Search Results (434)

In response to the critical demand for improved characterization of atmospheric stability effects in wind turbine wake prediction, this study proposes and systematically validates a new analytical wake model that incorporates atmospheric stability effects. In recent years, research on wake models with atmospheric stability effects has primarily followed two approaches: incorporating stability through high-fidelity numerical simulations or modifying classical analytical wake models. While the former offers clear mechanical insights, it incurs high computational costs, whereas the latter improves efficiency yet often suffers from near-wake prediction biases under stable stratification, lacks a unified framework covering the entire wake region, and relies heavily on case-specific calibration of key parameters. To overcome these limitations, this study introduces a stability-dependent turbulence expansion term with a square of a cosine function and the stability sign parameter, enabling the model to dynamically respond to varying atmospheric conditions and overcome the reliance of traditional models on neutral atmospheric assumptions. It achieves physically consistent descriptions of turbulence suppression under stable conditions and convective enhancement under unstable conditions. A newly developed far-field decay function effectively coordinates near-wake and far-wake evolution, maintaining computational efficiency while significantly improving prediction accuracy under complex stability conditions. The Present model has been validated against field measurements from the Scaled Wind Farm Technology (SWiFT) facility and the Alsvik wind farm, demonstrating superior performance in predicting wake velocity distributions on both vertical and horizontal planes. It also exhibits strong adaptability under neutral, stable, and unstable atmospheric conditions. This proposed framework provides a reliable tool for wind turbine layout optimization and power output forecasting under realistic atmospheric stability conditions. Full article

ATP-dependent chromatin remodeling complexes regulate gene expression by altering chromatin structure through ATP hydrolysis. They are classified into four families—SWI/SNF, ISWI, CHD, and INO80—which remodel chromatin via nucleosome sliding, eviction, assembly, and editing to control transcription. These complexes play critical roles in DNA repair, tumorigenesis, and organogenesis. Recent advances in low-input proteomics have highlighted their importance in vertebrate embryonic development. In mammals, they regulate embryonic genome activation, lineage specification, and stem cell fate determination. In non-mammalian models (e.g., Xenopus laevis), they function from blastocyst formation to pre-organogenesis stages (gastrulation and neurulation)—key windows for chromatin reprogramming and cell fate decisions. This review provides a systematic overview of chromatin remodeling complexes, detailing their classification and conserved mechanisms, and discusses their functions in early embryogenesis and embryonic stem cell maintenance. The collective evidence underscores the implications of these chromatin remodelers for understanding developmental defects and advancing regenerative medicine. Full article

The fungal pathogen Blumeria graminis forma specialis tritici (B.g. tritici) infects bread wheat (Triticum aestivum L.) to cause wheat powdery mildew disease. Elucidating the molecular mechanism underlying wheat susceptibility to the pathogenic fungus B.g. tritici could facilitate wheat genetic improvement. In this study, we identified the wheat TaSWI3B gene as a novel Susceptibility gene positively regulating wheat susceptibility to B.g. tritici. The TaSWI3B gene encodes the SWI3B subunit of the SWI/SNF chromatin remodeling complex. The overexpression of the TaSWI3B gene enhances wheat powdery mildew susceptibility, whereas TaSWI3B silencing results in attenuated wheat powdery mildew susceptibility. Importantly, we found that TaSWI3B could be enriched at the promoter regions of the salicylic acid (SA) biosynthesis activator gene TaSARD1, facilitating nucleosome occupancy and thereby suppressing TaSARD1 transcription and inhibiting SA biosynthesis. Silencing of TaSARD1 and TaICS1 encoding a key enzyme in SA biosynthesis could attenuate the SA biosynthesis and powdery mildew resistance potentiated by knockdown of TaSWI3B expression. Collectively, these results suggest that the SWI3B subunit of the wheat SWI/SNF chromatin remodeling complex negatively regulates SA biosynthesis by suppressing TaSARD1 transcription at the epigenetic level and thus facilitates wheat powdery mildew susceptibility. Full article

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, plays a context-dependent function in cancer, acting both as a tumor suppressor and, in certain conditions, as an oncogene. ARID1A, as a tumor suppressor, maintains transcriptional regulation, genomic stability, and cellular differentiation. In breast cancer, ARID1A loss-of-function leads to dysregulation of cell cycle checkpoints and impaired DNA repair and promotes epithelial-to-mesenchymal transition (EMT), jointly accelerating tumor proliferation and increasing therapeutic resistance. Notably, context-dependent ARID1A loss-of-function often concurs with activation of the PI3K/AKT signaling pathway and corresponds with poor prognosis. On the contrary, aberrant ARID1A overexpression can provoke oxidative stress and agitate the cytochrome P450 system, potentially facilitating early tumorigenesis. Consequently, understanding ARID1A’s dual and context-dependent role highlights its potential as a biomarker and therapeutic target in precision oncology. Full article

Background: ICU care is time critical and data dense, making it a promising but high-risk setting for AI decision support when tools are weakly validated. ICU AI evidence is heterogeneous, with limited external validation, inconsistent clinically actionable reporting, and scarce real-world impact data, yielding fragmented review conclusions. We mapped five prespecified ICU domains and assessed clinical and implementation maturity to identify key translational gaps. Methods: We performed a PRIOR-aligned overview of systematic reviews with prespecified maturity constructs. PubMed, Embase, and Web of Science were searched (title and abstract) on 13 December 2025, supplemented by backward citation searching. Two reviewers screened and extracted data with arbitration, assessed the review-level risk of bias using ROBIS, and synthesized findings without meta-analysis using a SWiM-guided narrative prioritizing AUROC ranges. Results: We included 34 systematic reviews (2017–2025) across five ICU domains, dominated by prognostic and early warning applications, mostly in adult populations and commonly using EHR and multimodal inputs. Reporting focused on discrimination, with AUROC ranges roughly 0.54–0.99 for prognostic tasks and 0.64–0.99 for diagnostic tasks, while calibration and clinical utility were rarely addressed and overlap suggested partial dependence. Maturity signals clustered at low-to-intermediate levels, with no evidence for routine, and regulated CDS deployment at the review level. Conclusions: Review-level evidence indicates a translational gap between retrospective performance and clinically mature, safely deployable ICU AI, supporting priorities for external validation, prospective impact studies, standardized reporting including calibration, and governance-focused implementation. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) represents the intricate interconnection of cardiovascular, kidney, and metabolic disorders, with systemic inflammation now recognized as a key driver of both pathogenesis and prognosis. This systematic review aimed to synthesize current evidence on the prognostic value of inflammatory biomarkers in individuals with CKMS. A systematic search of PubMed, Embase, CINAHL, Web of Science, and Scopus were conducted to identify studies published between 1 January 2024 and 30 June 2025, following the recognition of CKMS as a distinct syndrome in December 2023. Eligible studies included adults (aged ≥ 18 years) with CKMS, that assesses one or more inflammatory markers and reported prognostic outcomes such as mortality or disease progression. Data extracted included study characteristics, biomarker types, outcome measures, and key findings. In addition to longitudinal cohorts, we included a small number of cross-sectional studies and treated them as association (non-prognostic) evidence analyzed in a separate stream from prognostic cohorts. Risk of bias was evaluated using the Quality in Prognostic Studies (QUIPS) tool. Due to considerable variability in prognostic outcomes, follow-up durations, and inflammatory indices, a meta-analysis was not feasible. Instead, a narrative synthesis was undertaken to summarize the evidence, identify consistent associations, and emphasize the need for standardized approaches and biomarker validation in future CKMS research. Analysis was conducted in line with the SWiM guidelines. Thirteen studies (n = 13) comprising 282,016 participants (100,590 males; 97,295 females) were included from 1404 initial records. Five of the studies were cross-sectional, providing information on associations rather than prognostic outcomes. Most were large-scale cohort studies conducted in the USA and China. Frequently assessed biomarkers included systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (hs-CRP/HDL-C), dietary inflammatory index (DII), and triglyceride–glucose (TyG) index. Elevated levels of these biomarkers were consistently associated with higher risk of all-cause and cardiovascular mortality, CKMS progression, and adverse metabolic outcomes. This review highlights systemic inflammation as a critical and associated marker of CKMS prognosis. Inflammatory biomarkers may assist in hypothesis generation, but clinical utility remains to be established pending standardized adjustment and external validation. Because CKMS has only recently been operationalized, we limited inclusion to studies published from 1 January 2024 onward, enhancing definitional comparability but narrowing the evidence base and potentially emphasizing early-adopter regions (predominantly the U.S. and China). Accordingly, these findings should be interpreted as early signals that require replication in diverse settings and confirmation through longitudinal and interventional studies to inform integrative CKMS management strategies. Across observational studies, the certainty of evidence is low to moderate due to indirectness and imprecision; findings should be treated as associational signals pending external validation. Full article

Typhoon-induced hazards in South Korea exhibit strong spatial heterogeneity, requiring localized assessments to support impact-based early warning. This study develops a district-level typhoon hazard framework by integrating high-resolution meteorological fields with structural and hydrological vulnerability indicators. Two impact-oriented indices were formulated: the Strong Wind Risk Index (SWI), based on 3 s gust wind intensity and building-age fragility, and the Heavy Rainfall Risk Index (HRI), combining probable maximum precipitation with permeability and river-network density. Hazard levels were classified into four categories, Attention, Caution, Warning, and Danger, using district-specific percentile thresholds consistent with the THIRA methodology. Nationwide analysis across 250 districts revealed a pronounced coastal–inland gradient: mean SWI and HRI values in Busan were approximately 1.9 and 6.3 times higher than those in Seoul, respectively. Sub-district mapping further identified localized hotspots driven by topographic exposure and structural vulnerability. By establishing statistically derived, region-specific thresholds, this framework provides an operational foundation for integrating localized hazard interpretation into Korea’s Typhoon Ready System (TRS). The results strengthen the scientific basis for adaptive, evidence-based early warning and climate-resilient disaster-risk governance. Full article

Pathogenic fungus Blumeria graminisforma specialistritici (B.g. tritici) is the causal agent of the devastating wheat powdery mildew disease. Identifying the key regulators governing wheat susceptibility to the B.g. tritici pathogen is essential for developing wheat varieties with improved powdery mildew resistance. In this study, we demonstrated that the wheat chromatin remodeler TaSWI3D positively regulates wheat susceptibility to B.g. tritici. Overexpression of TaSWI3D gene attenuates wheat resistance against B.g. tritici, while silencing of TaSWI3D gene potentiates wheat powdery mildew resistance. TaSWI3D protein was found to be enriched at the promoter regions of the TaSARD1 gene encoding the salicylic acid (SA) biosynthesis activator, and silencing of TaSWI3D resulted in decreased nucleosome occupancy at the TaSARD1 promoter regions. Activated TaSARD1 transcription and increased SA accumulation were observed in the TaSWI3D-silenced wheat plants. Silencing of TaSARD1 and the SA biosynthesis gene TaICS1 resulted in attenuated SA biosynthesis and decreased powdery mildew resistance in the TaSWI3D-silenced wheat plants. These findings support that the chromatin remodeler TaSWI3D maintains epigenetic suppression of the SA biosynthesis activator gene TaSARD1 and negatively regulates SA biosynthesis, thereby positively contributing to wheat powdery mildew susceptibility. Full article

Carbonate reservoirs, which hold a significant portion of the world’s oil reserves, are particularly challenging for enhanced oil recovery (EOR) due to their predominantly oil-wet nature and low permeability. Smart water injection (a low-cost, environmentally friendly EOR method) has demonstrated potential to enhance recovery by modifying rock wettability. While numerous studies have examined smart-water mechanisms, the specific role of initial wettability (including Swi and core preservation state) in controlling its efficiency remains insufficiently quantified. This study addresses this critical gap by systematically investigating how initial wettability affects oil recovery during smart water flooding in a Middle Eastern carbonate reservoir. Core flooding experiments were conducted using brines enriched with potential-determining ions (SO₄²⁻, Ca²⁺, Mg²⁺) under varying wettability conditions. These tests were performed under controlled initial wettability conditions (Swi and preservation state) to ensure consistent and representative comparison across brine types. Results reveal that initial rock wettability plays a pivotal role in dictating the extent of wettability alteration and oil displacement. In strong oil-wet samples, sulfate-enriched brines induced substantial wettability shifts, significantly enhancing recovery. Conversely, ion saturation effects were observed, limiting further improvement beyond a threshold. Quantitatively, spontaneous water-displacement tests on core 122 at ambient conditions yielded 8.1% of OOIP at Swi = 10%, approximately twice the recovery of the same core in a dry (Swi = 0%) condition. Under reservoir-temperature core-flooding, seawater increased oil recovery from 38.3 to 53.1% OOIP in sample 122 and from 42.2 to 54.1% OOIP in sample 188 relative to formation water, corresponding to incremental gains of about 10–15 percentage points. These findings highlight the critical role of initial wettability characterization in designing effective smart-water EOR strategies. Tailoring brine composition to reservoir-specific wettability conditions enabled recovery improvements of approximately 10–15 percentage points relative to formation water at reservoir temperature. The results provide clear mechanistic insight into ion-specific interactions and offer practical guidance for optimizing smart-water formulation and deployment in carbonate reservoirs. Full article

Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a highly aggressive neoplasm of the central nervous system (CNS), most commonly affecting infants and young children. Originally recognized as a distinct entity following cytogenetic identification of monosomy 22 in renal Rhabdoid Tumors, AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex. The integration of immunohistochemical markers with advanced molecular diagnostics—including next-generation sequencing, DNA methylation profiling, and gene enrichment analyses—has facilitated robust tumor classification and the identification of three molecular subgroups: TYR, SHH, and MYC. Despite its distinctive histopathologic features, AT/RT remains diagnostically challenging in adolescent and adult populations due to age-related bias and potential morphologic heterogeneity. Differential considerations, including epithelioid sarcoma, poorly differentiated chordoma, CRINET, choroid plexus carcinoma, and rare composite tumors, further complicate the diagnostic landscape. A comprehensive, multimodal diagnostic approach combining histologic, immunophenotypic, and molecular data is essential to accurately identify AT/RT and guide clinical management, particularly in diagnostically ambiguous or atypical cases. Full article

Purpose: This study proposes a novel magnetic resonance (MRI)-based classification of cortical tubers (CTs) in tuberous sclerosis complex (TSC) patients that incorporates intralesional calcifications. We evaluated prevalence, temporal evolution, and genotype correlation of intra-tuberal calcifications in pediatric TSC patients, emphasizing susceptibility-weighted imaging (SWI) for detection. Materials and Methods: We retrospectively analyzed MRI scans of 57 unrelated pediatric TSC patients followed between 2014 and 2024 at a tertiary care center. Inclusion criteria included longitudinal imaging on the same 1.5T scanner, with T1w, T2w/FLAIR, and SWI sequences. CTs were classified into four MRI-based categories (A–D), with calcified tubers subdivided into micro-calcified and macro-calcified. Descriptive statistics, binomial tests, and Chi-square analyses were performed. Results: Calcified CTs were more prevalent than cystic ones. At baseline MRI, 63% of patients had calcified tubers (19% of all CTs), increasing to 77% at follow-up MRI (24% of all CTs). Micro-calcifications predominated at baseline MRI evaluation, though a significant proportion progressed to macro-calcifications over time. Calcified CTs always progressed from lower-grade lesions. Cystic tubers were rare (<1%). Longitudinal analysis showed significant variation in CTs with inner calcification count (p = 0.0000023), but not in CTs with cystic components (p = 0.42072). No significant genotype–radiological phenotype association emerged. Conclusions: Intralesional calcifications in CTs are dynamic and detectable with SWI. The inclusion of calcification patterns in CT classification could offer insights that may prove useful for future prognostic and risk-stratification frameworks in pediatric TSC. Full article

Ovarian cancer is the gynecologic malignancy that bears the highest mortality rate in the Western world. This is attributed to late diagnosis and limited therapeutic progress. Recent advances in molecular oncology have highlighted the pivotal role of epigenetic modifications—including DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and RNA methylation—in ovarian cancer development, progression, and treatment resistance. DNA methylation patterns affect key tumor suppressors and oncogenes, while histone modifications alter chromatin accessibility, influencing gene expression. Chromatin remodeling complexes, particularly the SWI/SNF complex, are frequently mutated in specific ovarian cancer subtypes, which is central in shaping their biological behavior. Non-coding RNAs, including microRNAs and long non-coding RNAs, further regulate tumor cell behavior and the immunosuppressive tumor microenvironment. Epigenetic profiles vary among histological subtypes and hold promise for biomarker development, early detection, prognosis, and therapeutic monitoring. Liquid biopsy approaches leveraging circulating tumor DNA methylation show diagnostic potential superior to conventional markers. Moreover, targeting epigenetic regulators—such as DNMT and HDAC inhibitors, EZH2 antagonists, and RNA-modifying enzymes—offers novel avenues for treatment, particularly in reversing chemoresistance and sensitizing tumors to immunotherapy. While promising, these strategies require further validation through clinical research to translate into effective clinical interventions. This review aims to summarize the current literature and highlights potential applications of epigenetic manipulation in day-to-day practice. Full article

Background: Chronological age is an imprecise proxy for cognitive aging. The Cognitive Age Delta (CAD)—the difference between predicted cognitive age and chronological age—offers a scalable, individualized marker of functional brain aging. We examined determinants of CAD in cognitively unimpaired (CU) adults stratified by Alzheimer’s disease (AD) and vascular biomarkers. Methods: We analyzed 177 CU participants from the Gipuzkoa Alzheimer Project (Basque Country, Northern Spain) classified as amyloid-negative/vascular-negative (CUA−V−, n = 140), amyloid-positive (CUA+, n = 23), or vascular-positive (CUV+, n = 14) using CSF and MRI criteria; vascular burden was defined as Fazekas ≥ 2 on T2-FLAIR or ≥4 microbleeds on SWI, excluding non-traumatic superficial siderosis and established ischemic lesions. MRI was used solely for vascular classification. Associations with demographic, genetic, lifestyle, and reserve measures were tested with General Linear Models. Results: CAD did not differ across biomarker groups (Kruskal–Wallis H(2) = 0.17, p = 0.91). Median (IQR) CAD values were 0.28 (−4.13, 4.69) for CUA−V−, −0.14 (−3.15, 2.87) for CUA+, and 0.77 (−2.22, 3.76) for CUV+, indicating comparable distributions. Higher vocabulary scores (proxy of cognitive reserve) related to a younger cognitive age in CUA−V− (β = −1.39, p < 0.001) and CUA+ (β = −2.08, p = 0.054). In CUA+, greater sedentary time—particularly computer-based sitting—was also associated with lower CAD (daily sitting β = −2.13, p = 0.009; workday computer sitting β = −2.32, p = 0.015). CAD showed no associations with CSF Aβ42, p-tau or t-tau, APOE ε4 load, or vascular risk factors (all p > 0.05). Conclusions: CAD captures interindividual resilience-related variability beyond classical AD biomarkers. Vocabulary, a marker of lifelong enrichment, emerged as a robust determinant of a younger cognitive age, while amyloid and vascular pathology exerted limited influence at preclinical stages. These findings support CAD as a sensitive, scalable endpoint for identifying protective factors and guiding personalized prevention in early Aging. Full article

Chronic musculoskeletal pain (CMP) is the leading global cause of disability and a major contributor to healthcare burden. Its pathogenesis reflects regenerative failure, driven by extracellular matrix (ECM) fibrosis, calcific deposition, mitochondrial dysfunction, and neuroimmune sensitization. Conventional pharmacological therapies such as NSAIDs, corticosteroids, and opioids offer only transient symptomatic relief while exposing patients to systemic complications. In contrast, energy-based, drug-free regenerative interventions directly address underlying pathology and restore physiological function. This Perspective synthesizes recent evidence (2020–2025) on three modalities that together form a regenerative triad: extracorporeal shockwave therapy (ESWT), high-intensity laser therapy (HILT), and ultrasound-guided mechanical needling with sterile water injection (SWI). ESWT promotes mechanotransduction, angiogenesis, and ECM remodeling; HILT enhances mitochondrial bioenergetics and downregulates inflammatory pathways; and SWI disrupts fibrosis and calcification while restoring neurovascular dynamics. Evidence from randomized controlled trials and meta-analyses supports moderate-to-high certainty (GRADE B–A–) for ESWT and HILT. SWI, initially supported by large observational cohorts and comparative studies, is now reinforced by a randomized comparative trial and meta-analyses of lavage effects, justifying an upgrade from moderate (B) to moderate-to-high certainty (B–A–). Risk of bias assessment using Cochrane RoB 2.0 and the Newcastle–Ottawa Scale (NOS) indicates overall low-to-moderate concerns across modalities. Together, these interventions integrate mechanistic biology with translational rehabilitation practice. This Perspective outlines their mechanistic foundations, clinical evidence, and alignment with the WHO decade of healthy ageing, offering a drug-free, mechanism-based framework for sustainable CMP management. Full article

Saltwater Intrusion (SWI) is threatening coastal archaeological sites, particularly in Crotone, southern Italy. The study area has been experiencing notable SWI due to over-pumping of groundwater, rising land subsidence, and climate change. Consequently, this study examines the applicability of polycaprolactone (PCL), a common biodegradable polymer, as a protective barrier for archaeological conservation. PCL films were synthesized via solvent casting and dried under controlled conditions. Physicochemical properties of the films were evaluated using six analytical techniques: (1) contact angle measurements for surface hydrophobicity, (2) Fourier-Transform Infrared Spectroscopy (FTIR) for chemical stability, (3) Scanning Electron Microscopy (SEM) for morphological characterization, (4) permeability testing for evaluating saltwater diffusion, (5) mechanical testing for tensile properties, and (6) biodegradability assays for degradation rates. All samples were evaluated at 0, 30, 60, and 90 days in natural seawater. Results from these tests indicate that unmodified PCL films exhibited moderate hydrophobicity, partial hydrolytic degradation, resistance to permeability, declining mechanical strength, and limited biodegradability over the testing period. Full article