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Objectives. The aim of the present study was to assess the performance of radiolabeled-PSMA PET/CT in a cohort of intermediate-risk prostate cancer (PCa) patients for initial staging. Methods. This is a retrospective, multicenter analysis of patients diagnosed with intermediate-risk PCa who were staged using radiolabeled PSMA PET/CT to evaluate the extent of the disease before initiating appropriate treatment. The study included patients from the Nuclear Medicine Units of the Humanitas group between 2021 and 2024. The change in management due to the PSMA PET/CT examination was assessed. Results. A total of 181 patients were enrolled across all three centers. Histopathological assessment from biopsy revealed that 51.4% of patients had favorable PCa, while 48.6% had unfavorable disease. PET/CT was positive for the primary lesions in all patients, but it revealed a positivity rate in 23 (12.7%) patients for nodes and distant organs, with a positivity rate of 0.21 in the unfavorable group and 0.05 in the favorable group (p < 0.005). Based on follow-up data, diagnostic accuracy was higher than 90% in both the favorable and unfavorable groups for lymph node and distant metastases. The inclusion of PSMA PET/CT in the diagnostic algorithm for patients with intermediate-risk PCa impacted patient management in 24 (13.3%) cases, based on the multidisciplinary team decision. Conclusions. PSMA PET/CT can affect the management of patients with intermediate-risk PCa in up to 13% of cases, mainly for unfavorable diseases. New imaging techniques as a first-line imaging procedure can help to plan the correct therapeutic approach in the intermediate-risk PCa group. [ABSTRACT FROM AUTHOR]

Attentional deficits have tragic consequences on road safety. These deficits are not solely caused by distraction, since they can also arise from other mental impairments such as, most frequently, mental fatigue. Fatigue is among the most prevalent impairing conditions while driving, degrading drivers' cognitive and physical abilities. This issue is particularly relevant for professional drivers, who spend most of their time behind the wheel. While scientific literature already documented the behavioral effects of driving fatigue, most studies have focused on drivers under sleep deprivation or anyhow at severe fatigue degrees, since it is difficult to recognize the onset of fatigue. The present study employed an EEG-driven approach to detect early signs of fatigue in professional drivers during a simulated task, with the aim of studying visual attention as fatigue begins to set in. Short-range and long-range professional drivers were recruited to take part in a 45-min-long simulated driving experiment. Questionnaires were used to validate the experimental protocol. A previously validated EEG index, the MDrow, was adopted as the benchmark measure for identifying the "fatigued" spans. Results of the eye-tracking analysis showed that, when fatigued, professional drivers tended to focus on non-informative portions of the driving environment. This paper presents evidence that an EEG-driven approach can be used to detect the onset of fatigue while driving and to study the related visual attention patterns. It was found that the onset of fatigue did not differentially impact drivers depending on their professional activity (short- vs. long-range delivery). [ABSTRACT FROM AUTHOR]

Ancient monumental complexes need continuous analysis and monitoring operations to preserve a good conservation status. For this reason, the analysis of decay and alteration phenomena represents one of the main activities for their preservation. At the same time, the diffusion of Heritage Building Information Modelling (HBIM) methodology opens new scenarios for the management of Architectural Heritage. The paper describes the workflow based on a Scan-to-BIM approach for the generation of a decay map in an HBIM model. The workflow was applied to a significant case study, the church of "Santa Maria della Grotta" in Marsala (Italy). This church, partially excavated in a sandstone bank, is part of a larger heritage site consisting of a series of hypogea and a Punic necropolis dating back more than a thousand years. The Scan-to-BIM process, relying on an integrated survey combining mobile laser scanning and photogrammetric technologies, enabled the achievement of a complete 3D parametric model of the monument and, altogether, a detailed decay map in a BIM environment. The mapping process focused on the production of thematic maps of perimetral walls according to an abacus of decays implemented in a BIM system, useful for the analysis and conservation of the church. The work demonstrates how the Scan-to-BIM process is an efficient approach for 3D data collection and how it could facilitate the identification and mapping of pathogenic phenomena. Furthermore, the inclusion of this kind of information in the BIM model represents an effective tool for the maintenance and restoration of built heritage. [ABSTRACT FROM AUTHOR]

Acute bacterial skin and skin structure infections (ABSSSI) and osteoarticular infections compound the burden of morbidity, mortality and prolonged hospitalizations among gram-positive infections. Dalbavancin, a second-generation, intravenous lipoglycopeptide, due to its prolonged half-life, can be a valuable alternative in their treatment when administered as inpatient treatment at the price of an extended hospital stay. Between October 2019 and September 2023, 31 children and adolescents were treated with dalbavancin because of bone and joint infections (n = 12 patients, 39%), ABSSSI (n = 13 patients, 42%), mainly for the limbs, facial cellulitis or complicated ABSSSI (n = 6 patients, 19%), at five Italian pediatric centers. Microbiological study provided gram-positive bacterial isolate in 16 cases, in 11 cases from a positive blood culture; 9 of them were MRSA. Twenty-five patients were initially treated with a different antibiotic therapy: beta-lactam-based in 18 patients (58%), glycopeptide-based in 15 patients (48%) and daptomycin in 6 (19%). The median time that elapsed between admission and start of dalbavancin was 18 days. A total of 61 doses of dalbavancin were administered to the 31 patients: 16 received a single dose while the remaining 15 patients received between two (n = 9) and nine doses. The frequency of administration was weekly in five cases or fortnightly in nine patients. Median length of stay in hospital was 16 days. Median time to discharge after the first dose of dalbavancin was 1 day. Treatment was very well-tolerated: of the 61 administered doses, only four doses, administered to four patients, were associated with an adverse event: drug extravasation during intravenous administration occurred in two patients, with no sequelae; however, in two patients the first administration was stopped soon after infusion start: in one (ID #11), due to headache and vomiting; in another (ID #12) due to a systemic reaction. In both patients, drug infusion was not repeated. None of the remaining 29 patients reported treatment failure (resistant or recurrent disease) or an adverse effect during a median follow-up time of two months. The use of dalbavancin was safe, feasible and also effective in shortening the hospital stay in children and adolescents.

Human mastadenoviruses, frequently denominated adenoviruses (HAdVs), may cause respiratory tract, gastrointestinal or, less frequently, other involvements. Epidemics of HAdV infections occur globally, in communities, and in closed or crowded settings. In our institution, a cluster of infants and children admitted for HAdV infection was recently observed. The aim of this study was to describe the pattern of their presenting features and investigate the possible correlation between the HAdV copy number and the clinical picture. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n = 67, cough n = 44; tonsillar exudate n = 17; other respiratory signs n = 4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n = 26, vomiting n = 8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN, and platelets, while CRP level approached statistical significance (p = 0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, the possible association between the level of CRP and the presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had tonsillar exudate and diarrhea significantly more often, while those in the lower tertile had a 4.4-day duration fever vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p = 0.006). The duration of hospitalization was not associated with the CRP level. The median time from the receipt of a positive HAdV PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of HAdV detected via PCR ranged between 47 million and 15/μL. Falling in the highest tertile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception being a significantly higher leukocyte count. The rapid turn-around of the results of the molecular testing of the HAdV genome on a pharyngeal swab allowed us to rapidly diagnose HAdV infection, allowing us to stop antibiotic therapy and immediately discharge the patients, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of HAdV from a pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing for the preferential use of qualitative rather than quantitative assay.

In the field of passive Brain–computer Interfaces (BCI), the need to develop systems that require rapid setup, suitable for use outside of laboratories is a fundamental challenge, especially now, that the market is flooded with novel EEG headsets with a good quality. However, the lack of control in operational conditions can compromise the performance of the machine learning model behind the BCI system. First, this study focuses on evaluating the performance loss of the BCI system, induced by a different positioning of the EEG headset (and of course sensors), so generating a variation in the control features used to calibrate the machine learning algorithm. This phenomenon is called covariate shift. Detecting covariate shift occurrences in advance allows for preventive measures, such as informing the user to adjust the position of the headset or applying specific corrections in new coming data. We used in this study an unsupervised Machine Learning model, the Isolation Forest, to detect covariate shift occurrence in new coming data. We tested the method on two different datasets, one in a controlled setting (9 participants), and the other in a more realistic setting (10 participants). In the controlled dataset, we simulated the movement of the EEG cap using different channel and reference configurations. For each test configuration, we selected a set of electrodes near the control electrodes. Regarding the realistic dataset, we aimed to simulate the use of the cap outside the laboratory, mimicking the removal and repositioning of the cap by a non-expert user. In both datasets, we recorded multiple test sessions for each configuration while executing a set of Workload tasks. The results obtained using the Isolation Forest model allowed the identification of covariate shift in the data, even with a 15-s recording sample. Moreover, the results showed a strong and significant negative correlation between the percentage of covariate shift detected by the method, and the accuracy of the passive BCI system (p-value < 0.01). This novel approach opens new perspectives for developing more robust and flexible BCI systems, with the potential to move these technologies towards out-of-the-lab use, without the need for supervision for use by a non-expert user.

Davide Sparasci,1 Francesco Fanfulla,2 Raffaele Ferri,3 Debora Aricò,3 Daniela Distefano,4 Emanuele Pravatà,4 Raphael Heinzer,5 José Haba-Rubio,5 Mathieu Berger,5 Gianna Carla Riccitelli,6– 8 Claudio Gobbi,6,8 Chiara Zecca,6,8,&ast; Mauro Manconi1,8,&ast; 1Sleep Medicine Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 2Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Pavia, Pavia, Italy; 3Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy; 4Neuroradiology Clinic, Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland; 5Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; 6Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Lugano, Switzerland; 7Neuropsychology and Behavioural Neurology Research Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 8Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland&ast;These authors contributed equally to this workCorrespondence: Raffaele Ferri, Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via Conte Ruggero 73, Troina, 94018, Italy, Email rferri@oasi.en.itBackground: Multiple sclerosis (MS) represents a risk factor for sleep disorders, but there are conflicting results about the prevalence and severity of sleep-related breathing disorders (SRBD) in MS. Most available data come from self-administered questionnaires.Objective: To conduct a polysomnographic study in MS focused on SRBD, compared to a group of healthy controls (HC), also considering the neuroimaging findings. To evaluate the impact of SRBD on vigilance, fatigue and depression in MS.Methods: In this cross-sectional, observational, instrumental study, 67 MS patients (men/women: 20/47; mean age: 50.6± 8.2 years) underwent PSG and maintenance of wakefulness test. Findings were compared to 67 age-, sex-, BMI-matched HC, by using parametric (Student’s t-test) and nonparametric statistics (chi-squared test). A subgroup analysis was then performed, evaluating the influence of brainstem (mesencephalic, pontine and medullary) lesions at neuroimaging on instrumental and clinical data: MS patients with at least one brainstem lesion vs MS patients without vs HC.Results: The frequency of SRBD was comparable in MS patients and HC. No MS patient had a central apnea index ≥ 2/h. The respiratory disturbance index (RDI) did not correlate to clinical parameters such as fatigue and depression. Patients with MS were drowsier than HC (47% vs 26%, p = 0.019) and showed a worse sleep pattern, in terms of duration, efficiency and architecture.Conclusion: Our study does not provide evidence of an association between MS-specific symptoms such as fatigue, sleepiness, depression and central or obstructive apneas, even in the presence of brainstem lesions.Keywords: sleep-related breathing disorders, multiple sclerosis, sleep quality, polysomnography

IntroductionParathyromatosis is a rare cause of primitive hyperparathyroidism characterized by the presence of numerous parathyroid tissue foci in the neck/mediastinum, due to hyperplasia of parathyroid embryologic residues (primary-form) or to local parathyroid tissue implantation (secondary-form). 63 cases have been described in the literature. In our patient parathyromatosis was due to a combination of two mutations.Case reportA 36-years-old woman was diagnosed with osteoporosis secondary to primary hyperparathyroidism. Subsequent right parathyroidectomy showed a parathyroid adenoma. The follow-up was negative but after 10 years she had a relapse. The genetic screening showed a rare intronic mutation of the MEN1 gene and a heterozygous mutation never described in exon 8 of the CASR gene, coding for the calcium receptor. Calcemia and PTH increased over the years with the onset of nephrocalcinosis and the worsening of osteoporosis despite the therapy with Cinacalcet, bisphosphonates and Vitamin D. She had therefore two additional surgical procedures (parathyroid tissue without malignancy). At follow-up she showed elevated levels of PTH (>1000 pg/ml) and calcium (11.2 mg/dl) and CT scans multiple subcentimetric nodules in the neck/upper mediastinum. Since the 68Ga-DOTATATE showed an increased uptake in the neck/mediastinum, lanreotide was added. After two months there was a significant biochemical response but, unfortunately, after six months, the patient showed a new worsening.Conclusionsa rare case of parathyromatosis due to a combination of two genetic alterations never described. The main issues concern the diagnosis and the radical treatment. Somatostatin analogues may have a useful role in both diagnosis and therapy.

BackgroundDisorders of Consciousness (DoC) are clinical conditions following a severe acquired brain injury (ABI) characterized by absent or reduced awareness, known as coma, Vegetative State (VS)/Unresponsive Wakefulness Syndrome (VS/UWS), and Minimally Conscious State (MCS). Misdiagnosis rate between VS/UWS and MCS is attested around 40% due to the clinical and behavioral fluctuations of the patients during bedside consciousness assessments. Given the large body of evidence that some patients with DoC possess “covert” awareness, revealed by neuroimaging and neurophysiological techniques, they are candidates for intervention with brain-computer interfaces (BCIs).ObjectivesThe aims of the present work are (i) to describe the characteristics of BCI systems based on electroencephalography (EEG) performed on DoC patients, in terms of control signals adopted to control the system, characteristics of the paradigm implemented, classification algorithms and applications (ii) to evaluate the performance of DoC patients with BCI.MethodsThe search was conducted on Pubmed, Web of Science, Scopus and Google Scholar. The PRISMA guidelines were followed in order to collect papers published in english, testing a BCI and including at least one DoC patient.ResultsAmong the 527 papers identified with the first run of the search, 27 papers were included in the systematic review. Characteristics of the sample of participants, behavioral assessment, control signals employed to control the BCI, the classification algorithms, the characteristics of the paradigm, the applications and performance of BCI were the data extracted from the study. Control signals employed to operate the BCI were: P300 (N = 19), P300 and Steady-State Visual Evoked Potentials (SSVEP; hybrid system, N = 4), sensorimotor rhythms (SMRs; N = 5) and brain rhythms elicited by an emotional task (N = 1), while assessment, communication, prognosis, and rehabilitation were the possible applications of BCI in DoC patients.ConclusionDespite the BCI is a promising tool in the management of DoC patients, supporting diagnosis and prognosis evaluation, results are still preliminary, and no definitive conclusions may be drawn; even though neurophysiological methods, such as BCI, are more sensitive to covert cognition, it is suggested to adopt a multimodal approach and a repeated assessment strategy.

On 31 March 2022, Public Health Scotland was alerted to five children aged 3–5 years, presenting to the Glasgow children’s hospital with severe hepatitis of unknown etiology within a 3-week period [...]

Not all elements displayed in a YouTube in-stream video ad are attributable to the ad itself. Some of those are automatically introduced by the platform, such as the countdown timer and the time progress bar. In recent years, some authors started exploring the effects associated with the presence of such non-ad items, providing valuable findings. However, objective evaluation of viewers’ visual attention is lacking in this context as well as emotional investigation. In addition, previous research showed how the manipulation of seemingly negligible details can yield dramatically different outcomes in the context of in-stream advertising. To extend knowledge, the authors explored the effects of the non-ad items’ presence by employing eye-tracking and facial coding techniques in combination with self-reports in a between-subjects experimental design focusing on the YouTube 15-s, mid-roll, non-skippable in-stream ad format. Results showed that the ad format currently employed by YouTube performs worse than its equivalent without the non-ad items on all the investigated measures and than its equivalent in which the non-ad items’ presence was experimentally reduced on facial coding disgust, self-reported disgust, ad irritation, and ad attitude. Managerial insights and challenges concerning the future of in-stream advertising and neuromarketing are highlighted.

When assessing trainees’ progresses during a driving training program, instructors can only rely on the evaluation of a trainee’s explicit behavior and their performance, without having any insight about the training effects at a cognitive level. However, being able to drive does not imply knowing how to drive safely in a complex scenario such as the road traffic. Indeed, the latter point involves mental aspects, such as the ability to manage and allocate one’s mental effort appropriately, which are difficult to assess objectively. In this scenario, this study investigates the validity of deploying an electroencephalographic neurometric of mental effort, obtained through a wearable electroencephalographic device, to improve the assessment of the trainee. The study engaged 22 young people, without or with limited driving experience. They were asked to drive along five different but similar urban routes, while their brain activity was recorded through electroencephalography. Moreover, driving performance, subjective and reaction times measures were collected for a multimodal analysis. In terms of subjective and performance measures, no driving improvement could be detected either through the driver’s subjective measures or through their driving performance. On the other side, through the electroencephalographic neurometric of mental effort, it was possible to catch their improvement in terms of mental performance, with a decrease in experienced mental demand after three repetitions of the driving training tasks. These results were confirmed by the analysis of reaction times, that significantly improved from the third repetition as well. Therefore, being able to measure when a task is less mentally demanding, and so more automatic, allows to deduce the degree of users training, becoming capable of handling additional tasks and reacting to unexpected events.

The current industrial environment relies heavily on maritime transportation. Despite the continuous technological advances for the development of innovative safety software and hardware systems, there is a consistent gap in the scientific literature regarding the objective evaluation of the performance of maritime operators. The human factor is profoundly affected by changes in human performance or psychological state. The difficulty lies in the fact that the technology, tools, and protocols for investigating human performance are not fully mature or suitable for experimental investigation. The present research aims to integrate these two concepts by (i) objectively characterizing the psychological state of mariners, i.e., mental workload, stress, and attention, through their electroencephalographic (EEG) signal analysis, and (ii) validating an innovative safety framework countermeasure, defined as Human Risk-Informed Design (HURID), through the aforementioned neurophysiological approach. The proposed study involved 26 mariners within a high-fidelity bridge simulator while encountering collision risk in congested waters with and without the HURID. Subjective, behavioral, and neurophysiological data, i.e., EEG, were collected throughout the experimental activities. The results showed that the participants experienced a statistically significant higher mental workload and stress while performing the maritime activities without the HURID, while their attention level was statistically lower compared to the condition in which they performed the experiments with the HURID (all p < 0.05). Therefore, the presented study confirmed the effectiveness of the HURID during maritime operations in critical scenarios and led the way to extend the neurophysiological evaluation of the HFs of maritime operators during the performance of critical and/or standard shipboard tasks.

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, belonging to the group of lysosomal storage diseases (LSDs). GD is caused by a defect in lysosomal glucocerebrosidase, responsible for glucosylceramide breakdown into glucose and ceramide. Because of this dysfunction, glucosylceramide progressively accumulates in the liver, spleen, bone marrow, bones, and in other tissues and organs, also causing anemia, hepatosplenomegaly, thrombocytopenia, and bone symptoms. Depending on neurological symptoms, GD is classified into three main types. Treatment options for LSDs, including enzyme replacement therapy, hematopoietic stem cell transplantation, small molecular weight pharmacologic chaperones, and, for some LSDs, gene therapy, are increasingly available. For this reason, many efforts are aimed at implementing newborn screening for LSDs since early detection accompanied by a prompt intervention has been demonstrated to be essential for reducing morbidity and mortality and for improved clinical outcomes. Herein, we report two siblings of preschool age, presenting with hepatosplenomegaly and thrombocytopenia. The initial suspicion of GD based on the clinical picture was further supported by biochemical confirmation, through newborn screening workflow, including first- and second-level testing on the same dried blood spot samples, and finally by molecular testing.

Abstract Objectives The primary objective of the study is to demonstrate the efficacy of low-dose IFN-β in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus control group within 28 days. Secondary objectives are: 1) To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-β versus control group within 28 days of randomization 2) To assess the reduction in number of deaths in IFN- β compared to control group (day 28) 3) To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-β -treated versus control group at Day 14 and Day 28 4) To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-β compared to control group (day 28) 5) To assess the safety of IFN-β -treated patients versus control group Trial design Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients). Randomization will be stratified by gender. Stratified randomization will balance the presence of male and female in both study arms. Participants Male and female adults aged 65 years or older with newly diagnosed SARS-CoV-2 infection and mild COVID-19 symptoms are eligible for the study. The trial is being conducted in Rome. Participants will be either hospitalized or home isolated. A group of physicians belonging to the Special Unit for Regional Continued Care (USCAR), specifically trained for the study and under the supervision of the National Institute for Infectious Diseases “Lazzaro Spallanzani”, will be responsible for the screening, enrolment, treatment and clinical monitoring of patients, thus acting as a bridge between clinical centers and territorial health management. Inclusion criteria are as follows: ≥ 65 years of age at time of enrolment; Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen < 72 hours prior to randomization; Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures; Understands and agrees to comply with planned study procedures; Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol; Being symptomatic for less than 7 days before starting therapy; NEWS2 score ≤2. Exclusion criteria are as follows: Hospitalized patients with illness of any duration, and at least one of the following: Clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air at rest or after walking test, OR Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen; Patients currently using IFN-β (e.g., multiple sclerosis patients); Patients undergoing chemotherapy or other immunosuppressive treatments; Patients with chronic kidney diseases; Known allergy or hypersensitivity to IFN (including asthma); Any autoimmune disease (resulting from patient anamnesis); Patients with signs of dementia or neurocognitive disorders; Patients with current severe depression and/or suicidal ideations; Being concurrently involved in another clinical trial; HIV infection (based on the anamnesis); Use of any antiretroviral medication; Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min); Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition); Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance; Lack or withdrawal of informed consent Intervention and comparator Control arm: No specific antiviral treatment besides standard of care. Treatment arm: 11μg (3MIU) of IFN-β1a will be injected subcutaneously at day 1, 3, 7, and 10 in addition to standard of care. The drug solution, contained in a pre-filled cartridge, will be injected by means of the RebiSmart® electronic injection device. Interferon β1a (Rebif®, Merck KGaA, Darmstadt, Germany) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS). The dose selected for this study is expected to exploit the antiviral and immunomodulatory properties of the cytokine without causing relevant toxicity or inducing refractoriness phenomena sometimes observed after high-dose and/or chronic IFNβ treatments. Main outcomes Primary endpoint of the study is the proportion of patients experiencing a disease progression, during at least 5 days, according to the National Early Warning Score (NEWS2). The NEWS2 score is a standardized approach aimed at promptly detecting signs of clinical deterioration in acutely ill patients and establishing the potential need for higher level of care. It is based on the evaluation of vital signs, including respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response. The resulting observations, compared to a normal range, are combined in a single composite “alarm” score. Any other clinical sign clearly indicating a disease worsening will be considered as disease progression. Randomization Sixty patients will be randomized 2:1 to receive IFN-β1a plus the standard of care or the standard of care only. Eligible patients will be randomized (no later than 36 h after enrolment) by means of a computerized central randomization system. All patients will receive a unique patient identification number at enrolling visit when signing the informed consent and before any study procedure is performed. This number remains constant throughout the entire study. The randomization of patients will be closed when 60 patients have been enrolled. The randomization will be stratified by sex; for each stratum a sequence of treatments randomly permuted in blocks of variable length (3 or 6) will be generated. Blinding (masking) This is an open-label study. After the randomization, patients will be notified whether they will be in the experimental arm or in the control arm. Numbers to be randomised (sample size) The study plans to enrol 60 patients: 40 in the IFN-β1a arm, 20 in the control arm, according to a 2:1 - treated: untreated ratio. Trial Status Protocol Version: 3.0 Version Date: 18/03/2021 The study is open for recruitment since 16/04/2021.Recruitment is expected to l be completed before 15/08/2021. Trial registration EudraCT N°: 2020-003872-42, registration date: 19/10/2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.”

Commercially available Purolite CT151 demonstrated to be an efficient acid catalyst for the synthesis of alkyl levulinates via alcoholysis of furfuryl alcohol (FA) at mild temperatures (80–120 °C) and short reaction time (5 h). Reaction conditions were first optimized for the synthesis of ethyl levulinate and then tested for the preparation of methyl-, propyl-, isopropyl-, butyl, sec-butyl- and allyl levulinate. Preliminary scale-up tests were carried out for most of the alkyl levulinates (starting from 5.0 g of FA) and the resulting products were isolated as pure by distillation in good yields (up to 63%). Furthermore, recycling experiments, conducted for the preparation of ethyl levulinate, showed that both the Purolite CT151 and the exceeding ethanol can be recovered and reused for four consecutive runs without any noticeable loss in the catalyst activity.

This paper starts from the hypothesis that Francesco Algarotti, a well-respected scientist and writer in Enlightenment-era Europe, wrote the biography of Castruccio Castracani, published as part of Lettere militari in the Zatta edition of 1759, because he was driven by the only seemingly peripheral endeavours of the Turkman known as Thāmasp Qoli Khān, later Nādir Shāh Afshār, whose fame had begun to spread among Europeans with his audacious plan to conquer territories on the border of the Hapsburg and Russian empires. Keen to measure himself against Machiavelli’s La vita di Castruccio Castracani, a book based on both reality and the author’s imagination, Algarotti indeed drew many parallels between the lives of Castruccio and Nādir and at the ‘Mars school’, created in Potsdam by Frederick II of Prussia, he planned his biography, procuring first hand accounts and reports, at times partial and incomplete, of the military campaigns which were in progress. Algarotti, like many of his contemporaries, saw Koulican as the peacemaker of those far-off countries, considered wholly advantageous to the geographical and economic power balances in Europe. With the passing of time, after the ferocious taking of Dehli in 1739, the despotic intentions of Nādir became clearer to Algarotti. In those years, in his unpublished Saggio critico del triumvirato di Crasso, Pompeo e Cesare he had explored the concealing talents of Caesar, whose coup d’état transformed the res publica into a dictatorship. From the unfinished biography of Nādir, it is possible to examine reconstructions of the battles between Koulican and the Afghans under Ashrāf as well as those against the Ottomans under Topāl Othmān Pashā from an intertextual perspective of the history of ideas. Written in lexically precise prose and a conversational tone, they were much appreciated by specialists and non-specialists alike and later became two Discorsi militari, published in 1764.

The capability of measuring specific neurophysiological and autonomic parameters plays a crucial role in the objective evaluation of a human’s mental and emotional states. These human aspects are commonly known in the scientific literature to be involved in a wide range of processes, such as stress and arousal. These aspects represent a relevant factor especially in real and operational environments. Neurophysiological autonomic parameters, such as Electrodermal Activity (EDA) and Photoplethysmographic data (PPG), have been usually investigated through research-graded devices, therefore resulting in a high degree of invasiveness, which could negatively interfere with the monitored user’s activity. For such a reason, in the last decade, recent consumer-grade wearable devices, usually designed for fitness-tracking purposes, are receiving increasing attention from the scientific community, and are characterized by a higher comfort, ease of use and, therefore, by a higher compatibility with daily-life environments. The present preliminary study was aimed at assessing the reliability of a consumer wearable device, i.e., the Fitbit Sense, with respect to a research-graded wearable, i.e., the Empatica E4 wristband, and a laboratory device, i.e., the Shimmer GSR3+. EDA and PPG data were collected among 12 participants while they performed multiple resting conditions. The results demonstrated that the EDA- and PPG-derived features computed through the wearable and research devices were positively and significantly correlated, while the reliability of the consumer device was significantly lower.

Introduction: In operational environments, human interaction and cooperation between individuals are critical to efficiency and safety. These states are influenced by individuals' cognitive and emotional states. Human factor research aims to objectively quantify these states to prevent human error and maintain constant performances, particularly in high-risk settings such as aviation, where human error and performance account for a significant portion of accidents. Methods: Thus, this study aimed to evaluate and validate two novel methods for assessing the degree of cooperation among professional pilots engaged in real-flight simulation tasks. In addition, the study aimed to assess the ability of the proposed metrics to differentiate between the expertise levels of operating crews based on their levels of cooperation. Eight crews were involved in the experiments, consisting of four crews of Unexperienced pilots and four crews of Experienced pilots. An expert trainer, simulating air traffic management communication on one side and acting as a subject matter expert on the other, provided external evaluations of the pilots' mental states during the simulation. The two novel approaches introduced in this study were formulated based on circular correlation and mutual information techniques. Results and discussion: The findings demonstrated the possibility of quantifying cooperation levels among pilots during realistic flight simulations. In addition, cooperation time is found to be significantly higher (p < 0.05) among Experienced pilots compared to Unexperienced ones. Furthermore, these preliminary results exhibited significant correlations (p < 0.05) with subjective and behavioral measures collected every 30 s during the task, confirming their reliability. [ABSTRACT FROM AUTHOR]

Ocular artifacts, including blinks and saccades, pose significant challenges in the analysis of electroencephalographic (EEG) data, often obscuring crucial neural signals. This tutorial provides a comprehensive guide to the most effective methods for correcting these artifacts, with a focus on algorithms designed for both laboratory and real-world settings. We review traditional approaches, such as regression-based techniques and Independent Component Analysis (ICA), alongside more advanced methods like Artifact Subspace Reconstruction (ASR) and deep learning-based algorithms. Through detailed step-by-step instructions and comparative analysis, this tutorial equips researchers with the tools necessary to maintain the integrity of EEG data, ensuring accurate and reliable results in neurophysiological studies. The strategies discussed are particularly relevant for wearable EEG systems and real-time applications, reflecting the growing demand for robust and adaptable solutions in applied neuroscience. [ABSTRACT FROM AUTHOR]

Mixed Reality (MR) environments hold immense potential for inducing a sense of embodiment, where users feel like their bodies are present within the virtual space. This subjective experience has been traditionally assessed using subjective reports and behavioral measures. However, neurophysiological approaches offer unique advantages in objectively characterizing embodiment. This review article explores the current state of the art in utilizing neurophysiological techniques, particularly Electroencephalography (EEG), Photoplethysmography (PPG), and Electrodermal activity (EDA), to investigate the neural and autonomic correlates of embodiment in MR for out-of-the-lab applications. More specifically, it was investigated how EEG, with its high temporal resolution, PPG, and EDA, can capture transient brain activity associated with specific aspects of embodiment, such as visuomotor synchrony, visual feedback of a virtual body, and manipulations of virtual body parts. The potential of such neurophysiological signals to differentiate between subjective experiences of embodiment was discussed, with a particular regard to identify the neural and autonomic markers of early embodiment formation during MR exposure in real settings. Finally, the strengths and limitations of the neurophysiological approach in the context of MR embodiment research were discussed, in order to achieve a more comprehensive understanding of this multifaceted phenomenon. [ABSTRACT FROM AUTHOR]

Since 5-(hydroxymethyl)furfural (HMF) has been labelled as the "sleeping giant" of the bio-based platform-chemical realm, numerous investigations have been devoted to the exploitation of this versatile molecule and its endless chemical transformations into novel monomers for producing bio-based polymers. However, beyond 2,5-furandicarboxylic acid (2,5-FDCA), little attention has been devoted to key aspects that deserve being addressed before bringing forward other HMF-derivatives into the bio-based plastic market, i.e., procedures, scaling-up of the syntheses, products' purification, physical–thermal properties, and above all green metrics (sustainability/greenness of procedures). This critical review focuses on the most investigated derivatives of HMF beyond 2,5-FDCA, assessing their exploitation as monomers for bio-based polymers. HMF-derived compounds have been classified according to their functionalities, i.e., aldehyde-, diol-, polyol-, amine-, acid-, ester-, carbonate-, acrylate-, and epoxy-based monomers. The related synthetic approaches are discussed, evaluating the sustainability of the procedures reported so far, based on green metrics such as the environmental factor (E-factor) and the process mass intensity (PMI). For each family of HMF derivatives, their use as monomers for the synthesis of bio-based polymers has been addressed, taking into consideration the efficiency of the polymerisation reactions, the physical–chemical and thermal properties of the resulting bio-based polymers, as well as their biodegradability if applicable. The overall picture that emerges is that much has been achieved for the synthesis of furan monomers; however, many obstacles still need to be overcome prior to massively introducing these compounds into the bio-based plastic market. Hopefully, the data reported in this review will shed light on the goals achieved so far, and on some critical issues that must still be tackled in the short- or medium-term for a more sustainable and however efficient industrial process. [ABSTRACT FROM AUTHOR]

Cochlear implants (CI) allow deaf patients to improve language perception and improving their emotional valence assessment. Electroencephalographic (EEG) measures were employed so far to improve CI programming reliability and to evaluate listening effort in auditory tasks, which are particularly useful in conditions when subjective evaluations are scarcely appliable or reliable. Unfortunately, the presence of CI on the scalp introduces an electrical artifact coupled to EEG signals that masks physiological features recorded by electrodes close to the site of implant. Currently, methods for CI artifact removal have been developed for very specific EEG montages or protocols, while others require many scalp electrodes. In this study, we propose a method based on the Multi-channel Wiener filter (MWF) to overcome those shortcomings. Nine children with unilateral CI and nine age-matched normal hearing children (control) participated in the study. EEG data were acquired on a relatively low number of electrodes (n = 16) during resting condition and during an auditory task. The obtained results obtained allowed to characterize CI artifact on the affected electrode and to significantly reduce, if not remove it through MWF filtering. Moreover, the results indicate, by comparing the two sample populations, that the EEG data loss is minimal in CI users after filtering, and that data maintain EEG physiological characteristics. [ABSTRACT FROM AUTHOR]