Search Results (162,027)

The urban heat island effect is well recognized and has been quantified using ground observations within and outside urban areas. Earth Observation has further revealed small-scale local spatial differences, especially in urban surface temperatures, that have been shown to be highly correlated with differences in the urban fabric. However, surface temperatures do not directly translate to human-experienced temperatures, and hence high-resolution air temperature data is of high relevance. However, air temperature is not easily measured from space, and seldom do ground measurements allow for small-scale differences to be quantified to a satisfactory degree. In the present study, we assessed the added value of an air temperature product downscaled using machine learning compared to the high-resolution reanalysis model that formed its foundation. The downscaled product was developed using satellite data, local observations from privately owned weather stations, and high-resolution reanalysis. The comparison focused on Denmark’s four largest urban areas and examined the two data product’s ability to describe the urban heat island effect at the city scale as well as intra-city differences in air temperatures. Both data products show similar urban heat island effects at the city scale, while the downscaled product shows greater intra-city variance in air temperature, with patterns that are somewhat correlated with both urban density and urban green spaces. Generally, the downscaling product offers city planners a better data basis for evaluating where to prioritize contingency and mitigation measures within the urban space. Full article

Urban parks are key components of metropolitan green infrastructure, contributing to residents’ well-being. However, perceptions of disorder and safety may substantially shape how these spaces are experienced, particularly during evening hours. This study investigates the structural relationships between perceived disorder, fear of crime, avoidance behaviors, perceived safety, and service satisfaction. The primary objective is to disentangle the pathways linking disorder perceptions to behavioral and perceptual outcomes using a Structural Equation Modeling (SEM) framework. A structured survey was administered to users of a large metropolitan urban park (N = 742). Latent constructs representing Perceived Disorder, Fear of Crime, Avoidance Behaviors, and Service Satisfaction were specified, controlling for Age and Gender. The SEM was estimated using robust methods for ordinal indicators. The measurement model demonstrated good reliability and validity. Results indicate that Perceived Disorder acts as a strong precursor to Fear of Crime. Fear of Crime emerged as a pivotal mediator, significantly increasing Avoidance Behaviors and strongly reducing Perceived Safety at night. Furthermore, significant demographic effects were observed: female users reported significantly higher levels of fear, while age showed a direct positive association with perceived safety. While disorder strongly impacted the emotional and behavioral dimensions (fear and avoidance), its direct link to Service Satisfaction was less prominent compared to safety perceptions. The findings suggest that the impact of disorder on the park experience is largely channeled through psychological mechanisms of fear. Integrated policies addressing social disorder and fear reduction are likely to be more effective than purely physical interventions to enhance safety perceptions and park usage. Full article

In the context of research aimed at identifying the causes of the progressive decline in cellular and tissue functions characteristic of aging, in recent decades, increasing attention has been devoted to the sirtuin family. Sirtuins are named after the Sir2 protein of Saccharomyces cerevisiae, a product of the SIR gene family, known as “silent information regulator 2”. Sirtuins are NAD⁺-dependent protein deacetylases and deacylases characterized by a conserved catalytic domain of approximately 275 amino acids. The removal of acetyl groups from acetyl-lysine residues on proteins is critical in regulating a wide range of biological functions, including gene silencing, genome stability, longevity, metabolism, and cellular physiology. In humans, the sirtuin family comprises seven isoforms (SIRT1–SIRT7), each with specific substrate preferences and primarily, but not exclusively, localized in the nucleus (SIRT1, SIRT6, and SIRT7), cytoplasm (SIRT2), and mitochondria (SIRT3, SIRT4, and SIRT5). Sirtuins may regulate numerous cellular processes associated with survival and longevity, including transcription and DNA repair, inflammation, glucose and lipid metabolism, oxidative stress, mitochondrial function, apoptosis, autophagy, and stress resistance. Sirtuins’ dependence on NAD⁺ allows them to function as cellular energy sensors, linking metabolic demands to selective lysine deacylation in various subcellular organelles. The aim of this review is to provide an update on this family of molecules, describing their molecular structures, physiological functions, roles in aging processes, and potential to be modulated to serve as a strategy for promoting healthy aging. Full article

Objectives: Medullary thyroid carcinoma (MTC) is a rare but biologically aggressive neuroendocrine tumor for which reliable preoperative prognostic biomarkers are still lacking. This study aimed to evaluate the association between preoperative blood immunological markers and disease recurrence in patients with MTC undergoing curative surgery. Methods: We conducted a retrospective cohort study at a single tertiary academic center including 52 consecutive patients who underwent curative surgery for MTC between January 1999 and December 2023. The study size was determined by including all eligible consecutive patients meeting predefined inclusion/exclusion criteria within the study period. Preoperative inflammatory indices (MLR, NLR, PLR, SII, SIRI) were calculated from standardized complete blood count tests performed within 30 days before surgery. Disease-free survival (DFS) was calculated using the Kaplan–Meier method. Cox proportional hazards regression analysis with a backward stepwise selection based on the Akaike Information Criterion was used to identify independent predictors of recurrence, adjusting for potential confounders. Results: The mean age was 55.0 years (range 31–75), and 73% of patients were female. The ROC-derived cut-off for preCT was 181 pg/mL. Locally advanced disease (T3-T4) was observed in 12% of cases, and cervical node metastases in 27%. With a mean follow-up of 75.48 months, the 3- and 5-year DFS rates were 91% and 86%, respectively. On multivariable Cox regression, a high monocyte-to-lymphocyte ratio (MLR ≥0.37), positive surgical margins, and pathological nodal involvement remained independently associated with worse DFS after confounder adjustment (HR 9.73, 10.78, and 17.71, respectively). Conclusions: Elevated MLR, histological node metastases, and positive surgical margins independently predict recurrence in MTC after curative treatment. Preoperative MLR may represent a simple, inexpensive, and reproducible biomarker to improve preoperative risk stratification and personalize surgical and follow-up strategies: patients with MLR ≥0.37 may benefit from more aggressive management and/or closer follow-up. Full article

Pomegranate marc is a major, underutilized juice industry by-product rich in lipophilic polyunsaturated fatty acids—notably conjugated α-linolenic acids (CLnAs)—and hydrophilic polyphenols with potent antioxidant and anti-inflammatory properties. Despite its potential for nutraceutical, cosmetic, and pharmaceutical applications, this matrix remains largely unexploited. This study presents a novel, sequential in-line extraction strategy combining supercritical CO₂ (ScCO₂) and subcritical water (scW) to recover complementary bioactive fractions. Both extraction steps were optimized via Response Surface Methodology (RSM). Box–Behnken optimization of ScCO₂ (43 MPa, 76 °C, 6.4 L min⁻¹, 124 min) yielded 30 g kg⁻¹ dry weight (dw) of oleoresin, achieving a 68% recovery of total oil. Subsequent scW extraction was optimized at 149 °C, with a 40 L kg⁻¹ water-to-solute ratio and 73 min extraction time, yielding 47 g kg⁻¹ dw of total phenolics (58% recovery). Strong agreement between experimental and predicted values confirmed the robustness of the models. Comprehensive profiling revealed a diverse phytocomplex including fatty acids, tocopherols, flavonoids, soluble sugars, and polysaccharides. Antioxidant assays confirmed that both γ-tocopherol and polyphenols significantly contribute to the extracts’ bioactivity. To improve physical handling, the aqueous fractions were converted into solid dispersions via spray drying with maltodextrin. Preliminary in vitro biological assessments on HEK-293 (human embryonic kidney) and MCF-7 (Michigan Cancer Foundation-7) cell lines suggested that the maltodextrin-based formulations may modulate the cytotoxic profile compared to the free extract, with exploratory results showing dosage-dependent variations in cell viability across the two lines. This work suggests a potentially scalable and sustainable biorefinery approach for the integral valorisation of pomegranate marc, offering a basis for a pathway to produce solvent-free bioactives. Full article

Beckwith–Wiedemann syndrome (BWS) is an overgrowth disorder caused by genetic and epigenetic alterations at chromosome 11p15.5. Increasing evidence suggests that imprinting defects may be accompanied by broader epigenomic perturbations affecting repetitive elements such as human endogenous retroviruses (HERVs). We quantified the transcriptional levels of the HERV-H, HERV-K, and HERV-W-pol genes, the HERV-derived env genes, Syncytin-1 (SYN1) and Syncytin-2 (SYN2), and the epigenetic regulators, TRIM28 and SETDB1, in whole blood from children and adolescents with BWS, stratified by molecular subtype (ICR2 loss of methylation, n = 14; UPD(11)pat, n = 10), and compared with age-matched healthy controls using quantitative real-time PCR. The BWS samples showed significantly increased transcription of HERV-H and HERV-K relative to controls, whereas HERV-W was unchanged. The SYN1 transcripts were significantly higher in UPD(11)pat compared with controls, while SYN2 did not differ between groups. TRIM28 and SETDB1 were significantly overexpressed in BWS, irrespective of molecular subtype, and no significant differences were observed between ICR2 and UPD(11)pat for HERV-H, HERV-K, HERV-W, TRIM28, or SETDB1. These findings indicate selective dysregulation of endogenous retroelements and key repressors in BWS, consistent with epigenetic alterations extending beyond canonical imprinted loci. Full article

Background/Objectives: Intravitreal injections (IVIs) are increasingly performed in outpatient settings, raising concerns regarding how to guarantee operating-theatre-level environmental safety. Mobile laminar airflow (LAF) units may create an ultraclean instrument field, but microbiological evidence from real-world IVI clinics is limited. Methods: We performed environmental monitoring during three IVI sessions, each including approximately 20 injections per session, in an outpatient procedure room equipped with a mobile LAF device (Operio Toul Mobile). Airborne microbial contamination was measured with a SAS Super 100 impactor (1 m³ per sample) at two locations, the procedure-room air and the LAF field, across seven predefined time points (T₋₁to T₅). Surface contamination of the instrument-covering drape was assessed at mid- and end-session using 24 cm² contact plates on four culture media. Colonies were expressed as CFU/m³ or CFU/24 cm² and analysed using a two-way repeated-measures ANOVA (location × time), with Holm-adjusted within-session paired post hoc comparisons at each time point. Results: During LAF operation (T₀–T₄), mean airborne load was 89.8 ± 10.8 CFU/m³ in room air versus 10.9 ± 4.6 CFU/m³ under LAF, corresponding to an 87.9% mean reduction (Holm-adjusted p < 0.01). At T₋₁ and T₅ (LAF off), counts were not significantly different between locations. Airborne microbial species consisted mainly of skin/oral commensals; no obligate pathogens were detected. All 24 drape samples showed 0 CFU. Conclusions: In this high-throughput outpatient IVI clinic, the mobile LAF device maintained a stable ultraclean microenvironment at the instrument field despite moderate background room contamination, supporting its use as an adjunct to standard aseptic measures, without the need to change the covering drape during the session. Full article

Background and Aim: The correct identification of patients presenting with chest pain and the stratification of their risk for major adverse cardiovascular events (MACE) is essential. The aim of this study was to evaluate subjects who came to the ED for chest pain through the chest pain score, the HEART score and the TIMI risk score in order to assess their validity and prognostic accuracy and to compare their performance. Methods: Patients included in the study met the following criteria: age ≥18 years, reported atraumatic chest pain, and consent to participate in the clinical study. Subsequently, the final scores were calculated based on the information collected and a follow-up was performed to assess the occurrence of adverse cardiovascular events (MACEs) at 30 days. The MACEs considered were a composite endpoint of STEMI or NSTEMI myocardial infarction, positive coronary angiography for critical lesions, percutaneous coronary angioplasty, coronary artery bypass grafting, and death. Results: A total of 102 patients were included in the study sample, divided into 76 patients who did not develop MACEs and 26 patients who experienced MACEs. The AUC values of the ROC curves of the chest pain score, HEART score and TIMI risk score were 0.8312, 0.9757 and 0.9378 respectively. Conclusions: All three scores examined were considered excellent tools to predict the onset of MACEs in patients with chest pain at different points of clinical management, although the HEART score outperformed both the chest pain score and the TIMI risk score in terms of prognostic accuracy. Full article

Carbon-Fiber-Reinforced Polyetheretherketone (CFR-PEEK) instrumentation is increasingly preferred in spinal oncology for its physical properties, minimizing imaging artifacts and facilitating precise postoperative radiotherapy planning and tumor surveillance. However, a significant technical limitation exists: the current unavailability of dedicated CFR-PEEK pedicle screws for the cervical spine. The smallest available implants are designed for thoracic use (minimum diameter 4.5 mm, minimum length 25 mm), posing substantial risks of neurovascular injury when applied to smaller cervical pedicles. We present a technical note/feasibility report illustrated by a single case of robot-assisted placement of thoracic CFR-PEEK screws in the cervical spine for the treatment of a C7 Giant Cell Tumor. Following neoadjuvant therapy with Denosumab, a single-stage, two-step circumferential resection and reconstruction was performed. The anterior step was complicated by an iatrogenic injury to the highly adherent left vertebral artery (VA), which was successfully repaired. Consequently, the posterior step required maximal precision to preserve the sole remaining intact VA on the right side. Given the anatomical mismatch between the 4.5 mm thoracic screws and the narrow cervical pedicles (measuring as narrow as 3.2 mm on the critical right side), robotic navigation (ExcelsiusGPS^®) was utilized to plan and execute safe trajectories. Specifically, on the side of the intact VA, a small, controlled medial cortical violation was planned to avoid lateral vascular compromise. The procedure resulted in rigid, artifact-free stabilization with no immediate neurological sequelae. This single-case experience suggests that robotic guidance may facilitate adaptation of thoracic CFR-PEEK instrumentation to the cervical spine in selected oncologic scenarios; reproducibility, costs, and long-term outcomes remain uncertain. Full article

Ischemia and reperfusion (IR) injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The consequences of IR are more evident in pathological steatotic livers. Spirulina (Arthrospira platensis) is known for its potential to modulate inflammatory responses and enhance antioxidant defenses. The current investigation assessed whether spirulina pretreatment mitigates hepatic IR injury exacerbated by steatosis in rats. Thirty male Wistar rats were divided into five groups: sham, IR, HFD, HFD + IR, and SP1000 (HFD + IR + spirulina 1000 mg/kg/day; oral gavage). Liver injury, oxidative stress, inflammatory signaling, and inflammasome/pyroptosis-related markers were assessed using serum transaminases, hematoxylin–eosin staining, immunofluorescence, and qRT-PCR. High-fat diet-fed rats developed steatosis, which significantly worsened IR-induced liver damage, as shown by the respective steatosis histological score, the elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher expression of inflammatory markers, including Toll-like receptor (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) and inflammasome/pyroptosis-related transcripts, namely NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-18 (IL18), and gasdermin D (GSDMD). Oxidative stress was exacerbated, as reflected by higher levels of malondialdehyde (MDA) and reduced antioxidant defenses (superoxide dismutase (SOD) activity, reduced glutathione (GSH) content, glutathione peroxidase (GPx) expression, and heme oxygenase-1 (HO-1) expression). Furthermore, HFD + IR upregulated sterol regulatory element-binding protein-1c (SREBP-1c) expression and downregulated AMP-activated protein kinase (AMPK) expression. Spirulina supplementation significantly attenuated liver injury and transaminase release, reduced MDA, restored antioxidant parameters, downregulated inflammatory and inflammasome-related gene expression, and shifted both SREBP-1c and AMPK expressions toward control levels. Full article

Background/Objectives Approximately 1 in 10 community-dwelling older adults are affected by or at risk of malnutrition, and this prevalence increases to nearly 1 in 3 among those receiving home care or recently hospitalized, contributing to higher rates of frailty, falls, hospitalization, functional decline, and mortality. Many of these individuals depend on informal or family caregivers for nutritional care, including assistance with grocery shopping meal preparation, feeding, and monitoring dietary intake. Thus, informal caregivers play an increasingly central role in supporting dietary intake and maintaining nutritional status. This narrative review aims at assessing the relationship between informal caregiver involvement and malnutrition in community-dwelling older adults who are dependent for nutritional-related needs, summarizing evidence on caregiver’s role and caregiver-associated determinants of malnutrition, as well as on interventions that incorporate caregivers into nutrition care. We discuss factors associated with malnutrition in later life, with particular emphasis on caregiver knowledge, burden, interventions and outcomes. In addition, caregiver-inclusive models of care and tools, including nutrition education and guidelines/recommendations, medical nutrition therapy, and multidisciplinary care models will be addressed. Methods: A structured review of the literature was conducted (date of last search December 2025), searching multiple databases for pertinent articles. Following identification of eligible articles for inclusion, a narrative synthesis of evidence was completed. Results and Conclusions: Despite the high degree of heterogeneity in methodology, observational studies demonstrate that several caregiver attributes influence the nutritional status of care recipients, including caregiver’s own nutritional status, burden, knowledge and literacy, psychosocial, environmental and economic factors. Intervention studies show that caregiver-focused, -inclusive and -delivered interventions have a positive impact on several outcomes, including improved older care recipient dietary intakes, nutritional status and quality of life without impacting on caregiver burden. Thus, strengthening caregiver support and integrating caregivers into nutrition screening and intervention frameworks may represent a critical opportunity to reduce malnutrition risk and improve health outcomes among older adults. Still, significant gaps remain in caregiver-focused intervention research, particularly in diverse cultural and social contexts. Full article

Understanding how climate and land use interact to shape freshwater quality remains challenging across heterogeneous river basins. This study analysed monthly citizen-science measurements of nitrate (NO₃), phosphate (PO₄), and turbidity, collected between 2016 and 2024, across seven Italian river basins representing contrasting climatic and land-use contexts. A non-parametric analytical framework combining Kruskal–Wallis tests, aligned rank transform analyses, principal component analysis (PCA), and basin-specific Somers’ D statistics was applied to ordinal concentration data. Significant differences among basins revealed persistent spatial structuring of water-quality regimes. PCA identified two largely independent gradients: a dominant nutrient axis defined by NO₃ and PO₄, and a secondary turbidity axis. Urban and industrial land use aligned with higher nutrient categories, while vegetated landscapes were associated with lower concentrations. Climatic effects were basin specific. Precipitation showed opposing relationships with NO₃, suggesting both mobilisation and dilution processes, whereas temperature was positively associated with PO₄ in several basins and negatively related to NO₃. Turbidity displayed variable links with precipitation and temperature, reflecting hydrological and seasonal controls. Overall, results indicate that land use represents the primary structural driver of nutrient variability, while climatic factors modulate basin-specific responses. The integration of citizen science observations with robust non-parametric approaches provides a scalable framework for detecting environmental drivers and supporting the targeted management of Mediterranean river systems. Full article

This study addresses the decarbonisation of the glass industry from an integrated energy system perspective, analysing the role of renewable electricity, furnace electrification, and hydrogen in meeting the high and continuous thermal demands of glass melting. While direct electrification represents the most energy-efficient option, its implementation is challenged by the intermittent nature and limited operating hours of renewable generation, scale constraints, and technological limitations in replacing fossil-based processes, highlighting a potential complementary role for hydrogen. A general methodological framework is first developed and then applied to a representative oxyfuel glass furnace using mixed-integer linear programming (MILP) optimisation that minimises melting costs while accounting for variable solar and wind generation, battery storage, and hydrogen production and storage. The results show that high levels of furnace electrification combined with wind-dominated renewable supply yield the lowest decarbonisation costs, which can become negative at moderate decarbonisation levels. Under the current solar–wind capacity expansion mix, the integration of battery and hydrogen storage extends achievable emission reductions from around 50% to 80%, with hydrogen acting as a complementary solution to electrification. Sensitivity analysis of energy and carbon prices, as well as technology investment costs, identifies the economic conditions in which storage-based solutions become cost-effective, highlighting the strategic role of hydrogen under conditions of low electricity prices and high fuel prices. The findings demonstrate viable pathways for deep decarbonisation of the glass sector and provide a transferable methodological framework for optimal renewable energy integration in other hard-to-abate industrial sectors facing similar constraints. Full article

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically diagnosed in the neonatal period, milder forms may present later in infancy or childhood, often triggered by respiratory infections. Case presentation: We report the case of 16-month-old male diagnosed with CCHS following an episode of hypoxemic–hypercapnic respiratory failure during respiratory syncytial virus (RSV) infection. His medical history included neonatal respiratory distress requiring oxygen therapy and recurrent wheezing. At 15 months, he developed acute respiratory distress with severe hypercapnia (PaCO₂ 70 mmHg), requiring admission to the Pediatric Intensive Care Unit and invasive mechanical ventilation. Persistent sleep-related hypercapnia and hypoxemia prompted evaluation for central hypoventilation, confirmed by means of transcutaneous capnography and nocturnal pulse oximetry. Genetic testing revealed a de novo nonsense mutation in exon 1 of PHOX2B (p.Tyr14Ter). Brain magnetic resonance imaging showed diffuse white matter changes suggestive of gliosis. Further investigations identified early-onset systemic hypertension, requiring antihypertensive therapy. The patient was discharged on nocturnal non-invasive ventilation and enrolled in a neurodevelopmental rehabilitation program. Conclusions: This case highlights the phenotypic variability of CCHS and the importance of considering this diagnosis in children presenting with unexplained hypercapnia and sleep-related hypoxemia. It underscores the need for comprehensive autonomic evaluation, including blood pressure monitoring. The p.Tyr14Ter variant may allow partial protein function, potentially accounting for the relatively mild phenotype. Full article

Background: Staphylococcal bloodstream infections (BSIs) and infective endocarditis (IE) are associated with high morbidity and mortality. Among the different antimicrobial combination strategies proposed to enhance antibacterial activity, the association of daptomycin and ceftobiprole may be valuable. The aim of this study was to assess the PK/PD target attainment, safety, and clinical outcomes of such combination therapy for BSI and IE treatment. Methods: This retrospective monocentric study included adult patients with targeted treatment of staphylococcal BSI or IE with daptomycin plus continuous infusion (CI) ceftobiprole. Therapeutic drug monitoring (TDM) was performed for both agents, including Bayesian estimation of daptomycin 24 h area under the concentration–time curve (AUC_24h). PK/PD targets were defined as daptomycin AUC_24h/MIC ≥666 and ≥1081, and ceftobiprole steady-state concentration/MIC ≥4. Dose adjustments, safety, microbiological response, and clinical outcomes were assessed. Results: Twenty-three patients (11 BSI and 12 IE) were included. Methicillin-resistant Staphylococci were identified in 91.3% of cases. At first TDM assessment, daptomycin PK/PD targets were achieved in all patients, while ceftobiprole targets were achieved in 91.6% of BSI cases and in all IE cases. PK-/PD-guided dose de-escalation was frequently feasible. Clinical cure was observed in 77.8% of evaluable patients with BSI and in 91.7% with IE. Creatine phosphokinase elevations occurred in two patients, while hyper-eosinophilia was observed in 69.6% and was manageable with monitoring. Conclusions: Targeted therapy with daptomycin plus CI ceftobiprole achieved high PK/PD target attainment and favorable clinical outcomes in staphylococcal BSI and IE. TDM and model-informed precision dosing may enable dose optimization and may improve the balance between efficacy and safety. Multicenter studies are warranted. Full article