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Abstract Background to analyze, at one year, the efficacy and safety of treat-and-extend (T&E) intravitreal (IV) Brolucizumab in patients affected by macular neovascularization (MNV). Both naïve and previously treated (i.e., switched) patients were included, and the data from the two groups were compared. Methods anatomical (i.e., central subfoveal thickness, CST; presence of fluid), functional (i.e., best corrected visual acuity, BCVA) and treatment-related (i.e., number of IV injections within the study period; number of patients reaching a 12-weeks interval between treatments) data from 41 eyes of 41 subjects (20 naïve and 21 switched) were analyzed. Patients were treated with 3 monthly IV injections followed by a T&E regimen based on a disease activity assessment performed at each scheduled IV treatment. Results significant CST reduction (from 412.1 ± 115.8 to 273.2 ± 61.6; p

Abstract Male infertility is a complex issue influenced by multiple environmental and pathological factors. In this context, the impact of Human papillomavirus (HPV) infection on male fertility remains controversial. The introduction of new WHO 2021 evaluation criteria, included in the 6th ed. of Laboratory Manual for the examination and processing of human semen, i.e. DNA fragmentation index (DFI), slow and rapid progressive motility, could provide additional information about this correlation. 121 semen samples of male partners of HPV-positive women attending In Vitro Fertilization (IVF) were evaluated following WHO 2021 and HPV-DNA test. Comparing HPV-negative and positive samples for rapid and slow progressive motility showed significantly different results (p = 0.0018, p = 0.0004), contrary to what was observed for total progressive motility. Regarding sperm DFI, only high-risk HPV infections affected DNA integrity. In addition, the correlation between the different semen parameters revealed a significant correlation between midpiece morphological defects and rapid progressive motility in the HPV-positive group (rho = 0.43, p = 0.0006). In conclusion, WHO 2021 provides additional information regarding HPV’s impact on seminal parameters. The correlation between HPV positivity, midpiece defects and a higher rapid progressive motility opens new research perspectives that may help unravel the issues surrounding the role of HPV in compromising sperm quality.

Abstract Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen. The asthenozoospermic samples were irradiated with an 810 nm diode laser, in continuous wave mode, at 0.25 W, 0.5 W, 1 W and 2 W for 60 s on a circular area of 1 cm2 through a novel handpiece with an innovative flat-top profile. Sperm motility was assessed immediately, after 30 and 60 min. A sample size calculator, unpaired t-test and one-way ANOVA with post-hoc Tukey HSD tests were used for statistics. One and 2 W were the most effective outputs in increasing progressive motility compared to control (p

Abstract Background To assess the reliability and comprehensibility of breast radiology reports simplified by artificial intelligence using the large language model (LLM) ChatGPT-4o. Methods A radiologist with 20 years’ experience selected 21 anonymized breast radiology reports, 7 mammography, 7 breast ultrasound, and 7 breast magnetic resonance imaging (MRI), categorized according to breast imaging reporting and data system (BI-RADS). These reports underwent simplification by prompting ChatGPT-4o with “Explain this medical report to a patient using simple language”. Five breast radiologists assessed the quality of these simplified reports for factual accuracy, completeness, and potential harm with a 5-point Likert scale from 1 (strongly agree) to 5 (strongly disagree). Another breast radiologist evaluated the text comprehension of five non-healthcare personnel readers using a 5-point Likert scale from 1 (excellent) to 5 (poor). Descriptive statistics, Cronbach’s α, and the Kruskal–Wallis test were used. Results Mammography, ultrasound, and MRI showed high factual accuracy (median 2) and completeness (median 2) across radiologists, with low potential harm scores (median 5); no significant group differences (p ≥ 0.780), and high internal consistency (α > 0.80) were observed. Non-healthcare readers showed high comprehension (median 2 for mammography and MRI and 1 for ultrasound); no significant group differences across modalities (p = 0.368), and high internal consistency (α > 0.85) were observed. BI-RADS 0, 1, and 2 reports were accurately explained, while BI-RADS 3–6 reports were challenging. Conclusion The model demonstrated reliability and clarity, offering promise for patients with diverse backgrounds. LLMs like ChatGPT-4o could simplify breast radiology reports, aid in communication, and enhance patient care. Relevance statement Simplified breast radiology reports generated by ChatGPT-4o show potential in enhancing communication with patients, improving comprehension across varying educational backgrounds, and contributing to patient-centered care in radiology practice. Key Points AI simplifies complex breast imaging reports, enhancing patient understanding. Simplified reports from AI maintain accuracy, improving patient comprehension significantly. Implementing AI reports enhances patient engagement and communication in breast imaging. Graphical Abstract

Abstract Background Research and monitoring of human resources available for vision rehabilitation services has been a neglected area of work in the past. This study aims to offer an overview of the vision rehabilitation workforce available in Italy, in order to profile the distribution and number of human resources for vision rehabilitation. Methods Data on the available vision rehabilitation professionals were collected from the yearly report on the state of implementation of policies relating to the prevention of blindness, education and vision rehabilitation, according to a law which was passed by the Italian Ministry of Health, Department of Health Prevention. The report presents a review of all professional workers dealing with low vision rehabilitation centers in Italy between January 2005 and December 2019. Data on the distribution and type of services of government-supported low vision centers across the country were also obtained and examined. Results Of the 289 low vision rehabilitation workers in 2019, 28% were ophthalmologists, 31% orthoptists, 19% psychologists, 17% nurses and 5% social workers. The health workforce densities across the Italian regions ranged from 1.62 to 0.12 per 100.000. The density of vision rehabilitation workers showed a no growing trend from 2006 to 2015. During the study period, it was found a weak but statistically significant association of workforce density with the number of government-supported low vision centers across the Italian territory (r2 = 0.3, p

Abstract We report a determination of the CKM angle ϕ 3, also known as γ, from a combination of measurements using samples of up to 711 fb −1 from the Belle experiment and up to 362 fb −1 from the Belle II experiment. We combine results from analyses of B + → DK +, B + → Dπ +, and B + → D * K + decays, where D is an admixture of D 0 and D ¯ 0 $$ {\overline{D}}^0 $$ mesons, in a likelihood fit to obtain ϕ 3 = (75.2 ± 7.6) ° . We also briefly discuss the interpretation of this result.

Abstract Background This pilot prospective study aimed to evaluate ultrasound-guided cryoablation of breast cancer (BC) by assessing: (i) technical efficacy as the presence of necrosis in surgical specimens and rate of complete tumor ablation; (ii) safety as incidence and severity of complications; and (iii) patients’ satisfaction using a dedicated questionnaire. In addition, (iv) we tested the capability of magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM) to predict cryoablation efficacy. Methods From 07/2022 to 01/2023, we enrolled 20 patients with early-stage BC scheduled for breast surgery. Ten of them, with a cryo-feasible cancer location, were sent to cryoablation (cryo-group) and ten to routine surgical practice (control group). Both groups underwent surgery and were asked to answer a satisfaction questionnaire. Results Of eleven patients screened for cryoablation, only one refused to be treated at another hospital (acceptance rate 10/11, 91%). Surgery was quadrantectomy in 19 cases and mastectomy in 1. In the cryo-group, the procedure was completed and steatonecrosis was observed in 10/10 cases, with complete tumor ablation in nine of them. The post-procedural status was evaluated with MRI in five patients, with CEM in four patients, and with ultrasound in one patient who refused MRI and CEM. MRI or CEM correctly predicted complete cryoablation in eight patients and incomplete cryoablation in one patient. Patients in both groups did not have serious complications and responded positively to satisfaction questionnaires. Conclusion Ultrasound-guided cryoablation of early-stage BC is well accepted by patients, effective, and safe. MRI and CEM were able to predict the procedure's technical efficacy. Trial registration https://clinicaltrials.gov/study/NCT05727813 updated February 14, 2023. Relevance statement Our pilot study showed that ultrasound-guided cryoablation is a promising nonsurgical alternative for treating early-stage BC. Key Points Ultrasound-guided cryoablation was effective and safe in early BC patients. The procedure was well-tolerated, with low morbidity and high patient satisfaction. MRI and CEM predicted cryoablation efficacy, in accordance with histopathologic findings. Cryoablation can be considered a potential alternative to surgery in selected patients. Graphical Abstract

Abstract The concept of love of life, which refers to a positive attitude towards one's own life, care for it and attachment to it, has recently captured the attention of researchers in the field of positive psychology. Despite its growing importance, there is a lack of research investigating the underlying mechanisms through which love of life impacts the flourishing and well-being of individuals. For the first time, the present study examined the mediating roles of optimism and hope in the association between love of life and flourishing in Turkish youth. The study comprised 374 young adults, aged between 18 and 24 years (55.3% female; Mean age = 20.94; SD = 1.78 years), who participated in an online survey assessing their levels of love of life, optimism, hope, and flourishing. Results from the mediation analysis revealed that love of life significantly predicted optimism, hope, and flourishing. Furthermore, optimism and hope had significant predictive effects on flourishing. Importantly, optimism and hope played a partial mediating role in explaining the positive influence of the love of life on individuals' flourishing. The findings suggest a positive association between love of life and heightened levels of optimism and hope. These psychological attributes, in turn, emerge as crucial factors contributing to increased flourishing. These results hold significant implications for the development of interventions focused on understanding how to foster the love of life and flourish through the cultivation of psychological strengths.

In this paper, the new dynamic geophysical and geochemical MUltiparametric DAtabase (MUDA) is presented. MUDA is a new infrastructure of the National Institute of Geophysics and Volcanology (INGV), published online in December 2023, with the aim of archiving and disseminating multiparametric data collected by multidisciplinary monitoring networks. MUDA is a MySQL relational database with a web interface developed in PHP, aimed at investigating possible correlations between seismic phenomena and variations in endogenous and environmental parameters in quasi real time. At present, MUDA collects data from different types of sensors such as hydrogeochemical probes for physical–chemical parameters in waters, meteorological stations, detectors of air radon concentration, diffusive flux of carbon dioxide (CO2) and seismometers belonging both to the National Seismic Network of INGV and to temporary networks installed in the framework of multidisciplinary research projects. MUDA publishes data daily, updated to the previous day, and offers the chance to view and download multiparametric time series selected for different time periods. The resultant dataset provides broad perspectives in the framework of future high-frequency and continuous multiparametric monitoring as a starting point to identify possible seismic precursors for short-term earthquake forecasting. MUDA can be accessed at https://doi.org/10.13127/muda (Massa et al., 2023).

Evelyn J Rizzo,1 Peter J Mallow,2 Aidan Jeffrey Noble,3 Kevin Foster4 1Mobility HEOR, Akron, OH, USA; 2Department of Health Services Administration, Xavier University, Cincinnati, OH, USA; 3The Ohio State University, Columbus, OH, USA; 4Arizona Burn Center, Valleywise Health, Phoenix, AZ, USACorrespondence: Evelyn J Rizzo, Email evelyn@mobilityheor.comAbstract: Over 40,000 patients in the United States (US) require hospitalization for burns annually. The treatment regimen can cost more than $6,000 a day and requires the use of numerous supplies to ensure the graft takes for successful wound healing. Irrigation of the wound is a critical step for burn treatment, yet little is known about the cost-effectiveness of different irrigation modalities. In a recent study, pure hypochlorous acid preserved wound cleanser (pHA) was shown to be safe and effective compared to mafenide. This study estimated the associated costs of two common wound irrigation modalities, pHA and mafenide solution, for the treatment of patients with burns. In this study, a patient-level Monte Carlo simulation model using data from a randomized control trial (RCT) was used to conduct the cost analysis from the US Hospital perspective. Based upon 100,000 simulated patients, pHA was expected to save $133 ($123 to $144, 10th to 90th percentile) for the hospital compared to using a mafenide solution over 14 days. Adoption of pHA should be considered a cost-saving strategy when treating patients with burns.Keywords: wound care, burn irrigation, economic evaluation

Abstract We present a study of Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ , Ξ c 0 → Ξ 0 η $$ {\Xi}_c^0\to {\Xi}^0\eta $$ , and Ξ c 0 → Ξ 0 η ′ $$ {\Xi}_c^0\to {\Xi}^0{\eta}^{\prime } $$ decays using the Belle and Belle II data samples, which have integrated luminosities of 980 fb −1 and 426 fb −1, respectively. We measure the following relative branching fractions B Ξ c 0 → Ξ 0 π 0 / B Ξ c 0 → Ξ − π + = 0.48 ± 0.02 stat ± 0.03 syst , B Ξ c 0 → Ξ 0 η / B Ξ c 0 → Ξ − π + = 0.11 ± 0.01 stat ± 0.01 syst , B Ξ c 0 → Ξ 0 η ′ / B Ξ c 0 → Ξ − π + = 0.08 ± 0.02 stat ± 0.01 syst $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.48\pm 0.02\left(\textrm{stat}\right)\pm 0.03\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.11\pm 0.01\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.08\pm 0.02\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right)\end{array}} $$ for the first time, where the uncertainties are statistical (stat) and systematic (syst). By multiplying by the branching fraction of the normalization mode, B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ , we obtain the following absolute branching fraction results B Ξ c 0 → Ξ 0 π 0 = 6.9 ± 0.3 stat ± 0.5 syst ± 1.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η = 1.6 ± 0.2 stat ± 0.2 syst ± 0.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η ′ = 1.2 ± 0.3 stat ± 0.1 syst ± 0.2 norm × 10 − 3 , $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=\left(6.9\pm 0.3\left(\textrm{stat}\right)\pm 0.5\left(\textrm{syst}\right)\pm 1.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)=\left(1.6\pm 0.2\left(\textrm{stat}\right)\pm 0.2\left(\textrm{syst}\right)\pm 0.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\varXi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)=\left(1.2\pm 0.3\left(\textrm{stat}\right)\pm 0.1\left(\textrm{syst}\right)\pm 0.2\left(\operatorname{norm}\right)\right)\times {10}^{-3},\end{array}} $$ where the third uncertainties are from B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ . The asymmetry parameter for Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ is measured to be α Ξ c 0 → Ξ 0 π 0 = − 0.90 ± 0.15 stat ± 0.23 syst $$ \alpha \left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=-0.90\pm 0.15\left(\textrm{stat}\right)\pm 0.23\left(\textrm{syst}\right) $$ .

Abstract Extracellular polysaccharides are crucial components for biofilm development. Although Bacillus subtilis is one of the most characterized Gram-positive biofilm model system, the structure-function of its exopolysaccharide, EpsA-O, remains to be elucidated. By combining chemical analysis, NMR spectroscopy, rheology, and molecular modeling, high-resolution data of EpsA-O structure from atom to supramolecular scale was obtained. The repeating unit is composed of the trisaccharide backbone [→3)-β-d-QuipNAc4NAc-(1→3)-β-d-GalpNAc-(1→3)-α-d-GlcpNAc-(1]n, and the side chain β-d-Galp(3,4-S-Pyr)-(1→6)-β-d-Galp(3,4-S-Pyr)-(1→6)-α-d-Galp-(1→ linked to C4 of GalNAc. Close agreement between the primary structure and rheological behavior allowed us to model EpsA-O macromolecular and supramolecular solution structure, which can span the intercellular space forming a gel that leads to a complex 3D biofilm network as corroborated by a mutant strain with impaired ability to produce EpsA-O. This is a comprehensive structure-function investigation of the essential biofilm adhesive exopolysaccharide that will serve as a useful guide for future studies in biofilm architecture formation.

Abstract Introduction Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project’s webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Abstract Defining the molecular mechanisms underlying cardiac resilience is crucial to find effective approaches to protect the heart. A physiologic level of ROS is produced in the heart by fatty acid oxidation, but stressful events can boost ROS and cause mitochondrial dysfunction and cardiac functional impairment. Melusin is a muscle specific chaperone required for myocardial compensatory remodeling during stress. Here we report that Melusin localizes in mitochondria where it binds the mitochondrial trifunctional protein, a key enzyme in fatty acid oxidation, and decreases it activity. Studying both mice and human induced pluripotent stem cell-derived cardiomyocytes, we found that Melusin reduces lipid oxidation in the myocardium and limits ROS generation in steady state and during pressure overload and doxorubicin treatment, preventing mitochondrial dysfunction. Accordingly, the treatment with the lipid oxidation inhibitor Trimetazidine concomitantly with stressful stimuli limits ROS accumulation and prevents long-term heart dysfunction. These findings disclose a physiologic mechanism of metabolic regulation in the heart and demonstrate that a timely restriction of lipid metabolism represents a potential therapeutic strategy to improve cardiac resilience to stress.

Explainable Artificial Intelligence (XAI) is a research area that clarifies AI decision-making processes to build user trust and promote responsible AI. Hence, a key scientific challenge in XAI is the development of methods that generate transparent and interpretable explanations while maintaining scalability and effectiveness in complex scenarios. Rule-based methods in XAI generate rules that can potentially explain AI inferences, yet they can also become convoluted in large scenarios, hindering their readability and scalability. Moreover, they often lack contrastive explanations, leaving users uncertain why specific predictions are preferred. To address this scientific problem, we explore the integration of computational argumentation—a sub-field of AI that models reasoning processes through defeasibility—into rule-based XAI systems. Computational argumentation enables arguments modelled from rules to be retracted based on new evidence. This makes it a promising approach to enhancing rule-based methods for creating more explainable AI systems. Nonetheless, research on their integration remains limited despite the appealing properties of rule-based systems and computational argumentation. Therefore, this study also addresses the applied challenge of implementing such an integration within practical AI tools. The study employs the Logic Learning Machine (LLM), a specific rule-extraction technique, and presents a modular design that integrates input rules into a structured argumentation framework using state-of-the-art computational argumentation methods. Experiments conducted on binary classification problems using various datasets from the UCI Machine Learning Repository demonstrate the effectiveness of this integration. The LLM technique excelled in producing a manageable number of if-then rules with a small number of premises while maintaining high inferential capacity for all datasets. In turn, argument-based models achieved comparable results to those derived directly from if-then rules, leveraging a concise set of rules and excelling in explainability. In summary, this paper introduces a novel approach for efficiently and automatically generating arguments and their interactions from data, addressing both scientific and applied challenges in advancing the application and deployment of argumentation systems in XAI.

Thoracic outlet syndrome (TOS) is a group of symptoms caused by the compression of neurovascular structures of the superior thoracic outlet. The knowledge of its clinical presentation with specific symptoms, as well as proper imaging examinations, ranging from plain radiographs to ultrasound, computed tomography and magnetic resonance imaging, may help achieve a precise diagnosis. Once TOS is recognized, proper treatment may comprise a conservative or a surgical approach.

Gaetana Pezzino,1 Alessia Calabrò,1 Fabiana Drommi,1 Stefania Campana,1 Riccardo Cavaliere,1,2 Irene Bonaccorsi,1 Paolo Carrega,1 Vincenzo Zammuto,3– 5 Maria Giovanna Rizzo,3 Concetta Gugliandolo,3,4 Guido Ferlazzo,6,7 Claudia De Pasquale1 1Laboratory of Immunology and Biotherapy, Department Human Pathology ”G. Barresi”, University of Messina, Messina, Italy; 2Division of Clinical Pathology, University Hospital Policlinico G. Martino, Messina, Italy; 3Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy; 4Research Centre for Extreme Environments and Extremophiles, Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy; 5ATHENA Green Solutions S.r.l., Messina, Italy; 6Department of Experimental Medicine (DIMES), University of Genoa, Genova, Italy; 7Unit of Experimental Pathology and Immunology, IRCCS Ospedale Policlinico San Martino, Genova, ItalyCorrespondence: Guido Ferlazzo, Unit of Experimental Pathology and Immunology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, Email guido.ferlazzo@unige.itBackground: Respiratory viral infections are a leading cause of severe diseases and mortality; therefore, novel treatments effective for their prevention are highly requested. Here, we identified a broad-spectrum antiviral activity of a natural exopolysaccharide, EPS T14, purified from a marine thermotolerant strain of Bacillus licheniformis strain T14.Methods: The effects on human normal nasal epithelial cells (HNEpCs) following treatment with EPS T14 was evaluated at different time points and with increasing concentration of compound. To assess the antiviral properties, viability of HNEpCs treated with EPS T14 was analysed following infection with different respiratory viruses.Results: Neither toxicity nor pro-inflammatory properties were observed in vitro on HNEpCs treated with EPS T14 up to high concentrations, thus ensuring its safety. Cell culture-based assays revealed that treatment of HNEpCs with EPS T14 (used at 400ug/mL) results in efficient prevention of cell infection by different respiratory viruses through physically hindering the entry of the viruses via cell surface receptors. Interestingly, in addition to this prophylactic antiviral activity, EPS T14 also shows a long-lasting efficacy by inhibiting viral spread in the cell culture. Finally, combination of EPS T14 with a hypertonic saline solution shows a synergistic antiviral activity.Conclusion: EPS T14 can exert both prophylactic and therapeutic antiviral activity by blocking viral attachment to cellular receptors and could therefore represent a promising antiviral agent for preventing infections by different respiratory viruses. Keywords: exopolysaccharides, infection prophylaxis, nasal epithelium, respiratory virus, viral infection, EPSs

Abstract We present the result of a search for the charged-lepton-flavor violating decay τ − → μ − μ + μ − using a 424 fb −1 sample of data recorded by the Belle II experiment at the SuperKEKB e + e − collider. The selection of e + e − → τ + τ − events is based on an inclusive reconstruction of the non-signal tau decay, and on a boosted decision tree to suppress background. We observe one signal candidate, which is compatible with the expectation from background processes. We set a 90% confidence level upper limit of 1.9 × 10 −8 on the branching fraction of the τ − → μ − μ + μ − decay, which is the most stringent bound to date.

Abstract The extended depth-of-focus AcrySof IQ Vivity intraocular lens technology offers promising features for presbyopia management, evaluated in this research in a 6 months real-world setting. Prospective interventional mono-centric study including 40 patients who underwent elective bilateral phacoemulsification. We performed one pre-operative visit (V0) and one evaluation six months post-operatively (V1), evaluating uncorrected and corrected visual acuity for near (UNVA/CNVA), intermediate (UIVA/CIVA) and far (UDVA/UCVA), slit-lamp evaluation, tomography with static pupillometry, endothelial cell count and contrast sensitivity chart. In order to assess post-operative Quality of Life, we administered the patients McAlinden’s Quality of Vision test and Morlock’s Patient-Reported Spectacle Independence Questionnaire. We divided eyes in with Toric-IOL and with non-Toric IOL. A total of 36 eyes received non-tonic IOL implantation, whereas 44 eyes received toric IOL implantation. There were no statistically significant disparities observed in visual outcome measures and contrast sensitivity between the toric group and the non-toric group. Furthermore, we assessed the predictive preoperative refractive astigmatism (PPRA) and residual refractive astigmatism (RRA) in both cohorts, and no statistical significance was found between the two cohorts (p = 0.08). Twenty-one (53%) patients reported total independence from their glasses at all distances. The mean difference between the predicted and measured refractive error, as calculated by spherical equivalent, was 0.09 D. AcrySof IQ Vivity is a well-tolerated and effective IOL with optimal refractive target for both distant and intermediate vision, needing slight spherical addition for the best near vision. Great questionnaire-based satisfaction was reported by the patients.

Abstract Background Positional plagiocephaly is an asymmetrical flattened skull deformity whose incidence increased significantly in the last decades. Osteopathic treatment has been suggested to tackle early deformational sequences, in order to ensure the correct development of the child. The aim of the study was to assess the effectiveness of osteopathic treatment of positional cranial deformities in infants. Methods Retrospective observational study carried out at the Section of Neonatology and Neonatal Intensive Care Unit of the Department of Interdisciplinary Medicine of University of Bari, Italy in collaboration with a specialized pediatric osteopath. Results 424 infants were enrolled. Isolated positional plagiocephaly affected the vast majority of infants (n. 390, 91.98%); 34 patients (8.02%) were diagnosed with positional brachycephaly. Both infant groups (positional plagiocephaly and positional brachycephaly) had a median severity score of 3 (IQR: 3 – 3 and 2 – 3, respectively) and benefited from a median of 3 osteopathic sessions (IQR 3–4 and 2–4, respectively). Higher severity scores of positional asymmetries were significantly more common in preterm neonates (Pearson chi2: 11.58; p-value: 0.021) and in males (Pearson chi2: 10.06; p-value: 0.039). Conclusions Significant improvements in positional cranial deformations of children were obtained after only five osteopathic treatments provided in the first months of life. The osteopathic treatment could positively impact the clinical history of patients with positional plagiocephaly and positional brachycephaly. Implication for practice • Positional plagiocephaly is increasingly common among infants and may cause moderate to severe neurodevelopmental adverse effects. • Osteopathic treatment may tackle early deformational sequences, in order to ensure the correct development of the child. • Our study reveals that cranial asymmetry of infants with positional plagiocephaly is significantly reduced after only five osteopathic treatments provided in the first months of life. • Osteopathic treatment should be offered as a first line approach to young infants diagnosed with positional plagiocephaly.

Purpose: To evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). Design: Interventional, open-label study started in January 2021 with follow-up at 12 months (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov NCT04636853). Participants: Thirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. Intervention: All 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-gauge needle. Main Outcomes and Measures: Best-corrected visual acuity (BCVA) with ETDRS letters, central macular thickness using OCT, and atrophic area measured on en face OCT images were assessed at baseline, 1, 3, 6, and 12 months. Results: The BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline, 40.84 ± 20.52 at 1 month, 40.07 ± 20.34 at 3 months, 39.38 ± 19.84 at 6 months, and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline, 51.54 ± 20.99 at 1 month, 46.62 ± 19.47 at 3 months, 46.85 ± 18.58 at 6 months, and 43.92 ± 17.97 at 12 months (2-way analysis of variance: interaction of treatment by eye or time, P = 0.084). Central macular thickness did not show a significant intereye difference at 12 months (P = 0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (P < 0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. Conclusions: Subretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed to understand whether the CB-PRP could have a role in the GA treatment. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance.Research design and methods An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women.Results The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9).Conclusions Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.

ABSTRACTBackground The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines.Research design and methods An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination.Results Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0–8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9–10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains.Conclusions Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

In this paper, the performance of a 5-level cascaded H-bridge inverter in unmanned aerial vehicle (UAV) applications is analized to identify, at the converter design stage, the better device choice depending on different UAV operation scenarios. Considering that regardless of the specific application there are some typical operations, such as take-off, climb, land, cruise, and potential recurring climbs and descents, the results can support the choice by considering the typical working conditions of the specific application where the UAV would be used. The results have been obtained by simulating the H-bridge inverter considering the circuit models of insulated-gate bipolar transistors (IGBTs), GaN high-electron-mobility transistors (HEMTs), and Si and SiC metal-oxide-semiconductor field-effect transistors (MOSFETs) provided by manufacturers. The study has highlighted that the choice of the device depends on the UAV usage, switching frequency, and load conditions. More specifically, considering the typical devices and systems costs in the case of a selective harmonic elimination procedure operating at the fundamental switching frequency, the Si devices should be used. Moreover, the preference for using IGBTs or Si MOSFETs depends on the typical working conditions of the UAV application. In the case of phase-shift carrier modulation technique, at 4 kHz the MOSFET is the best device and the choice between Si and SiC devices depends on the UAV application's main operation scenarios. At 20 kHz the SiC MOSFET is the best device, while at higher frequencies the GaN HEMT cost should be faced to take advantage of its best performance.

Abstract We present a measurement of the ratio R μ = B τ − → μ − ν ¯ μ ν τ / B τ − → e − ν ¯ e ν τ $$ {R}_{\mu }=\mathcal{B}\left({\tau}^{-}\to {\mu}^{-}{\overline{\nu}}_{\mu }{\nu}_{\tau}\right)/\mathcal{B}\left({\tau}^{-}\to {e}^{-}{\overline{\nu}}_e{\nu}_{\tau}\right) $$ of branching fractions B $$ \mathcal{B} $$ of the τ lepton decaying to muons or electrons using data collected with the Belle II detector at the SuperKEKB e + e − collider. The sample has an integrated luminosity of 362 ± 2 fb −1 at a centre-of-mass energy of 10.58 GeV. Using an optimised event selection, a binned maximum likelihood fit is performed using the momentum spectra of the electron and muon candidates. The result, R μ = 0.9675 ± 0.0007 ± 0.0036, where the first uncertainty is statistical and the second is systematic, is the most precise to date. It provides a stringent test of the light-lepton universality, translating to a ratio of the couplings of the muon and electron to the W boson in τ decays of 0.9974 ± 0.0019, in agreement with the standard model expectation of unity.

Abstract We present measurements of the branching fractions of eight B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ , B − → D (*)0 K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ decay channels. The results are based on data from SuperKEKB electron-positron collisions at the Υ(4S) resonance collected with the Belle II detector, corresponding to an integrated luminosity of 362 fb −1. The event yields are extracted from fits to the distributions of the difference between expected and observed B meson energy, and are efficiency-corrected as a function of m(K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) and m(D (*) K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) in order to avoid dependence on the decay model. These results include the first observation of B ¯ 0 $$ {\overline{B}}^0 $$ → D + K − K S 0 $$ {K}_S^0 $$ , B − → D* 0 K − K S 0 $$ {K}_S^0 $$ , and B ¯ 0 $$ {\overline{B}}^0 $$ → D* + K − K S 0 $$ {K}_S^0 $$ decays and a significant improvement in the precision of the other channels compared to previous measurements. The helicity-angle distributions and the invariant mass distributions of the K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ systems are compatible with quasi-two-body decays via a resonant transition with spin-parity J P = 1− for the K − K S 0 $$ {K}_S^0 $$ systems and J P = 1+ for the K − K* 0 systems. We also present measurements of the branching fractions of four B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ D s − $$ {D}_s^{-} $$ , B − → D (*)0 D s − $$ {D}_s^{-} $$ decay channels with a precision compatible to the current world averages.

Abstract The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p

This study investigates the rain-initiated mixing and variability in the mixing ratio of selected trace gases in the atmosphere over the central Amazon rain forest. It builds on comprehensive data from the Amazon Tall Tower Observatory (ATTO), spanning from 2013 to 2020 and comprising the greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4); the reactive trace gases carbon monoxide (CO), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2); and selected volatile organic compounds (VOCs). Based on more than 1000 analyzed rainfall events, the study resolves the trace gas mixing ratio patterns before, during, and after the rain events, along with vertical mixing ratio gradients across the forest canopy. The assessment of the rainfall events was conducted independently for daytime and nighttime periods, which allows us to elucidate the influence of solar radiation. The mixing ratios of CO2, CO, and CH4 clearly declined during rainfall, which can be attributed to the downdraft-related entrainment of pristine air from higher altitudes into the boundary layer, a reduction of the photosynthetic activity under increased cloud cover, and changes in the surface fluxes. Notably, CO showed a faster reduction than CO2, and the vertical gradient of CO2 and CO is steeper than for CH4. Conversely, the O3 mixing ratio increased across all measurement heights in the course of the rain-related downdrafts. Following the O3 enhancement by up to a factor of 2, NO, NO2, and isoprene mixing ratios decreased. The temporal and vertical variability of the trace gases is intricately linked to the diverse sink and source processes, surface fluxes, and free-troposphere transport. Within the canopy, several interactions unfold among soil, atmosphere, and plants, shaping the overall dynamics. Also, the mixing ratio of biogenic VOCs (BVOCs) clearly varied with rainfall, driven by factors such as light, temperature, physical transport, and soil processes. Our results disentangle the patterns in the trace gas mixing ratio in the course of sudden and vigorous atmospheric mixing during rainfall events. By selectively uncovering processes that are not clearly detectable under undisturbed conditions, our results contribute to a better understanding of the trace gas life cycle and its interplay with meteorology, cloud dynamics, and rainfall in the Amazon.

Abstract Identifying master epigenetic factors controlling proliferation and survival of cancer cells allows to discover new molecular targets exploitable to overcome resistance to current pharmacological regimens. In breast cancer (BC), resistance to endocrine therapy (ET) arises from aberrant Estrogen Receptor alpha (ERα) signaling caused by genetic and epigenetic events still mainly unknown. Targeting key upstream components of the ERα pathway provides a way to interfere with estrogen signaling in cancer cells independently from any other downstream event. By combining computational analysis of genome-wide ‘drop-out’ screenings with siRNA-mediated gene knock-down (kd), we identified a set of essential genes in luminal-like, ERα + BC that includes BRPF1, encoding a bromodomain-containing protein belonging to a family of epigenetic readers that act as chromatin remodelers to control gene transcription. To gather mechanistic insights into the role of BRPF1 in BC and ERα signaling, we applied chromatin and transcriptome profiling, gene ablation and targeted pharmacological inhibition coupled to cellular and functional assays. Results indicate that BRPF1 associates with ERα onto BC cell chromatin and its blockade inhibits cell cycle progression, reduces cell proliferation and mediates transcriptome changes through the modulation of chromatin accessibility. This effect is elicited by a widespread inhibition of estrogen signaling, consequent to ERα gene silencing, in antiestrogen (AE) -sensitive and -resistant BC cells and pre-clinical patient-derived models (PDOs). Characterization of the functional interplay of BRPF1 with ERα reveals a new regulator of estrogen-responsive BC cell survival and suggests that this epigenetic factor is a potential new target for treatment of these tumors.

Abstract Purpose Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement. Methods This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected. Results Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p

The wet-season atmosphere in the central Amazon resembles natural conditions with minimal anthropogenic influence, making it one of the rare preindustrial-like continental areas worldwide. Previous long-term studies have analyzed the properties and sources of the natural Amazonian background aerosol. However, the vertical profile of the planetary boundary layer (PBL) has not been assessed systematically. Since 2017, such a profile assessment has been possible with the 325 m high tower at the Amazon Tall Tower Observatory (ATTO), located in a largely untouched primary forest in the central Amazon. This study investigates the variability of submicrometer aerosol concentration, size distribution, and optical properties at 60 and 325 m in the Amazonian PBL. The results show significant differences in aerosol volumes and scattering coefficients in the vertical gradient. The aerosol population was well-mixed throughout the boundary layer during the daytime but became separated upon stratification during the nighttime. We also found a significant difference in the spectral dependence of the scattering coefficients between the two heights. The analysis of downdrafts and the related rainfall revealed changes in the aerosol populations before and after rain events, with absorption and scattering coefficients decreasing as optically active particles are removed by wet deposition. The recovery of absorption and scattering coefficients is faster at 325 m than at 60 m. Convective events were concomitant with rapid increases in the concentrations of sub-50 nm particles, which were likely associated with downdrafts. We found that the aerosol population near the canopy had a significantly higher mass scattering efficiency than at 325 m. There was also a clear spectral dependence, with values for λ=450, 525, and 635 nm of 7.74±0.12, 5.49±0.11, and 4.15±0.11 m2 g−1, respectively, at 60 m, while at 325 m the values were 5.26±0.06, 3.76±0.05, and 2.46±0.04 m2 g−1, respectively. The equivalent aerosol refractive index results, which were obtained for the first time for the wet season in the central Amazon, show slightly higher scattering (real) components at 60 m compared to 325 m of 1.33 and 1.27, respectively. In contrast, the refractive index's absorptive (imaginary) component was identical for both heights, at 0.006. This study shows that the aerosol physical properties at 60 and 325 m are different, likely due to aging processes, and strongly depend on the photochemistry, PBL dynamics, and aerosol sources. These findings provide valuable insights into the impact of aerosols on climate and radiative balance and can be used to improve the representation of aerosols in global climate models.

Dimitrios Patoulias,1,2 Theocharis Koufakis,2 Ieva Ru&zcaron;a,3 Mohamed El-Tanani,4 Manfredi Rizzo5 1Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, General Hospital “hippokration”, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Second Propedeutic Department of Internal Medicine, General Hospital “Hippokration”, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Endocrinology, Riga Eastern Clinical University Hospital, Riga Eastern Clinical University, Riga, Latvia; 4Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah, United Arab Emirates; 5Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Palermo, ItalyCorrespondence: Dimitrios Patoulias, Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, General Hospital “Hippokration”, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki, 54642, Greece, Email dipatoulias@gmail.com; patoulias@auth.grAbstract: Obesity is currently considered a global epidemic, with rising prevalence worldwide and rather pessimistic projections. Based on its close interconnection with various co-morbidities, such as diabetes mellitus and cardiovascular disease, obesity is associated with significant increases in morbidity and mortality, while it also poses a substantial economic burden for national healthcare systems. Apparently, the majority of individuals classified as obese do not achieve adequate weight loss with the adoption of a healthy lifestyle intervention, including dietary modification and physical activity. Fortunately, during the last decade, a significant progress in pharmacotherapy of obesity has been observed, with the introduction of agents that have gained approval from regulatory authorities, namely semaglutide, liraglutide and tirzepatide, due to their impressive results in body weight reduction, alongside their beneficial, pleiotropic effects. The aim of the present review article is to discuss on evidence retrieved from real-world studies regarding the efficacy of those agents in obesity treatment, with emphasis on cost-effectiveness data, towards an effort to tackle efficiently the progression of obesity epidemic.Keywords: obesity, body weight, semaglutide, liraglutide, tirzepatide, cost-effectiveness

Abstract Surface display of functional groups with specific reactivity around living cells is an emerging, low cost and highly eco-compatible technology that serves multiple applications, ranging from basic biochemical studies to biomedicine, therapeutics and environmental sciences. Conversely to classical methods exploiting hazardous organic synthesis of precursors or monovalent functionalization via genetics, here we perform functional decoration of individual living microalgae using suitable biocoatings based on polydopamine, a melanin-like synthetic polymer. Here we demonstrate the one-pot synthesis of a functional polydopamine bearing phenylboronic units which can decorate the living cell surfaces via a direct ester formation between boronic units and surface glycoproteins. Furthermore, biosorption of fluorescent sugars on functionalized cell membranes is triggered, demonstrating that these organic coatings act as biocompatible soft shells, still functional and reactive after cell engineering.

Background: Shoulder arthroplasty (SA) has been shown to improve quality of life, though outcomes may vary between individuals. Multiple factors may affect outcomes, including preoperative mental health conditions (MHCs). The goal of this systematic review was to evaluate the clinical and functional outcomes after SA in patients with MHC compared to patients without MHC. Methods: This systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines outlined by Cochrane Collaboration. A search of PubMed, the Medline Library, and EMBASE was conducted from inception until September 2023 to obtain studies reporting outcomes after total shoulder arthroplasty and reverse total shoulder arthroplasty in patients with and without MHC. Study characteristics and information on clinical and functional outcomes were collected. All included studies were case-control studies. The methodological quality of the included primary studies was appraised using the methodological index for nonrandomized studies scoring. Results: Eleven articles published between 2016 and 2023 met inclusion criteria. In total, 49,187 patients, 49,289 shoulders, and five different MHC were included. 8134 patients in the cohort had a diagnosed MHC. The mean patient age was 67.8 years (range, 63.5-71.6 years), and 52.6% of the patients were female. The mean follow-up time was 35.5 months (range, 16.2-58.3 months). Reverse total shoulder arthroplasty was the most common type of procedure (25,543 shoulders, 51.8%). Depression and anxiety were the most reported psychiatric diagnoses (7990 patients, 98.2%). Patients with versus without MHC reported mean improvements of 38 and 42 in American Shoulder and Elbow Surgeons shoulder score and mean Visual Analog Scale pain improvements of 4.7 and 4.9, respectively. Mean complication rates of 31.4% and 14.2% were observed in patients with versus without MHC, respectively. The most prevalent surgical complication in patients with MHC was infection (1.8%), followed by prosthetic complication (1.7%), and adhesive capsulitis (1.6%). Conclusions: Patients with MHC may have lower preoperative range of motion, worse postoperative shoulder function, and higher postoperative pain levels than patients without MHC. Patients with MHC demonstrated improvements in range of motion and functional outcomes after SA but had higher reported complication and revision rates when compared to patients without MHC. Depression and anxiety were the leading conditions correlated with lower outcomes in patients with MHC after SA. Preoperative physical therapy, mental health counseling, and expectation setting may help these patients reach the maximal achievable benefit from SA.

Abstract We present an analysis of the process e + e − → π + π − Υ(nS) (where n = 1, 2, or 3) reconstructed in 19.6 fb −1 of Belle II data during a special run of the SuperKEKB collider at four energy points near the peak of the Υ(10753) resonance. By analyzing the mass distribution of the π + π − Υ(nS) system and the Born cross sections of the e + e − → π + π − Υ(nS) process, we report the first observation of Υ(10753) decays to the π + π − Υ(1S) and π + π − Υ(2S) final states, and find no evidence for decays to π + π − Υ(3S). Possible intermediate states in the π + π − Υ(1S, 2S) transitions are also investigated, and no evidence for decays proceeding via the π ∓ Z b ± $$ {\pi}^{\mp }{Z}_b^{\pm } $$ or f 0(980)Υ(nS) intermediate states is found. We measure Born cross sections for the e + e − → π + π − Υ(nS) process that, combined with results from Belle, obtain the mass and width of Υ(10753) to be (10756.6 ± 2.7 ± 0.9) MeV/c 2 and (29.0 ± 8.8 ± 1.2) MeV, respectively. The relative ratios of the Born cross sections at the Υ(10753) resonance peak are also reported for the first time.

Abstract The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p

The Visceral Sensitivity Index (VSI) represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with irritable bowel syndrome (IBS) and chronic inflammatory bowel diseases (IBD)—such as ulcerative colitis and Crohn’s disease. However, an Italian version of the instrument is not yet available for the Italian-speaking population. This study utilized a national sample of 500 individuals divided into four groups: (a) patients with Crohn’s disease, (b) patients with ulcerative colitis, (c) patients with IBS, and (d) healthy controls (individuals without any diagnoses) to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, this research applied a questionnaire and the VSI through an online format to 500 participants. Confirmatory Factor Analysis (CFA) revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach’s α = 0.949) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with interoceptive awareness, type of disease, and gastrointestinal symptom severity, confirming its role in enhancing the understanding and management of IBD and IBS in Italy.

Abstract A product class characterization was requested on some plastic granular waste samples, already reduced in fine form with particles

Abstract Small non-coding RNAs (sncRNAs) make up ~1% of the transcriptome; nevertheless, they play significant roles in regulating cellular processes. Given the complexity of the central nervous system, sncRNAs likely hold particular importance in the human brain. In this study, we provide sncRNA transcriptomic profiles in a range of adult and prenatal brain regions, with a focus on piRNAs, due to their underexplored expression in somatic cells and tissue-specific nature. Using the WIND workflow, which combines two detection methods, we found 1333 (731 miRNAs, 249 piRNAs, 285 snoRNAs, and 68 other sncRNAs) and 1445 unique sncRNAs (770 miRNAs, 307 piRNAs, 289 snoRNAs, and 79 other sncRNAs) in developing and adult brains, respectively. Significant variations were found upon comparison of fetal and adult brain groups, with 82 miRNAs, 17 piRNAs, and 70 snoRNAs enriched in fetal brains and 22 miRNAs, 11 piRNAs in adult brains. This dataset represents a valuable resource for exploring the sncRNA roles in brain function, their involvement in neurological diseases, and the molecular mechanisms behind brain region interactions.

Abstract Background Effective pain management during labor induction for pregnancy termination is essential. However, to date, no effective treatment has been identified. The primary aim of this study was to measure the analgesic efficacy of a sufentanil sublingual tablet system during pregnancy termination and patient satisfaction by comparing nulliparous and multiparous women. The secondary aims were to characterize the safety profile by reporting any side effects or adverse events and to determine the need for rescue therapy. Methods We conducted an observational, retrospective, single-center study involving 48 women. The data retrieved for analysis included the total and hourly doses of sublingual sufentanil, evaluations of pain management satisfaction using a 5-point rating scale (ranging from 1, indicating “not satisfied” to 5, denoting “completely satisfied”), occurrence of side effects and adverse events, and the rate of rescue analgesic use. Categorical and numerical variables were compared between the two groups, and a correlation analysis was performed. Results The median total dose of sufentanil required was 60 mcg. Nulliparous women required a higher dose of sufentanil compared with multiparous women (105 mcg vs. 45 mcg; P = 0.01). Additionally, they underwent a longer labor, indirectly measured by the time of device usage (625 min vs. 165 min; P = 0.05). Regarding satisfaction, 40 patients (83.4%) were satisfied or completely satisfied, whereas only 8 patients (16.6%) reported dissatisfaction. Multiparous women exhibited higher satisfaction levels than did nulliparous women (P = 0.03). No adverse events were reported, and the most common side effects were nausea and vomiting (31.2%). Four patients (12%) required acetaminophen due to insufficient analgesia, with only one patient necessitating a switch to intravenous morphine. Conclusions Sublingual sufentanil was effective in both nulliparous and multiparous women with minimal side effects. Therefore, sublingual sufentanil can be considered a valid strategy for analgesia during labor induction for pregnancy termination.

Abstract Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC leads to mucosal inflammation as well as mucosal atrophy in the rectum and the colon. Innate immunity is considered the first line of defense against microbial invasion; among Toll-like receptors, TLR2 is the most important for defense against mycobacterial infection. TLR2 has been reported to have a lot of functions in infectious diseases and in other pathologies, such as chronic and acute inflammatory diseases. Alfa-Smooth Muscle Actin (α-SMA) is an important biomarker in IBDs. All myofibroblasts express α-SMA, which has been found to be upregulated in CD and UC. Paraformaldehyde-fixed intestinal tissues, from patients with CD and patients with UC, were analyzed by immunostaining for TLR2 and α-SMA. Our results showed that, in the samples obtained from UC patients with inflamed mucosa, TLR2-positive epithelial cells concentrated on the mucosal surface and scattered immune cells in the connective tissue; furthermore, numerous α-SMA-positive cells (subepithelial myofibroblasts) were detected in the lamina propria and around glands, while some myofibroblasts co-localizing with α-SMA and TLR2 could be inflammatory macrophages. In CD patients, TLR2-positive enterocytes and α-SMA-positive myofibroblasts in the lamina propria of the villus have been observed. In control samples, a low positivity to α-SMA and TLR2 was observed in subepithelial myofibroblasts and scattered immune cells of the lamina propria. These data showed the recall of α-SMA-positive myofibroblasts during the inflammatory state; in addition, TLR2 expression has been observed to change in the intestinal epithelium in IBDs, demonstrating that alterations in the innate system response may contribute to the pathogenesis of these diseases.

This review examines the latest advancements in compositional and quantitative cartilage MRI techniques, addressing both their potential and challenges. The integration of these advancements promises to improve disease detection, treatment monitoring, and overall patient care. We want to highlight the pivotal task of translating these techniques into widespread clinical use, the transition of cartilage MRI from technical validation to clinical application, emphasizing its critical role in identifying early signs of degenerative and inflammatory joint diseases. Recognizing these changes early may enable informed treatment decisions, thereby facilitating personalized medicine approaches. The evolving landscape of cartilage MRI underscores its increasing importance in clinical practice, offering valuable insights for patient management and therapeutic interventions. This review aims to discuss the old evidence and new insights about the evaluation of articular cartilage through MRI, with an update on the most recent literature published on novel quantitative sequences.

During the COVID-19 pandemic, young people have become overexposed to social media and online gaming, making them more vulnerable to online violence such as cyberbullying. The aim of this study was to determine whether social media and online gaming pose a risk for cyberbullying through time spent online and whether there is a sex that is more vulnerable to this phenomenon. The survey included a sample of 4338 students (52.4% girls; age range, 11–19 years, M 14.1 SD 1.6) attending lower and upper secondary schools. Multiple moderated mediation regression models by sex were conducted, showing a relationship between social media and online gaming, time spent online outside of school, and cyberbullying. The results show that young girls are at higher risk of cyberbullying via social media, and boys are at higher risk of cybervictimization through online gaming. The findings may encourage other researchers to study the phenomenon, taking into account the role of parents and other educators.

Background: Management of PICC dressing can be performed at home by the patient through adequate training and telenursing. This trial verifies that the incidence of catheter-related complications in home patients, assisted by telenursing, is not greater than that observed in outpatients. Methods: This clinical trial is composed of 72 patients with malignant tumors who underwent long-term chemotherapy with PICC insertion. They were randomly divided into an experimental group (33 cases) and a calibration group (39 cases). The control group received outpatient dressing for the PICC at the hospital, while the experimental group received a telenursing intervention about the management of the PICC. The incidence of catheter-related infections, the ability of self-management, and a rough cost/benefit estimation were compared between the two groups. This trial was performed according to the CONSORT 2010 checklist. Results: The two groups do not significantly differ in relation to age, sex, and PICCs in terms of the body side insertion, the type of dressing, and the agents used for cleaning. The analysis of the results showed that in the home-managed group, the clinical events reported during the connection were higher when compared with the outpatient group (p < 0.001). The patients in the homecare group developed frequent complications resulting from skin redness (p < 0.001). Conclusion: The use of telenursing for patient education in cancer centers can reduce nurses’ working time, improving the self-management capacity of patients with a long-term PICC. This trial was retrospectively registered with the Clinical Trial Gov on the 18 May 2023 with registration number NCT05880420.

Abstract Background Adopting high-value, cost-conscious care (HVCCC) principles into medical education is growing in importance due to soaring global healthcare costs and the recognition that efficient care can enhance patient outcomes and control costs. Understanding the current opportunities and challenges doctors face concerning HVCCC in healthcare systems is crucial to tailor education to doctors’ needs. Hence, this study aimed to explore medical students, junior doctors, and senior doctors’ experiences with HVCCC, and to seek senior doctors’ viewpoints on how education can foster HVCCC in clinical environments. Methods Using a mixed-methods design, our study involved a cross-sectional survey using the Maastricht HVCCC-Attitude Questionnaire (MHAQ), with a subset of consultants engaging in semi-structured interviews. Descriptive analysis provided insights into both categorical and non-categorical variables, with differences examined across roles (students, interns, junior doctors, senior doctors) via Kruskal-Wallis tests, supplemented by two-group analyses using Mann-Whitney U testing. We correlated experience with MHAQ scores using Spearman’s rho, tested MHAQ’s internal consistency with Cronbach’s alpha, and employed thematic analysis for the qualitative data. Results We received 416 responses to the survey, and 12 senior doctors participated in the semi-structured interviews. Overall, all groups demonstrated moderately positive attitudes towards HVCCC, with more experienced doctors exhibiting more favourable views, especially about integrating costs into daily practice. In the interviews, participants agreed on the importance of instilling HVCCC values during undergraduate teaching and supplementing it with a formal curriculum in postgraduate training. This, coupled with practical knowledge gained on-the-job, was seen as a beneficial strategy for training doctors. Conclusions This sample of medical students and hospital-based doctors display generally positive attitudes towards HVCCC, high-value care provision, and the integration of healthcare costs, suggesting receptiveness to future HVCCC training among students and doctors. Experience is a key factor in HVCCC, so early exposure to these concepts can potentially enhance practice within existing healthcare budgets.

Abstract A recent evidence gaps assessment of the clinical, health‐related quality of life, and economic burden associated with α‐thalassemia is lacking. We conducted a systematic literature review (SLR) following the methodological and reporting requirements of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and the Cochrane Handbook for Systematic Reviews, using available literature over the past decade. This SLR identified a considerable evidence gap with regard to understanding the current burden of α‐thalassemia as evident from paucity of studies published in the past 10 years. The limited data available still indicate that patients with α‐thalassemia experience substantial morbidity and quality of life/economic burden that is generally comparable to patients with β‐thalassemia.

Objectives: The present study aims to address the psychological motivations behind social media use, focusing on its under-explored regulatory function in the context of coping strategies and emotional regulation among teachers. This exploratory research explores the relationship between social media engagement and its impact on educators’ stress management and emotional regulation mechanisms. Methods: To investigate this relationship, the study utilized two key instruments: The coping inventory for stressful situations and the Italian version of the difficulties in emotion regulation scale. These tools were administered to a sample of 214 Italian teachers, predominantly female (90.7%), with ages ranging from 25 to 65 years (Mean±SD 47.19±9.02 years). The study employed correlation analysis to assess the associations between social media use in addition to various coping and emotional regulation strategies. Results: The correlation analysis revealed a nuanced relationship between the usage of certain social media platforms and a higher inclination toward a problem-oriented coping style, alongside a decreased sense of a lack of negative emotional control. Accordingly, while social media can serve as a tool for problem-oriented coping, it may also hinder the ability to disengage from negative emotional states. Discussion: The results of this study shed light on the potential of social media as a resource and a challenge in the emotional and professional lives of teachers. By identifying specific coping strategies that are positively and negatively associated with social media use, the research points toward possible interventions that could mitigate the adverse effects of social media. This could include developing targeted support mechanisms to enhance teachers’ ability to manage stress and regulate emotions effectively, thereby optimizing their use of social media in a way that supports their psychological well-being.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Siân Rizzo,1 Mathieu Varache,1 Edward J Sayers,2 Arwyn T Jones,2 Alex Tonks,3 David W Thomas,1 Elaine L Ferguson1 1Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, UK; 2School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 3Department of Haematology, School of Medicine, Cardiff University, Cardiff, UKCorrespondence: Elaine L Ferguson, Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, UK, Tel +44 2922 510663, Email FergusonEL@cardiff.ac.ukIntroduction: Acute myeloid leukemia (AML) remains difficult to treat due to its heterogeneity in molecular landscape, epigenetics and cell signaling alterations. Precision medicine is a major goal in AML therapy towards developing agents that can be used to treat patients with different ‘subtypes’ in combination with current chemotherapies. We have previously developed dextrin–colistin conjugates to combat the rise in multi-drug resistant bacterial infections and overcome dose-limiting nephrotoxicity. Recent evidence of colistin’s anticancer activity, mediated through inhibition of intracellular lysine-specific histone demethylase 1 (LSD1/KDM1A), suggests that dextrin–colistin conjugates could be used to treat cancer cells, including AML. This study aimed to evaluate whether dextrin conjugation (which reduces in vivo toxicity and prolongs plasma half-life) could enhance colistin’s cytotoxic effects in myeloid leukemia cell lines and compare the intracellular uptake and localization of the free and conjugated antibiotic.Results: Our results identified a conjugate (containing 8000 g/mol dextrin with 1 mol% succinoylation) that caused significantly increased toxicity in myeloid leukemia cells, compared to free colistin. Dextrin conjugation altered the mechanism of cell death by colistin, from necrosis to caspase 3/7-dependent apoptosis. In contrast, conjugation via a reversible ester linker, instead of an amide, had no effect on the mechanism of the colistin-induced cell death. Live cell confocal microscopy of fluorescently labelled compounds showed both free and dextrin-conjugated colistins were endocytosed and co-localized in lysosomes, and increasing the degree of modification by succinoylation of dextrin significantly reduced colistin internalization.Discussion: Whilst clinical translation of dextrin–colistin conjugates for the treatment of AML is unlikely due to the potential to promote antimicrobial resistance (AMR) and the relatively high colistin concentrations required for anticancer activity, the ability to potentiate the effectiveness of an anticancer drug by polymer conjugation, while reducing side effects and improving biodistribution of the drug, is very attractive, and this approach warrants further investigation. Keywords: polymer therapeutics, biodegradable, internalization, polysaccharide, antibiotic