Search Results (4,936)

Background/Objectives: Acute otitis media (AOM) remains a leading cause of pediatric morbidity and a primary indication for antibiotic prescription worldwide. Given the potential for serious complications and the evolving landscape of antimicrobial resistance, up-to-date epidemiological data on causative bacteria are essential. This study aimed to assess the global prevalence of major bacterial pathogens in pediatric AOM and evaluate variations across geographic regions and temporal periods (pre-2000 vs. post-2000). Methods: A systematic search of PubMed, Embase, and Web of Science (1980–2025) was conducted to identify studies reporting middle ear fluid culture results in children (0–18 years) with AOM. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 45 studies encompassing 16,305 AOM episodes were included. Data were synthesized from North America, Europe, the Middle East, Asia, Oceania, and Africa. Pooled prevalence estimates and 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was assessed via the I² statistic. Results: The overall pooled culture-positive rate was 66.6% (95% CI, 62.2–70.8%). Regional pooled estimates ranged from 56.1% in the Middle East (95% CI, 40.3–70.6%; underlying counts, 3776/10,652) to 77.5% in North America (95% CI, 68.2–84.7%; underlying counts, 1567/2125). Streptococcus pneumoniae was the most prevalent pathogen, with a pooled proportion of 29.0% (95% CI, 26.3–31.8%), followed by Haemophilus influenzae (22.3%; 95% CI, 19.3–25.6%) and Moraxella catarrhalis (4.6%; 95% CI, 3.4–6.1%). While S. pneumoniae remained the leading pathogen in most regions, H. influenzae showed marked geographic variability, peaking in the Middle East at 27.5% (95% CI, 17.0–41.2%; underlying counts, 2280/10,652) and reaching its lowest level in Asia at 13.5% (95% CI, 7.8–22.4%; underlying counts, 336/1854). The pooled culture-positive rate declined from 72.5% before 2000 (95% CI, 67.6–76.9%; underlying counts, 5769/8199) to 59.4% in 2000 and later (95% CI, 52.1–66.3%; underlying counts, 6661/15,707), although S. pneumoniae remained the predominant isolate in both periods. Conclusions: S. pneumoniae remains the primary bacterial driver of pediatric AOM globally. However, the observed geographic disparities and the temporal shift in pathogen prevalence following pneumococcal conjugate vaccine (PCV) introduction underscore the necessity for region-specific empirical antibiotic selection. These findings highlight the critical need for sustained microbiological surveillance to inform future vaccination and treatment strategies. Full article

Wild mushroom poisoning remains a major medical and toxicological challenge worldwide because of the diversity of toxic compounds, the broad spectrum of clinical manifestations, and the risk of severe hepatic or renal injury. Early differentiation between self-limiting gastrointestinal syndromes and potentially fatal intoxications with progressive organ failure remain a central clinical challenge. This review examines recent advances in the diagnosis, risk stratification, and therapeutic management of wild mushroom poisoning, with amatoxin intoxication serving as the principal clinical focus. Selected evidence from other mushroom toxic syndromes is also included to support differential diagnosis, highlight syndrome-specific variability, and provide comparative clinical and methodological context. The recent literature indicates a shift from predominantly symptom-based diagnosis toward integrated models combining clinical evaluation, laboratory biomarkers, toxicological testing, and analytical and molecular methods. Liquid chromatography, mass spectrometry, immunoassays, and the molecular identification of fungal species have improved diagnostic precision, particularly in cases with uncertain exposure history or delayed presentation. Current management relies on early multimodal strategies including intensive supportive care, targeted pharmacological interventions, extracorporeal detoxification, and, in selected severe cases, liver transplantation. Overall, clinical outcome depends not only on toxin profile, but also on timely diagnosis, accurate early risk stratification, and prompt coordinated treatment. Future research should prioritize standardized diagnostic pathways, validated prognostic models, and clinically applicable treatment algorithms that support earlier escalation of care in severe mushroom intoxication. Full article

In this study, TiO₂ nanotube (TNTs) array electrodes were fabricated by electrochemical anodization and subsequently modified through thermal annealing, hydrogenation heat treatment, and chemical decoration with copper species at various immersion times to enhance their electrochemical performance. The structural, morphological, semiconducting, and electrochemical properties of the modified nanotubes were systematically examined. FE-SEM and EDS analyses confirmed the formation of well-aligned TNTs and the successful deposition of copper species, with the most uniform surface distribution achieved for the sample decorated for 45 min. Raman spectroscopy and XRD results revealed that the anatase phase of TiO₂ remained stable after hydrogenation and copper decoration, while minor peak shifts indicated defect evolution and lattice distortion. Electrochemical evaluations, including linear sweep voltammetry, Tafel polarization, electrochemical impedance spectroscopy, and Mott–Schottky analysis, demonstrated a substantial enhancement in electrocatalytic activity following copper decoration. Compared with annealed and hydrogenated electrodes, the decorated samples exhibited markedly lower overpotentials, reduced cathodic Tafel slopes, and decreased charge-transfer resistance. Mott–Schottky analysis confirmed n-type semiconducting behavior for all electrodes, showing that hydrogenation increased donor density, whereas subsequent copper decoration slightly reduced it due to the partial substitution of oxygen vacancies by copper oxide species. Among all samples, the electrode decorated for 45 min (AA′HD45) exhibited the optimal balance between donor density, charge-transfer properties, and electrochemical performance. These results highlight the effectiveness of combining hydrogenation with optimized copper decoration to improve charge transport and interfacial kinetics in TNT electrodes for electrochemical applications. Full article

Metabolic heterogeneity within the cell microenvironment is a key driver of cancer progression and resistance to therapy. However, current approaches lack the spatial and temporal resolution required to capture its dynamics in living systems. While recent advances in 3D cell culture models and metabolomic profiling have improved our understanding of the tumor niche, their integration with real-time optical sensing remains underdeveloped. Here, we present an integrated platform combining a 3D-printed microreactor culture chamber with Raman spectroscopy to enable non-invasive, spatially resolved metabolic monitoring of living cell cultures. Our microreactor platform generates controlled oxygen and nutrient cues while simultaneously acquiring label-free Raman spectra, revealing extracellular metabolic fingerprints linked to cell catabolism (e.g., glucose and lactate shifts) and acidification. Analysis across four cell lines uncovered temporal evolution as the dominant source of metabolic variance, while spatial heterogeneity along oxygen gradients is a secondary factor. In particular, diffusion-limited regions exhibited localized acidification and accumulation of stress biomarkers—such as the release of nucleotides—features that cannot be detected using conventional bulk assays. By providing a versatile platform for real-time mapping, this work enables the mechanistic dissection of cell adaptation to microenvironmental stress and supports the prediction of metabolic signatures underlying drug response and treatment outcomes. Full article

The recirculating aquaculture system (RAS) marks a significant shift in global aquaculture, transitioning to controlled, land-based production. This review highlights technological advancements that enable the treatment and reuse of over 90% of water, thereby enhancing water quality and production efficiency. These features position RAS as a cornerstone of sustainable seafood production. This review introduces the RAS Readiness Level (RRL) framework which is a novel, structured approach to assess the commercial maturity of emerging RAS technologies. Applying the RRL to six key technological domains (from digital AI systems to biological PHB recovery) reveals a pervasive pilot-scale purgatory where most innovations stagnate at RRL 4–6. It further addresses advanced processes such as membrane bioreactors, denitrification reactors, and the conversion of waste into valuable products. Furthermore, this review addresses persistent challenges, including high energy demand, economic viability, and the accumulation of pathogens. Finally, it focuses on the emergent integration of the Internet of Things (IoT) and artificial intelligence (AI), which are revolutionizing RAS management through data-driven optimization. By synthesizing current innovations, this review envisions a future of intelligent, closed-loop RAS where advanced IoT- and AI-driven technologies optimize water quality and feeding strategies to minimize ecological impact while enhancing sustainability and productivity. Full article

Recent Phase 3 clinical trials of selective kappa-opioid (KOP) receptor antagonists aticaprant and navacaprant failed to demonstrate sufficient clinical efficacy in treatment-resistant depression (TRD). This highlights a critical gap in current strategies that target opioid-mediated hedonic suppression. We propose two hypotheses to explain these setbacks: (1) neutral antagonists are inherently ineffective in blocking constitutively active KOP receptor hyperactivation and (2) the nociceptin opioid (NOP) receptor provides functional redundancy that compensates for KOP receptor blockade. Gaining insights from paralogous compensation in drug-resistant tumors, we argue for shifting from selective opioid antagonists to dual KOP/NOP receptor blockers to meaningfully improve reward function. This concept provides a theoretical framework for overcoming clinical resistance where selective KOP targeting with neutral antagonists has failed. Thus, we advocate for the development of opioid inverse agonists (such as nor-BNI, CAS: 105618-26-6), pan-antagonists (such as AT-076, CAS: 1657028-64-2), and combinations of selective blockers. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by dysbiosis of the gut microbiota. Helminth infections are known to modulate host immunity and intestinal microbial composition; however, the therapeutic use of live parasites poses safety challenges. The recombinant Fasciola hepatica fatty acid-binding protein Fh15 is a helminth-derived molecule with anti-inflammatory effects in models of septic shock and dextran sulfate sodium (DSS)-induced colitis. Whether Fh15 also influences gut microbial composition during colitis remains unknown. Male C57BL/6 mice received 4% DSS in drinking water for 7 days to induce colitis and were treated intraperitoneally with Fh15 (2 mg/kg) on days 1, 3, and 5. Fecal samples were collected on days 2, 4, and 7 for 16S rRNA gene sequencing. Standard microbiota pipelines were used to evaluate community diversity. Acute DSS treatment disrupted gut microbial diversity and community structure compared with non-colitic controls. Fh15 treatment partially restored early microbial balance by shifting microbial composition toward that of healthy mice and reducing microbial dispersion, indicating enhanced community stability despite severe dysbiosis. Although alpha diversity did not return to control levels, Fh15 mitigated the expansion of pro-inflammatory genera (Enterococcus and Turicibacter) and preserved beneficial taxa, including Adlercreutzia. Full article

Transcatheter aortic valve replacement (TAVR) has transformed the management of severe aortic stenosis and is now widely used across a broad spectrum of surgical risk. With expanding indications and increasing use in younger patients, contemporary practice increasingly emphasizes lifetime management of aortic valve disease, a shift further supported by recent developments including findings from the EARLY TAVR trial and the May 2025 U.S. Food and Drug Administration approval of TAVR for asymptomatic severe aortic stenosis. This narrative review summarizes recent developments in TAVR, including advances in device technology, procedural techniques, and patient selection. Focus is placed on the importance of optimal first valve selection, prevention of prosthesis–patient mismatch (PPM), and planning for future reintervention such as valve-in-valve (ViV) TAVR. Emerging procedural strategies including bioprosthetic valve fracture and leaflet modification techniques have expanded treatment options for patients at risk of elevated gradients or coronary obstruction. The review also highlights evolving approaches to TAVR in complex clinical scenarios and discusses future directions in device design and imaging-based procedural planning. As TAVR continues to evolve, careful procedural planning and multidisciplinary heart team collaboration remain essential to optimizing long-term outcomes. Full article

Background/Objectives: Persistent gastrointestinal (GI) symptoms following oncologic treatment represent a major unmet need in survivorship care, often managed symptomatically without addressing underlying biological mechanisms. This study aimed to evaluate the clinical efficacy and biological correlates of an artificial intelligence (AI)-guided, personalized microbiome modulation strategy in oncology patients with chronic secondary GI dysfunction. Methods: We conducted a prospective, single-arm, open-label validation study including 29 adult female oncology patients with persistent GI symptoms lasting ≥3 months. Participants underwent baseline multidimensional assessment integrating shotgun metagenomic sequencing, inflammatory and nutritional biomarkers, and clinical symptom profiling. An AI-guided platform generated individualized dietary, supplement, and lifestyle recommendations. Outcomes were assessed at baseline and after a 3-month intervention, focusing on intra-individual changes in stool frequency (primary endpoint), self-reported energy, microbiome composition, and metabolic biomarkers. Paired statistical analyses, correlation testing, and multivariable regression were performed. Results: After three months, stool frequency significantly decreased (4.69 ± 2.41 to 2.07 ± 1.19 episodes/day; p < 0.0001), accompanied by a marked increase in energy levels (4.00 ± 1.04 to 7.24 ± 1.12; p < 0.0001). Microbiome analysis revealed consistent enrichment of butyrate-producing and barrier-supportive taxa, including Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia intestinalis, Akkermansia muciniphila, and Bifidobacterium longum. Butyrate-related biomarkers and vitamin-associated parameters (B-complex, vitamin D) showed significant improvement, while lactate levels normalized. Changes in Bifidobacterium longum were independently associated with stool frequency reduction (β = −0.783, p = 0.0082). Conclusions: AI-guided personalized microbiome modulation was associated with significant clinical improvement and biologically coherent microbial and metabolic shifts in oncology patients with persistent GI symptoms. These findings support a precision supportive-care approach targeting microbiome restoration, warranting further validation in randomized controlled trials. Full article

While diabetic retinal disease (DRD) has classically been viewed as a microvascular complication, emerging evidence places the photoreceptor at the center of its pathogenesis. Recognizing this central role provides a critical framework for resolving a major clinical paradox in diabetes: why the retina exhibits profound susceptibility to hyperglycemic damage, whereas closely related neural tissues like the brain are mostly spared. In this review, we synthesize the evidence for photoreceptor-driven DRD pathology by evaluating two primary mechanistic paradigms. In the first, hyperglycemia-induced damage to the blood vessels limits perfusion, creating an ischemic environment that selectively devastates tissues dependent on exceptionally high blood flow and energy delivery—specifically, the photoreceptors. In the second paradigm, hyperglycemia induces a direct shift in the metabolic profile of photoreceptors, triggering oxidative stress and dysregulated lipogenesis that subsequently place pathological strain on the local microvasculature. Regardless of whether the initial insult is vascular or neuronal, the photoreceptor remains the critical node of disease progression. Because current and investigational DRD treatments predominantly target downstream vascular consequences, exploring these dual mechanisms highlights an urgent need and a significant opportunity to develop novel therapies that target the photoreceptor to address DRD at its root. Full article

Intensive monoculture exacerbates soil compaction and sodification in the West Liao River Plain. This study evaluated legacy effects of diversified 3-year rotations on sodic soil health (ESP > 15%, ECe < 4 dS m⁻¹) during two subsequent maize seasons. Rotations incorporating salt-tolerant forages and deep-rooted crops (sugar beet–Echinochloa–sorghum and Echinochloa–tall fescue–silage corn) significantly reduced bulk density (8.6–13.1%) and exchangeable sodium percentage (up to 14.1 percentage points) relative to continuous monoculture. Treatments with maximum desalination (22.6% reduction) enhanced fungal α-diversity by 98.0%, while forage-dominated systems enriched Acidobacteriota by 35.2%, shifting bacterial communities toward oligotrophic dominance. Structural equation modeling confirmed that rotation effects on enzyme activity were mediated through reduced bulk density and ESP. These systems provide effective biological models for sustainable maize cultivation in sodic soils via synergistic physical-chemical-biological amelioration. Full article

Bias temperature instability (BTI) degradation is commonly described using empirical power-law kinetics; however, extraction of the time exponent and projection of lifetime remain highly sensitive to baseline definition and data representation. In conventional approaches, the threshold voltage shift is referenced to an initial value that cannot be measured simultaneously with stress, introducing uncertainty that can produce apparent curvature and variability in the extracted exponent. In this work, a baseline-independent linearization method is applied to representative published datasets spanning advanced silicon, SiC MOSFETs, and GaN power devices. By analyzing the measured degradation trajectories directly in a transformed time coordinate, the method removes curvature associated with baseline ambiguity and enables consistent extraction of the effective power-law exponent. Across all material systems examined, the extracted exponent exhibits systematic dependence on applied stress once baseline effects are reduced. This behavior challenges the commonly assumed constant-exponent formulation used in conventional lifetime projections and shows that even modest variations in the exponent can produce large differences in projected time-to-failure. A transformed lifetime representation based on is introduced, in which the influence of exponent variation is separated from the intrinsic voltage and temperature acceleration of the degradation rate. In this representation, the extracted acceleration parameters become more stable and physically interpretable. This formulation is consistent with standard reliability frameworks, including JEDEC JEP122G, in which the time exponent enters directly into the lifetime expression. These results demonstrate that baseline-independent analysis provides a unified framework for interpreting BTI degradation across disparate semiconductor technologies and suggest that explicit treatment of stress-dependent exponents is required for physically consistent lifetime modeling. Full article

Advanced gastric (GAC) or gastroesophageal junction (GEJAC) adenocarcinoma continues to carry a poor prognosis. Understanding GAC/GEJAC at the molecular level has provided a new understanding and the basis for individualized approaches to treatment. The current biomarker-driven therapy focuses on four areas: microsatellite instability (MSI), human epidermal growth factor receptor-2 (HER2), programmed death ligand-1 (PD-L1) combined positive score, and claudin 18.2 (CLDN18.2). However, because of improving technology, the focus has shifted to cancer cell-surface proteins and peptides. Each of these GAC/GEJAC subgroups provides a different treatment pathway. The agents utilized to treat advanced GAC/GEJAC include immune checkpoint inhibitors (ICIs), chemotherapy, monoclonal antibodies (mAbs), and antibody–drug conjugate (ADC) therapy, as well as bispecific antibodies (BsAbs), but they are certainly not limited to the above. Drug development has shifted in recent years to establish different mechanisms that are attempting more sophisticated and targeted approaches, such as BsAbs and ADCs. Meanwhile, the development of cytotoxics has tapered off. Along with these developments in drug therapy, more therapies directed at CLDN18.2, HER2, MSI, EGFR, HER3 and trophoblast cell-surface antigen 2 (TROP2) are underway. Here we review future areas in advanced GAC, including zanidatamab’s potential role in HER2-positive advanced GAC and deciphering the abundance of anti-CLDN18.2, extending beyond investigative therapies. Full article

Hydrochar has emerged as a promising carbonaceous amendment to enhance soil quality, yet its short-term effects on soil carbon (C) and nitrogen (N) dynamics and microbial functioning remain poorly understood. Here, a 77-day greenhouse pot experiment was conducted using a Cambisol cultivated with sunflower (Helianthus annuus L.) under two irrigation regimes simulating well-irrigated (WI) and water-deficit (WD) scenarios. Two doses of chicken-manure-derived hydrochar (3.25 and 6.5 t ha⁻¹, corresponding to 2.35 and 4.69 g kg⁻¹ of dry soil, respectively) and mineral fertilizer (MF) treatments providing equivalent N inputs were evaluated. Hydrochar promoted microbial growth and enhanced enzymatic and respiratory activities despite its low apparent C and nutrient input. After 77 days under WI, the addition of 6.5 t ha⁻¹ hydrochar enhanced the activity of phenol oxidase (POA) and acid phosphomonesterase (AcPA). Concomitantly, the availability of soluble C and N increased, whereas total organic C (TOC) and N decreased relative to the initial values. These responses may suggest enhanced mineralization potentially related to early-stage priming processes. The increase in POA relative to β-glucosidase is in line with a functional shift from a predominant degradation of labile compounds towards an increased oxidation of more complex structures. This interpretation is supported by solid-state ¹³C NMR data, revealing a higher degradation index of the soil organic matter. Under WD, the overall effects of hydrochar were attenuated or suppressed, particularly those related to C and N dynamics, emphasizing the interactive influence of moisture and amendment dose. Overall, our results show that hydrochar can modulate short-term soil biochemical processes, partly through enhanced microbial responses. Full article

Hepatitis C virus (HCV) infection is still a major worldwide health concern. It is distinguished by a high degree of genetic variation that affects the course of the illness and the effectiveness of treatment. The epidemiological profile of HCV is prone to rapid change in areas where there is significant human migration, like Turkey. The purpose of this study was to evaluate the impact of long-term migration on local viral diversity by analyzing the distribution and temporal trends of HCV genotypes among Turkish citizens and asylum seekers in Kayseri, Turkey, over an eight-year period. From January 2014 to December 2021. 1173 HCV RNA-positive patients at Kayseri City Training and Research Hospital were the subject of a retrospective analysis. Genotypes were determined using the Abbott RealTime HCV Genotype II assay and Montania 4896 assay (Anatolia Geneworks, Türkiye). The most prevalent genotypes were Genotype 1b (48.3%, 95% CI: 45.5–51.2%), Genotype 4 (25.0%, 95% CI: 22.5–27.5%), and Genotype 1a (10.3%, 95% CI: 8.6–12.1%). Turkish patients exhibited the highest prevalence of Genotype 1b (98.2%), while asylum seekers demonstrated greater relative burdens of Genotype 4 (8.5% of total GT4) and Genotype 5 (83.3% of total GT5). Genotype 3a emerged in 2018, with a predominance in males (73.9%). The Cochran–Armitage trend test revealed statistically significant increasing trends for Genotype 3 (Z = 3.572, p = 0.0004) and Genotype 3a (Z = 2.600, p = 0.009). This eight-year retrospective study demonstrates that the HCV genotype distribution in Kayseri has undergone significant changes in the context of migration and demographic shifts. The statistically significant increasing trends of Genotypes 3 and 3a, particularly among younger male populations, suggest evolving transmission dynamics. These findings underscore the necessity of demographically targeted and culturally appropriate screening and treatment strategies for both resident and migrant populations to achieve HCV elimination goals. Full article