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The implementation of advanced recycling techniques represents a key strategy for mitigating the mismanagement and the environmental impact of plastic waste. A limited array of plastic polymers can be efficiently recycled, while a notable portion of plastic waste remains unrecyclable. In Italy, this residual, heterogeneous fraction is referred to as Plasmix. Because of its complexity and non-homogeneous composition, Plasmix is primarily directed towards low-value applications. However, recent developments in laboratory-scale mechanical recycling have enabled the creation of new plastic materials from Plasmix. Prior to their application, these materials must undergo rigorous eco-safety evaluation. The present study aims to assess the potential toxicity of microplastics (MPs) from Plasmix-based materials on the freshwater crustacean Daphnia magna. Specifically, this study investigated sub-individual and individual effects induced by a 21-day exposure to different concentrations of MPs generated from the grinding of naïve and Additivated Plasmix-based materials (hereafter referred to as Px-MPs and APx-MPs, respectively). Sub-individual endpoints focused on changes in oxidative status, including the modulation of antioxidant and detoxifying enzyme activities, as well as oxidative damage, such as lipid peroxidation. Individual level endpoints included alterations in survival and reproduction. Microscopy analyses confirmed the ingestion of both Px-MPs and APx-MPs by D. magna individuals. An oxidative stress condition raised in organisms exposed to Px-MPs, whereas no effect was observed in individuals exposed to APx-MPs. Although survival was not affected, a significant impairment in reproductive output was detected at the end of exposure to all the concentrations of both MP types. These findings suggest that even low concentrations of Px-MPs and APx-MPs could negatively affect the health status of D. magna, underscoring the need for further research to complete the risk assessment of Plasmix-based materials prior to their use in consumer products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Marco Parolini reports financial support was provided by University of Milan. Marco Parolini reports a relationship with University of Milan that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Raised emissions of biologically reactive nitrogen (N) have intensified N deposition, enhancing tree productivity globally. Nonetheless, the drivers of forest sensitivity to N deposition remain unknown. We used stem growth data from 62,000 trees across Europe combined with N deposition data to track the effects of air temperature and precipitation on tree growth's sensitivity to N deposition and how it varied depending on leaf form over the past 30 years. Overall, N deposition enhanced conifer growth (until 30 kg N ha -1  yr -1 ) while decreasing growth for broadleaved angiosperms. Lower temperatures led to higher growth sensitivity to N deposition in conifers potentially exacerbated by N limitation. In contrast, higher temperatures stimulated growth sensitivity to N deposition for broadleaves. Higher precipitation equally increased N deposition sensitivity in all leaf forms. We conclude that air temperature and leaf form are decisive in disentangling the effect of N deposition in European forests, which provides crucial information to better predict the contribution of N deposition to land carbon sink enhancement., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The aim of this study is to develop a radiomic and deep learning-based signature for survival analysis of patients with Non-Small Cell Lung Cancer., Methods: Four-hundred twenty-two patients from "Lung1" dataset were included in the study. A 3D convolutional autoencoder (AE) was built and features from the latent space extracted for further analysis. Radiomic features were derived from the 3D volume of the tumor region using PyRadiomics. Both radiomic and AE-based features underwent feature selection, by removing: i) highly correlated and ii) constant features. The selected variables were then used to derive both mono-domain (radiomics, AE and clinic) and multi-domain signatures fitting a Cox Proportional Hazard model with LASSO penalization and evaluated considering the concordance (C)-index as performance metric., Results: Both mono-domain and multi-domain signatures could significantly differentiate high risk from low risk patients. Among the mono-domain signatures, the highest hazard ratio (HR) in the test set was obtained using radiomics (HR = 1.5428) followed by the AE-based signature (HR = 1.5012) and the clinical signature (HR = 1.4770). The best overall performance was achieved by combining all three signatures, resulting in the highest HR (HR = 1.7383), while the combination of AE-based and clinical signatures yielded the highest C-index (C-index = 0.6309)., Conclusions: These preliminary results show that combining information carried by AE, radiomic and clinical domain shows potential for improving the prediction of overall survival in NSCLC patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Meri Ferretti reports financial support was provided by Italian Minister of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Although many studies highlighted the potential of COVID-19 to reshape existing models of wildlife management, empirical research on this topic has been scarce, particularly in Europe. We investigated the potential of COVID-19 pandemic to accelerate the ongoing decline in an aging population of recreational hunters in Italy. Namely, we modelled spatiotemporal trends between 2011 and 2021 in the number of recreational hunters in 50 Italian provinces with a varying incidence of COVID-19, and temporally delayed waves of infection. Compared to projections from 2011-2019 data, we detected a lower number of hunters who enrolled for the hunting season, both in 2020 (14 provinces) and in 2021 (15 provinces). The provinces with the highest incidence of COVID-19 in the Lombardy and Emilia-Romagna regions were also those experiencing the most marked decrease in hunting participation. Our findings revealed that a wildlife management system based on recreational hunting can be rapidly destabilized by epidemics and their associated public health measures, particularly when the average age of hunters is high, like in Italy. Considered the high incidence attained by COVID-19 in many European countries, where hunters are pivotal for the management of large ungulates and where they were already declining before the pandemic, our findings call for further large-scale research about the impact of COVID-19 on hunting participation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cerri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hallux valgus (lateral angulation of the great toe towards the lesser toes, commonly known as bunions) presents in 23% to 35% of the population. This condition leads to poor balance and increases the risk of falling, adding to the difficulty in fitting into shoes and pain. Conservative (non-surgical) interventions treating pain rather than curing deformity are usually first-line treatments. When surgery is indicated, the overall best surgical procedure is an ever-evolving topic of discussion., Objectives: To assess the benefits and harms of different types of surgery compared with placebo or sham surgery, no treatment, non-surgical treatments and other surgical interventions for adults with hallux valgus., Search Methods: We searched CENTRAL, MEDLINE, Embase and trial registries to 20 April 2023. We did not apply any language or publication restrictions., Selection Criteria: We included randomised controlled trials evaluating surgical interventions for treating hallux valgus compared to placebo surgery or sham surgery, no treatment, non-surgical treatment or other surgical interventions. The major outcomes were pain, function, quality of life, participant global assessment of treatment success, reoperation (treatment failure), adverse events and serious adverse events., Data Collection and Analysis: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and the certainty of evidence using GRADE., Main Results: We included 25 studies involving 1597 participants with hallux valgus. All studies included adults and most were women. One study compared surgery (V-shaped osteotomy) with no treatment and with non-surgical treatment. Fifteen studies compared different surgical techniques, including a V-shaped osteotomy (Chevron osteotomy), to other types of osteotomy. Nine studies compared different simple osteotomy techniques to each other or to a mid-shaft Z-shaped osteotomy (Scarf osteotomy). Most trials were susceptible to bias: in particular, selection (80%), performance (88%), detection (96%) and selective reporting (64%) biases. Surgery versus no treatment Surgery may result in a clinically important reduction in pain. At 12 months, mean pain was 39 points (0 to 100 visual analogue scale, 100 = worst pain) in the no treatment group and 21 points in the surgery group (mean difference (MD) -18.00, 95% confidence interval (CI) -26.14 to -9.86; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in a slight increase in function. At 12 months, mean function was 66 points (0 to 100 American Orthopedics Foot and Ankle Scale (AOFAS), 100 = best function) in the no treatment group and 75 points in the surgery group (MD 9.00, 95% CI 5.16 to 12.84; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in little to no difference in quality of life. At 12 months, mean quality of life (0 to 100 on 15-dimension scale, 100 = higher quality of life) was 93 points in both groups (MD 0, 95% CI -2.12 to 2.12; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in a slight increase in participant global assessment of treatment success. At 12 months, mean participant global assessment of treatment success was 61 points (0 to 100 visual analogue scale, 100 = completely satisfied) in the no treatment group and 80 points in the surgery group (MD 19.00, 95% CI 8.11 to 29.89; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may have little effect on reoperation (relative effect was not estimable), adverse events (risk ratio (RR) 8.75, 95% CI 0.48 to 159.53; 1 study, 140 participants; very low-certainty evidence), and serious adverse events (relative effect was not estimable), but we are uncertain. Surgery versus non-surgical treatment Surgery may result in a clinically important reduction in pain; a slight increase in function and participant global assessment of treatment success; and little to no difference in quality of life (1 study, 140 participants; low-certainty evidence). We are uncertain about the effect on reoperation, adverse events and serious adverse events (1 study, 140 participants; very low-certainty evidence). Complex versus simple osteotomies Complex osteotomies probably result in little to no difference in pain compared with simple osteotomies (7 studies, 414 participants; moderate-certainty evidence). Complex osteotomies may increase reoperation (7 studies, 461 participants; low-certainty evidence), and may result in little to no difference in participant global assessment of treatment success (8 studies, 462 participants; low-certainty evidence) and serious adverse events (12 studies; data not pooled; low-certainty evidence). We are uncertain about the effect of complex osteotomies on function and adverse events (very low-certainty evidence). No study reported quality of life., Authors' Conclusions: There were no trials comparing surgery to placebo or sham. Surgery may result in a clinically important reduction in pain when compared to no treatment or non-surgical treatment. Surgery may also result in a slight increase in function and participant global assessment of treatment success compared to no treatment or non-surgical treatment. There may be little to no difference in quality of life between surgery and no treatment or non-surgical treatment. We are uncertain about the effect of surgery on reoperation (treatment failure), adverse events or serious adverse events, when compared to no treatment or non-surgical treatment. Complex and simple osteotomies demonstrated similar results for pain. Complex osteotomies may increase reoperation (treatment failure) and may result in little to no difference in participant global assessment of treatment success and serious adverse events compared to simple osteotomies. We are uncertain about the effect of complex osteotomies on function, quality of life and adverse events., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The role of strengthening the lower limbs to optimize the biomechanics of the hip, knee and ankle during walking in patients with knee osteoarthritis, is still unclear. This study aimed to analyse the walking biomechanics of individuals with symptomatic mild to moderate knee osteoarthritis before and after a simplified lower limb resistance training protocol, focused on knee joint exercises with individualized load., Methods: Forty-one patients with symptomatic and radiographic mild to moderate knee osteoarthritis underwent 3D gait analysis pre-post 8 weeks lower limb resistance training protocol performed 3 times a week. Parameters investigated were spatiotemporal, sagittal range of motion, flexion and extension minimum and maximum values, power and moment of hip, knee and ankle, as well as self-reported pain and physical function by the Western Ontario MacMaster University Osteoarthritis Index. Paired t test, Wilcoxon, Spearman's correlation and a logistic model were used for statistical analysis, with p < 0.05. Pain improvement more than 2 points was considered clinically relevant. The effect size (ES) was calculated using Cohen's d., Results: Post protocol walking speed increased 6.7% (ES: 0.711), cadence 3.7% (ES: 0.655), stride length 2.6% (ES: 0.542), and double support time reduced 6.9% (ES:0.459). It was also observed a significant increase in one maximum repetition test for legpress 46%, knee extension 23% and knee flexion chair 27% (p < 0.001). Patients reported a 62.5% reduction in pain (ES:1.518) and 64.9% improvement in physical function (ES:1.376). 82% of the patients presented more than 2 points improvement in pain. No evidence of strong correlations between pain, strength gains and gait parameters were found., Conclusions: There was a significant and clinical improvement of spatiotemporal gait parameters, pain, physical function, and strength after 8-week lower limb resistance training protocol. Patients who had a clinically relevant pain improvement presented better gait performance., Competing Interests: Declaration of competing interest The authors declared that they have no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The length of 3' untranslated regions (3'UTR) is highly regulated during many transitions in cell state, including T cell activation, through the process of alternative polyadenylation (APA). However, the regulatory mechanisms and functional consequences of APA remain largely unexplored. Here we present a detailed analysis of the temporal and condition-specific regulation of APA following activation of primary human CD4 + T cells. We find that global APA changes are regulated temporally and CD28 costimulatory signals enhance a subset of these changes. Most APA changes upon T cell activation involve 3'UTR shortening, although a set of genes enriched for function in the mTOR pathway exhibit 3'UTR lengthening. While upregulation of the core polyadenylation machinery likely induces 3'UTR shortening following prolonged T cell stimulation; a significant program of APA changes occur prior to cellular proliferation or upregulation of the APA machinery. Motif analysis suggests that at least a subset of these early changes in APA are driven by upregulation of RBM3, an RNA-binding protein which competes with the APA machinery for binding. Together this work expands our understanding of the impact and mechanisms of APA in response to T cell activation and suggests new mechanisms by which APA may be regulated., (© 2024. The Author(s).)

Aim: Recent literature has shown epidemiological changes in bronchiolitis with an increased incidence in the post-SARS-CoV-2 pandemic period but reports regarding disease severity are conflicting. We aimed to describe the epidemiology, disease severity, and microbiology of bronchiolitis during the 2022-2023 cold season compared to the previous 5 years., Methods: This single-center retrospective observational study at IRCCS Gaslini, Italy, included all children aged 0-2 years hospitalized for bronchiolitis from 1 September 2017 to 31 August 2023. Findings from the 2022-2023 season were compared to the previous 5 years., Results: We observed a statistically significant increase in the 2022-2023 season in the absolute number of bronchiolitis admissions. Children who required mechanical ventilation (MV) dramatically increased from a total of seven patients in the previous five seasons to 17 in the 2022-2023 season alone (p = .001). All other severity parameters significantly increased: the need for respiratory support (p = .002), the median length of stay (5 days vs. 4 days, p = .001), and the median duration of respiratory support (4 days vs. 3 days, p = .016)., Conclusions: We report a substantial increase in the severity of bronchiolitis in the season 2022-2023 with a remarkable number of previously healthy infants requiring MV. Further studies are needed to confirm whether our findings are an isolated phenomenon or part of a true global trend. Health systems need to be prepared and protective preventive measures should be implemented for all newborns., (© 2024 Wiley Periodicals LLC.)

Competing Interests: LC-A is the scientific project manager of the Women's Brain Project. ASC is the co-founder and pro bono CEO of the WBP. ASC is also the pro bono Euresearch Vice President. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Competing Interests: Competing interests: None declared.

Forest soils harbor hyper-diverse microbial communities which fundamentally regulate carbon and nutrient cycling across the globe. Directly testing hypotheses on how microbiome diversity is linked to forest carbon storage has been difficult, due to a lack of paired data on microbiome diversity and in situ observations of forest carbon accumulation and storage. Here, we investigated the relationship between soil microbiomes and forest carbon across 238 forest inventory plots spanning 15 European countries. We show that the composition and diversity of fungal, but not bacterial, species is tightly coupled to both forest biotic conditions and a seven-fold variation in tree growth rates and biomass carbon stocks when controlling for the effects of dominant tree type, climate, and other environmental factors. This linkage is particularly strong for symbiotic endophytic and ectomycorrhizal fungi known to directly facilitate tree growth. Since tree growth rates in this system are closely and positively correlated with belowground soil carbon stocks, we conclude that fungal composition is a strong predictor of overall forest carbon storage across the European continent., (© 2024. The Author(s).)

In this contribution, the performance of powdered titanium dioxide (TiO 2 )-based photocatalysts was evaluated in a pilot photocatalytic plant for the degradation of different dyes, with an investigated volume of 1 L and solar simulated light as irradiation source. Five different samples, synthesized in our laboratories, were tested in the pilot plant, each consisting of TiO 2 nanoparticles (NPs) coupled with a different material (persistent luminescent material and semiconductor material) and treated in different thermal conditions. All synthesized samples have been subjected to X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller analysis (BET), and transmission electron microscopy (TEM) characterization, to shed light on the influence of introducing other materials on titania characteristics. To study and evaluate the significance of the parameters affecting the process in the pilot plant, a chemometric approach was applied, by selecting a mathematical model (D-Optimal) to simultaneously monitor a large number of variables (i.e., 7), both qualitative and quantitative, over a wide range of levels. At the same time, the recovery of the synthesized photocatalysts was studied following a novel promising recuperation method, i.e., annulling the surface charge of the suspended samples by reaching the isoelectric point (pH PZC ) of each sample, for the quantitative precipitation of TiO 2 nanoparticles., (© 2024. The Author(s).)

Aim: To provide a comprehensive description of the clinical features, biochemical characteristics, and outcomes of infants up to 90 days old with COVID-19. Moreover, to assess the severity of the disease and propose an effective management pathway., Methods: Retrospective single-center study spanning three years. Patient data includes age, sex, symptoms, comorbidities, blood and urine test results, cultures, admission, length of stay, therapies, intensive care unit admission, and mortality., Results: A total of 274 patients were enrolled in the study, comprising 55% males. Among them, 60 patients (22%) were under the age of 29 days, while 214 (78%) fell within the 29 to 90 days age range. The overall incidence of SARS-CoV-2 infections was 0.28 per 10,000 Pediatric Emergency Department admissions. Blood inflammatory markers showed no significant abnormalities, and there were no recorded instances of positive blood cultures. Less than 1% of infants showed urinary tract infections with positive urine cultures, and 1.5% of patients had a concurrent RSV infection. Hospitalization rates were 83% for neonates and 67% for infants, with a median length of stay (LOS) of 48 h for both age groups. None of the patients required admission to the Pediatric or Neonatal Intensive Care Unit, and only one required High Flow Nasal Cannula (HFNC). No secondary serious bacterial infections were observed, and all hospitalized patients were discharged without short-term sequelae. No deaths were reported., Discussion and Conclusions: Infants with COVID-19 generally exhibit milder or asymptomatic forms of the disease, making home management a viable option in most cases. Blood tests, indicative of a mild inflammatory response, are recommended primarily for children showing symptoms of illness. Hospitalization precautions for infants without apparent illness or comorbidities are deemed unnecessary. Given the evolving nature of experiences with COVID-19 in infants, maintaining a high level of clinical suspicion remains imperative.

The aim of this study was to describe the 2022-2023 bronchiolitis epidemic season (the second after COVID-19 pandemic and the first without social restriction), focusing on patients discharged home from a pediatric emergency department (PED) and on those revisited within 72 h. We performed a retrospective observational study in an Italian tertiary care children's hospital, reviewing PED accesses from 1 October 2022 to 31 March 2023. The number of hospitalizations for bronchiolitis was extracted from hospital discharge forms. A total of 512 patients diagnosed with bronchiolitis were admitted to PED (2.8% of total admissions). Accesses increased sharply from November to January, with a peak in December, in both admissions and hospitalizations. More than half of the patients (55.5%) were safely discharged home, while 38 (13.4%) came back to PED for a revisit. Overall PED accesses and hospitalizations for bronchiolitis increased since the previous epidemic season, and particularly compared to the pandemic and pre-pandemic eras. Empowering the collaboration between all healthcare provisioners is fundamental to suitable management of patients. Monitoring the epidemiology and seasonality of bronchiolitis is a starting point for an effective internal organization of pediatric departments and to further evaluate its socio-economic burden.

Many lung diseases, first, tumors, are smoking-related, and it is very likely to find more than one pattern in the same patient. Airspace enlargement with fibrosis (AEF) is one of them, but it has not been deeply understood or studied yet. In fact, we think that it might still be wrongly assimilated with other conditions that have different radiological features altogether and different prognoses. This pictorial essay is aimed at pointing out AEF so that radiologists and pulmonologists get acquainted with it and use the proper terminology, as AEF might not be that rare., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

To examine the effectiveness of Mind Over Matter (MOM), a group psychosocial intervention based on CBT, ACT, and mind-body interventions, from data collected during a quality improvement project. MOM was offered in person prior to COVID-19 and via telehealth after COVID-19 began., Distress, as measured by anxiety, depression, the severity of physical symptoms and the impact of physical symptoms on daily functioning, was measured pre- and post-MOM., The sample included 46 participants with an experience of cancer ranging in age from 31 to 75., Overall, there were significant differences in anxiety, depression, and physical symptom severity and interference pre and post MOM. The in-person intervention showed significant differences in anxiety, depression, and physical symptom interference. There were significant differences in anxiety and physical symptom severity reported in the telehealth groups., MOM may be an effective psychosocial intervention for addressing cancer-related physical and emotional challenges making it a valuable resource for institutions trying to meet needs identified by distress screenings.

This retrospective chart review study investigates the long-term clinical outcome of Biodentine® (Tricalcium silicate) as a medicament for pulpotomy in primary molars. Data in this retrospective study was collected from the dental records of all patients that had at least one primary molar receive pulpotomy treatment (CDT code: D3221) between 01 July 2012 and 01 July 2015. This data includes child's age, medical history, dental history, dental radiographs, pulpotomy procedure details and follow-up clinical notes. Kaplan-Meier Estimate was used to measure the fraction of successful pulpotomy procedures for up to 24 months. A total of 1758 pulpotomy procedures were performed on 1032 patients in our institute in the three-year period and 21.4% of them (N = 376) had follow-up dental records that qualified for the study. Eleven teeth out of 376 teeth were excluded from the statistical analysis due to loss of/broken stainless steel crowns (3.1%). Seventeen pulpotomy failures were identified out of the remaining 365 procedures. The survival probablity of using Biodentine® as a pulpotomy medicament is 96.3% for 18-month follow-up and 95.4% for 24-month follow-up. Biodentine®, a tricalcium silicate formulation, used as a pulpotomy medicament demonstrates a high clinical success rate (95.4%) over a 24-month peroid in primary molars., Competing Interests: The authors declare no conflict of interest. Gerald A. Ferretti is serving as one of the Editorial Board members of this journal. We declare that Gerald A. Ferretti had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to GS., (©2024 The Author(s). Published by MRE Press.)

Background: Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in SMA type 1 patients via structured light plethysmography (SLP). SLP measures the thoraco-abdominal movements by projecting a light grid onto the anterior thoraco-abdominal surface., Methods: Cross-sectional study of consecutive children with SMA type 1. All children underwent motor assessment (CHOP-INTEND) and one-minute tidal breathing recording by SLP in supine position while self-ventilating in room air. The Respiratory rate , the abdominal vs. chest contribution to breath ( Relative Expired Abdomen% , Relative Expired Chest% ) and the severity of thoraco-abdominal paradox ( Phase Angle ) were acquired., Results: Nineteen patients were included, median (IQR) age 2.3 years (1.4-7.9). Their respiratory pattern captured via SLP showed a raised median (IQR) respiratory rate per age of 33.5 bpm (26.6-41.7), a prevalent abdominal contribution to tidal breathing with median (IQR) Relative Expired Abdomen 77% (68-90) vs. Chest 23% (10-32). Thoracoabdominal paradox was detected (median Phase Angle 48.70°) and its severity correlated negatively with CHOP-INTEND (r -0.8, p < 0.01)., Conclusions: SLP captured and quantified the respiratory features of infants and children with SMA type 1.

Objective: Misdiagnosed/chronic Achilles tendon injuries are rare and disabling for patients. The surgical treatment of these rare injuries aims to ensure the tendon heals mechanically and biologically. This is the prerequisite for a good clinical and functional outcome and reduces recurrences. The main aim of the study is to present a surgical technique that has proven to be original, reproducible, and capable of guaranteeing solid tendon repair and optimal tissue regeneration., Methods: We treated five patients, four males and one female, with the one-step double augmentation technique. All patients of this study complained of pain, but above all severe functional limitation that Achilles tendon injury had been causing for more than a month. In this study, we widely described the surgical technique, original and not found in the literature, which provides a biological graft (allograft of decellularized dermis) and homologous, thrombin-activated, platelet-rich plasma (H-PRP) in a single step. Surgical approach, always used by the first author, respected predefined steps: careful dissection and preparation of the peritendinous tissues from suture to the end of the procedure, tenorrhaphy, and augmentation with allopatch to obtain a mechanically effective repair to avoid recurrences, and finally "biological" augmentation with a unit of homologous, thrombin activated, PRP. We offered to all patients a regenerative rehabilitation program post-operatively., Results: All patients were evaluated clinically (functional clinical tests and questionnaires) and instrumentally (elastic-sonography and perfusion MRI). The obtained results have been evaluated at a minimum follow-up of 18 months and a maximum of 24 months. In all patients pain was resolved, and district function and kinetic chains improved with resumption of daily activities, work, and sports., Conclusion: The present study confirmed the regenerative potential of decellularized dermis allograft and PRP (homologous and thrombin-activated). The same approach can also be exploited in cases of severe tendon destructuring and limited "intrinsic" regenerative potential at any age. The proposed one-step surgical technique of a double augmentation therefore appears useful, safe, reproducible, and applicable in all chronic tendon lesions with low regenerative potential., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Alphaviruses are a large group of re-emerging arthropod-borne RNA viruses. The compact viral RNA genomes harbor diverse structures that facilitate replication. These structures can be recognized by antiviral cellular RNA-binding proteins, including DExD-box (DDX) helicases, that bind viral RNAs to control infection. The full spectrum of antiviral DDXs and the structures that are recognized remain unclear. Genetic screening identified DDX39A as antiviral against the alphavirus chikungunya virus (CHIKV) and other medically relevant alphaviruses. Upon infection, the predominantly nuclear DDX39A accumulates in the cytoplasm inhibiting alphavirus replication, independent of the canonical interferon pathway. Biochemically, DDX39A binds to CHIKV genomic RNA, interacting with the 5' conserved sequence element (5'CSE), which is essential for the antiviral activity of DDX39A. Altogether, DDX39A relocalization and binding to a conserved structural element in the alphavirus genomic RNA attenuates infection, revealing a previously unknown layer to the cellular control of infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 10 6 cells/kg bw ) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Background: Spontaneous coronary artery dissection (SCAD) often presents with acute coronary syndrome and underlying pathophysiology involves the interplay between predisposing factors and precipitating stressors, such as emotional and physical triggers. In our study we sought to compare clinical, angiographic and prognostic features in a cohort of patients with SCAD according to the presence and type of precipitating stressors., Methods: Consecutive patients with angiographic evidence of SCAD were divided into three groups: patients with emotional stressors, patients with physical stressors and those without any stressor. Clinical, laboratoristic and angiographic features were collected for each patient. The incidence of major adverse cardiovascular events, recurrent SCAD and recurrent angina was assessed at follow-up., Results: Among the total population (64 subjects), 41 [64.0%] patients presented with precipitating stressors, including emotional triggers (31 [48.4%] subjects) and physical efforts (10 [15.6%] subjects). As compared with the other groups, patients with emotional triggers were more frequently female (p = 0.009), had a lower prevalence of hypertension (p = 0.039] and dyslipidemia (p = 0.039), were more likely to suffer from chronic stress (p = 0.022) and presented with higher levels of C-reactive protein (p = 0.037) and circulating eosinophils cells (p = 0.012). At a median follow-up of 21 [7; 44] months, patients with emotional stressors experienced higher prevalence of recurrent angina (p = 0.025), as compared to the other groups., Conclusions: Our study shows that emotional stressors leading to SCAD may identify a SCAD subtype with specific features and a trend towards a worse clinical outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Due to the aging of population, materials able to repair damaged tissues are needed. Among others, bioactive glasses (BGs) have attracted a lot of interest due to their outstanding properties both for hard and soft tissues. Here, for the first time, two new BGs, which gave very promising results in preliminary in vitro-tests, were implanted in animals in order to evaluate their regenerative potential. The new BGs, named BGMS10 and Bio&#95;MS and containing specific therapeutic ions, were produced in granules and implanted in rabbits' femurs for up to 60 days, to test their biocompatibility and osteoconduction. Additionally, granules of 45S5 Bioglass® were employed and used as a standard reference for comparison. The results showed that, after 30 days, the two novel BGs and 45S5 displayed a similar behavior, in terms of bone amount, thickness of new bone trabeculae and affinity index. On the contrary, after 60 days, 45S5 granules were mainly surrounded by wide and scattered bone trabeculae, separated by large amounts of soft tissue, while in BGMS10 and Bio&#95;MS the trabeculae were thin and uniformly distributed around the BG granules. This latter scenario could be considered as more advantageous, since the features of the two novel BG granules allowed for the neo-formation of a uniformly distributed bony trabeculae, predictive of more favorable mechanical behavior, compared to the less uniform coarse trabeculae, separated by large areas of soft tissue in 45S5 granules. Thus, BGMS10 and Bio&#95;MS could be considered suitable products for tissue regeneration in the orthopedic and dental fields., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

The aim of this study is to apply and characterize eXplainable AI (XAI) to assess the quality of synthetic health data generated using a data augmentation algorithm. In this exploratory study, several synthetic datasets are generated using various configurations of a conditional Generative Adversarial Network (GAN) from a set of 156 observations related to adult hearing screening. A rule-based native XAI algorithm, the Logic Learning Machine, is used in combination with conventional utility metrics. The classification performance in different conditions is assessed: models trained and tested on synthetic data, models trained on synthetic data and tested on real data, and models trained on real data and tested on synthetic data. The rules extracted from real and synthetic data are then compared using a rule similarity metric. The results indicate that XAI may be used to assess the quality of synthetic data by (i) the analysis of classification performance and (ii) the analysis of the rules extracted on real and synthetic data (number, covering, structure, cut-off values, and similarity). These results suggest that XAI can be used in an original way to assess synthetic health data and extract knowledge about the mechanisms underlying the generated data.

Background: Drowning is a serious and underestimated public health problem, with the highest morbidity and mortality reported among children. Data regarding pediatric outcomes of drowning are often inadequate, and data collection is poorly standardized among centers. This study aims to provide an overview of a drowning pediatric population in pediatric emergency department, focusing on its main characteristics and management and evaluating prognostic factors., Methods: This is a retrospective multicenter study involving eight Italian Pediatric Emergency Departments. Data about patients between 0 to 16 years of age who drowned between 2006 and 2021 were collected and analyzed according to the Utstein-style guidelines for drowning., Results: One hundred thirty-five patients (60.9% males, median age at the event 5; interquartile range, 3-10) were recruited and only those with known outcome were retained for the analysis (133). Nearly 10% had a preexisting medical conditions with epilepsy being the most common comorbidity. One third were hospitalized in the intensive care unit (ICU) and younger males had a higher rate of ICU admission than female peers. Thirty-five patients (26.3%) were hospitalized in a medical ward while 19 (14.3%) were discharged from the emergency department and 11 (8.3%) were discharged after a brief medical observation less than 24 hours. Six patients died (4.5%). Medium stay in the ED was approximately 40 hours. No difference in terms of ICU admission was found between cardiopulmonary resuscitation performed by bystanders or trained medical personnel ( P = 0.388 vs 0.390)., Conclusions: This study offers several perspectives on ED victims who drowned. One of the major finding is that no difference in outcomes was seen in patients who received cardiopulmonary resuscitation performed by bystanders or medical services, highlighting the importance of a prompt intervention., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Applying a digital health intervention to measure health and wellbeing status offers opportunities to guide and augment healthcare and promotion. In our scenario, we consider mainly digital-native patients and present an evaluation of a new Healthcare Magenta Scorecard towards this end., Methods: Grounded in the six domains of health and promotion (physical activity; sleep quality; nutrition; habits/lifestyle; mental health; quality of life) we developed a health Magenta Scorecard (Magenta Score), a mobile based Electronic Patient Reported Outcomes (e-PRO) that measures patients health and wellbeing every 3-5 months. The Magenta Scorecard was derived from previously published evidence-based instruments. We collected data as patients were onboarded into our healthcare system (T0 and T1, time span between measurements, 141 days) and provided correlations among our domains of care., Results: A total of 1,622 participants responded to T0 and T1 our Magenta Scorecard. Participants mean age was 31.3 [95% confidence interval (CI): 31.2-31.5] years and female (63.4%). Fifty-five percent (n=892) of our sample were categorized as relating to Health and Wellbeing promotion, 8.5% (n=138) disease management, 35.7% (n=579) self-care care support and only 0.8% (n=13) pertained to case management. From our care coordination guided approach, our Magenta Scorecards reported mean improvement across the study cohort of 26 ± standard deviation (SD) points, from T0 (649, 95% CI: 643-656) to T1 (675, 95% CI: 668-682). Our Magenta Scorecard domains had significant, albeit weak spearman correlations., Conclusions: We demonstrated our Magenta Scorecard rationale and its guided approach. The Magenta Scorecard displayed adequate responsiveness and was significantly correlated across all of the domains investigated. Further prospective research is needed to validate our results in the long term., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://mhealth.amegroups.com/article/view/10.21037/mhealth-22-56/coif). All authors report that they are Alice employees with close relations with the company. The authors have no other conflicts of interest to declare., (2023 mHealth. All rights reserved.)

Objective: SARS-COV-2 pandemic profoundly impacted acute bronchiolitis epidemiology worldwide, especially respiratory syncytial virus (RSV) diffusion and the burden of disease, with remarkable implications on the management of health resources. We aimed to study the epidemiology and clinical course of bronchiolitis in the past 5 years in our region and to assess the trends that occurred during and after the SARS-COV-2 pandemic., Methods: We conducted an observational study including all children aged 0-2 years with bronchiolitis admitted to a tertiary children's hospital during the last 5 years. Demographic, clinical, and microbiological data were collected. Comparisons between patient subgroups were carried out., Results: A total of 647 patients admitted for bronchiolitis were included (median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 51.5% of patients in prepandemic years and 74.5% in pandemic years. Through the study period, we observed a progressive increase in the number of children requiring respiratory support, RSV infections, and children with a history of prematurity. Conversely, this was not true for mechanical ventilation, duration of respiratory support, intensive care unit admission, and length of stay., Conclusions: Clinical course and epidemiology of bronchiolitis showed a significant change through the study years with a heavy impact during the 2021-2022 season. The increase in the number of patients requiring respiratory support, although not associated with an increase in mechanical ventilation, may be explained by the higher prevalence of RSV. The change in epidemiology highlights the importance of surveillance systems to monitor RSV circulation, to plan prophylactic strategies, and prepare healthcare systems., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objective  To compare the level of quality of life and satisfaction after two years of total knee arthroplasties between individuals above and below 65 years of age and to identify predictor factors of poor clinical outcome and low level of satisfaction in patients undergoing arthroplasty. Methods  This is a retrospective cohort with data from patients diagnosed with knee osteoarthritis submitted to primary total knee arthroplasty from 2014 to 2018 ( n  = 190). Clinical outcomes were assessed using the following scores: visual analog scale (VAS) of pain, EQ-5D-3L and EUROQOL-VAS (quality of life scales), patient satisfaction level, and functional scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), collected through a questionnaire applied preoperatively, as well as 1, 3, 12 and 24 months after surgery. Results  Patients < 65 years old presented significantly lower values (clinical worsening) in KOOS-pain and KOOS-symptoms. There are no differences in the principal clinical scores that assess pain, function, and quality of life after the procedure, as well as in the rate of satisfaction with the procedure, among patients < 65 years old when compared with patients ≥ 65 years old. It was also observed that patients who were not satisfied with the procedure in the 24-month evaluation presented clinical results in some analyzed scores (KOOS-pain and EQ-VAS) similar to patients who declared themselves satisfied. Conclusion  Scores that assess pain, function, quality of life, as well as satisfaction rate are similar between patients < 65 years old and those ≥ 65 years old., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: There has been an increase in interest in the use of biological therapies in orthopaedic conditions such as knee osteoarthritis. Platelet-rich plasma (PRP) is one of these therapies, but it still lacks consistent results., Purpose: To evaluate the effects (benefits and harms) of PRP intra-articular injection compared with other nonsurgical methods for the treatment of knee osteoarthritis., Study Design: Systematic review and meta-analysis of randomized and quasi-randomized controlled trials; Level of evidence, 2., Methods: Three electronic databases were searched to identify relevant studies published before January 2021. The primary outcomes were pain, function, and failure of treatment. Risks of bias of all trials were assessed using a Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation System was used to assess the quality of evidence of included studies., Results: A total of 40 studies with 3035 participants were included. Analysis of this review focused on comparing PRP with hyaluronic acid, corticosteroid, and saline, as we believe they are the most relevant comparisons with the most studies available. At 6-month follow-up, PRP was as effective as and in some studies more effective than other therapies regarding pain, function, and stiffness. However, current evidence is of low or very low quality and is based on trials with high risk of bias and great heterogeneity among them. No significant difference among treatments was found concerning major adverse events and treatment failure., Conclusion: Although studies suggest that PRP may be more effective than or at least as effective as other modalities of nonsurgical treatment for knee osteoarthritis in terms of pain, function, and adverse events, serious limitations and methodological flaws are considerable in the current literature. Therefore, the authors are not able to make recommendations for clinical practice regarding PRP for knee osteoarthritis.

It's known that a magnesium (Mg)-deficient diet is associated with an increased risk of osteoporosis. The aim of this work is to investigate, by a histological approach, the effects of a Mg-deprived diet on the bone of 8-weeks-old C57BL/6J male mice. Treated and control mice were supplied with a Mg-deprived or normal diet for 8 weeks, respectively. Body weight, serum Mg concentration, expression of kidney magnesiotropic genes, and histomorphometry on L5 vertebrae, femurs, and tibiae were evaluated. Body weight gain and serum Mg concentration were significantly reduced, while a trend toward increase was found in gene expression in mice receiving the Mg-deficient diet, suggesting the onset of an adaptive response to Mg depletion. Histomorphometric parameters on the amount of trabecular and cortical bone, number of osteoclasts, and thickness of the growth plate in femoral distal and tibial proximal metaphyses did not differ between groups; these findings partially differ from most data present in the literature showing that animals fed a Mg-deprived diet develop bone loss and may be only in part explained by differences among the experimental protocols. However, the unexpected findings we recorded on bones could be attributed to genetic differences that may have developed after multiple generations of inbreeding.

By killing or weakening trees, drought could change the partitioning of growth between tree sizes or species, thereby altering stand structure. Growth partitioning, often quantified using the growth dominance coefficient (DC) or the shape of tree size versus growth relationships (SGR), indicates the relative contribution of differently sized trees to the total stand growth. Changes in growth partitioning due to droughts are rarely examined but provide valuable information that links tree- and stand-level responses to droughts. The objective of this study was to test whether the 2018 European megadrought altered the growth partitioning among tree sizes and species. For this purpose, we first evaluated whether DC or SGR can be calculated from small sample sizes of trees typical of individual forest inventory plots. DC, and particularly SGR, were sensitive to sample size, forest type (even-aged and uneven-aged), target variable (tree diameter, basal area or stem mass) and range of tree sizes within the sample. SGR could therefore not be used for our analyses. We found no differences in DC prior to and during the 2018 drought. However, when considering only beech (Fagus sylvatica)-dominated stands, DC was lower during post-drought years than during the 2018 drought. The growth of larger trees, especially beech, was more negatively affected during post-drought years. Therefore, an extreme drought event can indeed alter the growth partitioning within forest stands. The DC indicates such changes in partitioning and, hence, which trees can be selected for commercial thinning, or released from competition, to minimize potential impacts of droughts., (© 2021 The Authors. Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

Rapid on-site evaluation (ROSE) is a procedure that allows immediate assessment of adequacy of cytological specimens obtained by fine needle aspiration (FNA). The application of ROSE diagnostic categories has been applied in various organs, but not in thoracic pathology. We aimed to retrospectively assess the concordance with the final diagnosis of a categorization from C1 (inadequate) to C5 (neoplastic) during ROSE performed with bronchoscopic or percutaneous sampling procedures of thoracic lesions in a large series of consecutive cases. This retrospective single-center study evaluated 2282 consecutive ROSEs performed on 1827 patients from January 2016 to December 2020 in 994 cases of transbronchial needle aspiration (TBNA) in peripheral pulmonary lesions, in 898 transthoracic FNAs, in 318 ultrasound-guided TBNAs, in 50 conventional TBNAs and in 22 endobronchial TBNAs. False positive and false negative cases of ROSE were 43 (1.88%) and 73 (3.2%), respectively, when compared with the definitive diagnosis. The sensitivity, specificity and the positive and negative prognostic values of ROSE were 94.84%, 95.05%, 96.89% and 91.87%, respectively. Overall concordance between ROSE and the final diagnosis was 0.8960 (Cohen's kappa). No significant differences were observed in terms of sampling procedures and type and location of the lesions. A tiered classification scheme of ROSE from C1 to C5 during bronchoscopic and percutaneous sampling procedures is helpful in effectively guiding clinical management of patients with thoracic lesions.

Arthropod-borne viruses, including the alphavirus chikungunya virus (CHIKV), cause acute disease in millions of people and utilize potent mechanisms to antagonize and circumvent innate immune pathways including the type I interferon (IFN) pathway. In response, hosts have evolved antiviral counterdefense strategies that remain incompletely understood. Recent studies have found that long noncoding RNAs (lncRNAs) regulate classical innate immune pathways; how lncRNAs contribute to additional antiviral counterdefenses remains unclear. Using high-throughput genetic screening, we identified a cytoplasmic antiviral lncRNA that we named antiviral lncRNA prohibiting human alphaviruses (ALPHA), which is transcriptionally induced by alphaviruses and functions independently of IFN to inhibit the replication of CHIKV and its closest relative, O'nyong'nyong virus (ONNV), but not other viruses. Furthermore, we showed that ALPHA interacts with CHIKV genomic RNA and restrains viral RNA replication. Together, our findings reveal that ALPHA and potentially other lncRNAs can mediate non-canonical antiviral immune responses against specific viruses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective  To assess the risk factors involving longer hospital stays and early postoperative complications (first 30 days after surgery) in patients undergoing total knee arthroplasty (TKA). Materials and Methods  A cross-sectional study was conducted with collection of data of patients who underwent TKA in a private hospital between 2015 and 2019. The following data were collected: age, gender, body mass index, and clinical comorbidities. We also collected intraoperative data such as the grade on the classification of the American Society of Anesthesiologists (ASA), the duration of the surgery, the length of stay, the postoperative complications, and readmission within 30 days. Statistical models were used to investigate the possible risk factors associated with longer hospital stays and postoperative complications. Results  There was evidence of an increase in the length of hospital stay in older patients, with higher grades on the ASA classification or who suffered postoperative complications. For each increase in 1 year of age, we expect the length of stay to be multiplied by 1.008 (95% confidence interval [95%CI]: 1.004 to 1.012; p  < 0,001). In patients who were ASA grade III, the time is expected to be multiplied by 1.297 (95%CI: 1.083 to 1.554; p  = 0,005) when compared with grade-I patients. In patients who suffered postoperative complications, the time is expected to be multiplied by 1.505 (95%CI: 1.332 to 1.700; p  < 0.001) compared with patients without complications. Conclusion  The present study demonstrated that, in patients who underwent primary TKA, preoperative characteristics such as older age and ASA grade ≥ III, as well as the development of postoperative complications, independently predict the increase in the length of hospital stay., Competing Interests: Conflito de Interesses Os autores não têm conflitos de interesse a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

X-ray fluorescence spectroscopy is a non-destructive technique employed for elemental analysis of a wide range of materials. Its advantages are especially valued in archaeometry, where portable instruments are available. Considering ancient glass, such instruments allow for the detection of some major, minor, and trace elements linked to the deliberate addition of specific components or to impurities in the raw materials of the glass batch. Besides some undoubted advantages, portable XRF (p-XRF) has some limitations that are addressed in this study. The performance assessment of four different p-XRF units and the reconciling of their output were conducted. The results show the limitations in cross-referencing the data obtained from each unit and suggest procedures to overcome the issues. The p-XRF units were tested on the set of Corning reference glasses and on a small set of archaeological glasses with known composition. The compatibility of the output was assessed using multivariate statistical tools. Such a workflow allows us to consider data from multiple sources in the same frame of reference.

The assessment of Visible Foliar Symptoms (VFS) is commonly adopted by forest monitoring programs to evaluate ozone impact on vegetation. The occurrence of ozone VFS may differ among individuals of the same species at the same site, and within leaves of the same individual. The aim of this study was to identify site and plant characteristics as well as functional leaf traits associated with the occurrence and severity of VFS in Viburnum lantana (an ozone-sensitive species) and at the scale of an individual site. V. lantana plants growing at one site of the ViburNeT monitoring network (Trentino, North Italy) experiencing high ozone levels were surveyed in relation to 1) sun exposure, 2) shading effect from neighbor vegetation, 3) plant height and 4) presence and severity of VFS. Leaves from three different sections of each plant were subjected to a phenotypic characterization of leaf area, dry weight, specific leaf area (SLA), chlorophyll content (ChlSPAD), percentage of VFS, and adaxial and abaxial trichome density (Tr). We showed that plants at high irradiation levels had significantly lower SLA (p<0.05), higher Tr (p<0.01) and greater ChlSPAD (p<0.01) when compared to shaded and/or west- and north-exposed plants, thus indicating a strong influence of site-specific characteristics on leaf trait plasticity. Similar differences were observed for taller vs. shorter plants and apical vs. basal branches (p<0.05). Ozone-induced VFS at leaf level were associated with lower SLA (p<0.001) and higher Tr in the abaxial leaf surface (p<0.05). Both leaf traits showed significant differences also within the south and east exposed plant category, thus suggesting the increase in leaf thickness and Tr as a potential adaptive strategy under multiple stress conditions. Our results provide evidence of a strong relationship between VFS, leaf traits and site-specific variables, offering new insights for interpreting data on the impact of ozone on vegetation., Competing Interests: The authors have declared that no competing interests exist.

Background: Neurological disorders pose a profound unmet medical need for which new solutions are urgently needed. The consideration of both biological (sex) and socio-cultural (gender) differences between men and women is necessary to identify more efficacious, safer and tailored treatments. Approaches for putting sex and gender medicine into practice have gathered momentum across Europe, but it is currently unclear to what extent they have been implemented in the field of neurology and neuroscience., Methods: We mapped current activities in research, funding and education aimed at integrating sex and gender consideration in neuroscience and neurology in Europe. We examined and analyzed data gathered from (1) literature searches, (2) policy documents and reports by the European Commission and national funding agencies, (3) web-based searches, (4) "Web of Science", and (5) searches of project databases of funding agencies. An informative / non-systematic search was performed for sections on policies and funding, education, basic research, while a systematic literature and database review was conducted forquantitative analysis of research output and funded projects in terms of sex and gender analysis., Results: Our mapping shows that there is a growing interest and attention towards sex and gender consideration in neurological fields, both from funding agencies and researchers. However, most activities, especially for education, are limited to the individual motivation of researchers and are not organically built within curricula and strategic research priorities., Discussion: We recommend actions that might help increase the consideration of sex and gender specifically in the field of neuroscience and neurology., (This article is protected by copyright. All rights reserved.)

The material characterization of nineteenth-century artifacts is of great interest, due both to the breakthrough technological advances and to the unprecedented spread of forgeries of antiquities which took place in that period. However, this type of artifacts has been largely overlooked in the past. In this paper we present the compositional analysis of gold jewels by the Castellani, one of the most important families of goldsmiths in nineteenth-century Europe. The use of a portable micro-XRF spectrometer, specifically developed for jewellery analysis at the Centro Nacional de Aceleradores (Seville), allowed us to analyse, in a completely non-invasive way, the alloys, joining techniques and surface treatments of the jewels of the Castellani collection at the National Etruscan Museum of Villa Giulia in Rome. The addition to the spectrometer of a second X-rays detector with a zinc filter allowed us to check the possible presence of low amounts of cadmium, a metal added to gold soldering only from the nineteenth century and often used in authenticity studies. Moreover, the relative intensities of the Au X-ray lines were studied in order to check non-invasively the presence of surface enrichments in gold., (© 2022. The Author(s).)

Objective: Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries., Methods: Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events., Results: Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases., Conclusion: The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76.

Most trees form symbioses with ectomycorrhizal fungi (EMF) which influence access to growth-limiting soil resources. Mesocosm experiments repeatedly show that EMF species differentially affect plant development, yet whether these effects ripple up to influence the growth of entire forests remains unknown. Here we tested the effects of EMF composition and functional genes relative to variation in well-known drivers of tree growth by combining paired molecular EMF surveys with high-resolution forest inventory data across 15 European countries. We show that EMF composition was linked to a three-fold difference in tree growth rate even when controlling for the primary abiotic drivers of tree growth. Fast tree growth was associated with EMF communities harboring high inorganic but low organic nitrogen acquisition gene proportions and EMF which form contact versus medium-distance fringe exploration types. These findings suggest that EMF composition is a strong bio-indicator of underlying drivers of tree growth and/or that variation of forest EMF communities causes differences in tree growth. While it may be too early to assign causality or directionality, our study is one of the first to link fine-scale variation within a key component of the forest microbiome to ecosystem functioning at a continental scale., (© 2021. The Author(s).)

Background: Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC)., Methods: The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades., Results: We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen., Conclusion: Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer., (© 2022. The Author(s).)