Search Results (150)

Automated generative design is increasingly used across engineering disciplines to accelerate innovation and reduce costs. Generative design offers the prospect of simplifying manual design tasks by exploring the efficacy of solutions automatically. However, existing generative design frameworks rely heavily on expensive optimisation procedures and often produce customised solutions, lacking reusable generative rules that transfer across different problems. This work presents a bioinspired generative design algorithm utilising the concept of evolutionary development (EvoDevo). This evolves a set of developmental rules that can be applied to different engineering problems to rapidly develop designs without the need to run full optimisation procedures. In this approach, an initial design is decomposed into simple entities called cells, which independently control their local growth over a development cycle. In biology, the growth of cells is governed by a gene regulatory network (GRN), but there is no single widely accepted model for this in artificial systems. The GRN responds to the state of the cell induced by external stimuli in its environment, which, in this application, is the loading regime on a bridge truss structure (but can be generalised to any engineering structure). Two GRN models are investigated: graph neural network (GNN) and graph-based Cartesian genetic programming (CGP) models. Both GRN models are evolved using a novel genetic search algorithm for parameter search, which can be re-used for other design problems. It is revealed that the CGP-based method produces results similar to those obtained using the GNN-based methods while offering more interpretability. In this work, it is shown that this EvoDevo approach is able to produce near-optimal truss structures via growth mechanisms such as moving vertices or changing edge features. The technique can be set up to provide design automation for a range of engineering design tasks. Full article

In November 2024, the fourth annual Symposium focusing on early-age onset cancer (EAOC) was hosted by the Colorectal Cancer Resource & Action Network (CCRAN), assembling clinicians, researchers, and patients virtually to discuss challenges in early detection and diagnosis of individuals afflicted with EAOC across tumour types. The meeting addressed the rising rates of EAOC and identified strategies to overcome barriers to timely detection and diagnosis by closing gaps in public and healthcare provider knowledge on symptoms of cancer in younger adults and reducing inequities in standard screening for younger age groups. Discussions also encompassed the various factors that serve as impediments to accessing diagnostic testing and obtaining results, as well as the critical need for access to diagnostics such as comprehensive genomic profiling (CGP), the results of which could be imperative in helping to guide clinical decisions regarding effective and well-tolerated targeted therapies. The Symposium generated key calls to action regarding increasing EAOC education and awareness among primary care providers and the public, re-evaluation of cancer screening programs’ eligibility criteria to include younger populations, and mechanisms to reduce waiting times for diagnostic testing by addressing technologist shortages and improving access to CGP through national collaborative strategies and increased funding. Full article

Background/Objectives: The neurotrophic tropomyosin receptor kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 encode tyrosine kinase receptors, and their fusion genes are known as the oncogenic driver genes for cancer. This study aimed to compare the diagnostic ability of NTRK fusion among five types of multi-cancer genome profiling tests (multi-CGP tests) and determine a useful multi-CGP test for NTRK fusion, recorded in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to compare the diagnostic results for NTRK fusions among the five different CGP tests. Methods: A total of 88,688 tumor cases were enrolled in the C-CAT profiling database from 2019 to 2024. The detection frequency of NTRK fusion genes was compared to the results for five multi-CGP tests: NCC Oncopanel, FoundationOne CDx (F1), FoundationOne Liquid (F1L), GenMineTOP (GMT), and Guardant360. Results: NTRK fusion genes were detected in 175 (0.20%) of the 88,688 total cases. GMT, which is equipped with RNA sequencing function, frequently detected NTRK fusion genes (20 of 2926 cases; 0.68%) in comparison with the other four multi-CGP tests that do not have RNA sequencing analysis. GMT showed significantly (p < 0.05) higher diagnostic ability for NTRK fusions compared with the other four multi-CGP tests. Especially, NTRK2 fusion was significantly (p < 0.001) more highly determined by GMT than it was by the other four multi-CGP tests. The detection rates for FGFR1 and FGFR3 were significantly higher in GMT than in other multi-CGP tests. In contrast, the detection rates of the ALK and RET fusion genes were significantly higher in F1L. Conclusions: GMT, which is equipped with RNA sequencing analysis, might show a useful diagnostic ability for NTRK fusions, especially for NTRK2 fusion genes. Full article

The upcoming wave of personalized medicine, driven by genomic diagnostics and artificial intelligence, demands clearly defined pre-laboratory and laboratory procedures to ensure the acquisition of DNA and RNA of sufficient quantity and quality. In prostate cancer oncogenetics, diagnostic and prognostic assessments increasingly rely on personalized approaches, including Comprehensive Genomic Profiling (CGP). In this pilot study, we aimed to establish optimal pre-analytical and analytical conditions for selected genetic diagnostic methods using tissue samples acquired through multiparametric MRI-guided biopsy. Tissue specimens from thirteen patients were processed for DNA isolation, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Comparative analyses were performed on DNA derived from both fresh and formalin-fixed, paraffin-embedded (FFPE) samples. Sequencing quality metrics demonstrated markedly superior performance in fresh tissue compared to FFPE. These results highlight the importance of standardized tissue collection and processing protocols to enable reliable molecular diagnostics in prostate cancer. Our findings support the feasibility of integrating high-quality genomic testing into routine biopsy workflows and emphasize the need for further large-scale validation. Full article

This study aimed to improve the mechanical properties and water resistance of calcined gypsum from phosphogypsum (CGP) by incorporating organic additives and inorganic admixtures. The effects of the dosage of these additives—including kaolin, nano-SiO₂, polycarboxylic acid superplasticizer, and sodium methyl silicate—on the properties (flexural strength, compressive strength, water absorption, and softening coefficient) of CGP composites (CGPCs) were investigated. A high water resistance of the CGPCs was achieved using nano-SiO₂ and sodium methyl silicate modification, superplasticizer addition, and the partial replacement of gypsum with mineral admixtures. The results showed that the flexural and compressive strength of the composites hit 4.61 MPa and 19.54 MPa, respectively, while the softening coefficient was 0.70 and the water absorption rate was 19.85%. Microstructural investigation confirmed that the combination of nano-SiO₂ and kaolin led to the formation of calcium silicate hydrate. Additionally, the superplasticizer played a crucial role in reducing the water-to-cement ratio, while unhydrated mineral particles had a filling effect, thereby enhancing the density of the hardened paste. The sodium methyl silicate formed a hydrophobic film on the surface of the hardened paste, increasing the contact angle to 109.01° and improving the water resistance of the CGPCs. Full article

Coal gangue is a fine-grained mineral with nutrient content, which can be used as a potential soil amendment. Nevertheless, current research on using coal gangue to improve soil water and support plant growth is still insufficient. In this study, coal gangue powder (CGP) was added to aeolian sandy soil. We compared the soil hydraulic properties and plant growth of original aeolian sandy soil (CK) and different CGP application rates (10% and 20%). The results indicated that the application of CGP transformed the soil texture from sandy to loamy, significantly reduced soil bulk density and saturated hydraulic conductivity (Ks) values, altered the soil water characteristic curve, enhanced soil water-holding capacity, and increased plant-available water. Compared with the CK group, the emergence rate of alfalfa seeds increased from approximately 50% to over 70% after CGP application. During the growth process, CGP application significantly elevated the net photosynthetic rate, transpiration rate, and stomatal conductance of alfalfa leaves. Rapid fluorescence kinetics monitoring of leaves demonstrated that alfalfa treated with CGP had a higher efficiency in light energy utilization. However, the photosynthetic capacity of leaves did not improve as the CGP application rate increased from 10% to 20%, suggesting that excessive CGP addition did not continuously benefit plant gas exchange. In conclusion, CGP application can improve the soil hydraulic properties of aeolian sandy soil and support plant growth and development, which is conducive to reducing the accumulated amount of coal gangue, alleviating plant water stress, and promoting ecological restoration in arid mining areas. We recommend a 10% addition of coal gangue powder as the optimal amount for similar soils. Full article

In this study, the mechanical properties and failure characteristics of concrete with 10–20 mm recycled coarse aggregate at 0%, 25%, 50%, 75%, and 100% substitution rates were studied. In addition, the influence of coal gangue powder (CGP) on the mechanical properties of concrete was studied under the dosages of 5%, 10%, 15%, and 20%. The research results show that the peak strength of recycled concrete decreases with the increase in the replacement rate of 10–20 mm recycled coarse aggregate. When the replacement rate is 25%, the decrease in strength is the smallest. When the content of CGP increases from 0 to 20%, the peak strength of recycled concrete increases first and then decreases. When the content of CGP is 15%, the peak strength reaches the maximum value. The peak strength increases slightly. The density of pores and cracks in recycled concrete increases with the increase of 10–20 mm recycled coarse aggregate replacement rate. When the substitution rate exceeds 25%, the proportion of cracks increases by nearly 1.7 times. After adding CGP to recycled concrete, the pore density and crack ratio inside a specimen are significantly reduced. When the CGP content exceeds 15%, the crack ratio tends to be stable. When the CGP content is 15%, the crack ratio is 0.519%, which is 23.5% lower than that of the RAC-25 specimen. When the content exceeds 15%, the crack ratio tends to be stable. Full article

So far, the molecular functions of the angiotensin-type-2 receptor (AT2) interacting protein (ATIP1) have remained unclear, although expression studies have revealed high levels of ATIP1 in the heart. To unravel its physiological function, we investigated ATIP1-KO mice. They develop a spontaneous cardiac hypertrophy with a significantly increased heart/bodyweight ratio, enlarged cardiomyocyte diameters, and augmented myocardial fibrosis. Hemodynamic measurements revealed an increased ejection fraction (EF) in untreated ATIP1-KO mice, and reduced end-systolic and end-diastolic volumes (ESV and EDV), which, in sum, reflect a compensated concentric cardiac hypertrophy. Importantly, no significant differences in blood pressure (BP) were observed. Chronic angiotensin II (AngII) infusion resulted in increases in BP and EF in ATIP1-KO and WT mice. Reductions in ESV and EDV occurred in both ATIP1-KO and WT but to a lesser extent in ATIP1-KOs. Isolated cardiomyocytes exhibited a significantly increased contractility in ATIP1-KO and accelerated Ca²⁺ decay. AngII treatment resulted in increased fractional shortening in WT but decreased shortening in ATIP1-KO, accompanied by accelerated cell relaxation in WT but absent effects on relaxation in ATIP1-KO cells. The AT2 agonist CGP42112A increased shortening in WT cardiomyocytes but, again, did not affect shortening in ATIP1-KO cells. Relaxation was accelerated by CGP42112A in WT but was unaffected in ATIP1-KO cells. We show that ATIP1 deficiency results in spontaneous cardiac hypertrophy in vivo and that ATIP1 is a downstream signal in the AT2 pathway regulating cell contractility. We hypothesize that the latter effect is because of a disinhibition of the AT1 pathway by impaired AT2 signaling. Full article

We have previously shown that the compound CGP37157, a mitochondrial Na⁺/Ca²⁺ exchanger inhibitor, increases lifespan and improves muscle and mitochondrial structure during aging in wild-type C. elegans nematodes. We used here a rotenone model of Parkinson’s disease in C. elegans to test the ability of CGP37157 to rescue the alterations induced by the toxicant. Rotenone, a mitochondrial respiratory chain complex I inhibitor, reduced worm lifespan and muscle activity, measured as worm mobility, pharyngeal pumping, and defecation rate. It also increased ROS production, decreased mitochondrial membrane potential, and disorganized mitochondrial structure. Moreover, it induced degeneration of dopaminergic neurons and changes in behavior. We found that CGP37157 produced a partial or complete reversal of most of these alterations. These results are consistent with our previous proposal that Ca²⁺ homeostasis is important in the development of neurodegenerative diseases, and modulation of the Ca²⁺ signaling toolkit may be a novel target for their treatment. Full article

Soft tissue sarcomas (STSs) constitute a group of tumors with heterogeneous alterations and different biological behavior. Genetic profiling techniques have immense potential to revolutionize sarcoma classification, detection, and treatment. Cell-free DNA (cfDNA) analysis offers a minimally invasive approach to profiling tumor alterations, including tracking specific mutations or targeted panels of cancer-related genes via DNA sequencing methods. Circulating tumor DNA (ctDNA) platforms have gained popularity as a noninvasive alternative to tissue biopsies, offering a less invasive approach to tumor profiling. Nonetheless, ctDNA profiling in concordance with standard solid tumor comprehensive genomic profiling (CGP) is poorly characterized for STSs. Ultra-low-pass whole-genome sequencing and whole exome sequencing of cfDNA have yet to be fully leveraged in patients with sarcomas. This comprehensive review provides an overview of the application of ctDNA in STSs. Full article

Inflammatory periodontal diseases, despite all the efforts of modern dentistry, remain an important predictor of tooth loss worldwide. Oxidative stress plays a crucial role in the pathogenesis of periodontitis, making the use of antioxidants an attractive option for its treatment. Our attention was drawn to the selenium compound Selenase as an antioxidant therapeutic agent. In this study, we modeled a calcium-deficient prooxidant chronic generalized periodontitis (CGP) model in white non-linear rats. Then, after 14 days, Selenase (50 μg/kg) and Mexidol (250 mg/kg) were administered intragastrically. Blood samples from the animals were analyzed using ELISA and biochemical methods to determine Cu-Zn SOD, nitrotyrosine, GPX-4, iNOS, NO_x, GSH, and GSSG levels. The CGP model led to the typical clinical signs of periodontitis, including hyperemia, edema, gingival pocket formation, bleeding, tooth mobility, as well as an increase in molecular–biochemical markers of nitrosative stress and a reduction of endogenous antioxidants in the blood. Selenase resulted in a decrease in the clinical manifestations of CGP, reduced iNOS, nitrotyrosine, and NO_x levels, and an increase in Cu-Zn SOD and GPX-4 compared to the control group (p < 0.05). Mexidol had a less pronounced effect on these markers compared to Selenase (p < 0.05). Full article

Traditional multi-agent reinforcement learning (MARL) algorithms typically implement global parameter sharing across various types of heterogeneous agents without meticulously differentiating between different action semantics. This approach results in the action semantic conflict problem, which decreases the generalization ability of policy networks across heterogeneous types of agents and decreases the cooperation among agents in intricate scenarios. Conversely, completely independent agent parameters significantly escalate computational costs and training complexity. To address these challenges, we introduce an adaptive MARL algorithm named Generalized Action-Prediction Optimization (GAPO). First, we introduce the Generalized Action Space (GAS), which represents the union of all agent actions with distinct semantics. All agents first compute their unified representation in the GAS, and then generate their heterogeneous action policies with different available action masks. Second, in order to further improve cooperation between heterogeneous groups, we propose a Cross-Group Prediction (CGP) loss, which adaptively predicts the action policies of other groups by leveraging trajectory information. We integrate the GAPO into both value-based and policy-based MARL algorithms, giving rise to two practical algorithms: G-QMIX and G-MAPPO. Experimental results obtained within the SMAC, MPE, MAMuJoCo, and RPE environments demonstrate the superiority of G-QMIX and G-MAPPO over several state-of-the-art MARL methods, validating the effectiveness of our proposed adaptive generalized MARL approach. Full article

The explosion in biomarker testing over the past two decades continues to transform cancer care in Canada and around the world. Precision medicine is supported by identifying actionable mutations that direct therapeutic choices, thus improving survival and quality of life, especially for patients with advanced/metastatic disease. In addition, our growing understanding of the genetic basis of cancer is advanced by research employing ever-expanding databases of genetic mutations, therapies and outcomes. Despite this promising progress, however, access to biomarker testing remains inequitable across Canada, to the detriment of patients. Several underlying factors contribute to this situation, including the need for investment in and standardization of laboratory medicine infrastructure and processes, and the lack of suitable methods for cost/benefit evaluations to inform funding decisions. In 2024, a Canadian conference brought together patients, clinicians, researchers, policy-makers and scientists to address “Equitable Access to Advanced Biomarker Testing for Canadian Metastatic Cancer Patients”. Two major themes arose from the conference: the urgent need to adopt comprehensive genomic profiling (CGP) as a standard of care across Canada, and the emerging role of liquid biopsy in accelerating access to biomarker testing for patients with advanced/metastatic cancer. Full article

This study investigates the impact of green innovation (GI) on corporate environmental performance (CEP), while examining the moderating roles of corporate governance practices (CGPs) and environmental policy pressure (EPP). This study uses advanced statistical methods to ensure the reliability of the results. These include techniques such as propensity score matching (PSM), difference-in-differences (DID) analysis with China’s National Green Development Fund (2020) as the policy intervention, and the generalized method of moments (GMM), and this study examines how internal governance mechanisms and external regulatory pressures influence the GI-CEP relationship. The results show that GI significantly increases CEP, and that this effect is amplified by robust CGPs and EPP. By analyzing data from 4026 firm-year observations of A-share listed Chinese companies (2017–2022), the findings highlight the importance of innovation, governance, and policy in achieving sustainable environmental outcomes. This study provides valuable insights for firms and policymakers to foster green innovation and align corporate strategies with global sustainability goals. Full article

Background: The widespread adoption of precision medicine in routine cancer care remains a critical challenge, even as advanced technologies expand and personalized therapies demonstrate remarkable success in certain cancer types. While breakthrough innovations in targeted treatments have revolutionized outcomes for specific cancers, translating these scientific advances into standard clinical practice continues to be an evolving and complex endeavor. Croatia has a nationwide project of precision oncology through the comprehensive genomic profiling (CGP) analysis. Since collecting and analyzing real-world data is crucial for clinical research and defining the value of CGP in precision oncology, we aimed to present the data from everyday clinical practice given the opportunities and challenges we faced. Methods: This was a retrospective observational study conducted at the national level in all patients whose tumor samples were subjected to CGP between 1 January 2020 and 31 December 2021. Results: In total, 481 patients with CGP results were included in this study. Gastrointestinal and reproductive malignancies were the most common, accounting for 29.1% and 28.9% of all tested tumors, respectively. Specifically, colorectal tumors made up 19.1% of cases, while uterine tumors represented 11.2%. At least one clinically relevant genomic alteration was found in 76.7% of patients, with the KRAS mutation (27.2%) being the most common. During the two-year study period, 26,709 individuals lost their lives to cancer in Croatia. Combining this with the CGP selection criteria valid at the time, there was an estimated population of approximately 13,350 potentially eligible patients for the CGP analysis, meaning that only 3.6% of potentially eligible patients were tested. Conclusions: The analysis identified clinically actionable genomic alterations in approximately 80% of the evaluated patients, suggesting they could be candidates for targeted therapeutic interventions. The adoption of CGP remains limited, with estimates indicating that under 5% of metastatic cancer patients received testing in the initial two-year implementation period, despite established national insurance coverage guidelines. This low utilization rate suggests a significant gap in access to genomic testing, leaving many eligible cancer patients without the potential benefits of this diagnostic approach. Full article