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Abstract Aims Disease staging and prognostic scoring in wild‐type transthyretin‐related cardiac amyloidosis (ATTRwt‐CA) can be captured by two systems (NAC and Columbia scores). However, uncertainty remains as epidemiology of the disease is evolving rapidly. We evaluated features associated with staging systems across ATTRwt‐CA patients from different diagnostic pathways, and their association with prognosis. Methods We performed an analysis on DIAMOND patients with available data to evaluate NAC and Columbia score. DIAMOND was a retrospective study from 17 Italian referral centres for CA, enrolling 1281 patients diagnosed between 2016 and 2021, and aimed at describing characteristics of pathways leading to ATTRwt‐CA diagnosis. Of the original cohort, 811 patients were included in this analysis. Each patient had NAC and Columbia score calculated. Patients were grouped according to NAC and Columbia scoring classes. We described characteristics of patients according to staging classes and diagnostic pathways at diagnosis. Prevalence of early diagnoses, defined as NAC Ia, NYHA class I, no use of diuretics, no history of heart failure (HF) hospitalizations nor of atrial fibrillation prior to diagnosis, was investigated. Finally, prognostic variables were tested alone and grouped as NAC or Columbia scores in Cox univariate and multivariate regression analyses. Prognosis was investigated as all‐cause mortality, in the whole population and dividing patients in HF versus other diagnostic pathways. Results Only 1% of the study population had an early ATTRwt‐CA diagnosis. Distribution of prognostic variables and of NAC and Columbia classes was heterogeneous across diagnostic pathways. The prevalence of NAC III and Columbia III was higher in the HF diagnostic pathway, but all NAC and Columbia classes were present in all pathways. Both NAC and Columbia scores were associated with all‐cause mortality at univariate Cox regression analysis in the whole population, in patients from the HF diagnostic pathway and in those from other pathways. At multivariate analysis, Columbia score remained significantly associated with the outcome, together with age at diagnosis, left ventricular ejection fraction and maximal wall thickness. Conclusions In this contemporary nationwide cohort, an ATTRwt‐CA early diagnosis was very rare. Disease staging with NAC and Columbia scoring systems determined classes of patients with heterogeneous features. Both scores were significantly associated with mortality, but other variables also had prognostic significance.

Objective: This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED). Methods: Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 h of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015–June 2022), were analysed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility. Results: Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, P < 0.001) and associated with ESBL production (OR = 2.202, P = 0.031) and urosepsis (OR = 1.688, P = 0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, P < 0.001) and methicillin resistance (7.9% vs. 3.6%, P = 0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, P < 0.001). Conclusions: Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED.

Purpose: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. Design: Prospective study. Methods: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. .Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA. Results: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17 % vs. 52.99 ± 2.52%; p < 0.001), as well as in the parafovea (53.01 ± 6.69 % vs. 55.30 ± 2.61%; p = 0.002), and fovea (21.38 ± 9.01 % vs. 30.31 ± 5.84 %; p < 0.001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07 % vs. 50.83 ± 5.46%; p = 0.005), as well as in the parafovea (56.76 ± 6.26 % vs. 52.59 ± 5.46%; p = 0.001), and fovea (38.75 ± 8.59 % vs. 33.43 ± 8.68 %; p < 0.001). Conclusion: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.

Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

Lichen sclerosus (LS) is a chronic scleroatrophic dermatosis of unknown etiology that usually affects the anogenital area and occasionally the extragenital sites, which has no definitive cure. LS patients are at higher risk of developing squamous cell carcinoma (SCC) in their lifetime compared to the general population. Through a retrospective study, we evaluated the impact of regenerative medicinebased therapies on SCC onset in the context of genital LS. LS patients treated in our institute from March 2013 to December 2022 were reviewed. A total of 319 patients, including 34 treated with adipose-derived stem cells (ADSCs) graft, 31 treated with ADSCs graft and PRP, and 254 treated with platelet-rich plasma (PRP) were identified. In parallel, data extracted from the histologic institutional database searching for SCC in the anogenital area were matched to surgical records. None of the 319 LS patients developed skin SCC in the anogenital area. Our data suggest that cellular and acellular therapies achieving therapeutic control prevent continuous tissue remodeling and its evolution and, therefore, neoplastic degeneration. Regenerative approaches are considered a valid strategy for treating LS patients symptomatic despite prolonged first-line medical treatment. Studying genital carcinogenesis of LS cases, we reported for the first time a protective role of PRP, ADSCs, and combined therapies. Thus, in terms of cancer prevention, we propose that regenerative therapies ameliorating disease control of non-responders to conventional therapy represent an important innovative tool.

In recent years, the growing number of vehicles on the road have exacerbated issues related to safety and traffic congestion. However, the advent of the Internet of Vehicles (IoV) holds the potential to transform mobility, enhance traffic management and safety, and create smarter, more interconnected road networks. This paper addresses key road safety concerns, focusing on driver condition detection, vehicle monitoring, and traffic and road management. Specifically, various models proposed in the literature for monitoring the driver’s health and detecting anomalies, drowsiness, and impairment due to alcohol consumption are illustrated. The paper describes vehicle condition monitoring architectures, including diagnostic solutions for identifying anomalies, malfunctions, and instability while driving on slippery or wet roads. It also covers systems for classifying driving style, as well as tire and emissions monitoring. Moreover, the paper provides a detailed overview of the proposed traffic monitoring and management solutions, along with systems for monitoring road and environmental conditions, including the sensors used and the Machine Learning (ML) algorithms implemented. Finally, this review also presents an overview of innovative commercial solutions, illustrating advanced devices for driver monitoring, vehicle condition assessment, and traffic and road management.

Background: Antipsychotic drugs appear to be related to reduced bone mineral density (BMD). We conducted a narrative review to collect the available literature investigating the relationship between antipsychotic use and bone fragility. Methods: A review of the published literature was conducted and reported through PubMed/Scopus/Cochrane libraries. We included studies using any antipsychotic treatment where the bone metabolism, osteoporosis, and/or risk of fractures has been assessed. Results: After screening 1707 items, we finally included 15 papers. A total of 3245 initial patients were identified, of whom 1357 patients with a mean age of 43.8 years underwent antipsychotic treatment and were analyzed. The mean antipsychotic treatment duration of the treated group was 15.8 ± 13.9 years. Among the included studies, two reported a statistically significant difference in lumbar BMD reduction between the antipsychotic exposed group and the control group. Femoral neck BMD levels had been reported in four of the case–control studies; two reported a statistically significant difference in femoral neck BMD reduction between the antipsychotic exposed group and the control group. Conclusions: Prolonged use of antipsychotic treatment seems to be associated with an increased risk of reduced BMD, and, consequentially, with an augmented risk of bone fragility and fractures. This effect is not limited to vulnerable groups, such as those with significant medical comorbidities, the elderly, and postmenopausal women, but may also apply to anyone using antipsychotics in the long-term. Clinicians’ awareness of antipsychotic prescriptions should optimize their potential while reducing this risk.

Introduction: Childhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. Methods: We approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. Results: The final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (β = 0.39; p

Purpose: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. Design: Prospective study. Methods: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA Results: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17% vs. 52.99 ± 2.52 %; p < 0.001), as well as in the parafovea (53.01 ± 6.69% vs. 55.30 ± 2.61 %; p = 0.002), and fovea (21.38 ± 9.01% vs. 30.31 ± 5.84 %; p < 0.0001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07% vs. 50.83 ± 5.46 %; p = 0.005), as well as in the parafovea (56.76 ± 6.26% vs. 52.59 ± 5.46 %; p = 0.0001), and fovea (38.75 ± 8.59% vs. 33.43 ± 8.68 %; p < 0.0001). Conclusion: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.

BackgroundClinical staging, already widespread in medicine, represents a new frontier in psychiatry. Our goal was to convert the existing theoretical staging model for schizophrenia into a feasible tool to have a timely assessment of patients’ health status applicable in any psychiatric facility.MethodsWe assessed the empirical soundness of a staging model for schizophrenia spectrum disorders (SSDs), primarily centered on their current status. This model delineated six sequential stages (1, 2A, 2B, 3A, 3B, and 4) based on factors like symptom recurrence, persistence, and progression, including functional decline. Our analysis involved data from 137 individuals affected by SSDs. We examined 22 baseline variables, 23 construct-related variables, and 31 potentially modifiable clinical variables.ResultsThe latter stages demonstrated significantly poorer outcomes compared to the early stages across various measures, indicating medium to large effect sizes and a dose–response pattern. This pattern confirmed the validity of the model. Notably, stages 2 and 3A exhibited pronounced differences in comparison to other stages, although variables from each validation category also distinguished between consecutive stages, particularly 3A and beyond.ConclusionBaseline predictors, such as familial predisposition to schizophrenia, neurodevelopmental impairment, childhood adversities, treatment delay, negative symptoms, neurological impairment, and inadequate early response to treatment, independently largely explained the staging variance. The clinical staging model, grounded in the extended course of psychosis, exhibited sound validity and feasibility, even without the use of biological or neuroimaging markers, which could greatly improve the sensitivity of the model. These findings provide insights into stage indicators and predictors of clinical stages from the onset of psychosis.

This study explores the extent to which a unique and disruptive experience (a field trip to a prison) combined with reflective writing resulted in transformative learning by students enrolled in an accounting ethics course. Students were provided with clearly defined steps ('prompts') designed to encourage them to think logically and to reflect upon their experience, with student narratives collected before, and following the field trip. Analysis of these narratives reveals evidence of transformative learning in that students articulated not just the content of learning but changes in their perspectives of accounting practice, white-collar offenders and what it should mean to be a professional accountant.

The Internet of Things (IoT) has radically changed the industrial world, enabling the integration of numerous systems and devices into the industrial ecosystem. There are many areas of the manufacturing industry in which IoT has contributed, including plants’ remote monitoring and control, energy efficiency, more efficient resources management, and cost reduction, paving the way for smart manufacturing in the framework of Industry 4.0. This review article provides an up-to-date overview of IoT systems and machine learning (ML) algorithms applied to smart manufacturing (SM), analyzing four main application fields: security, predictive maintenance, process control, and additive manufacturing. In addition, the paper presents a descriptive and comparative overview of ML algorithms mainly used in smart manufacturing. Furthermore, for each discussed topic, a deep comparative analysis of the recent IoT solutions reported in the scientific literature is introduced, dwelling on the architectural aspects, sensing solutions, implemented data analysis strategies, communication tools, performance, and other characteristic parameters. This comparison highlights the strengths and weaknesses of each discussed solution. Finally, the presented work outlines the features and functionalities of future IoT-based systems for smart industry applications.

Proteins involved in antibiotic resistance (resistome) and with antimicrobial activity are present in biological specimens. This study aims to explore the presence and abundance of antimicrobial peptides (AMPs) and resistome proteins in bovine milk from diverse breeds and from intensive (Pezzata rossa, Bruna alpina, and Frisona) and non-intensive farming (Podolica breeds). Liquid atmospheric pressure matrix-assisted laser desorption/ionization (LAP-MALDI) mass spectrometry (MS) profiling, bottom-up proteomics, and metaproteomics were used to comprehensively analyze milk samples from various bovine breeds in order to identify and characterize AMPs and to investigate resistome proteins. LAP-MALDI MS coupled with linear discriminant analysis (LDA) machine learning was employed as a rapid classification method for Podolica milk recognition against the milk of other bovine species. The results of the LAP-MALDI MS analysis of milk coupled with the linear discriminant analysis (LDA) demonstrate the potential of distinguishing between Podolica and control milk samples based on MS profiles. The classification accuracy achieved in the training set is 86% while it reaches 98.4% in the test set. Bottom-up proteomics revealed approximately 220 quantified bovine proteins (identified using the Bos taurus database), with cathelicidins and annexins exhibiting higher abundance levels in control cows (intensive farming breeds). On the other hand, the metaproteomics analysis highlighted the diversity within the milk’s microbial ecosystem with interesting results that may reflect the diverse environmental variables. The bottom-up proteomics data analysis using the Comprehensive Antibiotic Resistance Database (CARD) revealed beta-lactamases and tetracycline resistance proteins in both control and Podolica milk samples, with no relevant breed-specific differences observed.

Within an industrial plant, the handling of randomly arranged objects is becoming increasingly popular. The technology industry has introduced ever more powerful devices to the market, but they are often unable to meet the demands of the industry in terms of processing times. Using a multi-component feeder, which facilitates the automatic picking of objects arranged in bulk, is the ideal element to speed up the identification of objects by the vision system. The innovative designed feeder eliminates the dead time of the vision system since the feeder has two working surfaces, thus making the viewing time hidden in relation to the total handling cycle time. In addition, the step feeder integrated into the feeder structure allows for control over the number of objects that fall onto the work surface, optimizing the material flow. The feeder was designed to palletize aluminum hinge fins but can also handle other products with different shapes and sizes. A two-dimensional (2D) vision system is integrated into the robotic cell to identify the components to be palletized, obtaining a reduced cycle time. The innovative feeder is fully adaptable to industrial applications and allows for easy integration into the robotic cell in which it is installed; by testing its operation with different aluminum fins, male and female, significant results were obtained in terms of cycle times ranging from 1.44 s to 1.68 s per piece, with an average productivity level (PL) of 1175 pcs every 30 min.

Abstract We study the inclusive H b → X s γ decay with H b a beauty baryon, in particular Λ b , employing an expansion in the heavy quark mass at O m b − 3 $$ \mathcal{O}\left({m}_b^{-3}\right) $$ at leading order in α s , keeping the dependence on the hadron spin. For a polarized baryon we compute the distribution d 2 Γ dy d cos θ P $$ \frac{d^2\Gamma}{dy\ d\cos {\theta}_P} $$ , with y = 2E γ /m b , E γ the photon energy and θ P the angle between the baryon spin vector and the photon momentum in the H b rest-frame. We discuss the correlation between the baryon and photon polarization, and show that effects of physics beyond the Standard Model can modify the photon polarization asymmetry. We also discuss a method to treat the singular terms in the photon energy spectrum obtained by the OPE.

Abstract Background Impaired metabolic response such as blood glucose fast fluctuations may be hypothesized in binge eating disorder (BED) and food addiction (FA) by virtue of the repetitive consumption of highly processed food. Conversely, rapid changes in plasma glucose (i.e., hypoglycemia) may trigger craving for the same food products. The investigation of early glycemic disturbances in BED and FA could enhance the understanding of the metabolic mechanisms involved in the maintenance of the disorders. Present study investigated hypoglycemia events during a 5-h-long oral glucose tolerance test (OGTT) in people with BED, FA, and the comorbid phenotype. Further, the association between the severity of eating psychopathology and the variability in hypoglycaemia events was explored. Methods Two-hundred participants with high weight and no diabetes completed the extended OGTT and were screened for BED, FA, BED-FA, or no-BED/FA. The four groups were compared in hypoglycemia events, OGTT-derived measures, and eating psychopathology. The association between predictors (eating psychopathology), confounders (demographics, metabolic features), and the outcomes (hypoglycemia, early/late hypoglycemia, severe hypoglycemia, reactive hypoglycemia) was examined through logistic regression. Results Hypoglycemia in general, and reactive hypoglycemia were highly frequent (79% and 28% of the sample, respectively). Hypoglycemia events (

Introduction Newborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions but raises practical and ethical issues. Evidence from prospectively ascertained cohorts is required to guide policy and future implementation. This study aims to develop, implement and evaluate a genomic NBS (gNBS) pilot programme.Methods and analysis The BabyScreen+ study will pilot gNBS in three phases. In the preimplementation phase, study materials, including education resources, decision support and data collection tools, will be designed. Focus groups and key informant interviews will also be undertaken to inform delivery of the study and future gNBS programmes. During the implementation phase, we will prospectively recruit birth parents in Victoria, Australia, to screen 1000 newborns for over 600 severe, treatable, childhood-onset conditions. Clinically accredited whole genome sequencing will be performed following standard NBS using the same sample. High chance results will be returned by genetic healthcare professionals, with follow-on genetic and other confirmatory testing and referral to specialist services as required. The postimplementation phase will evaluate the feasibility of gNBS as the primary aim, and assess ethical, implementation, psychosocial and health economic factors to inform future service delivery.Ethics and dissemination This project received ethics approval from the Royal Children’s Hospital Melbourne Research Ethics Committee: HREC/91500/RCHM-2023, HREC/90929/RCHM-2022 and HREC/91392/RCHM-2022. Findings will be disseminated to policy-makers, and through peer-reviewed journals and conferences.