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This study presents an automated methodology for evaluating micro-channels fabricated using a femtosecond laser on stainless steel substrates. We utilize 3D surface topography and metrological analyses to extract geometric features and detect fabrication defects. Standardized samples were analyzed using a light interferometer, and the resulting data were processed with Principal Component Analysis (PCA) and RANSAC algorithms to derive channel characteristics, such as depth, wall taper, and surface roughness. The proposed method identifies common defects, including bumps and V-defects, which can compromise the functionality of micro-channels. The effectiveness of the approach is validated by comparisons with commercial solutions. This automated procedure aims to enhance the reliability and precision of femtosecond laser micro-milling for industrial applications. The detected defects, combined with fabrication parameters, could be ingested in an AI-based process to optimize fabrication processes.

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions.

The carbon source/sink nature and the water balance of a drip-irrigated and mulched watermelon cultivated under a semi-arid climate were investigated. Biodegradable films, plants and some fruits were left on the soil as green manure. The study spanned from watermelon planting to the subsequent crop (June–November 2023). The eddy covariance technique was employed to monitor water vapor (H2O) and carbon dioxide (CO2) fluxes, which were partitioned into transpiration, evaporation, photosynthesis and respiration, respectively, using the flux variance similarity method.This method utilizesthe Monin–Obukhov similarity theory to separate stomatal (photosynthesis and transpiration) from non-stomatal (respiration and evaporation) processes. The results indicate that mulching films contribute to carbon sequestration in the soil (+19.3 g C m−2). However, the mulched watermelon crop presented in this study functions as a net carbon source, with a net biome exchange, representing the net rate of C accumulation in or loss from ecosystems, equal to +230 g C m−2. This is primarily due to the substantial amount of carbon exported through marketable fruits. Fixed water scheduling led to water waste through deep percolation (approximately 1/6 of the water supplied), which also contributed to the loss of organic carbon via leaching (−4.3 g C m−2). These findings recommend further research to enhance the sustainability of this crop in terms of both water and carbon balances.

(1) Multiple sclerosis (MS) is identified by a complex interaction between central inflammation and neurodegeneration. Genetic individual variability could play a significative role in clinical presentation. The interleukin-5 (IL-5) rs2069812 single-nucleotide polymorphism (SNP) seems to define the clinical course of Th2 autoimmune diseases, while its role in MS has never been investigated. (2) In a group of 230 patients diagnosed with relapsing–remitting MS (RR-MS) or progressive MS (P-MS) and controls (IC), rs2069812 polymorphism, cerebrospinal fluid (CSF) levels of inflammatory mediators, and clinical and demographic characteristics were determined. In RR-MS patients, No Evidence of Disease Activity (NEDA-3) at three years of follow-up was detected. (3) We identified higher levels of proinflammatory cytokines, particularly IL-2 (median [IQR], RR-MS = 0.2 [0–0.7]; P-MS = 0.1 [0–1.6]; IC = 0.1 [0.0–0.1]; p < 0.005), IL-6 (RR-MS = 0.9 [0.3–2.3]; P-MS = 0.8 [0.1–2.7]; IC = 0.1 [0.0–0.5]; p < 0.005), IL-12 (RR-MS = 0.5 [0–1.1]; P-MS = 0.5 [0–1.1]; IC = 0.0 [0.0–0.3]; p < 0.005), and GM-CSF (RR-MS = 15.6 [4.8–26.4]; P-MS = 14 [3.3–29.7]; IC = 8.9 [4.7–11.7]; p < 0.005) in MS patients compared with IC. Conversely, anti-inflammatory cytokines, specifically IL-5 (RR-MS = 0.65 [0–2.4]; P-MS = 0.1 [0–0.8]; IC = 1.7 [0.6–2.8]; p < 0.005) and IL-1ra (RR-MS = 14.7 [4.9–26.4]; P-MS = 13.1 [4.7–22.2]; IC = 27.8 [17.7–37.6]; p < 0.005) were higher in controls. According to rs2069812, in MS patients, the T-allele was associated with higher concentrations of proinflammatory mediators (IL-2, CT/TT = 0.2 [0.0–2.0]; CC = 0.1 [0.0–0.4], p = 0.015; IL-6, CT/TT = 1.2 [0.4–3.2] vs. CC = 0.7 [0.1–1.7], p = 0.007; IL-15, CT/TT = 0.1 [0.0–9.5] vs. CC = 0.0 [0.0–0.1], p = 0.019; and GM-CSF, CT/TT = 0.1 [0.0–0.6] vs. CC = 0.05 [0.0–0.1], p < 0.001), and CC was associated with anti-inflammatory mediators (IL-5, CT/TT = 0.03 [0.0–1.9] vs. CC = 1.28 [0.0–2.7], p = 0.001; IL-1ra, CT/TT = 12.1 [4.1–25.9] vs. CC = 18.1 [12.1–26.9], p = 0.006). We found the same differences in RR-MS patients (IL-2, T-allele median [IQR] = 0.3 [0.0–2.0] vs. C-allele, median [IQR] = 0.04 [0.0–0.3]; p = 0.005; IL-6, T-allele, median [IQR] = 1.3 [0.4–3.3] vs. C-allele, median [IQR] = 0.6 [0.03–1.5]; p = 0.001; IL-15, T-allele, median [IQR] = 0.1 [0.0–9.5] vs. C-allele, median [IQR] = 0.0 [0.0–0.1]; p = 0.008; GM-CSF, T-allele, median [IQR] = 0.1 [0.0–97.9] vs. C-allele, median [IQR] = 0.0 [0.0–0.001]; p < 0.001; IL-5, T-allele, median [IQR] = 0.02 [0.0–2.2] vs. C-allele, median [IQR] = 1.5 [0.0–2.9]; p = 0.016; and IL-1ra, T-allele, median [IQR] = 12.1 [4.3–26.4] vs. C-allele, median [IQR] = 18.5 [12.7–28.3]; p = 0.006) but not in P-MS, except for IL-5 (T-allele, median [IQR] = 0.1 [0–0.23] vs. C-allele, median [IQR] = 0.6 [0.0–2.5]; p = 0.022). Finally, we identified an association between CC in RR-MS patients and NEDA-3 after three years of follow-up (p = 0.007). (4) We describe, for the first time, the role of an SNP of the IL-5 gene in regulating central neuroinflammation and influencing clinical course in MS patients.

Arrhythmogenic cardiomyopathy (ACM) is a rare cardiac disease, characterized by the progressive replacement of myocardial tissue with fibrous and fatty deposits. It can involve both the right and left ventricles. It is associated with the development of life-threatening arrhythmias and culminates in sudden cardiac death. Electrocardiography (ECG) has emerged as a pivotal tool, offering diagnostic insights and prognostic information. The specific ECG abnormalities observed in ACM not only contribute to early detection but also hold the key to the prediction of the likelihood of severe complications. The recognition of these nuanced ECG manifestations has become imperative for clinicians as it guides them in the formulation of tailored therapeutic strategies that address both the present symptoms and the potential future risks.

Background: At the same conditions of delivered power and contact force, open-irrigated radiofrequency ablation catheters are believed to create deeper lesions, while non-irrigated ones produce shallower lesions. This ex vivo study aims to directly compare the lesion dimensions and characteristics of an irrigated ablation catheter with a flexible tip and a non-irrigated solid-tip catheter. Methods: Radiofrequency lesions were induced on porcine myocardial slabs using both open-tip irrigated and non-irrigated standard 4 mm catheters at three power settings (20 W, 30 W, and 40 W), maintaining a fixed contact force of 10 gr. A lesion assessment was conducted including the lesion depth, depth at the maximum diameter, and lesion surface diameters, with the subsequent calculation of the lesion volume and area being undertaken. Results: Irrigated catheters produced lesions with significantly higher superficial widths at all power levels (3.8 vs. 4.4 mm at 20 W; 3.9 mm vs. 4.4 mm at 30 W; 3.8 mm vs. 4.5 mm at 40 W; p = 0.001, p = 0.019, p = 0.003, respectively). Non-irrigated catheters resulted in significantly higher superficial areas at all power levels (23 mm2 vs. 18 mm2 at 20 W; 25 mm2 vs. 19 mm2 at 30 W; 26 mm2 vs. 19 mm2 at 40 W; p = 0.001, p = 0.005, p = 0.001, respectively). Irrigated catheters showed significantly higher values of lesion maximum depth at 40 W (4.6 mm vs. 5.5 mm; p = 0.007), while non-irrigated catheters had a significantly higher calculated volume at 20 W (202 µL vs. 134 µL; p = 0.002). Conclusions: Radiofrequency ablation using an irrigated catheter with a flexible tip has the potential to generate smaller superficial lesion areas compared with those obtained using a non-irrigated catheter.

Different studies and systematic reviews have reported weight increase after tonsillectomy. However, the odds of a child being overweight or obese after tonsillectomy were no different than before surgery, according to a few studies. This systematic review aims to analyze the impact of adenotonsillectomy (TA) on weight gain and identify subgroups of children and adolescents at risk of experiencing weight gain. A systematic search included studies published in the last ten years. The PICO framework was used in the selection process, and evidence was assessed using the GRADE system. A total of 26 studies were included, and moderate–high level quality ones showed that children who underwent TA could present an increase in BMI z-score. However, this weight gain was significant in individuals younger than six years old and was considered catch-up growth in underweight subjects at baseline. In contrast, for normal-weight or overweight individuals, TA did not lead to overweight per se. At the same time, diet changes and overfeeding did not have a leading role in weight gain. In conclusion, TA may not be an independent risk factor for unfavorable weight gain in children; however, individuals who were underweight pre-operatively or younger than six years reported more weight gain after TA than expected.

Background: Physiological pacing has gained significant interest due to its potential to achieve optimal hemodynamic response. This study aimed to assess left ventricular performance in terms of electrical parameters, specifically QRS duration and mechanical performance, evaluated as myocardial work. We compared His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP) to evaluate their effects. Methods: Twenty-four patients with class I or IIa indications for pacing were enrolled in this study, with twelve patients undergoing HBP implantation and another twelve undergoing LBBAP implantation. A comprehensive analysis of myocardial work was conducted. Results: Our findings indicate that there were no major differences in terms of spontaneous and HBP activation in myocardial work, except for global wasted work (217 mmHg% vs. 283 mmHg%; p 0.016) and global work efficiency (87 mmHg% vs. 82 mmHg%; p 0.049). No significant differences were observed in myocardial work between spontaneous activation and LBBAP. Similarly, no significant differences in myocardial work were found between HBP and LBBAP. Conclusions: Both pacing modalities provide physiological ventricular activation without significant differences when compared to each other. Moreover, there were no significant differences in QRS duration between HBP and LBBAP. However, LBBAP demonstrated advantages in terms of feasibility, as it achieved better lead electrical parameters compared to HBP (threshold@0.4 ms 0.6 V vs. 1 V; p = 0.045—sensing 9.4 mV vs. 2.4 mV; p < 0.001). Additionally, LBBAP required less fluoroscopy time (6 min vs. 13 min; p = 0.010) and procedural time (81 min vs. 125 min; p = 0.004) compared to HBP.

Our review delves into the realm of peroral endoscopic myotomies (POEMs) in the upper gastrointestinal tract (UGT). In recent years, POEMs have brought about a revolution in the treatment of UGT motility disorders. Esophageal POEM, the first to be introduced, has now been validated as the primary treatment for achalasia. Subsequently developed, G-POEM displays promising results in addressing refractory gastroparesis. Over time, multiple endoscopic myotomy techniques have emerged for the treatment of Zenker’s diverticulum, including Z-POEM, POES, and hybrid approaches. Despite the well-established efficacy outcomes, new challenges arise in the realm of POEMs in the UGT. For esophageal POEM, the future scenario lies in customizing the myotomy extent to the minimum necessary, while for G-POEM, it involves identifying patients who can optimally benefit from the treatment. For ZD, it is crucial to validate an algorithm that considers various myotomy options according to the diverticulum’s size and in relation to individual patients. These challenges align with the concept of precision endoscopy, personalizing the technique for each subject. Within our text, we comprehensively examine each myotomy technique, analyzing indications, outcomes, and adverse events. Additionally, we explore the emerging challenges posed by myotomies within the context of the evolving field of precision endoscopy.

Gastroparesis (GP) is a chronic disease characterized by upper gastrointestinal symptoms, primarily nausea and vomiting, and delayed gastric emptying (GE), in the absence of mechanical GI obstruction. The underlying pathophysiology of GP remains unclear, but factors contributing to the condition include vagal nerve dysfunction, impaired gastric fundic accommodation, antral hypomotility, gastric dysrhythmias, and pyloric dysfunction. Currently, gastric emptying scintigraphy (GES) is considered the gold standard for GP diagnosis. However, the overall delay in GE weakly correlates with GP symptoms and their severity. Recent research efforts have focused on developing treatments that address the presumed underlying pathophysiological mechanisms of GP, such as pyloric hypertonicity, with Gastric Peroral Endoscopic Myotomy (G-POEM) one of these procedures. New promising diagnostic tools for gastroparesis include wireless motility capsule (WMC), the 13 carbon-GE breath test, high-resolution electrogastrography, and the Endoluminal Functional Lumen Imaging Probe (EndoFLIP). Some of these tools assess alterations beyond GE, such as muscular electrical activity and pyloric tone. These modalities have the potential to characterize the pathophysiology of gastroparesis, identifying patients who may benefit from targeted therapies. The aim of this review is to provide an overview of the current knowledge on diagnostic pathways in GP, with a focus on the association between diagnosis, symptoms, and treatment.

The purpose of the present study was to document pathological findings on retromode imaging in choroidal nevi and evaluate its diagnostic validity, using the confocal scanning laser ophthalmoscope Nidek Mirante (cSLO). A total of 41 choroidal nevi from 41 patients were included. All patients underwent multicolor fundus (mCF), infrared reflectance (IR), green fundus autofluorescence (FAF), dark-field (DF) and retromode (RM) imaging and optical coherence tomography (OCT) scans. We investigated retromode images to evaluate choroidal nevus features by comparing the results with those of mCF, IR, FAF, DF and OCT. In 100% of available images, retromode scanning laser ophthalmoscopy was able to detect choroidal nevi with a characteristic “hypo-retro-reflective” pattern, even the cases not visible on mCF, IR and FAF images. It also made it possible to delineate the margins of lesions with the highest rate of sharpness and accuracy among the imaging modalities examined. These findings seem to demonstrate how RM-SLO is an innovative diagnostic tool to detect and follow up choroidal nevi in a fast, reliable and non-invasive way.

The magnetron sputtering technique has been investigated in recent years with ever-growing interest as a verifiable solid target manufacturing technology aimed at the production of medical radionuclides by using low-energy cyclotron accelerators. However, the possible loss of high-cost materials prevents access to work with isotopically enriched metals. The need for expensive materials for the supply of the growing demand for theranostic radionuclides makes the material-saving approach and recovery essential for the radiopharmaceutical field. To overcome the main magnetron sputtering drawback, an alternative configuration is proposed. In this work, an inverted magnetron prototype for the deposition of tens of μm film onto different substrates is developed. Such configuration for solid target manufacturing has been proposed for the first time. Two ZnO depositions (20–30 μm) onto Nb backing were carried out and analysed by SEM (Scanning Electron Microscopy) and XRD (X-ray Diffractogram). Their thermomechanical stability under the proton beam of a medical cyclotron was tested as well. A possible improvement of the prototype and the perspective of its utilisation were discussed.

The anti-SARS-CoV-2 vaccination has probably been the most effective tool for preventing the infection and negative outcomes of the COVID-19 disease, and therefore for interrupting the pandemic state. The first licensed SARS-CoV-2 vaccine was BNT162b2, an mRNA vaccine that has been widely used since the earliest stages of the global vaccination campaign. Since the beginning of the vaccination campaign, some cases of suspected allergic reactions to BNT162b2 have been described. Epidemiological data, however, have provided reassuring results of an extremely low prevalence of these hypersensitivity reactions to anti-SARS-CoV-2 vaccines. In this article, we describe the results of a survey carried out through the use of a questionnaire, administered to all the health personnel of our university hospital after the first two doses of the BNT162b2 vaccine, which investigated the development of adverse reactions after a vaccination. We analyzed the responses of 3112 subjects subjected to the first dose of the vaccine; among these, 1.8% developed symptoms compatible with allergic reactions and 0.9% with clinical manifestations of possible anaphylaxis. Only 10.3% of the subjects who had allergic reactions after the first injection experienced similar reactions after the second dose and none of them experienced anaphylaxis. In conclusion, the anti-SARS-CoV-2 vaccination is rarely associated with severe allergic reactions and the second dose of vaccine is safe for this group of patients.

An important issue that is often neglected is the difference between male and female genders in response to medical treatments. In the context of COVID-19 vaccine administration, despite identical protocol strategies, it has been observed that females often suffer more adverse consequences than males. Here, we analyzed the adverse events (AEs) of the Comirnaty vaccine in a population of 2385 healthcare workers as a function of age, sex, COVID-19 history and BMI. Using logistic regression analysis, we showed that these variables may contribute to the development of AEs, particularly in young subjects, females and individuals with a BMI below 25 kg/m2. Moreover, partial dependence plots indicate a 50% probability of developing a mild AE for a long period of time (≥7 days) or a severe AE of any duration in women below 40 years old and with a BMI < 20 kg/m2. As this effect is more evident after the second dose of the vaccine, we propose to reduce the amount of vaccine for any additional booster dose in relation to age, sex and BMI. This strategy might reduce adverse events without affecting vaccine efficacy.

Background: Endoscopic treatment of post-esophagectomy/gastrectomy anastomotic dehiscence includes Self-Expandable Metal Stents (SEMS), which have represented the “gold standard” for many years, and Endoscopic Vacuum Therapy (EVT), which was recently introduced, showing promising results. The aim of the study was to compare outcomes of SEMS and EVT in the treatment of post-esophagectomy/gastrectomy anastomotic leaks, focusing on oncologic surgery. Methods: A systematic search was performed on Pubmed and Embase, identifying studies comparing EVT versus SEMS for the treatment of leaks after upper gastro-intestinal surgery for malignant or benign pathologies. The primary outcome was the rate of successful leak closure. A meta-analysis was conducted, performing an a priori-defined subgroup analysis for the oncologic surgery group. Results: Eight retrospective studies with 357 patients were eligible. Overall, the EVT group showed a higher success rate (odd ratio [OR] 2.58, 95% CI 1.43–4.66), a lower number of devices (pooled mean difference [pmd] 4.90, 95% CI 3.08–6.71), shorter treatment duration (pmd −9.18, 95% CI −17.05–−1.32), lower short-term complication (OR 0.35, 95% CI 0.18–0.71) and mortality rates (OR 0.47, 95% CI 0.24–0.92) compared to stenting. In the oncologic surgery subgroup analysis, no differences in the success rate were found (OR 1.59, 95% CI 0.74–3.40, I2 = 0%). Conclusions: Overall, EVT has been revealed to be more effective and less burdened by complications compared to stenting. In the oncologic surgery subgroup analysis, efficacy rates were similar between the two groups. Further prospective data need to define a unique management algorithm for anastomotic leaks.

Background: Osteopontin, an extracellular matrix protein involved in bone remodeling, tissue repair and inflammation, has previously been associated with increased inflammation and neurodegeneration in multiple sclerosis (MS), promoting a worse disease course. Osteopontin is also likely involved in acute MS relapses. Methods: In 47 patients with relapsing-remitting MS, we explored the correlation between the time elapsed between the last clinical relapse and lumbar puncture, and the cerebrospinal fluid (CSF) levels of osteopontin and a group of inflammatory cytokines and adipokines such as resistin, plasminogen activator inhibitor-1, osteoprotegerin, interleukin (IL)-1β, IL-2, IL-6 and IL-1 receptor antagonist (IL-1ra). We also analyzed the correlations between CSF levels of osteopontin and the other CSF molecules considered. Results: Osteopontin CSF concentrations were higher in patients with a shorter time interval between the last clinical relapse and CSF withdrawal. In addition, CSF levels of osteopontin were positively correlated with the proinflammatory cytokines IL-2 and IL-6 and negatively correlated with the anti-inflammatory molecule IL-1ra. Conclusions: Our results further suggest the role of osteopontin in acute MS relapses showing that, in proximity to relapses, osteopontin expression in CSF may be increased along with other proinflammatory mediators and correlated with decreased concentrations of anti-inflammatory molecules.

Dissolved oxygen (DO) is deeply involved in preserving the life of cellular tissues and human beings due to its key role in cellular metabolism: its alterations may reflect important pathophysiological conditions. DO levels are measured to identify pathological conditions, explain pathophysiological mechanisms, and monitor the efficacy of therapeutic approaches. This is particularly relevant when the measurements are performed in vivo but also in contexts where a variety of biological and synthetic media are used, such as ex vivo organ perfusion. A reliable measurement of medium oxygenation ensures a high-quality process. It is crucial to provide a high-accuracy, real-time method for DO quantification, which could be robust towards different medium compositions and temperatures. In fact, biological fluids and synthetic clinical fluids represent a challenging environment where DO interacts with various compounds and can change continuously and dynamically, and further precaution is needed to obtain reliable results. This study aims to present and discuss the main oxygen detection and quantification methods, focusing on the technical needs for their translation to clinical practice. Firstly, we resumed all the main methodologies and advancements concerning dissolved oxygen determination. After identifying the main groups of all the available techniques for DO sensing based on their mechanisms and applicability, we focused on transferring the most promising approaches to a clinical in vivo/ex vivo setting.

The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies.

In multiple sclerosis (MS), fatigue is a frequent symptom that negatively affects quality of life. The pathogenesis of fatigue is multifactorial and inflammation may play a specific role. To explore the association between fatigue, central inflammation and disease course in MS in 106 relapsing-remitting (RR)-MS patients, clinical characteristics, including fatigue and mood, were explored at the time of diagnosis. NEDA (no evidence of disease activity)-3 status after one-year follow up was calculated. Cerebrospinal fluid (CSF) levels of a set of proinflammatory and anti-inflammatory molecules and peripheral blood markers of inflammation were also analyzed. MRI structural measures were explored in 35 patients. A significant negative correlation was found at diagnosis between fatigue measured with the Modified Fatigue Impact Scale (MFIS) and the CSF levels of interleukin (IL)-10. Conversely, no significant associations were found with peripheral markers of inflammation. Higher MFIS scores were associated with reduced probability to reach NEDA-3 status after 1-year follow up. Finally, T2 lesion load showed a positive correlation with MFIS scores and a negative correlation with CSF IL-10 levels at diagnosis. CSF inflammation, and particularly the reduced expression of the anti-inflammatory molecule IL-10, may exacerbate fatigue. Fatigue in MS may reflect subclinical CSF inflammation, predisposing to greater disease activity.

The Lightning Network (LN) has emerged as one of the prominent solutions to overcome the biggest limit of blockchain based on PoW: scalability. LN allows for creating a layer on top of an existing blockchain where users can send payments and micro-payments without waiting long confirmation times. One of the key features of LN is that payments can also be sent towards nodes that are not directly connected. From the routing perspective, the balance of an edge that connects two nodes is known, but the distribution between the two involved ends is unknown. Thus, the process of sending payments is based on a trial and error approach, and the routing can be considered probabilistic. Probabilistic Logic Programming (PLP) is a powerful formalism that allows the representation of complex relational domains characterized by uncertainty. In this paper, we study the problem of reasoning about the existence of a path between two nodes that can route a payment of a given size leveraging multiple models based on PLP. We adopt some recently proposed extensions of PLP and develop several models that can be adapted to represent multiple scenarios.

The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80–98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease.

Short-term adverse events are common following the BNT162b2 vaccine for SARS-Cov-2 and have been possibly associated with IgG response. We aimed to determine the incidence of adverse reactions to the vaccine and the impact on IgG response. Our study included 4156 health-care professionals who received two doses of the BNT162b2 vaccine 21 days apart and obtained 6113 online questionnaires inquiring about adverse events. The serum response was tested in 2765 subjects 10 days after the second dose. Adverse events, most frequently a local reaction at the site of injection, were reported by 39% of subjects. Multivariate analysis showed that female sex (odds ratio—OR—1.95; 95% confidence interval—CI—1.74–2.19; p < 0.001), younger age (OR 0.98 per year, p < 0.001), second dose of vaccine (OR 1.36, p < 0.001), and previous COVID-19 infection (OR 1.41, p < 0.001) were independently associated with adverse events. IgG response was significantly higher in subjects with adverse events (1110 AU/mL—IQR 345-1630 vs. 386 AU/mL, IQR 261-1350, p < 0.0001), and the association was more pronounced in subjects experiencing myalgia, fever, and lymphadenopathy. We demonstrate that a more pronounced IgG response is associated with specific adverse events, and these are commonly reported by health care professionals after the BNT162b2 vaccine for SARS-Cov-2.

Background: Astrocytes and microglia play an important role in the inflammatory process of multiple sclerosis (MS). We investigated the associations between the cerebrospinal fluid (CSF) levels of glial fibrillary acid protein (GFAP) and soluble triggering receptors expressed on myeloid cells-2 (sTREM-2), inflammatory molecules, and clinical characteristics in a group of patients with relapsing-remitting MS (RRMS). Methods: Fifty-one RRMS patients participated in the study. Clinical evaluation and CSF collection were performed at the time of diagnosis. The CSF levels of GFAP, sTREM-2, and of a large set of inflammatory and anti-inflammatory molecules were determined. MRI structural measures (cortical thickness, T2 lesion load, cerebellar volume) were examined. Results: The CSF levels of GFAP and sTREM-2 showed significant correlations with inflammatory cytokines IL-8, G-CSF, and IL-5. Both GFAP and sTREM-2 CSF levels positively correlated with age at diagnosis. GFAP was also higher in male MS patients, and was associated with an increased risk of MS progression, as evidenced by higher BREMS at the onset. Finally, a negative association was found between GFAP CSF levels and cerebellar volume in RRMS at diagnosis. Conclusions: GFAP and sTREM-2 represent suitable biomarkers of central inflammation in MS. Our results suggest that enhanced CSF expression of GFAP may characterize patients with a higher risk of progression.

Nowadays, micro-machining techniques are commonly used in several industrial fields, such as automotive, aerospace and medical. Different technologies are available, and the choice must be made considering many factors, such as the type of machining, the number of lots and the required accuracy specifications in terms of geometrical tolerances and surface finish. Lasers and electric discharge machining (EDM) are widely used to produce micro-components and are similarly unconventional thermal technologies. In general, a laser is particularly appreciated by the industry for the excellent machining speeds and for the possibility to machine essentially any type of materials. EDM, on the other hand, has a poor material removal rate (MRR) but can produce microparts on only electrically conductive workpieces, reaching high geometrical accuracy and realizing steep walls. The most common micro-application for both the technologies is drilling but they can make also milling operations. In this work, a comparison of femto-laser and EDM technologies was made focusing on micro-milling. Two features were selected to make the comparison: micro-channels and micro-pillars. The depth was varied on two levels for both features. As workpiece material, aluminum, stainless steel and titanium alloy were tested. Data regarding the process performance and the geometrical characteristics of the features were analyzed. The results obtained with the two technologies were compared. This work improves the knowledge of the micro-manufacturing processes and can help in the characterization of their capabilities.

Magnetron sputtering (MS) is a relatively new deposition technique, which is being considered among the cyclotron solid target (CST) manufacturing options now available, aiming at the medical radioisotopes yield for radiopharmaceutical production. However, the intrinsic high material losses during the deposition process do not permit its use with extremely expensive target materials, such as isotopically enriched metals/oxides. In this study, R&D technology for a new recovering shield is instead proposed to assess the dissipation of target material during the sputtering processes and, thus, an estimate of the material recovery that may be feasible and the related amount. The weight-loss analysis method is used to assess the material losses level inside the chamber during processing. In all tests carried out, a high-purity copper (99.99%) was used as a target material. As a result of this study, the material distribution for both magnetron and diode sputtering depositions can be calculated. The feasibility of the ultra-thick coatings growing, devoted to CST production, is demonstrated.

The region of Lombardy was the epicenter of the COVID-19 outbreak in Italy. Emergency Hospital 19 (EH19) was built in the Milan metropolitan area during the pandemic’s second wave as a facility of Humanitas Clinical and Research Center (HCRC). The present study aimed to assess whether the implementation of EH19 was effective in improving the quality of care of COVID-19 patients during the second wave compared with the first one. The demographics, mortality rate, and in-hospital length of stay (LOS) of two groups of patients were compared: the study group involved patients admitted at HCRC and managed in EH19 during the second pandemic wave, while the control group included patients managed exclusively at HCRC throughout the first wave. The study and control group included 903 (56.7%) and 690 (43.3%) patients, respectively. The study group was six years older on average and had more pre-existing comorbidities. EH19 was associated with a decrease in the intensive care unit admission rate (16.9% vs. 8.75%, p < 0.001), and an equal decrease in invasive oxygen therapy (3.8% vs. 0.23%, p < 0.001). Crude mortality was similar but overlap propensity score weighting revealed a trend toward a potential small decrease. The adjusted difference in LOS was not significant. The implementation of an additional COVID-19 hospital facility was effective in improving the overall quality of care of COVID-19 patients during the first wave of the pandemic when compared with the second. Further studies are necessary to validate the suggested approach.

Evidence suggests that physical exercise has effects on neuronal plasticity as well as overall brain health. This effect has been linked to exercise capacity in modulating the antioxidant status, when the oxidative stress is usually linked to the neuronal damage. Although high-intensity interval training (HIIT) is the training-trend worldwide, its effect on brain function is still unclear. Thus, we aimed to assess the neuroplasticity, mitochondrial, and redox status after one-week HIIT training. Male (C57Bl/6) mice were assigned to non-trained or HIIT groups. The HIIT protocol consisted of three days with short bouts at 130% of maximum speed (Vmax), intercalated with moderate-intensity continuous exercise sessions of 30 min at 60% Vmax. The mass spectrometry analyses showed that one-week of HIIT increased minichromosome maintenance complex component 2 (MCM2), brain derived neutrophic factor (BDNF), doublecortin (DCX) and voltage-dependent anion-selective channel protein 2 (VDAC), and decreased mitochondrial superoxide dismutase 2 (SOD 2) in the hippocampus. In addition, one-week of HIIT promoted no changes in H2O2 production and carbonylated protein concentration in the hippocampus as well as in superoxide anion production in the dentate gyrus. In conclusion, our one-week HIIT protocol increased neuroplasticity and mitochondrial content regardless of changes in redox status, adding new insights into the neuronal modulation induced by new training models.

Triple-negative breast cancer (TNBC) stands out for its aggressiveness and accelerated rate of proliferation. Evidence shows that exercise may exert antitumorigenic effects, but the biochemical mechanisms underlying them remain unclear. Our objective was to evaluate the ability of exercise to modulate tumor growth and energy metabolism in an experimental TNBC model. Female BALB/c mice were sedentary or trained for 12 weeks and inoculated with 1 × 104 4T1 cells in the eighth week. Analyzes of macronutrient oxidation, mitochondrial respiration, and expression of genes related to cell metabolism were performed. The results showed that the trained group had a smaller tumor mass and the mitochondria in the tumors presented lower respiratory rates in the state of maximum electron transport capacity. Additionally, the tumors of the exercised group showed a higher expression of genes related to tumor suppressors, while the genes linked with cellular growth were similar between groups. Furthermore, the training modulated the corporal macronutrient oxidation to almost exclusive carbohydrate oxidation, while the sedentary condition metabolized both carbohydrate and lipids. Therefore, the exercise reduced tumor growth, with an impact on mitochondrial and macronutrient metabolism. Our results shed light on the understanding of the antitumorigenic effects of physical exercise, particularly regarding the metabolic transformations in TNBC.

Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3–[OCH2CH2]n–) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.

Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol)-350 (mPEG-350) or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport.

Obesity and related comorbidities are a major health concern. The drugs used to treat these conditions are largely inadequate or dangerous, and a well-researched approach based on nutraceuticals would be highly useful. Pterostilbene (Pt), i.e., 3,5-dimethylresveratrol, has been reported to be effective in animal models of obesity, acting on different metabolic pathways. We investigate here its ability to induce browning of white adipose tissue. Pt (5 µM) was first tested on 3T3-L1 mature adipocytes, and then it was administered (352 µmol/kg/day) to mice fed an obesogenic high-fat diet (HFD) for 30 weeks, starting at weaning. In the cultured adipocytes, the treatment elicited a significant increase of the levels of Uncoupling Protein 1 (UCP1) protein—a key component of thermogenic, energy-dissipating beige/brown adipocytes. In vivo administration antagonized weight increase, more so in males than in females. Analysis of inguinal White Adipose Tissue (WAT) revealed a trend towards browning, with significantly increased transcription of several marker genes (Cidea, Ebf2, Pgc1α, PPARγ, Sirt1, and Tbx1) and an increase in UCP1 protein levels, which, however, did not achieve significance. Given the lack of known side effects of Pt, this study strengthens the candidacy of this natural phenol as an anti-obesity nutraceutical.

In Bitcoin, if a miner is able to solve a computationally hard problem called proof of work, it will receive an amount of bitcoin as a reward which is the sum of the fees for the transactions included in a block plus an amount inversely proportional to the number of blocks discovered so far. At the moment of writing, the block reward is several orders of magnitude greater than the sum of transaction fees. Usually, miners try to collect the largest reward by including transactions associated with high fees. The main purpose of transaction fees is to prevent network spamming. However, they are also used to prioritize transactions. In order to use the minimum amount of fees, users usually have to find a compromise between fees and urgency of a transaction. In this paper, we develop a probabilistic logic model to experimentally analyze how fees affect confirmation time and miner’s revenue and to predict if an increase of average fees will generate a situation when the miner gets more reward by not following the protocol.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrinoless double beta decay that has been able to reach the 1-ton scale. The detector consists of an array of 988 TeO 2 crystals arranged in a cylindrical compact structure of 19 towers, each of them made of 52 crystals. The construction of the experiment was completed in August 2016 and the data taking started in spring 2017 after a period of commissioning and tests. In this work we present the neutrinoless double beta decay results of CUORE from examining a total TeO 2 exposure of 86.3 kg yr , characterized by an effective energy resolution of 7.7 keV FWHM and a background in the region of interest of 0.014 counts / ( keV kg yr ) . In this physics run, CUORE placed a lower limit on the decay half-life of neutrinoless double beta decay of 130 Te > 1.3 · 10 25 yr (90% C.L.). Moreover, an analysis of the background of the experiment is presented as well as the measurement of the 130 Te 2 ν β β decay with a resulting half-life of T 1 / 2 2 ν = [ 7.9 ± 0.1 ( stat . ) ± 0.2 ( syst . ) ] × 10 20 yr which is the most precise measurement of the half-life and compatible with previous results.

CUPID-0 is the first large array of scintillating Zn 82 Se cryogenic calorimeters (bolometers) implementing particle identification for the search of the neutrinoless double beta decay (0 ν β β ). The detector consists of 24 enriched Zn 82 Se bolometers for a total 82 Se mass of 5.28 kg and it has been taking data in the underground LNGS (Italy) since March 2017. In this article we show how the dual read-out provides a powerful tool for the α particles rejection. The simultaneous use of the heat and light information allows us to reduce the background down to (3.2 − 1.1 + 1.3 )×10 − 3 counts/(keV kg year), an unprecedented level for cryogenic calorimeters. In a total exposure of 5.46 kg year Zn 82 Se we set the most stringent limit on the 0 ν β β decay 82 Se half-life T 1 / 2 0 ν > 4.0 × 10 24 year at 90% C.I.