’ (BO) to optimize energy consumption on mobile devices. Big ICT companies like Google already batch multiple API calls instead of putting the device into an active state many times. This is supposed to save tail energy consumption in communication peripherals. To confirm this, we set up an experiment where we compare energy consumption and carbon emission when BO is applied to two communication peripherals on Android mobile device: 4G and GPS. Results show that (1) BO can save up to 40% energy when sending HTTP requests, resulting in an equivalent reduction in CO2 emissions. (2) no advantages for the GPS interface.

Yield estimation is a key point theme for precision agriculture, especially for small fruits and in-field scenarios. This paper focuses on the metrological validation of a novel deep-learning model that robustly estimates both the number and the radii of grape berries in vineyards using color images, allowing the computation of the visible (and total) volume of grape clusters, which is necessary to reach the ultimate goal of estimating yield production. The proposed algorithm is validated by analyzing its performance on a custom dataset. The number of berries, their mean radius, and the grape cluster volume are converted to millimeters and compared to reference values obtained through manual measurements. The validation experiment also analyzes the uncertainties of the parameters. Results show that the algorithm can reliably estimate the number (MPE=−5%, σ=6%) and the radius of the visible portion of the grape clusters (MPE=0.8%, σ=7%). Instead, the volume estimated in px3 results in a MPE=0.4% with σ=21%, thus the corresponding volume in mm3 is affected by high uncertainty. This analysis highlighted that half of the total uncertainty on the volume is due to the camera–object distance d and parameter R used to take into account the proportion of visible grapes with respect to the total grapes in the grape cluster. This issue is mostly due to the absence of a reliable depth measure between the camera and the grapes, which could be overcome by using depth sensors in combination with color images. Despite being preliminary, the results prove that the model and the metrological analysis are a remarkable advancement toward a reliable approach for directly estimating yield from 2D pictures in the field.

Three-dimensional (3D) applications lead the digital transition toward more immersive and interactive multimedia technologies. Point clouds (PCs) are a fundamental element in capturing and rendering 3D digital environments, but they present significant challenges due to the large amount of data typically needed to represent them. Although PC compression techniques can reduce the size of PCs, they introduce degradations that can negatively impact the PC’s quality and therefore the object representation’s accuracy. This trade-off between data size and PC quality highlights the critical importance of PC quality assessment (PCQA) techniques. In this article, we review the state-of-the-art no-reference (NR) objective quality metrics for PCs, which can accurately estimate the quality of generated and compressed PCs solely based on feature information extracted from the distorted PC. These characteristics make NR PCQA metrics particularly suitable in real-world application scenarios where the original PC data are unavailable for comparison, such as in streaming applications.

There are numerous methods in the literature for Direction-of-Arrival (DOA) estimation, including both classical and machine learning-based approaches that jointly estimate the Number of Sources (NOS) and DOA. However, most of these methods do not fully leverage the potential synergies between these two tasks, which could yield valuable shared information. To address this limitation, in this article, we present a multi-task Convolutional Neural Network (CNN) capable of simultaneously estimating both the NOS and the DOA of the signal. Through experiments on simulated data, we demonstrate that our proposed model surpasses the performance of state-of-the-art methods, especially in challenging environments characterized by high noise levels and dynamic conditions.

This study investigated the psycho-physiological impact of a black belt examination. Older brown-belt judoka (Tori, F = 2, M = 4; age = 75.6 ± 4.5 yrs) and their 2nd–5th Dan black-belt coaches (Uke; M = 6; age = 36.5 ± 10.8 yr) were evaluated during a simulated and official examination and a resting day. Participants’ trait anxiety (STAI-Y2) was recorded prior to the study. State anxiety (STAI-Y1), ratings of perceived exertion (RPE), enjoyment (ENJ), and fear of falling (FoF) were collected 15 min before and after the experimental conditions. Saliva samplings at awakening (T0), PRE (T1), and POST (T2) exercise and during the recovery (15 min-T3, 30 min-T4, 60 min-T5) were collected for cortisol (sC), testosterone (sT), and alpha-amylase (sAA). Participants showed normal age-reference population trait anxiety. A difference (p ≤ 0.05) for role emerged for ENJ and sT only. For STAI-Y1, higher PRE values with respect to POST ones emerged (p = 0.005), and the highest values (p = 0.007) for PRE of the examination were with respect to the simulation. For sAA, differences for sampling were found in the examination conditions only, with peak values at T2 (370.3 ± 78.6 U/mL, p = 0.001). For sC, a significant peak value (0.51 ± 0.09 μg/dL, p = 0.012) emerged at T2 in the examination condition. With respect to Tori, Uke showed higher mean sT values in all conditions (p ≤ 0.05) and the highest T2 during examination (712.5 ± 57.2 pg/mL). Findings suggest the relevance of monitoring psycho-physiological stress-related responses in judo for optimizing both coaching effectiveness and sport performance, especially in older judo practitioners.

Trigeminal neuralgia is a neuropathic pain syndrome responsive to botulinum toxin type A therapy. This review had the goal of analyzing the different studies published from 2002 to January 2024 to better define the techniques and the types of botulinum toxin type A used, the doses, the injection routes, and the different populations of trigeminal neuralgia patients treated. We considered only articles in which the therapy was administered to humans to treat trigeminal neuralgia. Case reports, case series, open-label, retrospective, and RCT studies were considered. The research was conducted on MEDLINE and the keywords included (trigeminal neuralgia) and (botulinum). Thirty-five articles were considered suitable for this review. Botulinum toxin type A was shown to be an effective therapy for TN pain in all the articles analyzed, albeit there is a lack of standardization in methods and outcomes. The techniques, the doses, and the injection approaches were very heterogeneous among the studies. Only two botulinum toxin type A formulations have been used in this setting: onabotulinumtoxinA and lanbotulinumtoxinA. There were 300 patients treated with onabotulinumtoxinA and 760 treated with lanbotulinumtoxinA overall (in 42 patients, the formulation was not specified). The distinction between etiological and clinical types of TN has been made by only a small portion of the studies. The main adverse event was transient facial asymmetry. Botulinum toxin type A is indeed a promising therapy that is clearly effective for trigeminal neuralgia. OnabotulinumtoxinA is the most common formulation used in Western countries; however, the meager sample of TN patients treated, and the lack of standardization are not sufficient for this therapy to be approved by the FDA or EMA. Indeed, more studies with standardized methods and larger samples are needed for this purpose.

In the framework of the analogous Hawking effect, we significantly improve our previous analysis of the master equation that encompasses very relevant physical systems, like Bose–Einstein condensates (BECs), dielectric media, and water. In particular, we are able to provide two significant improvements to the analysis. As our main result, we provide a complete set of connection formulas for both the subluminal and superluminal cases without resorting to suitable boundary conditions, first introduced by Corley, but simply on the grounds of a rigorous mathematical setting. Moreover, we provide an extension to the four-dimensional case, showing explicitly that, apart from obvious changes, adding transverse dimensions does not substantially modify the Hawking temperature in the dispersive case. Furthermore, an important class of exact solutions of the so-called reduced equation that governs the behavior of non-dispersive modes is also provided.

Background/Objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against S. Paratyphi A. Here we describe the design of a S. Paratyphi A conjugate. Methods: The serovar-specific O-antigen (O:2) was linked to the CRM197 carrier protein (O:2–CRM197) and a panel of conjugates differing for structural characteristics were compared in mice and rabbits. Results: We identified the O-antigen molecular size, polysaccharide to protein ratio, conjugate cross-linking, and O:2 O-acetylation level as critical quality attributes and identified optimal design for a more immunogenic vaccine. Conclusions: This work guides the development of the O:2–CRM197 conjugate to be combined with TCV in a bivalent formulation against enteric fever.

Alterations of the BRAF gene and the resulting changes in the BRAF protein are one example of molecular cancer profiling in humans and dogs. We tested 227 samples of canine carcinomas from different anatomical sites (anal sac (n = 23), intestine (n = 21), liver (n = 21), lungs (n = 19), mammary gland (n = 20), nasal cavity (n = 21), oral epithelium (n = 18), ovary (n = 20), prostate (n = 21), thyroid gland (n = 21), urinary bladder (n = 22)) with two commercially available primary anti-BRAFV600E antibodies (VE1 Ventana, VE1 Abcam). The immunohistochemical results were confirmed with droplet digital PCR (ddPCR). BRAFV595E-mutated cases were found in canine prostatic (16/21), urothelial (17/22), and oral squamous cell carcinomas (4/18), while other carcinoma types tested negative. Both antibodies showed consistent results, with intracytoplasmic immunolabeling of tumour cells, making them reliable tools for detecting the BRAFV595E mutation in canine carcinomas. In conclusion, identifying BRAF mutations from biopsy material offers a valuable opportunity to enhance cancer treatment strategies (BRAF inhibitors) in canine urothelial carcinomas, prostatic carcinomas, and oral squamous cell carcinomas.

Saliva has emerged as a promising diagnostic fluid for viral infections, enabling the direct analysis of viral genetic material and the detection of infection markers such as proteins, metabolites, microRNAs, and immunoglobulins. This comprehensive review aimed to explore the use of saliva as a diagnostic tool for viral infections, emphasizing its advantages and limitations. Saliva stands out due to its simplicity and safety in collection, along with the convenience of self-collection without the need for healthcare supervision, while potentially being comparable to urine and blood in terms of effectiveness. Herein, we highlighted the significant potential of saliva in assessing viral loads and diagnosing viral infections, such as herpesviruses, HPV, PyV, TTV, SARS-CoV-2, and MPXV. The detection of viral shedding in saliva underscores its utility in early diagnosis, the monitoring of infection progression, and evaluating treatment responses. The non-invasive nature of saliva collection makes it an appealing alternative to more invasive methods, promoting better patient compliance and facilitating large-scale screening and surveillance. As such, we further highlight current evidence on the use of saliva as a prognostic tool. Although a significant amount of data is already available, further investigations are warranted to more comprehensively assess the added benefit from the utilization of salivary biomarkers in the clinics. Salivary biomarkers show great promise for the early detection and prevention of viral infection complications, potentially improving disease management and control at the population level. Integrating these non-invasive tools into routine clinical practice could enhance personalized healthcare strategies and patient outcomes. Future studies should focus on establishing standardization protocols, validating the accuracy of salivary diagnostics, and expanding clinical research to enhance the diagnostic and monitoring capabilities of salivary biomarkers.

The currently available point-of-care hemostasis tests are burdened by criticisms concerning the use of different activators and inhibitors and the lack of dynamic flow. These operating conditions may constitute an impediment to the determination of the patient’s hemostatic condition. Hence, the diffusion of these tests in clinical practice is still limited to specific scenarios. In this work, we present a new method for analyzing the patient’s global hemostasis based on the visualization of the main components of the coagulation process and its computerized quantitative image analysis. The automated “Smart Clot” point-of-care system presents a micro-fluidic chamber in which whole blood flows, without the addition of any activator or inhibitor. In this micro-channel, platelet adhesion, activation and aggregation to the type I collagen-coated surface take place (primary hemostasis), leading to the production of endogenous thrombin on the surface of platelet aggregates and the consequent fibrin mesh and thrombus formation (secondary hemostasis). These observations are verified by inhibiting primary hemostasis with the antiplatelet drugs Indomethacin (−70% on platelet aggregation, −60% on fibrin(ogen) formation) and Tirofiban (complete inhibition of platelet aggregation and fibrin(ogen) formation) and secondary hemostasis with the antithrombin drugs Heparin (−70% on platelet aggregation, −80% on fibrin(ogen) formation) and Lepirudin (−80% on platelet aggregation, −90% on fibrin(ogen) formation). Smart Clot, through a single test, provides quantitative results concerning platelet aggregation and fibrin formation and is suitable for undergoing comparative studies with other coagulation point-of-care devices.

Silk sericin, the glue protein binding fibroin fibers together, is present in the Bombyx mori silkworms’ cocoons. In recent years, sericin has gained attention for its wide range of properties and possible opportunities for various applications, as evidenced by the meta-analysis conducted in this review. Sericin extraction methods have evolved over the years to become more efficient and environmentally friendly, preserving its structure. Due to its biocompatibility, biodegradability, anti-inflammatory, antibacterial, antioxidant, UV-protective, anti-tyrosinase, anti-aging, and anti-cancer properties, sericin is increasingly used in biomedical fields like drug delivery, tissue engineering, and serum-free cell culture media. Beyond healthcare, sericin shows promise in industries such as textiles, cosmetics, and food packaging. This review aims to highlight recent advancements in sericin extraction, research, and applications, while also summarizing key findings from earlier studies.

Background and Objectives: The Albumin-to-Alkaline Phosphatase ratio (AAPR) is an easily applicable and cost-effective marker investigated as an outcome predictor in solid cancers. Preliminary evidence in breast cancer suggests that a low AAPR correlates with a poor response to neoadjuvant chemotherapy (NAC) in primary tumors. However, data regarding the axillary response are lacking. This study aims to evaluate whether the AAPR can predict the axillary response in initially nodal-positive (cN+) breast cancer patients undergoing NAC. Materials and Methods: Clinical and biochemical variables of cN+ breast cancer patients undergoing NAC were collected. Pre-NAC albumin and alkaline phosphatase serum values were utilized in the AAPR calculation. Fisher’s exact test was performed to identify differences between the two groups of patients (high and low AAPR according to the cut-off reported in the literature). The primary outcome was the nodal pathologic complete response (pCR) rate in the two groups of patients. Results: Nodal pCR was achieved in 20/45 (44.4%) patients. A total of 36/45 (80%) patients had an AAPR > 0.583. Among patient and tumor characteristics, the only statistically significant difference between the two groups was the axillary pCR between the low and high AAPR groups (p-value = 0.03, OR = 0.129, 95% CI = 0.00–0.835). Conclusions: This pilot study suggests that the pre-treatment AAPR might be an early predictor of axillary response in cN+ breast cancer patients undergoing NAC. This result justifies further investigation in larger prospective trials to validate this finding.

Many species of the genus Pseudomonas are known to be highly tolerant to solvents and other environmental stressors. Based on phylogenomic and comparative genomic analyses, several Pseudomonas species were recently transferred to a new genus named Halopseudomonas. Because of their unique enzymatic machinery, these strains are being discussed as novel biocatalysts in biotechnology. In order to test their growth parameters and stress tolerance, five Halopseudomonas strains were assessed regarding their tolerance toward different n-alkanols (1-butanol, 1-hexanol, 1-octanol, 1-decanol), as well as to salt stress and elevated temperatures. The toxicity of the solvents was investigated by their effects on bacterial growth rates and presented as EC50 concentrations. Hereby, all Halopseudomonas strains showed EC50 values up to two-fold lower than those previously detected for Pseudomonas putida. In addition, the activity of the cis-trans isomerase of unsaturated fatty acids (Cti), which is an urgent stress response mechanism known to be present in all Pseudomonas species, was monitored in the five Halopseudomonas strains. Although several of the tested species were known to contain the cti gene, no significant phenotypic activity could be detected in the presence of the assayed stressors. A bioinformatic analysis of eight cti-carrying Halopseudomonas strains examining promotor binding sites, binding motifs and signal peptides showed that most of the cti genes have a lipoprotein signal peptide and promotor regions and binding motifs that do not coincide with those of Pseudomonas. These insights represent putative reasons for the absence of the expected Cti activity in Halopseudomonas, which in turn has always been observed in cti-carrying Pseudomonas. The lack of Cti activity under membrane stress conditions when the cti gene is present has never been documented, and this could represent potential negative implications on the utility of the genus Halopseudomonas for some biotechnological applications.

Viral spillover represents the transmission of pathogen viruses from one species to another that can give rise to an outbreak. It is a critical concept that has gained increasing attention, particularly after the SARS-CoV-2 pandemic. However, the term is often used inaccurately to describe events that do not meet the true definition of spillover. This review aims to clarify the proper use of the term and provides a detailed analysis of the mechanisms driving zoonotic spillover, with a focus on the genetic and environmental factors that enable viruses to adapt to new hosts. Key topics include viral genetic variability in reservoir species, biological barriers to cross-species transmission, and the factors that influence viral adaptation and spread in novel hosts. The review also examines the role of evolutionary processes such as mutation and epistasis, alongside ecological conditions that facilitate the emergence of new pathogens. Ultimately, it underscores the need for more accurate predictive models and improved surveillance to better anticipate and mitigate future spillover events.

Lyme disease, a zoonotic infection caused by the bacterium Borrelia burgdorferi, is transmitted to humans through the bites of infected ticks. Its diagnosis primarily relies on serological methods; however, the existing borreliosis techniques have shown a variable sensitivity and specificity. Our study aimed to map IgG epitopes from five outer membrane proteins (Omp) from B. burgdorferi [Filament flagellar 41kD (PI1089), flagellar hook-associated protein (Q44767), Flagellar hook k2 protein (O51173), Putative Omp BURGA03 (Q44849), and 31 kDa OspA (P0CL66)] lipoprotein to find specific epitopes for the development of accurate diagnosis methods. Using the spot synthesis technique, a library of 380 peptides was constructed to identify linear B cell epitopes recognized by human IgG in response to specific B. burgdorferi-associated proteins. The reactivity of this epitope when chemically synthesized was then evaluated using ELISA with a panel of the patient’s sera. Cross-reactivity was assessed through data bank access and in vitro analysis. Among the 19 epitopes identified, four were selected for further investigation based on their signal intensity, secondary structure, and peptide matching. Validation was performed using ELISA, and ROC curve analysis demonstrated a sensitivity of ≥85.71%, specificity of ≥92.31, accuracy of ≥90.7, and AUC value of ≥0.91 for all peptides. Our cross-reactivity analysis demonstrated that the Burg/02/huG, Burg/03/huG, and Burg/12/huG peptides were not reactive to antibodies from patients with Leptospirosis and syphilis compared to those from the B. burgdorferi group. These peptides indicated an excellent performance in distinguishing between B. burgdorferi-infected and non-infected individuals and exhibited a neglected reactivity to antibodies in sera from patients with Leptospirosis and syphilis. These peptides are promising targets for recombinant development, potentially leading to more accurate serological tests and vaccines.

Background: Lithium is a cornerstone in the treatment of bipolar disorder (BD). However, lithium use requires careful monitoring of thyroid function due to associated dysfunctions. The aim of our real-world study is to retrospectively evaluate the impact of lithium on thyroid function and how these thyroid alterations can be measured and managed. Methods: A retrospective observational study was performed on 150 patients with BD who started lithium treatment at the University Hospital of Siena. Thyroid function was assessed at baseline and after the introduction of lithium by measuring TSH, T3, and T4 levels at baseline and after 3, 6, 9, and 12 months, during which changes in psychiatric symptoms were also evaluated using specific psychometric scales. Results: Significant increases in TSH levels were observed at 3 and 6 months, while T3 and T4 levels decreased significantly at 3 months. Transient thyroid dysfunction occurred in 36.7% of patients, but normalized without the discontinuation of lithium or need for thyroid replacement therapy in most cases; however, replacement therapy was initiated in 8.7% of patients. There were no significant differences in treatment response between patients with and without thyroid abnormalities, as the abnormalities were transient or resolved. Conclusions: In our sample, lithium induced some cases of hypothyroidism, which, being transient or corrected with replacement therapy, did not interfere with symptomatic improvement. These findings underscore the necessity for continuous thyroid function monitoring during lithium therapy. Clinicians should be prepared to initiate thyroid replacement therapy, when necessary, as timely management can prevent the interruption of lithium treatment and ensure ongoing symptomatic improvement in BD patients. Future studies could include larger and more diverse populations to validate these findings further, extending the follow-up period beyond 12 months to better observe long-term thyroid function trends and management outcomes.

Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis.