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Vincenzo Vestuto,1,* Marisa Conte,1,* Mariapia Vietri,1,* Francesca Mensitieri,2 Valentina Santoro,1,3 Anna Di Muro,1 Mariaevelina Alfieri,4 Maria Moros,5,6 Maria Rosaria Miranda,1,3 Chiara Amante,1 Matteo Delli Carri,1 Pietro Campiglia,1 Fabrizio Dal Piaz,2,7 Pasquale Del Gaudio,1 Nunziatina De Tommasi,1,3 Antonietta Leone,1 Ornella Moltedo,1 Giacomo Pepe,1,3 Elisa Cappetta,1 Alfredo Ambrosone1 1Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy; 2Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 84081, Italy; 3National Biodiversity Future Center (NBFC), Palermo, 90133, Italy; 4Clinical Pathology, Santobono-Pausilipon Children’s Hospital, AORN, Naples, 80122, Italy; 5Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 7Operative Unit of Clinical Pharmacology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, 84131, Italy*These authors contributed equally to this workCorrespondence: Alfredo Ambrosone; Elisa Cappetta, Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy, Email aambrosone@unisa.it; ecappetta@unisa.itPurpose: Extracellular vesicles (EVs) are promising tools for nanomedicine and nanobiotechnology. The purification of mammalian-derived EVs involves intensive processes, and their therapeutic application raises multiple safety and regulatory issues. Plants have the potential to serve as nonconventional sources of therapeutically relevant EVs. In this context, we recently identified hairy roots (HRs) of medicinal plants as a novel biotechnological platform to produce EVs for human health.Methods: Herein, we report the purification, omics profiling, and bioactivity of EVs isolated from HRs of the medicinal plants S. sclarea and S. dominica. EVs were isolated from conditioned media of HR cultures using differential ultracentrifugation (dUC) and size exclusion chromatography (SEC). The isolated EVs were characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The proteomic and metabolomic profiles of the EVs were determined using mass spectrometry. Uptake studies and bioactivity assays, including confocal microscopy, MTT, flow cytometry, ROS quantification, and untargeted metabolomics analyses, were conducted in SH-SY5Y cells treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to evaluate the therapeutic potential of EVs in an in vitro model of Parkinson’s disease.Results: S. sclarea HRs released nanosized round-shaped EVs with a distinctive molecular signature. HR EVs from S. sclarea and S. dominica revealed conserved cargo of secondary metabolites, predominantly triterpenoids, which are known for their antioxidant properties. We showed that HR EVs are safe, enter the cells, and strongly inhibit apoptosis in a cellular model of Parkinson’s disease. Cellular metabolomics revealed that EVs preserved metabolic homeostasis and mitigated cellular oxidative stress when co-administered with 6-OHDA. Mechanistically, HR EVs inhibited 6-OHDA autoxidation and substantially reduced the accumulation of its oxidative products, which are responsible for 6-OHDA-induced toxicity.Conclusion: Collectively, our findings provide compelling evidence that EVs isolated from the hairy roots of Salvia species are promising, non-mammalian alternative for the design of novel therapies targeting neurological disorders. Keywords: non-mammalian EV source, Salvia extracellular vesicles, hairy roots, nanomedicine, neuroprotection, Parkinson’s disease

The European Spallation Source, which is under construction in Lund, Sweden, aims to be the world's brightest source of neutrons. During the first phase of construction, users will have access to a suite of 15 instruments, which will produce neutrons through a butterfly-shaped moderator system located above the spallation target. The HighNESS project, funded by the European Union Horizon 2020 program, has the goal of providing a new design for the second moderator, which will be situated below the spallation target and will be the most intense neutron source in the world. The new moderator will provide a higher intensity of neutrons in the cold, very cold, and ultracold energy regions, which will advance research in several areas of condensed matter and offer unique opportunities in fundamental physics. Work Package 2 of the HighNESS project is focused on supporting the design of the second moderator by providing nuclear data support for neutronics calculations and improving the accompanying physics software. This paper showcases recent advancements in NJOY + NCrystal, a tool for creating thermal neutron scattering–evaluated nuclear data files and continued work on nanodiamonds as advanced neutron reflectors. [ABSTRACT FROM AUTHOR]

High-intensity neutron beams, such as those available at the European Spallation Source (ESS), provide new opportunities for fundamental discoveries. Here, we discuss a novel Ramsey neutron-beam experiment to search for ultralight axion dark matter through its coupling to neutron spins, which would cause the neutron spins to rotate about the velocity of the neutrons relative to the dark matter halo. We estimate that experiments at the HIBEAM beamline with a 50 m free flight path at the ESS can improve the sensitivity to the axion-neutron coupling compared to the current best laboratory limits by up to 2-3 orders of magnitude over the axion mass range 10^{-22}  eV-10^{-16}  eV.

Background/Objectives : Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety are limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods : Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsychiatric AE and one of the MM-approved mAbs as the suspected drug (i.e., daratumumab, elotuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results : Unknown signals of disproportionate reporting (SDR) included the following: cerebral infarction for daratumumab ( n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC 025 -IC 075 = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); an altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guillain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthostatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elotuzumab (4; 28.31, 10.58-75.73; 5, 3.24-6.08). Conclusions : Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsychiatric AEs, including GBS, further investigations are necessary.

Background: To translate and cross-culturally adapt the Parkinson's Disease Caregiver Burden questionnaire (PDBC) into Italian language and to evaluate the psychometric properties of the Italian version in terms of test-retest reliability, internal consistency, and construct validity., Methods: The PDBC-I was developed by forward-backward translation to establish correspondence with the original English latest version. Psychometric properties were estimated in a sample of primary caregivers of individuals with Parkinson's disease. Reliability testing included internal consistency (Cronbach's alpha), test-retest reliability (ICC), the standard error of measurement (SEM) and the minimal detectable change (MDC), also expressed as percentage (MDC%). Validity was estimated by comparing the PDBC -I to the Caregiver Burden Inventory (CBI) and the Short Form 36 (SF-36) (Pearson correlation coefficient)., Results: The questionnaire was administered to 65 caregivers, showing internal consistency of 0.934. ICC value was 0.811 (95% CI 0.708-0.880) for test-retest reliability, and the SEM and the MDC (MDC%) were 5.04 and 13.97 (38.21%), respectively. Low to moderate correlation with all other investigated scales (CBI: r=0.693; SF-36 physical score: r=-0.309; SF-36 mental score: r=-0.588; SF36 total score: -0.470) were found., Conclusions: Despite the PDCB-I holds acceptable psychometric properties to be used in clinical settings of Italian-speaking Countries as a measure of caregiver burden in caregivers of individuals with Parkinson Disease, the caregiver might require the support of a clinician to finalize the compilation of the questionnaire.

Introduction: The current investigation presents a two-fold approach to rediscovering the potential of Sonchus asper as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of S. asper , thus enhancing economic profits., Methods: Liquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves. The antioxidant activity, the hypoglycaemic effect and the incorporation into liposomes were evaluated., Results: 38 compounds and 6 essential amino acids were identified. The incorporation into liposomes maximized the health-promoting properties for potential pharmaceutical or food applications., Discussion: The commercialization of S. asper could: (i) contribute to improving the well-being of rural and urban communities, being S. asper a wild edible plant available at low cost, environmentally friendly, resilient, and adaptable; (ii) generate landowner economic returns., Competing Interests: Author AV was employed by Spinoff TNcKILLERS srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Parisi, Santoro, Faraone, Benedetto, Vassallo, De Tommasi, Milella, Nesticò, Maselli, Fadda and Caddeo.)

Purpose: Return to work after maternity leave represents a radical change in women's lives. This paper aims to present a new metaphor categorization system based on two studies, which could assist working mothers in expressing the nuances of their experience when returning to work after maternity leave., Methods: We carried out the analysis of the metaphors according to the method for thematic analysis, through a multistep, iterative coding process. To ensure the researchers encode the data similarly, inter-coder reliability was achieved through the judges' agreement method. The level of agreement between the two judges was measured by Cohen's kappa., Results: In Study 1, we established a system comprising ten metaphor categories (namely, Natural event and/or element, Challenge and destination, Movement and/or action, Fresh start, Fight, Game and hobby, Animal, Alternate reality, Means of transport, Hostile place). In Study 2, we recognized the same metaphor categories observed in Study 1, except "Means of transport", even with data sourced from a distinct participant group, an indicator of credibility in terms of inter-coder reliability., Conclusion: Findings highlight the usefulness of this new metaphor categorization system (named Meta4Moms@Work-Metaphors system for Moms back to Work) to facilitate a more straightforward elicitation of the meanings employed by working mothers to depict their return to work after maternity leave. Leveraging these insights, researchers/practitioners can develop and execute primary and secondary interventions aimed to enhance working mothers' work-life balance, well-being, and mental health., (© 2024. The Author(s).)

This paper describes the physical modelling of neutron scattering in two polycrystalline inclusion compounds, fully deuterated clathrate hydrate andC60, each with paramagnetic oxygen as guest molecules. For studying the suitability of these materials for neutron moderation to very low energies, the model includes, in addition to the magnetic neutron scattering by the oxygen, the nuclear scattering by all constituents. The theoretical total cross sections are calculated based on the phonon density of states obtained by density functional theory and molecular dynamics simulations. At low temperatures, the developed scattering kernels are in good agreement with experimental neutron scattering data reported in the literature. At 20 K and above, a Lorentzian distribution for the zero-field splitting of the magnetic substates of the spin triplet of the oxygen molecules helps to reproduce magnetic peaks observed in inelastic neutron scattering experiments better than the original theory based on a single-valued splitting constant. Neutron spectra obtained by Monte Carlo simulations in infinite media are presented, highlighting the potential use ofO2-containing fully deuterated clathrate hydrate as a neutron moderator for the production of very cold neutrons., (© 2024 IOP Publishing Ltd.)

Background : Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph nodes; instead, para-aortic lymph nodes are considered as distant metastases. The aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Methods : This is a retrospective analysis. De novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; the pattern of recurrence was also evaluated. A propensity score matching (PSM) was applied to create comparable cohorts. The primary end-point was the progression-free survival (PFS). The secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS), and pattern of relapse. Results : In total, 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. The median PFS was 20 and 11 months in pelvic and para-aortic patients, respectively ( p = 0.042). The difference was not confirmed in the multivariate analysis ( p = 0.06). The median BRFS was 16 and 9 months, respectively, in the pelvic and para-aortic group ( p = 0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-year LPFS was 90.5%. In PSM, no statistically significant differences for all the study end-points were detected. Conclusions : Patients affected by para-aortic disease might have a PFS comparable to pelvic disease; local control is high in both cohorts. Our results also support the use of SBRT for para-aortic metastases.

Background/aim: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting., Patients and Methods: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts., Results: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2., Conclusion: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In the course of the Horizon 2020 project HighNESS, a second moderator concept has been developed for the European Spallation Source, which complements the currently built moderator and is optimized for high intensity with a large viewable surface area. In this work we introduce conceptual designs for neutron instruments for condensed matter research designed to make optimal use of the capabilities of this moderator. The focus is on two concepts for small-angle neutron scattering and one neutron imaging instrument, which are intended to complement corresponding instruments that are already under construction at the European Spallation Source. One small-angle neutron scattering instrument concept resembles a conventional pinhole collimator geometry and aims to profit from the proposed second moderator by enabling to illuminate larger samples and providing particularly high resolution, drawing on a 30 m collimation and corresponding detector distance. A second small-angle neutron scattering instrument concept adopts nested mirror optics that enable to efficiently exploit the large moderator size and provide high resolution by focusing on the detector. The neutron imaging instrument concept is a typical pinhole instrument that can be found at continuous sources and draws on the corresponding strengths of high flux and large homogeneous fields-of-view, while still providing moderate wavelength resolution for advanced imaging methods., (© 2024. The Author(s).)

Calabrian Glycyrrhiza glabra is one of the most appreciated licorice varieties worldwide, and its leaves are emerging as a valuable source of bioactive compounds. Nevertheless, this biomass is usually discarded, and its valorization could contribute to boost the economic value of the licorice production chain. In this study, the effects of production area and harvest time on the specialized metabolite content of G. glabra leaves (GGL) and also the antioxidant and anti-aging properties are evaluated to explore the potential of this untapped resource and to select the most optimal harvesting practices. GGL exhibited high levels of specialized metabolites (4-30 g/100 g of dry leaf) and the most abundant ones are pinocembrin, prenylated flavanones (licoflavanone and glabranin), and prenylated dihydrostilbenes. Their levels and antioxidant capacity in extracts are influenced by both production area and harvest time, showing a decisive role on specialized metabolites accumulation. Interestingly, GGL extracts strongly attenuate the toxicity of α-synuclein, the intracellular reactive oxygen species (ROS) content, and cellular senescence on Saccharomyces cerevisiae expressing human α-synuclein model, showing great potential to prevent aging and age-related disorders. These results provide insights into the phytochemical dynamics of GGL, identifying the best harvesting site and period to obtain bioactive-rich sources with potential uses in the food, nutraceutical, and pharmaceutical sectors.