Search Results (5,701)

Antimicrobial resistance (AMR) in Gram-negative pathogens represents a critical global health challenge. Combining cefepime with novel β-lactamase inhibitors (enmetazobactam, taniborbactam, zidebactam, and nacubactam) revitalizes the role of this fourth-generation cephalosporin in contemporary therapy. We present a narrative review according to the Scale for the Assessment of Narrative Review Articles (SANRA) criteria, summarizing the existing literature regarding new cefepime combinations with β-lactamase inhibitors. Based on 68 identified studies, data were structured by molecule. Each section explores in vitro activity, preclinical in vivo data, PK/PD parameters, clinical evidence, and dosage. Findings demonstrate that these inhibitors successfully restore cefepime’s efficacy against diverse resistance mechanisms, notably ESBLs, AmpC, KPC, OXA-48, and metallo-β-lactamases. “Cefepime 2.0” therapies expand the therapeutic armamentarium against severe multidrug-resistant infections, offering vital carbapenem-sparing strategies. Because they possess distinct microbiological spectra, these agents serve complementary rather than interchangeable roles. Their clinical success demands targeted integration into antimicrobial stewardship programs to optimize efficacy and safely reduce carbapenem dependence. Full article

Background/Objectives: Hypothermic oxygenated perfusion (HOPE) improves graft preservation in whole liver transplantation, yet evidence supporting its use in split grafts for pediatric transplantation remains limited. Mitochondrial injury assessed during HOPE through spectroscopic measurement of flavin mononucleotide (FMN) has been associated with graft function in whole-organ transplantation. Here, we evaluate a human liver assessment pathway integrating mitochondrial viability testing with ex situ liver splitting during HOPE. Methods: Following standard procurement and transport, twelve discarded extended criteria human donor livers were evaluated for split feasibility and underwent HOPE (VitaSmart^®). Donors were between 40 and 72 years with a BMI of 23.4–42.7 kg/m² and 4–22 h of cold storage prior to HOPE. After two hours of portal-venous HOPE treatment, different split procedures were performed. Perfusates and tissues were analyzed for mitochondrial injury and inflammatory responses. Results: Four grafts met previously reported FMN thresholds for transplant suitability in whole-graft HOPE studies (FMN ≤ 0.02 μg/mL at 60 min). Livers with low FMN release demonstrated lower Complex I and II injury, greater ATP recovery, and reduced inflammatory signaling during HOPE. Conclusions: These findings indicate that mitochondrial injury during HOPE can be monitored during ex situ splitting and suggest that FMN-guided metabolic assessment may support graft evaluation within split liver transplantation pathways for pediatric recipients. Full article

Background: Epstein–Barr virus (EBV) has long been linked to systemic lupus erythematosus (SLE), mainly through molecular mimicry, altered B-cell biology, defective antiviral immune surveillance and intermittent viral reactivation. However, the detection of EBV DNA in clinical samples does not necessarily indicate transcriptionally active infection or direct viral modulation of host pathways. Methods: Peripheral blood samples from 39 pediatric patients with SLE and 29 healthy controls were analyzed for host immune and apoptotic gene expression, including NFKB1, IL10, TLR3, BCL2, BAX and CASP3. EBV DNA was assessed in both patients and controls. In EBV DNA-positive SLE samples, the expression of EBV transcripts representative of latent, lytic and immunomodulatory programs, including LMP1, EBNA1, BZLF1, and viral IL-10, was also evaluated. Host gene expression was additionally compared between EBV DNA-positive and EBV DNA-negative patients with SLE. Results: EBV DNA was detected in 8 of 39 patients with SLE (20.5%) and in none of the 29 healthy controls (0%; Fisher’s exact test, p = 0.0171). None of the EBV DNA-positive samples showed detectable expression of LMP1, EBNA1, BZLF1 or viral IL-10. Compared with healthy controls, patients with SLE showed increased CASP3 expression that remained significant after FDR correction, whereas the reduction in IL10 expression was nominally significant only in the unadjusted analysis. NFKB1, TLR3, BCL2, and BAX did not differ significantly. In the exploratory comparison between EBV DNA-positive and EBV DNA-negative patients with SLE, no host gene remained significantly associated with EBV DNA status after false discovery rate correction. Conclusions: EBV DNA was detected more frequently in patients with SLE than in healthy controls, but this finding was not accompanied by detectable expression of the selected EBV transcripts under the analytical conditions used or by a consistent host transcriptional signature associated with EBV DNA positivity. These findings emphasize the importance of distinguishing EBV DNA detection from detectable viral transcript expression in SLE. Full article

Globally, approximately three hundred million individuals undergo non-cardiac surgery each year. Perioperative mortality results from a complex interplay between patient-related factors and procedural variables, including both surgical and anesthetic aspects. Although cardiac surgery has a well-established risk profile for acute cardiovascular events, major non-cardiac surgery also carries significant—yet often underrecognized—cardiovascular risks. Approximately half of postoperative deaths following non-cardiac procedures are attributable to cardiovascular complications. Surgical and anesthetic stress responses may induce myocardial injury through several pathophysiological mechanisms. However, the absence of a universally accepted definition of perioperative myocardial injury complicates both diagnosis and management. Furthermore, these injuries frequently occur without symptoms, making them clinically silent and often undetected. Consequently, unexpected postoperative deaths may occur and may lead to allegations of medical malpractice. We conducted a narrative review of existing literature on perioperative myocardial injury and its implications for forensic investigation and medico-legal assessment. This paper highlights the importance of a comprehensive forensic evaluation of perioperative deaths, integrating clinical documentation, autopsy findings, histopathological evidence and ancillary investigations to support accurate medico-legal assessment, recognizing that no single element is sufficient to establish the cause of death in all cases. Four illustrative case studies are presented to demonstrate the medico-legal challenges associated with these events. A structured forensic investigation is essential for accurately determining the cause of death and for distinguishing preventable medical errors from unavoidable adverse outcomes within the context of complex perioperative care. Full article

This paper presents the metrological characterization of low-cost sensors integrated into a multi-sensor system for Indoor Environmental Quality monitoring, developed within the MIRABLE project. The analysis focuses on two domains: the thermal domain, using Sensirion SHT45 and SEN55 temperature sensors; and the Indoor Air Quality (IAQ) domain, using an Infineon photoacoustic spectroscopy (PAS)-based sensor for carbon dioxide (CO₂). All tests were conducted under controlled laboratory conditions using calibrated reference instruments. In the thermal domain, the influence of sensor integration within the device case was investigated at temperature (T) between 15 °C and 35 °C and relative humidities (RH) between 30 %rh and 60 %rh. The results revealed self-heating effects in the desk unit, causing temperature biases of up to 0.6 °C. In the IAQ domain, the repeatability and the impact of T and RH on CO₂ measurements were evaluated. T was identified as the main influencing factor; whereas, RH had a negligible effect. These results were supported by statistical analysis ANOVA. A correction strategy based on concentration intervals is proposed for operation between 15 °C and 25 °C, with an expanded uncertainty (k = 2) of (3.26–6.42) ppm for the with-case configuration. These results support the reliable use of the MIRABLE system. Full article

(1) Background: Acute diarrhea is a frequent clinical manifestation in dogs, often involving dysbiosis and mucosal barrier impairment. This study evaluated the efficacy of Florentero Complex^® (Candioli S.r.l.), a multi-targeted dietary supplement combining probiotics, prebiotics, and antioxidant components, in supporting the recovery of dogs with acute diarrhea. (2) Methods: In a randomized, controlled trial, 28 client-owned dogs presenting with acute diarrhea for 3–4 days were assigned to either a Treated Group (TRT: standard commercial diet plus supplement) or a Control Group (CTR: standard commercial diet alone) for 7 days. Daily defecation frequency (nDEF), fecal score (FS), and inflammatory markers (fecal cytology and C-reactive protein) were monitored throughout the study. (3) Results: Both groups showed a reduction in nDEF over time, with no significant difference observed between groups. However, a significant intergroup difference in FS was observed, with the supplemented dogs showing a faster and more pronounced improvement in stool consistency than the CTR. Fecal cytology and serum CRP levels also showed a trend toward reduced inflammation in the TRT group. (4) Conclusions: Florentero Complex^® appears to provide nutritional support that improves clinical signs and stool quality beyond standard dietary management alone. Full article

The increasing complexity of construction projects has made traditional planning methods inadequate for managing dynamic variables. In this context, the integration of building information modelling (BIM) and artificial intelligence (AI) has been increasingly investigated as a promising approach to improve estimation accuracy, decision-making, and sustainable project execution. This systematic literature review, conducted according to the PRISMA guidelines, analysed 47 articles on BIM-AI integration for construction cost and time planning, categorising them into three clusters: time-oriented, cost-oriented, and multi-objective planning. The reviewed studies indicate that BIM-AI workflows may improve planning efficiency, estimation accuracy, and resource allocation. A limited subset of studies directly incorporated energy consumption, carbon emissions, or lifecycle performance into the optimisation objectives. By contrast, broader benefits related to material waste, rework, equipment idle time, and safety were mainly inferred from improvements in scheduling and resource management rather than directly quantified across the reviewed studies. Artificial Neural Networks (ANNs) and Genetic Algorithms (GAs) emerged as the most frequently adopted and consistently reported techniques, while Revit was the most adopted BIM platform. Despite its potential, BIM-AI integration still faces challenges related to software interoperability, data quality, interdisciplinary coordination, and the limited integration of explicit sustainability indicators within optimisation models. Future research should focus on developing standardised and adaptable frameworks that jointly address cost, time, resource efficiency, environmental impact, and lifecycle performance across different construction contexts. Full article

Cultural heritage faces accelerating threats from armed conflict and climate-induced disasters, generating emergency scenarios in which the window for documentation may be measured in hours. Traditional high-fidelity workflows such as Terrestrial Laser Scanning and survey-grade Structure-from-Motion campaign can be operationally incompatible with these constraints due to costly hardware and specialist-team requirements. Emergency image acquisition can be undertaken with consumer-grade equipment, while the same photographic dataset can subsequently support both an SfM-MVS mesh for metric and geometric analysis and a 3D Gaussian Splatting (3DGS) representation for view-dependent visual interpretation. This paper evaluates an accessible, entirely graphical workflow for producing these complementary outputs, with particular attention paid to the 3DGS stage and without requiring programming or command-line expertise. We develop a theoretical case drawing on Brandinian restoration theory and the international conservation framework, introducing the concept of informational amnesia, the irreversible loss of a site’s documentary record, as a distinct and undertheorized category of heritage failure. We further argue that the democratization of 3DGS documentation cannot be measured by licensing cost alone: a tool distributed as open-source code but requiring command-line expertise presents an effective accessibility barrier functionally equivalent to a commercial paywall. True accessibility requires installable, graphical software operable by non-specialist practitioners in the field. We present a proof-of-concept application of this accessible pipeline, namely DJI Mini 5 Pro, RealityScan for photogrammetric reconstruction, and Lichtfeld Studio for 3DGS generation, to the Fontana d’Ercole at the Reggia di Venaria Reale (UNESCO World Heritage, Turin, Italy). Visual results show photorealistic, navigable 3DGS surrogates of architecturally complex heritage assets achievable by non-specialist operators within hours of acquisition and establish the empirical foundation for future quantitative evaluation. Full article

Understanding river channel evolution is essential for effective management, as lateral erosion shapes riverbeds, floodplains, and riparian habitats. Despite advancements in remote sensing, translating these technologies into operational tools for institutional monitoring remains a challenge. This study introduces a semi-automated framework designed to bridge this gap by quantifying lateral mobility and bank retreat rates in high-energy, gravel-bed rivers. The methodology utilizes a Random Forest classifier applied to Copernicus Sentinel-2 time series (2016–2024) across five rivers in Piedmont (Italy). By detecting pixel-level class shifts between water, vegetation, and sediment, the procedure provides a proxy for lateral mobility. Validated against 120 km of manual delineations, the model achieved high spatial accuracy for both bank retreat rates and eroded bank lengths measurements (Mean Absolute Deviation of 2.64 m/yr and 4.34%, respectively). Integrating discharge data and the hydraulic infrastructure cadaster of the Sesia River, the proposed framework effectively detects reaches prone to significant geomorphic changes, isolates their underlying drivers, simulates 10-year evolutionary trajectories, and demonstrates strong predictive capabilities regarding future channel–infrastructure interactions. This study marks a shift from sporadic, labor-intensive assessments to a dynamic, systematic monitoring framework. Leveraging free satellite data, it provides competent authorities with an objective, cost-effective tool to prioritize interventions, supporting flood risk reduction and river restoration. Full article

Background/Objectives: Local anesthetics (LAs) are used in a variety of different contexts, from loco-regional anesthesia to analgesia. In cardiothoracic surgery, fascial plane blocks are deserving of attention, including erector spinae plane block (ESPB). In this context, ropivacaine is convenient, due to its peculiar pharmacokinetic/pharmacodynamic properties. Nevertheless, LAs can still cause systemic toxicity (LAST), due to erroneous injection and/or variable systemic adsorption/distribution. This interindividual pharmacokinetic variability can be intensified by the tendency to use a fixed ropivacaine dose in ESPB. The aims of this work were investigating systemic exposure to ropivacaine during ESPB in the context of cardiac and thoracic surgery, comparing it to the literature-reported maximum tolerated concentrations, and identifying potential predictors of exposure. Methods: Patients receiving ultrasound-guided injection of 40 mL of ropivacaine 0.375% solution for ESPB were enrolled. Arterial blood was sampled at 5, 15, 30, 45, 60, 120, and 180 min after the injection, and total and free concentrations of ropivacaine were determined by means of LC-MS/MS analysis of arterial plasma. Results: Concentrations showed wide variability, particularly during the first hour post-dose. Significant differences were observed between patients undergoing cardiac and thoracic surgery, with the latter showing higher concentrations, potentially above the cutoff values predictive of LAST. Pharmacokinetic differences were mainly explained by anthropometric (body weight and BSA) and clinical/hemodynamic (NYHA score) characteristics. Conclusions: This study shows that about 5% of patients could reach arterial plasma concentrations of ropivacaine above the cutoff level for LAST after ESPB with a 150 mg dose. Considering patients’ weight could be beneficial to maintain exposure below the toxicity cutoff. Full article

The construction sector generates over one-third of all waste in Europe, yet the reuse of building components remains marginal compared to recycling, and circular strategies are rarely aligned on the territorial scale at which materials, stakeholders and infrastructure operate. This paper investigates the regulatory, institutional, infrastructural and operational conditions under which reuse to become a systemic practice. A desk-based comparative analysis of six European contexts (Belgium, the Netherlands, Switzerland, Germany, France, Denmark) was conducted on 282 documents, using a framework of seven dimensions grouped into three macro-families drawn from the literature on territorial circular ecosystems. The findings show that these conditions form a dependency chain of five ordered links: legal recognition of the non-waste status; a standardized pre-demolition audit; preparation and storage physical hubs, in parallel with research infrastructures, absorbing technical uncertainty; a guarantee system covering performance, liability and insurability; and a demand-side activation. The guarantee link is a constraint and a key element in demand activation. Regulation is necessary but not sufficient, since binding instruments target recycling or auditing while reuse remains voluntary in all six contexts. The chain yields a typology of ecosystem configurations and a replicable diagnostic instrument, whose transferability is assessed on the Italian case. Full article

Resistance spot welding (RSW) is the primary joining technology for automotive advanced high-strength steels (AHSSs), where the inherent severe thermal cycles profoundly alter the heat-affected zone (HAZ) microstructure, leading to localized variations in mechanical properties. Characterizing the spatial gradients in microstructure and the resulting mechanical properties remains a major challenge in weld failure analysis due to the small size of the HAZ and its complex thermal history. In this study, the HAZ of two prominent AHSS grades, a first-generation press hardening steel (PHS1500) and a third-generation quenching and partitioning steel (Q&P1180), was physically simulated using a Gleeble^® 3180 thermomechanical simulator to achieve precise control over the localized thermal cycles. The investigation first evaluated the role of thermal cycle duration, governed by the welding time parameter (300 ms vs. 800 ms), on the microstructural evolution of the PHS1500 steel. Increasing the weld time from 300 ms to 800 ms reduced the cooling rate under the nominal 1400 °C condition from approximately 3000 K/s to 2500 K/s; however, no marked change was observed in the overall microstructural and hardness trends within the investigated range. Subsequently, using the 300 ms thermal profile as a reference baseline, a comparative metallurgical study was conducted between PHS1500 and Q&P1180. Under the same 300 ms thermal history, the maximum hardness reduction relative to the corresponding base material was approximately 42% for PHS1500 and 12% for Q&P1180. The hardness minima were located within FE-estimated temperature ranges close to the Ac₁ region for PHS1500 and around 600 °C for Q&P1180, respectively. This comparison highlighted the distinct microstructural responses of the two generations across the upper-critical (UCHAZ), inter-critical (ICHAZ), and sub-critical (SCHAZ) zones. Moreover, microhardness profiles were correlated with the microstructural findings, establishing a correlation among the simulated thermal history, the observed microstructural evolution, and localized mechanical performance. Full article

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with limited therapeutic options and poor prognosis. The increasing complexity of molecular stratification and treatment selection has stimulated interest in computational and biological modeling approaches for precision oncology. Objective. This narrative review aims to provide a comprehensive overview of digital twins (DTs), DT-enabling computational models, and biological twins (BTs) in CCA, discussing their applications, limitations, and potential integration within hybrid precision medicine frameworks. Methods: A narrative literature review was conducted. To inform the twin-focused sections, a structured PubMed search was performed using predefined keywords related to CCA and twin-related technologies, including organoids, xenografts, organ-on-chip systems. Particular attention was devoted to recent studies addressing computational modeling, patient-derived experimental systems, and translational applications. Results: DT development in CCA is supported by an ecosystem of DT-enabling technologies, including radiomics, artificial intelligence, multi-omics integration, and simulation-based models. However, fully realized medical DTs remain unavailable. BTs, including patient-derived organoids, xenografts, and microfluidic platforms, enable functional validation of therapeutic hypotheses but face challenges related to scalability, standardization, and clinical feasibility. Emerging hybrid DT-BT frameworks seek to combine computational prediction with biological validation through iterative feedback loops, potentially improving patient stratification and treatment personalization. Conclusions: DTs and BTs represent complementary components of an evolving precision oncology ecosystem in CCA. Although technical, biological, regulatory, and implementation challenges remain, the convergence of computational models, longitudinal molecular monitoring, and patient-derived systems may facilitate clinically actionable hybrid twin frameworks. Successful translation will require both technological innovation and healthcare-system improvements to precision medicine access. Full article

Objectives: Eligibility for Lutetium-177 labeled prostate-specific membrane antigen ([¹⁷⁷Lu]Lu-PSMA) radioligand therapy depends on PSMA PET/CT interpretation and may vary across observers and centres. We aimed to identify imaging and clinical correlates of VISION-like PSMA PET-defined eligibility and to compare exploratory clinical, PET-based, and combined models. Materials and Methods: Seventy-six consecutive patients with de novo metastatic prostate cancer undergoing PSMA PET/CT were retrospectively assessed for [¹⁷⁷Lu]Lu-PSMA eligibility. Candidacy was determined by consensus of two nuclear medicine physicians using VISION-like criteria. Three stepwise logistic regression models used clinical variables, PSMA PET/CT variables, or both, and were internally validated with bootstrap out-of-bag predictions. Results: Forty-three patients (56.6%) met VISION-like criteria for RLT. Internally validated area under the curve (AUC) values were 0.731, 0.817, and 0.829 for the clinical, PSMA PET/CT, and combined models. PET-defined candidacy was associated with higher PSMA-positive lesion count, greater PET-derived tumour burden, and higher mean standardised uptake value (SUVmean). Clinically, CHAARTED low-volume disease and prior docetaxel exposure were linked to lower probability, whereas disease state at imaging was not significant. In the combined multivariable model, SUVmean was independently associated with higher candidacy (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.04–1.42; p = 0.015), whereas prior docetaxel showed the opposite association (OR: 0.10, 95% CI: 0.0129–0.776; p = 0.028). Conclusions: PSMA-positive lesion count and SUVmean were the most reproducible determinants of VISION-like eligibility. Prior docetaxel exposure was associated with lower candidacy in the combined model, although the exposed subgroup was small and the confidence interval wide. Whether systemic therapy modifies PSMA expression, and with it access to subsequent PSMA-targeted lines, requires paired imaging before and after treatment in the same patients. Full article

Rift Valley fever virus (RVFV) is a zoonotic, vector-borne disease affecting livestock and humans. The consumption of raw unpasteurized milk has been epidemiologically linked to RVFV exposure in humans and recognized as a potentially important non-vector route for RVFV transmission. This study aims to investigate the potential of RVFV transmission to humans through the consumption of infected raw milk. For this purpose, we conducted agent-based stochastic simulations to assess the potential for RVFV transmission through ingestion of contaminated raw milk. We created synthetic populations of cows, humans, and mosquitoes representing local farm dynamics in Kisumu, Kenya. A total of 1000 farms were simulated with binomial and Poisson distributions utilized to generate cow and human populations, respectively. Given our prior field data, we varied the probability of consuming raw milk from 1% to 80%. We also varied the probability of infectious raw milk causing RVFV infection at 10% and 40%. Results indicate that when the probability of infectious raw milk causing an infection is set at 10%, the cumulative incidence of RVFV infections in humans through raw milk consumption varies between 0.4 and 13% during the inter-epidemic periods. When the probability of infectious raw milk causing an infection is set at 40%, the percentage of cumulative milk infections ranges from 3.7 to 28%. Findings highlight the great potential for RVFV infection and spread through infectious milk consumption and the need for further evaluation of milk as a potential pathway of RVFV transmission to humans. Raw milk consumption in RVFV endemic settings remains an ongoing public health threat. Full article