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A submerged elevation located off the coast of Le Castella, a small village on the Ionian Coast of Calabria (Italy) populated for thousands of years that features notable archaeological remains from the Great Greece (Magna Graecia) and the Middle Ages, was investigated through in-depth, multidisciplinary, geoarchaeological research. This submarine elevation, once aligned with the marine terrace MIS 3 of Le Castella and still completely emerged between 10 and 8 ka years ago, slowly sank due to erosion and local tectonic-structural subsidence and was also favoured by a submerged normal fault that cuts the terrace in two. The dismantling and sinking of this part of the marine terrace has significantly changed the Late Holocene shorelines, with notable consequences on a topographic and archaeological level. In fact, one of the consequences of the sinking of this ancient promontory was the disappearance of two small islands that were reported to be right in front of Le Castella by numerous historical and cartographic sources. In the last decades, there has been a scientific debate over the existence of these islets, but no convincing evidence has been found about their actual presence up until now. This research, funded by the Marine Protected Area “Capo Rizzuto”, was conducted by means of underwater archaeological and geological surveys, geophysical seabed mapping systems, and both direct and instrumental optical surveys made with an Autonomous Surface Vehicle. The outcomes allow us to confirm the presence of these two partially emerged rock bodies up to half a millennium ago. In addition, the presence of anthropogenic extrabasinal materials in a marine area corresponding to one of the highest points of the submerged elevation allows us to define the exact position of one of the two islets. These archaeological findings have been subject, for the first time ever, to a thorough topographical and architectural analysis, then compared with other near and very similar submerged structures. On the basis of these comparisons, the findings should be attributed to the Byzantine Age or, at most, to the Middle Ages. In-depth archival research on portolan charts and navigation maps, in many cases unpublished and dating from the Middle Ages to the early 18th century, supports the results of our marine investigations from a historical point of view.

Abstract Vast alteration of the biosphere by humans is causing a sixth mass extinction, driven in part by an increase in infectious diseases. The emergence of the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) has devastated global amphibian biodiversity. Given the lack of any broadly applicable methods to reverse these impacts, the future of many amphibians appears grim. The Sierra Nevada yellow-legged frog (Rana sierrae) is highly susceptible to Bd infection and most R. sierrae populations are extirpated following disease outbreaks. However, some populations persist and eventually recover, and frogs in these recovering populations have increased resistance against infection. Here, we conduct a 15-year reintroduction study and show that frogs collected from recovering populations and reintroduced to vacant habitats can reestablish populations despite the presence of Bd. In addition, the likelihood of establishment is influenced by site, cohort, and frog attributes. Results from viability modeling suggest that many reintroduced populations have a low probability of extinction over 50 years. These results provide a rare example of how reintroduction of resistant individuals can allow the landscape-scale recovery of disease-impacted species, and have broad implications for amphibians and other taxa that are threatened with extinction by novel pathogens.

Abstract The existence of different male morphologies within a single species is associated with alternative mating tactics across different animal groups, offering textbook examples of evolutionary biology. The European stag beetle Lucanus cervus is a flagship species which has long fascinated naturalists for its charismatic appearance and behavior, with males possessing large mandibles used in ritualized ground fights for females. Males are polymorphic, with larger males possessing disproportionately larger mandibles and being better fighters, while smaller males require less food to develop and may have better chances to escape predation. We discovered an alternative mating tactic that opens a new interpretation on the evolution of the smaller males, based on aggregations of flying males competing to catch flying females in mid-air. Flight aggregations occur earlier in the season and in sites with sparser canopy cover as compared to ground fight aggregations, but most importantly, smaller males tend to prevail due to their greater agility in flight. Competition between males is crucial for reproductive success in this species, and alternative mating tactics involving flight were unknown in beetles, advocating for further research on the ecology and evolution of the iconic male polymorphism of stag beetles.

Abstract Background Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC. Methods HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches. Results HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment. Conclusions These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction. Graphical abstract

Background: Multiple Sclerosis (MS) is the most prevalent autoimmune neurological condition in the world, leading to a wide variety of symptoms, including balance disorders. Objective: To evaluate the angular vestibulo–ocular reflex (aVOR) of all six semicircular canals (SCCs) through Head Impulse (HIMP) and Suppression HIMP (SHIMP) paradigms and any correlations with clinical balance scales. Methods: All participants were assessed using the Expanded Disability Status Scale (EDSS), Berg Balance Scale (BBS), and Mini-BESTest (MBT). Vestibular function was measured by video Head Impulse Test (vHIT), obtaining aVOR gain for each SSC. Results: Twenty-seven PwMS (mean age 47.93 ± 8.51 years old, 18 females) were recruited. Most of the patients (81.48%) presented abnormal aVOR gains for at least one SSC. A moderate to strong correlation between aVOR gains of the left anterior SSC and, respectively, the MBT and the BBS was found. The subgroup analysis, based on the EDSS class, confirmed the correlation with the BBS in the patients with the most significant disability. Conclusions: People with MS may present impairments of the aVOR in one or more semicircular canals. The aVOR gain impairment of the vertical semicircular canals correlates with balance and gait disorders identified through clinical scales in PwMS.

Abstract Background Discomfort can be the cause of noninvasive respiratory support (NRS) failure in up to 50% of treated patients. Several studies have shown how analgosedation during NRS can reduce the rate of delirium, endotracheal intubation, and hospital length of stay in patients with acute respiratory failure. The purpose of this project was to explore consensus on which medications are currently available as analgosedatives during NRS, which types of patients may benefit from analgosedation while on NRS, and which clinical settings might be appropriate for the implementation of analgosedation during NRS. Methods The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects of the use of analgesics and sedatives during NRS treatment. The methodology applied is in line with the principles of the modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales which were then subjected to blind votes for consensus. Results The use of an analgosedation strategy in adult patients with acute respiratory failure of different origins may be useful where there is a need to manage discomfort. This strategy should be considered after careful assessment of other potential factors associated with respiratory failure or inappropriate noninvasive respiratory support settings, which may, in turn, be responsible for NRS failure. Several drugs can be used, each of them specifically targeted to the main component of discomfort to treat. In addition, analgosedation during NRS treatment should always be combined with close cardiorespiratory monitoring in an appropriate clinical setting. Conclusions The use of analgosedation during NRS has been studied in several clinical trials. However, its successful application relies on a thorough understanding of the pharmacological aspects of the sedative drugs used, the clinical conditions for which NRS is applied, and a careful selection of the appropriate clinical setting.

Abstract Background The growing diffusion of artificial intelligence, data science and digital health has highlighted the role of collection of data and biological samples, thus raising legal and ethical concerns regarding its use and dissemination. Further, the expansion of biobanking, from the basic collection of frozen specimens to the virtual biobanks of specimens and associated data that exist today, has given a revolutionary potential on healthcare systems, particularly in the field of neurological diseases, due to the inaccessibility of central nervous system and the need of non-invasive investigation approaches. Informed Consent (IC) is considered mandatory in all research studies and specimen collections, and must specifically take into account the ethical respect to the individuals to whom the used biological material and data belong. Methods We evaluated the attitudes of patients with neurological diseases (NP) and healthy volunteers (HV) towards the donation of biological samples to a biobank for future research studies on neurological diseases, and limitations on the use of data, related to the requirements set by the General Data Protection Regulation (GDPR). The study involved a total of 1454 subjects, including 502 HVs and 952 NPs, recruited at Santa Lucia Foundation IRCCS, Rome, from 2020 to 2024. Results We found that (i) almost all subjects agreed with the participation in biobanking (ii) and authorization to genetic studies (HV = 99.1%; NP = 98.3%); Regarding the return of results, (iii) we found a statistically significant difference between NP and HV, the latter preferring not to be informed of potential results (HV = 43%; NP = 11.3%; p

Background: Interventional radiology techniques have become pivotal in recent years in managing metastatic bone disease, which frequently results in skeletal complications such as fractures and severe pain. Thermoablative methods like radiofrequency ablation (RFA) and microwave ablation (MWA), when combined with vertebroplasty (VP), are proving increasingly beneficial for these patients. Methods: The search was independently conducted by two radiologists on MEDLINE databases, using specified strings up to April 2024. Methodological quality was assessed using PRISMA guidelines. Studies meeting inclusion criteria investigated thermoablation techniques (RFA and/or MWA) combined with VP, focusing on pain management and disease control outcomes in adults. Results: Among 147 results, 42 articles met the criteria, with varied prospective and retrospective designs and sample sizes averaging 49 patients, predominantly involving RFA (30 studies), MWA (11 studies), and one comparative study. Our review highlights significant pain reduction, effective local tumor control, and favorable safety of combined RFA or MWA with VP, supporting its potential in managing vertebral pathologies and warranting further clinical integration. Conclusions: The combined treatment of RFA/MWA with VP demonstrates significant pain reduction and local tumor control, with a rapid onset of analgesic effect. These findings support its crucial role in clinical practice for managing vertebral metastases.

Abstract The work addresses the topic of the thermal study of high-voltage power cables installed inside plastic pipes in the absence of filling. The presence of air inside the pipe creates an insulating layer that does not favor heat exchange and makes the calculation of the flow rate more complex, as it is necessary to take into account the thermal phenomena of natural convection and radiation between the surface of the cable and the internal surface of the tube. The numerical model based on the finite element calculation was compared with the experimental results obtained on a simulacrum in which the temperatures on the different layers of the cable were measured. After this validation, some typical installation configurations of single and double energy transport triads were analyzed.

(1) This study evaluates the impact of the CT-guided SIRIO augmented reality navigation system on the procedural efficacy and clinical outcomes of neuroprotection in vertebral thermal ablation (RTA) for primary and metastatic bone tumors. (2) Methods: A retrospective non-randomized analysis of 28 vertebral RTA procedures was conducted, comparing 12 SIRIO-assisted and 16 non-SIRIO-assisted procedures. The primary outcomes included dose-length product (DLP) and epidural dissection time. The secondary outcomes included technical success, complication rates, and pain scores at procedural time (VAS Time 0) and three months post-procedure (VAS Time 1). The statistical analyses included t-tests, Mann–Whitney U tests, and multiple regression. (3) Results: SIRIO-assisted procedures significantly reduced DLP (307.42 mGycm vs. 460.31 mGycm, p = 2.23 × 10−8) and procedural epidural dissection time (13.48 min vs. 32.26 min, p = 2.61 × 10−12) compared to non-SIRIO-assisted procedures. Multiple regression confirmed these reductions were significant (DLP: β = −162.38, p < 0.001; time: β = −18.25, p < 0.001). Pain scores (VAS Time 1) did not differ significantly between groups, and tumor type did not significantly influence outcomes. (4) Conclusions: The SIRIO system enhances neuroprotection efficacy and safety, reducing radiation dose and procedural time during spine tumoral ablation while maintaining consistent pain management outcomes.

Abstract Speech-language therapists/pathologists (SLT/Ps) are key professionals in the management and treatment of primary progressive aphasia (PPA), however, there are gaps in education and training within the discipline, with implications for skills, confidence, and clinical decision-making. This survey aimed to explore the areas of need amongst SLT/Ps working with people living with PPA (PwPPA) internationally to upskill the current and future workforce working with progressive communication disorders. One hundred eighty-six SLT/Ps from 27 countries who work with PwPPA participated in an anonymous online survey about their educational and clinical experiences, clinical decision-making, and self-reported areas of need when working with this population. Best practice principles for SLT/Ps working with PwPPA were used to frame the latter two sections of this survey. Only 40.7% of respondents indicated that their university education prepared them for their current work with PwPPA. Competency areas of “knowing people deeply,” “practical issues,” “connectedness,” and “preventing disasters” were identified as the basic areas of priority and need. Respondents identified instructional online courses (92.5%), sample tools and activities for interventions (64.8%), and concrete training on providing care for advanced stages and end of life (58.3%) as central areas of need in their current work. This is the first international survey to comprehensively explore the perspectives of SLT/Ps working with PwPPA. Based on survey outcomes, there is a pressing need to enhance current educational and ongoing training opportunities to better promote the well-being of PwPPA and their families, and to ensure appropriate preparation of the current and future SLT/P workforce.

In this scoping review, we delve into the transformative potential of artificial intelligence (AI) in addressing challenges inherent in whole-genome sequencing (WGS) analysis, with a specific focus on its implications in oncology. Unveiling the limitations of existing sequencing technologies, the review illuminates how AI-powered methods emerge as innovative solutions to surmount these obstacles. The evolution of DNA sequencing technologies, progressing from Sanger sequencing to next-generation sequencing, sets the backdrop for AI’s emergence as a potent ally in processing and analyzing the voluminous genomic data generated. Particularly, deep learning methods play a pivotal role in extracting knowledge and discerning patterns from the vast landscape of genomic information. In the context of oncology, AI-powered methods exhibit considerable potential across diverse facets of WGS analysis, including variant calling, structural variation identification, and pharmacogenomic analysis. This review underscores the significance of multimodal approaches in diagnoses and therapies, highlighting the importance of ongoing research and development in AI-powered WGS techniques. Integrating AI into the analytical framework empowers scientists and clinicians to unravel the intricate interplay of genomics within the realm of multi-omics research, paving the way for more successful personalized and targeted treatments.

Abstract Background Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. Main body Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ (“A”), tau (“T”), and neurodegeneration (“N”), by incorporating a novel inflammatory component (“I”). Conclusions The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.

Abstract Taste perception plays a pivotal role in guiding nutrient intake and aiding in the avoidance of potentially harmful substances through five basic tastes - sweet, bitter, umami, salty, and sour. Taste perception originates from molecular interactions in the oral cavity between taste receptors and chemical tastants. Hence, the recognition of taste receptors and the subsequent perception of taste heavily rely on the physicochemical properties of food ingredients. In recent years, several advances have been made towards the development of machine learning-based algorithms to classify chemical compounds’ tastes using their molecular structures. Despite the great efforts, there remains significant room for improvement in developing multi-class models to predict the entire spectrum of basic tastes. Here, we present a multi-class predictor aimed at distinguishing bitter, sweet, and umami, from other taste sensations. The development of a multi-class taste predictor paves the way for a comprehensive understanding of the chemical attributes associated with each fundamental taste. It also opens the potential for integration into the evolving realm of multi-sensory perception, which encompasses visual, tactile, and olfactory sensations to holistically characterize flavour perception. This concept holds promise for introducing innovative methodologies in the rational design of foods, including pre-determining specific tastes and engineering complementary diets to augment traditional pharmacological treatments.

Abstract The rapid expansion of urban areas and soil sealing is enhancing the Urban Heat Island (UHI) phenomenon, especially during heat waves. The different thermal inertia of the building materials compared to natural surfaces is one of the major driving factors of UHI. The present contribution aims to test a methodology for mapping the Apparent Thermal Inertia (ATI)—a proxy that can be derived from remote sensing data—of roofing surfaces at the scale of an entire city and with a high spatial resolution. Day and night aerial thermal images with the resolution of 0.5 m were acquired over two test areas in Bologna (Italy), together with satellite multispectral data. Statistics on the buildings in the test areas are computed considering different classes of roofing materials (e.g. bituminous sheath, clay tiles, metal sheet, gravel tiles). Observed median ATI values for each class range from 0.03 to 0.09 K $$^{-1}$$ - 1 with interquartile ranges between 0.02 and 0.14 K $$^{-1}$$ - 1 , so the intra-class variability in some cases appears higher than the variability among different material classes, proving the importance of ATI mapping for UHI investigations.

Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Abstract Background The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. Methods Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28–30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). Results Between high (median [interquartile range] 20 cmH2O [18–21]) and low PEEP, median R/I was 1.08 [0.88–1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182–288] and 385 ml [318–668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29–0.44] at high PEEP and 0.59 [0.46–0.80] at low PEEP (p

Abstract This paper introduces a novel approach for designing a Wireless Power Transfer (WPT) system with LCC‐S compensation. Since WPT systems operate under resonant conditions, even small deviations of the components from the nominal values can result in a significant reduction of the power transferred to the load, and in an increment of the circulating currents, reducing the system efficiency. The design techniques available today in the literature provide a unique combination of passive components capable of transferring a certain power to the load. This is a limitation, because, in practice, there are several combinations that allow reaching the desired output power, but they are usually neglected because they are extremely difficult to compute analytically. For this reason, in this paper, the authors present an innovative design procedure that enables, through a Genetic Algorithm, the identification of multiple feasible combinations of the LCC‐S components capable of achieving the desired output power. Moreover, the authors evaluate the effects of the component tolerances on the output power to determine which combinations are more robust to component variations. This task is performed by calculating the probability that a particular combination yields the desired output power, once the tolerances have been considered, following a Monte Carlo approach. This information is utilized to decide whether it is possible to reduce the component quality (worsening the tolerance) without affecting the performance. Finally, an optimal solution granting both low‐cost and robustness against component tolerances can be individuated. The proposed design procedure is applied to a case study and validated experimentally.

The present communication describes the first case of nest protection of a breeding pair of Montagu’s harrier Circus pygargus in the Municipality of Predosa, Province of Alessandria. To protect the nest, an electrified fence has been installed (around the area), 50 m long and 90 cm high. From a clutch of four eggs, three chicks hatched and fledged successfully thanks to these protection measures. Despite this, a chick was found preyed just beyond the fence during its first flight tests, suggesting the use of large fences for future interventions. From 2017, the frequent observations referred to migrating and summer visitors of Montagu’s harrier in the municipality of Predosa (which is characterized by extensive stable meadows and melliferous and uncultivated patches) could be related to an increase in the breeding pairs in neighbouring territories with traditional agricultural vocation. This suggests carrying out new surveys at provincial and regional scales to update the distribution and the consistency of breeding pairs of Montagu’s harrier, for which there have been no updates for about twenty-five years. [Article in Italian]

Rationale The impact of extracorporeal carbon dioxide removal (ECCO2R) on work of breathing and aeration in exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly understood.Objectives The study explores the impact of non-invasive ventilation (NIV) and ECCO2R on respiratory drive, effort and distribution of ventilation in AECOPD.Methods Patients enrolled in a randomised controlled study of the addition of ECCO2R to NIV compared with NIV underwent oesophageal pressure measurement, electrical impedance tomography and parasternal electromyography.Measurements and main results 18 patients were enrolled, nine in each arm. Of these, eight in the NIV arm and seven in the ECCO2R arm underwent physiological assessment. Patients randomised to ECCO2R, had a period of NIV combined with ECCO2R and, after removal of NIV, a period of ECCO2R alone. The removal of NIV whilst remaining on ECCO2R resulted in a respiratory acidosis (pH 7.34 (7.31–7.34) vs. 7.31 (7.31–7.34), p

Developing Electrophoretic Deposition (EPD) for Composite Structural Batteries (CSBs) could revolutionise energy storage technology. CSBs offer an innovative solution by seamlessly integrating batteries into structures and effectively reducing weight and space constraints. Despite its successful implementation across various fields, EPD method still lacks comprehensive understanding of the underlying physical and chemical processes due to the number of variables involved. In this study the effects of key parameters associated with the process are investigated with a coupled FEM and analytical approach to find correlations with the deposition process. A Taguchi Design of Experiment with five parameters, namely voltage, concentration, relative weight ratio of LiFePO4 – carbon black particles, length and perimeter of the electrodes is implemented to identify the correlations with mass deposited, thickness of the coating and yield rate when LiFePO4 and Carbon Black particles in ethanol suspension are used. In order to capture the variation over time, each parameter is studied at six different time of deposition. A concentration that optimises yield rate resulting in thickness and mass deposition is identified. The resistivity of the suspension dictates the yield rate dynamics, allowing it to be designed within a specific range to meet requirements of different applications.

Background Available empirical evidence on participant-level factors associated with dropout from psychotherapies for post-traumatic stress disorder (PTSD) is both limited and inconclusive. More comprehensive understanding of the various factors that contribute to study dropout from cognitive-behavioural therapy with a trauma focus (CBT-TF) is crucial for enhancing treatment outcomes.Objective Using an individual participant data meta-analysis (IPD-MA) design, we examined participant-level predictors of study dropout from CBT-TF interventions for PTSD.Methods A comprehensive systematic literature search was undertaken to identify randomised controlled trials comparing CBT-TF with waitlist control, treatment-as-usual or another therapy. Academic databases were screened from conception until 11 January 2021. Eligible interventions were required to be individual and in-person delivered. Participants were considered dropouts if they did not complete the post-treatment assessment.Findings The systematic literature search identified 81 eligible studies (n=3330). Data were pooled from 25 available CBT-TF studies comprising 823 participants. Overall, 221 (27%) of the 823 dropped out. Of 581 civilians, 133 (23%) dropped out, as did 75 (42%) of 178 military personnel/veterans. Bivariate and multivariate analyses indicated that military personnel/veterans (RR 2.37) had a significantly greater risk of dropout than civilians. Furthermore, the chance of dropping out significantly decreased with advancing age (continuous; RR 0.98).Conclusions These findings underscore the risk of premature termination from CBT-TF among younger adults and military veterans/personnel.Clinical implication Understanding predictors can inform the development of retention strategies tailored to at-risk subgroups, enhance engagement, improve adherence and yield better treatment outcomes.

Introdução: Depressão é o transtorno mental mais frequente entre pessoas vivendo com HIV (PVHIV), com impacto negativo nesta população. É conhecido que Espiritualidade protege contra depressão na população em geral, mas há poucos estudos em PVHIV. Questionários estruturados podem avaliar espiritualidade, através da avaliação do bem-estar espiritual (BEE), como o FACIT-Sp (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being). Objetivo: Investigar a associação entre espiritualidade e depressão em PVHIV em acompanhamento ambulatorial. Materiais e Métodos: Estudo transversal com PVHIV em acompanhamento ambulatorial em um Hospital Universitário no Rio de Janeiro. Além do questionário sócio-demográfico, foi realizada entrevista com o M.I.N.I. (Mini International Neuropsychiatric Interview Brazilian version 5.0) para investigação de episódio depressivo maior (EDM). Para avaliação da espiritualidade foi utilizado o FACIT-Sp, que permite a análise do BEE global. Para análise estatística foi aplicado o teste t, regressão linear e um modelo para análise multivariada por regressão logística, em que idade, sexo, afiliação religiosa e pontuação do FACIT-Sp foram incluídas como variáveis independentes para a presença de EDM, considerando um nível de significância de 5%. Resultados: Dos 104 participantes incluídos, 50,5% era do sexo feminino e a idade média foi de 47,1 ± 11,2 anos. A prevalência de EDM foi de 25% (n = 26). Entre aqueles com e sem EDM foi observada pontuação total do FACIT-Sp de 28,5 ± 9,6 pontos e 39,5 ± 7,2 pontos [t(104) = 6,14; p < 0.001], respectivamente. Na análise multivariada, a única variável associada com EDM foi a pontuação do FACIT-Sp (OR = 0,861; IC95% 0,804-0,921; p; p < 0,001). Conclusão: Maior BEE foi associado à menor depressão em PVHIV em acompanhamento ambulatorial e portanto maior espiritualidade foi um fator de proteção para depressão em PVHIV. Palavras-chave: Espiritualidade, HIV, Depressão. Conflitos de interesse: Declarações de interesse: Nenhum. Ética e financiamentos: Não houve financiamento e não houve conflitos de interesse. Juliana Freiha: realizou mestrado profissional na Unirio-HUGG /HIV e Hepatites Virais, sem bolsa); Beatriz Lacombe: aluna de graduação de Medicina da Unirio HUGG (bolsista de monitoria); Otávio Grasso: aluno de graduação da Medicina da Unirio-HUGG (bolsista de extensão); Julio Tolentino: professor da Unirio e da disciplina de Espiritualidade.

IntroductionPavlovian fear conditioning is an experimental paradigm used to study the acquisition and extinction of fear responses and the various aspects of fear and anxiety. We developed a virtual reality (VR) version of this paradigm to leverage the benefits of virtual reality, such as ecological validity, standardization, safety, and therapeutic applications. Our objective was to create an open-source and immersive environment for studying fear-related responses using Unity Engine 3D and the Oculus Rift device.MethodsIn this virtual environment, the participants encountered a monster screaming at 100 dB approaching them as the fear-inducing stimulus (unconditioned stimulus or US). Our protocol included three sessions: habituation, acquisition, and extinction, with two stimuli associated with different doors (blue vs. red). The blue door (CS+) was linked to the US, while the red door (CS−) was the control. We tested this VR paradigm on 84 young participants, recording their skin conductance response (SCRs) and fear stimulus ratings (FSRs) on a 10-point Likert scale.ResultsThe findings showed significantly higher SCRs and FSRs for CS+ as compared to CS− during the acquisition phase and higher SCRs and FSRs for CS+ during the acquisition phase as compared to the habituation and extinction sessions.Discussion and conclusionsThese results supported the reliability of the protocol for studying fear and anxiety-related conditions.

Historically, low-moisture foods were considered to have minimal microbial risks. However, they have been linked to many high-profile multistate outbreaks and recalls in recent years, drawing research and extension attention to low-moisture food safety. Limited studies have assessed the food safety research and extension needs for the low-moisture food industry. The objectives of this needs assessment were to explore the food safety culture and education needs, identify the food safety challenges and data gaps, and understand the barriers to adopting food-safety-enhancing technologies in the U.S. low-moisture food industry. This needs assessment was composed of two studies. In Study 1, food safety experts from the low-moisture food industry upper management participated in online interviews and a debriefing discussion session. In Study 2, an online anonymous survey was disseminated to a different group of experts with experience in the low-moisture food industry. The qualitative data were analyzed using deductive and inductive coding approaches, while the quantitative data were analyzed via descriptive analysis. Twenty-five experts participated in the studies (Study 1: n = 12; Study 2: n = 13). Common commodities that participants had worked with included nuts and seeds, spices, flour, and dried fruits and vegetables. A food safety culture conceptual framework was adapted, which included three main components: infrastructure conditions (foundation), individual’s food safety knowledge, attitudes, and risk perceptions; and organizational conditions (supporting pillars). Major barriers to establishing a positive food safety culture were identified to be limited resources, difficulties in risk communication, and difficulties in behavioral change. For continual improvement in food safety performance, two major themes of food safety challenges and data gaps were identified: cleaning, sanitation, and hygienic design; and pathogen reduction. Participants perceived the main barriers discouraging the low-moisture food industry from adopting food-safety-enhancing technologies were: (1) budgetary priorities, (2) operation constraints, (3) technology validation, (4) consumer acceptance, and (5) maintaining desired product characteristics such as quality and sensory functionality. The findings of this needs assessment provide guidance for the food industry, academia, and government agencies about the direction of future research and the development of targeted extension programs that might help improve food safety in the low-moisture food industry.

Abstract Reintroduction efforts are increasingly used to mitigate biodiversity losses, but are frequently challenged by inadequate planning and uncertainty. High quality information about population status and threats can be used to prioritize reintroduction and restoration efforts and can transform ad hoc approaches into opportunities for improving conservation outcomes at a landscape scale. We conducted comprehensive environmental DNA (eDNA) and visual encounter surveys to determine the distribution of native and non-native aquatic species in two high-priority watersheds to address key uncertainties—such as the distribution of threats and the status of existing populations—inherent in restoration planning. We then used these occurrence data to develop a menu of potential conservation actions and a decision framework to benefit an endangered vertebrate (foothill yellow-legged frog, Rana boylii) in dynamic stream systems. Our framework combines the strengths of multiple methods, allowing managers and conservation scientists to incorporate conservation science and site-specific knowledge into the planning process to increase the likelihood of achieving conservation goals.

Accurate cave surveying is crucial for understanding their genesis, current state, and potential hazards, especially in challenging environments marked by limited accessibility and poor visibility. This study applies geomatics techniques, including Terrestrial Laser Scanning (TLS), SLAM-based Mobile Mapping Systems (MMS), and digital photogrammetry, to create three-dimensional models of artificial caves in Gravina in Puglia, Apulia region, southern Italy. The research aims to assess these methodologies' accuracy, reliability, and performance for structural monitoring and hazard assessment. Despite challenges such as rough conditions, limited accessibility and poor visibility, the study reveals promising insights into the capabilities of these techniques for efficient surveying in complex underground environments. While highlighting the potential of MMS for cost-effective and rapid data acquisition, digital photogrammetry using spherical cameras also emerges as a viable alternative, offering comprehensive data collection capabilities with minimal capture time. Further research is warranted to optimize these techniques for enhanced hazard assessment and structural monitoring in challenging underground environments.

Multiple strategies are continuously being explored to expand the drug target repertoire in solid tumors. We devised a novel computational workflow for transcriptome‐wide gene expression outlier analysis that allows the systematic identification of both overexpression and underexpression events in cancer cells. Here, it was applied to expression values obtained through RNA sequencing in 226 colorectal cancer (CRC) cell lines that were also characterized by whole‐exome sequencing and microarray‐based DNA methylation profiling. We found cell models displaying an abnormally high or low expression level for 3533 and 965 genes, respectively. Gene expression abnormalities that have been previously associated with clinically relevant features of CRC cell lines were confirmed. Moreover, by integrating multi‐omics data, we identified both genetic and epigenetic alternations underlying outlier expression values. Importantly, our atlas of CRC gene expression outliers can guide the discovery of novel drug targets and biomarkers. As a proof of concept, we found that CRC cell lines lacking expression of the MTAP gene are sensitive to treatment with a PRMT5‐MTA inhibitor (MRTX1719). Finally, other tumor types may also benefit from this approach.

Abstract Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress–strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient’s stress–strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8–33.2] cmH2O versus 11.4 [10.3–14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress–strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Background: Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains. Methods: From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates. Results: A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates. Conclusion: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

We report on a 20-year-old pregnant woman who tested positive for SARS-CoV-2 and was diagnosed with KILT syndrome, a rare condition that increases the risk of thrombotic events. The patient showed signs of deep vein thrombosis that extended from the bilateral iliac vein to the inferior vena cava (IVC), which was treated with placement of an IVC filter and endovascular thromboaspiration/thrombolysis. The IVC was successfully recanalized; however, during follow-up, thrombotic restenosis occurred at the filter level, requiring filter removal. This case highlights the potential benefits of endovascular thromboaspiration/thrombolysis and IVC filter placement in patients with KILT syndrome presenting with acute thrombotic events.

The Basso Ferrarese area in the Po Delta is an undecided place, suspended between land and sea, in search of its future. Its current conformation derives from a history linked first to a large marshy basin, then to centuries of reclamation. Although the reclamations have helped the agricultural use of the land, at the same time they have caused the disentanglement between population and site. At the same time, the threat of rising sea levels is looming. Through a series of journeys, the current landscapes of that sea of land that today forms the Basso Ferrarese have been recorded. A sea made up of many levels that limit and direct the reclamation channels. In a strong state of abandonment, what can be the future of the area? Through the creation of an imaginary for the water space and the study of the needs of a case study, 5 design actions have been identified to decolonize the delta from the land and regain contact with the water, at the same time preparing for the rise of the sea.

Abstract Objective The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high‐grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. Methods All patients diagnosed with high‐grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan–Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. Results A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow‐up period was 29.2 months. Notably, group 2 demonstrated significantly enhanced overall and metastasis‐free survival rates compared to group 1. At 47.8 months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis‐free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6 months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Conclusion Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high‐grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.

Abstract Progressive cartilage deterioration leads to chronic inflammation and loss of joint function, causing osteoarthritis (OA) and joint disease. Although symptoms vary among individuals, the disease can cause severe pain and permanent disability, and effective therapies are urgently needed. Human Adipose-Derived Stem Cells (ADSCs) may differentiate into chondrocytes and are promising for treating OA. Moreover, recent studies indicate that electromagnetic fields (EMFs) could positively affect the chondrogenic differentiation potential of ADSCs. In this work, we investigated the impact of EMFs with frequencies of 35 Hertz and 58 Hertz, referred to as extremely low frequency-EMFs (ELF–EMFs), on the chondrogenesis of ADSCs, cultured in both monolayer and 3D cell micromasses. ADSC cultures were daily stimulated for 36 min with ELF–EMFs or left unstimulated, and the progression of the differentiation process was evaluated by morphological analysis, extracellular matrix deposition, and gene expression profiling of chondrogenic markers. In both culturing conditions, stimulation with ELF–EMFs did not compromise cell viability but accelerated chondrogenesis by enhancing the secretion and deposition of extracellular matrix components at earlier time points in comparison to unstimulated cells. This study showed that, in an appropriate chondrogenic microenvironment, ELF–EMFs enhance chondrogenic differentiation and may be an important tool for supporting and accelerating the treatment of OA through autologous adipose stem cell therapy.

Abstract Ribonucleotides represent the most common non-canonical nucleotides found in eukaryotic genomes. The sources of chromosome-embedded ribonucleotides and the mechanisms by which unrepaired rNMPs trigger genome instability and human pathologies are not fully understood. The available sequencing technologies only allow to indirectly deduce the genomic location of rNMPs. Oxford Nanopore Technologies (ONT) may overcome such limitation, revealing the sites of rNMPs incorporation in genomic DNA directly from raw sequencing signals. We synthesized two types of DNA molecules containing rNMPs at known or random positions and we developed data analysis pipelines for DNA-embedded ribonucleotides detection by ONT. We report that ONT can identify all four ribonucleotides incorporated in DNA by capturing rNMPs-specific alterations in nucleotide alignment features, current intensity, and dwell time. We propose that ONT may be successfully employed to directly map rNMPs in genomic DNA and we suggest a strategy to build an ad hoc basecaller to analyse native genomes.

Abstract In this work, we identified the trail pheromone of the ant Crematogaster scutellaris. We combined gas chromatography–mass spectrometry analysis of extracts from the hind tibia, the location of the respective glands, with automated trail following assays. The study found tridecan-2-ol to be the strongest discriminator between hind tibia and other body part extracts. Tridecan-2-ol elicited trail-following behaviour at concentrations of 1 ng/µL. A separation of the enantiomers showed responses to (R)-tridecan-2-ol already at 0.001 ng/µL and only at a 1000-fold higher concentration for (S)-tridecan-2-ol, suggesting that only the R enantiomer is used by C. scutellaris in its natural environment. We also found strong behavioural responses to 2-dodecanol, a substance that was not detectable in the hind tibia extract of C. scutellaris, but which has been reported to be the trail pheromone of the related species C. castanea. We discuss the contribution of these results to the 'dissection and reconstruction' of strategies and mechanisms underlying the social organization of ants.

This study examines the online communication practices of research institutes affiliated with the Italian National Research Council. The analysis employs a combination of quantitative and qualitative methods to evaluate whether these institutes leverage digital technologies to transition from a unidirectional, strategic approach to communication towards a more dialogic and engaging approach with the public. Specifically, the study analyses the institutes’ websites, assessing their use of communication tools, content, target audience, knowledge flows, and contextualization of communication activities, while also highlighting disciplinary-based differences. Although recent research identified Research Institutes’ level as a promising ground for research communication to flourish, our study suggests that, on average, they still employ digital technologies in the same way as traditional media, disseminating information about institutional advancements rather than fostering interactive dialogue. Communication styles remain grounded in Dissemination and Strategic models, which restricts the ability of research institutes to develop a dynamic and transformative relationship with society.

The maintenance of good milk quality standards is still a challenge for dairy farmers that requires a rapid control system that is compatible with both the environment and production cost. A patented Hazard Analysis and Critical Control Points-like remote diagnostic (sensor driven) system named BEST was implemented to enable both quality monitoring and traceability in the dairy chain. BEST was daily tested in a dairy farm to identify new reliable indicators of anomalies (safety and quality) in milk production based on a Machine-Learning approach. The database obtained in four months of sensoristic analysis was subjected to a statistical study with AI algorithm to identify outliers. BEST proved ability to spot cows with specific characteristics in the whole herd's database. In particular, AI highlighted the sole cow from a different breed, the only cow that recently gave birth and the only cow in the herd that received treatment with the drug Micospectone® (Lincomycin + Spectinomycin).

IntroductionDespite the advancements in oncological medicine and research, cancer remains the second leading cause of death in Europe with Central and Eastern European countries, such as Slovakia and Croatia, showing the highest mortality rates and disparities in access to appropriate and comprehensive cancer care. Therefore, the primary aim of the current study is to investigate cancer patients’ perspectives and experiences to understand the possible underlying reasons for cancer disparities.MethodsCroatian cancer patients (n=15) and Slovak patients (n=11) were recruited through social media platforms, patients’ organisations, and hospital websites and offered participation in online focus group discussions on perceived disparities, barriers or malfunctioning during and after their cancer journey. Transcripts of video and audio recordings of the interviews were translated and analysed using Thematic analysis.ResultsSix Croatian and five Slovak themes emerged from the focus group discussions highlighting encountered barriers and perceived disparities, as well as suggestions or unmet needs. Most of the themes are common to both groups, such as the lack of information and use of the internet, and the taboos regarding cancer or psycho-oncological support. However, some themes are specific to each group, for instance, Slovak cancer patients remarked the fact that they do not mind travelling to get treatment as long as they can be treated in the west of Slovakia, while Croatian patients highlighted the need for more information after the illness and the socioeconomic impact deriving from a cancer diagnosis.DiscussionUrgent intervention is needed in addressing disparities in Central and Eastern Europe. Present results could inform dedicated guidelines or better resource allocation strategies to reduce disparities in cancer care and promote inclusive healthcare.

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

IntroductionRecent studies have shown gender differences in cardiovascular outcomes after left atrial appendage closure (LAAC), highlighting different complication rates and adverse events, particularly in short-term assessments. As a result, there remains a significant knowledge gap on how these differences directly impact the efficacy and safety of LAAC procedures. The aim of this retrospective study was to investigate the clinical outcomes of LAAC in women and men using the Watchman FLX device.MethodsThis retrospective, multicenter study analyzes gender-specific outcomes in 650 patients who underwent LAAC with the Watchman FLX device between March 2019 and May 2022, drawn from the ITALIAN-FLX registry.ResultsThe results show comparable rates of all-cause mortality, stroke, transient ischemic attack and major bleeding in men and women 12 months after the procedure. Notably, no significant gender differences were found for periprocedural complications.ConclusionIn conclusion, this study shows that LAAC with the Watchman FLX device has comparable clinical outcomes between genders at both short-term and long-term follow-up.

Salmonella is capable of surviving dehydration within various foods, such as dried fruit. Dried fruit, including apple slices, have been the subject of product recalls due to contamination with Salmonella. A study was conducted to determine the fate of Salmonella on apple slices, following immersion in three antimicrobial solutions (viz., ε-polylysine [epsilon-polylysine or EP], sodium bisulfate [SBS], or peracetic acid [PAA]), and subsequent hot air dehydration. Gala apples were aseptically cored and sliced into 0.4 cm thick rings, bisected, and inoculated with a five-strain composite of desiccation-resistant Salmonella, to a population of 8.28 log CFU/slice. Slices were then immersed for 2 min in various concentrations of antimicrobial solutions, including EP (0.005, 0.02, 0.05, and 0.1%), SBS (0.05, 0.1, 0.2, and 0.3%), PAA (18 or 42 ppm), or varying concentrations of PAA + EP, and then dehydrated at 60°C for 5 h. Salmonella populations in positive control samples (inoculated apple slices washed in sterile water) declined by 2.64 log after drying. In the present study, the inactivation of Salmonella, following EP and SBS treatments, increased with increasing concentrations, with maximum reductions of 3.87 and 6.20 log (with 0.1 and 0.3% of the two compounds, respectively). Based on preliminary studies, EP concentrations greater than 0.1% did not result in lower populations of Salmonella. Pretreatment washes with either 18 or 42 ppm of PAA inactivated Salmonella populations by 4.62 and 5.63 log, respectively, following desiccation. Combining PAA with up to 0.1% EP induced no greater population reductions of Salmonella than washing with PAA alone. The addition of EP to PAA solutions appeared to destabilize PAA concentrations, reducing its biocidal efficacy. These results may provide antimicrobial predrying treatment alternatives to promote the reduction of Salmonella during commercial or consumer hot air drying of apple slices.

Abstract Protein residues within binding pockets play a critical role in determining the range of ligands that can interact with a protein, influencing its structure and function. Identifying structural similarities in proteins offers valuable insights into their function and activation mechanisms, aiding in predicting protein–ligand interactions, anticipating off-target effects, and facilitating the development of therapeutic agents. Numerous computational methods assessing global or local similarity in protein cavities have emerged, but their utilization is impeded by complexity, impractical automation for amino acid pattern searches, and an inability to evaluate the dynamics of scrutinized protein–ligand systems. Here, we present a general, automatic and unbiased computational pipeline, named VirtuousPocketome, aimed at screening huge databases of proteins for similar binding pockets starting from an interested protein–ligand complex. We demonstrate the pipeline's potential by exploring a recently-solved human bitter taste receptor, i.e. the TAS2R46, complexed with strychnine. We pinpointed 145 proteins sharing similar binding sites compared to the analysed bitter taste receptor and the enrichment analysis highlighted the related biological processes, molecular functions and cellular components. This work represents the foundation for future studies aimed at understanding the effective role of tastants outside the gustatory system: this could pave the way towards the rationalization of the diet as a supplement to standard pharmacological treatments and the design of novel tastants-inspired compounds to target other proteins involved in specific diseases or disorders. The proposed pipeline is publicly accessible, can be applied to any protein–ligand complex, and could be expanded to screen any database of protein structures.

Background/Aim: Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice. Patients and Methods: Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pylori infection was computed. Results: A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett’s oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pylori was present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p = 0.001), and peptic ulcers were more frequently detected in patients with H. pylori (9.4% vs. 2.3%; p = 0.001) and in males (5.8% vs. 1.6%; p = 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p = 0.001). Conclusions: The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.

Abstract The interspecific transmission of pathogens can occur frequently in the environment. Among wild bees, the main spillover cases are caused by pathogens associated with Apis mellifera, whose colonies can act as reservoirs. Due to the limited availability of data in Italy, it is challenging to accurately assess the impact and implications of this phenomenon on the wild bee populations. In this study, a total of 3372 bees were sampled from 11 Italian regions within the BeeNet project, evaluating the prevalence and the abundance of the major honey bee pathogens (DWV, BQCV, ABPV, CBPV, KBV, Nosema ceranae, Ascosphaera apis, Crithidia mellificae, Lotmaria passim, Crithidia bombi). The 68.4% of samples were positive for at least one pathogen. DWV, BQCV, N. ceranae and CBPV showed the highest prevalence and abundance values, confirming them as the most prevalent pathogens spread in the environment. For these pathogens, Andrena, Bombus, Eucera and Seladonia showed the highest mean prevalence and abundance values. Generally, time trends showed a prevalence and abundance decrease from April to July. In order to predict the risk of infection among wild bees, statistical models were developed. A low influence of apiary density on pathogen occurrence was observed, while meteorological conditions and agricultural management showed a greater impact on pathogen persistence in the environment. Social and biological traits of wild bees also contributed to defining a higher risk of infection for bivoltine, communal, mining and oligolectic bees. Out of all the samples tested, 40.5% were co-infected with two or more pathogens. In some cases, individuals were simultaneously infected with up to five different pathogens. It is essential to increase knowledge about the transmission of pathogens among wild bees to understand dynamics, impact and effects on pollinator populations. Implementing concrete plans for the conservation of wild bee species is important to ensure the health of wild and human-managed bees within a One-Health perspective.

We report a case of a 40-year-old female with a solitary plasmacytoma of the right transverse apophysis of C1 who underwent combined transoral ablation using a curved steerable needle and cementoplasty under CBCT and infra-red augmented reality navigation system. An imaging work-up revealed an osteolytic lesion determining partial collapse of the right lateral mass of C1 and involving the vertebral foramen. After a biopsy, that revealed a solid tissue consistent with plasmacytoma, it was decided to proceed with radiation therapy. Subsequent PET-CT restaging scans showed residual tumors treated with a transoral percutaneous approach, combining ablation and cementoplasty. This report evaluates the benefits of this combined procedure and the transoral approach, focusing on the advantages of steerable devices and navigation systems.

Objective To show the effectiveness of goal-oriented proprioceptive training in subacute stroke for balance, autonomy, and fall risk. Methods Out a total of 35 patients, consistent in age (75.31±8.65 years), type of stroke (ischemic, 3 to 11 weeks before), and motor impairment, 18 patients underwent solely proprioceptive rehabilitation, the other 17 dual task exercises. The study assessed autonomy using Barthel Index, fall risk with Timed Up and Go Test (TUG), balance through Berg Balance Scale (BBS) and Tinetti test. Results After two months, significant improvements were recorded in Barthel Index, BBS (p

In confined and hazardous environments where human access is severely limited, hyper-redundant manipulators play a crucial role in preserving operator safety and mitigating operational risks. Their numerous degrees of freedom and compact design make them particularly well-suited in the context of nuclear fusion reactors, whose distinct geometry, restricted spaces and heavy loads to be handled, pose unique challenges that conventional manipulators struggle to overcome. This paper proposes a bidirectional control interface for the teleoperation of hyper-redundant robots, with an application to the inspection and maintenance of magnetic fusion reactors. The proposed strategy provides the operator with an intuitive interface and optimises the robot configuration while reducing unnecessary moments of its bulky parts, which may impact the overall system performance and operation safety. It includes two control modes: position and velocity control, which can be selected based on the operator’s preferences. Additionally, the strategy integrates Virtual Fixtures (VFs) in both master and slave control to provide haptic feedback and prevent the slave robot from reaching singular configurations, joint and torque limits, or colliding with the environment. Tests were performed on the DTT Hyper-Redundant Manipulator which was teleoperated through a haptic device by 9 volunteers. The achieved results demonstrated that using VFs allows the robot teleoperation more efficiently and effectively, keeping it within the joint position and torque safety ranges and far from forbidden regions of the environment, while concurrently reducing the movement of the bulky parts.

This paper presents Hybrid Cascode Compensation with Hybrid Q–Factor Control (HCCHQ), for three-stage feedback operational transconductance amplifiers (OTA) capable of handling any load capacitor ( $C_{L}$ ). The design incorporates an enhanced Miller compensation strategy, exploiting cascode-Miller compensation with hybrid pathways to effectively separate the dominant pole from non-dominant poles for bandwidth expansion. It also combines a hybrid quality factor (Q–factor) control with a local impedance attenuation (LIA) module, adjusting the Q–factor of non-dominant poles by mitigating the ringing in the time response and the frequency peaking for lighter $C_{L}$ s. The new design can accommodate unlimited capacitive loads, owing to the Miller– and load-compensated solutions for the light and heavy $C_{L}$ s, respectively. Fabricated in a 180-nm standard CMOS process, a prototype of the proposed amplifier demonstrates a quiescent current of $25~\mu $ A under a 1.8 V single supply. It boasts a compact 0.0055 mm2 area and exhibits unconditional stability when configured as a voltage buffer driving any $C_{L}$ . With a mean DC gain of 115 dB, the average unit-gain frequency (UGF) is 2.30 MHz and 0.11 MHz for 0.1 and 47 nF external capacitive loads, respectively. The mean 1% settling time is measured as $2.41~\mu $ s and $40~\mu $ s for the same capacitive loads, respectively, when a 0.4 V pulse signal is applied to the input.