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Breast cancer is a complex and highly heterogeneous disease, and its management is increasingly moving towards the principles of precision medicine. In this context, the androgen receptor (AR) has emerged as a promising therapeutic target, particularly within the challenging subgroup of triple-negative breast cancers (TNBCs) that express it. This scoping review provides a comprehensive and detailed analysis of the multifaceted role of AR in breast cancer. We delve into its intricate molecular structure, its differential function in ER-positive vs. TNBC subtypes, and the detailed molecular mechanisms that govern its activity. We provide a thorough examination of the landmark clinical trials with antiandrogen agents, including not only enzalutamide but also other first- and second-generation compounds, and discuss the emerging data on their efficacy. Furthermore, we will explore the critical challenges that hinder their widespread clinical adoption, such as primary and acquired resistance mechanisms, the need for robust predictive biomarkers, and the heterogeneity of AR expression. Finally, we outline future research directions, focusing on novel combination therapies and the development of next-generation agents and predictive tools to optimize patient selection and improve clinical outcomes. Full article

(This article belongs to the Section Breast Cancer)

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15 pages, 1755 KB

Open AccessArticle

Simulation Study on Injection/Withdrawal Scenarios of Hydrogen-Blended Methane in a Depleted Gas Reservoir

by Yujin Kim and Hochang Jang

Energies 2026, 19(2), 374; https://doi.org/10.3390/en19020374 (registering DOI) - 12 Jan 2026

Abstract

This study presents a quantitative simulation analysis of hydrogen-enriched methane (HENG) storage with nitrogen as the cushion-gas in a depleted gas reservoir by varying three key operational parameters: the injection/withdrawal period, hydrogen blending ratio (5–20%), and injection depth. Ten injection–withdrawal cycles were modeled for each scenario, and performance was evaluated using cycle-averaged and cumulative hydrogen purity, recovery factors, and the mixing zone size. Extending the injection period increased hydrogen purity to 20.00–20.26% and reduced nitrogen to 0.001–0.003%, but recovery decreased from 65.63 to 53.83–41.09% due to enhanced dispersion and residual trapping. The blending ratio was the dominant control: 20% blending yielded 19.9–20.0% purity with nitrogen as low as 0.00–0.03%, whereas 5–10% blending produced lower purity but minimized nitrogen production to 0.97–1.08%. Injection depth affected nitrogen recovery more than purity, increasing from 0.72–1.20% (upper) to 1.46–1.61% (lower), along with thicker mixing zones. Final mixing zone size ranged from 3176 to 5546 blocks, with smaller zones consistently linked to higher purity and lower nitrogen breakthrough. The shut-in period further reduced nitrogen recovery from 6.49 to 1.33% and stabilized mixing behavior. Overall, minimizing late-cycle mixing zone thickness is essential for maintaining HENG storage performance. Although this study provides quantitative insights into HENG operational strategies, the use of a homogeneous grid and simplified fluid properties limits representation of geological heterogeneity and reactive processes. Future work will incorporate heterogeneity and reaction modeling into field-scale simulations to validate and refine these operating strategies for practical deployment. Full article

(This article belongs to the Topic Exploitation and Underground Storage of Oil and Gas)

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21 pages, 684 KB

Open AccessArticle

The Impact of Green Shipping Practices on Customer Satisfaction and Customer Retention in the Container Shipping Industry: Evidence from Maritime Freight Forwarders

by Chun-Hsiang Chang and Rong-Her Chiu

Sustainability 2026, 18(2), 775; https://doi.org/10.3390/su18020775 (registering DOI) - 12 Jan 2026

Abstract

This study established an empirical structural equation model to examine whether the adoption of green shipping practices (GSPs) will influence customer satisfaction and customer retention in the container shipping industry from the perspective of freight forwarders, while accounting for the effectiveness of marketing activities. Through questionnaire survey, 114 responding data were collected from freight forwarders in the Taiwan area. The main results discovered are as follows: (1) adoption of GSPs was found to positively influence companies’ environmental performance in terms of perceived green capability (PGC); (2) the most significant finding in this study is the irrelevance of PGC to both CS and CR from the perspective of freight forwarders. In addition, after discussing the managerial implications, this study examined whether adopting GSPs to improve the environmental and productivity performance of liner carriers remains an ongoing debate and if it warrants a further investigation. Full article

(This article belongs to the Section Economic and Business Aspects of Sustainability)

28 pages, 1995 KB

Open AccessArticle

Decision Support Framework for Digital Music Integration in Education Reform Using Picture Fuzzy FUCA and Industry–Academia Collaboration

by Yunjian Hu and Linhua Duan

Symmetry 2026, 18(1), 145; https://doi.org/10.3390/sym18010145 - 12 Jan 2026

Abstract

The incorporation of digital music into the reform of education has become one of the primary methods to improve educational outcomes, increase creativity, and innovate the practices in the classroom. This combination, together with the close industry–academia cooperation, presents the possibilities to integrate educational strategies in accordance with the technological and creative demands of the contemporary world. Nevertheless, uncertainty, reluctance, symmetry, and subjectivity in expert ratings are significant problems to cope with when considering multi-criteria decision-making (MCDM). To resolve them, this paper suggests a Picture Fuzzy Faire Un Choix Adequat (PF-FUCA) decision support model, where fifteen options will be rated by seven criteria, depending on the contribution of four professional decision-makers. These findings indicate that the PF-FUCA framework is effective and superior to the current PF-MCDM models, as illustrated by sensitivity and comparison analysis. The identified best strategies based on the framework are blockchain-based music copyright education and integrated music–STEM platforms that, when combined, offer a viable policy instrument to policymakers, educators, and industry stakeholders. Full article

(This article belongs to the Section Mathematics)

24 pages, 1356 KB

Open AccessArticle

Prediction of Targets and Mechanisms of Top Ten Core “Food–Medicine Homologous Traditional Chinese Medicines” in Delaying Vascular Aging: An Integrative Computational Study

by Yiling Bai, Qian Liu, Qing Zhou, Pengyang Xiao and Lina Xia

Pharmaceuticals 2026, 19(1), 131; https://doi.org/10.3390/ph19010131 - 12 Jan 2026

Abstract

Background and Objectives: Many “food–medicine homologous traditional Chinese medicines (TCMs)” have been shown to delay vascular aging. In this study, we will select “food–medicine homologous TCMs” with the most potential to delay human-origin vascular aging and predict their core targets and mechanisms. Methods: Human-origin vascular-aging-related genes were screened from the NCBI and Aging Atlas databases. Candidate “food–medicine homologous TCMs” were initially filtered by constructing a protein–protein interaction network, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Key targets were validated in the Gene Expression Omnibus database and further screened by least absolute shrinkage and a selection operator. Finally, molecular docking and molecular dynamics simulations identified core targets. Results: Ten core “food–medicine homologous TCMs” with potential to delay human-derived vascular aging were identified: Crocus Sativus L., Glycyrrhiza uralensis Fisch., Chrysanthemum morifolium Ramat., Astragalus membranaceus (Fisch.) Bunge, Sophora japonica L., Hippophae rhamnoides L., Portulaca oleracea L., Lonicera japonica Thunb., Citrus aurantium L. var. amara Engl., and Morus alba L. Further analysis indicated that β-Carotene within these core “food–medicine homologous TCMs” may represent a potential active component targeting matrix metalloproteinase-1, with its action potentially linked to the interleukin-17 signaling pathway. The present study highlights the new hypothesis that immunosenescence (Th17/IL-17) is involved in vascular aging, suggesting that the top ten core “food–medicine homologous TCMs” may delay vascular aging by regulating immune cell function. Conclusions: The top ten “food–medicine homologous TCMs” provide potential candidates for functional products that delay vascular aging and provide computationally predicted mechanistic insights and a scientific basis for novel therapies. Full article

23 pages, 4276 KB

Open AccessArticle

Improvement of Certain Composite Structures’ Quality by the Ultrasonic Field

by Dan Florin Nitoi, Oana Chivu, Florea Bogdan, Augustin Semenescu, Vili Pasare, Constantin Dumitrascu and Dragoş-Florin Marcu

Appl. Sci. 2026, 16(2), 781; https://doi.org/10.3390/app16020781 - 12 Jan 2026

Abstract

This paper presents the activities carried out to improve the quality of certain composite structures by manufacturing them with the assistance of an ultrasonic field. As many composite materials use epoxy resins as base materials, an important problem was noted, namely their high curing time, as well as the problems of lack of adhesion and delamination, which are also known and experienced in the case of composite structures made with metallic materials as a support. The application of an ultrasonic field can successfully solve both problems. To demonstrate this improvement, the manufacturing of cylinders used in braking stands in the automotive industry was considered the main application. The proposed technology will be then extended to conveyor belts or to the manufacturing of other high-adhesion surfaces. This article presents the traditional method and the new ultrasonic field deposition technology. The design of the ultrasonic system is presented based on an analytical calculation, FEM modal analysis, followed by the construction of the ultrasonic system, as well as by bending tests and infrared thermography to demonstrate the advantages of presented method. Full article

(This article belongs to the Topic Numerical Simulation of Composite Material Performance)

15 pages, 318 KB

Open AccessArticle

Reconfiguring Asia Through the Lens of Buddhism: India and Okakura Tenshin’s The Ideals of the East

by Yuanyuan Liao

Religions 2026, 17(1), 84; https://doi.org/10.3390/rel17010084 - 12 Jan 2026

Abstract

The Japanese scholar and art critic Okakura Tenshin traveled to colonial India from January to September 1902 and made three visits to the Buddhist holy site of Bodh Gaya. There, he attempted to purchase a piece of land from the landowner, the Mahant, to build a vihāra (resthouse) for Japanese Buddhist devotees. His purchase request was rejected by the British colonial authority for his foreigner status, despite no legal prohibition against land sales to foreigners under Bodh Gaya’s land management laws at the time. The year after his journey to India, Okakura Tenshin published The Ideals of the East, wherein the renowned declaration that “Asia is one” subsequently evolved to be the intellectual cornerstone of twentieth-century Asianism (or Pan-Asianism). How did Okakura’s Indian journey and his experience of the failed attempt to purchase land in Bodh Gaya catalyze his conception of “Asia is One”? This essay first traces the Buddhist revival movements in late nineteenth-century India and Japan, elucidating how Buddhism helped forge a sense of transnational solidarity between the two nations, which Okakura also embraced. It then examines Okakura’s trip to India and his plan to purchase land at Bodh Gaya, uncovering the underlying geopolitical struggle between the British Empire and the New Asian Power Japan. In this context, the analysis will show that Okakura’s frustrating experience of failed land purchase underscored for him the necessity for the solidarity between Japan and India and the need for a unitary idea of Asia to articulate that solidarity. Finally, a comparative textual analysis between The Ideals of the East (1903) and Okakura’s “History of Japanese Art” lectures given at the Tokyo Fine Arts School before his trip to India explicates how Buddhism, which was being revived by a collective of various groups in and outside its place of origin India, served as a cohesive discursive agent in Okakura’s construction of the narrative of an Asian unity. This Buddhist framework helped Okakura to reconstruct the interlinked cultural histories of India, China, and Japan into a unified notion of Asia within which he crystallized a unique and favored cultural identity for Japan. Full article

(This article belongs to the Special Issue Religion, Liberalism and the Nation in East Asia)

13 pages, 263 KB

Open AccessArticle

Incidence and Risk Factors of Nasal Pressure Injuries in Neonates Receiving Noninvasive Ventilation

by Blgeis Elgadra, Lina Abdullah, Hafsa Alsharif, Abdelrahman Dirar, Janet Estalilla, Quennie Fernandes, Habeebah Fazlullah, Jojo Furigay, Roderick Pedron, Bilal Kanth, Mohammad A. A. Bayoumi and Ashraf Gad

J. Clin. Med. 2026, 15(2), 615; https://doi.org/10.3390/jcm15020615 - 12 Jan 2026

Abstract

Background/Objective: Nasal pressure injuries following non-invasive ventilation (NIV) have remained a common complication. Available evidence on injury severity characteristics, timing, and predictors of progression to moderate–severe injury, especially in large cohorts, is limited. The objective was to assess the incidence, characteristics and risk factors for nasal pressure injuries among neonates on NIV in a large tertiary neonatal intensive care unit (NICU). Methods: This retrospective observational study recruited all infants who experienced nasal pressure injury while on NIV from March 2018 to November 2022. The severity of the injury was categorized by the Fischer classification. Demographics, perinatal, respiratory, and device-related factors were examined. Multivariable logistic regression revealed independent predictors of moderate to severe injury. Results: There were 237 nasal injury episodes in 226 infants (0.406 per 100 device-days), considering 17,004 NICU admissions and 58,363 NIV device-days. Most injuries were mild (Stage I 81%) while 19% were moderate–severe (Stage II–III). Early injuries (≤3 days after NIV) were present in 83.5% of patients and were often related to the nasal bridge. In particular, late-onset injuries (>3 days) were more likely in infants with previous injury, exposure to postnatal steroids, longer prior intubation, or septal involvement. Moreover, multivariable analysis identified three specific independent predictors of moderate–severe injury previous nasal injury (aOR 6.25, 95% CI 1.11–35.35), septal or combined bridge/septum involvement (aOR 2.98, 95% CI 1.04–8.43), and prolonged period of positive pressure ventilation at birth (aOR 1.23 per minute, 95% CI 1.04–1.45). Conclusions: Most nasal pressure injuries seen during NIV are mild and early; however, recurrence, septal involvement, and prolonged resuscitative ventilation markedly increase the risk of severe injury. Improving surveillance on early NIV use, monitoring of septal pressure points, and proactive interventions with interface management will aid in minimizing preventable nasal morbidity. Full article

(This article belongs to the Section Clinical Pediatrics)

60 pages, 1123 KB

Open AccessArticle

Meditation Transcending Signs: Seven Concepts for a Buddhist Psychosemiotics

by Federico Divino

Philosophies 2026, 11(1), 7; https://doi.org/10.3390/philosophies11010007 - 12 Jan 2026

Abstract

This paper aims to provide an in-depth and detailed overview of the relationship between language and cognition in Pāli Buddhist texts. These reflections will touch on several fundamental themes, such as the role of signs in structuring cognitive processes and semiosis as a force linked to the proliferation of concepts and percepts, whose organization underlies the constitution of a shared and partly subjective “world”. The paper will engage with linguistics, semiotics, and biosemiotics in order to acquire a vocabulary capable of better understanding the Buddhist reflections on these issues, and, where possible, it will also offer a genealogical inquiry that explains why the theme of language takes on the pivotal role it holds in Pāli Buddhism. Full article

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25 pages, 2813 KB

Open AccessReview

PSMA-Based Radiopharmaceuticals in Prostate Cancer Theranostics: Imaging, Clinical Advances, and Future Directions

by Ali Cahid Civelek

Cancers 2026, 18(2), 234; https://doi.org/10.3390/cancers18020234 - 12 Jan 2026

Abstract

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

(This article belongs to the Section Cancer Therapy)

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20 pages, 3991 KB

Open AccessReview

Review on Mining Robust Lactic Acid Bacteria for Next-Generation Silage Inoculants via Multi-Omics

by Yanyan Liu, Mingxuan Zhao, Shanyao Zhong, Guoxin Wu, Fulin Yang and Jing Zhou

Life 2026, 16(1), 108; https://doi.org/10.3390/life16010108 - 12 Jan 2026

Abstract

Lactic acid bacteria (LAB), as the core microorganisms in silage fermentation, play a crucial role in improving silage quality and ensuring feed safety, making the screening, identification, and functional characterization of LAB strains a significant research focus. Researchers initially isolate and purify LAB from various samples, followed by identification through a combination of morphological, physiological, biochemical, and molecular biological methods. Systematic screening has been conducted to identify LAB strains tolerant to extreme environments (e.g., low temperature, high temperature, high salinity) and those possessing functional traits such as antimicrobial activity, antioxidant capacity, production of feruloyl esterase and bacteriocins, as well as cellulose degradation, yielding a series of notable findings. Furthermore, modern technologies, including microbiomics, metabolomics, metagenomics, and transcriptomics, have been employed to analyze the structure and functional potential of microbial communities, as well as metabolic dynamics during the ensiling process. The addition of superior LAB inoculants not only facilitates rapid acidification to reduce nutrient loss, inhibit harmful microorganisms, and improve fermentation quality and palatability but also demonstrates potential functions such as degrading mycotoxins, adsorbing heavy metals, and reducing methane emissions. However, its application efficacy is directly constrained by factors such as strain-crop specific interactions, high dependence on raw material conditions, limited functionality of bacterial strains, and relatively high application costs. In summary, the integration of multi-omics technologies with traditional methods, along with in-depth exploration of novel resources like phyllosphere endophytic LAB, will provide new directions for developing efficient and targeted LAB inoculants for silage. Full article

(This article belongs to the Section Microbiology)

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9 pages, 395 KB

Open AccessArticle

Ideas on New Fluid Dynamic Theory Based on the Liutex Rigid Rotation Definition

by Kuncan Zheng, Zhi Pan, You Fan, Yiting Liu, Dapeng Zhang and Yonghong Niu

Fluids 2026, 11(1), 20; https://doi.org/10.3390/fluids11010020 - 12 Jan 2026

Abstract

In recent years, a novel decomposition of fluid motion has been proposed, which mathematically defines a type of fluid rigid rotation distinct from vorticity, termed the Liutex quantity. Since its introduction, Liutex has been successfully applied to describe fluid vortices and has emerged as an internationally recognized third-generation vortex identification method. This new motion decomposition undoubtedly leads to a revised description of rotational and deformational motions, thereby necessitating a new description of dynamics. Therefore, based on the Stokes assumption and the novel Liutex decomposition, this paper constructs a new constitutive equation and derives a new set of fluid dynamic equations. The research findings reveal two key insights: first, the new shear stress in the fluid is no longer symmetric; second, in addition to traditional forces such as body force, pressure, and viscous force, an additional force induced by Liutex-based rigid rotation is identified. Furthermore, the new dynamic framework encompasses traditional fluid dynamics, with the latter being a special case when Liutex equals the traditional vorticity. It is anticipated that the proposed equations will find significant applications in the study of fluid vortices and turbulence and will undoubtedly stimulate research interest in the field of fluid mechanics. Full article

(This article belongs to the Special Issue Vortex Definition and Identification)

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51 pages, 2840 KB

Open AccessArticle

Policy Synergy Scenarios for Tokyo’s Passenger Transport and Urban Freight: An Integrated Multi-Model LEAP Assessment

by Deming Kong, Lei Li, Deshi Kong, Shujie Sun and Xuepeng Qian

Energies 2026, 19(2), 366; https://doi.org/10.3390/en19020366 - 12 Jan 2026

Abstract

To identify the emission reduction potential and policy synergies of Tokyo’s road passenger and urban road freight transport under the “carbon neutrality target,” this paper constructs an assessment framework for megacities. First, based on macroeconomic socioeconomic variables (population, GDP, road length, and employment), regression equations are used to predict traffic turnover for different modes of transport from 2021 to 2050. Then, the prediction results are imported into the LEAP (Long-range Energy Alternatives Planning) model. By adjusting three policy levers—vehicle technology substitution (ZEV: EV/FCEV), energy intensity improvement, and upstream electricity and hydrogen supply decarbonization—a “single-factor vs. multi-factor (policy synergy)” scenario matrix is designed for comparison. The results show that the emission reduction potential of a single measure is limited; upstream decarbonization yields the greatest independent emission reduction effect, while the emission reduction effect of deploying zero-emission vehicles and improving energy efficiency alone is small. In the most ambitious composite scenario, emissions will decrease by approximately 83% by 2050 compared to the baseline scenario, with cumulative emissions decreasing by over 35%. Emissions from rail and taxis will approach zero, while buses and freight will remain the primary residual sources. This indicates that achieving net zero emissions in the transportation sector requires not only accelerated ZEV penetration but also the simultaneous decarbonization of electricity and hydrogen, as well as policy timing design oriented towards fleet replacement cycles. The integrated modeling and scenario analysis presented in this paper provide quantifiable evidence for the formulation of a medium- to long-term emissions reduction roadmap and the optimization of policy mix in Tokyo’s transportation sector. Full article

(This article belongs to the Special Issue Sustainable Energy Systems: Progress, Challenges and Prospects)

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24 pages, 1445 KB

Open AccessReview

Usefulness of Transanal Irrigation and Colon Hydrotherapy in the Treatment of Chronic Constipation and Beyond: A Review with New Perspectives for Bio-Integrated Medicine

by Raffaele Borghini, Francesco Borghini, Alessia Spagnuolo, Agnese Borghini and Giovanni Borghini

Gastrointest. Disord. 2026, 8(1), 6; https://doi.org/10.3390/gidisord8010006 - 12 Jan 2026

Abstract

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

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34 pages, 5602 KB

Open AccessReview

Liquid Biopsy in Early Screening of Cancers: Emerging Technologies and New Prospects

by Hanyu Zhu, Zhenyu Li, Kunxin Xie, Sajjaad Hassan Kassim, Cheng Cao, Keyu Huang, Zipeng Lu, Chenshan Ma, Ying Li, Kuirong Jiang and Lingdi Yin

Biomedicines 2026, 14(1), 158; https://doi.org/10.3390/biomedicines14010158 - 12 Jan 2026

Abstract

Liquid biopsy is moving beyond mutation-centric assays to multimodal frameworks that integrate cell-free DNA (cfDNA) signals with additional analytes such as circulating tumor cells (CTCs) and extracellular vesicles (EVs). In this review, we summarize emerging technologies across analytes for early cancer detection, emphasizing sequencing and error-suppression strategies and the growing evidence for multi-cancer early detection (MCED), tissue-of-origin (TOO) inference, diagnostic triage, and longitudinal surveillance. At low tumor fractions, fragmentomic and methylation features preserve tissue and chromatin context; when combined with radiomics using deep learning, they support blood-first, high-specificity risk stratification, increase positive predictive value (PPV), reduce unnecessary procedures, and enhance early prediction of treatment response and relapse. Building on these findings, we propose a pathway-aware workflow: initial blood-based risk scoring, followed by organ-directed imaging, and targeted secondary testing when indicated. We further recommend that model reports include not only discrimination metrics but also calibration, decision-curve analysis, PPV/negative predictive value (NPV) at fixed specificity, and TOO accuracy, alongside multi-site external validation and blinded dataset splits to improve generalizability. Overall, liquid biopsy is transitioning from signal discovery to deployable multimodal decision systems; standardized pre-analytical and analytical workflows, robust error suppression, and prospective real-world evaluations will be pivotal for clinical implementation. Full article

(This article belongs to the Special Issue Emerging Technologies in Liquid Biopsy of Cancers)

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