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Abstract Background Despite the importance of Ultrasound-guided Regional Anaesthesia (UGRA) in Emergency Medicine (EM), there is significant variability in UGRA training among emergency physicians. We recently developed a one-day (8 h), simulation-based UGRA course, specifically tailored to help emergency physicians to integrate these skills into their clinical practice. Methods In this pre/post intervention study, emergency physicians attended a course consisting of a 4-hour teaching on background knowledge and a practical part structured as follows: a scanning session on a healthy individual; a needling station with an ex-vivo model (turkey thighs); a simulation-based learning experience on local anaesthetic toxicity (LAST); a session on the UGRA simulator BlockSim™. Participants rated their level of knowledge across several domains of UGRA practice; for this purpose, we used a 5-points Likert scale (from 0 to 4). Participants also rated the perceived utility of the practical sessions. We extrapolated baseline characteristics of participants, and we paired the answers of pre- and post-course questionnaires using Wilcoxon signed-rank test. Results Seventy-four emergency physicians across ten Italian regions and Switzerland completed the pre-and post- course questionnaire. Most of them were EM residents (75.68%) who had never performed UGRA. Median self-reported knowledge significantly improved from 1 to 3 in the following domains of UGRA indications: Knowledge of contraindications and UGRA techniques [pre-course 1 (IQR 1–2), post-course 3 (IQR 2–3)]; Equipment and drugs [pre-course 1(IQR 1–1), post-course 3 (IQR2-3)]; LAST recognition [pre-course 1 (IQR 1–2), post-course 3 (IQR 2–4)]; LAST management [pre-course 1 (IQR 1–1,75), post-course 3 (IQR 2–3)] (p

Abstract Aims Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. Methods and results From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2‐year follow‐up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow‐up paths, as well as specific end‐stages conditions of the disease. Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53–71], male gender n = 3973 (81.5%), NYHA class I–II n = 3576 (73.3%), III–IV n = 1300 (26.7%), LVEF = 33 [25.5–39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8–67.2]), with a minimum 2‐year follow‐up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end‐stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5‐year follow‐up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P

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.

Developing robust benchmarking methods is crucial to evaluate the standing stability of bipedal systems, including humanoid robots and exoskeletons. This paper presents a standardized benchmarking procedure based on the Linear Inverted Pendulum Model and the Capture Point concept to normalize the maximum angular momentum before falling. Normalizing these variables establishes absolute and relative benchmarks achieving comprehensive comparisons across different bipedal systems. Simulations were conducted on two humanoid robots, COMAN and WALK-MAN, to validate the approach, demonstrating its applicability to various sizes and configurations of robots. Furthermore, the same benchmarking method was applied to the therapeutic exoskeleton H3, illustrating its potential to optimize mechanical design and therapeutic performance. The results indicate that this standardized procedure provides a valuable tool for assessing and improving the stability of anthropomorphic robotic systems, providing insights into both hardware capabilities and control strategies.

Abstract Introduction Pain is one of the most frequently reported symptoms in hemodialyzed (HD) patients, with prevalence rates between 33% and 82%. Risk factors for chronic pain in HD patients are older age, long-lasting dialysis history, several concomitant diseases, malnutrition, and others. However, chronic pain assessment in HD patients is rarely performed by specialists in pain medicine, with relevant consequences in terms of diagnostic and treatment accuracy. Furthermore, no study has used the recently introduced International Association for the Study of Pain (IASP) pathophysiological classification. Methods In this observational, cross-sectional study in a tertiary HD center in Northern Italy, we analyzed data regarding HD patients, evaluated for 5 months in 2021 by specialists in pain medicine and aimed to identify and characterize chronic pain according to the IASP definition and the last 2019 classification of chronic pain for ICD-11. Pain severity was evaluated by the pain severity score of the brief pain inventory tool. Results Among 213 patients, 65 (31%) suffered from chronic pain. The average age was 73.1 years; 55.5% of the patients were male; 53.7% had diabetes, and 39.2% had arterial hypertension. Of the 54 patients subjected to an in-depth evaluation, data regarding 113 pain diagnoses were extracted, particularly related to osteoarthritis, obliterating arterial disease, and low back pain with or without radiculopathy. On the basis of these diagnoses, the pain classification according to the IASP pathophysiological definition highlighted a predominant nociceptive pain type (53.9% of all the diagnoses), followed by neuropathic (22.1%), mixed (22.1%), nociplastic (2.6%), and idiopathic (2.6%) pain. According to the IASP classification for ICD-11, the clinical diagnosis of chronic pain secondary to obliterating arterial disease and diabetes-related foot ulcers could not be assigned to any diagnostic category as a result of the lack of a specific item in the aforementioned classification. Conclusion This study confirmed that chronic pain is a common, burdening issue in hemodialysis patients and that it is of a prevalent nociceptive nature. Our study highlights some limitations of the last IASP ICD-11 classification, especially the lack of specific items for some pain features that are very frequent in hemodialysis patients, and not only in that population. Finally, this study underlines the importance of mutual collaboration between pain physicians and nephrologists for the well-being of patients of high clinical complexity, such as those undergoing chronic hemodialysis.

Abstract Electrodes functionalised with weak electroactive microorganisms offer a viable alternative to conventional chemical sensors for detecting priority pollutants in bioremediation processes. Biofilm-based biosensors have been proposed for this purpose. However, biofilm formation and maturation require 24–48 h, and the microstructure and coverage of the electrode surface cannot be controlled, leading to poorly reproducible signal and sensitivity. Alternatively, semiconductive biocompatible coatings can be used for viable cell immobilization, achieving reproducible coverage and resulting in a stable biosensor response. In this work, we use a polydopamine (PDA)-based coating to immobilize Saccharomyces cerevisiae yeast viable cells on carbon screen printed electrodes (SPE) for Cu(II) detection, with potassium ferricyanide (K3[Fe (CN)6]) as a redox mediator. Under these conditions, the current output correlates with Cu (II) concentration, reaching a limit of detection of 2.2 µM, as calculated from the chronoamperometric response. The bioelectrochemical results are supported by standard viability assays, microscopy, and electrochemical impedance spectroscopy. The PDA coatings can be functionalised with different mutant strains, thus expanding the toolbox for biosensor design in bioremediation.

Abstract The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men. Transcriptomic profiling confirms the upregulation of genes associated with the interferon-gamma and -alpha responses in peripheral blood T cells of infertile men with oligo-astheno-teratozoospermia or non-obstructive azoospermia, with distinct T cell signatures of exhaustion and senescence discriminating the two infertile conditions. These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures and unravel the potential link between infertility and the risk of developing secondary diseases.

Abstract Biofunctionalized magnetite nanoparticles offer unique multifunctional capabilities that can drive nanomedical innovations. Designing synthetic bioorganic coatings and controlling their molecular behavior is crucial for achieving superior performance. However, accurately describing the interactions between bio-inorganic nanosystem components requires reliable computational tools, with empirical force fields at their core. In this work, we integrate first-principles calculations with mainstream force fields to construct and simulate atomistic models of pristine and biofunctionalized magnetite nanoparticles with quantum mechanical accuracy. The practical implications of this approach are demonstrated through a case study of PEG (polyethylene glycol)-coated magnetite nanoparticles in physiological conditions, where we investigate how polymer chain length, in both heterogeneous and homogeneous coatings, impacts key functional properties in advanced nanosystem design. Our findings reveal that coating morphology controls polymer ordering, conformation, and polymer corona hydrogen bonding, highlighting the potential of this computational toolbox to advance next-generation magnetite-based nanosystems with enhanced performance in nanomedicine.

Abstract Background Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated. Methods Electron microscopy, q-RT-PCR, single-cell mass cytometry (CyTOF), flow cytometry, plaque assays, immunohistochemistry, and Western blot analysis were used to assess RV infection of both myeloma and immune cells. Immune fluorescence, flow cytometry, and luciferase reporter assays were used to assess NF-κB pathway activation upon RV treatments. Immune profiling changes, both ex vivo and in MM patients, were analyzed by flow cytometry and CyTOF analysis. T-cell receptor (TCR) sequencing was also conducted both in immune competent MM mice and in patients enrolled in a phase 1b trial per a standard 3 + 3 dose escalation schedule. Results Here we show ex vivo and in vivo that proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on NF-κB activation and that this effect is impaired by the addition of PIs. Conversely, the addition of PIs to RV therapy supports immune activation and killing of MM, independently of direct PI sensitivity. To validate the importance of PIs in enhancing oncolytic viral therapy independently of their killing activity on cancer cells, we then conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated PI-resistant MM patients. Objective responses, which were associated with active reovirus replication in MM cells, T cell activation, and monocytic expansion, were noted in 70% of patients. Conclusions Although characterized as immunosuppressive drugs, PIs improved RV delivery to MM cells but also enhanced anti-MM efficacy through immune-mediated killing of myeloma cells, independently of their PI sensitivity. These results highlight a more generalizable use of PIs as therapeutic companions to support oncolytic-based therapies in cancers. Trial registration clinicaltrials.gov, NCT 02101944.

Sliding mode controllers (SMCs) are commonly used in permanent-magnet synchronous machines (PMSMs) for current control due to their robustness and simplicity. However, high gains used in traditional discontinuous SMC implementations can induce chattering. To address this, disturbance observers are employed to maintain robustness without resorting to high gains. This article introduces a novel continuous asymptotic SMC method for PMSM currents that avoids the need for disturbance observers, resulting in reduced complexity and tuning efforts. The control laws of the two $dq$-axes currents are obtained through the sensitivity of the tracking errors with respect to the controller outputs. The robustness and convergence properties of the proposed control laws are theoretically studied using the Lyapunov approach. Numerical simulations are used to evaluate the performance and robustness of the proposed controller, followed by experiments to compare it to a discontinuous terminal SMC with and without a disturbance observer. The results clearly demonstrate the superiority of the proposed controller that ensures fast convergence, low chattering, and high robustness to parameter variations without requiring the design of additional disturbance observers.

Abstract Aromia bungii is an invasive Cerambycidae of major concern at the global scale because of the damage caused to Rosaceae. Given the major phytosanitary relevance of A. bungii, predicting its spread in invaded areas and identifying possible new suitable regions worldwide remains a key action to develop appropriate management practices and optimise monitoring and early detection campaigns. To improve the predictive power of the modelling framework, a habitat suitability model (HSM), which includes host plants, was combined with a bioclimatic suitability model (BSM), both of which were calibrated on native occurrences. The range of A. bungii was substantially limited by the bioclimate, while habitat conditions acted as limiting factors in the species’ distribution. Host plants were the most important variable that positively influenced habitat suitability. Bioclimatic suitability improved as rainfall in the warmest quarter and average temperatures in the wettest quarter increased and as isothermality decreased. According to the combination of HSM and BSM, Japan is the most suitable area outside the native range of the species. In Europe, despite its high habitat suitability, it is difficult to expect a species to expand its range except through a substantial change in its bioclimatic niche.

Abstract Reservoir computing is a machine learning algorithm for processing time dependent data which is well suited for experimental implementation. Tuning the hyperparameters of the reservoir is a time-consuming task that limits is applicability. Here we present an experimental validation of a recently proposed optimisation technique in which the reservoir receives both the input signal and a delayed version of the input signal. This augments the memory of the reservoir and improves its performance. It also simplifies the time-consuming task of hyperparameter tuning. The experimental system is an optoelectronic setup based on a fiber delay loop and a single nonlinear node. It is tested on several benchmark tasks and reservoir operating conditions. Our results demonstrate the effectiveness of the delayed input method for experimental implementation of reservoir computing systems.

Abstract Objective Autism spectrum disorder (ASD) is characterized by high rates of comorbidity with other mental disorders, including anxiety disorders and obsessive–compulsive disorder. Beyond a mere concept of comorbidity, recent literature is speculating the existence of a neurodevelopmental nature of such mental disorders. The aim of the study is to investigate the distribution of social-phobic, obsessive–compulsive and panic-agoraphobic traits within a sample of individuals with ASD, social anxiety disorder (SAD), obsessive–compulsive disorder (OCD) and panic disorder (PD). Methods 40 participants with ASD, 40 with SAD, 40 with OCD, 40 with PD and 50 HC were assessed with the Social Anxiety Spectrum—Short Version (SHY-SV) questionnaire, the Obsessive—Compulsive Spectrum—Short Version (OBS-SV) questionnaire and the Panic Agoraphobic Spectrum—Short Version (PAS-SV) questionnaire. Statistical analyses included Kruskal–Wallis test and Chi-square test. Results When analyzing SHY-SV scores, the SAD group obtained the highest scores, with individuals with ASD following closely, significantly surpassing the scores of the remaining diagnostic groups. In the examination of OBS-SV questionnaire scores, individuals with ASD once again secured the second-highest scores, trailing only the OCD group. These scores were notably higher than those of both the PD group and healthy controls. In the analysis of PAS-SV scores, the ASD group once again achieved the highest scores after the PD individuals, although this time the difference was not statistically significant compared to the other diagnostic groups. Discussion These findings highlight the central role of the autism spectrum in SAD and OCD diagnoses. They provide support for the hypotheses of a neurodevelopmental basis for social anxiety and OCD, contributing to the growing body of evidence supporting a dimensional and interconnected view of mental health conditions.

Abstract Background Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule. Methods To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients’ sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets. Therefore, to assess the significance of its trafficking, we inhibited monocarboxylate transporter 1 (MCT1) by its selective antagonist, AZD3965, eventually finding a mitigation of lactate-mediated immunosuppressive subsets expansion. To further dig into the impact of lactate in tumor microenvironment, we evaluated the effect of this metabolite on mesenchymal stromal cells (MSCs) reprogramming. Results Our results show an activation of a cancer-associated phenotype (CAF) related to mineralized matrix formation and early fibrosis development. Strikingly, MF serum, enriched in lactate, causes a strong deposition of collagen in healthy stromal cells, which was restrained by AZD3965. To corroborate these outcomes, we therefore generated for the first time a TPOhigh zebrafish model for the establishment of experimental fibrosis. By adopting this model, we were able to unveil a remarkable increase in lactate concentration and monocarboxylate transporter 1 (MCT1) expression in the site of hematopoiesis, associated with a strong downregulation of lactate export channel MCT4. Notably, exploiting MCTs expression in biopsy specimens from patients with myeloproliferative neoplasms, we found a loss of MCT4 expression in PMF, corroborating changes in MCT expression during BM fibrosis establishment. Conclusions In conclusion, our results unveil lactate as a key regulator of immune escape and BM fibrotic transformation in MF patients, suggesting MCT1 blocking as a novel antifibrotic strategy.

Abstract Background The coronavirus disease 2019 (COVID-19) emergency has represented a profound upheaval in the dynamics of infectious diseases transmission worldwide. This phenomenon has been at least in part driven by the introduction of non-pharmaceutical interventions (NPIs), implemented to counteract viral transmission. Our study aimed to assess the magnitude and the features of the impact of the COVID-19 pandemic on the incidence of notifiable infectious diseases (NIDs) in the Lazio region, Italy. Methods Data on NIDs in the Lazio Region with symptom onset date included in the time interval from 1 January 2017 to 31 December 2023 were collected from different surveillance system databases available at SERESMI/Lazio Region Unit and classified into five categories based on the main transmission route of the disease. Descriptive statistics were performed and interrupted time series (ITS) analysis was used to assess the effect of the COVID-19 pandemic and subsequent recovery period on monthly NIDs cases. Results Immediately after the start of the COVID-19 pandemic, a significant, sharp and immediate reduction in monthly cases was recorded for all NIDs (-86.73%), regardless of the transmission route. The decrease was particularly significant for vector-borne, food-borne and respiratory-transmitted diseases (RDs), and in general in females. During the COVID-19 recovery phase, monthly cases of all NIDs showed a significant positive level change, particularly significant for sexually transmitted/blood-borne diseases, contact diseases and RDs. Discussion The COVID-19 pandemic has been responsible for the disruption of all NIDs transmission patterns, while the magnitude and dynamics of its effects varied depending on the transmission route; furthermore, the impact of the pandemic wave was still noticeable during the post-COVID-19 era and the incidence trajectories of NIDs in this phase were peculiar for each disease category.

Sensory ataxia and cerebellar ataxia share common manifestations including dysmetria, intentional tremor and lack of smoothness. We formulated a theoretical framework to describe the patients’ sensory and cerebellar ataxic behavior as consequences of a forward model impairment. To test this framework, the present study aimed to compare upper limb movement kinematics in an index-to-nose task between three groups: healthy controls, people with CNS focal lesions and cerebellar deficits and people with CNS focal lesions and somatosensory impairment. We recruited 12 healthy controls (age $= 29.0\pm 2.9$ years, female = 5) and 20 participants with focal CNS lesions. We divided the sample according to the lesion site in participants with lesions in areas involved in the somatosensory information processing (n = 12, age $= 62.4\pm 13.6$ years, female = 5) and participants with lesions in the cerebellum or cerebellar peduncle (n = 8, age $= 64.3\pm 13.9$ years, female = 1). Movement features concerning movement efficiency (average velocity, peak velocity), accuracy (spatial error when pointing to the nose) and motor planning (timing and spatial occurrence of velocity peak, velocity and deviation from ideal trajectory at 150ms after the movement onset) were computed. Both the groups of participants with CNS lesions performed the movement slower than healthy controls. When comparing results from the two groups of patients, we showed that participants with cerebellar lesions were characterized by greater trial-to-trial variability of the velocity peak (repeated measure ANOVA group effect: F = 5.242, p = 0.012) and its timing (condition*group interaction: F = 5.38, p = 0.011). Our findings suggested that both participants with cerebellar and somatosensory deficits showed signs of anticipatory motor control impairment.

Abstract The Checkerboard conformal field theory is an interesting representative of a large class of non-unitary, logarithmic Fishnet CFTs (FCFT) in arbitrary dimension which have been intensively studied in the last years. Its planar Feynman graphs have the structure of a regular square lattice with checkerboard colouring. Such graphs are integrable since each coloured cell of the lattice is equal to an R-matrix in the principal series representations of the conformal group. We compute perturbatively and numerically the anomalous dimension of the shortest single-trace operator in two reductions of the Checkerboard CFT: the first one corresponds to the Fishnet limit of the twisted ABJM theory in 3D, whereas the spectrum in the second, 2D reduction contains the energy of the BFKL Pomeron. We derive an analytic expression for the Checkerboard analogues of Basso-Dixon 4-point functions, as well as for the class of Diamond-type 4-point graphs with disc topology. The properties of the latter are studied in terms of OPE for operators with open indices. We prove that the spectrum of the theory receives corrections only at even orders in the loop expansion and we conjecture such a modification of Checkerboard CFT where quantum corrections occur only with a given periodicity in the loop order.

Abstract The Economy of action hypothesis postulates that bodily states rescale the perception of the individual’s environment’s spatial layout. The estimation of distances and slopes in navigation space (i.e. the space reachable by locomotion) is influenced by sensations relating to body condition and the metabolic cost of the actions. The results of the studies investigating the impact of pain on distance estimation remain inconclusive. 28 women suffering from chronic pain and fibromyalgia (FM), and 24 healthy women (HC) were assessed for musculoskeletal, neuropathic, and visceral pain by means of the Widespread Pain Index, the Symptom Severity Scale and an ad-hoc devised questionnaire for pain (the Verona Pain Questionnaire). In a VR-mediated task, they observed a 3D scenario and estimated the distance of a flag positioned at different distances (1, 2, 3, 4 or 5 m) on virtual ramps with either a 4% or 24% inclination in two different conditions: sitting and standing. Overestimation of distances in the steeper ramp condition was expected, if participants executed the task by internally simulating the movement. The results showed a dissociation between the effects of musculoskeletal and visceral-neuropathic pain on distance estimations. While, according to the Economy of Action hypothesis, the HCs estimated the distances as being farther away when the ramp was more inclined (i.e. with a 24% inclination), there was no effect related to the different ramp inclinations in the FM group. Furthermore, visceral and neuropathic pain were found to affect the performance of the FM group. These results suggest that chronic and widespread pain conditions, that typically characterize fibromyalgia, can affect space representations. In line with the Economy of Action hypothesis, bodily based estimation of distances is compromised in these patients.

Abstract Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified PDCD1, encoding the immune checkpoint PD-1, and SPP1, encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. TXNIP, encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including SPP1) and depleted (including TXNIP) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease.

Abstract To fully harness mesenchymal-stromal-cells (MSCs)’ benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP. Liver NMP induced specific, liver-tailored, changes in MSCs’ secretome. Rat livers exposed to bioreactor-based perfusion produced more bile, released less damage and pro-inflammatory biomarkers, and showed improved mithocondrial function than those subjected to standard NMP. MSC-bioreactor integration into a clinical device resulted in no machine failure and perfusion-related injury. This proof-of-concept study presents a novel MSC-based liver NMP platform that could reduce the deleterious effects of ischemia/reperfusion before transplantation.

Abstract Background There is still a significant proportion of patients with rheumatoid arthritis (RA) in whom multiple therapeutic lines are ineffective. These cases are defined by the EULAR criteria as Difficult-to-Treat RA (D2T-RA) for which there is limited knowledge of predisposing factors. Objective To identify the clinical features associated with D2T-RA in real-life practice. Methods We retrospectively collected demographic, clinical, and serological data on 458 patients consecutively seen for RA between January 2019 and January 2023. We compared patients fulfilling the D2T-RA criteria with the remaining RA cohort using univariate comparisons and logistic regression to determine the impact of clinical features, comorbidities on outcome variable, adjusted for confounders. Results Seventy-one/458 (16%) patients fulfilled the 2021 EULAR criteria for D2T-RA with no significant differences for age (median 62 years interquartile range -IQR- 58- 65 vs. 62 IQR 60 – 63 in non-D2T), gender prevalence (23% in both groups) and positivity rates for rheumatoid factors (62% vs. 62% in non-D2T) and Anti-Citrullinated Protein Antibodies (ACPA) (69% vs. 61% in non-D2T). Conversely, D2T-RA cases had significant longer disease duration (median 15 years IQR 13–17 vs. 10 years IQR 9–11 in non-D2T; p

The operation of modern free-electron lasers (FELs) necessitates precise knowledge of electron beam properties at the undulator to ensure the level of control required by increasingly demanding experiments. In seeded FELs, where only electrons interacting with the seed laser contribute to the process, it is crucial to determine the local values of these properties. We present a novel method, based on accurate modeling of the FEL process in high-gain harmonic generation, to accurately retrieve the electron beam slice energy spread, current and laser-induced energy modulation. Understanding these values is essential for enabling advanced FEL schemes and optimally setting advanced seeding schemes such as echo-enabled harmonic generation. We describe the method and provide an experimental application to the FERMI FEL-1, where a slice energy spread in the range 40–100 keV with a few keV accuracy is measured.

The comparability of methods applied to environmental DNA (eDNA) samples across laboratories remains a significant challenge for biodiversity monitoring on a global scale. Performance differences between protocols can jeopardize effective conservation strategies across regions and focal species. To address potential discrepancies amongst four international partners within a collaborative eDNA initiative, an inter-laboratory comparison (i.e., ring test) was conducted to compare efficiencies of established DNA extraction methodologies based on 39 eDNA samples. Each laboratory contributed eight to eleven samples collected throughout the North-East Atlantic and the Mediterranean Sea near sperm whales, porbeagle sharks, basking sharks, bottlenose dolphins and common dolphins. After lysis, aliquots were exchanged between laboratories before subsequent DNA extraction using each facility’s preferred method. Extracts were returned to the lysates’ respective laboratories of origin for measurements of total DNA concentration, as well as quantitative PCR using three novel species-specific assays for marine megafauna. Our findings revealed similar concentrations of total DNA, yet a significant reduction in extraction performance for targeted qPCR reactions by one laboratory, who has therefore modified their extraction method to be used for the remainder of this project. Overall, detection success differed based on the target taxa with sharks being less often detected (and at lower concentrations) than marine mammals. Significant interaction effects were found between combinations of laboratories and species, suggesting a link between extraction protocols and variable environmental conditions. Our study serves as a foundational step towards establishing reproducible practices that are crucial for the success of multinational eDNA projects to enable comparable results.

Abstract We assessed the performance of large language models’ summarizing clinical dialogues using computational metrics and human evaluations. The comparison was done between automatically generated and human-produced summaries. We conducted an exploratory evaluation of five language models: one general summarisation model, one fine-tuned for general dialogues, two fine-tuned with anonymized clinical dialogues, and one Large Language Model (ChatGPT). These models were assessed using ROUGE, UniEval metrics, and expert human evaluation was done by clinicians comparing the generated summaries against a clinician generated summary (gold standard). The fine-tuned transformer model scored the highest when evaluated with ROUGE, while ChatGPT scored the lowest overall. However, using UniEval, ChatGPT scored the highest across all the evaluated domains (coherence 0.957, consistency 0.7583, fluency 0.947, and relevance 0.947 and overall score 0.9891). Similar results were obtained when the systems were evaluated by clinicians, with ChatGPT scoring the highest in four domains (coherency 0.573, consistency 0.908, fluency 0.96 and overall clinical use 0.862). Statistical analyses showed differences between ChatGPT and human summaries vs. all other models. These exploratory results indicate that ChatGPT’s performance in summarizing clinical dialogues approached the quality of human summaries. The study also found that the ROUGE metrics may not be reliable for evaluating clinical summary generation, whereas UniEval correlated well with human ratings. Large language models may provide a successful path for automating clinical dialogue summarization. Privacy concerns and the restricted nature of health records remain challenges for its integration. Further evaluations using diverse clinical dialogues and multiple initialization seeds are needed to verify the reliability and generalizability of automatically generated summaries.

Abstract Introduction and objectives High flow nasal cannula (HFNC) therapy is an increasingly popular mode of non-invasive respiratory support for the treatment of patients with acute hypoxemic respiratory failure (AHRF). Previous experimental studies in healthy subjects have established that HFNC generates flow-dependent positive airway pressures, but no data is available on the levels of mean airway pressure (mPaw) or positive end-expiratory pressure (PEEP) generated by HFNC therapy in AHRF patients. We aimed to estimate the airway pressures generated by HFNC at different flow rates in patients with AHRF, whose functional lung volume may be significantly reduced compared to healthy subjects due to alveolar consolidation and/or collapse. Materials and methods We developed a high-fidelity mechanistic computational model of the cardiopulmonary system during HFNC therapy using data from healthy subjects, and then measured the mPaw and PEEP levels produced when different amounts of alveolar consolidation/collapse were incorporated into the model. Results When calibrated to represent normal lung physiology in healthy subjects, our model recapitulates the airway pressures produced by HFNC at different flow rates in healthy volunteers who were breathing normally, with their mouths closed or open. When different amounts of alveolar consolidation/collapse are implemented in the model to reflect the pathophysiology of AHRF, the mPaw and PEEP produced by HFNC at all flow rates increase as the functional lung volume decreases (up to a mPaw of 11.53 and a PEEP of 11.41 cmH2O at 60 L/min with the mouth closed when 50% of the model’s alveolar compartments are non-aerated). When the model was matched to individual patient data from a cohort of 58 patients with AHRF receiving HFNC at 60 L/min, the mean (standard deviation) of the mPaw / PEEP produced by HFNC in the models of these patients was 8.56 (1.50) / 8.92 (1.49) cmH2O with mouths closed, and 1.73 (0.31) / 1.36 (0.36) cmH2O with mouths open. Conclusions Our results suggest that the airway pressures produced by HFNC in patients with AHRF could be higher than is currently assumed based on experimental data from healthy subjects, particularly in patients whose mouths remain closed. Higher levels of PEEP could be beneficial if they lead to alveolar recruitment and improved lung compliance, but could cause alveolar overdistension if they do not, motivating the close monitoring of the effects of HFNC on lung mechanics. Further clinical studies are warranted to directly measure the airway pressures produced by HFNC in patients with different severities of AHRF.

There is growing interest toward the use of artificial intelligence (AI) directly onboard satellites for quick analysis and rapid response to critical events such as natural disasters. This article presents a blueprint to the mission designer for the development of a modular and efficient deep learning payload to address multiple onboard inference tasks. In particular, we design a self-supervised lightweight backbone that provides features to efficient task-specific heads. The latter can be developed independently and with reduced data labeling requirements thanks to the frozen backbone. Experiments on three sample tasks of cloud segmentation, flood detection, and marine debris classification on a 7-W embedded system show competitive results with inference quality close to high-complexity state-of-the-art models and high throughput in excess of 8 Megapixel/s.

This qualitative study examines the risk management, communication, and crisis response competencies of city information officers in San Pablo City, Philippines local government, focusing on how these officers effectively handle emergencies and manage public communication. Through semi-structured interviews with 15 regular staff members and 5 job-order workers, the study provides in-depth insights into their strengths and areas for improvement in crisis management. Thematic analysis of the interview data revealed that, while officers face certain challenges, such as occasional communication delays and limited formal training in risk management, they have demonstrated resilience and adaptability in high-pressure situations. Participants shared successful strategies they have employed, such as leveraging existing networks and utilizing local knowledge to ensure timely information dissemination during emergencies. Additionally, strong teamwork and interdepartmental collaboration were noted as strengths, enabling more efficient crisis response. The study highlights opportunities for further enhancing these competencies through targeted professional development programs in risk management and crisis communication. The findings suggest that, with the right support and training, city information officers can continue to improve their effectiveness in managing public communication during emergencies, ensuring better coordination and quicker responses to crises. This research provides practical recommendations for local government units to capitalize on existing strengths while addressing training gaps to further bolster their crisis management capabilities.

Abstract The diffusion of offshore wind power plants (OWPPs), useful to fulfil renewable diffusion policy targets, implies several technological challenges for integration in power transmission network. The definition of the OWPP connection to the transmission network affects possible exploitation of the assets, involves an evaluation of active power losses and loadability and points out the need for compensation devices, in order to comply with connection rules fixed by the grid operator. This paper proposes a methodology to determine the most suitable electric connection for an OWPP based on high‐voltage alternating current (HVAC) cables, for providing indications for transmission system operators. In particular, different HVAC connection schemes for OWPPs are analysed, focusing on new 66 kV standard voltage and high‐voltage levels, providing technical insight on transmission cable optimal operation conditions. An economic analysis is carried out by proper estimation of construction costs and production forecast, accounting for active power losses and reliability impact. The most suitable connection solution depending on OWPP size and distance in Italian framework is evaluated by means of synthetic techno‐economic indicators, further analysing possible sensitivities of energy price and capacity factor.

New Italian data on the distribution of some of the Annex I Habitats are reported in this contribution. Specifically, 16 records are presented including 9 new occurrences in Natura 2000 sites, and 27 new cells are added in the EEA 10 km × 10 km reference grid. The new data refer to the Italian administrative regions of Abruzzo, Apulia, Latium, Marche, Lombardy, Piedmont, Sardinia, Sicily, Tuscany, and Veneto.

Abstract The transcription factor GLI1 is the main and final effector of the Hedgehog signaling pathway, which is involved in embryonic development, cell proliferation and stemness. Whether activated through canonical or non-canonical mechanisms, GLI1 aberrant activity is associated with Hedgehog-dependent cancers, including medulloblastoma, as well as other tumoral contexts. Notwithstanding a growing body of evidence, which have highlighted the potential role of post translational modifications of GLI1, the complex mechanisms modulating GLI1 stability and activity have not been fully elucidated. Here, we present a novel role played by SMURF1 and SMURF2 in the suppression of the Hedgehog/GLI signaling pathway through a direct targeting of GLI1. Indeed, the two SMURFs can interact with GLI1, exploiting the proline rich regions present on GLI1 protein, and trigger its polyubiquitination and proteasomal degradation, leading to a suppression of the Hedgehog pathway activity and a reduction of Hh-dependent tumor cell proliferation. Overall, this study adds new relevance to a tumor suppressive role of SMURFs on the Hedgehog pathway and confers upon them the status of potential therapeutic tools, either in canonical or non-canonical Hedgehog pathway aberrant activation.

Abstract Parvovirus B19 (B19V) is a significant pathogen responsible for a wide range of clinical manifestations, particularly in children and pregnant women. While B19V is most commonly recognized as the cause of Fifth disease, a mild erythematous illness in children, its clinical impact extends far beyond this condition. B19V can lead to severe complications, including transient aplastic crisis in individuals with chronic hemolytic anemias, arthralgia, and more severe joint diseases. During pregnancy, B19V infection poses serious risks, such as spontaneous abortion, non-immune hydrops fetalis, and fetal anemia, particularly when infection occurs between 9 and 20 weeks of gestation. Moreover, B19V is associated with a variety of organ system involvements, including cardiac, neurological, hepatic, and renal complications. These manifestations can range from mild to life-threatening, necessitating a broad spectrum of therapeutic approaches, including symptomatic care, immunoglobulins, corticosteroids, and supportive therapies. Despite the significant clinical burden posed by B19V, no specific antiviral treatment or vaccine is currently available, making early recognition and prompt management crucial for improving patient outcomes. This review provides a comprehensive overview of the diverse clinical presentations of B19V infection, with a focus on pediatric and pregnancy-related complications. It underscores the need for ongoing research into targeted therapies and highlights the importance of vigilant clinical management to mitigate the severe consequences of this pervasive virus.

Abstract This study aimed to identify the clinico-pathological variables predictive of radiologic complete response (rCR) to first-line anti-HER2 therapy in patients with HER2-positive metastatic breast cancer. Patients were selected from the database of the GIM14 study and classified according to the best radiologic response obtained to first-line anti-HER2 therapy and upon time-to-treatment-discontinuation (TTD). A total of 545 patients were included in the analysis. Eighty patients experienced a rCR to first-line anti-HER2 therapy with a TTD > 3 months and HER2 Immunohistochemistry score 3+, presence of non-visceral metastases and 1 metastatic site were significantly associated with higher odds of obtaining a CR. Of the 80 patients achieving a rCR, 56 experienced a CR with a TTD > 18 months, with anti-HER2 therapy being the only variable significantly associated with a higher probability of achieving such sustained CR.

Abstract Background Severely abused nonpatient women report a high number of gastrointestinal (GI) symptoms and GI syndromes. Little is known about whether the abuse‒symptom relationship varies across different life, social, and community conditions. Objective To comparatively assess the timing, type and severity of physical and/or sexual abuse and GI symptoms of nonpatient women who contacted a lawyer for legal support with those who sought shelter in antiviolence centers. Subjects and methods Forty-six lawyer controls (LCs) (aged 29–80 years) and 67 women (aged 18–58 years) sheltered in antiviolence (V) centers completed an identical anonymous questionnaire with medical and abuse sections. The severity of abuse was assessed with the 0–6 Abuse Severity Measure (ASM). The associations between abuse characteristics and the number of symptoms were assessed with the Poisson regression model. Results Among the LC women, 65% experienced physical and/or sexual abuse in childhood and/or adulthood, whereas 100% of the V women did. In both groups, most women experienced combined sexual and physical abuse in childhood and adulthood. The ASM was 2 reported more GI symptoms than those with an ASM of 5 reported significantly more GI symptoms than control women with ASM

Abstract Background The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) that is involved in the mobilization of endocytosed cholesterol. Loss-of-function mutations in the NPC1 gene lead to the accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2), interactors of the SARS-CoV-2 Spike protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry. Results In this study, we show that inhibition of the cholesterol transporter activity of NPC1 in cells that express both ACE2 and TMPRSS2, considerably reduces SARS-CoV-2 infectivity, evaluated as early as 4 h post-infection. Mechanistically, treatment with NPC1 specific inhibitor U18666A relocalizes ACE2 from the plasma membrane to the autophagosomal/lysosomal compartment, thereby reducing SARS-CoV-2 entry into treated cells. Reduction of viral entry was observed for both fully infectious SARS-CoV-2 virus and with a pseudotyped VSV-Spike-GFP virus. For instance, U18666A-treated Caco-2 cells infected with the pseudotyped VSV-Spike-GFP showed a > threefold and > 40-fold reduction in virus titer when infectivity was measured at 4 h or 24 h post-infection, respectively. A similar effect was observed in CRISP/R-Cas9-edited Caco-2 cells, which were even more resistant to SARS-CoV-2 infection as indicated by a 97% reduction of viral titers. Conclusion Overall, this study provides compelling evidence that the inhibition of NPC1 cholesterol transporter activity generates a cellular environment that hinders SARS-CoV-2 entry. ACE2 depletion from the plasma membrane appears to play a major role as limiting factor for viral entry.

Background: Hearing loss is a highly prevalent condition in the world population that determines emotional, social, and economic costs. In recent years, it has been definitely recognized that the lack of physiological binaural hearing causes alterations in the localization of sounds and reduced speech recognition in noise and reverberation. This study aims to explore the psycho-social profile of adult workers affected by single-sided deafness (SSD), without other major medical conditions and otological symptoms, through comparison to subjects with normal hearing. Methods: This is a cross-sectional, case-control study. Subjects aged between 24 and 65 years, all currently employed and affected by SSD, were enrolled. They were administered both disease-specific and psychometric tests, such as the Hearing Handicap Inventory for Adults (HHIA), the Profile Questionnaire for Rating Communicative Performance, the Psychological General Well-Being Index (PGWBI), and the Social Functioning Questionnaire (SFQ). Results: A total of 149 subjects (mean age = 49.9; SD ± 8.5) were enrolled in the period 2021–2023; 68 were males (45.6%), and 81 were females (54.4%). The normal hearing group was composed of 95 subjects, and the SSD sample was composed of 54 subjects. The results of our study show that the levels of psychological well-being and social functioning in subjects with SSD are statistically worse than in the group of subjects with normal hearing in most subscales. Conclusions: This study definitely outlined evidence for a significantly worse psychological health status and a poorer social attitude of working adults affected by SSD with respect to their normal-hearing counterparts. Understanding the impact of SSD on patients’ work environment suggests a multidisciplinary approach to such patients in order to increase their quality of life through adequate counseling, acceptance, and role modeling.

Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS.

The aim of this work is to identify a suitable methodology capable of integrating multiscale spatial information about an historic center drawn from a Geographic Information System (GIS) and Historical Building Information Modeling (HBIM). The method is based on a multiscale development system that can efficiently handle different types of geospatial information by exploring geomatic techniques and software for semantic and parametric modeling. Our case study of the historic center of Popoli (Italy) shows the quality of the proposed model and HGIS-BIM integration for building geometric models rich in semantic and parametric information, taking into account development at different levels of detail.

Accurate knowledge of the flow rate is essential for hydraulic systems, enabling the calculation of hydraulic power when combined with pressure measurements. These data are crucial for applications such as predictive maintenance. However, most flow rate sensors in fluid power systems operate invasively, disrupting the flow and producing inaccurate results, especially under transient conditions. Utilizing pressure transducers represents a non-invasive soft sensor approach since no physical flow rate sensor is used to determine the flow rate. Usually, this approach relies on the Hagen–Poiseuille (HP) law, which is limited to steady and incompressible flow. This paper introduces a novel soft sensor with an analytical model for transient, compressible pipe flow based on two pressure signals. The model is derived by solving fundamental fluid equations in the Laplace domain and converting them back to the time domain. Using the four-pole theorem, this model contains a relationship between the pressure difference and the flow rate. Several unsteady test cases are investigated and compared to a steady soft sensor based on the HP law, highlighting our soft sensor’s promising capability. It exhibits an overall error of less than 0.15% for the investigated test cases in a distributed-parameter simulation, whereas the HP-based sensor shows errors in the double-digit range.

Urbanisation is a global phenomenon responsible for negative processes in natural ecosystems, such as degradation, loss of habitat and fragmentation. Large urban green areas could, however, represent shelter for animal species, promoting biodiversity conservation. Urban green spaces can also provide useful habitats for threatened species. Wild bees are amongst the most important and efficient pollinating insects and play an indispensable role in ecosystem functioning. Approximately half of the European wild bee species have been reported from Italy, making it a biodiversity hotspot for this group of insects. Many studies have been conducted on pollinating insects in recent years, but few data and incomplete knowledge on wild bee faunas in strictly urban environments exist. Georeferenced faunal data would be important for conservation efforts and understanding the effects that large cities such as Rome may have on the diversity of wild bee communities.This work focused on the diversity of wild bees in nature reserves belonging to the RomaNatura network within the urban area of Rome, Italy. A total of 208 wild bee species belonging to 36 genera and six families were identified. Amongst the species surveyed, one species was classified as Endangered (EN) and seven species were classified as Near Threatened (NT) by the European Red List of wild bees. Twenty-four species are new reports for the urban area of Rome. Sampling took place from April to September 2022. The most represented family in terms of abundance was Halictidae, accounting for 36% of all bees collected, followed by Apidae (24% of samples), Andrenidae (17% of samples), Megachilidae (15% of samples), Colletidae (7% of samples) and Melittidae (1% of samples). The Megachilidae family was the richest in terms of the number of species, accounting for 25% of the total species sampled. This research aimed to provide a set of standardised and georeferenced wild bee occurrences that constitute the baseline for any faunistic, ecological and conservation activity of Rome's nature reserves. In addition, the research aims to demonstrate the importance of large urban green areas in one of the largest European cities as biodiversity reservoirs for wild bees.

Abstract Background In South Kivu (Eastern Democratic Republic of the Congo [DRC]), health districts (HDs) affected by chronic armed conflicts are devising coping mechanisms to continue offering healthcare services to the population. Nonetheless, this alone does not suffice to make them fully resilient to such conflicts. This study aims to explore the characteristics of these HDs’ resilience. Methods This study uses mixed methods (triangulation) and an extreme case study design to compare a HD with no history of armed conflict (Idjwi, Case 1) and another one experiencing armed conflict (Fizi, Case 2) in South Kivu. The Kruk et al. (BMJ 23:357, 2017) index was employed as a theoretical framework for exploring resilience characteristics. Qualitative data were collected through a document review using a pre-set review grid and semi-structured individual interviews with purposively sampled key stakeholders. They were subjected to deductive-inductive thematic analysis. Quantitative data were collected using a Likert scale questionnaire (administered to stakeholders in the selected HDs using non-probabilistic methods – purposive and snowball sampling). These data were subsequently analysed for comparative descriptive purposes. Results Recurring short-term shocks as well as chronic stress factors whether or not linked to chronic armed conflicts were identified. According to most respondents (> 98%), essential components of a resilient HDs were prior knowledge of the strengths and weaknesses as well as the public health risk posed by the crisis (awareness), together with community and non-health actors’ involvement during the crisis (Integration). Common resilience mechanisms (e.g. epidemic management plan, crisis management committee) were identified, and Case 2 implemented additional mechanisms, including DRC armed forces involvement, community healthcare sites and mobile clinics, specific warning system, and regular socio-demographic monitoring of displaced persons alongside promotion of activities for social cohesion strengthening. Conclusions For meaningful resilience to emerge, HDs must be better resourced in “normal” times. If this condition is fulfilled, quality of care could improve and spare capacity could be created to withstand disturbances.

Abstract Objectives The objective of this study is to evaluate the diagnostic performance of perineal access cannulas tethered to a biplanar ultrasound probe in cognitive transperineal prostate biopsies of targets identified by multiparametric magnetic resonance imaging (mpMRI) by comparing the results of the PrecisionPoint (PP) Transperineal Access System with the double‐freehand (DFH) technique. Patients and methods All patients who underwent cognitive transperineal prostate biopsy of mpMRI targets using the PP or DFH technique between November 2020 and September 2023 were enrolled. All data related to mpMRI target biopsies were stratified by technique, visibility in transrectal ultrasound and analysed by comparing PP versus DFH. A standardised anaesthesia protocol with 1% mepivacaine was used in all biopsies. The tolerability of the procedures was assessed using a visual analogue scale (VAS). Results The number of mpMRI targets sampled was 166 in PP and 242 in DFH. In target biopsies, the PP system was associated with better diagnostic performance for clinically significant prostate cancer (Gleason score ≥3 + 4) compared to DFH for both ultrasound‐visible targets (61.4% vs. 48.0%) and non‐visible targets (41.4% vs. 14.9%) (p = 0.02). A higher rate of positive cores was obtained from targets sampled with PP (57.7% vs. 49.6%, p = 0.0002). The PP system was associated with the retrieval of significantly longer cores (p

Abstract The present contribution, starting from theoretical reflections on the role of ecomuseums in the valorisation of territorial resources and the idea of landscape dynamics as connectors that link communities to places also through sensorial experience, presents the case study of the Grotte Vaporose of Sciacca, in South-Western Sicily. Through an approach based on the so-called walking methods, this work aims at returning the perceptual, critical and analytical outcomes of a flânerie in an ecomuseum.

Abstract Sherpa is a general-purpose Monte Carlo event generator for the simulation of particle collisions in high-energy collider experiments. We summarise new developments, essential features, and ongoing improvements within the Sherpa 3 release series. Physics improvements include higher-order electroweak corrections, simulations of photoproduction and hard diffraction at NLO QCD, heavy-flavour matching in NLO multijet merging, spin-polarised cross section calculations, and a new model of colour reconnections. In addition, the modelling of hadronisation, the underlying event and QED effects in both production and decay has been improved, and the overall event generation efficiency has been enhanced.

Abstract Light manipulation at the nanoscale is essential both for fundamental science and modern technology. The quest to shorter lengthscales, however, requires the use of light wavelengths beyond the visible. In particular, in the extreme ultraviolet regime these manipulation capabilities are hampered by the lack of efficient optics, especially for polarization control. Here, we present a method to create periodic, polarization modulations at the nanoscale using a tailored configuration of the FERMI free electron laser and demonstrate its capabilities by comparing the dynamics induced by this polarization transient grating with those driven by a conventional intensity grating on a thin ferrimagnetic alloy. While the intensity grating signal is dominated by the thermoelastic response, the polarization grating excitation minimizes it, uncovering helicity-dependent responses previously undetected. We anticipate nanoscale polarization transient gratings to become useful for the study of physical, chemical and biological systems possessing chiral symmetry.

Abstract The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages. mAbs with the most consistent potential to mediate infection were those targeting a conserved region of the receptor binding domain (RBD; group 1/class 4). Infection was closely related to the neutralising concentration of the mAbs, with peak infection occurring below the IC50, while pre-treating cells with remdesivir or FcγRI-blocking antibodies inhibited infection. Studies performed in primary macrophages demonstrated high-level and productive infection, with infected macrophages appearing multinucleated and syncytial. Infection was not seen in the absence of antibody with the same quantity of virus. Addition of ruxolitinib significantly increased infection, indicating restraint of infection through innate immune mechanisms rather than entry. High-level production of pro-inflammatory cytokines directly correlated with macrophage infection levels. We hypothesise that infection via antibody-FcR interactions could contribute to pathogenesis in primary infection, systemic virus spread or persistent infection.

Near-infrared spectroscopy (NIRS) is essential for monitoring cerebral oxygenation in anaesthesia and critical care, offering non-invasive insights into regional cerebral oxygen saturation (rSO2). However, extracerebral contamination can compromise NIRS accuracy. The O3™ regional oximetry system, with its advanced multi-wavelength technology, may contribute by providing more accurate measurements. In a study involving brain-dead organ donors, near-normal rSO2 values were initially observed despite cerebral anoxia, suggesting extracerebral signal interference. Following aortic clamping and cessation of circulation, rSO2 levels dropped but remained above zero, indicating potential limitations in accurately detecting severe hypoxia. This case study demonstrated the effectiveness of the O3™ system in monitoring rSO2 in such critical situations, uniquely supported by the cerebral haemoglobin index, oxygenated haemoglobin index, and deoxygenated haemoglobin index. The findings emphasise the importance of understanding oxygen transport mechanisms and haemoglobin affinity to accurately interpret NIRS data, especially in brain-dead patients and organ donation procedures.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high disability and mortality. The purpose of the present manuscript is to critically summarize evidence about the effectiveness of yoga for this condition. A bibliographic search was conducted in the main database sources (PubMed, Embase, and Scopus). Articles in English about the effectiveness of yoga in AN were included. Two hundred thirty-three articles were initially identified and 5 articles were included in the present review. With the exception of one study, all had several methodological limitations such as the presence of confounding factors (e.g., psychiatric comorbidity) or a too limited sample of patients. However, globally yoga seems to ameliorate AN symptoms, especially those regarding emotional dysregulation. Yoga is a candidate complementary treatment for the management of AN, but more randomized controlled studies with larger samples and limited bias are necessary to draw robust conclusions. It would be also interesting to verify in comparative trials the effectiveness of yoga with respect to other treatments such as psychotherapy or the administration of pharmacological compounds. Finally, the practice should be modified adapting to the specific needs of this type of patient.

Abstract We use vector meson dominance to calculate non-perturbative contributions to the branching ratio of the rare decay K ± → π ± ν ν ¯ $$ {K}^{\pm}\to {\pi}^{\pm}\nu \overline{\nu} $$ stemming from matrix elements involving up-quark loops. The importance of this observable as well as of K 0 → π 0 l + l − and of the direct CP violation parameter ϵ K ′ $$ {\epsilon}_K^{\prime } $$ is then discussed in the context of a Unitarity Triangle sqtudy based on Kaon sector observables only.