Search Results (645)

Arrhythmogenic cardiomyopathy (ACM; MIM #107970) is a primitive heart muscle disease characterized by progressive myocardial loss and fibrosis or fibrofatty replacement, predisposing patients to ventricular arrhythmias, sudden cardiac death, and heart failure. Despite advances in imaging and genetics, early diagnosis remains challenging due to incomplete penetrance, variable phenotypic expressivity, and the fact that fatal arrhythmic events may often occur in the early stages of the disease. In this context, the identification of reliable biomarkers could enhance diagnostic accuracy, support risk stratification, and guide clinical management. This narrative review examines the current landscape of potential and emerging biomarkers in ACM, including troponins, natriuretic peptides, inflammatory proteins, microRNAs, fibrosis-related markers, and other molecules. Several of these biomarkers have demonstrated associations with disease severity, arrhythmic burden, or structural progression, although their routine clinical utility remains limited. The increasing relevance of genetic testing and non-invasive tissue characterization—particularly through cardiac imaging techniques—should also be emphasized as part of a multimodal diagnostic strategy in which biomarkers may play a complementary role. Although no single biomarker currently meets the criteria for a standalone diagnostic application, ongoing research into multi-marker panels and novel molecular targets offers promising perspectives. In conclusion, the integration of circulating biomarkers with imaging findings, genetic data, and clinical parameters may open new avenues for improving early detection and supporting personalized therapeutic strategies in patients with suspected ACM. Full article

Metal Injection Molding (MIM) is based on the processing of highly filled polymers via the well established polymer injection molding process. It offers a highly efficient processing route for the indirect manufacturing of especially small and complex metal parts. In this regard, polyoxymethylene (POM) is often used as a primary binder component in MIM feedstocks due to its high debinding rate through a time-saving catalytic debinding process, utilizing the acid-catalyzed degradation of POM for polymer removal. However, thermally induced degradation of POM under processing conditions can also lead to changes in processing behavior, which is particularly important in highly filled polymers due to their already challenging processability. In this context, the present work demonstrates the impact of POM homopolymers (POM-H) and copolymers (POM-C) with varying viscosities on feedstock characteristics, their influence on the thermal processing stability, and their significance for the properties of the green parts. Within the study, the thermal degradation of both material types was assessed by viscosity measurements and thermogravimetry, with POM-H exhibiting more significant degradation compared to the thermally more stable POM-C, especially at higher temperatures. Catalytic debinding performance was found to be adequate for all materials. However, lower viscosity POM-C grades are preferred to optimize processability in MIM. Full article

With the increasing diversity of remote sensing modalities, multimodal image fusion improves target recognition accuracy but also introduces new security risks. Adversaries can inject small, imperceptible perturbations into a single modality to mislead model predictions, which undermines system reliability. Most existing defences are designed for single-modal inputs and face two key challenges in multimodal settings: 1. vulnerability to perturbation propagation due to static fusion strategies, and 2. the lack of collaborative mechanisms that limit overall robustness according to the weakest modality. To address these issues, we propose CAGMC-Defence, a cross-attention-guided multimodal collaborative defence framework for multimodal remote sensing. It contains two main modules. The Multimodal Feature Enhancement and Fusion (MFEF) module adopts a pseudo-Siamese network and cross-attention to decouple features, capture intermodal dependencies, and suppress perturbation propagation through weighted regulation and consistency alignment. The Multimodal Adversarial Training (MAT) module jointly generates optical and SAR adversarial examples and optimizes network parameters under consistency loss, enhancing robustness and generalization. Experiments on the WHU-OPT-SAR dataset show that CAGMC-Defence maintains stable performance under various typical adversarial attacks, such as FGSM, PGD, and MIM, retaining 85.74% overall accuracy even under the strongest white-box MIM attack ($ϵ=0.05$), significantly outperforming existing multimodal defence baselines. Full article

Background: Rectal cancer is common and frequently treated with neoadjuvant radiotherapy prior to surgery to reduce the risk of tumour recurrence. However, the therapeutic benefits and side effects of radiotherapy can vary between patients, and there are currently no validated biomarkers to predict treatment response. Tumour cell density (TCD) and tumour-infiltrating lymphocyte (TIL) density are proven prognostic biomarkers in colorectal cancer; however, their utility in predicting radiotherapy response remains unclear. We assessed the prognostic and predictive value of TCD and TIL density in rectal cancer patients treated with radiotherapy. Methods: TCD was quantified using a manual point-counting method in 253 pre-treatment biopsies and across the entire tumour area of 569 resection specimens from the MRC CR07 clinical trial, which randomised patients to either neoadjuvant short-course radiotherapy (SCRT) or straight to surgery (control). TIL density was measured in 102 biopsies and matched resection specimens (73 SCRT, 29 control) across different tumour areas using deep learning-based cell detection in MIM (HeteroGenius Ltd., Leeds, UK). Cutoffs for low/high-TCD and TIL density were both pre-defined and derived from survival data using the survminer R package. Survival analyses were performed to evaluate the predictive and prognostic value of TCD/TIL in relation to overall and cancer-specific survival. Results: TCD in the resection specimens was lower in the SCRT group (19.9%, IQR 12.9–26.7%) than the control group (34.3%, IQR 27.7–40.5%, p < 0.001). In control resections, low-TCD was associated with a higher risk of all-cause mortality (HR 2.20, 95% CI 1.41–3.44, p < 0.001) and cancer-related death (HR 2.69, 95% CI 1.41–5.13, p = 0.0026). In contrast, after SCRT, low resection TCD was associated with a reduced risk of death (HR 0.63, 95% CI 0.40–0.98, p = 0.04). In the SCRT group, low biopsy TCD prior to radiotherapy was associated with a reduced risk of cancer-related death (HR 0.34, 95% CI 0.13–0.89, p = 0.028). Across both trial arms, TIL density was higher in pre-treatment biopsies than resections (2492 vs. 1304/mm², p < 0.001). Low biopsy TIL density was associated with an increased risk of all-cause mortality (HR 2.43, 95% CI 1.24–4.76, p = 0.01). The SCRT group had lower TIL density in the resection compared with controls (1210 vs. 1615/mm², p < 0.001), and low resection TIL density across the whole tumour area was associated with a higher risk of death (HR 2.55, 95% CI 1.11–5.87, p = 0.027). Conclusions: Our findings support the role of TCD and TIL density as quantitative biomarkers in rectal cancer patients. TCD can be used to assess the degree of response to radiotherapy, and contrasting survival associations are observed between straight-to-surgery and SCRT-treated patients. This study raises the possibility of using TCD as both a prognostic and predictive biomarker. TIL density failed to show predictive value but demonstrated expected prognostic associations. Full article

Metal–organic frameworks (MOFs) are promising materials for drug delivery due to their structural tunability and high surface area. This work reports on the synthesis of ZIF-8 for the in situ encapsulation of hesperidin, a flavonoid with poor water solubility used in the treatment of circulatory system disorders, as a gastric-targeted drug delivery system (DDS). A 2³ full factorial design was used to optimize drug loading, investigating the effects of DMSO concentration, 2-MIm/Zn²⁺ molar ratio, and final solution volume (water content). The materials were characterized by ATR-FT-IR, TG, XRD, and SEM analyses, confirming successful ZIF-8 synthesis and partial hesperidin encapsulation. Drug release kinetics were evaluated at pH 1.0 and 6.86. The system showed a faster and more pronounced release at pH 1.0, driven by MOF degradation, demonstrating its potential as a gastric-targeted DDS. This study confirms the feasibility of ZIF-8 to improve hesperidin solubility and bioavailability, highlighting a novel strategy for its therapeutic application. Full article

This paper presents a W-band high-efficiency and high-output-power power amplifier (PA) based on a 130 nm AlGaN/GaN-on-SiC HEMT process. The PA is designed to deliver optimal output power and gain performance across the entire W-band. A balanced architecture is adopted, combining two amplifier units through Lange couplers. High- and low-impedance microstrip lines are employed for input, output, and inter-stage matching. Each amplifier core adopts a three-stage configuration with gate width ratios of 1:2:4 to enhance gain. The bias network incorporates MIM capacitors and thin-film resistors to improve stability. Measured results indicate a small signal gain exceeding 17 dB under a gate voltage of −2.2 V and a drain voltage of +20 V. Within the 80–86 GHz frequency range, the PA achieves an output power above 34 dBm with a 22 dBm input power, corresponding to a power gain above 12 dB and a power-added efficiency (PAE) greater than 20%. The chip occupies a compact area of 2.65 mm × 3.75 mm. Compared with previously reported works, the proposed PA demonstrates the highest PAE within the 80–86 GHz band. Full article

Early and accurate detection of plant diseases is essential for ensuring food security and maintaining sustainable agricultural productivity. However, most deep learning models for plant disease classification rely heavily on large-scale annotated datasets, which are expensive, labor-intensive, and often impractical to obtain in real-world farming environments. To address this limitation, we propose a unified self-supervised learning (SSL) framework that leverages unlabeled plant imagery to learn meaningful and transferable visual representations. Our method integrates three complementary objectives—Bootstrap Your Own Latent (BYOL), Masked Image Modeling (MIM), and contrastive learning—within a ResNet101 backbone, optimized through a hybrid loss function that captures global alignment, local structure, and instance-level distinction. GPU-based data augmentations are used to introduce stochasticity and enhance generalization during pretraining. Experimental results on the challenging PlantDoc dataset demonstrate that our model achieves an accuracy of 77.82%, with macro-averaged precision, recall, and F1-score of 80.00%, 78.24%, and 77.48%, respectively—on par with or exceeding most state-of-the-art supervised and self-supervised approaches. Furthermore, when fine-tuned on the PlantVillage dataset, the pretrained model attains 99.85% accuracy, highlighting its strong cross-domain generalization and practical transferability. These findings underscore the potential of self-supervised learning as a scalable, annotation-efficient, and robust solution for plant disease detection in real-world agricultural settings, especially where labeled data is scarce or unavailable. Full article

Resistive switching (RS) phenomena are nowadays one of the most studied topics in the area of microelectronics. It can be observed in Metal–Insulator–Metal (MIM) structures that are the basis of resistive switching random-access memories (RRAMs). In the case of commercial use of RRAMs, it is beneficial that the applied materials would have to be compatible with Complementary Metal-Oxide-Semiconductor (CMOS) technology. Fabricating methods of these materials can determine their stoichiometry and structural composition, which can have a detrimental impact on the electrical performance of manufactured devices. In this study, we present the influence of the Ar/N₂ ratio during reactive magnetron sputtering of titanium nitride (TiN) electrodes on the resistive switching behavior of MIM devices. We used silicon oxide (SiOx) as a dielectric layer, which was characterized by the same properties in all fabricated MIM structures. The composition of TiN thin layers was controlled by tuning the Ar/N₂ ratio during the deposition process. The fabricated conductive materials were characterized in terms of chemical and structural properties employing X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis. Structural characterization revealed that increasing the Ar content during the reactive sputtering process affects the crystallite size of the deposited TiN layer. The resulting crystallite sizes ranged from 8 Å to 757.4 Å. The I-V measurements of fabricated devices revealed that tuning the Ar/N₂ ratio during the deposition of TiN electrodes affects the RS behavior. Our work shows the importance of controlling the stoichiometry and structural parameters of electrodes on resistive switching phenomena. Full article

Structure–property relationships in imidazolium-based hybrid Sb(III) chlorides provide critical guidance for designing high-performance materials. Three zero-dimensional metal halides, namely, [C₃mmim]₂SbCl₅ (1, [C₃mmim]⁺ = 1-propyl-2,3-dimethylimidazolium), [C₅mmim]₂SbCl₅ (2, [C₅mmim]⁺ = 1-pentyl-2,3-dimethylimidazolium), and [C₅mim]₂SbCl₅ (3, [C₅mim]⁺ = 1-pentyl-3-methylimidazolium), are synthesized by ionothermal methods. These compounds exhibit markedly distinctly photophysical properties at their optimal excitation wavelengths. Structural analyses reveal that elongated alkyl chains in compounds 2 and 3 increase Sb–Sb distances compared to that in 1, effectively isolating [SbCl₅]²⁻ units, suppressing inter-center energy transfer, and reducing non-radiative transitions, thereby enhancing the photoluminescence quantum yield (PLQY). Furthermore, methyl substitution at the C2-position of the imidazolium ring in compounds 1 and 2 induces asymmetric coordination environments around the [SbCl₅]²⁻ emission centers, leading to pronounced structural distortion. This distortion promotes non-radiative decay pathways and diminishes luminescent efficiency. Furthermore, temperature-dependent spectroscopy analysis and fitting of the Huang–Rhys factor (S) reveal significant electron–phonon coupling in compounds 1–3, which effectively promotes the formation of self-trapped excitons (STEs). However, compound 1 exhibits extremely high S, which significantly enhances phonon-mediated non-radiative decay and ultimately reduces its PLQY. Overall, compound 3 has the highest PLQYs. Full article

The control of crystal polymorphs is central to the design of pharmaceuticals and functional materials. Conventionally, crystal polymorph production has been controlled primarily by adjusting chemical and thermodynamic parameters. In this study, we developed a device capable of emitting infrared radiation at selected wavelengths using a novel material having a “MIM structure” which is a type of metamaterial. With this device, we propose a new approach to crystal polymorph control through the irradiation of narrow-band infrared radiation that coincides with the infrared absorption band of specific functional groups. In this paper, we present the design and operating principle of a new crystallization system, and as an application example, we report the experimental results of controlling the crystal polymorphs of Ritonavir, an active pharmaceutical ingredient. Full article

In this study, tin oxide (SnO₂) resistive random-access memory (RRAM) thin films were fabricated using the thermal evaporation and radiofrequency and dc frequency sputtering techniques for metal–insulator–metal (MIM) structures. The fabrication process began with the deposition of a silicon dioxide (SiO₂) layer onto a silicon (Si) substrate, followed by the deposition of a titanium nitride (TiN) layer to serve as the bottom electrode. Subsequently, the tin oxide (SnO₂) layer was deposited as the resistive switching insulator. Two types of top electrodes were developed to investigate the influence of different oxygen concentrations on the bipolar switching, electrical characteristics, and performance of memory devices. An aluminum (Al) top electrode was deposited using thermal evaporation, while a platinum (Pt) top electrode was deposited via dc sputtering. As a result, two distinct metal–insulator–metal (MIM) memory RRAM device structures were formed, i.e., Al/SnO₂/TiN/SiO₂/Si and Pt/SnO₂/TiN/SiO₂/Si. In addition, the symmetry bipolar switching characteristics, electrical conduction mechanism, and oxygen concentration factor of the tin oxide-based memory devices using rapid thermal annealing and different top electrodes were determined and investigated by ohmic, space-charge-limit-current, Schottky, and Poole–Frenkel conduction equations in this study. Full article

In this study, a correlative approach using Raman spectroscopy and scanning electron microscopy (SEM) is introduced to meet the challenges of identifying impurities, especially carbon-related compounds in metal injection-molded (MIM) Mg-0.6Ca specimens designed for biomedical applications. This study addresses, for the first time, the issue of carbon residuals in the binder-based powder metallurgy (PM) processing of Mg-0.6Ca materials. A deeper understanding of the material microstructure is important to assess the microstructure homogeneity at submicron levels as this later affects material degradation and biocompatibility behavior. Both spectroscopic and microscopic techniques used in this study respond to the concerns of secondary phase distributions and their possible stoichiometry. Our micro-Raman measurements performed over a large area reveal Raman modes at ~1370 cm⁻¹ and ~1560 cm⁻¹, which are ascribed to the elemental carbon, and at ~1865 cm⁻¹, related to C≡C stretching modes. Our study found that these carbonaceous residuals/contaminations in the material microstructure originated from the polymeric binder components used in the MIM fabrication route, which then react with the base material components, including impurities, at elevated thermal debinding and sintering temperatures. Additionally, using evidence from the literature on thermal carbon cracking, the presence of both free carbon and calcium carbide phases is inferred in the sintered Mg-0.6Ca material in addition to the Mg₂Ca, oxide, and silicate phases. This first-of-its-kind correlative characterization approach for PM-processed Mg biomaterials is fast, non-destructive, and provides deeper knowledge on the formed residual carbonaceous phases. This is crucial in Mg alloy development strategies to ensure reproducible in vitro degradation and cell adhesion characteristics for the next generation of biocompatible magnesium materials. Full article

The manufacturing supply chain has been exposed to natural disasters and geopolitical risks whose impacts, such as disruptions in the supply of materials and parts, can be devastating. In recent years, the data space has become more widely implemented, and it is expected to be used as a platform for widespread collaboration between companies. This article discusses how companies participating in the manufacturing supply chain cooperate to recover from disruption and mitigate risks using a data space platform and a flexible manufacturing system. Employing enterprise architecture modeling, we explore a comprehensive strategy for enhancing the resilience of a data space-based manufacturing supply chain. The proposed strategy adopts a comprehensive approach to addressing physical security and cybersecurity risks from a security perspective. By combining enterprise architecture modeling with the Unified Architecture Framework and conducting a scenario-based simulation, we discovered that an alternative manufacturing process with a flexible method in the data space can be a key security control measure for mitigating the risk associated with parts supply. The results of the alternative manufacturing simulation show that flexible manufacturing using BJT and MIM methods elicits better performance in terms of parts production volume and cost compared with conventional methods. The proposed method and the findings of this study contribute to consolidating a profound understanding of security and the mitigation of disruptive situations in a data space-based manufacturing supply chain. Full article

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

The MIM1-BH3 mimetic, which inhibits the Mcl-1 antiapoptotic protein, may be an efficacious molecule able to induce apoptosis. Previously, we found that moxifloxacin (MXFL) is able to modulate Mcl-1 protein expression. Therefore, in the current study, we assessed the impact of the MXFL, MIM1, and MXFL/MIM1 mixtures on viability and apoptosis in amelanotic A375 and melanotic G361 melanoma cells. The obtained results showed that MXFL and MIM1 exerted high cytotoxic and proapoptotic potential. In the case of two-component models, we have demonstrated that the use of the MIM1 and MXFL mixtures resulted in a significant intensification of both cytotoxic and proapoptotic activity, shown as a modulatory effect on the early and late phases of apoptosis toward the analyzed melanoma cells when compared with MIM1 or MXFL alone. We report, for the first time, the high proapoptotic activity of MIM1 and MXFL applied in a two-component model toward melanoma cells, pointing to the Mcl-1 protein as an important molecular target. The observed potential synergistic mode of action—expressed as cytotoxic and proapoptotic activity enhancement, detected for MIM1 and MXFL—may represent a new direction for further in vitro and in vivo experiments concerning the role of the Mcl-1 protein in the treatment of melanoma. Moreover, the presented results certainly contribute to expanding the knowledge of the pharmacology of both fluoroquinolones and BH3 mimetics, and also enable a better understanding of melanoma cell biology. Full article