Search Results (488)

Land-use changes and unsustainable agricultural practices can alter soil properties, thereby increasing soil erodibility and the risk of land degradation. This study assessed the impact of converting forest to grassland and cropland on soil erodibility in the Kolubara watershed (western Serbia) using soil samples collected at two depths (0–15 and 15–30 cm). Soil erodibility was determined using the following indicators: clay ratio (CR), soil structure stability index (SSI), mean weight diameter (MWD), soil organic carbon cementing agent index (SCAI), saturated hydraulic conductivity (Ks), the K-factor, and a comprehensive soil erodibility index (CSEI) calculated by a weighted summation method. Most soil indicators differed significantly among land uses. Forest soils exhibited the highest MWD (2.94 mm), Ks (1119.15 mm h⁻¹), and SSI (5.86), whereas the lowest values were recorded in cropland soils (1.64 mm, 29.68 mm h⁻¹, and 3.07, respectively). In contrast, cropland soils showed the highest CR (0.005) and K-factor (0.038 t ha h ha⁻¹ MJ⁻¹ mm⁻¹), while the lowest values occurred in forest soils (0.003 and 0.032 t ha h ha⁻¹ MJ⁻¹ mm⁻¹). The significantly higher CSEI in cropland (0.75) compared with forest soils (0.62) corresponded to reduced soil structural stability and lower organic matter–related indicators. Grassland soils generally showed intermediate values for most indicators. Soil depth significantly influenced only SSI and Ks. Differences in soil erodibility among land uses are closely related to soil physical and chemical properties, particularly soil organic carbon and soil structure-related properties (total porosity and bulk density). These findings emphasize the substantial impact of land-use change on soil erodibility and highlight the need to implement effective soil conservation practices to improve soil stability and mitigate erosion. Full article

Atopic dermatitis (AD) is a common chronic inflammatory condition of the skin that has increased dramatically over the past decade and significantly impacts individual quality of life. Corticosteroids are still the primary therapy for AD, but there are limitations to their continued use due to potential adverse effects, particularly when used in sensitive areas. Topical calcineurin inhibitors (CNIs), such as tacrolimus and pimecrolimus, are available as a safe, steroid-sparing alternative that directly inhibit calcineurin-mediated activation of T cells and have been shown to be efficacious according to varying clinical study designs including randomized controlled trials, registry studies and meta-analyses. Although there was controversy regarding the safety of CNIs subsequent to the FDA’s black-box warning in 2006, the preponderance of evidence supports their continued safety when used as directed. In contrast to biologics and JAK inhibitors, CNIs occupy an inherently unique therapeutic niche for use in pediatric patients, have demonstrated historical efficacy, and can provide localized affordable treatment in sensitive areas including the face, eyelids and intertriginous surfaces. Furthermore, the role of CNIs in the context of precision dermatology continues to be defined through new innovations including barrier-repair strategies used in combination with topical medications, microneedle systems, and nanocarrier formulations. Hence, the role of CNIs in the current AD treatment paradigm is crucial and lies at the interface between topical corticosteroids and systemic immunomodulatory agents. The narrative review discusses recent advances in formulation strategies, combination approaches, and targeted delivery systems, underscoring how CNIs continue to bridge established practice and emerging therapeutic innovation in AD. Full article

Background/Objectives: Contrast-enhanced (CE) breast MRI is highly sensitive for evaluating breast cancer extent and response to neoadjuvant therapy (NAT) but requires intravenous administration of gadolinium-based contrast agents (GBCA), increasing cost, time, patient discomfort, and health concerns. This study explored the feasibility of reducing GBCA use in treatment monitoring using a deep learning (DL) model to synthesize CE-MRI from non-contrast MRI. Methods: This IRB-approved retrospective pilot study evaluated women with breast cancer enrolled in an ongoing trial using serial MRI to monitor NAT prior to surgery. A pre-trained DL model was used to synthesize CE-MRI from T1-, T2-, and diffusion-weighted MRI. Changes in tumor volume at early (post-1-cycle NAT) and mid-treatment were measured on synthetic and acquired CE-MRI. Performance for predicting residual cancer burden (RCB) class 0/1 was evaluated using AUC and compared with DeLong’s test. Results: 27 women were included in the study (median age, 47 years [range = 28–75]); 14 (52%) achieved RCB class 0 and six (22%) achieved class 1. Synthetic CE-MRI-derived tumor volumes showed strong correlation with those from acquired CE-MRI at pre-treatment ($\rho$ = 0.92, p < 0.001) and early treatment ($\rho$ = 0.83, p < 0.001), but lower agreement at mid-treatment ($\rho$ = 0.57, p = 0.002). Change in tumor volume on synthetic CE-MRI was numerically similar to acquired CE-MRI for predicting RCB class 0/1 vs. 2/3 at both early (AUC = 0.84 vs. 0.86, p = 0.83) and mid-treatment (AUC = 0.73 vs. 0.75, p = 0.80). Conclusions: Synthetic CE-MRI demonstrates preliminary feasibility as a non-contrast surrogate for predicting favorable outcomes (RCB class 0/1) in this pilot study, but inconsistencies in tumor volume measurement vs. acquired CE-MRI warrant further model refinement and validation. Full article

Objectives: Contrast-enhanced magnetic resonance imaging (CE-MRI) plays an important role in the diagnosis, treatment monitoring, and follow-up of brain tumors. However, the use of gadolinium-based contrast agents (GBCAs) is limited in patients with contraindications, such as severe renal impairment or situations requiring repeated examinations. This study aimed to develop a diffusion model-based Difference-Aware Guided Control Network (DAGCN) for synthesizing high-quality contrast-enhanced T1-weighted MRI (T1-CE) from non-contrast T1-weighted images in combination with an auxiliary sequence. Methods: Using the BraTS 2021 dataset, we proposed a two-stage generative framework that first localizes lesion-related enhancement cues and then guides image synthesis. In the first stage, a Difference-Aware Fusion and Prediction (DAFP) module was designed to extract complementary information from non-contrast T1-weighted images and an auxiliary sequence (T2-weighted or FLAIR) through dual-branch feature extraction and cross-modal channel attention fusion, followed by prediction of a lesion-related discrepancy map. In the second stage, the predicted discrepancy map was concatenated with the original T1-weighted images and introduced into a ControlNet-guided diffusion model to constrain the reverse denoising process and generate the target T1-CE image. Model performance was evaluated by visual comparison, quantitative metrics including peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), visual information fidelity (VIF), and normalized cross-correlation (NCC), as well as blinded radiologist scoring of image quality (IQ), clinical replaceability (IC), contrast enhancement (CE), and lesion conformity (CF). Results: DAGCN generated synthetic T1-CE images with preserved global anatomical structure and faithful local lesion enhancement without the need for contrast agent administration. Compared with baseline methods, DAGCN achieved the highest PSNR and NCC under both T1 + T2 and T1 + FLAIR settings, while showing competitive SSIM and VIF performance. Visual comparison and radiologist-based subjective evaluation further indicated improved lesion-focused enhancement fidelity and reduced false-positive enhancement. Among the two auxiliary sequence settings, the T1 + FLAIR configuration provided more specific lesion localization and cleaner background suppression than the T1 + T2 configuration, particularly by reducing interference from cerebrospinal fluid signals. Conclusions: The proposed DAGCN framework enables the synthesis of clinically informative contrast-enhanced-like MRI from non-contrast multi-sequence inputs and may provide a promising alternative for patients in whom gadolinium administration is contraindicated or should be avoided. In particular, the FLAIR-guided setting showed advantages in lesion specificity, background cleanliness, and overall diagnostic quality. Full article

Therapeutic cancer vaccines represent a rational immunotherapeutic strategy aimed at inducing tumor-specific adaptive immune responses in patients with established malignancies. In contrast to prophylactic vaccines, these approaches must function within immunosuppressive tumor microenvironments characterized by antigenic heterogeneity, immune dysfunction, and dynamic tumor evolution. Effective vaccine design requires the integration of three essential components: the selection of appropriate tumor-associated or tumor-specific antigens, efficient delivery platforms that enable antigen presentation, and adjuvant systems that promote robust T-cell priming and expansion. Initial clinical investigations in B-cell malignancies and multiple myeloma demonstrated that idiotype-based vaccines can elicit tumor-specific immune responses. However, durable clinical benefit has been inconsistent, reflecting limitations in antigen selection, suboptimal immunogenicity, and tumor-mediated immune evasion. Over the past decade, advances in tumor genomics, next-generation sequencing, and immune monitoring have enabled the development of next-generation vaccine platforms, including dendritic cell-based approaches, personalized neoantigen vaccines, and mRNA-based technologies. Emerging evidence suggests that vaccine efficacy is highly dependent on disease context. Biologically favorable settings such as minimal residual disease (MRD) and post-transplant immune reconstitution provide reduced tumor burden and improved immune competence, thereby enhancing the likelihood of effective immune priming. In parallel, combination strategies incorporating immune checkpoint inhibitors, immunomodulatory agents, and cellular therapies are increasingly being explored to overcome tumor-induced immunosuppression. This review synthesizes current knowledge of therapeutic cancer vaccines in B-cell malignancies and multiple myeloma, with emphasis on immunologic mechanisms, antigen selection, vaccine platforms, and clinical evidence. We further propose a conceptual framework integrating tumor biology, immune context, and combination strategies to guide the rational development of next-generation vaccine therapies. Full article

The genus Burkholderia encompasses both plant pathogenic and beneficial species, yet the genomic determinants underlying this lifestyle divergence remain poorly understood. Using 16S rRNA sequencing of 100 rice cultivars, our companion study demonstrated that resistant varieties are enriched in beneficial Burkholderiaceae, leading to the isolation of three phenotypically contrasting strains. Here, we present comparative genomic analyses of non-pathogenic biocontrol strain Burkholderia vietnamiensis J14EpLeaf2 and pathogenic strains Burkholderia gladioli A1EpSeed5 and Burkholderia cepacia J14Eple. Pathogenic strains possess significantly larger genomes (8.36–8.46 Mb) enriched in mobile genetic elements compared to the streamlined 6.95 Mb genome of B. vietnamiensis. CAZyme analysis revealed broader repertoires of glycoside hydrolases and polysaccharide lyases in pathogens, consistent with enhanced plant cell wall degradation. B. gladioli possesses a complete T3SS and expanded T6SS with 301 predicted effectors, while B. cepacia lacks structural T3SS genes but harbors 271 candidate effectors predicted to be secreted via alternative secretion pathways, compared to 180 in B. vietnamiensis. Notably, B. cepacia harbors cystic fibrosis-associated markers (cable pili, ZmpA/ZmpB), raising significant biosafety concerns that preclude its agricultural application. LC-MS validated IAA, ornibactin, and AHL production in B. vietnamiensis, supporting its plant growth-promoting and biocontrol functions. Computational PPI networks predicted distinct interaction landscapes requiring experimental validation. This study provides a genomic framework for distinguishing pathogenic from beneficial Burkholderia and supports B. vietnamiensis as a safe biocontrol agent while cautioning against B. cepacia J14Eple. Full article

This study examines how urban transportation systems influence the spatial spread of infectious diseases by developing a modified Susceptible–Exposed–Infected–Recovered (SEIR) model with explicit intercity travel dynamics. The model distinguishes between two mobility mechanisms: travel volume, represented by the departure rate g, and travel speed, represented by the arrival rate $\alpha$. Using the next-generation matrix (NGM) approach, we derive the basic reproduction number $R_0$ and analyse how within-city and transit-phase transmission contribute to epidemic spread. The results show that travel volume and travel speed affect mobility-driven transmission through distinct mechanisms. Increasing g increases the number of travelers entering the transit system and therefore amplifies the aggregate number of transit-mediated infections, although the per-capita transit reproduction expression is governed primarily by $\alpha$ and ${\beta }_d^T$ under the reduced next generation matrix formulation formulation. By contrast, increasing $\alpha$ shortens the time spent in transit, reduces the exposure window during travel, and lowers the per-capita contribution of transit-based infection to $R_0$. Numerical simulations illustrate these effects and support the conclusion that reducing travel volume can mitigate intercity epidemic spread by decreasing the number of potentially exposed travelers. Comparative case studies for Brazil, New Zealand, China, and Algeria are used to evaluate the model under different epidemiological settings and socioeconomic contexts. These socioeconomic indicators are treated as contextual background rather than as direct inputs to the mathematical model. The qualitative predictions of the ordinary differential equation (ODE) model are further cross-validated using an agent-based simulation implemented in NetLogo. Overall, the study shows that separating travel volume from travel speed provides a more precise understanding of mobility-driven disease transmission and can support the design of targeted travel-related control measures. Full article

Purpose: Myocardial iron overload has been demonstrated to have a heterogeneous distribution. A segmental T2* CMR approach, with correction factors applied to account for artifacts, has been demonstrated to be feasible and has permitted a reduction in cardiac morbidity and mortality, by better capturing the heterogeneous distribution of myocardial iron overload. To the best of our knowledge, commercially available software does not provide a segmental T2* technique. Our aims were to prospectively examine a large population of healthy volunteers, stratified by sex and age, using the Black Blood MEGE T2* mapping technique, to obtain normative values of the myocardium, to assess their relationship with physiological variables, and to fix correction factors for a segmental approach by using a commercially available software. Methods: Fifty healthy subjects (M:F = 1:1, 20–69 years) underwent CMR without a contrast agent. Segmental T2* values were obtained using cvi42 software; global values were the mean. Inter-study, and intra- and inter-operator reproducibility were assessed to confirm the stability of the acquired data. The association of T2* values with physiological characteristics, and myocardial wall thickness were assessed. The fluctuation of all segments versus the mid-septum was calculated to obtain a correction factor for each segment for the software used. Regional T2* differences were examined. A p-value <0.05 was considered statistically significant. Results: Twenty-five males and females, five for each decade (mean age 43 ± 13.8 years), were included. The native T2* values in all subjects averaged at 34.03 ± 6.65 ms (range 29.9–37.9 ms). Reproducibility analyses showed good correlations between the various datasets (ICC > 0.80). A weakly negative correlation was observed between age and T2* (p = 0.04). Segmental correction factors were developed and found to be significantly different from correction factors developed by non-commercially available software on non-state-of-the-art technology for sequences and scanners. Conclusions: Age-specific normative values and higher normal cut-off values than the conservative 20 ms are recommended to avoid systematic biases in the identification of pathological findings. Moreover, the correction factors developed by using the most reproducible Black Blood MEGE sequences and a commercially available software on a scanner of the current era could be a significant step toward spreading a more sensitive T2* segmental approach in the clinical arena worldwide. Full article

Metal–organic frameworks (MOFs) possess unique structural tunability, abundant coordination sites, and outstanding biosafety, rendering them highly advantageous for the development of high-performance magnetic resonance imaging (MRI) contrast agents. In light of the significant advancements in MOF-derived theranostic platforms, a comprehensive overview focusing on their classification and clinically oriented applications is urgently required. This review provides an in-depth examination of various categories of MOF-derived contrast agents, including T1, T2, dual-mode, ratiometric and 19F imaging systems, and analyzes the correlation between structural characteristics and imaging performance. Furthermore, it highlights typical MRI-guided therapeutic applications, such as those related to atherosclerosis, bacterial infections, and cancer immunotherapy. The review systematically addresses existing challenges, including issues related to biodegradability, metabolic behavior, and biosafety. It also summarizes the rational design principles for novel MOF contrast agents, aiming to facilitate their transition from fundamental research to clinical applications. Full article

Decidualization in the human endometrium is not merely a hormone-dependent differentiation process; rather, it represents a multilayered adaptive program characterized by the tight integration of immune regulation, metabolic reprogramming, and cellular stress responses. In this review, endoplasmic reticulum (ER) stress and the associated unfolded protein response (UPR) are proposed as central regulatory mechanisms governing this process. Triggered by increased protein synthesis and secretory demand, UPR activation under physiological conditions preserves proteostasis and supports the secretory capacity of stromal cells. In contrast, chronic or dysregulated activation leads to a maladaptive response characterized by apoptosis, inflammation, and metabolic dysfunction. UPR signaling pathways shape immune tolerance through their effects on macrophage polarization, uterine natural killer (uNK) cell function, and T cell balance. At the metabolic level, adenosine monophosphate-activated protein kinase (AMPK) regulates cellular adaptation through bidirectional interactions with mitochondrial function and redox homeostasis. Within this framework, the ER stress–immune–metabolic axis operates not as a linear pathway but as a dynamic network incorporating multiple feedback loops, thereby constituting a critical threshold mechanism that determines the success of decidualization. Disruption of this axis provides a shared mechanistic basis for pathologies such as recurrent implantation failure, pregnancy loss, and preeclampsia. From a therapeutic perspective, agents including chemical chaperones, UPR modulators, AMPK activators, and anti-inflammatory compounds hold translational potential by targeting these pathological feedback circuits. However, key knowledge gaps remain, particularly regarding the cell type-specific and temporal regulation of ER stress, the molecular boundaries defining the transition from adaptive to pathological states, and interspecies differences. Future studies employing single-cell omics approaches and functional in vivo models will be essential to elucidate the dynamic organization of this axis and to enable the development of targeted and personalized therapeutic strategies. Full article

Background: Neuroendocrine neoplasms are frequently diagnosed after the detection of liver metastases, often when the primary tumor remains occult. Accurate non-invasive differentiation of neuroendocrine liver metastases (NELMs) from other focal hepatic lesions is therefore crucial. This study aimed to characterize the magnetic resonance imaging (MRI) features of NELMs using hepatocyte-specific contrast agents and to identify a potential radiologic “signature” that may suggest a neuroendocrine origin. Methods: This retrospective study included three cohorts: patients with histologically confirmed NELMs (n = 51; 146 lesions), patients with colorectal cancer liver metastases (n = 18; 46 lesions), and patients with benign hepatic hemangiomas (n = 28; 51 lesions). All subjects underwent standardized liver MRI with Gd-EOB-DTPA. Lesions were evaluated for size, diffusion-weighted imaging characteristics, apparent diffusion coefficient values, arterial-phase enhancement, T2-weighted signal, hepatobiliary-phase appearance, and hemorrhagic components. Statistical analyses included univariate and multivariate testing and receiver operating characteristic curve analysis. Results: NELMs commonly demonstrated arterial hyperenhancement, diffusion restriction, and variable T2 and hepatobiliary-phase signal heterogeneity. Compared with colorectal metastases and hemangiomas, NELMs showed distinctive patterns, particularly higher rates of hepatobiliary-phase heterogeneity and arterial enhancement. Lesion size, ADC metrics, T2 heterogeneity, and hemorrhage were significant discriminators. Conclusions: Hepatocyte-specific MRI enables identification of characteristic imaging features of NELMs. An integrated assessment of morphologic, diffusion, and hepatobiliary-phase findings may facilitate early recognition of neuroendocrine metastases, even when the primary tumor is unknown, improving diagnostic confidence and clinical management. Full article

The emergence of antibiotic resistance in aquaculture not only makes antibiotic treatments ineffective in aquaculture but also poses a threat to public health. In order to overcome this, novel strategies to control bacterial diseases are needed. Antivirulence therapy, which disrupts virulence without affecting bacterial viability, represents a promising alternative approach. This study evaluated the antivirulence activity of Qstatin against pathogenic vibrios belonging to the Harveyi clade. Qstatin specifically inhibited the three-channel quorum sensing system in Vibrio campbellii, significantly downregulated the expression of quorum sensing-regulated virulence genes (flaA, flaK, vpsR, vpsT, and vhp) and attenuated the corresponding phenotypes: swimming motility was reduced by up to 57% and biofilm formation by up to 76%. Protease activity, in contrast, was slightly increased rather than decreased. Finally, treatment with 100 μM Qstatin significantly increased the survival of gnotobiotic brine shrimp larvae upon challenge with each of 13 tested pathogenic Harveyi clade strains (belonging to the species V. campbellii, V. harveyi, or V. parahaemolyticus), without an impact on Vibrio densities in the rearing water. These findings indicate that Qstatin has a broad-spectrum antivirulence activity against Harveyi clade vibrios by inhibiting quorum sensing, thus supporting its potential as a sustainable disease control agent. Full article

Background: Tranexamic acid (TXA) is a synthetic lysine analog widely used as an antifibrinolytic agent. Large randomized trials have demonstrated life-saving benefits when TXA is administered early in acute hemorrhage, but results regarding prophylactic administration have been conflicting, and several trials have not shown improved clinical outcomes. The mechanisms underlying this discrepancy remain incompletely understood. Objectives: To investigate the molecular and structural mechanisms that determine TXA efficacy in purified fibrin clots under conditions mimicking therapeutic versus prophylactic administration. Methods: We examined fibrinolysis induced by tissue plasminogen activator (tPA) in vitro using confocal microscopy, viscoelastic testing (ClotPro), turbidimetry, and plasmin generation assays at physiologically and therapeutically relevant concentrations of plasminogen and TXA. Scanning electron microscopy (SEM) was employed to assess fibrin structure. Results: When TXA was incorporated into fibrin clots before the addition of tPA, physiological plasminogen concentrations (2.5 µM) reversed the antifibrinolytic effect, resulting in paradoxical acceleration of lysis. By contrast, when clotting and fibrinolysis occurred simultaneously in the presence of TXA and tPA, TXA consistently prolonged lysis time irrespective of plasminogen concentration. SEM demonstrated that TXA, even at concentrations as low as 16 µM, doubled the top-quartile values of the fibrin fiber diameter, altering susceptibility to plasmin-mediated degradation without accelerating plasminogen activation. Conclusions: TXA efficacy is determined not only by dose but also by timing and the plasminogen availability in the clot microenvironment. These findings provide mechanistic insight into the failure of prophylactic TXA administration and highlight the importance of context in optimizing its clinical use. Full article

Asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are major non-communicable respiratory diseases (NCD-RDs) with high morbidity and mortality. Despite distinct clinical features, they share overlapping mechanisms including oxidative stress, epithelial injury, and immune dysregulation. Asthma is mainly driven by type 2 inflammation, with IL-4, IL-5, and IL-13 inducing eosinophilia, IgE production, mucus hypersecretion, and airway remodeling. Biologics targeting IgE, IL-5, and IL-4Rα have transformed treatment, and agents directed against TSLP and IL-33 further extend the range of targeted interventions. In contrast, COPD involves chronic inflammation with macrophages, neutrophils, and CD8+ T cells, persisting after smoking cessation. Advances include biologics such as dupilumab and benralizumab in eosinophilic COPD, and novel inhaled therapies such as ensifentrine, the first dual PDE3/4 inhibitor delivered via inhalation. IPF, on the other hand, arises from defective epithelial repair and fibroblast activation, causing progressive fibrosis. Approved antifibrotics (nintedanib, pirfenidone) slow lung function decline, while new strategies target TGF-β, CTGF, and fibroblast-directed pathways. Across these diseases, biomarkers and the treatable traits framework are reshaping precision care. Personalized approaches integrating biomarkers, omics, and targeted therapies represent the most promising path for improved outcomes. Full article

In volatile environments, teams must rapidly adapt to complex internal and external pressures. Although paradoxical leadership (PL) has been linked to enhanced team adaptability, the motivational pathways driving this systemic outcome remain underexplored. To address this gap, we examine how collective goal orientations—treated as resource-allocation rules—mediate the relationship between PL and team adaptability. Grounded in Conservation of Resources theory, we tested the model in a three-wave, multi-source study of 114 high-tech specialist teams, where team members rated PL at T1 and team goal orientations at T2, while supervisors rated team adaptability at T3. Our findings reveal that, within this dataset and context, PL’s indirect association with team adaptability operates largely through a performance approach orientation, an agentic strategy that mobilizes resources for visible competence in the short term. In contrast, while a team learning orientation predicts adaptability when assessed alone, its unique mediating effect becomes non-significant when performance approach orientation is taken into account, consistent with conceptual and empirical overlap between the two constructs. Moreover, although PL reduces performance avoidance orientation, this reduction does not significantly enhance team adaptability. In the present dataset and context, these findings indicate performance approach orientation as the more robust motivational pathway linking PL to team adaptability, thereby providing a foundation for further inquiry into how systemic levers might selectively shape distinct team motivational states. Full article