Search

Abstract Background Chronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation. Methods This observational retrospective analysis of Italian administrative healthcare data from the Fondazione Ricerca e Salute (ReS) database identified patients aged ≥ 45 years with COPD in 2019 and 2020. At least 6 years of look-back period and absence of concomitant asthma were required. COPD patients were categorized by treatment (SI–single/MI–multiple inhalers, TT–triple therapy, DT–dual therapy, other respiratory treatments, untreated) at index date (first dispensation during accrual period). Occurrence of moderate/severe exacerbation during one-year preceding index date and treatments during one-year preceding the exacerbation (possible switch) were evaluated. Results From ~ 4.7 million beneficiaries of the Italian National Health Service in 2019 and 2020, respectively, 105,828 and 103,729 (43 and 41 × 1,000 inhabitants aged ≥ 45 years) were identified as having COPD. Of 2019/2020 patients: 3.4%/5.2% received SI-TT, 20.7%/17.5% MI-TT, 35.9%/38.1% DT, 33.0%/33.1% other treatments, and 7.0%/6.0% were untreated. Males were prevalent and median age was > 73 years for all groups. Of 2019/2020 cohorts, heart failure and coronary artery disease affected 24/20%, 18/17%, and 11%/16% patients with SI-TT, MI-TT, DT, and other treatments, respectively. A previous moderate/severe exacerbation (2019/2020 patients) occurred to 60.5%/56.6%, 39.9%/37.4%, 30.8%/29.2% and 31.9%/29.7% patients treated with SI-TT, MI-TT, DT, and other treatments, respectively. Of 2019/2020 patients experiencing moderate/severe exacerbation: 6.0%/7.0% receiving DT, 5.1%/7.0% receiving other treatments and 4.5%/10.0% untreated, switched to SI-TT; 23.7%/16.9% receiving DT, 21.4%/17.7% receiving other treatments and 15.4%/12.0% untreated, switched to MI-TT. Conclusions COPD patients receiving TT were older and had more comorbidities, especially cardiovascular diseases, than patients receiving DT or other treatments. The limited number of patients switching after exacerbation suggests that many COPD patients may be inappropriately treated. Ensuring early and adequate treatment, combination of in-hospital and outpatient management, and integration of specialist and primary care is pivotal for the appropriate clinical management of COPD patients.

Abstract Background Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022–2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluate the concordance and calculate the performance metrics of the methylation test. Results Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information. Conclusions The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients’ clinical data.

Abstract Background Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. Methods This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. Results A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. Conclusion This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Abstract Objectives to evaluate over a 48-month follow-up period the: 1) long-term effectiveness and safety; 2) drug retention rate (DRR); 3) impact of comorbidities and bDMARDs line on MDA and DAPSA remission/low disease activity (LDA) of secukinumab in a multicenter Italian cohort of PsA patients. Methods Consecutive PsA patients receiving secukinumab were followed prospectively in Italian centers between 2016 and 2023. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were recorded. Treatment response was evaluated at 6 and 12 months after initiation, and every year up to 48 months (T48). DRR was assessed according to clinical and demographic features, comorbidities and bDMARDs line. Adverse events (AE) were recorded. Results Six hundred eighty-five patients [42.5% male] were enrolled; 32.9% naïve received secukinumab; 74.2% had ≥ 1 comorbidity. Overall, secukinumab yielded improved outcomes at T48: naïve maintained lower disease activity vs. non-naïve [DAPSA 4.0 (1.4–8.1) vs. 6.0 (2.2–10.4);p = 0.04]; 76.9% naïve and 66.2% non-naïve achieved MDA; MDA no comorbidities vs. 1–3 comorbidities 78.8% vs. 73.3% (p 3 comorbidities 78.8% vs. 48.7% (p 3 comorbidities. Treatment was discontinued in 233 patients due to loss of effectiveness, and in 41 due to AE. The overall DRR at T48 was 66%, with differences according to bDMARDs line (p

Abstract Here we present the growth of molecular beam epitaxy (MBE) CsPbBr3 perovskite films in the orthorhombic crystal structure, with unique structural and morphological properties. CsPbBr3 MBE perovskite films, with thickness ranging from a few nm to 300 nm, were grown in ultra-high vacuum on a Si(111)7 × 7 reconstructed surface, and after the formation of about 2 nm of SiO2, obtained exposing the clean reconstructed Si surface to molecular oxygen that serves to decouple the film from substrate. X-ray diffraction, and electron microscopies, such as scanning electron microscopy and high-angle annular dark-field scanning transmission electron microscopy measurements showed remarkable structural, as well as morphological features, indicating extremely high crystallinity over a large area and across the bulk of the perovskite film. Through the X-ray diffraction patterns we found very narrow (002) and (110) reflections of CsPbBr3 in pure orthorhombic phase, exhibiting a full width at half maximum of only 0.035°, value similar to a bulk Si single crystals, and a surface morphology composed of flat areas up to micrometres in lateral size. Our results shed new light both on preparation of high crystal quality perovskite films, and on the intrinsic properties of this striking fully-inorganic materials, which are exploitable for potential applications in electronic/optoelectronic devices and next generation photovoltaic solar cells.

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

Abstract The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.

Abstract Prostate cancer (PC) is an age-related disease and represents, after lung cancer, the second cause of cancer death in males worldwide. Mortality is due to the metastatic disease, which mainly involves the bones, lungs, and liver. In the last 20 years, the incidence of metastatic PC has increased in Western Countries, and a further increase is expected in the near future, due to the population ageing. Current treatment options, including state of the art cancer immunotherapy, need to be more effective to achieve long-term disease control. The most significant anatomical barrier to overcome to improve the effectiveness of current and newly designed drug strategies consists of the prostatic stroma, in particular the fibroblasts and the extracellular matrix, which are the most abundant components of both the normal and tumor prostatic microenvironment. By weaving a complex communication network with the glandular epithelium, the immune cells, the microbiota, the endothelium, and the nerves, in the healthy prostatic microenvironment, the fibroblasts and the extracellular matrix support organ development and homeostasis. However, during inflammation, ageing and prostate tumorigenesis, they undergo dramatic phenotypic and genotypic changes, which impact on tumor growth and progression and on the development of therapy resistance. Here, we focus on the characteristics and functions of the prostate associated fibroblasts and of the extracellular matrix in health and cancer. We emphasize their roles in shaping tumor behavior and the feasibility of manipulating and/or targeting these stromal components to overcome the limitations of current treatments and to improve precision medicine’s chances of success.

Abstract Introduction The use of pneumoperitoneum is an essential step for performing laparoscopic and robotic surgery. Pneumoperitoneum insufflation can cause complications such as pneumothorax, subcutaneous emphysema, and pneumomediastinum. The purpose of this meta-analysis is to compare the safety of using the conventional insufflation system versus a Valveless insufflation system as devices for manufacturing pneumoperitoneum in robotic-assisted nephrectomy. Methods A comprehensive literature search was conducted on PUBMED, EMBASE, SCOPUS, and Cochrane, from inception until January 2024. Randomized and nonrandomized prospective studies were included in the meta-analysis, performed by the R+ Rstudio. Results Three publications encompassing 478 patients were included. We observed no difference in SCE (OR 0.60, CI 95% 0.27;1.34, p = 0.134, I2 = 0), PNM (OR 0.82, CI 95% 0.24;2.78, p = 0.558, I2 = 0), When comparing groups conventional insufflation system (CIS) versus AirSealTM insufflation system (AIS) with pneumoperitoneum pressure of 15 mmHg or 12 mmHg. Conclusion The presented data showed no difference between the AIS when compared with CIS in Pneumoperitoneum insufflation-related complications.

Varicose veins are associated with conditions that impair venous return, such as pregnancy, physical inactivity, valve failure and post-thrombotic syndrome. We report the case of a 50-year-old female patient with history of intermittent calf pain, worsening with prolonged standing posture. She had no previous medical history of either lower extremity trauma or infection. Physical examination showed medial pretibial soft tissue swelling. CT and MRI showed images suggestive of anomalous intraosseous venous drainage with associated bone edema and periosteal reaction. Knowledge of this rare entity is fundamental for proper patient management.

This study investigates the degradation behavior of three distinct Fe-based alloys immersed in three pseudo-physiological solutions. These alloys, which have varied Mn and C contents, include a commercially available Fe-0.15C alloy, namely Fe–C, and two newly developed alloys, that is Fe–5Mn-0.2C (namely Fe–5Mn) and Fe–18Mn-0.6C (namely Fe–18Mn). The aim was to understand the effect of alloying elements and the testing solution on the in-vitro degradation behavior of these Fe-based materials. Static immersion degradation and potentiodynamic corrosion tests were carried out using three pseudo-physiological solutions with albumin supply, that is modified Hanks’ saline solution (MHSS), phosphate buffered saline solution (PBS), and sodium chloride solution (NaCl). After two weeks of static immersion, the results revealed that Fe–5Mn, characterized by a mixture of ferrite and martensite, showed the highest degradation rate, while Fe–C, composed solely of ferrite, showed the lowest rate of degradation. The predominant degradation products in MHSS and PBS were phosphates and carbonates. In PBS, these products formed a remarkably stable protective layer on the surface, contributing to the lowest degradation rate. In contrast, porous hydroxides appeared as the main degradation products for samples immersed in NaCl solution, leading to the highest degradation rate. These results provided important insights into the customization of Fe–Mn–C alloys for a range of biomedical applications, meeting a variety of clinical requirements, and highlighting the considerable potential of Fe–Mn–C alloys for biomedical applications.

Abstract We construct rigid non-supersymmetric heterotic vacua with reduced rank and no tachyons in six and four dimensions. These configurations are based on asymmetric orbifold compactifications which do not admit neutral deformation moduli and represent, to the best of our knowledge, the first instances of non-tachyonic non-supersymmetric heterotic vacua with reduced rank.

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

Abstract Prompt Gamma Imaging (PGI) is a promising technique for range verification in Particle Therapy. This technique was already tested in clinical environment with a knife-edge-collimator camera for proton treatments but remains relatively unexplored for Carbon Ion Radiation Therapy (CIRT). Previous FLUKA simulations suggested that PG profile shifts could be detected in CIRT with a precision of $$\sim$$ 4 mm ( $$2 \sigma$$ ) for a particle statistic equal to $$5 \cdot 10^{7}$$ C-ions using a 10 × 10 cm2 camera. An experimental campaign was carried out at CNAO (Pavia, Italy) to verify these results, using a knife-edge-collimator camera prototype based on a 5 × 5 cm2 pixelated LYSO crystal. PG profiles were measured irradiating a plastic phantom with a C-ion pencil beam at clinical energies and intensities, also moving the detector to extend the FOV to 13 × 5 cm2. The prototype detected Bragg-peak shifts with $$\sim$$ 4 mm precision for a statistic of $$\sim 4 \cdot 10^{8}$$ C-ions ( $$3 \cdot 10^{8}$$ for the extended FOV), slightly larger than expected. Nevertheless, the detector demonstrated significant potential for verifying the precision in dose delivery following a treatment fraction, which remains fundamental in the clinical environment. For the first time to our knowledge, range verification based on PGI was applied to a C-ion beam at clinical energy and intensities.

Abstract In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation. Using a propensity score, we selected 40 alive study participants having similar clinical and virological records compared to the deceased group. 13 HIV unexposed (HU) healthy children were additionally used as controls. Baseline plasma samples were analyzed using a targeted proteomic approach, and to assess pathogen-associated and damage-associated molecular patterns (PAMPs, DAMPs) levels. Data from deceased participants were compared to both control groups, with multivariate logistic regression models used to evaluate the association between mortality and plasma proteins. We developed a machine learning model to predict mortality risk, finding that IL-6 and CXCL11 not only were higher in deceased children than Matched-children with HIV (p

Abstract A fundamental understanding of the active sites in working catalysts can guide the rational design of new catalysts with improved performances. In this work, we have followed the evolution of homogeneous and heterogeneous Pd catalysts under the reaction conditions for aerobic oxidative coupling of toluene for the production of 4,4′-bitolyl. We have found that subnanometer Pd clusters made with a few Pd atoms are the working active sites in both homogeneous and heterogeneous catalytic systems. Moreover, water can promote the activity of Pd clusters by nearly one-order magnitude for oxidative coupling reaction by facilitating the activation of O2. These new insights lead to the preparation of a catalyst made with Pd clusters supported on a two-dimensional zeolite, which expands the scope of the oxidative coupling of aromatics to larger substrates.

Abstract Being able to robustly interact with and navigate a dynamic environment has been a long-standing challenge in intelligent transportation systems. Autonomous agents can use models that mimic the human brain to learn how to respond to other participants’ actions in the environment and proactively coordinate with the dynamics. Modeling brain learning procedures is challenging for multiple reasons, such as stochasticity, multimodality, and unobservant intents. Active inference may be defined as the Bayesian modeling of a brain with a biologically plausible model of the agent. Its primary idea relies on the free energy principle and the prior preference of the agent. It enables the agent to choose an action that leads to its preferred future observations. An exploring action-oriented model is introduced to address the inference complexity and solve the exploration–exploitation dilemma in unobserved environments. It is conducted by adapting active inference to an imitation learning approach and finding a theoretical connection between them. We present a multimodal self-awareness architecture for autonomous driving systems where the proposed techniques are evaluated on their ability to model proper driving behavior. Experimental results provide the basis for the intelligent driving system to make more human-like decisions and improve agent performance to avoid a collision.

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

Abstract Background Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD. Methods The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively. Results The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed. Conclusions The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.

(1) Background: The observational retrospective study aimed to investigate the prevalence of personality disorders (PDs) and their association with psychopathological symptoms in a group of patients with cocaine addiction. (2) Methods: Ninety-five medical records of the Pathological Addictions Service of the National Health Service of Lecce (Italy) were analyzed. PDs were diagnosed using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) and psychopathological symptoms were investigated through the Symptom Checklist 90-Revised (SCL-90-R). (3) Results: Ninety-two out of ninety-five patients met the criteria for at least one PD (96.8%), almost 35% had two Cluster B PDs, and over 25% had three Cluster B PDs. Nine out of ninety-five people met the criteria for all Cluster B PDs. Among the Cluster B PDs, it emerged that the most frequent diagnosis was that of narcissistic–borderline–antisocial (over 20% of the total sample). The analysis highlighted that mental suffering is prevalent in those with multiple comorbid Cluster B PDs. Specifically, depression and psychoticism exceed the clinical cut-off (T score > 63) in all patient groups. At the same time, anxiety and obsessions–compulsions are complained of only by those with more than two PDs as well as the level of general distress. Furthermore, anxiety, hostility, and paranoid ideation are significantly higher in the group of patients with more than three PDs. (4) Conclusions: Further studies should better investigate the relationship between the two aspects and describe the causal effects of PDs on psychopathological symptoms or, on the contrary, the effects of the substance on mental health and the worsening of personality alterations.

Abstract This paper completes the analysis initiated in the companion work arXiv:2403.02283 — referred to as Paper I — by showing how Vasiliev’s 4D higher-spin gravity (HSG) and 3D coloured conformal matter fields coupled to conformal higher-spin gauge fields and colour gauge fields (coloured conformal HSG, or CCHSG) emerge as consistent reductions of a common parent model. The latter is a Frobenius-Chern-Simons model with superconnection valued in a fractional-spin extension of Vasiliev’s higher-spin algebra, and was defined and studied in Paper I. Here, we i) realize HSG as a subcase of a more general 4D reduction, describing HSG coupled to coloured, fractional-spin matter, which we refer to as 4D fractional-spin gravity; ii) study the CCHSG model, in particular exhibiting the crucial role played by novel colour gauge fields in coupling conformal matter to conformal HSG, thereby completing the models due to Vasiliev and Nilsson; iii) extract conformal currents and composite coloured sources in an expansion of the CCHSG model around 3D Minkowskian leaves; and iv) compare our results with Vasiliev’s holography proposal of arXiv:1203.5554. The common origin of HSG and CCHSG, besides relating the two models directly, is the starting point for establishing the holographic correspondence between the two models via overlap conditions, to be presented separately.

Abstract Background Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD. Methods This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported. Results Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment. Conclusions The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

Abstract Background A large fraction of the disease burden in the Italian population is due to behavioral risk factors. The objective of this work is to provide a tool to estimate the impact of preventive interventions that reduce the exposure to smoking and sedentary lifestyle of the Italian population, with the goal of selecting optimal interventions. Methods We construct a Markovian model that simulates the state of each subject of the Italian population. The model predicts the distribution of subjects in each health status and risk factor status for every year of the simulation. Based on this distribution, the model provides a rich output summary, such as the number of incident and prevalent cases for each tracing disease and the Disability Adjusted Life Years (DALY), used to assess the impact of preventive interventions, and how this impact is shaped in time. Results This paper focuses on the methodological aspects of the model. The proposed model is flexible and can be applied to estimate the impact of complex interventions on the two risk factors and adapted to consider different cohorts. We validate the model by simulating the evolution of the Italian population from 2009 to 2017 and comparing the output with historical data. Furthermore, as a case-study, we simulate a counterfactual scenario where both tobacco and sedentary lifestyle are eradicated from the Italian population in 2019 and estimate the impact of such intervention over the following 20 years. Conclusions We propose a Markovian model to estimate how interventions on smoking and sedentary lifestyle can affect the reduction of the disease burden, and validate the model on historical data. The model is flexible and allows to extend the analysis to consider more risk factors in future research. However, we are aware that, given the ever-increasing availability of data, it is necessary in the future to increase the complexity of the model, to be closer to reality and to provide decision-making support to the policy-makers.

Abstract Background Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART. Methods Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed. Results The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data. Conclusions This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation.

Abstract We report the clinical case of a patient with acute myocardial infarction due to coronary stent compression as first manifestation of a large thymoma. The patient underwent a coronarography and thrombus aspiration + plain old balloon angioplasty restoring the stent patency. The mass resection was performed through left robotic‐assisted thoracic surgery (RATS), resulting in a type A thymoma pT1a, IIb Masaoka‐Koga. An uncommon presentation led to early diagnosis and treatment of a thymoma with both oncological and functional significance.

Abstract Objective The aim of this study is to describe the pre‐ and post‐operative developmental and intellectual functions in a cohort of patients who underwent surgery for drug‐resistant epilepsy (DRE) before the age of 5 years. Method We retrospectively reviewed the medical records and neurodevelopmental assessments of a cohort of 80 surgically treated pediatric patients with DRE. We included patients if they had at least one pre‐ and one post‐surgical neuropsychological assessments; 27 met the inclusion criteria. We evaluated Developmental Quotient (DQ) and Intelligence Quotient (IQ) before and after surgery. We identified two groups based on psychological evaluation outcome: Group 1, with stable or improved developmental and intellectual functions, and Group 2, experiencing developmental and intellectual loss. Results The mean age at seizure onset was 1.2 ± 1.0 years, and the mean age at surgery was 2.9 ± 1.2 years. At the last follow‐up (mean 4 years, SD ± 2), 19/27 (70%) patients were seizure‐ and drug‐free; 18/27 patients (67%) fit in Group 1, and 9/27 (33%) fit in Group 2. The mean age at surgery was 2.6 years (SD ± 1.1; range 1.2–5.1) in Group 1 and 3.4 years in Group 2 (SD ± 1.1; range 1.6–5.0). Group 1 had a lower pre‐operative DQ/IQ total score than Group 2 (median DQ/IQ respectively 82 vs 108, p = 0.05). Between pre‐ and post‐assessments, we found that in Group 1, Performance scores improved (82.7 vs 102, p = 0.001), while in Group 2, the Total and Verbal scores worsened (respectively 108 vs 75, p = 0.008, and 100 vs 76, p = 0.021). Significance Our study's results emphasize the positive impact of surgery before the age of 5 years on developmental and intellectual outcomes. Despite limitations such as a small sample size, lack of a control group, and diverse etiologies, our findings support the crucial role of early intervention in preserving or enhancing developmental and intellectual functions in young patients with DRE. Plain Language Summary This retrospective study, conducted at the Bambino Gesù Children Hospital in Italy, reports neuropsychological and developmental and/or cognitive data for children undergoing early epilepsy surgery (before the age of 5). It found that children with lower developmental or cognitive profiles gained the highest scores on post‐operative neuropsychological evaluations. This study provides information on the potential benefits of early surgery in shortening the duration of epilepsy, preventing or arresting deterioration, and enhancing plasticity and recovery.

Abstract Objective Lennox–Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult‐to‐control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long‐term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long‐term functional and adaptive behavior in adult patients with LGS. Methods This cross‐sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS‐II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS‐II scores. Results The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS‐II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS‐II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. Significance This study provides relevant insights into the long‐term challenges faced by adults with Lennox–Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. Plain Language Summary This study examined adults with Lennox–Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long‐term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Abstract Background Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days. Results Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH2O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP. Conclusions Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch. Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT03201263.

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Iron and its alloys are attractive as biodegradable materials because of their low toxicity and suitable mechanical properties; however, they generally have a slow degradation rate. Given that corrosion is an electrochemical phenomenon where an exchange of electrons takes place, the application of magnetic fields from outside the body may accelerate the degradation of a ferrous temporary implant. In the present study, we have investigated the effect of alternating and direct low magnetic field (H = 6.5 kA/m) on the corrosion process of pure iron (Fe) and an iron-manganese alloy (FeMnC) in modified Hanks' solution. A 14-day static immersion test was performed on the materials. The corrosion rate was assessed by mass and cross-sectional loss measurements, scanning electron microscopy, X-ray diffractometry, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy before and after degradation. The results show that the presence of magnetic fields significantly accelerates the degradation rate of both materials, with the corrosion rate being twice as high in the case of Fe and almost three times as high for FeMnC. In addition, a homogenous degradation layer is formed over the entire surface and the chemical composition of the degradation products is the same regardless of the presence of a magnetic field.

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) 30 cm s−1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.

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

Abstract Iodine and bromine play central roles in polar atmospheric chemistry: iodine influences the atmospheric oxidative capacity and can generate cloud condensation nuclei, while bromine participates in ozone depletion reactions, known as bromine explosions. Here we present a very sensitive analytical method for Br and I speciation by coupling the ion chromatography system (IC) with an inductively coupled plasma sector field mass spectrometer (ICP-SFMS). We achieved sub-picogram-per gram (pg g−1) as limits of detection (LODs) ranging from 0.4 pg g−1 for I−, 0.8 pg g−1 for IO3 −, 4 pg g−1 for Br−, and 1 pg g−1 for BrO3 −, respectively. These values represent a decrease of up to 30 times compared to the LODs reported in other studies. The method was validated using deep snow samples from the Svalbard Islands, collected at the end of the polar night to quantify various oxidized compounds during their seasonal minimum. In the future, this method could prove useful in the paleoclimatic study of ice cores and snow, as well as in ice chemistry research.

Abstract Background Some chromatinopathies may present with common clinical findings (intellectual disability, brain and limb malformation, facial dysmorphism). Furthermore, one of their cardinal shared features is growth dysregulation.We aimed to assess and deepen this resemblance in three specific conditions, namely Wiedemann-Steiner (WDSTS), Kleefstra (KLEFS1) and Coffin-Siris syndrome (CSS1), with a particular focus on possible metabolic roots. Methods Eleven patients were enrolled, three with WDSTS, five with KLEFS1 and three with CSS1, referring to Fondazione IRCCS Ca’ Granda Ospedale Maggiore, Milan, Italy. We performed both a physical examination with detailed anthropometric measurements and an evaluation of the patients’ REE (rest energy expenditure) by indirect calorimetry, comparing the results with age- and sex-matched healthy controls. Results We observed new clinical features and overlap between these conditions suggesting that different disturbances of epigenetic machinery genes can converge on a common effect, leading to overlapping clinical phenotypes. The REE was not distinguishable between the three conditions and healthy controls. Conclusions Epigenetic machinery plays an essential role both in growth regulation and in neurodevelopment; we recommend evaluating skeletal [craniovertebral junction abnormalities (CVJ) polydactyly], otolaryngological [obstructive sleep apnea syndrome (OSAs), recurrent otitis media], dental [tooth agenesis, talon cusps], and central nervous system (CNS) [olfactory bulbs and cerebellum anomalies] features. These features could be included in monitoring guidelines. Further studies are needed to deepen the knowledge about energy metabolism.

Abstract Background Advances in understanding the etiology of intellectual disability (ID) has led to insights in potential (targeted) treatments and personalized care. Implications of ID on health are often complex and require a multidisciplinary approach. The aim was to investigate the reporting of genetic diagnoses in multidisciplinary ID care and to identify associated clinical and demographic factors. Methods A retrospective chart review was performed on a randomly selected sample of individuals (n = 380) of a large ID care organization in the Netherlands. Data on genetic etiology, including genetic testing and diagnoses, and clinical and demographic characteristics were collected from files held by multidisciplinary team members. Results Reports on genetic etiology were available in 40% of the study sample (n = 151), with a genetic diagnosis recorded in 34% (n = 51), which is 13% of the total sample. In those with reported genetic diagnoses, this was reported in 90% of medical, 39% of psychodiagnostic, and 75% of professional caregivers’ files. Older age, mild ID, and the legal representative not being a family member were associated with less reported information on genetic etiology. Conclusions This study revealed that genetic diagnoses were often not reported in ID care files. Recommendations were formulated to reduce delay in diagnosis, and enable personalized care for individuals with ID.

This work describes an automated pilot plant for the extraction of rare-earth (RE) permanent magnets from computer hard-disk drives (HDDs), demonstrating a commercially viable way to exploit these abundant sources of end-of-life (EOL) magnets. A mobile approach is provided for the on-site destruction of the HDDs in server farms, in compliance with the European Data Protection Regulation (GDPR), enabling both separation of the magnets and automated shredding of the data carrier. This fully automated process identifies (both optically and magnetically) the location of the rare-earth magnets and cuts off the corner of the hard drive containing the rare-earth material in the voice coil motor. This allows for a significant reduction in magnet extraction time (6 s per HDD) compared to previously reported semi-automated (2 min) and manual (5 min) dismantling times. This work will also help to transfer the experience gained in the mobile pilot plant to other future sources of EOL materials such as drive motors and mixed electronic scrap.

Glioblastoma is the most frequent form of adult-type diffuse gliomas, and it carries a very poor prognosis. Magnetic resonance imaging (MRI) is an indispensable tool for diagnosing and monitoring brain tumors, potentially influencing choices like repeat surgery, biopsy, or alternative management strategies. However, interpreting post-surgical MRI for gliomas can be particularly demanding, especially in differentiating between tumor progression and treatment effects. Recently, a novel score specifically designed for classifying and reporting post-treatment brain tumors on MRI was proposed by a team of neuroradiologists, neurosurgeons, and neuro-oncologists: the Brain Tumor Reporting and Data System (BT-RADS). This review examines the current body of evidence regarding the use of BT-RADS in monitoring adult-type diffuse gliomas following surgery. This classification has demonstrated a number of benefits in terms of prognostic value, treatment decisions, reliability, and the quality of radiology reports. On the other hand, despite the promising diagnostic value in identifying recurrent glioblastoma, there is still some uncertainty in defining the presence or absence of tumor recurrence in the intermediate category 3. In such a category, incorporating advanced techniques such as perfusion-weighted imaging and diffusion-weighted imaging may improve the stratification of patients, avoiding repeat surgery on false positive findings.

Abstract In this work and in the companion paper arXiv:2403.02301, we initiate an approach to holography based on the AKSZ formalism. As the first step, we refine Vasiliev’s holography proposal in arXiv:1203.5554 by obtaining 4D higher-spin gravity (HSG) and 3D coloured conformal higher-spin gravity (CCHSG) — i.e., coloured conformal matter fields coupled to conformal higher-spin gauge fields and colour gauge fields — as two distinct and classically consistent reductions of a single parent theory. The latter consists, on-shell, of a flat superconnection valued in a fractional-spin extension of Vasiliev’s higher-spin algebra. The HSG and CCHSG reductions are characterized by dual structure groups and two-form cohomology elements, and their embedding in a common parent model provides a rationale for deriving holographic relations from multi-dimensional AKSZ partition functions on cylinders with dual boundary conditions, to appear separately. In this work we i) construct the underlying non-commutative geometry as a metaplectic operator algebra represented in a Hermitian module of a pair of conformal particles; ii) identify a discrete modular group, arising from twisted boundary conditions of the first-quantized system, and connecting different boundary conditions of the second-quantized system; and iii) identify the holonomies, structure groups and two-form cohomology elements that characterize the HSG and CCHSG reductions, and equate the dual second Chern classes.

Abstract Playing music is a complex task that relies on the combination of musicians’ technical and expressive skills. While the literature has investigated the effects of musical expressivity on the listeners, the way how technical difficulty and emotional expressivity affect musicians during playing has surprisingly received no attention. In an attempt to fill this gap in the literature, we collected behavioral and physiological data from twelve violinists playing 29 pieces that included both technical exercises and excerpts from classical repertoire for violin. After playing each stimulus, participants rated it for emotional expressivity and technical difficulty. During the entire session, cardiac parameters and electrodermal activity were collected, together with the kinematic parameters of the bowing gesture. A set of Linear Mixed-Effect (LME) models suggested that emotional expressivity attributed to music affected the fluidity of bowing (i.e., smoothness), with the excerpts rated as more expressive being performed in a less smooth way. In contrast, LME models revealed no effects of expressivity and technical difficulty on any of the physiological parameters of violinists. Our results offer novel insights into the psychophysiological dynamics that link motor parameters with musical expressivity. These findings could influence educational practices in music and deepen our understanding of aesthetic emotions.

Abstract Two-dimensional transition metal dichalcogenides, particularly MoS2, are interesting materials for many applications in aerospace research, radiation therapy and bioscience more in general. Since in many of these applications MoS2-based nanomaterials can be placed in an aqueous environment while exposed to ionizing radiation, both experimental and theoretical studies of their behaviour under these conditions is particularly interesting. Here, we study the effects of tiny imparted doses of 511 keV photons to MoS2 nanoflakes in water solution. To the best of our knowledge, this is the first study in which ionizing radiation on 2D-MoS2 occurs in water. Interestingly, we find that, in addition to the direct interaction between high-energy photons and nanoflakes, reactive chemical species, generated by γ-photons induced radiolysis of water, come into play a relevant role. A radiation transport Monte Carlo simulation allowed determining the elements driving the morphological and spectroscopical changes of 2D-MoS2, experimentally monitored by SEM microscopy, DLS, Raman and UV–vis spectroscopy, AFM, and X-ray photoelectron techniques. Our study demonstrates that radiolysis products affect the Molybdenum oxidation state, which is massively changed from the stable + 4 and + 6 states into the rarer and more unstable + 5. These findings will be relevant for radiation-based therapies and diagnostics in patients that are assuming drugs or contrast agents containing 2D-MoS2 and for aerospace biomedical applications of 2DMs investigating their actions into living organisms on space station or satellites.

Fibers collected from the husk of areca nut trees were chopped to a length of 30 mm and were either used as such or subjected to alkaline treatment by immersion in a 5% sodium hydroxide (NaOH) solution. The untreated and treated fibers were investigated using thermogravimetric analysis (TGA) before the fabrication of composites using an epoxy matrix. Different amounts of fibers were introduced in the matrix, fabricating the composite by compression molding. The composites were subjected to tensile, flexural, and Charpy impact and Shore D hardness testing, which all demonstrated the considerable advantage obtained with the growing quantity of fibers, especially when employing treated fibers, except in the case of hardness, where limited advantages were encountered. Wear tests were carried out on treated fiber composites and the surface morphology of the worn-out samples was studied, which also demonstrated the improvement in fiber-matrix bonding obtained with the growing amount of fibers. The main limitation of the fibers was their low elongation even after treatment. The fibers hardly reached 4%, which might represent a quite normal value for this kind of fibers, possibly due to with tendency to fibrillation. This would somehow compare these composites with others with similar amounts and lengths of natural fibers.

Background: Individuals may exhibit altered foot pronation during gait when fatigue sets in. Therefore, a more evidence-based understanding of these fatigue-induced changes may be helpful for future gait analysis and return-to-play tests since fatigue can provide new insights that might explain a person’s complaints. Methods: A total of 25 healthy individuals (12♂, 13♀; 24.3 ± 2.7 years; 174.9 ± 9.09 cm; 70 ± 14.2 kg; BMI: 22.7 ± 2.8) participated in this controlled non-randomized study of unilateral fatigue of the right foot’s stabilizing muscles with regard to the pronation of the foot, measured by navicular drop (ND) in static (statND; standing) and dynamic (dynND; walking) states. The left foot served as the control. Surface electromyography was used to verify fatigue. Results: While the statND did not change, the dynND increased significantly by 1.44 ± 2.1 mm (=22.3%) after the foot-stabilizing muscles experienced fatigue. No correlation was found between the statND and dynND. Conclusions: Muscular fatigue can affect foot pronation. The dynND appears to be more representative of the loads in everyday life, whereby most studies use the statND.

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4–10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission – a step closer to the concept of cure – a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients.

Abstract Background Milk is essential for mammalian nutrition because it provides vital nutrients for growth and development. Milk composition, which is influenced by genetic and environmental factors, supports lactation, a complex process crucial for milk production and quality. Recent research has focused on noncoding RNAs, particularly microRNAs (miRNAs), which are present in body fluids and regulate gene expression post-transcriptionally. This study comprehensively characterizes miRNAs in milk of four livestock species, namely Bubalus bubalis, Capra hircus, Equus asinus, and Ovis aries and identifies potential target genes. Results High-throughput sequencing of milk RNA resulted in distinct read counts across species: B. bubalis (8,790,441 reads), C. hircus (12,976,275 reads), E. asinus (9,385,067 reads), and O. aries (7,295,297 reads). E. asinus had the highest RNA mapping rate (94.6%) and O. aries the lowest (84.8%). A substantially greater proportion of miRNAs over other small RNAs was observed for the donkey milk sample (7.74%) compared to buffalo (0.87%), goat (1.57%), and sheep (1.12%). Shared miRNAs, which included miR-200a, miR-200b, miR-200c, and miR-23a among others, showed varying expression levels across species, confirmed by qPCR analysis. Functional annotation of predicted miRNA target genes highlighted diverse roles, with an enrichment in functions linked to metabolism and immunity. Pathway analysis identified immune response pathways as significant, with several miRNAs targeting specific genes across species, suggesting their regulatory function in milk. Conclusions Both conserved and species-specific miRNAs were detected in milk of the investigated species. The identified target genes of these miRNAs have important roles in neonatal development, adaptation, growth, and immune response. Furthermore, they influence milk and meat production traits in livestock.

Abstract Background Multicomponent interventions based on a comprehensive geriatric assessment (CGA) could promote active aging and improve health status in older people with Noncommunicable Chronic Diseases (NCDs), but conflicting evidences are available. Aim To evaluate the efficacy of a CGA-based multicomponent personalized preventive program (PPP) in reducing unplanned hospitalization rates during 12-month follow-up in community-dwelling older people with NCDs. Materials and methods In this randomized clinical trial (RCT), 1216 older adults recruited by 33 general practitioners (GPs) will be randomly allocated to intervention group (IG) or usual care control group (CG). The IG will receive a multicomponent PPP developed on the findings of the CGA-based Multidimensional Prognostic Index short-form (Brief-MPI), including structured interventions to improve functional, physical, cognitive, and nutritional status, to monitor NCDs and vaccinations, and to prevent social isolation. Participants in the CG will receive usual care. Brief-MPI, resilience, and health-related quality of life will be assessed after 6 and 12 months. Moreover, saliva samples will be collected at baseline in IG to measure biomarkers of oxidative stress, inflammatory cytokines, and oral microbiome. Expected results The CGA-based PPP might reduce unplanned hospitalization rates and potentially institutionalization rates, emergency department (ED) and unplanned GP visits, and mortality. Further outcomes explored in the IG will be the adherence to PPP, resilience, health-related quality of life, and multidimensional frailty as assessed by the Brief-MPI. Conclusions Results will suggest whether the CGA-based multicomponent PPP is able to improve specific outcomes in a primary care setting. Trial registration ClinicalTrials.gov; identifier: NCT06224556 ; Registered January 25, 2024.

Abstract Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.

Abstract In the last two decades, an exponentially growing number of meta-analyses (MAs) synthesize thousands of peer-reviewed studies on the environmental impacts of farming practices (FPs). This paper describes the iMAP-FP evidence library, a comprehensive dataset on the effects of 34 categories of FPs (such as agronomic practices, cropping and livestock systems, land management options and mitigation techniques) on 34 impacts including climate mitigation, soil health, environmental pollution, water use, nutrients cycling, biodiversity, and agricultural productivity. Through systematic screening, 570 MAs published since 2000 were selected and categorized according to the type of FP. We assessed their impacts, the geographic regions covered, and their quality. We extracted 3,811 effects and their statistical significance associated with sustainable FPs (intervention) compared to a control (typically conventional agriculture) across 223 different intervention-control pairs. Our dataset is accompanied with an online free-access library, which includes a catalogue of synthetic reports summarizing the available evidence on each evaluated FP.

Abstract Do cities have a collective identity? The latest advancements in generative artificial intelligence (AI) models have enabled the creation of realistic representations learned from vast amounts of data. In this study, we test the potential of generative AI as the source of textual and visual information in capturing the place identity of cities assessed by filtered descriptions and images. We asked questions on the place identity of 64 global cities to two generative AI models, ChatGPT and DALL·E2. Furthermore, given the ethical concerns surrounding the trustworthiness of generative AI, we examined whether the results were consistent with real urban settings. In particular, we measured similarity between text and image outputs with Wikipedia data and images searched from Google, respectively, and compared across cases to identify how unique the generated outputs were for each city. Our results indicate that generative models have the potential to capture the salient characteristics of cities that make them distinguishable. This study is among the first attempts to explore the capabilities of generative AI in simulating the built environment in regard to place-specific meanings. It contributes to urban design and geography literature by fostering research opportunities with generative AI and discussing potential limitations for future studies.

Abstract The significant impact of acute respiratory tract infections on healthcare systems is well-documented, given their contribution to emergency department admissions, hospitalizations, and increased use of antibiotics and other medications. However, further research is needed to understand the burden of acute respiratory tract infections in pediatric community care to develop effective public health interventions and improve child health outcomes. Real-world data were retrieved from Pedianet, an Italian network of over 200 family pediatricians. Acute respiratory tract infection visits were identified and analysed using an infection-duration algorithm to extract individual cases. The number of follow-up visits per 100 cases was calculated to assess the burden on the Italian National Health Service. Comparisons were made overall and stratified by type of acute respiratory tract infections and epidemiological season. A total of 1,402,953 acute respiratory infections-related visits were recorded, with an overall rate of 12 visits per 100 cases. Upper respiratory tract infections had an average of 9 visits per 100 cases. Lower respiratory tract infections exhibited a higher burden, with 29 visits per 100 cases. Pneumonia showed a declining trend in the pre-pandemic era (62 to 48 visits) but rebounded in the post-COVID-19 years (32 to 42 visits). This study underscores the importance of monitoring and managing acute respiratory infections, especially lower respiratory tract infections, in pediatric care.