Search Results (10,489)

Cyanobacteria are prolific producers of secondary metabolites, some of which are potent cyanotoxins that threaten ecosystem integrity and human health. Although blooms have been extensively studied in temperate regions, Southeast Asia’s (SEA’s) tropical marine and estuarine ecosystems remain comparatively underexplored despite their ecological richness and socio-economic importance. This review consolidates current knowledge on marine cyanobacteria and cyanotoxins in SEA, drawing on ecological surveys, ecotoxicological studies, and cyanobacterial bloom case reports. Diverse taxa including Trichodesmium, Lyngbya, Oscillatoria, Neolyngbya, and Aliinostoc, have been documented in SEA’s marine waters, many producing cyanotoxins with various toxic effects. Ecotoxicological risks are intensified by monsoonal variability, nutrient enrichment, and climate-driven shifts that collectively amplifies cyanoblooms and toxin production. Detection methods such as PCR-based assays, LC-MS/MS, and biosensor technologies are increasingly applied to identify toxin biosynthesis genes, cryptic species, and novel metabolites. Environmental challenges including eutrophication from wastewater discharge, trophic transfer of toxins, and climate induced shifts in species distribution, further complicates bloom dynamics and management. Mitigating this requires a multi-pronged approach: advancing biosensors for rapid detection, embedding monitoring within predictive climate frameworks, and expanding molecular surveillance to capture cryptic diversity and gene transfer events. Such strategies are essential for environmental management of cyanobacterial blooms in SEA. Full article

This paper investigates decentralized demand-side management in renewable energy communities with limited and uncertain renewable energy resources. Consumer interactions are modeled as a Bayesian game in which self-interested consumers schedule flexible loads between daytime and nighttime periods to minimize electricity costs under time-of-use tariffs. Consumer heterogeneity is captured through private information describing both risk preferences and forecasts of renewable energy availability. Analytical conditions under which dominant strategies or mixed-strategy Bayesian Nash equilibria (BNE) exist are derived. Based on this analysis, two distributed algorithms that operate without a central coordinator are developed. The first is an iterative best-reply (BR) algorithm, while the second is a novel Demand Agreement (DA) algorithm that directly exploits the equilibrium conditions to reduce computation and communication requirements. The proposed decentralized mechanisms are compared against a centralized social-cost minimization benchmark. The results further demonstrate that the DA algorithm consistently converges to the minimum-cost equilibrium whenever a BNE exists, while requiring substantially lower communication overhead than BR. In contrast, the BR algorithm may converge even when the BNE conditions are not satisfied. Finally, the analysis quantifies the impact of consumer risk preferences and renewable generation uncertainty on BNE existence, scheduling decisions, and overall system performance. Full article

Strategic bidding in day-ahead electricity markets requires generation companies to maximize expected profits while managing financial risks arising from market uncertainty and competitors’ strategic behavior. This paper proposes a game-theoretic risk-aware strategic bidding framework based on a Supply Function Nash Equilibrium (SFNE) for dominant market operators in a uniform-pricing day-ahead market. Each operator strategically determines cluster-level bidding markups for its heterogeneous generation portfolio while anticipating competitors’ strategies. Demand uncertainty is represented by a finite scenario set, and Conditional Value-at-Risk (CVaR) of profit shortfall is incorporated into each operator’s expected-profit objective. The resulting non-cooperative equilibrium is solved using a relaxed Nikaido–Isoda (NI) best-response algorithm with convergence criteria based on the relative NI gap, strategy variation, and utility variation. The framework is validated using publicly available Italian day-ahead market offer data, where technology-oriented clustering reduces the strategic decision dimension while preserving portfolio heterogeneity. The proposed algorithm satisfies all convergence criteria within approximately 54 iterations. Numerical results show that the proposed risk-aware SFNE reduces aggregate downside-profit risk by approximately 7% compared with the risk-neutral SFNE while maintaining comparable expected profitability and slightly lowering market-clearing prices and procurement costs. A realistic 24 h market simulation further confirms the robustness and applicability of the proposed framework under time-varying market conditions. Overall, the proposed framework provides an economically interpretable and computationally tractable benchmark for risk-aware strategic bidding in day-ahead electricity markets. Full article

Acne vulgaris is an inflammatory cutaneous condition that disproportionately affects the pediatric population. While there are several risk factors, emerging evidence suggests that ultra-processed foods (UPFs), as part of Western dietary patterns, may contribute to acne pathophysiology through activation of inflammatory pathways, such as mTORC1. This comprehensive review synthesizes current evidence regarding acne pathogenesis in conjunction with diet-associated inflammatory cascades to better illustrate the potential role of diet as an adjunct to clinical management in pediatric patients. The current literature suggests that increased insulin/IGF-1 levels may contribute to alterations in the skin and gut microbiota. Additionally, components commonly found in UPFs have been proposed to activate the mechanistic target of rapamycin complex (mTORC1) through insulin/IGF-1-dependent and -independent mechanisms, perpetuating inflammatory pathways that give rise to acne pathogenesis. However, the majority of available evidence is derived from adult cohorts; pediatric-specific evidence remains limited. While studies have demonstrated clinical significance in acne severity with dietary interventions, future high-quality studies are required. Through understanding the relationship between diet and acne pathogenesis, future therapeutic and preventative strategies may be developed to improve pediatric acne clinical outcomes. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of pharmacological treatment for osteoarthritis (OA) and are recommended by international guidelines for the management of symptomatic pain. Despite their well-established efficacy, substantial interindividual variability exists in treatment response, with some patients experiencing meaningful pain relief while others derive little clinical benefit despite appropriate drug selection and dosing. This variability reflects, at least in part, the biological heterogeneity of OA pain. Objective: To review the mechanisms underlying variability in NSAID responsiveness in OA and to propose a practical framework for personalized NSAID prescribing based on pain phenotype, individual safety profile, and treatment timing. Methods: A narrative review of the contemporary scientific literature was conducted using major biomedical databases to summarize the current evidence on phenotype-guided NSAID therapy in OA. Particular attention was given to the emerging concepts of nociceptive, nociplastic, and neuropathic-like pain phenotypes and their implications for personalized anti-inflammatory therapy. Results: Current evidence indicates that OA pain is a heterogeneous and dynamic condition in which inflammatory nociceptive, nociplastic, and neuropathic-like mechanisms coexist to varying degrees. NSAIDs primarily target inflammatory nociceptive pain by inhibiting cyclooxygenase (COX)-mediated prostaglandin synthesis and reducing peripheral sensitization. Consequently, patients with predominantly inflammatory nociceptive pain are the most likely to benefit from NSAID therapy, whereas those with predominant nociplastic or neuropathic-like pain mechanisms may require alternative or multimodal treatment strategies. Beyond pain phenotype, optimal NSAID selection should integrate cardiovascular, gastrointestinal, and renal risk assessment, recognizing the important pharmacological and safety differences among individual agents. Treatment timing is also clinically relevant, as anti-inflammatory therapy appears most effective when initiated during periods of active inflammatory nociceptive pain. Based on the available evidence, we propose a conceptual clinical decision framework integrating patient selection, NSAID choice, and treatment timing. Conclusions: Personalized NSAID prescribing should move beyond a diagnosis-based approach toward a mechanism-based strategy that integrates pain phenotyping, individualized safety assessment, and appropriate treatment timing. The proposed framework is built upon three complementary principles, identifying the right patient, selecting the right treatment, and initiating therapy at the right time. It provides a practical foundation for implementing precision medicine in the pharmacological management of OA. Full article

Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy. Full article

This study evaluates the short-term effects of nine commercially available fire retardants (FRs) on water quality under controlled laboratory conditions. FRs were diluted to a 1:10 FR:water stock solution to approximate readily water-extractable fractions, and ion solubility was quantified together with key physicochemical parameters, including pH, electrical conductivity (EC), and dissolved oxygen (DO). Results revealed substantial heterogeneity among formulations in the concentrations of solubilized ions. Notably, FR4 (NP+) exhibited exceptionally high concentrations of NH₄⁺, NO₃⁻, NO₂⁻, PO₄³⁻, and Br⁻, as well as elevated Ca²⁺ and Na⁺. Other formulations also released considerable loads of common nutrients, particularly NO₃⁻ and PO₄³⁻, although at lower magnitudes. Despite the pronounced ionic enrichment, pH and DO remained relatively stable across most treatments. However, DO decreased in several cases at higher FR concentrations, suggesting increased oxygen demand associated with dissolved constituents. EC displayed strong, concentration-dependent increases across treatments, reflecting the rapid dissolution of ionic components in water. Cluster analysis identified three distinct groups of FRs based on their water-quality responses. The PCA biplot further revealed two main gradients structuring the formulations: mineralization and compositional diversity (PC1), and physicochemical solution conditions (PC2), which together distinguish the chemical and physicochemical signatures of the tested products. Overall, the results highlight substantial formulation-specific differences in nutrient and metal release, with potential short-term implications for aquatic chemistry and ecosystem functioning. Although derived from controlled laboratory conditions, these findings provide a first-order assessment of FR impacts on water quality and underscore the importance of considering formulation composition in watershed risk assessments and post-fire water quality management strategies. Full article

Harmful cyanobacteria blooms (CyanoHABs) have become a common problem in freshwater ecosystems. Monitoring at the federal and state level in response to this threat has increased over the last decade across the United States. In 2018, Pennsylvania environmental agencies began collecting CyanoHAB data to inform state regulatory and management efforts. 998 discrete samples from 138 waterbodies were collected over four years. These data were used to determine if indicators often used in CyanoHAB monitoring co-occurred with toxic conditions. Cyanotoxins were detected in more than half of the samples in Pennsylvania’s monitoring program with anatoxin, saxitoxins, and microcystins detected in similar proportions. It is important to note that the monitoring program is not designed to be representative of all Pennsylvania lakes but instead is targeted toward sites with greater exposure (recreational beaches) or sites with suspected blooms. Our findings suggest that cyanobacteria growth and cyanotoxin production may be driven by independent variables, as only microcystins concentrations were positively correlated with cyanobacteria counts. While increased cyanobacteria counts were related to all environmental variables considered in this study (warmer water temperatures, increased dissolved oxygen concentrations, and reduced water clarity), the relationships between cyanotoxins and environmental variables were mixed. Our analyses highlight the complexities of bloom occurrence and severity, and the challenges of incorporating these factors into monitoring and management strategies. Long-term monitoring approaches like the one analyzed here can inform management strategies that rely on environmental cues and cyanobacteria enumeration to evaluate risk of cyanotoxin presence. Full article

Hypertension remains a major global health burden, and control rates remain suboptimal because of poor medication adherence and limitations of existing therapies, including escape within the renin–angiotensin–aldosterone system. Zilebesiran, a first-in-class, subcutaneously administered small interfering RNA therapeutic, represents a promising advance in hypertension management. Through N-acetylgalactosamine-mediated hepatic delivery, zilebesiran selectively silences angiotensinogen (AGT) messenger RNA, the transcript encoding the common precursor of all angiotensin peptides. This upstream intervention reduces AGT production and produces durable blood pressure lowering that can persist for up to 6 months after a single dose. This review summarizes the mechanism of action of zilebesiran, its pharmacokinetic and pharmacodynamic properties, and the available phase 1 and phase 2 clinical evidence, including the KARDIA program. We also place zilebesiran within the evolving antihypertensive landscape by comparing it with aldosterone synthase inhibitors, dual endothelin receptor antagonists, and brain aminopeptidase A inhibitors. Finally, we discuss translational challenges, including reversal strategies for emergency situations, monitoring considerations, and potential roles for personalized dosing. Early-phase and phase 2 trials show dose-dependent and durable reductions in serum AGT and blood pressure with infrequent dosing; however, long-term safety, cardiovascular outcome benefit, and generalizability in diverse high-risk populations remain to be established, and zilebesiran remains investigational while phase 3 outcome testing is underway. Full article

Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to examine the role of vitamin D in the pathophysiology of MetS from a multisystem perspective. Specifically, it synthesizes current evidence on the molecular mechanisms through which vitamin D may influence inter-organ communication, insulin resistance, adipose tissue dysfunction, hepatic metabolism, skeletal muscle function, chronic inflammation, oxidative stress, and mitochondrial homeostasis, highlighting its potential contribution to the prevention and management of MetS. Current evidence indicates that MetS should not be regarded merely as a cluster of isolated metabolic abnormalities but rather as a disorder characterized by disrupted molecular signaling and impaired communication among metabolically active organs. In this context, experimental and preclinical evidence suggests that vitamin D, through activation of the vitamin D receptor (VDR), modulates key signaling pathways, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR-γ), thereby influencing insulin sensitivity, inflammation, oxidative stress, mitochondrial function, and metabolic homeostasis. Nevertheless, clinical evidence remains heterogeneous due, in part, to the lack of consensus regarding serum 25-hydroxyvitamin D thresholds for defining vitamin D status, as well as differences in baseline vitamin D concentrations, supplementation regimens, study populations, and methodological designs. Overall, the available evidence suggests that vitamin D should be considered an adjunct to lifestyle-based interventions rather than a stand-alone therapeutic strategy. Future research is warranted to clarify its clinical utility in the prevention and management of MetS. Full article

Closed-loop autonomous driving increasingly combines model-centric architectural development with data-centric learning. These two directions are complementary: model-centric methods improve representation, prediction, planning, and control capabilities, whereas data-centric methods improve how training samples, supervision signals, and closed-loop failures are selected and reused. A key remaining challenge is therefore how to use heterogeneous driving logs more effectively to improve closed-loop policy learning. Existing methods have made certain progress in aspects such as representation learning, generative planning, and closed-loop evaluation. This paper proposes a data-centric closed-loop autonomous driving learning framework. Combining risk-aware data valuation, supervision-calibrated distillation, and counterfactual attribution-guided corrective replay, the framework adjusts the training distribution, calibrates sample-level supervision, and converts training-side failure trajectories into intervention-validated corrective signals. Closed-loop experiments on Bench2Drive demonstrate improved driving performance, while NAVSIM provides supplementary non-reactive cross-platform evaluation under the tested benchmark conditions. The experimental results show that data-centric optimization strategies can help reduce performance degradation under the evaluated perturbations and provide a feasible approach to high-risk sample management, supervision-quality calibration, and failure-informed corrective replay. Full article

Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its central role in nociceptive transduction and peripheral sensitization. Capsaicin, a selective TRPV1 agonist, induces receptor desensitization and has shown potential in chronic pain modulation; however, its efficacy in orofacial conditions remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of capsaicin in managing orofacial pain, compared to placebo or other pharmacological interventions. Following PRISMA guidelines, a comprehensive search of five databases (PubMed, Scopus, Web of Science, CDSR, and LILACS) was conducted without language or date restrictions. Studies involving human participants with orofacial pain treated with capsaicin were included. The protocol was registered in PROSPERO (CRD420251004538). Risk of bias was assessed using the RoB2, RoB2 crossover trial and ROBINS-I checklist, and meta-analyses were performed using random-effects models. Nine studies enrolling a total of 164 participants met the eligibility criteria and encompassed temporomandibular disorders, burning mouth syndrome, oral mucositis, trigeminal neuralgia, and neuropathic facial pain. Although placebo-controlled comparisons showed a trend toward pain reduction that did not reach statistical significance (MD = –1.87; [95% CI: –3.94, 0.19]; p = 0.08; I² = 86%), and no significant difference was found between capsaicin concentrations (MD = 0.46; [95% CI: –2.67, 3.60]; p = 0.77, I² = 66%), pre–post analyses of uncontrolled (single-arm) studies demonstrated a significant and clinically meaningful reduction in pain following capsaicin treatment (MD = –6.39; [95% CI: –7.40, –5.38; p < 0.001, I² = 0%). Capsaicin also showed an acceptable safety profile: although adverse events were significantly more frequent than with control (OR = 19.84; [95% CI: 4.32–91.21]; p < 0.001, I² = 0%), these were mild, localized, and self-limited. Capsaicin may provide clinically meaningful pain relief in selected orofacial conditions, particularly burning mouth syndrome, where uncontrolled evidence was most consistent (I² = 0%); evidence for temporomandibular disorders was more heterogeneous and did not reach significance in pooled placebo-controlled analyses. Full article

The increasing detection of small, non-palpable testicular lesions has challenged the traditional paradigm that every solid intratesticular mass should be managed by radical orchiectomy. Many incidental lesions, particularly in infertile men and in patients with negative tumour markers, are benign or non-neoplastic, making overtreatment a clinically relevant concern. In this setting, ultrasound has become central to a more conservative and individualised diagnostic strategy. By combining high-resolution grey-scale imaging with Doppler, microvascular imaging, CEUS and elastography, multiparametric ultrasound provides complementary information on lesion morphology, vascularity, stiffness and interval change. When integrated with clinical presentation, tumour markers, fertility status, syndromic background and patient history, these features can help characterise lesions and estimate the likelihood of malignancy in the appropriate clinical context. Although imaging cannot replace histology, it can refine pre-test probability, support active surveillance in selected low-risk lesions, guide testis-sparing surgery, and improve assessment of the operated testis. This review examines the role of multiparametric ultrasound in characterisation of focal testicular lesions across different clinical settings, including incidentalomas, acute scrotal pain, trauma, bilateral disease, heterogeneous parenchyma, genetic and endocrine syndromes, and the postoperative testis. A structured, context-sensitive imaging approach may help reduce unnecessary orchiectomy while preserving timely detection of malignant, persistent, recurrent or metachronous disease. Full article

Objectives: Functional tricuspid regurgitation (TR) recurrence after concomitant mitral–tricuspid surgery remains associated with adverse long-term outcomes, while reintervention on the isolated tricuspid valve carries substantial operative risk. Despite increasing awareness of the prognostic importance of functional TR, concomitant tricuspid valve repair remains inconsistently adopted in contemporary practice, particularly in technically demanding procedures. We sought to identify predictors of recurrent TR and develop an individualized prediction model to support patient-tailored surgical planning. Methods: This single-center ambispective study included 178 consecutive patients undergoing concomitant mitral–tricuspid surgery between January 2012 and June 2019. Baseline clinical, echocardiographic and operative variables were retrospectively collected, whereas long-term clinical and echocardiographic follow-up was prospectively completed after Ethics Committee approval. Clinical, echocardiographic and operative variables were first evaluated by univariable Cox proportional hazards analysis. Based on their univariable association with recurrent TR, biological plausibility and clinical relevance, candidate predictors were subsequently entered into a multivariable Cox proportional hazards model while limiting model complexity according to the number of available outcome events. Internal validation was performed by bootstrap resampling, and regression coefficients were transformed into an exploratory individualized perioperative nomogram estimating 5-year tricuspid regurgitation recurrence-free survival. Results: Univariable analysis identified female sex, dyslipidemia, left ventricular ejection fraction <45%, severe pre-operative TR, indexed tricuspid annular diameter and suture-based annuloplasty as predictors of recurrent TR. Multivariable analysis identified surgical repair strategy as the only independent predictor associated with recurrent TR, with suture-based annuloplasty showing a significantly higher recurrence risk than prosthetic ring annuloplasty. These variables were integrated into an exploratory individualized prediction model estimating 5-year recurrence-free survival: the FuTURe nomogram. Conclusions: Our findings confirm the association between prosthetic ring annuloplasty and a lower risk of recurrent TR, consistent with current evidence supporting ring implantation as the preferred repair strategy. Beyond identifying predictors of recurrence, the FuTURe study proposes an exploratory perioperative individualized prediction model intended to complement current guideline recommendations. Consistent with its acronym, the FuTURe study shifts the focus from immediate procedural success to the patient’s future clinical trajectory, highlighting the value of individualized recurrence-risk assessment from a lifetime management perspective. Full article

Hip fractures are among the most devastating fragility fractures, associated with excess mortality, disability, loss of independence, and substantial healthcare costs. Although age-standardized incidence has declined in several high-income countries, absolute case numbers continue to rise because of population aging. This review summarizes contemporary PubMed-indexed evidence on the epidemiology, risk stratification, and prevention of proximal femoral fractures, with emphasis on hip-fracture outcomes rather than vertebral or composite endpoints alone. We discuss secular trends, FRAX-based case findings and screening, non-pharmacologic strategies, pharmacologic therapy, and health-system interventions relevant to both primary and secondary prevention. Among non-pharmacologic measures, long-term balance-challenging and resistance-based exercise has the most consistent evidence for reducing falls and likely contributes to fracture prevention, whereas multifactorial interventions, home hazard modification, calcium/vitamin D supplementation, and hip protectors are best targeted to selected high-risk populations and care settings. Among medications, bisphosphonates, denosumab, and romosozumab-based sequential strategies show the strongest evidence for reducing hip-fracture risk, while teriparatide and abaloparatide have important roles in very-high-risk patients despite less direct hip-fracture evidence. Menopausal hormone therapy reduces hip fractures in younger postmenopausal women but is limited by extra-skeletal risk, and selective estrogen receptor modulators are primarily vertebral-fracture agents. A major message of this review is that effective prevention depends not only on drug efficacy but also on implementation. Fracture liaison services, orthogeriatric co-management, prompt treatment after fragility fracture, and sustained adherence support are essential to close persistent care gaps. Preventing hip fractures therefore requires an integrated, risk-stratified approach that combines skeletal protection, falls prevention, and reliable health-system delivery. Full article