Search Results (4,439)

Background: Obesity represents a major public health challenge worldwide and contributes substantially to the burden of type 2 diabetes and hypertension. While body mass index (BMI) is widely used in clinical practice, indices reflecting central adiposity may provide additional prognostic value. This study aimed to assess the prevalence of general and central obesity in an adult population across different age groups from Stara Zagora, Bulgaria, and to examine their associations with cardiometabolic outcomes and lifestyle factors. Methods: A quasi-representative cross-sectional study was conducted among 3512 adults (mean age 53.7 ± 14.9 years). Anthropometric indices, including BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Cardiometabolic outcomes included diabetes, hypertension, and their combined presence. Multicollinearity was assessed using the Variance Inflation Factor (VIF), and the discriminatory ability of indices was evaluated using Receiver Operating Characteristic (ROC) analysis and DeLong’s test. Results: The prevalence of overweight/obesity (BMI ≥25) was 68.4%, while central obesity (WHtR ≥0.5) affected 66.9% of participants. BMI demonstrated the highest discriminatory ability in this dataset for hypertension (AUC = 0.852) and diabetes (AUC = 0.796), significantly outperforming WC and WHR (p < 0.05). However, 24.4% of individuals with normal BMI exhibited high-risk central adiposity. Significant sex-specific differences were observed: short sleep duration (<6 h) was a strong predictor of obesity in women (aOR = 2.98), whereas smoking showed stronger associations in men. Age-stratified analyses revealed that while BMI stabilizes in the oldest age group (75–89 years), WHtR continues to increase, reflecting age-related redistribution of visceral fat. A strong protective effect of physical activity was observed, supported by quasi-complete separation in active subgroups. Conclusions: General and central obesity represent a substantial health burden in this urban population. While BMI remains a robust screening tool, the integration of WHtR enhances the identification of “hidden” cardiometabolic risk particularly in older adults and individuals with normal BMI. Given the quasi-representative nature of the sample, these findings are primarily generalizable to similar urban populations and may inform targeted regional public health strategies. Full article

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have revolutionized treatment for relapsed/refractory hematologic malignancies, targeting CD19 in B-cell neoplasms and BCMA in multiple myeloma, with response rates exceeding 80%. However, long-term risks, including therapy-related myeloid neoplasms, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are emerging 6–24 months post infusion, potentially linked to lymphodepleting chemotherapy, clonal hematopoiesis expansion, and inflammatory milieus. This FAERS pharmacovigilance analysis quantified MDS/AML reporting across seven FDA-approved CAR-T products to detect antigen-specific signals unattainable in pivotal trials with limited follow-up. Methods: Adverse event reports from FAERS (1 January 2013–10 February 2025) were queried for tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, obecabtagene autoleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel, focusing on MedDRA terms for MDS/AML. Duplicates and ambiguous cases were excluded. Disproportionality was assessed using reporting odds ratios (RORs; lower 95% CI >1 signaling significance), comparing CAR-T-event pairs to database background, with subgroup analyses by antigen target. Results: Among 14,093,557 reports, CAR-T products linked to 303 MDS (brexucabtagene autoleucel ROR 97.93 [72.18–132.87], n = 44; axicabtagene ciloleucel ROR 58.70 [50.34–68.44], n = 172) and 129 AML cases (axicabtagene ciloleucel ROR 22.89 [18.23–28.73], n = 76). Signals were consistent across CD19- and BCMA-directed agents, absent only for recently approved obecabtagene autoleucel. Conclusions: CAR-T therapies exhibit disproportionate MDS/AML reporting in FAERS, supporting class-wide late hematologic toxicity in pretreated patients with clonal hematopoiesis. Enhanced surveillance, baseline profiling, and marrow evaluation for cytopenias are warranted, balancing curative benefits. Full article

Asthma is a chronic respiratory disease characterized by airway hyperresponsiveness, obstruction, and persistent inflammation, arising from complex interactions among genetic, epigenetic, immune, and environmental factors. To elucidate the stage-specific molecular mechanisms underlying asthma progression, we constructed candidate genome-wide genetic and epigenetic networks (GWGENs) of human cells through large-scale biological database mining. Using a system order detection scheme, false-positive interactions were pruned to identify real GWGENs corresponding to three clinical stages of asthma: quiet, exacerbation, and follow-up. Core GWGENs were subsequently extracted from each real network using the principal network projection (PNP) method to highlight dominant regulatory structures and pathogenic pathways. Based on the inferred core networks, key stage-specific biomarkers were identified and further explored as potential drug targets. Drug–target relationships were investigated by integrating gene expression perturbation profiles from the Connectivity Map (cMap), comprising microarray data for 14,207 genes across 1327 compounds. This network-guided analysis enabled the qualitative design of multi-molecule drug combinations tailored to each disease stage. Our results suggest that asthma onset is associated with reduced innate immunity, increased disease susceptibility, and impaired endothelial barrier recovery influenced by microenvironmental factors such as cigarette smoke and lipopolysaccharides, together with genetic and epigenetic alterations. During the exacerbation stage, enhanced differentiation of T cells toward the T helper 2 lineage contributes to airway inflammation and tissue injury. In the follow-up stage, T helper 1–mediated responses are linked to mucus hypersecretion, airway obstruction, and sustained inflammation. Collectively, these findings demonstrate that a systems-level, network-based framework can uncover stage-specific pathogenic mechanisms of asthma and provide hypothesis-generating insights for network-informed drug repurposing strategies. Full article

Background/Objectives: Melioidosis, caused by Burkholderia pseudomallei, is a severe tropical infectious disease associated with high mortality in endemic regions. Early diagnosis remains challenging because conventional diagnostic methods, including culture, serological assays, and molecular techniques, have limitations in sensitivity, specificity, processing time, and accessibility in resource-limited settings. This review evaluates current diagnostic approaches and highlights the potential of short peptide biomarkers for improving melioidosis detection. Methods: A narrative literature review was conducted using four electronic databases (PubMed, Scopus, Web of Science, and Google Scholar) covering publications from 2000 to 2024. Relevant studies were identified using predefined keywords related to melioidosis diagnostics, biomarkers, and peptide-based approaches, and were screened based on relevance to diagnostic methods and peptide biomarker development in Burkholderia pseudomallei. Results: Several biomarkers have been investigated for melioidosis diagnostics, including capsular polysaccharide (CPS), type III secretion system 1 (TTS1), and other virulence-associated proteins such as Hcp1 and BPSS1187. Among these, CPS and TTS1 are highly conserved and specific targets widely used in molecular and antigen-based detection methods. Short peptide epitopes derived from these antigens demonstrate promising advantages over whole proteins, including improved stability, high specificity, easier synthesis, and reduced production costs. Advances in epitope prediction technologies and peptide-based biosensors have further expanded the potential applications of short peptides in rapid diagnostic platforms, including ELISA, lateral flow immunoassays, and biosensor-based detection systems. Conclusions: Short peptide–based biomarkers represent a promising strategy for developing rapid, sensitive, and cost-effective diagnostic tools for melioidosis, particularly in endemic and resource-limited settings. Full article

Background: Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported and to assess consistency of dosing patterns across published studies. Methods: A literature search was conducted in PubMed, Wiley/Cochrane Library, and EBSCO/CINAHL using a structured search strategy informed by PRISMA guidelines. Studies published within the last 10 years reporting on onabotulinumtoxinA treatment in post-stroke upper-limb spasticity with muscle-specific dosing data were included. Studies not providing muscle-level dosing or not allowing extraction of post-stroke upper-limb data were excluded. Data were summarized descriptively and compared across studies. Results: Twenty-seven full-text articles were assessed, and five studies met the inclusion criteria. Muscle-specific dosing was consistently reported for commonly treated muscles such as biceps brachii and wrist and finger flexors, whereas other muscles were less frequently targeted. Variability in dosing between studies was observed, particularly in multicenter real-world datasets. Standardized high-dose protocols contrasted with individualized dosing strategies, which generally showed more moderate dose ranges. Expert recommendations often suggest higher doses than those observed in routine clinical practice. Conclusions: Muscle-specific dosing of onabotulinumtoxinA in post-stroke upper-limb spasticity is reported infrequently, and substantial variability exists between studies and clinical practice. Standardized reporting of muscle-level dosing and its relationship to baseline spasticity severity is needed to improve clinical applicability and reproducibility. Full article

In remote sensing image oriented object detection tasks, weakly supervised learning methods based on horizontal bounding boxes have attracted much attention due to their lower annotation costs compared to fully supervised methods. However, remote sensing images, characterized by complex backgrounds, exhibit a wide range of target scales and diverse geometric characteristics across target categories. Existing methods exhibit inadequate exploitation of background and angular information under weak supervision, resulting in compromised perception of dense and high-aspect-ratio targets. Neglecting the imbalance in angle estimation samples further leads to excessively low detection accuracy for few-shot categories. To address the aforementioned issues, this paper proposes a Geometry-Aware Enhancement Network (WSOOD-GAEN) for weakly supervised oriented object detection tasks. First, in the backbone network stage, a channel-space deformable attention module (DAE-ResNet) was constructed. Through deformable sampling and screening of key regions, feature extraction has both morphological adaptability to complex shapes and semantic discriminability of key features in complex backgrounds. Secondly, in the feature pyramid stage, an Angle-Guided Feature Pyramid Network (AG-FPN) is proposed. This module dynamically applies rotation transformation to the sampling offsets of deformable convolutions, thereby enhancing the feature representation of objects with different orientations and scales. Furthermore, an adaptive geometric perception loss (AGL) was designed. Based on the geometric characteristics of different categories, it automatically learns differentiated rotation and flip consistency weights, thereby improving the prediction accuracy of small sample categories. Experiments on the DOTA-v1.0, HRSC, and RSAR datasets validate our approach. Specifically, under the AP75 evaluation metric, the proposed method outperforms existing weakly supervised methods by 1.51%, 9.86%, and 3.28%, respectively. Full article

Background: Midkine (MDK), a secreted heparin-binding growth factor, is involved in tumor progression and metastasis. While serum MDK is widely recognized as a potential prognostic biomarker for colorectal cancer (CRC), its specific functional role and underlying mechanisms in CRC development are not fully understood. Methods: The four publicly available CRC microarray datasets—GSE41258, GSE44076, GSE81558, and GSE117606—along with TCGA-COAD and TCGA-READ datasets and their associated clinical data were obtained. MDK expression was measured at both the mRNA and protein levels using quantitative real-time PCR (qRT-PCR) and Western blotting. To investigate its oncogenic functions, a comprehensive set of assays was performed: transwell and wound healing assays for invasion and migration; CCK-8 and colony formation assays for proliferation; and tail vein/spleen injection models combined with xenograft models to study metastasis and tumor growth in vivo. To uncover underlying mechanisms, Western blotting was used to examine the involvement of epithelial–mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results: MDK is significantly overexpressed in CRC tissues and cells compared to normal tissues and cells. Notably, patients with high MDK levels show poorer overall survival (OS). Overexpression of MDK increases CRC invasion, migration, proliferation, and metastasis both in vivo and in vitro, while its knockdown reverses these effects. Mechanistically, MDK activates the PI3K/AKT pathway, leading to increased AP2A1 expression and promotion of EMT in CRC. Conclusions: MDK promotes invasion, migration, proliferation, metastasis, and EMT in CRC cells through the PI3K/AKT pathway by inducing AP2A1 expression, which could serve as a diagnostic marker. The PI3K inhibitor LY294002 significantly reduces AP2A1 levels and inhibits MDK-induced malignant behaviors. Targeting MDK-related signaling pathways may offer new strategies for CRC treatment. Full article

Background/Objectives: Type 2 diabetes mellitus (DM) commonly coexists with heart failure (HF) and is associated with increased cardiovascular (CV) morbidity and mortality. Although dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used for glycemic control, their CV safety in patients with established HF, particularly across HF phenotypes, remains uncertain. To evaluate the association between DPP-4 inhibitor use and 6-month CV mortality in patients with DM and HF, and to assess whether this association differs across HF phenotypes: HF with preserved ejection fraction (HFpEF), HF with mildly reduced ejection fraction (HFmrEF), HF with reduced ejection fraction (HFrEF). Methods: We conducted a retrospective cohort study at King Abdulaziz Medical City from January 2017 to December 2024 that included adults with DM and echocardiographically confirmed HF. Patients receiving DPP-4 inhibitors were compared with non-users. The primary outcome was 6-month CV mortality. Propensity score overlap weighting targeting the average treatment effect in the overlap population was applied to balance baseline characteristics. Weighted logistic regression with interaction terms was used to assess effect modification by HF phenotype. Results: Among 3435 patients (median age 69 years; 51.3% female), 1921 (55.9%) received a DPP-4 inhibitor, predominantly sitagliptin. In unadjusted analyses, CV mortality was numerically lower among DPP-4 inhibitor users across HF phenotypes. However, after overlap weighting, CV mortality was similar between users and non-users within HFpEF (7.1% vs. 8.0%; OR 0.88, 95% CI 0.51–1.52; p = 0.646), HFmrEF (2.6% vs. 5.0%; OR 0.50, 95% CI 0.09–2.86; p = 0.436), and HFrEF (6.4% vs. 6.4%; OR 1.00, 95% CI 0.48–2.07; p = 0.992). No significant interaction was observed between DPP-4 inhibitor use and HF phenotype (interaction p > 0.05). Conclusions: In this large real-world cohort of patients with DM and established HF, DPP-4 inhibitor use was not associated with increased or reduced 6-month CV mortality after robust adjustment. The neutral association was consistent across HF phenotypes, supporting the CV safety of DPP-4 inhibitors, predominantly sitagliptin, in contemporary HF management. Full article

Background/Objectives: Childhood hearing loss (HL) affects auditory, linguistic, and social development. Alongside conventional rehabilitation, music-based interventions have gained increasing attention for their potential to support both auditory and non-auditory domains. This narrative review aims to summarize current evidence on the use of music-based interventions in children with HL. Methods: A narrative review of the literature was conducted, examining studies involving pediatric cochlear implant or hearing aid users. Publications were categorized into three main areas: musical auditory perception, musical training, and music therapy. Results: Studies on musical auditory perception demonstrate persistent limitations in pitch and timbre perception in children with HL, while rhythmic abilities appear relatively preserved. Musical training interventions, particularly those targeting rhythm, have been associated with improvements in auditory perception, linguistic processing, and selected cognitive skills, although parental involvement and long-term designs remain limited. Existing literature on music therapy is scarce but suggests potential benefits extending beyond auditory skills to emotional regulation, social interaction, and quality of life. Conclusions: Music-based interventions represent a promising complementary approach in pediatric hearing rehabilitation. While musical training is more widely studied, music therapy is still underrepresented despite its holistic focus. Further structured studies are needed to define standardized protocols and outcome measures for music therapy in children with HL. Full article

Signals of opportunity (SoO) enable emission-free passive sensing, but low Earth orbit (LEO) satellite illumination with unmanned aerial vehicle (UAV) array receivers exhibits rapid geometry variation. As a result, the received phase evolves in a space–time coupled manner, and the array snapshots become nonstationary even within one coherent processing interval (CPI), degrading conventional stationary-snapshot direction-of-arrival (DOA) estimators. This paper proposes a decomposition-based sparse reconstruction with successive interference cancellation (D-SR-SIC) framework for dynamic DOA estimation in LEO SoO UAV passive sensing. The proposed estimator leverages a sparse-reconstruction signal model and is implemented via a computationally efficient decomposition-based search-and-cancel procedure. A short-CPI parameterized space–time phase model captures the common motion-induced phase history and the time-varying steering drift; the coupled multi-parameter estimation is decomposed into two low-dimensional correlation searches followed by least-squares amplitude estimation and multi-target peeling. Optional local refinement and multi-beam pre-screening improve robustness to off-grid mismatch, near–far interference, and wide field-of-view operation. Simulations show that the proposed method achieves about 0.11${}^{\circ }$ DOA root-mean-square error (RMSE) at $-20$ dB signal-to-noise ratio (SNR) in a representative highly dynamic setting. Full article

Bacillus and Paenibacillus species are common and widely distributed microorganisms in food systems, often implicated in food spoilage and quality issues. Bacillus subtilis, in particular, has been associated with gas production and package bulging in seasoned foods. In this study, we developed a rapid and visual detection method for Bacillus subtilis by integrating (Recombinase Polymerase Amplification) RPA with (Clustered Regularly Interspaced Short Palindromic Repeats) CRISPR/Cas12a technology (designated as RPA-CRISPR/Cas12a). Specific RPA primers and probes were designed based on the conserved gyrB gene of Bacillus subtilis. Two sets of crRNA were designed according to the number of T-rich PAM sites on the RPA-amplified target sequence, and the reaction conditions were optimized in combination with the CRISPR/Cas12a trans-cleavage detection technology. Under optimized conditions, the crRNA3 guide (with a TT-rich PAM site) demonstrated superior cleavage efficiency compared to crRNA2 (TTT-rich PAM), while crRNA1 (TTTT-rich PAM) showed no activity. The assay achieved a detection limit of 150 pg/μL for genomic DNA and 5.5 CFU/mL for bacterial suspensions within 10 min at 37 °C. The method exhibited high specificity and sensitivity, providing a robust tool for early and on-site detection of Bacillus subtilis in food products. Full article

Background/Objectives: Atopic dermatitis (AD)-related skin inflammation involves the release of cytokines and chemokines from keratinocytes; therefore, keratinocyte-based models are widely used to evaluate the anti-inflammatory potential of botanical extracts. This study examined the relationship between phytochemical profiles and anti-inflammatory potential of baobab fruit 30% and 70% ethanol extracts (BE-30 and BE-70, respectively) in a TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocyte model. Methods: The anti-inflammatory effects of both extracts were evaluated by measuring cytokine and chemokine secretion in TI-stimulated HaCaT cells. Phytochemical characterization was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and targeted high-performance liquid chromatography (HPLC). Results: Both extracts were non-cytotoxic. TI-stimulation markedly increased interleukin (IL)-6, IL-8 and monocyte chemotactic protein (MCP)-1 secretion, while BE-30 and BE-70 significantly reduced all three mediators in a dose-dependent manner. At comparable doses, BE-70 exhibited greater inhibition than BE-30. BE-30 showed a non-monotonic IL-8 response at low concentrations, whereas BE-70 consistently reduced IL-8 in a dose-dependent manner. LC–MS/MS profiling revealed a polyphenol-rich composition, including flavonol glycosides and related phenolic compounds. HPLC confirmed the presence of four marker analytes (procyanidin B2, epicatechin, rutin and tiliroside), which were enriched in BE-70. The content of these four polyphenols was 1.94-fold higher in BE-70. Conclusions: Baobab fruit extracts exhibit anti-inflammatory activity associated with polyphenols. These findings suggest that they could be used as analytical standards and in dermatological applications. Full article

Background: Tartary buckwheat (Fagopyrum tataricum) serves as an excellent model for studying plant water adaptation mechanisms due to its exceptional drought tolerance. While aquaporins (AQPs) mediate the transmembrane transport of water and solutes in plants, their fine-tuned regulatory networks underlying stress resilience in Tartary buckwheat remain largely elusive. Methods: Here, we combined bioinformatics and transcriptomics to systematically identify 30 highly conserved FtAQP genes at the genome-wide level. Results: Cross-validated by qRT-PCR, our analysis revealed their distinct expression patterns across different organs. Based on our transcriptomic data, we hypothesize that FtAQP family members potentially participate in a coordinated whole-plant water management network through differential spatiotemporal expression. Specifically, the robust transcription of FtAQP8, FtAQP12, and FtAQP28 in roots is associated with the initial water uptake process. As water undergoes long-distance transport, the synergistic upregulation of FtAQP13, FtAQP17, FtAQP20, and FtAQP29 in the stem suggests a potential role in facilitating critical lateral water flow. Furthermore, during reproductive development, FtAQP27 exhibits extreme tissue specificity in floral organs, implying its possible involvement in maintaining local osmotic homeostasis. Furthermore, the promoter regions of FtAQPs are highly enriched with cis-acting elements responsive to light, abscisic acid (ABA), and cold stress, suggesting they are intimately regulated by a coupling of endogenous phytohormones and environmental cues. Conclusions: Ultimately, this study provides valuable insights into the potential molecular basis of multidimensional water regulation in Tartary buckwheat, and identifies candidate genetic targets for improving water use efficiency in dryland agriculture through the precise manipulation of aquaporins. Collectively, while these observational findings provide valuable predictive models, future in vivo experimental validations are required to confirm their exact biological functions. Full article

Entropic soft-min operators are widely used to obtain smooth approximations of minimum and argmin mechanisms in optimization, machine learning, and reinforcement learning. The quality of this approximation is controlled by an inverse temperature parameter that governs the trade-off between smoothness and fidelity, yet its selection is usually based on global heuristics or worst-case bounds that do not account for the geometry of the candidate cost vector. This study investigates the calibration of the inverse temperature parameter from a geometry-aware perspective, with explicit guarantees on the approximation error between the entropic soft-min and the exact minimum value. After establishing the structural properties of the relaxation error, including monotonicity with respect to the inverse temperature and its dependence on the geometry of the near-optimal set, we introduce a conformal calibration rule that selects the smallest inverse temperature, ensuring that a prescribed upper quantile of the approximation error remains below a target tolerance with distribution-free finite-sample validity. The resulting selector adapts to the geometry distribution represented in the calibration population and provides a principled alternative to mean-based and worst-case tuning rules. Numerical experiments, including geometry-controlled benchmarks and a contextual bandit setting illustrating the impact of geometry-aware calibration on decision-making under estimated action values, show that the proposed method accurately tracks oracle calibration temperatures, preserves the desired operator-level coverage, and makes explicit how geometric heterogeneity governs the effective sharpness required by the soft-min approximation. Additional shifted evaluations illustrate the role of exchangeability in the validity guarantee and the consequences of transferring temperatures across populations with different near-optimal geometries. Full article

Background/Objectives: AP-2δ, encoded by TFAP2D, is one of the least characterized members of the AP-2 transcription factor family, although available evidence suggests biologically relevant roles in lung cancer that have not yet been thoroughly examined. The aim of the present study was to provide an integrated characterization of AP-2δ/TFAP2D in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: LUAD and LUSC data were obtained from The Cancer Genome Atlas. The analysis comprised the expression profiling of AP-2δ target genes, survival-guided TFAP2D stratification, clinical profiling, differential expression and intersection analyses, methylation-derived chromatin compartment profiling, TFAP2D-associated cofactor rewiring, and genome-wide enrichment of AP-2δ targets. In parallel, pocket prioritization was performed using an AlphaFold model of AP-2δ with cross-tool consensus mapping. Results: TFAP2D stratification delineated biologically-distinct states in both histological subtypes (LUAD and LUSC). AP-2δ target genes showed subtype-specific expression patterns and functional organization. The consistent survival association was observed for progression-free interval rather than uniformly across all endpoints. Clinical profiling was more closely associated with molecular subtype composition than broad clinicopathological differences. Differential expression analyses identified both shared and histology-dependent programs associated with TFAP2D. In the chromatin-compartment analysis, LUSC showed a broader and more coherent footprint, whereas LUAD displayed more selective cofactor rewiring. Structure-based analysis prioritized a small set of reproducible candidate pockets concentrated within ordered regions of the TF_AP-2 domain. Conclusions: AP-2δ marks biologically meaningful but histologically non-uniform regulatory states in lung cancer. These findings provide an integrated framework for understanding TFAP2D-dependent regulation in LUAD and LUSC, highlighting AP-2δ as a candidate for future mechanistic and translational investigation. Full article