Search Results (17,474)

Anaerobic digestion (AD) is widely used for organic waste stabilization and bio-energy recovery, but its performance is often constrained by process instability, slow syntrophic metabolism, and sensitivity to acidification, ammonia, organic overloading, and inhibitory contaminants. Biochar has emerged as a promising strategy to enhance AD, with benefits extending beyond increased methane yield. This review examines how biochar properties, including pore structure, surface functional groups, alkalinity, and electrical conductivity, regulate different AD stages and improve process stability. Biochar provides microbial habitats, buffers pH, adsorbs inhibitors, accelerates volatile fatty acid conversion, and facilitates interspecies electron transfer. The effects of biochar dosage, feedstock type, reactor configuration, and operational conditions on digestion performance and resource recovery are critically evaluated. Broader contributions to organic waste valorization are also discussed. Future research should prioritize tailored biochar design, standardized characterization, long-term validation in continuous reactors, techno-economic analysis, and life-cycle assessment. These efforts are essential for translating laboratory findings into reliable and sustainable applications for organic solid waste treatment and resource recovery. Full article

Background: Appropriate diagnostic testing is essential to quality pediatric allergy care, affecting diagnostic accuracy, treatment decisions, resource use, and patient outcomes. This study aimed to develop evidence-based recommendations for specialist consultations and diagnostic investigations in children with food allergies, eosinophilic gastrointestinal diseases, urticaria, angioedema, and atopic dermatitis. Methods: A multidisciplinary panel convened for the Italian National Institute of Health formulated and prioritized clinical questions using the PICO framework and structured expert consensus. A systematic review of the literature from 2015 to 2026 informed the recommendations, with certainty of evidence assessed using GRADE methodology. Results: In food allergy, sensitization tests alone are insufficient for diagnosis, while oral food challenges remain central to diagnostic confirmation. Endoscopic biopsies are essential for diagnosing eosinophilic gastrointestinal diseases. In chronic urticaria, specialist consultation is recommended, whereas routine allergy testing should be avoided without a suggestive clinical history. In angioedema, distinguishing histaminergic from bradykinin-mediated forms is critical, with targeted laboratory testing for hereditary or acquired conditions. In atopic dermatitis, standardized severity assessment should guide management and consideration of biologic therapies, while patient and family education represent key components of care. Conclusions: These recommendations provide a framework for standardized pediatric allergy diagnostic pathways, aiming to improve quality and equity of care while reducing unnecessary investigations and optimizing healthcare resource use. Full article

Hereditary hemolytic anemias (HHAs) have very similar clinical manifestations, complicating differential diagnosis and determining treatment strategies, such as splenectomy. To differentiate between hereditary spherocytosis (HS), pyruvate kinase deficiency (PKD), and hereditary stomatocytosis (HSt), we proposed measuring erythrocyte filterability using membrane filters with a pore diameter of 3 or 3.5 μm. Our modified method provides improved reproducibility, reducing the scattering in results caused by differences in the filters used. Erythrocytes’ filterability differs significantly between patients with HS, HSt, and PKD (medians and 95% confidence intervals were 0.025 [0.004; 0.100] (n = 86); 0.645 [0.520; 0.730] (n = 10), and 0.760 [0.700; 0.782] (n = 26), respectively). The specificity of the filterability test for the HS diagnosis was 99.1%, comparable with the best available tests, while its sensitivity (85.4%) was slightly lower than that of some alternative methods. Only the filterability test was able to identify a second subgroup of HS patients (14.0%) with higher filterability (close to normal), but the diagnosis of HS in these patients could be confirmed by reduced filterability on a 3-μm filter. This subgroup requires further detailed study. The proposed method for measuring filterability is promising for diagnosing HS. It has high sensitivity and specificity and can be performed quickly without expensive equipment. Full article

Skin aging is characterized by various changes, including epidermal thinning, barrier dysfunction, dermis alteration, and dermal–epidermal junction flattening. These changes lead to wrinkles and loss of skin radiance. This study investigates the potential of a supercritical CO₂ extract derived from Helichrysum italicum distillation co-products (CO₂SC extract) to serve as a botanical anti-aging product, targeting epidermal renewal, barrier reinforcement, dermal–epidermal junction organization, and engagement of retinoid-related gene networks. CO₂SC extract’s effects were examined at 0.005% in aged-human-skin equivalents via histology, immunohistology, and transcriptomics. Furthermore, CO₂SC extract was investigated at 0.1% in human skin explants using label-free proteomics in comparison with retinol (ROL) at 0.1% and 0.3%. The clinical effectiveness and tolerability of 0.1% CO₂SC extract were determined by conducting a randomized, intra-individual comparison with a 0.1% ROL formulation. In aged-human-skin equivalents, CO₂SC extract at 0.005% increased epidermal thickness, enhanced expression of differentiation- and barrier-related genes, and stimulated dermal remodeling by increasing type I and III collagens while promoting type VII collagen at the dermal–epidermal junction. Transcriptomic analysis revealed upregulation of genes involved in ROL metabolism and retinoic-acid-responsive signaling. Proteomic profiling further highlighted treatment-associated molecular signatures in comparison with ROL. Clinically, 0.1% CO₂SC extract significantly improved wrinkles by day 28, with improvements of comparable magnitude to those observed with the 0.1% ROL arm under the tested conditions and good tolerability, with no signs of irritation reported, including in sensitive-skin participants. CO₂SC extract displays anti-aging activity at the molecular, histological, and clinical levels under the tested conditions, modulating gene networks related to ROL metabolism and retinoid signaling while reinforcing barrier integrity and dermal regeneration. Together with its favorable tolerability profile, these findings suggest that this CO₂SC extract triggers retinoid-associated programs while maintaining a molecular profile distinct from that of ROL, supporting further evaluation as a botanical anti-aging ingredient agent. Full article

Background/Objective: Lactobacillus reuteri DSM 17938 is among the most studied probiotic strains for pediatric functional abdominal pain disorders (FAPDs), but prior trials and systematic reviews have reached inconsistent conclusions. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of L. reuteri DSM 17938 in children and adolescents with FAPDs. Methods: This review was registered in PROSPERO (CRD42024618099). PubMed, Cochrane Library, Embase, Web of Science, Scopus, CINAHL, and LILACS were searched from inception to 8 April 2026, for randomized controlled trials (RCTs) enrolling children ≤ 18 years with Rome III/IV-defined FAPDs receiving L. reuteri DSM 17938 versus placebo. Random-effects meta-analyses were performed for pain severity, pain frequency, quality of life, and adverse events; risk of bias was assessed with RoB 2 and certainty of evidence with GRADE. Results: Seven RCTs (513 participants) were included. Pain severity showed no significant difference at end of follow-up (SMD −0.58; 95% CI −1.32 to 0.16; I² = 89.3%) but a significant reduction at end of treatment (SMD −0.49; 95% CI −0.93 to −0.06; p = 0.027; I² = 82.0%), an effect not robust to sensitivity analysis. Pain frequency showed no significant difference at end of follow-up (MD −0.15 episodes/week; 95% CI −1.18 to 0.87) or end of treatment. No trial assessed quality of life. Adverse events were reported narratively only. Certainty of evidence was very low for pain outcomes and low for adverse events. Conclusions: Current evidence does not support a consistent beneficial effect of L. reuteri DSM 17938 on pain severity or frequency in pediatric FAPDs, and safety data remain limited. Certainty of evidence was low to very low across outcomes, underscoring the need for larger, methodologically rigorous trials. Full article

Phosphogypsum (PG) governance is a persistent challenge in industrial solid waste management, particularly in regions where large-scale stockpiling, uneven resource-utilization capacity, and policy implementation pressures coexist. Existing studies have paid considerable attention to regulatory instruments and recycling technologies, but less is known about how governments, waste-generating enterprises, and waste-utilizing enterprises adjust their strategies under bounded rationality. This study develops a tripartite evolutionary game model incorporating prospect theory. The technology–organization–environment (TOE) perspective is used as a parameter-identification lens to capture three external conditions: policy incentive intensity, enterprise governance input, and resource-utilization technology maturity. Based on case-informed parameter calibration from Guizhou and related policy-industrial evidence, numerical simulations are conducted to examine evolutionary paths, equilibrium conditions, and parameter sensitivity. The results show that PG governance may evolve from systemic inaction to policy-driven transformation and then to market-oriented sustainability. Technological maturity plays a threshold role, while excessive loss aversion can destabilize cooperative evolution. The interaction analysis further indicates that policy incentives are effective only when they are aligned with enterprise treatment behavior and viable market-entry conditions. These findings suggest that PG governance should move beyond short-term administrative intervention toward staged policy support, technical standardization, and market cultivation. Full article

Background: Precision diagnostics are more and more important in intensive care units (ICUs), where rapid identification of infectious agents and antimicrobial resistance determinants is crucial for timely and appropriate treatment. Conventional microbiological methods are frequently limited by long turnaround times and reduced sensitivity, which may delay appropriate treatment. Nanopore sequencing allows rapid, direct, and long-read sequencing of DNA/RNA molecules without the need for amplification, avoiding biases introduced by NGS during amplification and library preparation and generating data in real time. Objectives: This narrative review aims to summarize current knowledge of nanopore technology in the ICU, discuss nanopore principles and current clinical applications in intensive care medicine, highlight its advantages and limitations, and explore future perspectives for integrating nanopore-based diagnostics into precision critical care. Methods: A literature search was performed using PubMed and Web of Science. The literature search was conducted with no lower restriction, covering English-language publications. Results: Nanopore sequencing enables real-time, long-read, single-molecule analysis of native nucleic acid molecules, rapid pathogen identification, antimicrobial resistance profiling, metagenomic analysis, and direct sequencing without amplification. Recent studies have proved the clinical utility of nanopore sequencing in critically ill patients with sepsis, bloodstream infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and fungal and viral infections. Its portability, rapid turnaround time, and potential for point-of-care implementation make it particularly attractive for ICU settings. Conclusions: Nanopore sequencing technology represents a promising molecular diagnostic tool, but wider clinical implementation warrants further larger studies with clinical outcome endpoints, standardized bioinformatic pipelines, and clearer validation pathways. Full article

The performance of coatings, corrosion barriers, photocatalysts, and tribological materials is greatly influenced by in situ surface properties, requiring highly sensitive and reproducible operando surface characterization methods. We previously developed a temperature-programmed photoelectron emission (TPPE) method to clarify electron transfer behavior on light-irradiated metal surfaces. TPPE is sensitive to surface temperature and prior chemical exposure, which affect the total photoemitted electron count (N_T), the photothreshold, and the activation energy derived from Arrhenius plots of N_T obtained during heating–cooling cycles. This study examines the reproducibility of TPPE data and the TPPE mechanisms for Cu₂O/Cu surfaces subjected to mechanical abrasion, cleaning, plasma treatment, and subsequent immersion in organic liquids. The resulting Arrhenius plots reveal both positive and negative activation energies, depending on the treatment conditions. Negative activation energies during cooling are associated with photoredox-mediated emission. TPPE is attributed to oxygen vacancies within the Cu₂O surface layer, which is interfaced with metallic Cu, serving as a direct probe of these vacancy-related states. The TPPE characteristics (N_T intensity and activation energy) following exposure to various polar and nonpolar organic molecules (e.g., acetone, toluene, hexane, and ethanol) correlate with the electronic properties of these vacancies, consistent with previous observations for ambient air, alcohol, and water vapor exposure. Under illumination, Cu₂O vacancy states enhance photocarrier extraction (electrons and holes) and accelerate surface redox reactions within adsorbed thin films, thereby improving photocatalytic performance. Notably, the solvent’s reciprocal dielectric constant significantly influences TPPE, indicative of electrostatic surface–solvent interactions. Finally, the TPPE mechanism is discussed in the context of antiviral inactivation at the metallic copper–environment interface. Full article

Immune checkpoint blockade has become an important component of treatment for several gynecologic malignancies, but its clinical value varies substantially by tumor lineage, molecular subtype, disease setting, and treatment backbone. This narrative review summarizes the biological rationale, clinical evidence, predictive biomarkers, combination strategies, toxicity considerations, and future directions of immunotherapy across gynecologic cancers. In cervical cancer, checkpoint blockade has evolved from later-line recurrent disease to first-line systemic therapy and, more recently, to curative-intent chemoradiotherapy combinations. In endometrial cancer, mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) tumors show the clearest sensitivity to programmed cell death protein 1 (PD-1) blockade, whereas mismatch repair-proficient/microsatellite stable (pMMR/MSS) disease generally requires combination strategies. In ovarian cancer, broad unselected checkpoint inhibitor strategies have generally failed; ENGOT-ov65/KEYNOTE-B96 demonstrated statistically significant progression-free survival (PFS) and overall survival (OS) improvement with pembrolizumab plus weekly paclitaxel, with or without bevacizumab, in a defined platinum-resistant population, although the absolute median PFS gain in PD-L1 combined positive score (CPS) ≥1 disease was modest. Gestational trophoblastic neoplasia (GTN) offers a biologically distinctive setting because of trophoblastic immune tolerance, whereas selected rare gynecologic malignancies may be considered for immunotherapy on the basis of HPV association, tumor-agnostic biomarkers, or signals observed in clear-cell cohorts. Accordingly, the clinical value of immunotherapy should be interpreted according to tumor lineage, disease setting, validated biomarkers, treatment backbone, and the incremental contribution of each treatment component. Full article

Background: Type 2 diabetes mellitus (T2DM) is clinically heterogeneous, and routinely available renal, inflammatory, and hepatic measures may add information beyond glycemic assessment. Methods: Among 811 screened adults, 809 had a standardized baseline assessment and six-month follow-up; two were excluded because a required baseline clustering variable was missing, leaving 807 complete cases for phenotype derivation. Twelve-month data were available for 320 participants. Nine baseline variables were standardized, with UACR and CRP analyzed after ln(x + 1) transformation. Candidate two- to six-cluster solutions were assessed using silhouette, Calinski–Harabasz, and Davies–Bouldin indices, 200 bootstrap resamples, and a consistent-transformation sensitivity analysis. Longitudinal outcomes were evaluated using generalized estimating equations including time, phenotype, and their interaction. Results: The final stored four-cluster solution comprised a comparatively favorable-profile phenotype (n = 294), a cardiorenal–fibrotic phenotype (n = 239), an inflammatory–metabolic phenotype (n = 141), and a severe hyperglycemic–obesity phenotype (n = 133). Internal separation was modest (silhouette 0.118; Calinski–Harabasz 87.6; Davies–Bouldin 2.118), bootstrap agreement was moderate (median adjusted Rand index 0.445), and the consistent ln(x + 1) sensitivity solution showed substantial agreement with the stored assignment (adjusted Rand index 0.776). Significant phenotype-by-time interactions were observed for HbA1c, BMI, TyG, triglycerides, UACR, eGFR, FIB-4, and CRP after false-discovery-rate correction, but not for LDL cholesterol. Baseline characteristics did not differ detectably between participants with and without twelve-month follow-up after correction. Marked treatment changes occurred by T2, particularly increased use of GLP-1 receptor agonists and SGLT2 inhibitors. Conclusions: The four phenotypes provide an exploratory multidimensional description of this cohort. Longitudinal differences should not be attributed to phenotype biology alone because regression to the mean and treatment intensification are plausible contributors; external validation remains necessary. Full article

Open-channel hydraulic analysis often requires repeated solution of implicit nonlinear equations and numerical integration of gradually varied flow (GVF), which can become computationally demanding in inverse, optimization, and sensitivity applications. This study develops a hydraulically informed artificial neural network (ANN) surrogate framework comprising ten independently trained models for normal and critical depths, alternative and conjugate depths, GVF-related water-surface behavior, and profile-based discharge inference. Hydraulic information is introduced through physically meaningful, and where appropriate dimensionless, variables and reference solutions derived from established governing equations or numerical hydraulic models, while ANN optimization remains data driven. Equation-generated test sets quantified surrogate fidelity, whereas HEC-RAS comparisons were treated as numerical hydraulic cross-verification rather than independent physical validation. The forward surrogates reproduced their reference mappings with high accuracy within the represented domains. Benchmarking against Random Forest, support vector regression, and Gaussian Process Regression for Models 1, 5, and 7 showed no universal algorithmic superiority; however, ANN provided a favorable trade-off among accuracy, relative-error robustness, compactness, and repeated-inference efficiency. For Model 7, ANN inference was approximately 249 times faster than conventional GVF calculation, with development cost recovered after about 1.03 × 10⁵ evaluations. Model 9 inferred discharge with a 4.75% error in the profile-based test. Observation-based assessment using 16 historical Missouri River stage–discharge events showed that direct HEC-RAS inversion yielded a MAPE of 44.71%, whereas observation-only ANN and hybrid HEC-RAS-ANN discrepancy correction reduced MAPE to 10.25% and 9.83%, respectively. The framework is therefore a computational complement to established hydraulic equations and numerical models, with broader field validation and explicit uncertainty treatment required for general deployment. Full article

Background and Objectives: Although modern oncologic therapies have substantially improved cancer survival and overall prognosis, they have also led to an increasing burden of cardiovascular toxicity. Preventing severe complications such as heart failure and death remains a major priority, while maintaining the need for effective and potentially curative cancer therapy. Careful patient monitoring and early detection of cardiovascular complications may allow the timely implementation of cardioprotective strategies and treatments that could delay or prevent myocardial toxicity. Materials and Methods: A total of 92 women with breast cancer were enrolled in a prospective observational cohort study. All patients received an anthracycline-based chemotherapy regimen, cyclophosphamide, docetaxel and trastuzumab. Biomarker assessment, including NT-proBNP, high-sensitivity cardiac troponin I (hs-cTnI), Gal-3, and GDF-15, was performed at baseline and at the initiation of trastuzumab-based therapy. A comprehensive diastolic function assessment was performed, including transmitral Doppler flow parameters and tissue velocities. Patients were followed for 12 months, and all cardiovascular events occurring during the follow-up period were recorded. Results: Biological and ecocardiographic parameters were analyzed and multiple models of prediction were made. To identify predictors of estimated left ventricular filling pressure (eLVFP), stepwise multiple linear regression analyses were performed, and four significant predictors of left ventricular end-diastolic filling pressure were identified: one echocardiographic parameter (baseline LV filling pressure) and three biological variables (changes in Gal-3, GDF-15, and hs-cTnI levels after treatment). The overall regression model was highly significant (p < 0.001) and explained 77.07% of the variance in the dependent variable. Gal-3 was the strongest predictor of left ventricular filling pressure (p < 0.001). Conclusions: The regression analyses suggest that this phenotype is multifactorial, with echocardiographic indices capturing the functional component and circulating biomarkers reflecting complementary aspects of the underlying biological response. This multimodal approach may therefore help identify patients with early treatment-related cardiac changes and potentially those at increased risk of subsequent CTRCD, particularly during a period when conventional LVEF-based surveillance may still appear reassuring. Full article

As a noninvasive liquid biopsy approach, extracellular vesicle (EV)-based detection offers significant advantages in reflecting real-time tumor dynamis and overcoming the limitations of conventional tissue biopsy. EVs, nanoscale vesicles secreted by cells, carry diverse biomolecules such as proteins and nucleic acids, playing key roles in tumor progression, metastasis, and immune evasion, and have emerged as promising biomarkers for cancer liquid biopsy. Surface-enhanced Raman spectroscopy (SERS), characterized by high sensitivity, resistance to photobleaching, minimal sample consumption, and multiplexing capability, has shown great potential in EV analysis. This review systematically summarizes current methods for EV isolation, characterization, and storage, with a focus on label-free and label-based SERS detection strategies for early cancer diagnosis, treatment response monitoring, and prognosis evaluation. Furthermore, the integration of SERS with machine learning and deep learning algorithms has substantially improved diagnostic accuracy and cancer subtyping. Despite remaining challenges, such as optimization of SERS substrate performance, intelligent processing of Raman spectral fingerprints, and clinical translation, EV-based SERS technology holds great promise for precision oncology. Full article

Background/Objectives: Oral structural and functional impairment and depressive outcomes frequently coexist in older adults, but the strength and interpretation of their association remain uncertain. This systematic review and meta-analysis evaluated whether poorer oral status or function is associated with depressive outcomes in older populations. Methods: Six databases were searched for observational studies published from 1 January 2016 to 5 January 2026, with an update on 19 April 2026. Eligible studies examined oral impairment as the exposure and depressive outcomes as the endpoint in older adults. Risk of bias was assessed using Newcastle–Ottawa criteria and certainty using GRADE. Comparable adjusted odds ratios (ORs) were pooled using random-effects meta-analysis with restricted maximum likelihood and Hartung–Knapp adjustment; non-comparable metrics were synthesized separately. Results: Thirty studies were included; fifteen contributed to the primary OR meta-analysis. In the primary model, poorer oral status or function was associated with higher odds of adverse depressive outcomes (OR = 1.61, 95% CI: 1.31–1.99), although between-study heterogeneity was substantial (I² = 88.1%). In the trim-and-fill sensitivity analysis, the pooled estimate decreased to OR = 1.29 (95% CI: 0.99–1.69; p = 0.0584) and no longer reached conventional statistical significance. The certainty of the primary evidence was very low. Conclusions: Poorer oral structural or functional status is associated with worse depressive outcomes in older adults, but the magnitude is heterogeneous and sensitive to small-study-effect assumptions. The evidence remains observational and of very low certainty and should be interpreted as hypothesis-generating rather than causal or treatment evidence. Full article

The benefits of lenalidomide, which leverages TP53-dependent apoptosis and promotion of megakaryocytic differentiation, in lower-risk MDS (LR-MDS) with del(5q) are well-established and drive its frequent use in clinical practice. In parallel, advances in molecular testing have elucidated the clear impact of TP53 mutations on response to therapies and prognosis, with diversity in the latter informed by variant allele frequency (VAF) and/or predicted allelic state. In this review, we discuss the converging pre-clinical and clinical evidence that implicates TP53 mutations not only as a driver of lenalidomide resistance in del(5q) LR-MDS, but as a source of selective clonal advantage under lenalidomide exposure. Lenalidomide-induced CK1α degradation triggers TP53-mediated apoptosis in wild-type clones, inadvertently favoring the survival and expansion of TP53-mutated cells. Clinically, this dynamic has been demonstrated across multiple studies, with rising TP53 variant allele frequency and clonal evolution observed following treatment. These findings underscore the importance of baseline molecular assessment in patients with MDS and, in select cases, serial monitoring during therapy. Investigational approaches for del(5q) LR-MDS with the TP53 mutation include GATA2-directed strategies aimed at restoring lenalidomide sensitivity, as well as immune-based therapies targeting the tumor microenvironment characteristic of TP53-mutated disease. Full article