Search Results (27)

Thyroid cancer, the most frequently occurring endocrine neoplasm, comprises a heterogeneous group of histological subtypes, spanning from the indolent papillary thyroid carcinoma (PTC) to the rapidly progressive and lethal anaplastic thyroid carcinoma (ATC). Although conventional therapies, such as surgery and radioactive iodine (RAI), are effective for differentiated thyroid cancers, treatment resistance and poor prognosis remain major challenges in advanced and undifferentiated forms. In current times, growing attention has been directed toward the potential of Natural Killer (NK) cells as a promising immunotherapeutic avenue. These innate immune cells are capable of direct cytotoxicity against tumor cells, but their efficiency is frequently compromised by the immunosuppressive tumor microenvironment (TME), which inhibits NK cell activation, infiltration, and persistence. This review explores the dynamic interaction between NK cells and the TME in thyroid cancer, detailing key mechanisms of immune evasion, including the impact of suppressive cytokines, altered chemokine landscapes, and inhibitory ligand expression. We further discuss latest advancements in NK cell-based immunotherapies, including strategies for ex vivo expansion, genetic modification, and combinatorial approaches with checkpoint inhibitors or cytokines. Additionally, emerging modalities, such as NK cell-derived extracellular vesicles, are addressed. By combining mechanistic insights with advancing therapeutic techniques, this review provides a comprehensive perspective on NK cell-based interventions and their future potential in improving outcomes for patients with thyroid cancer. Full article

Brain aging is driven by interconnected processes, including impaired autophagy, chronic inflammation, mitochondrial dysfunction, and cellular senescence, all of which contribute to neurovascular decline and neurodegenerative diseases such as Alzheimer’s disease (AD). Targeting these mechanisms simultaneously offers a promising therapeutic approach. This review explores the rationale for combining metformin, benzimidazole derivatives, phosphodiesterase-5 (PDE5), and acetylsalicylic acid (ASA) as a multi-targeted strategy to restore proteostasis, reduce senescence-associated secretory phenotype (SASP) factors, and enhance mitochondrial and lysosomal function. Metformin activates AMP-activated protein kinase (AMPK) and promotes autophagy initiation and chaperone-mediated autophagy, whilst benzimidazole derivatives enhance lysosomal fusion through JIP4–TRPML1 pathways independently of mTOR signaling; and ASA augments autophagic flux while suppressing NF-κB-driven inflammation and promoting specialized pro-resolving mediator pathways. This combinatorial approach targets both upstream autophagy initiation and downstream autophagosome–lysosome fusion, while concurrently attenuating inflammation and cellular senescence. Patient stratification based on the biomarkers of autophagy impairment, inflammation, and metabolic dysfunction could optimize therapeutic responses. While this strategy shows strong preclinical promise, careful attention to timing, dosing, and cell-specific responses is crucial to maximize benefits and avoid adverse effects. Future studies integrating biomarker-guided precision medicine frameworks are essential to validate the potential of this therapeutic combination in preventing or slowing cognitive decline and promoting healthy brain aging. Full article

Background: Combination therapies for cancer have gained considerable attention due to their potential for enhancing therapeutic efficacy and decreasing drug resistance. Introducing nanodrug delivery systems in this context may further improve the therapy due to targeted delivery, improved drug stability, sustained drug release, and prevention of rapid clearance from circulation. This study evaluates the combinatorial effects of two cytotoxic drugs, cabazitaxel (CBZ) and RSL3 (RAS-selective lethal 3), in free form as well as encapsulated within poly(2-ethyl butyl cyanoacrylate) (PEBCA) nanoparticles (NPs) in breast cancer cell lines. Methods: Cell proliferation was assessed using IncuCyte technology, and synergistic drug effects were determined with SynergyFinder Plus. Cell viability was measured with the MTT assay. Additionally, we investigated whether the combinatorial effects were reflected in alterations of metabolic activity or reactive oxygen species (ROS) production using Seahorse technology and the CM-H₂DCFDA assay, respectively. Results: The data presented reveal, for the first time, that CBZ and RSL3 exhibit synergistically or additively combinatorial effects on various breast cancer cell lines. The pattern of cytotoxic effects was consistent, whether the drugs were in free form or encapsulated in NPs. Moreover, the combinatorial effects were not observed to be associated with early changes in metabolic activity or ROS production. Conclusion: This study highlights the potential of CBZ and RSL3 in combinatorial nanomedicine as they may act synergistically. Further studies are warranted to better understand the mechanisms behind these combinatorial effects. Full article

The quantity of wind and photovoltaic power-based distributed generators (DGs) is continually rising within the distribution network, presenting obstacles to its safe, steady, and cost-effective functioning. Active distribution network dynamic reconfiguration (ADNDR) improves the consumption rate of renewable energy, reduces line losses, and optimizes voltage quality by optimizing the distribution network structure. Despite being formulated as a highly dimensional and combinatorial nonconvex stochastic programming task, conventional model-based solvers often suffer from computational inefficiency and approximation errors, whereas population-based search methods frequently exhibit premature convergence to suboptimal solutions. Moreover, when dealing with high-dimensional ADNDR problems, these algorithms often face modeling difficulties due to their large scale. Deep reinforcement learning algorithms can effectively solve the problems above. Therefore, by combining the graph attention network (GAT) with the deep deterministic policy gradient (DDPG) algorithm, a method based on the graph attention network deep deterministic policy gradient (GATDDPG) algorithm is proposed to online solve the ADNDR problem with the uncertain outputs of DGs and loads. Firstly, considering the uncertainty in distributed power generation outputs and loads, a nonlinear stochastic optimization mathematical model for ADNDR is constructed. Secondly, to mitigate the dimensionality of the decision space in ADNDR, a cyclic topology encoding mechanism is implemented, which leverages graph-theoretic principles to reformulate the grid infrastructure as an adaptive structural mapping characterized by time-varying node–edge interactions Furthermore, the GATDDPG method proposed in this paper is used to solve the ADNDR problem. The GAT is employed to extract characteristics pertaining to the distribution network state, while the DDPG serves the purpose of enhancing the process of reconfiguration decision-making. This collaboration aims to ensure the safe, stable, and cost-effective operation of the distribution network. Finally, we verified the effectiveness of our method using an enhanced IEEE 33-bus power system model. The outcomes of the simulations demonstrate its capacity to significantly enhance the economic performance and stability of the distribution network, thereby affirming the proposed method’s effectiveness in this study. Full article

Large Language Models (LLMs) have immensely advanced the field of Artificial Intelligence (AI), with recent models being able to perform chain-of-thought reasoning and solve complex mathematical problems, ranging from theorem proving to ones involving advanced calculus. The success of LLMs derives from a combination of the Transformer architecture with its attention mechanism, the autoregressive training methodology with masked attention, and the alignment fine-tuning via reinforcement learning algorithms. In this research, we attempt to explore a possible solution to the fundamental NP-hard problem of combinatorial optimization, in particular, the Traveling Salesman Problem (TSP), by following the LLM approach in terms of the architecture and training algorithms. Similar to the LLM design, which is trained in an autoregressive manner to predict the next token, our model is trained to predict the next node in a TSP graph. After the model is trained on random TSP graphs with known near-optimal solutions, we fine-tune the model using Direct Preference Optimization (DPO). The tour generation in a trained model is autoregressive one-step generation with no need for iterative refinement. Our results are very promising and indicate that, for TSP graphs up to 100 nodes, a relatively small amount of training data yield solutions within a few percent of the optimal. This optimization improves if more data are used to train the model. Full article

We propose SAT-GATv2, a graph neural network (GNN)-based model designed to solve the Boolean satisfiability problem (SAT) through graph-based deep learning techniques. SAT-GATv2 transforms SAT formulas into graph structures, leveraging message-passing neural networks (MPNNs) to propagate local information and dynamic attention mechanisms (GATv2) to accurately capture inter-node dependencies and enhance node feature representations. Unlike traditional heuristic-driven SAT solvers, SAT-GATv2 adopts a data-driven approach, learning structural patterns directly from graph representations and providing a complementary framework to existing methods. Experimental results demonstrate that SAT-GATv2 achieves an accuracy improvement of 1.75–5.51% over NeuroSAT on challenging random 3-SAT(n) instances, highlighting its effectiveness in handling difficult problem distributions, and outperforms other GNN-based models on SR(n) datasets, showcasing its scalability and adaptability. Ablation studies validate the critical roles of MPNNs and GATv2 in improving prediction accuracy and scalability. While SAT-GATv2 does not yet surpass CDCL-based solvers in overall performance, it addresses their limitations in scalability and adaptability to complex instances, offering an efficient graph-based alternative for tackling larger and more complex SAT problems. This study establishes a foundation for integrating deep learning with combinatorial optimization, emphasizing its potential for applications in artificial intelligence and operations research. Full article

The Vehicle Routing Problem (VRP) is a classic combinatorial optimization problem commonly encountered in the fields of transportation and logistics. This paper focuses on a variant of the VRP, namely the Vehicle Routing Problem with Stochastic Travel Cost (VRP-STC). In VRP-STC, the introduction of stochastic travel costs increases the complexity of the problem, rendering traditional algorithms unsuitable for solving it. In this paper, the GAT-AM model combining Graph Attention Networks (GAT) and multi-head Attention Mechanism (AM) is employed. The GAT-AM model uses an encoder–decoder architecture and employs a deep reinforcement learning algorithm. The GAT in the encoder learns feature representations of nodes in different subspaces, while the decoder uses multi-head AM to construct policies through both greedy and sampling decoding methods. This increases solution diversity, thereby finding high-quality solutions. The REINFORCE with Rollout Baseline algorithm is used to train the learnable parameters within the neural network. Test results show that the advantages of GAT-AM become greater as problem complexity increases, with the optimal solution generally unattainable through traditional algorithms within an acceptable timeframe. Full article

The vehicle routing problem with time windows (VRPTW) is a widely studied combinatorial optimization problem in supply chains and logistics within the last decade. Recent research has explored the potential of deep reinforcement learning (DRL) as a promising solution for the VRPTW. However, the challenge of addressing the VRPTW with many conflicting objectives (MOVRPTW) still remains for DRL. The MOVRPTW considers five conflicting objectives simultaneously: minimizing the number of vehicles required, the total travel distance, the travel time of the longest route, the total waiting time for early arrivals, and the total delay time for late arrivals. To tackle the MOVRPTW, this study introduces the MTMO/DRP-AT, a multi-task multi-objective evolutionary search algorithm, by making full use of both DRL and the multitasking mechanism. In the MTMO/DRL-AT, a two-objective MOVRPTW is constructed as an assisted task, with the objectives being to minimize the total travel distance and the travel time of the longest route. Both the main task and the assisted task are simultaneously solved in a multitasking scenario. Each task is decomposed into scalar optimization subproblems, which are then solved by an attention model trained using DRL. The outputs of these trained models serve as the initial solutions for the MTMO/DRL-AT. Subsequently, the proposed algorithm incorporates knowledge transfer and multiple local search operators to further enhance the quality of these promising solutions. The simulation results on real-world benchmarks highlight the superior performance of the MTMO/DRL-AT compared to several other algorithms in solving the MOVRPTW. Full article

Spatiotemporal information on individual trajectories in urban rail transit is important for operational strategy adjustment, personalized recommendation, and emergency command decision-making. However, due to the lack of journey observations, it is difficult to accurately infer unknown information from trajectories based only on AFC and AVL data. To address the problem, this paper proposes a spatiotemporal probabilistic graphical model based on adaptive expectation maximization attention (STPGM-AEMA) to achieve the reconstruction of individual trajectories. The approach consists of three steps: first, the potential train alternative set and the egress time alternative set of individuals are obtained through data mining and combinatorial enumeration. Then, global and local potential variables are introduced to construct a spatiotemporal probabilistic graphical model, provide the inference process for unknown events, and state information about individual trajectories. Further, considering the effect of missing data, an attention mechanism-enhanced expectation-maximization algorithm is proposed to achieve maximum likelihood estimation of individual trajectories. Finally, typical datasets of origin-destination pairs and actual individual trajectory tracking data are used to validate the effectiveness of the proposed method. The results show that the STPGM-AEMA method is more than 95% accurate in recovering missing information in the observed data, which is at least 15% more accurate than the traditional methods (i.e., PTAM-MLE and MPTAM-EM). Full article

To more accurately predict short-term traffic flow, this study posits a sophisticated integrated prediction model, CNN-BiGRU-AAM, based on the additive attention mechanism of a convolutional bidirectional gated recurrent unit neural network. This model seeks to enhance the precision of traffic flow prediction by integrating both historical and prospective data. Specifically, the model achieves prediction through two steps: encoding and decoding. In the encoding phase, convolutional neural networks are used to extract spatial correlations between weather and traffic flow in the input sequence, while the BiGRU model captures temporal correlations in the time series. In the decoding phase, an additive attention mechanism is introduced to weigh and fuse the encoded features. The experimental results demonstrate that the CNN-BiGRU model, coupled with the additive attention mechanism, is capable of dynamically capturing the temporal patterns of traffic flow, and the introduction of isolation forests can effectively handle data anomalies and missing values, improving prediction accuracy. Compared to benchmark models such as GRU, the CNN-BiGRU-AAM model shows significant improvement on the test set, with a 47.49 reduction in the Root Mean Square Error (RMSE), a 30.72 decrease in the Mean Absolute Error (MAE), and a 5.27% reduction in the Mean Absolute Percentage Error (MAPE). The coefficient of determination ($R^2$) reaches 0.97, indicating the high accuracy of the CNN-BiGRU-AAM model in traffic flow prediction. It provides a good solution for short-term traffic flow with spatio-temporal features, thereby enhancing the efficiency of traffic management and planning and promoting the sustainable development of transportation. Full article

Solving combinatorial problems on complex networks represents a primary issue which, on a large scale, requires the use of heuristics and approximate algorithms. Recently, neural methods have been proposed in this context to find feasible solutions for relevant computational problems over graphs. However, such methods have some drawbacks: (1) they use the same neural architecture for different combinatorial problems without introducing customizations that reflects the specificity of each problem; (2) they only use a nodes local information to compute the solution; (3) they do not take advantage of common heuristics or exact algorithms. Following this interest, in this research we address these three main points by designing a customized attention-based mechanism that uses both local and global information from the adjacency matrix to find approximate solutions for the Minimum Vertex Cover Problem. We evaluate our proposal with respect to a fast two-factor approximation algorithm and a widely adopted state-of-the-art heuristic both on synthetically generated instances and on benchmark graphs with different scales. Experimental results demonstrate that, on the one hand, the proposed methodology is able to outperform both the two-factor approximation algorithm and the heuristic on the test datasets, scaling even better than the heuristic with harder instances and, on the other hand, is able to provide a representation of the nodes which reflects the combinatorial structure of the problem. Full article

As a new abstract computational model in evolutionary transfer optimization (ETO), single-objective to multi-objective optimization (SMO) is conducted at the macroscopic level rather than the intermediate level for specific algorithms or the microscopic level for specific operators; this method aims to develop systems with a profound grasp of evolutionary dynamic and learning mechanism similar to human intelligence via a “decomposition” style (in the abstract of the well-known “Transformer” article “Attention is All You Need”, they use “attention” instead). To the best of our knowledge, it is the first work of SMO for discrete cases because we extend our conference paper and inherit its originality status. In this paper, by implementing the abstract SMO in specialized memetic algorithms, key knowledge from single-objective problems/tasks to the multi-objective core problem/task can be transferred or “gathered” for permutation flow shop scheduling problems, which will reduce the notorious complexity in combinatorial spaces for multi-objective settings in a straight method; this is because single-objective tasks are easier to complete than their multi-objective versions. Extensive experimental studies and theoretical results on benchmarks (1) emphasize our decomposition root in mathematical programming, such as Lagrangian relaxation and column generation; (2) provide two “where to go” strategies for both SMO and ETO; and (3) contribute to the mission of building safe and beneficial artificial general intelligence for manufacturing via evolutionary computation. Full article

Hepatocellular carcinoma (HCC) is one of the most refractory cancers with a high rate of recurrence. Iron is an essential trace element, and iron chelation has garnered attention as a novel therapeutic strategy for cancer. Since intracellular metabolism is significantly altered by inhibiting various proteins by iron chelation, we investigated combination anticancer therapy targeting metabolic changes that are forcibly modified by iron chelator administration. The deferoxamine (DFO)-resistant cell lines were established by gradually increasing the DFO concentration. Metabolomic analysis was conducted to evaluate the metabolic alterations induced by DFO administration, aiming to elucidate the resistance mechanism in DFO-resistant strains and identify potential novel therapeutic targets. Metabolom analysis of the DFO-resistant Huh7 cells revealed enhanced glycolysis and salvage cycle, alternations in glutamine metabolism, and accumulation of dipeptides. Huh7 cultured in the absence of glutamine showed enhanced sensitivity to DFO, and glutaminase inhibitor (CB839) showed a synergistic effect with DFO. Furthermore, the effect of DFO was enhanced by an autophagy inhibitor (chloroquine) in vitro. DFO-induced metabolic changes are specific targets for the development of efficient anticancer combinatorial therapies using DFO. These findings will be useful for the development of new cancer therapeutics in refractory liver cancer. Full article

Graph convolutional networks (GCNs), which extend convolutional neural networks (CNNs) to non-Euclidean structures, have been utilized to promote skeleton-based human action recognition research and have made substantial progress in doing so. However, there are still some challenges in the construction of recognition models based on GCNs. In this paper, we propose an enhanced adjacency matrix-based graph convolutional network with a combinatorial attention mechanism (CA-EAMGCN) for skeleton-based action recognition. Firstly, an enhanced adjacency matrix is constructed to expand the model’s perceptive field of global node features. Secondly, a feature selection fusion module (FSFM) is designed to provide an optimal fusion ratio for multiple input features of the model. Finally, a combinatorial attention mechanism is devised. Specifically, our spatial-temporal (ST) attention module and limb attention module (LAM) are integrated into a multi-input branch and a mainstream network of the proposed model, respectively. Extensive experiments on three large-scale datasets, namely the NTU RGB+D 60, NTU RGB+D 120 and UAV-Human datasets, show that the proposed model takes into account both requirements of light weight and recognition accuracy. This demonstrates the effectiveness of our method. Full article

Safety helmets are essential in various indoor and outdoor workplaces, such as metallurgical high-temperature operations and high-rise building construction, to avoid injuries and ensure safety in production. However, manual supervision is costly and prone to lack of enforcement and interference from other human factors. Moreover, small target object detection frequently lacks precision. Improving safety helmets based on the helmet detection algorithm can address these issues and is a promising approach. In this study, we proposed a modified version of the YOLOv5s network, a lightweight deep learning-based object identification network model. The proposed model extends the YOLOv5s network model and enhances its performance by recalculating the prediction frames, utilizing the IoU metric for clustering, and modifying the anchor frames with the K-means++ method. The global attention mechanism (GAM) and the convolutional block attention module (CBAM) were added to the YOLOv5s network to improve its backbone and neck networks. By minimizing information feature loss and enhancing the representation of global interactions, these attention processes enhance deep learning neural networks’ capacity for feature extraction. Furthermore, the CBAM is integrated into the CSP module to improve target feature extraction while minimizing computation for model operation. In order to significantly increase the efficiency and precision of the prediction box regression, the proposed model additionally makes use of the most recent SIoU (SCYLLA-IoU LOSS) as the bounding box loss function. Based on the improved YOLOv5s model, knowledge distillation technology is leveraged to realize the light weight of the network model, thereby reducing the computational workload of the model and improving the detection speed to meet the needs of real-time monitoring. The experimental results demonstrate that the proposed model outperforms the original YOLOv5s network model in terms of accuracy (Precision), recall rate (Recall), and mean average precision (mAP). The proposed model may more effectively identify helmet use in low-light situations and at a variety of distances. Full article