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Background/Objective: Skin fibrosis is the result of aberrant processes leading to abnormal deposition of extracellular matrix (ECM) in the dermis. In healthy skin, keratinocytes participate to maintain skin homeostasis by actively crosstalking with fibroblasts. Within the wide spectrum of fibrotic skin disorders, relatively little attention has been devoted to the role of keratinocytes for their capacity to participate to skin fibrosis. This systematic review aims at summarizing the available knowledge on the reciprocal interplay of keratinocytes with fibroblasts and their soluble mediators in physiological states, mostly wound healing, and conditions associated with skin fibrosis.Methods: We performed a systematic literature search on PubMed to identify in vitro and ex vivo human studies investigating the keratinocyte characteristics and their interplay with fibroblasts in physiological conditions and within fibrotic skin disorders including hypertrophic scars, keloids, and systemic sclerosis. Studies were selected according to pre-specified eligibility criteria. Data on study methods, models, stimuli and outcomes were retrieved and summarized according to pre-specified criteria.Results: Among the 6,271 abstracts retrieved, 73 articles were included, of which 14 were specifically dealing with fibrotic skin pathologies. Fifty-six studies investigated how keratinocyte may affect fibroblast responses in terms of ECM-related genes or protein production, phenotype modification, and cytokine production. Most studies in both physiological conditions and fibrosis demonstrated that keratinocytes stimulate fibroblasts through the production of interleukin 1, inducing keratinocyte growth factor (KGF) and metalloproteinases in the fibroblasts. When the potential of keratinocytes to modulate collagen synthesis by healthy fibroblasts was explored, the results were controversial. Nevertheless, studies investigating keratinocytes from fibrotic skin, including keloids, hypertrophic scar, and scleroderma, suggested their potential involvement in enhancing ECM deposition. Twenty-three papers investigated keratinocyte proliferation differentiation and production of soluble mediators in response to interactions with fibroblasts. Most studies showed that fibroblasts modulate keratinocyte viability, proliferation, and differentiation. The production of KGF by fibroblast was identified as key for these functions.Conclusions: This review condenses evidence for the active interaction between keratinocytes and fibroblasts in maintaining skin homeostasis and the altered homeostatic interplay between keratinocytes and dermal fibroblasts in scleroderma and scleroderma-like disorders.

Abstract Introduction Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. Methods The EYE-LIGHT® device employs two wavelengths, 590 nm (yellow) and 630 nm (red), in both continuous and pulsed modes. Patients over 50 years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4 weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. Results This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). Conclusion These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment’s short-term efficacy. Trial Registration ClinicalTrials.gov identifier NCT06046118.

Abstract Considering the increasing demand for personalized surgical care, as well as current healthcare resources limitations, the use of anatomical accurate 3D physical phantoms is becoming increasingly important for the training of surgeons and the test of surgical instruments. A lack of physical models is nowadays denoted regarding the training in electrosurgery, despite its wide diffusion in medical practice. This work reports an extensive characterization of electrosurgical physical phantoms fabricated with tissue‐mimicking ionogels and hydrogels. A careful design of the conductive gels allow the fine tuning of their mechanical and electrical properties, in order to match those of biological tissues. The manufacturing of a novel multi‐material skin stratification bench‐top pad is reported together with its use for training in both cold and electrical surgery. Furthermore, a feasibility study is reported, showing the use of conductive ionogels for simulating the coagulation of cortical vessels during brain surgery.

Vegetation structural complexity is an important component of forest ecosystems, influencing biodiversity and functioning. Due to the heterogeneous distribution of vegetation elements, structural complexity underpins ecological dynamics, species composition, microclimate, and habitat diversity. Field measurements and Light Detection and Ranging (LiDAR) data, such as airborne (ALS) and terrestrial (TLS), can assess structural characteristics of forest and agroforestry systems at various spatial scales. This assessment is urgently needed for monitoring ecosystem restoration in degraded lands (e.g., in oil palm landscapes), where it is not well-known how structural measures derived from these different approaches relate to each other. Here, we compared the degree of correlation between individual and multivariate datasets of vegetation structural complexity metrics derived from ALS, TLS, and ground-based inventory approaches. The study was conducted in a 140 ha oil palm monoculture, enriched with 52 plots in the form of tree islands representing agroforestry systems of varying sizes and planted diversity levels in Sumatra, Indonesia. Our datasets comprised 25 ALS, five TLS, and nine ground-based inventory metrics. We studied correlations among metrics related to traditional stand summary, heterogeneity, and vertical and horizontal stand structure. We used principal component analysis for data dimensionality reduction, correlation analysis to quantify the strength of relationships between metrics, and Procrustes analysis to investigate the agreement between datasets. Significant correlations were found between ALS and TLS metrics for canopy density (r = 0.79) and maximum tree height (r = 0.58) and between ALS and ground-based inventory measures of stand heterogeneity and height diversity (r between 0.60 and −0.63). Further, we observed significant agreements between the ordinations of multivariate datasets (r = 0.56 for ALS − TLS; and r = 0.46 for ALS – ground-based inventory). Our findings underline the ability of ALS to capture structural complexity patterns, especially for canopy gap dynamics and vegetation height metrics, as captured by TLS, and for measures of heterogeneity and vertical structure as captured by ground-based inventories. Our study highlights the strength of each approach and underscores the potential of integrating ALS and TLS with ground-based inventories for a comprehensive characterization of vegetation structure in complex agroforestry systems, which can provide guidance for their management and support ecosystem restoration monitoring efforts.

Abstract γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.

Study region: Shallow coastal aquifer located in the southern part of the Venice lagoon (Italy). Study focus: This study aims to improve the understanding of coastal aquifers’ hydrodynamics by implementing systematic time-series analyses of data. A collection of non-intrinsically consistent time series from hydrological (surface water and groundwater) and meteo-mareographic monitoring networks was obtained from different institutions. Each signal was broken down through a frequency decomposition analysis, isolating the main driving forces to focus on phenomena that occur at different time and spatial scales. New hydrological insights for the region: Results highlighted that the aquifer is highly connected with the Venice lagoon, with a clear fluctuation of piezometric heads induced by tidal major constituents, decreasing landward. Besides, the effects exerted by reclamation canals and pumping stations were also determined and found to increase landward. Despite the relatively simple behaviour of piezometric heads, the groundwater salinity is influenced by additional local factors, like probe depth, wells’ screen length, and vertical salinity distribution along the aquifer. These findings suggested how to make use of limited and sparse data to enhance the conceptual model of coastal aquifer hydrodynamics, while highlighting the limitations of existing monitoring networks. This outcome justified the need for an intrinsically-consistent network of dedicated multi-level samplers to avoid intra-borehole mixing and reliably characterize the groundwater salinity distribution.

ABSTRACTComputational models are not just appealing because they can simulate and predict the development of biological phenomena across multiple spatial and temporal scales, but also because they can integrate information from well-established in vitro and in vivo models and test new hypotheses in cancer biomedicine. Agent-based models and simulations are especially interesting candidates among computational modeling procedures in cancer research due to the capability to, for instance, recapitulate the dynamics of neoplasia and tumor – host interactions. Yet, the absence of methods to validate the consistency of the results across scales can hinder adoption by turning fine-tuned models into black boxes. This review compiles relevant literature that explores strategies to leverage high-fidelity simulations of multi-scale, or multi-level, cancer models with a focus on verification approached as simulation calibration. We consolidate our review with an outline of modern approaches for agent-based models’ validation and provide an ambitious outlook toward rigorous and reliable calibration.

Planning an immediate and multidisciplinary rehabilitation is crucial to reduce the significant physical, cognitive, and psychosocial impact resulting from head trauma. This study highlights the importance of ongoing cognitive rehabilitation in conjunction with other rehabilitation therapies, such as motor, occupational, and speech therapy, for a 19-year-old woman who suffered an acquired traumatic brain injury in a high-energy vehicle accident. When the patient was admitted to the hospital, their cognitive functioning (LCF) was 4 (confused-agitated state), their Barthel index was 0, their Glasgow coma scale (GCS) was 7, and their disability rating scale (DRS) was 7. The patient’s cognitive functioning improved to LCF 8 (purposeful-appropriate), numerical rating scale: 0/10, Barthel index: 53, GCS:15, and DRS: 5 at the time of discharge from the neurorehabilitation unit. In conclusion, early cognitive intervention in a multidisciplinary rehabilitation program is essential to maximizing the patient’s potential and improving the rehabilitation’s outcome.

Abstract Background Mechanistic modelling of normal tissue toxicities is unfolding as an alternative to the phenomenological normal tissue complication probability models. The latter, currently used in the clinics, rely exclusively on limited patient data and neglect spatial dose distribution information. Among the various approaches, agent-based models are appealing as they provide the means to include patient-specific parameters and simulate long-term effects in complex systems. However, Monte Carlo tools remain the state-of-the-art for modelling radiation transport and provide measurements of the delivered dose with unmatched precision. Methods In this work, we develop and characterize a coupled 3D agent-based – Monte Carlo model that mechanistically simulates the onset of the radiation-induced lung fibrosis in an alveolar segment. To the best of our knowledge, this is the first such model. Results Our model replicates extracellular matrix patterns, radiation-induced lung fibrosis severity indexes and functional subunits survivals that show qualitative agreement with experimental studies and are consistent with our past results. Moreover, in accordance with experimental results, higher functional subunits survival and lower radiation-induced lung fibrosis severity indexes are achieved when a 5-fractions treatment is simulated. Finally, the model shows increased sensitivity to more uniform protons dose distributions with respect to more heterogeneous ones from photon irradiation. Conclusions This study lays thus the groundwork for further investigating the effects of different radiotherapeutic treatments on the onset of radiation-induced lung fibrosis via mechanistic modelling.

The underwater environment is among Earth’s most challenging domains, where failures incur elevated risks and costs for both technology and human endeavors. As a consequence, forecasting the behavior of mechatronic systems through simulation has become increasingly important. Underwater Robotic Simulators (URSs) allow researchers and engineers to safely develop and assess submarine systems. The selection of an appropriate URS from the list of available tools is not trivial. Moreover, the integration of this software with the Digital Twin (DT) concept presents numerous advantages, particularly the ability to link the simulated environment with actual underwater vehicles. This connection is facilitated by performing validation and simulation tests using Software In the Loop (SIL), Model In the Loop, and Hardware In the Loop (HIL) techniques. This paper extensively reviews URSs in the context of both robots and unmanned vehicles in light of the DT paradigm. The article critically examines distinctions among existing URSs, offering valuable insights to aid researchers in selecting the most fitting tool for their specific applications. Additionally, the review explores the practical applications of the identified simulators, categorizing their usage across different fields to illuminate the preferences within the scientific community and showcase prominent case studies.

Abstract Riboflavin Transporter Deficiency (RTD) is a rare genetic, childhood-onset disease. This pathology has a relevant neurological involvement, being characterized by motor symptoms, ponto-bulbar paralysis and sensorineural deafness. Such clinical presentation is associated with muscle weakness and motor neuron (MN) degeneration, so that RTD is considered part of the MN disease spectrum. Based on previous findings demonstrating energy dysmetabolism and mitochondrial impairment in RTD induced Pluripotent Stem cells (iPSCs) and iPSC-derived MNs, here we address the involvement of intrinsic apoptotic pathways in disease pathogenesis using these patient-specific in vitro models by combined ultrastructural and confocal analyses. We show impaired neuronal survival of RTD iPSCs and MNs. Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) documents severe alterations in patients’ cells, including deranged mitochondrial ultrastructure, and altered plasma membrane and nuclear organization. Occurrence of aberrantly activated apoptosis is confirmed by immunofluorescence and TUNEL assays. Overall, our work provides evidence of a role played by mitochondrial dysfunction in RTD, and identifies neuronal apoptosis as a contributing event in disease pathogenesis, indicating intrinsic apoptosis pathways as possible relevant targets for more effective therapeutical approaches.

Abstract Background The clam Chamelea gallina is an ecologically and economically important marine species in the Northwestern Adriatic Sea, which currently suffers from occasional, and still unexplained, widespread mortality events. In order to provide some glimpses in this direction, this study explores the connections between microbiome variations at the clam-sediment interface and the nutritional status of clams collected at four Italian production sites along the Emilia Romagna coast, with different mortality incidence, higher in the Northern sites and lower in the Southern sites. Results According to our findings, each production site showed a peculiar microbiome arrangement at the clam-sediment interface, with features that clearly differentiate the Northern and Southern sites, with the latter also being associated with a better nutritional status of the animal. Interestingly, the C. gallina digestive gland microbiome from the Southern sites was enriched in some health-promoting microbiome components, capable of supplying the host with essential nutrients and defensive molecules. Furthermore, in experiments conducted under controlled conditions in aquaria, we provided preliminary evidence of the prebiotic action of sediments from the Southern sites, allowing to boost the acquisition of previously identified health-promoting components of the digestive gland microbiome by clams from the Northern sites. Conclusions Taken together, our findings may help define innovative microbiome-based management strategies for the preservation of the productivity of C. gallina clams in the Adriatic Sea, through the identification and maintenance of a probiotic niche at the animal-sediment interface.

The integration of analytical functions into machine learning-based engine models represents a significant advancement in predictive performance and operational efficiency. This paper focuses on the development of hybrid approaches to model engine combustion and temperature indices and on the synergistic effects of combining traditional analytical methods with modern machine learning techniques (such as artificial neural networks) to enhance the accuracy and robustness of such models. The main innovative contribution of this paper is the integration of analytical functions to improve the extrapolation capabilities of the data-driven models. In this work, it is demonstrated that the integrated models achieve superior predictive accuracy and generalization performance across dynamic engine operating conditions, with respect to purely neural network-based models. Furthermore, the analytical corrective functions force the output of the complete model to follow a physical trend and to assume consistent values also outside the domain of values assumed by the input features during the training procedure of the neural networks. This study highlights the potential of this integrative approach based on the implementation of the effects superposition principle. Such an approach also allows us to solve one of the intrinsic issues of data-driven modeling, without increasing the complexity of the training data’s collection and pre-processing.

The southern Gabès aquifer in southeastern Tunisia faces significant stress due to unsustainable groundwater extraction. This study employs a SEAWAT model to evaluate groundwater losses, salinization mechanisms, and the interaction between the confined aquifer and the Mediterranean Sea. The model, incorporating well pumping rates, regional freshwater inflows from the Matmata Mountain Range, and the Mediterranean Sea boundary, demonstrated high accuracy in simulating hydraulic heads. Findings reveal that regional inflow is only half of the current pumping rate, indicating unsustainable groundwater use. The study also assessed salinity dynamics by modeling the Mediterranean Sea as a constant head and salinity boundary. Results suggest limited exchange between the aquifer and the sea, challenging previous assumptions. While the immediate risks of salinization are low, continued over-extraction could compromise the aquifer’s long-term sustainability. This research highlights the need for stricter local groundwater management, offers insights into regional coastal aquifer interactions, and contributes to global discussions on managing stressed aquifer systems.

Questo articolo presenta una recente esperienza didattica rivolta a studenti delle scuole secondarie di primo e secondo grado italiane tramite la costruzione di una escape room virtuale. Tale esperienza ha coinvolto oltre 50 scuole e 1500 studenti nell’occasione del Pi Day 2023, la Giornata Internazionale della Matematica. L’articolo si concentra sull’idea progettuale dei problemi matematici presentati e sulle modalità di realizzazione di un contesto virtuale che riproduca fedelmente l’esperienza di gioco escape room.

IntroductionCardiovascular diseases are the leading cause of death among women. Prevention programmes underscore the need to address women-specific risk factors. Additionally, mental well-being is a significant aspect to consider when grappling with cardiovascular disease in women, particularly depression, anxiety, distress, and personality traits. This study aimed to create “at-risk” psychological profiles for women without prior cardiovascular disease history and to evaluate the association between anxiety, depression, distress, and Type-D personality traits with increased cardiovascular risk over 10 years.Methods219 women voluntarily participated in the “Monzino Women's Heart Centre” project for primary prevention and early diagnosis of cardiovascular diseases. Psychological profiles were developed utilising cluster analysis.ResultsThe primary finding indicating that belonging to the “at-risk” psychological cluster was associated with a surge in the 10-year cardiovascular risk prediction score, despite the number of comorbid risk factors (Psychological “at-risk” cluster: β = .0674; p = .006; Risk factors: β = .0199; p = .242).ConclusionsThis finding suggests that psychological well-being of women should be assessed from the very beginning of cardiovascular prevention programmes.

Abstract Introduction Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]) and mucosal regions (mucosal LP [MLP]). Several existing patient-reported outcome measures (PROMs) were identified for potential use in LP clinical development programs. This study aimed to assess the content validity and psychometric measurement properties of the Dermatology Life Quality Index (DLQI), Epworth Sleepiness Scale (ESS), Scalpdex and Oral Lichen Planus Symptom Severity Measure (OLPSSM) in an LP population. Methods Patients completed the PROs at various time points as part of an international Phase 2 clinical study in adults with MLP (n = 37), LPP (n = 37) and CLP (n = 37). Test-retest reliability, construct validity and sensitivity to change were assessed. In addition, qualitative cognitive debriefing interviews were conducted with adults with MLP (n = 20), LPP (n = 19) and CLP (n = 19) in the USA and Germany to examine the PROM content validity. Results The DLQI demonstrated adequate reliability and validity, although its ability to detect change was modest and most items were considered not relevant in qualitative interviews. The ESS had good reliability but limited evidence of validity and ability to detect change. Conceptual relevance varied according to the qualitative interview data. The Scalpdex was miscellaneous across domains, but the ‘Symptoms’ domain performed well overall. Overall, Scalpdex concepts were reported as relevant by most LPP patients interviewed. The OLPSSM demonstrated good psychometric properties and strong evidence of content validity. Conclusions The psychometric and qualitative findings support the use of the OLPSSM and Scalpdex within specific LP subtypes but cautioned use of the DLQI. Administration of the ESS is not recommended in LP because of its poor psychometric performance. Given these limitations, further validation of non-specific disease measures is needed and/or the development of additional LP-specific PROMs. Trial Registration NCT04300296.

Abstract Background and objective N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient’s hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis. The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF. Methods We analyzed blood samples of patients with HFrEF at baseline (before sacubitril/valsartan treatment), after 1, 2, and 3 months (respectively, after a month taking the 24/26 – 49/51 – 97/103 mg twice daily, or b.i.d., doses), and 6 months after the maximum-tolerated dose was reached (end study). Results We obtained samples from 72 patients with HFrEF (age 64.0 ± 10.5 years, 83% males). NT-proBNP and sST2 values progressively and significantly reduced to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p < 0.001). Specifically, NT-proBNP reduced from 1144 [593–2586] pg/mL to 743 [358–1524] pg/mL and sST2 from 27.3 [20.5–35.0] ng/mL to 23.1 [15.9–30.7] ng/mL, p for trend < 0.001 in both cases. The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP. No significant changes in renal function and potassium levels were recorded. Conclusion These findings suggest that, in patients with HF, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-fibrotic, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.

Since its first introduction more than 30 years ago, optical coherence tomography (OCT) has revolutionized ophthalmology practice, providing a non-invasive in vivo cross-sectional view of the structures of the eye. Mostly employed in the clinical setting due to its tabletop configuration requiring an upright patient positioning, the recent advent of microscope-integrated systems now allows ophthalmologists to perform real-time intraoperative OCT (iOCT) during vitreoretinal surgical procedures. Numerous studies described various applications of this tool, such as offering surgeons feedback on tissue–instrument interactions in membrane peeling, providing structural images in macular hole repair, and showing residual subretinal fluid or perfluorocarbon in retinal detachment surgery. This narrative review aims at describing the state of the art of iOCT in vitreoretinal procedures, highlighting its modern role and applications in posterior segment surgery, its current limitations, and the future perspectives that may improve the widespread adoption of this technology.

The increase in atmospheric and soil temperatures in recent decades has led to unfavorable conditions for plants in many Mediterranean coastal environments. A typical example can be found along the coast of the Campania region in Italy, within the “Volturno Licola Falciano Natural Reserve”, where a pine forest suffered a dramatic loss of trees in 2021. New pines were planted in 2023 to replace the dead ones, with a larger tree layout and interspersed with Mediterranean bushes to replace the dead pine forest. A direct (in situ) monitoring program was planned to analyze the determinants of the pine salinity stress, coupled with Sentinel-2 L2A data; in particular, multispectral indices NDVI and NDMI were provided by the EU Copernicus service for plant status and water stress level information. Both the vadose zone and shallow groundwater were monitored with continuous logging probes. Vadose zone monitoring indicated that salinity peaked at a 30 cm soil depth, with values up to 1.9 g/L. These harsh conditions, combined with air temperatures reaching peaks of more than 40 °C, created severe difficulties for pine growth. The results of the shallow groundwater monitoring showed that the groundwater salinity was low (0.35–0.4 g/L) near the shoreline since the dune environment allowed rapid rainwater infiltration, preventing seawater intrusion. Meanwhile, salinity increased inland, reaching a peak at the end of the summer, with values up to 2.8 g/L. In November 2023, salts from storm-borne aerosols (“sea spray”) deposited on the soil caused the sea-facing portion of the newly planted pines to dry out. Differently, the pioneer vegetation of the Mediterranean dunes, directly facing the sea, was not affected by the massive deposition of sea spray. The NDMI and NDVI data were useful in distinguishing the old pine trees suffering from increasing stress and final death but were not accurate in detecting the stress conditions of newly planted, still rather short pine trees because their spectral reflectance largely interfered with the adjacent shrub growth. The proposed coupling of direct and remote sensing monitoring was successful and could be applied to detect the main drivers of plant stress in many other Mediterranean coastal environments.

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Remotely operated vehicles (ROVs) provide practical solutions for a wide range of activities in a particularly challenging domain, despite their dependence on support ships and operators. Recent advancements in AI, machine learning, predictive analytics, control theories, and sensor technologies offer opportunities to make ROVs (semi) autonomous in their operations and to remotely test and monitor their dynamics. This study moves towards that goal by formulating a complete navigation, guidance, and control (NGC) system for a six DoF BlueROV2, offering a solution to the current challenges in the field of marine robotics, particularly in the areas of power supply, communication, stability, operational autonomy, localization, and trajectory planning. The vehicle can operate (semi) autonomously, relying on a sensor acoustic USBL localization system, tethered communication with the surface vessel for power, and a line of sight (LOS) guidance system. This strategy transforms the path control problem into a heading control problem, aligning the vehicle’s movement with a dynamically calculated reference point along the desired path. The control system uses PID controllers implemented in the navigator flight controller board. Additionally, an infrastructure has been developed that synchronizes and communicates between the real ROV and its digital twin within the Unity environment. The digital twin acts as a visual representation of the ROV’s movements and considers hydrodynamic behaviors. This approach combines the physical properties of the ROV with the advanced simulation and analysis capabilities of its digital counterpart. All findings were validated at the Point Rouge port located in Marseille and at the port of Ancona. The NGC implemented has proven positive vehicle stability and trajectory tracking in time despite external interferences. Additionally, the digital part has proven to be a reliable infrastructure for a future bidirectional communication system.

Abstract Introduction Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]), and mucosal regions (mucosal LP [MLP]). Qualitative exploration of the patient experience of LP, notably symptoms and impacts on health-related quality of life (HRQoL), is limited. A scarcity of research was also identified relating to emotional wellbeing impacts of CLP patients. Two qualitative studies were conducted with LP patients to address these gaps. Methods Study 1 consisted of exit interviews conducted with a subset of adult patients with MLP (n = 5), CLP (n = 4), and LPP (n = 4) enrolled in an LP clinical study in the United States (US) to explore the patient experience. Study 2 consisted of independent qualitative interviews conducted with adult CLP patients (n = 13) from the US and Germany to further explore impacts on emotional wellbeing. Results Exit interviews found that itch , pain, and skin lesions were most frequently reported as signs/symptoms of LP. Itch and skin lesions were experienced across all LP subtypes, while pain was only reported by CLP and MLP patients. These signs/symptoms impacted HRQoL including emotional wellbeing (frustration, embarrassment), daily activities (oral hygiene, clothing options), social functioning (intimacy, social activities), and physical functioning (chewing/swallowing, opening/moving mouth). Impacts on activities of daily living (ADL) and physical functioning were mostly experienced by MLP patients. Independent qualitative interviews, which further explored impacts of CLP on patients’ emotional wellbeing, identified frustration, worry, sadness, embarrassment, and depression as the most frequently experienced. Conclusion The findings contribute to the literature by providing qualitative insights into signs/symptoms and HRQoL impacts of LP, from the adult patient perspective. The findings also highlight the importance of considering assessment of HRQoL impacts in future clinical LP research, particularly impacts on emotional wellbeing when selecting instruments for assessment of HRQoL in the CLP population. Trial Registration NCT04300296.

Abstract Vegetation canopy height is a relevant proxy for aboveground biomass, carbon stock, and biodiversity. Wall‐to‐wall information of canopy height with high spatial resolution and accuracy is not yet available on large scales. For the globally consistent TanDEM‐X data, simplifications are necessary to estimate canopy height with semi‐empirical models based on polarimetric synthetic aperture radar interferometry (PolInSAR). We trained the semi‐empirical models with sampled GEDI data, because the assumptions behind the application of such simplifications are not always valid for TanDEM‐X. General linear as well as sinc models and empirical parameterizations of these models were applied to estimate the canopy height in tropical landscapes of Sumatra, Indonesia. Airborne laser scanning (ALS) data were consistently used as an independent reference. The general simplified models were compared with the trained empirical versions to assess the potential improvement of the empirical parameterization of the models. The residuals of the different canopy height models were further evaluated in relation to land use and structural information of the vegetation. Our results indicated that the empirical parameters substantially improved the estimation from a root‐mean‐square‐error (RMSE) of 10.3 m (55.8%) to 8.8 m (47.7%), when using the linear model. In contrast, the improvement of the sinc model with empirical parameters was not substantial compared to the general sinc model (7.4 m [40.4%] vs. 6.9 m [37.5%]). A consistent improvement was observed in the linear model, whereas the improvement of the sinc model was dependent on the land‐use type. Structural attributes like the canopy height itself and vegetation cover had a significant effect on the accuracies, with higher and denser vegetation generally resulting in higher residuals. We demonstrate the potential of the combined exploitation of the TanDEM‐X and GEDI missions for a wall‐to‐wall canopy height estimation in a tropical region. This study provides relevant findings for a consistent mapping of vegetation canopy height in tropical landscapes and on large scales with spaceborne laser and SAR data.

Objectives. The aims of this study were to assess the morphologic features of peri-implant defects, as measured on 2D intraoral radiographs, and to investigate the possible correlation between such morphology and other parameters related to the position and characteristics of the implant or the implant-supported prosthesis. Materials and Methods. Implants with peri-implantitis were included in this retrospective study. Data collected were related both to the patients and to the position/characteristics of the implants and the implant-supported prosthesis. Measurements of the morphologic defects were performed by two operators on digitalized intraoral periapical radiographs. Results and Conclusion. In total, 73 implants in 27 patients were included. The measurements of the periapical radiograph suggested that the most common defect conformation was crateriform, with both intraosseous and horizontal components. An inverse correlation was found between the extension of the peri-implant lesion and the time between the radiographic assessment and the implant placement. The total lesion area was strongly correlated to oral hygiene levels. No correlations between lesion extension and smoking, diabetes, history of periodontal were found. In conclusion, the results from this 2D radiographic study showed the prevalence of crateriform peri-implant defects, with a hygiene-correlated extension, perceptible on the mesial and distal aspects; 3D imaging could be used when available for further research and clinical investigation.

How astrophysical systems translate the kinetic energy of bulk motion into the acceleration of particles to very high energies is a pressing question. SS 433 is a microquasar that emits TeV γ -rays indicating the presence of high-energy particles. A region of hard X-ray emission in the eastern lobe of SS 433 was recently identified as an acceleration site. We observed this region with the Imaging X-ray Polarimetry Explorer and measured a polarization degree in the range 38%–77%. The high polarization degree indicates the magnetic field has a well-ordered component if the X-rays are due to synchrotron emission. The polarization angle is in the range −12° to +10° (east of north), which indicates that the magnetic field is parallel to the jet. Magnetic fields parallel to the bulk flow have also been found in supernova remnants and the jets of powerful radio galaxies. This may be caused by interaction of the flow with the ambient medium.

Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a therapeutic option to cure patients affected by hematologic malignancies. The kinetics and the quality of immune-reconstitution (IR) impact the clinical outcome of h-HSCT and limit the onset of life-threatening Human Cytomegalovirus (HCMV) infection/reactivation. Natural Killer (NK) cells are the first lymphocytes that recover after h-HSCT and they can provide rapid innate immune responses against opportunistic pathogens. By performing a longitudinal single-cell analysis of multiparametric flow-cytometry data, we show here that the persistence at high frequencies of CD158b1b2jneg/NKG2Apos/NKG2Cneg/NKp30pos/NKp46pos (KIRneg) NK cells is associated with HCMV infection/reactivation control. These KIRneg NK cells are “unlicensed”, and are not terminal-differentiated lymphocytes appearing early during IR and mainly belonging to CD56bright/CD16neg and CD56bright/CD16pos subsets. KIRneg NK cells are enriched in oxidative and glucose metabolism pathways, produce interferon-γ, and are endowed with potent antiviral activity against HCMV ex vivo. Decreased frequencies of KIRneg NK cells early during IR are associated with clinically relevant HCMV replication. Taken together, our findings indicate that the prolonged persistence of KIRneg NK cells after h-HSCT could serve as a biomarker to better predict HCMV infection/reactivation. This phenomenon also paves the way to optimize anti-viral immune responses by enriching post-transplant donor lymphocyte infusions with KIRneg NK cells.

This article explores how design thinking can be tailored to address projects that focus on assessing the value of technology adoption within an organization and designing an appropriate application. We studied seven innovation projects conducted within a European Design Factory. We identified common patterns that define an adapted design thinking process called "Tech to Organization" to address such technology-driven project effectively. Results show how classic design thinking tools are adapted in such a process (e.g., technology abilities, technology problem-framing, technolgoy proof of value) and how the phases and milestones of the process change

We present the case of two patients with a diagnosis of treatment-resistant major drug depression (TR-MDD) treated with Vagal Nerve Stimulation (VNS) surgery in 2006 and 2007, respectively. Before surgery the symptoms of sadness, frustration, guilty feelings and loss of interest in socialization severely interfere with everyday life and were worsened by epilepsy in one of the two cases. After surgery both patients experienced great improvement in MDD symptoms and in quality of life that persisted in the last 15 and 16 years. We report these cases since the literature lacks of long-term follow-up for VNS treatment in TR-MDD patients.

The placement of a short peripheral intravenous catheter (sPIVC) is the most common invasive clinical procedure for patients requiring fluid infusion and multiple blood draws. Phlebitis and infiltration represent the most common catheter-related complications. Occlusions, dislocations, and infections are less frequent. Insufficient knowledge and skills may increase the risk of these complications. This review aims to evaluate the effectiveness of training programmes to reduce sPIVC failure amongst hospitalised patients. We will search PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Vascular Specialized Register through the Cochrane Register of Studies, and Google Scholar. We defined the search query using the PICO framework (Participants: health professionals; Intervention: training programme; Comparison: No training programme; Outcomes: all-cause catheter failure). We will include experimental studies evaluating an educational programme to reduce early sPIVC failure amongst hospitalised patients. Two reviewers will independently screen studies for inclusion, extract data, and perform the risk of bias assessment using the Cochrane Effective Practice and Organisation of Care Risk of Bias tool for randomised controlled trials. This review will highlight important perspectives for future studies on the effectiveness of educational programmes focused on reducing the rate of sPIVC complications.

Abstract Background Nabiximols (Sativex®) is a cannabinoid approved for multiple sclerosis (MS)-related spasticity. Its mechanism of action is partially understood, and efficacy is variable. Objective To conduct an exploratory analysis of brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with nabiximols. Methods We identified a group of MS patients treated with Sativex® at Verona University Hospital, who underwent RS brain fMRI in the 4 weeks before (T0) and 4–8 weeks after (T1) treatment start. Sativex® response was defined as ≥ 20% spasticity Numerical Rating Scale score reduction at T1 vs. T0. Connectivity changes on fMRI were compared between T0 and T1 in the whole group and according to response status. ROI-to-ROI and seed-to-voxel connectivity were evaluated. Results Twelve MS patients (7 males) were eligible for the study. Seven patients (58.3%) resulted Sativex® responders at T1. On fMRI analysis, Sativex® exposure was associated with global brain connectivity increase (particularly in responders), decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas. Conclusions Nabiximols administration is associated with brain connectivity increase of MS patients with spasticity. Modulation of sensorimotor cortical areas and cerebellum connectivity could play a role in nabiximols effect.