Search Results (154)

Large language models, despite their strong performance, frequently produce hallucinated content due to excessive reliance on pre-trained knowledge while insufficiently integrating newly provided context. We introduce LACD, a technique that dynamically rebalances probability distributions across layers, ensuring critical context is not overshadowed. By emphasizing new prompt information, LACD alleviates lower-layer dominance and mitigates hallucinations. On the HotPotQA dataset, LACD outperforms basic context injection baselines by approximately 2.2% in exact match (EM) and matches or exceeds advanced methods such as DoLa and CAD. LACD also demonstrates robust gains on SQuAD, underscoring its capacity to reduce hallucinations while improving factual consistency. Overall, these findings highlight the importance of carefully integrating newly provided context with pre-trained knowledge to achieve more reliable language generation. Full article

Human type I interferons are crucial regulators of immune responses, essential for controlling infections and activating immune cells. Among them, Interferon Beta (IFNB1) plays a key role in inflammation, and its dysregulation is linked to various diseases, driving efforts to understand the molecular events governing its expression. Here, we identified Mitogen-Activated Protein Kinase 15 (MAPK15) as a novel regulator of IFNB1. Using luciferase reporter assays, gene expression analysis and Enzyme-Linked Immunosorbent Assay (ELISA), we found that MAPK15 downregulation enhanced IFNB1 and Interferon-Stimulated Genes expression and increased IFNB1 secretion. To unveil the underlying mechanisms, we investigated the transcription factors acting on the IFNB1 promoter, revealing that MAPK15 downregulation induced JUN activation. Importantly, pharmacological inhibition of c-Jun N-terminal Kinases (JNKs) supported a key role for this enzyme in JUN activation and consequent IFNB1 expression. Ultimately, by using the antioxidant N-acetylcysteine ethyl ester (NACET), we demonstrated that oxidative stress, induced by MAPK15 downregulation, was responsible for JUN activation and IFNB1 expression. Overall, our findings unveil a novel mechanism by which MAPK15 modulates IFNB1 expression, positioning this kinase as a pivotal regulator of this gene. This insight opens promising avenues for therapeutic intervention, as targeting MAPK15 activity could offer a strategy to rebalance cytokine expression in chronic inflammatory diseases characterized by immune dysregulation. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease characterised by inflammation, demyelination, and neurodegeneration within the central nervous system. The pathogenesis of MS involves an immune-mediated attack on myelin and neurons, accompanied by blood–brain barrier dysfunction and chronic CNS inflammation. Central to MS pathology is dysregulation of the kynurenine pathway, which metabolises tryptophan into neuroactive compounds. Kynurenine pathway (KP) activation, driven by inflammatory cytokines, leads to the production of both neuroprotective (e.g., kynurenic acid, KYNA) and neurotoxic (e.g., quinolinic acid, QUIN) metabolites. Imbalance between these metabolites, particularly increased QUIN production, exacerbates glutamate excitotoxicity, oxidative stress, and mitochondrial dysfunction, contributing to neuronal and oligodendrocyte damage. Mitochondrial dysfunction plays a critical role in the pathophysiology of MS, exacerbating neurodegeneration through impaired energy metabolism and oxidative stress. This review integrates the current understanding of KP dysregulation in multiple sclerosis across disease stages. In RRMS, heightened KP activity correlates with inflammation and neuroprotection attempts through increased KYNA production. In contrast, SPMS and PPMS are associated with a shift towards a more neurotoxic KP profile, marked by elevated QUIN levels and reduced KYNA, exacerbating neurodegeneration and disability progression. Understanding these mechanisms offers insights into potential biomarkers and therapeutic targets for MS, emphasising the need for strategies to rebalance KP metabolism and mitigate neurotoxicity in progressive disease stages. Full article

Background/Objectives: Overuse or misuse of antibiotics could cause adverse effects such as gut microbiota dysbiosis and intestinal barrier dysfunction. Probiotic intervention could effectively alleviate these symptoms. However, the precise efficacy of Bifidobacterium animalis subsp. lactis PB200 (B. lactis PB200) in mitigating antibiotic-induced intestinal injury remains unclear. Objective: The aim of this study was to systematically evaluate the effects of B. lactis PB200 on intestinal barrier injury and gut microbiota dysbiosis in a murine model of antibiotic-induced intestinal injury. Methods: BALB/c mice were administered ceftriaxone sodium via oral gavage for seven consecutive days, followed by probiotic intervention daily via gastric gavage for 4 weeks. Results: The results indicated that B. lactis PB200 played a positive role in enhancing intestinal barrier function, as evidenced by the restored intestinal morphology, and elevated the expression of tight junctions including ZO-1, Claudin-4 and Occludin (2.76-fold, 4.39-fold, and 2.61-fold, respectively) compared to that in the Model group. B. lactis PB200 normalized the levels of serum pro- and anti-inflammatory factors, including IL-1β, IL-6, TNF-α and IL-10, and elevated the diversity and richness of gut microbiota. B. lactis PB200 significantly elevated the levels of propionic acid and butyric acid, with increases of 1.67-fold and 2.82-fold, respectively, compared to the Model group. Notably, B. lactis PB200 reduced the abundance of Enterocloster and increased the abundance of Parabacteroides, promoting the rebalance of gut microbiota. Conclusions: Taken together, these findings highlighted the significant potential of B. lactis PB200 in alleviating intestinal barrier damage and restoring the balance of gut microbiota caused by an antibiotic. Full article

This study estimates the impact of some socio-economic, real estate, and accessibility factors on the demographic change of the Italian provinces. Migration rates were analysed for one hundred and thirteen provincial capitals, or former provincial capitals, and their territories, and the correlation between them and various socio-economic and accessibility variables was studied. The data analysis showed significant heterogeneity between the different territorial areas of the country, highlighting the well-known phenomenon of migration from southern to northern regions. The aim of this paper is to investigate whether and to what extent accessibility variables have a direct influence on internal migration phenomena, in addition to the other socio-economic variables involved. Multiple linear regression models were specified and calibrated to correlate migration rates with various socio-economic and accessibility variables. The results show a non-negligible impact of certain accessibility variables on the migration phenomenon and suggest the need to work on the infrastructure front to rebalance the country’s demographic and socio-economic structure. Full article

Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is frequently complicated by extraintestinal manifestations such as functional hyposplenism. Increasing evidence highlights its pathogenesis as a multifactorial interplay of gut dysbiosis, intestinal barrier dysfunction, and dysregulated immune responses. While probiotics, particularly Lactobacillus spp., have emerged as potential therapeutics for IBD, restoring intestinal homeostasis, their systemic immunomodulatory effects remain underexplored. Here, we investigated the protective role of Lactobacillus johnsonii N5 in DSS-induced colitis, focusing on inflammation inhibition and splenic T cell regulation. Pretreatment with L. johnsonii N5 significantly attenuated colitis severity, as evidenced by preserved body weight, reduced disease activity index, and prevention of colon shortening. N5 suppressed colonic pro-inflammatory factors such as TNF-α, Il-1b, Il-6, and CXCL1, while elevating anti-inflammatory IL-10 at both mRNA and protein levels. Transcriptomic analysis of the spleen revealed that N5 mediated the downregulation of inflammatory pathways, including the IL-17 and TNF signaling pathways, as well as the HIF-1 signaling pathway, and modulated the metabolic pathway of oxidative phosphorylation. Flow cytometry analysis demonstrated that N5 rebalanced splenic Treg/Th17 responses by expanding the Treg population and reducing the production of IL-17A in Th17 cells. Notably, Th17-associated IL-17A positively correlated with intestinal pro-inflammatory mediators, emphasizing the role of Th17 cells in driving colitis. In contrast, splenic Treg abundance positively correlated with colonic IL-10 levels, suggesting a link between systemic immune regulation and intestinal anti-inflammatory responses. Our study underscores the therapeutic potential of targeting gut–immune crosstalk through probiotics, thereby offering valuable insights for developing live bacterial-based interventions for IBD and other inflammatory disorders. Full article

Against the backdrop of global climate change, extreme weather events, such as heavy rainfall, typhoons, tsunamis, and rising sea levels, have become frequent, posing unprecedented challenges to human society. As an important strategy for coastal cities to respond to climate change, climate-induced evacuation is influenced by complex and diverse factors. This study delves into the driving mechanisms of population migration willingness, revealing the dynamic balance of push, pull, and resistance factors and their interaction with individual value orientations affecting migration decisions. By constructing a Logistic Regression Model, this research quantitatively analyzes the significant impacts of personal circumstances, family characteristics, living conditions, risk perception, compensation relocation, and supportive policies on climate-induced migration willingness, using Shanghai as a case study. The findings indicate that age, education level, household size, housing type, risk perception, and compensation policies are key factors. Building upon the multidimensional capital interaction mechanisms and dynamic threshold response patterns identified in the research, this study proposes a three-phase progressive policy framework: initially, establishing an integrated human–material–social capital framework to implement tiered relocation incentive programs, which address decision window constraints through cognitive empowerment and asset replacement strategies; subsequently, creating a dynamic compensation adjustment mechanism by developing policy toolkits aligned with inverted U-shaped utility curves while enhancing synergistic effects between cultural cognition transformation and vocational training; and ultimately, innovating an institutional–cultural co-governance paradigm that rebalances public service dependency and place attachment through spatial equity redistribution. Specific recommendations encompass designing modular risk education curricula, establishing social network transplantation mechanisms, piloting climate citizenship regimes, and constructing cross-border governance knowledge platforms. These multidimensional interventions encompassing capital restructuring, threshold responsiveness, and cultural adaptation offer valuable policy insights for resolving the “development resilience–migration inertia” paradox in coastal cities. Full article

Balancing tourism seasonality remains a significant challenge in the management of tourist attractions. Despite existing research on the impact of seasonality from the perspectives of tourist intention cognition and spatial theory, gaps still exist in the relevant literature. This study examines 16 5A-level scenic spots in China with peak season, flat season, and off-season themes, utilizing 8385 tourist reviews from Ctrip.com as data. The LDA topic model is employed to analyze tourism destination image (TDI) under seasonality of destination, and the spatial level (SLs) model is combined to analyze the spatial hierarchy of these images. The findings reveal an association between TDI and SLs under seasonality of destination. For instance, peak season TDI themes (e.g., ‘viewing the scenery’) exhibit a support level of 0.789, while off-season themes (e.g., ‘relaxed itinerary’) reach 0.682, reflecting tourists’ prioritization of functional versus psychological dimensions across seasons. The proposed TDI-SLs correlation theory bridges supply-side spatial resource allocation with tourists’ perceptual dynamics, offering a novel framework to rebalance seasonal demand–supply gaps through strategic spatial planning and image recalibration. Practically, this framework guides destination managers to design season-specific strategies, such as optimizing crowd management in peak seasons or promoting immersive experiences in off-seasons. Full article

This article outlines our plan to rebalance the patrimonial heritage from the sacred: a strategy of attention to the needs and social demands, both religious—primarily—and other kinds, of the inhabitants of these communities. Our plan provides an attentive and unprejudiced view of service that proposes new uses for structures of great patrimonial and sentimental value. These are complexes recognized by societies but incapable of being maintained without intervention, given that their use has greatly diminished in today’s society. All this must be considered while additional legitimate demands have arisen that do not find an adequate response in the same community. It is not a matter of competition but of an effective adaptation or a rebalancing through the reprogramming of some properties. We cannot forget that non-religious cultural and social demands also apply to the faithful. Being a believer does not exclude one from being a lover of music or museums. Full article

This article proposes a force rebalance control scheme based on a mode-localized resonant accelerometer (ML-RXL), which is applied to address the limited measurement range problem of the ML-RXL. For the first time, an empirical response model of the weakly coupling resonators for the amplitude ratio output is established. Based on this, this paper builds an overall model of the force rebalance control system to analyze the sensitivity characteristics by simulations, which demonstrates that the scheme can effectively broaden the linear measurement range. It is demonstrated that the sensor exhibits a highly linear output within a measurement range of ±1 g, with a sensitivity of the feedback-control voltage output measured at 2.94 V/g. The measurement range is expanded by at least 6.7 times. Moreover, the results show that the minimum input-referred acceleration noise density of the sensor for the force rebalance control scheme is 3.29 μg/rtHz, and that the best bias instability is optimized to 5.34 μg with an integral time of 0.64 s. Full article

The rapid expansion of the Internet of Things (IoT) has uncovered a significant asymmetry in cybersecurity, where low-power edge devices must face sophisticated threats from adversaries backed by ample resources. In our study, we employ a symmetry-based approach to rebalance these uneven scenarios. We propose a Hybrid Neural Network Intrusion Detection System (Hybrid NNIDS) that uses LightGBM to filter anomalies at the traffic level and MobileNetV2 for further detection at the packet level, creating a viable compromise between detection accuracy and computational cost. Additionally, the proposed Hybrid NNIDS model, on the ACI-IoT-2023 dataset, outperformed other intrusion detection models with an accuracy of 94%, an F1-score of 91%, and a precision rate of 93% in attack detection. The results indicate the developed asymmetry algorithm can greatly reduce processing overhead while still being able to be implemented in IoT environments. The focus of future work will be on the real-world deployment of these security infrastructures in the IoT and their adaptation to newer types of attack vectors that may be developed by malware. Full article

Imbalanced data have become an essential stumbling block in the field of machine learning. In this paper, a novel oversampling method based on local density estimation, namely LD-SMOTE, is presented to address constraints of the popular rebalance technique SMOTE. LD-SMOTE initiates with k-means clustering to quantificationally measure the classification contribution of each feature. Subsequently, a novel distance metric grounded in Jaccard similarity is defined, which accentuates the features that are more intricately linked to the minority class. Utilizing this metric, we estimate the local density with a Gaussian-like function to control the quantity of synthetic samples around every minority sample, thus simulating the distribution of the minority class. Additionally, the generation of synthetic samples occurs within a triangular region constructed by this minority sample and its two chosen neighbors in LD-SMOTE, instead of on the line connecting the minority sample and one of its neighbors. Experimental comparisons between LD-SMOTE and 16 existing resampling methods on 19 datasets reveal a significant average increase in LD-SMOTE with 6.4% in accuracy, 4.4% in the F-measure, 5.4% in the G-mean, and 4.0% in AUC. This result indicates that LD-SMOTE can be an alternative oversampling method for imbalanced datasets. Full article

Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata’s oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis. Full article

Hemostasis describes the process of blood clotting homeostasis. Hemostasis reflects a balance of procoagulant and anticoagulant mechanisms that aim to prevent both bleeding and thrombosis. If hemostasis is disrupted, and bleeding or thrombosis occur, then laboratory testing may ensue to either diagnose the reason for bleeding or thrombosis, or to manage patients under therapy or treatment for bleeding or thrombosis. A wide range of tests of hemostasis are available to laboratories and to clinicians, from routine coagulation assays to specialized hemostasis assays and platelet function. In the current narrative review, we highlight some of the history of innovative diagnostic solutions, such as the integration of chemiluminescence and flow cytometry in the hemostasis diagnostic armamentarium, as well as providing a glimpse to the possible future of diagnostic hemostasis testing. Future directions include the potential for artificial intelligence in diagnostics, the development of more global test systems that can assess both primary and secondary hemostasis, and several innovations to enable the ongoing evolution of therapies to rebalance hemostasis and requiring precise monitoring. This review underscores the ongoing need for innovation to enhance the diagnostic landscape of hemostasis, ensuring better patient outcomes through more accurate and efficient diagnostic methods. Full article

Endocannabinoids have attracted great interest for their ability to counteract the neuroinflammation underlying Alzheimer’s disease (AD). Our study aimed at evaluating whether this activity was also due to a rebalance of autophagic mechanisms in cellular and animal models of AD. We supplied URB597, an inhibitor of Fatty-Acid Amide Hydrolase (FAAH), the degradation enzyme of anandamide, to microglial cultures treated with Aβ_25-35, and to Tg2576 transgenic mice, thus increasing the endocannabinoid tone. The addition of URB597 did not alter cell viability and induced microglia polarization toward an anti-inflammatory phenotype, as shown by the modulation of pro- and anti-inflammatory cytokines, as well as M1 and M2 markers; moreover microglia, after URB597 treatment released higher levels of Bdnf and Nrf2, confirming the protective role underlying endocannabinoids increase, as shown by RT-PCR and immunofluorescence experiments. We assessed the number and area of amyloid plaques in animals administered with URB597 compared to untreated animals and the expression of autophagy key markers in the hippocampus and prefrontal cortex from both groups of mice, via immunohistochemistry and ELISA. After URB597 supply, we detected a reduction in the number and areas of amyloid plaques, as detected by Congo Red staining and a reshaping of microglia activation as shown by M1 and M2 markers’ modulation. URB597 administration restored autophagy in Tg2576 mice via an increase in BECN1 (Beclin1), ATG7 (Autophagy Related 7), LC3 (light chain 3) and SQSTM1/p62 (sequestrome 1) as well as via the activation of the ULK1 (Unc-51 Like Autophagy Activating Kinase 1) signaling pathway, suggesting that it targets mTOR/ULK1-dependent autophagy pathway. The potential of endocannabinoids to rebalance autophagy machinery may be considered as a new perspective for therapeutic intervention in AD. Full article