Feasibility Study on the Use of Infrared Cameras for Skin Cancer Detection under a Proposed Data Degradation Model.

Infrared thermography is considered a useful technique for diagnosing several skin pathologies but it has not been widely adopted mainly due to its high cost. Here, we investigate the feasibility of using low-cost infrared cameras with microbolometer technology for detecting skin cancer. For this purpose, we collected infrared data from volunteer subjects using a high-cost/high-quality infrared camera. We propose a degradation model to assess the use of lower-cost imagers in such a task. The degradation model was validated by mimicking video acquisition with the low-cost cameras, using data originally captured with a medium-cost camera. The outcome of the proposed model was then compared with the infrared video obtained with actual cameras, achieving an average Pearson correlation coefficient of more than 0.9271. Therefore, the model successfully transfers the behavior of cameras with poorer characteristics to videos acquired with higher-quality cameras. Using the proposed model, we simulated the acquisition of patient data with three different lower-cost cameras, namely, Xenics Gobi-640, Opgal Therm-App, and Seek Thermal CompactPRO. The degraded data were used to evaluate the performance of a skin cancer detection algorithm. The Xenics and Opgal cameras achieved accuracies of 84.33% and 84.20%, respectively, and sensitivities of 83.03% and 83.23%, respectively. These values closely matched those from the non-degraded data, indicating that employing these lower-cost cameras is appropriate for skin cancer detection. The Seek camera achieved an accuracy of 82.13% and a sensitivity of 79.77%. Based on these results, we conclude that this camera is appropriate for less critical applications.

Synergistic Antifungal Effect and In Vivo Toxicity of a Monoterpene Isoespintanol Obtained from Oxandra xylopioides Diels.

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.

Isoespintanol Antifungal Activity Involves Mitochondrial Dysfunction, Inhibition of Biofilm Formation, and Damage to Cell Wall Integrity in Candida tropicalis.

The growing increase in infections caused by C. tropicalis, associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of fungal biofilms, the mitochondrial membrane potential (ΔΨm), and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.

[Osteosarcoma as a GES-Listed Pathology: 7-Year Experience at a National Reference Center]. / Osteosarcoma como patología GES. Experiencia de 7 años en Centro de Referencia Nacional.

BACKGROUND: Osteosarcoma (OS) is the most frequent malignant primary bone tumor. The explicit health guarantee (GES) plan in Chile, a law that guarantees diagnosis, treatment, and rehabilitation, incorporated OS in 2014. OBJECTIVES: To describe the characteristics of the population over 15 years, with a histopathological diagnosis of OS, to define survival rate and complications, and to identify variables that affect these outcomes. METHODS: A retrospective study from 2014 to 2020, including all patients affiliated with the public health system diagnosed with OS, with histological confirmation. From clinical records, we extracted demographic data, anatomical OS location, histopathological findings, admission stage, presence of metastases, treatment, complications, and survival. We determined prognostic factors by multivariate analysis. RESULTS: 133 patients, 58.8% men, the average age was 31 years, and the most frequent location was the distal femur (34.9%). 56.4% of the patients were admitted in Enneking stage IIB, and 36.4% presented metastasis at admission. 14.3% presented complications, the most frequent periprosthetic infection (6 cases). 16% of patients evolved with local recurrence. The multivariate model showed that age and metastases at admission constitute independent prognostic variables, with a hazard ratio of 1.017 for age (p = 0.016) and 3.13 for metastases (p = 0.0000). In the subgroup analysis, patients without metastases at diagnosis had a 5-year survival of 54% versus 11% for the group with metastases. Adjusting for age, the 5-year survival for the non-metastatic and metastatic groups was 73% and 22%, respectively. CONCLUSION: This is our country's first demographic description study of patients with OS. In our series, the age of presentation and the presence of metastases at admission were factors that significantly affect prognosis. When adjusting for age, the survival percentages are comparable to those reported in other international centers specialized in sarcomas.

Lizards as Silent Hosts of Trypanosoma cruzi.

We assessed 4 lizard species in Chile for Trypanosoma cruzi, the causative agent of Chagas disease, and 1 species for its ability to transmit the protozoan to uninfected kissing bugs. All lizard species were infected, and the tested species was capable of transmitting the protozoan, highlighting their role as T. cruzi reservoirs.

Entropy-Based Diversification Approach for Bio-Computing Methods.

Nature-inspired computing is a promising field of artificial intelligence. This area is mainly devoted to designing computational models based on natural phenomena to address complex problems. Nature provides a rich source of inspiration for designing smart procedures capable of becoming powerful algorithms. Many of these procedures have been successfully developed to treat optimization problems, with impressive results. Nonetheless, for these algorithms to reach their maximum performance, a proper balance between the intensification and the diversification phases is required. The intensification generates a local solution around the best solution by exploiting a promising region. Diversification is responsible for finding new solutions when the main procedure is trapped in a local region. This procedure is usually carryout by non-deterministic fundamentals that do not necessarily provide the expected results. Here, we encounter the stagnation problem, which describes a scenario where the search for the optimum solution stalls before discovering a globally optimal solution. In this work, we propose an efficient technique for detecting and leaving local optimum regions based on Shannon entropy. This component can measure the uncertainty level of the observations taken from random variables. We employ this principle on three well-known population-based bio-inspired optimization algorithms: particle swarm optimization, bat optimization, and black hole algorithm. The proposal's performance is evidenced by solving twenty of the most challenging instances of the multidimensional knapsack problem. Computational results show that the proposed exploration approach is a legitimate alternative to manage the diversification of solutions since the improved techniques can generate a better distribution of the optimal values found. The best results are with the bat method, where in all instances, the enhanced solver with the Shannon exploration strategy works better than its native version. For the other two bio-inspired algorithms, the proposal operates significantly better in over 70% of instances.

Kaposi's Sarcoma-Associated Herpesvirus Viral Interleukin-6 Signaling Upregulates Integrin ß3 Levels and Is Dependent on STAT3.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of two B-cell lymphoproliferative diseases and Kaposi's sarcoma, an endothelial-cell-driven cancer. KSHV viral interleukin-6 (vIL-6) is a viral homolog of human IL-6 (hIL-6) that is expressed in KSHV-associated malignancies. Previous studies have shown that the expression of the integrin ß3 (ITGB3) subunit is induced upon KSHV infection. Here we report that KSHV vIL-6 is able to induce the expression of ITGB3 and increase surface expression of the αVß3 integrin heterodimer. We demonstrated using small interfering RNA (siRNA) depletion and inhibitor studies that KSHV vIL-6 can increase ITGB3 by inducing STAT3 signaling. Furthermore, we found that secreted vIL-6 is capable of inducing ITGB3 in endothelial cells in a paracrine manner. Importantly, the ability to induce ITGB3 in endothelial cells seems to be specific to vIL-6, as overexpression of hIL-6 alone did not affect levels of this integrin. Our lab and others have previously shown that vIL-6 can induce angiogenesis, and we investigated whether ITGB3 was involved in this process. We found that siRNA depletion of ITGB3 in vIL-6-expressing endothelial cells resulted in a decrease in adhesion to extracellular matrix proteins. Moreover, depletion of ITGB3 hindered the ability of vIL-6 to promote angiogenesis. In conclusion, we found that vIL-6 can singularly induce ITGB3 and that this induction is dependent on vIL-6 activation of the STAT3 signaling pathway.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies: multicentric Castleman's disease, primary effusion lymphoma, and Kaposi's sarcoma. Kaposi's sarcoma is a highly angiogenic tumor that arises from endothelial cells. It has been previously reported that KSHV infection of endothelial cells leads to an increase of integrin αVß3, a molecule observed to be involved in the angiogenic process of several malignancies. Our data demonstrate that the KSHV protein viral interleukin-6 (vIL-6) can induce integrin ß3 in an intracellular and paracrine manner. Furthermore, we showed that this induction is necessary for vIL-6-mediated cell adhesion and angiogenesis, suggesting a potential role of integrin ß3 in KSHV pathogenesis and development of Kaposi's sarcoma.

Compact, Automated, Inexpensive, and Field-Deployable Vacuum-Outlet Gas Chromatograph for Trace-Concentration Gas-Phase Organic Compounds.

The identification and quantification of gas-phase organic compounds, such as volatile organic compounds (VOCs), frequently use gas chromatography (GC), which typically requires high-purity compressed gases. We have developed a new instrument for trace-concentration measurements of VOCs and intermediate-volatility compounds of up to 14 carbon atoms in a fully automated (computer-free), independent, low-cost, compact GC-based system for the quantitative analysis of complex mixtures without the need for compressed, high-purity gases or expensive detectors. Through adsorptive analyte preconcentration, vacuum GC, photoionization detectors, and need-based water-vapor control, we enable sensitive and selective measurements with picogram-level limits of detection (i.e., under 15 ppt in a 4 L sample for most compounds). We validate performance against a commercial pressurized GC, including resolving challenging isomers of similar volatility, such as ethylbenzene and  m/ p-xylene. We employ vacuum GC across the whole column with filtered air as a carrier gas, producing long-term system stability and performance over a wide range of analytes. Through theory and experiments, we present variations in analyte diffusivities in the mobile phase, analyte elution temperatures, optimal linear velocities, and separation-plate heights with vacuum GC in air at different pressures, and we optimize our instrument to exploit these differences. At 2-6 psia, the molecular diffusion coefficients are 6.4-2.1 times larger and the elution temperatures are 39-92 °C lower than with pressurized GC with helium (at 30 psig) depending on the molecular structure, and we find a wide range of optimal linear velocities (up to 60 cm s-1) that are faster with broader tolerances than with pressurized-N2 GC.

Toward a Robust Multi-Objective Metaheuristic for Solving the Relay Node Placement Problem in Wireless Sensor Networks.

During the last decade, Wireless sensor networks (WSNs) have attracted interest due to the excellent monitoring capabilities offered. However, WSNs present shortcomings, such as energy cost and reliability, which hinder real-world applications. As a solution, Relay Node (RN) deployment strategies could help to improve WSNs. This fact is known as the Relay Node Placement Problem (RNPP), which is an NP-hard optimization problem. This paper proposes to address two Multi-Objective (MO) formulations of the RNPP. The first one optimizes average energy cost and average sensitivity area. The second one optimizes the two previous objectives and network reliability. The authors propose to solve the two problems through a wide range of MO metaheuristics from the three main groups in the field: evolutionary algorithms, swarm intelligence algorithms, and trajectory algorithms. These algorithms are the Non-dominated Sorting Genetic Algorithm II (NSGA-II), Strength Pareto Evolutionary Algorithm 2 (SPEA2), Multi-Objective Evolutionary Algorithm based on Decomposition (MOEA/D), Multi-Objective Artificial Bee Colony (MO-ABC), Multi-Objective Firefly Algorithm (MO-FA), Multi-Objective Gravitational Search Algorithm (MO-GSA), and Multi-Objective Variable Neighbourhood Search Algorithm (MO-VNS). The results obtained are statistically analysed to determine if there is a robust metaheuristic to be recommended for solving the RNPP independently of the number of objectives.

Fine-grained parallelization of fitness functions in bioinformatics optimization problems: gene selection for cancer classification and biclustering of gene expression data.

BACKGROUND: Metaheuristics are widely used to solve large combinatorial optimization problems in bioinformatics because of the huge set of possible solutions. Two representative problems are gene selection for cancer classification and biclustering of gene expression data. In most cases, these metaheuristics, as well as other non-linear techniques, apply a fitness function to each possible solution with a size-limited population, and that step involves higher latencies than other parts of the algorithms, which is the reason why the execution time of the applications will mainly depend on the execution time of the fitness function. In addition, it is usual to find floating-point arithmetic formulations for the fitness functions. This way, a careful parallelization of these functions using the reconfigurable hardware technology will accelerate the computation, specially if they are applied in parallel to several solutions of the population. RESULTS: A fine-grained parallelization of two floating-point fitness functions of different complexities and features involved in biclustering of gene expression data and gene selection for cancer classification allowed for obtaining higher speedups and power-reduced computation with regard to usual microprocessors. CONCLUSIONS: The results show better performances using reconfigurable hardware technology instead of usual microprocessors, in computing time and power consumption terms, not only because of the parallelization of the arithmetic operations, but also thanks to the concurrent fitness evaluation for several individuals of the population in the metaheuristic. This is a good basis for building accelerated and low-energy solutions for intensive computing scenarios.

Phylogenetic incongruence inferred with two mitochondrial genes in Mepraia spp. and Triatoma eratyrusiformis(Hemiptera, Reduviidae).

Mitochondrial DNA (mtDNA) is widely used to clarify phylogenetic relationships among and within species, and to determine population structure. Due to the linked nature of mtDNA genes it is expected that different genes will show similar results. Phylogenetic incongruence using mtDNA genes may result from processes such as heteroplasmy, nuclear integration of mitochondrial genes, polymerase errors, contamination, and recombination. In this study we used sequences from two mitochondrial genes (cytochrome b and cytochrome oxidase subunit I) from the wild vectors of Chagas disease, Triatoma eratyrusiformis and Mepraia species to test for topological congruence. The results showed some cases of phylogenetic incongruence due to misplacement of four haplotypes of four individuals. We discuss the possible causes of such incongruence and suggest that the explanation is an intra-individual variation likely due to heteroplasmy. This phenomenon is an independent evidence of common ancestry between these taxa.

Application of the artificial bee colony algorithm for solving the set covering problem.

The set covering problem is a formal model for many practical optimization problems. In the set covering problem the goal is to choose a subset of the columns of minimal cost that covers every row. Here, we present a novel application of the artificial bee colony algorithm to solve the non-unicost set covering problem. The artificial bee colony algorithm is a recent swarm metaheuristic technique based on the intelligent foraging behavior of honey bees. Experimental results show that our artificial bee colony algorithm is competitive in terms of solution quality with other recent metaheuristic approaches for the set covering problem.

A prefiltered cuckoo search algorithm with geometric operators for solving Sudoku problems.

The Sudoku is a famous logic-placement game, originally popularized in Japan and today widely employed as pastime and as testbed for search algorithms. The classic Sudoku consists in filling a 9 × 9 grid, divided into nine 3 × 3 regions, so that each column, row, and region contains different digits from 1 to 9. This game is known to be NP-complete, with existing various complete and incomplete search algorithms able to solve different instances of it. In this paper, we present a new cuckoo search algorithm for solving Sudoku puzzles combining prefiltering phases and geometric operations. The geometric operators allow one to correctly move toward promising regions of the combinatorial space, while the prefiltering phases are able to previously delete from domains the values that do not conduct to any feasible solution. This integration leads to a more efficient domain filtering and as a consequence to a faster solving process. We illustrate encouraging experimental results where our approach noticeably competes with the best approximate methods reported in the literature.

Comparing evolutionary strategies on a biobjective cultural algorithm.

Evolutionary algorithms have been widely used to solve large and complex optimisation problems. Cultural algorithms (CAs) are evolutionary algorithms that have been used to solve both single and, to a less extent, multiobjective optimisation problems. In order to solve these optimisation problems, CAs make use of different strategies such as normative knowledge, historical knowledge, circumstantial knowledge, and among others. In this paper we present a comparison among CAs that make use of different evolutionary strategies; the first one implements a historical knowledge, the second one considers a circumstantial knowledge, and the third one implements a normative knowledge. These CAs are applied on a biobjective uncapacitated facility location problem (BOUFLP), the biobjective version of the well-known uncapacitated facility location problem. To the best of our knowledge, only few articles have applied evolutionary multiobjective algorithms on the BOUFLP and none of those has focused on the impact of the evolutionary strategy on the algorithm performance. Our biobjective cultural algorithm, called BOCA, obtains important improvements when compared to other well-known evolutionary biobjective optimisation algorithms such as PAES and NSGA-II. The conflicting objective functions considered in this study are cost minimisation and coverage maximisation. Solutions obtained by each algorithm are compared using a hypervolume S metric.

A Novel Approach to Combinatorial Problems: Binary Growth Optimizer Algorithm.

The set-covering problem aims to find the smallest possible set of subsets that cover all the elements of a larger set. The difficulty of solving the set-covering problem increases as the number of elements and sets grows, making it a complex problem for which traditional integer programming solutions may become inefficient in real-life instances. Given this complexity, various metaheuristics have been successfully applied to solve the set-covering problem and related issues. This study introduces, implements, and analyzes a novel metaheuristic inspired by the well-established Growth Optimizer algorithm. Drawing insights from human behavioral patterns, this approach has shown promise in optimizing complex problems in continuous domains, where experimental results demonstrate the effectiveness and competitiveness of the metaheuristic compared to other strategies. The Growth Optimizer algorithm is modified and adapted to the realm of binary optimization for solving the set-covering problem, resulting in the creation of the Binary Growth Optimizer algorithm. Upon the implementation and analysis of its outcomes, the findings illustrate its capability to achieve competitive and efficient solutions in terms of resolution time and result quality.

Skin Cancer Detection and Classification Using Neural Network Algorithms: A Systematic Review.

In recent years, there has been growing interest in the use of computer-assisted technology for early detection of skin cancer through the analysis of dermatoscopic images. However, the accuracy illustrated behind the state-of-the-art approaches depends on several factors, such as the quality of the images and the interpretation of the results by medical experts. This systematic review aims to critically assess the efficacy and challenges of this research field in order to explain the usability and limitations and highlight potential future lines of work for the scientific and clinical community. In this study, the analysis was carried out over 45 contemporary studies extracted from databases such as Web of Science and Scopus. Several computer vision techniques related to image and video processing for early skin cancer diagnosis were identified. In this context, the focus behind the process included the algorithms employed, result accuracy, and validation metrics. Thus, the results yielded significant advancements in cancer detection using deep learning and machine learning algorithms. Lastly, this review establishes a foundation for future research, highlighting potential contributions and opportunities to improve the effectiveness of skin cancer detection through machine learning.

Enhancing the Efficiency of a Cybersecurity Operations Center Using Biomimetic Algorithms Empowered by Deep Q-Learning.

In the complex and dynamic landscape of cyber threats, organizations require sophisticated strategies for managing Cybersecurity Operations Centers and deploying Security Information and Event Management systems. Our study enhances these strategies by integrating the precision of well-known biomimetic optimization algorithms-namely Particle Swarm Optimization, the Bat Algorithm, the Gray Wolf Optimizer, and the Orca Predator Algorithm-with the adaptability of Deep Q-Learning, a reinforcement learning technique that leverages deep neural networks to teach algorithms optimal actions through trial and error in complex environments. This hybrid methodology targets the efficient allocation and deployment of network intrusion detection sensors while balancing cost-effectiveness with essential network security imperatives. Comprehensive computational tests show that versions enhanced with Deep Q-Learning significantly outperform their native counterparts, especially in complex infrastructures. These results highlight the efficacy of integrating metaheuristics with reinforcement learning to tackle complex optimization challenges, underscoring Deep Q-Learning's potential to boost cybersecurity measures in rapidly evolving threat environments.

Autonomous Parameter Balance in Population-Based Approaches: A Self-Adaptive Learning-Based Strategy.

Population-based metaheuristics can be seen as a set of agents that smartly explore the space of solutions of a given optimization problem. These agents are commonly governed by movement operators that decide how the exploration is driven. Although metaheuristics have successfully been used for more than 20 years, performing rapid and high-quality parameter control is still a main concern. For instance, deciding the proper population size yielding a good balance between quality of results and computing time is constantly a hard task, even more so in the presence of an unexplored optimization problem. In this paper, we propose a self-adaptive strategy based on the on-line population balance, which aims for improvements in the performance and search process on population-based algorithms. The design behind the proposed approach relies on three different components. Firstly, an optimization-based component which defines all metaheuristic tasks related to carry out the resolution of the optimization problems. Secondly, a learning-based component focused on transforming dynamic data into knowledge in order to influence the search in the solution space. Thirdly, a probabilistic-based selector component is designed to dynamically adjust the population. We illustrate an extensive experimental process on large instance sets from three well-known discrete optimization problems: Manufacturing Cell Design Problem, Set covering Problem, and Multidimensional Knapsack Problem. The proposed approach is able to compete against classic, autonomous, as well as IRace-tuned metaheuristics, yielding interesting results and potential future work regarding dynamically adjusting the number of solutions interacting on different times within the search process.

Challenging the Limits of Binarization: A New Scheme Selection Policy Using Reinforcement Learning Techniques for Binary Combinatorial Problem Solving.

In this study, we introduce an innovative policy in the field of reinforcement learning, specifically designed as an action selection mechanism, and applied herein as a selector for binarization schemes. These schemes enable continuous metaheuristics to be applied to binary problems, thereby paving new paths in combinatorial optimization. To evaluate its efficacy, we implemented this policy within our BSS framework, which integrates a variety of reinforcement learning and metaheuristic techniques. Upon resolving 45 instances of the Set Covering Problem, our results demonstrate that reinforcement learning can play a crucial role in enhancing the binarization techniques employed. This policy not only significantly outperformed traditional methods in terms of precision and efficiency, but also proved to be extensible and adaptable to other techniques and similar problems. The approach proposed in this article is capable of significantly surpassing traditional methods in precision and efficiency, which could have important implications for a wide range of real-world applications. This study underscores the philosophy behind our approach: utilizing reinforcement learning not as an end in itself, but as a powerful tool for solving binary combinatorial problems, emphasizing its practical applicability and potential to transform the way we address complex challenges across various fields.

Amivantamab efficacy in wild-type EGFR NSCLC tumors correlates with levels of ligand expression.

Amivantamab is an FDA-approved bispecific antibody targeting EGF and Met receptors, with clinical activity against EGFR mutant non-small cell lung cancer (NSCLC). Amivantamab efficacy has been demonstrated to be linked to three mechanisms of action (MOA): immune cell-mediated killing, receptor internalization and degradation, and inhibition of ligand binding to both EGFR and Met receptors. Among the EGFR ligands, we demonstrated that amphiregulin (AREG) is highly expressed in wild-type (WT) EGFR (EGFRWT) NSCLC primary tumors, with significantly higher circulating protein levels in NSCLC patients than in healthy volunteers. Treatment of AREG-stimulated EGFRWT cells/tumors with amivantamab or with an AREG-targeting antibody inhibited ligand-induced signaling and cell/tumor proliferation/growth. Across 11 EGFRWT NSCLC patient-derived xenograft models, amivantamab efficacy correlated with AREG RNA levels. Interestingly, in these models, amivantamab anti-tumor activity was independent of Fc engagement with immune cells, suggesting that, in this context, the ligand-blocking function is sufficient for amivantamab maximal efficacy. Finally, we demonstrated that in lung adenocarcinoma patients, high expression of AREG and EGFR mutations were mutually exclusive. In conclusion, these data 1) highlight EGFR ligand AREG as a driver of tumor growth in some EGFRWT NSCLC models, 2) illustrate the preclinical efficacy of amivantamab in ligand-driven EGFRWT NSCLC, and 3) identify AREG as a potential predictive biomarker for amivantamab activity in EGFRWT NSCLC.