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Search Results (10,564)

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21 pages, 1796 KB  
Review
Mechanisms of Visuomotor Interception
by Inmaculada Márquez and Mario Treviño
Brain Sci. 2026, 16(5), 435; https://doi.org/10.3390/brainsci16050435 (registering DOI) - 22 Apr 2026
Abstract
Background/Objectives: Visuomotor interception requires aligning action with the future state of moving targets under sensory and motor delays. This constraint provides a tractable framework to examine how predictive and feedback-driven processes interact. This narrative review evaluates theoretical and empirical accounts of interception, with [...] Read more.
Background/Objectives: Visuomotor interception requires aligning action with the future state of moving targets under sensory and motor delays. This constraint provides a tractable framework to examine how predictive and feedback-driven processes interact. This narrative review evaluates theoretical and empirical accounts of interception, with emphasis on how prediction and online control are integrated across behavioral and neural levels. Methods: We conducted a narrative synthesis of behavioral, eye-tracking, computational, and neurophysiological studies on visuomotor interception. Literature was identified through searches of PubMed, Web of Science, and Google Scholar using search terms including “visuomotor interception,” “predictive motor control,” “eye–hand coordination,” “time-to-contact,” “sensorimotor delay,” and related combinations. Studies published between 1986 and 2026 were considered, with emphasis on peer-reviewed empirical and theoretical work. Preprints were included only when directly relevant and are identified as such. The review compares internal model, ecological, and hybrid frameworks, and organizes evidence around spatial (“where”) and temporal (“when”) components of control. Results: Across paradigms, interception behavior is not well accounted for by purely predictive or reactive mechanisms. Instead, trajectories reflect a continuous interaction between anticipatory guidance and online correction. Spatial and temporal components show partial dissociation across tasks and manipulations. Available evidence supports the involvement of distributed circuits, including parietal, frontal, cerebellar, and subcortical systems, while indicating that eye movements play an active role in both information sampling and motor planning. Conclusions: Interception is best understood as the product of interacting biological, environmental, and learned constraints. Similar behavioral signatures can arise from distinct mechanisms, arguing against a unitary account. Progress requires integrating behavioral analyses with model-based and neural approaches to dissociate underlying computations. Full article
(This article belongs to the Section Behavioral Neuroscience)
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13 pages, 1228 KB  
Article
Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregulation, Elastase Suppression, and Scaffold Reinforcement
by Sanghyun Ye, Seongsu Kang, Eui Taek Jeong, Seung-Hyun Jun and Nae-Gyu Kang
Curr. Issues Mol. Biol. 2026, 48(5), 431; https://doi.org/10.3390/cimb48050431 (registering DOI) - 22 Apr 2026
Abstract
Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. [...] Read more.
Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging. Full article
(This article belongs to the Special Issue Exploring Molecular Pathways in Skin Health and Diseases)
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18 pages, 2863 KB  
Article
AI-Driven Durian Leaf Disease Classification Using Benchmark CNN Architectures for Precision Agriculture
by Rapeepat Klangbunrueang, Wirapong Chansanam, Natthakan Iam-On and Tossapon Boongoen
Appl. Sci. 2026, 16(9), 4062; https://doi.org/10.3390/app16094062 - 22 Apr 2026
Abstract
Durian (Durio zibethinus Murray) is Thailand’s most economically significant fruit export, yet foliar diseases pose a major threat to productivity and crop quality. Early-stage symptoms of several durian leaf diseases are visually similar, making reliable diagnosis difficult for farmers and even trained [...] Read more.
Durian (Durio zibethinus Murray) is Thailand’s most economically significant fruit export, yet foliar diseases pose a major threat to productivity and crop quality. Early-stage symptoms of several durian leaf diseases are visually similar, making reliable diagnosis difficult for farmers and even trained agronomists. This study aims to develop and evaluate an automated deep learning-based system for durian leaf disease classification under realistic field conditions. A dataset of 6119 leaf images representing six classes—Leaf_Healthy, Leaf_Colletotrichum, Leaf_Algal, Leaf_Phomopsis, Leaf_Blight, and Leaf_Rhizoctonia—was compiled from public datasets and field-collected samples. Six convolutional neural network (CNN) architectures—ConvNeXt, ResNet, DenseNet201, InceptionV3, EfficientNet-B3, and MobileNetV3—were benchmarked using a unified transfer-learning training protocol. Class imbalance was addressed using weighted cross-entropy loss, and performance was evaluated on a stratified held-out test set using accuracy, precision, recall, and F1-score metrics. The results show that ConvNeXt achieved the highest performance with 98.00% accuracy and a weighted F1-score of 0.98, followed by ResNet (96.82%) and DenseNet201 (96.09%), while efficiency-oriented models plateaued near 91%. Confusion matrix analysis revealed consistent misclassification among visually similar disease categories—Leaf_Algal, Leaf_Blight, and Leaf_Phomopsis—indicating biological similarity in lesion appearance rather than model limitations. The best-performing model was deployed as a publicly accessible web application using Gradio, enabling real-time disease diagnosis with an average inference time of approximately 0.54 s per image. Unlike prior studies, this work combines large-scale architecture benchmarking, class imbalance mitigation, and real-world deployment within a single unified framework. These findings demonstrate that modern CNN architectures can provide highly accurate and scalable disease detection tools, supporting precision agriculture by enabling early diagnosis, reducing inappropriate pesticide use, and improving decision-making for durian farmers. Full article
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17 pages, 926 KB  
Article
High-Throughput Sequencing Reveals Previously Undetected Viruses and Mixed Infections in Pepper (Capsicum annuum) in Hungary
by Emese Demián, Réka Sáray, Asztéria Almási, Kata Pogácsás and Katalin Salánki
Viruses 2026, 18(4), 481; https://doi.org/10.3390/v18040481 - 21 Apr 2026
Abstract
The increasing global movement of plant material and the complexity of viral communities associated with cultivated crops complicate routine plant virus diagnostics. High-throughput sequencing (HTS) has therefore become an important tool for the comprehensive characterization of plant viromes. In this study, symptomatic pepper [...] Read more.
The increasing global movement of plant material and the complexity of viral communities associated with cultivated crops complicate routine plant virus diagnostics. High-throughput sequencing (HTS) has therefore become an important tool for the comprehensive characterization of plant viromes. In this study, symptomatic pepper (Capsicum annuum) samples submitted to our laboratory between 2020 and 2025 were investigated using HTS following unsuccessful routine diagnostic assays, despite the presence of virus-like symptoms. Virome analysis revealed the presence of multiple viruses with distinct biological characteristics. Eggplant mottled dwarf virus (EMDV) sequences were identified, representing, to our knowledge, the first sequence data from Hungary. In addition, sequences related to tobacco vein clearing virus (TVCV) showed highest similarity to endogenous viral element present in Capsicum annuum genome assemblies. Persistent viruses, including bell pepper alphaendornavirus (BPEV) and pepper cryptic virus 2 (PCV2), were also detected. These findings demonstrate the complex viral communities associated with cultivated pepper and highlight the limitations of strictly targeted diagnostic approaches. The results emphasize the value of HTS for comprehensive virome characterization in horticultural crops. Full article
17 pages, 775 KB  
Article
UHPLC–MS/MS Method for the Simultaneous Quantification of 12 Antiretroviral Drugs in Human Plasma Using Dried Sample Spot Devices: Development, Validation, and Stability Evaluation
by Sara Soloperto, Elisa Martina, Alice Palermiti, Elisa Barnini, Greta Sabbia, Gianluca Bianco, Martina Billi, Camilla Martino, Alessandra Manca, Marco Simiele, Jessica Cusato, Antonio D’Avolio and Amedeo De Nicolò
Pharmaceutics 2026, 18(4), 513; https://doi.org/10.3390/pharmaceutics18040513 - 21 Apr 2026
Abstract
Background/Objectives: In several contexts, Dried Sample Spot Devices (DSSDs) offer a convenient and safe alternative for sampling, storage, and shipment, allowing the transport and storage of biological samples at room temperature, reducing shipment costs and improving access to diagnostics in faraway sites. [...] Read more.
Background/Objectives: In several contexts, Dried Sample Spot Devices (DSSDs) offer a convenient and safe alternative for sampling, storage, and shipment, allowing the transport and storage of biological samples at room temperature, reducing shipment costs and improving access to diagnostics in faraway sites. This can be pivotal for the use of the therapeutic drug monitoring of anti-HIV treatment: therefore, this study aimed to develop and validate a UHPLC–MS/MS method for the simultaneous quantification of 12 antiretroviral drugs, including the recently introduced long-acting agents, in Dry Plasma Spots (DPSs). Methods: First, 100 µL of plasma sample and 100 µL of internal standard solution were spotted on each DSSD. After complete drying, DPSs were added with an acidifying solution (ammonium acetate buffer pH 4), and then, each sample underwent extraction with hexane-dichloromethane 50:50 (v/v). After tumbling, the organic phase was evaporated and reconstituted for injection. An Acquity UPLC HSS T3 1.8 µm, 2.1 × 150 mm column at 50 °C enabled separation, performed using H2O + F.A. 0.05% (phase A) and ACN + F.A. 0.05% (phase B) as the mobile phase in gradient elution mode, for a total run time of 15 min. Results: The method was validated over the clinically relevant concentration ranges. For all quality control levels, accuracies ranged from 98.2% to 114.1%, and intra-day and inter-day RSD values ranged from 2.7% to 9.7% and 5.2% to 13.9%, respectively. All analytes demonstrated satisfactory short- and long-term stability in DPSs, confirming the suitability of shipment and storage at room temperature. Conclusions: The method demonstrated robustness and reproducibility in accordance with FDA and EMA guidelines. It ensures satisfactory accuracy and rapid analysis, supporting its application in clinical practice, including for monitoring the newest long-acting drugs. Full article
20 pages, 892 KB  
Systematic Review
Evidence Mapping of ctDNA Reporting in Pancreatic Ductal Adenocarcinoma: Toward a Shared Quantitative Language for ctDNA
by Daniel Croagh and Saeed Aslani
Cancers 2026, 18(8), 1318; https://doi.org/10.3390/cancers18081318 - 21 Apr 2026
Abstract
Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping [...] Read more.
Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping review evaluates current quantitative reporting approaches in pancreatic ductal adenocarcinoma (PDAC) and examines the potential role of KRAS mutant ctDNA as a biologically grounded reference metric. Methods: A systematic literature search was conducted across PubMed/MEDLINE and Scopus to identify studies reporting quantitative ctDNA metrics in PDAC. Eligible studies included those measuring plasma KRAS mutations and/or reporting variant allele frequency, tumour fraction, or multi-locus aggregate metrics. Additional relevant primary studies identified through broader manual searching of PubMed were assessed against the same prespecified eligibility and classification criteria before inclusion. Data were synthesised narratively, focusing on reporting frameworks, units of measurement, assay characteristics, and the interpretability of quantitative outputs across platforms. Results: Substantial heterogeneity was observed in ctDNA quantification methods and reporting standards. Ratio-based metrics such as variant allele frequency and tumour fraction were commonly used but varied according to assay design, plasma input volume, and background cell-free DNA levels. Few studies reported absolute mutant molecule counts per unit volume. Given that approximately 90–95% of PDACs harbour truncal activating KRAS mutations, plasma KRAS was consistently represented across platforms and demonstrated potential as a shared quantitative anchor. Limited standardisation was noted in distinguishing detectability from quantifiability based on sampling depth and counting statistics. Conclusions: Current ctDNA reporting in PDAC lacks a shared quantitative reference, limiting cross-study comparability. Reporting KRAS mutant molecules per millilitre and adopting an assay-agnostic framework distinguishing detection from quantification may improve interpretability, support harmonisation across platforms, and facilitate cumulative learning in pancreatic cancer ctDNA research. Full article
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28 pages, 5409 KB  
Article
A Tiered Approach to Human Synapse Proteomics: Optimized LC-MS/MS Analysis of Whole-Tissue Lysate and Synaptosome Preparations from Frozen Post-Mortem Brain Samples
by Femke C. Roig-Kuhn, Remco V. Klaassen, Frank T. W. Koopmans, Tiara S. Z. Koolman, August B. Smit and Sabine Spijker
Cells 2026, 15(8), 736; https://doi.org/10.3390/cells15080736 (registering DOI) - 21 Apr 2026
Abstract
Recent advancements in neuroproteomics have enabled detailed analysis of protein expression in the human brain, yet resolving synaptic dysfunction—a central feature of many neurological and psychiatric disorders—requires careful methodological consideration. Leveraging the high sensitivity of modern liquid chromatography-tandem mass spectrometry (LC-MS/MS), we evaluated [...] Read more.
Recent advancements in neuroproteomics have enabled detailed analysis of protein expression in the human brain, yet resolving synaptic dysfunction—a central feature of many neurological and psychiatric disorders—requires careful methodological consideration. Leveraging the high sensitivity of modern liquid chromatography-tandem mass spectrometry (LC-MS/MS), we evaluated the utility of whole-tissue lysates versus enriched synaptosome preparations for detecting synaptic protein signatures. First, we optimized and standardized a sample preparation protocol for frozen human gray matter (GM) by refining the suspension trapping (sTRAP) digestion method using thin human tissue sections. We accomplished low technical variation by minimizing sample handling and achieved a highly reproducible sample preparation workflow by rigorously applying standardization and randomization across dissection, processing, and LC-MS/MS runs. Second, comparative LC-MS/MS analysis showed that while whole-tissue lysates provide a high-throughput survey of the synaptic proteome, synaptosome isolation is required to investigate synapse-specific proteins to detect alterations at the terminal that are obscured in the soma. Because these methods offer distinct but synergistic levels of information, we recommend a tiered neuroproteomics strategy. This approach utilizes whole-tissue lysates for broad disease-associated screening and consistent quantification in large cohorts, followed by targeted synaptosome proteomics to provide a unique window of insight into synaptic composition and stability. This integrated workflow respects the biological necessity of spatial resolution while maintaining the reproducibility required for robust human brain proteomics. Furthermore, initial tissue-level analysis provides the necessary context to correctly interpret synaptosome data in cases of global synapse loss or gain. Full article
(This article belongs to the Special Issue Proteomic Applications in Ageing and Neurodegenerative Conditions)
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14 pages, 868 KB  
Brief Report
A Functional HMOX2 Genetic Variant Is Associated with Resting Diastolic and Mean Arterial Pressure in Healthy Humans
by Vincent Beauchamps, Julianne Touron, Danielle Gomez-Merino, Adrien Lagraniere, Carine Malle, Marie-Claire Erkel, Damien Léger, Mounir Chennaoui, Fabien Sauvet and Pierre A. Fabries
Antioxidants 2026, 15(4), 518; https://doi.org/10.3390/antiox15040518 - 21 Apr 2026
Abstract
Basal blood pressure (BP) is partly determined by systemic vascular resistance, which is modulated by vasoactive pathways, including gaseous messengers. Carbon monoxide (CO), continuously generated by the constitutive enzyme heme oxygenase-2 (HO-2) encoded by HMOX2, promotes vascular smooth muscle relaxation and may [...] Read more.
Basal blood pressure (BP) is partly determined by systemic vascular resistance, which is modulated by vasoactive pathways, including gaseous messengers. Carbon monoxide (CO), continuously generated by the constitutive enzyme heme oxygenase-2 (HO-2) encoded by HMOX2, promotes vascular smooth muscle relaxation and may contribute to interindividual variability in resting BP. The functional single-nucleotide polymorphism rs4786504_T>C has been associated with higher HMOX2 expression in C-allele carriers, providing a plausible biological link between genetic variation in the HO-2/CO pathway and vascular redox signaling. We investigated this association in forty young, healthy, normotensive adults studied under controlled laboratory conditions during a 4-day sleep deprivation protocol, with repeated standardized daytime BP measurements (478 observations). Linear mixed-effects models were adjusted for major physiological and behavioral covariates. T-allele carriers (C/T + T/T) exhibited higher diastolic BP (β = +6.08 mmHg, 95%CI [1.32–10.84], p = 0.017) and mean arterial pressure (β = +5.28 mmHg, 95%CI [0.28–10.29], p = 0.046) than C/C homozygotes, with no effect on systolic BP or heart rate. The association remained consistent across sensitivity and additive genetic models. This hypothesis-generating study provides preliminary evidence in humans, albeit limited by sample size, of a link between a functional HMOX2 variant and resting BP, consistent with a possible contribution of constitutive HO-2 activity to BP regulation. Full article
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21 pages, 1311 KB  
Article
A Dual Malnutrition Challenge in Tanzania Explored Through Logistic Regression Analysis
by Maryam Siddiqa, Gulzar H. Shah, Mahnoor Shahid Butt, Tehreem Asif and Bushra Shah
Nutrients 2026, 18(8), 1301; https://doi.org/10.3390/nu18081301 - 20 Apr 2026
Abstract
Background and Objectives: The double burden of malnutrition (DBM), characterized by the coexistence of malnutrition and overweight within the same household, has become a significant public health concern in low- and middle-income countries. Tanzania is undergoing a nutritional transition marked by persistent child [...] Read more.
Background and Objectives: The double burden of malnutrition (DBM), characterized by the coexistence of malnutrition and overweight within the same household, has become a significant public health concern in low- and middle-income countries. Tanzania is undergoing a nutritional transition marked by persistent child malnutrition alongside increasing maternal overweight. This study examined socio-demographic, maternal, and child-level factors associated with DBM among children under five years in Tanzania. Methods: This cross-sectional study used data from the 2022 Tanzania Demographic and Health Survey, including a weighted sample of 5744 children under five and their mothers aged 15–49 years. DBM was defined as the presence of child malnutrition, measured using the Composite Index of Anthropometric Failure (CIAF), in households where the mother was overweight or obese. Bivariate chi-square tests and binary logistic regression analyses were conducted in STATA 17. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were estimated to identify predictors of DBM. Results: DBM was more prevalent in rural areas. Significant predictors included birth order (AOR = 0.611, p = 0.030), child sex (AOR = 0.708, p = 0.011), perceived birth size (AOR = 0.270, p = 0.004), child age (AOR = 0.474, p < 0.001), maternal age (AOR = 0.599, p = 0.045), and maternal education (AOR = 0.604, p = 0.035). Higher maternal education reduced the likelihood of DBM, while firstborn male and small-sized children were at greater risk. Conclusions: DBM in Tanzania is influenced by both biological and socio-demographic factors. Integrated, multi-sectoral interventions targeting maternal education, prenatal care, and optimal maternal nutrition are essential to reduce DBM and achieve global malnutrition reduction targets. Full article
(This article belongs to the Section Nutrition and Public Health)
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18 pages, 1192 KB  
Review
Pathogen Reduction of Transfused Blood Components—The End of the Beginning Rather than the Beginning of the End
by Albert Farrugia, Laurence Corash, Raymond Goodrich and Leni von Bonsdorff
Pathogens 2026, 15(4), 442; https://doi.org/10.3390/pathogens15040442 - 20 Apr 2026
Viewed by 31
Abstract
Therapeutics derived from donated blood or its constituents are classifiable into blood components and plasma derivatives. The latter are defined as medicines/drugs/pharmaceuticals produced from the industrial fractionation of thousands of pooled plasma donations and characterised with relative precision to a pre-defined specification through [...] Read more.
Therapeutics derived from donated blood or its constituents are classifiable into blood components and plasma derivatives. The latter are defined as medicines/drugs/pharmaceuticals produced from the industrial fractionation of thousands of pooled plasma donations and characterised with relative precision to a pre-defined specification through sampling of a homogenous pharmaceutical batch. The former are defined as components/biologicals produced using relatively simple (but increasingly complex) technologies in blood centres from single or small pools of isolated components from whole blood and are pre-specified through regulatory standards with relatively wide limits because of the inherent biologic variability of individual donors. This review discusses the evolution of technology to reduce the risk of pathogen transmission by blood-derived therapeutics, assess the state of the approved technologies for pathogen-reduced blood components, and examine the features of the blood-provider and regulatory framework globally that have shaped, and in some instances impeded, the implementation of component pathogen reduction to an extent equivalent to that achieved for plasma derivatives. The ensuing risks to the public’s confidence in the blood supply are discussed, and remedial actions are proposed. The features of a new paradigm for blood safety are outlined. Full article
(This article belongs to the Special Issue Globalisation of Pathogen Safety Threats to the Blood Supply)
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13 pages, 869 KB  
Article
An Initial Indonesian Genome-Wide SNP-Array Study with Functional Variant Prioritization Reveals NASP and GPR78 Candidate SNVs in Hepatocellular Carcinoma
by Toar Jean Maurice Lalisang, Vania Myralda Giamour Marbun, Linda Erlina, Nathaniel Jason Zacharia, Kezia Nathania Limbong Allo, Fadilah Fadilah and Aisyah Fitriannisa Prawiningrum
Biomedicines 2026, 14(4), 931; https://doi.org/10.3390/biomedicines14040931 - 20 Apr 2026
Viewed by 67
Abstract
Background/Objectives: Population-specific genomic data are essential for understanding hepatocellular carcinoma (HCC) biology, particularly in underrepresented regions. This study aimed to perform exploratory single-nucleotide polymorphism (SNP)-array-based profiling of HCC tumor samples from Indonesian patients and to prioritize candidate functional variants using a systematic [...] Read more.
Background/Objectives: Population-specific genomic data are essential for understanding hepatocellular carcinoma (HCC) biology, particularly in underrepresented regions. This study aimed to perform exploratory single-nucleotide polymorphism (SNP)-array-based profiling of HCC tumor samples from Indonesian patients and to prioritize candidate functional variants using a systematic in silico framework. Methods: This retrospective cross-sectional study included 15 resected HCC cases with available formalin-fixed paraffin-embedded (FFPE) tumor tissue. Genome-wide SNP genotyping was performed using the Illumina Asian Screening Array. Following quality control and filtering, variants were annotated using the Ensembl Variant Effect Predictor. A case-only functional prioritization approach incorporating multiple in silico prediction tools was applied, followed by gene-level burden aggregation. Results: After multistep filtering, 11 samples and 104 prioritized variants were retained for analysis. Variants consisted predominantly of splice-region, missense, and regulatory changes. Gene-level burden analysis identified Nuclear Autoantigenic Sperm Protein (NASP, rs775916096) as the highest-ranked candidate gene, while G protein-coupled receptor 78 (GPR78, rs558447540) emerged as a secondary candidate with predicted functional annotations but currently limited biological evidence in HCC. Given the tumor-only design without matched normal tissue, the prioritized variants cannot be distinguished from rare germline variants. Conclusions: This exploratory SNP-array study provides a hypothesis-generating framework for functional variant prioritization in Indonesian HCC. NASP and GPR78 represent preliminary candidates that require validation in larger cohorts with matched normal tissue and sequencing-based confirmation. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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28 pages, 5249 KB  
Article
Integrative In Silico and FFPE Tissue Analyses Elucidate Upregulated Genes in Colorectal Cancer Enriched for Tie2-Expressing Macrophages/Monocytes
by Eman Amin M. Ali, Alaa Muayad Altaie, Reem Sami Alhamidi, Nival Ali, Anania Boghossian, Marwa Almazrouei, Vidya Bijosh Mohan, Riyad Bendardaf, Rawia Mohamed, Iman M. Talaat and Rifat Hamoudi
Int. J. Mol. Sci. 2026, 27(8), 3645; https://doi.org/10.3390/ijms27083645 - 19 Apr 2026
Viewed by 193
Abstract
Tumor-associated Tie2-expressing monocytes/macrophages (TEMs) have been implicated in promoting angiogenesis and metastasis in colorectal cancer (CRC), yet the molecular mechanisms linking TEMs infiltration to tumor metastasis and progression remain incompletely defined. This study investigated the distribution of TEMs in CRC and their association [...] Read more.
Tumor-associated Tie2-expressing monocytes/macrophages (TEMs) have been implicated in promoting angiogenesis and metastasis in colorectal cancer (CRC), yet the molecular mechanisms linking TEMs infiltration to tumor metastasis and progression remain incompletely defined. This study investigated the distribution of TEMs in CRC and their association with gene expression profiles, microvessel density (MVD), and clinical outcomes. Immunohistochemistry on 30 formalin-fixed paraffin-embedded (FFPE) primary CRC samples revealed that TEMs, which characteristically express tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2) receptor and CD14, preferentially localize to perivascular regions and are associated with higher histological grade, tumor size, lymph node metastasis, and increased MVD. However, Tie2/CD14+ macrophages and CD68+ tumor-associated macrophages (TAMs) showed uniform stromal distribution. Gene set enrichment analysis (GSEA) of in silico transcriptomic datasets of metastatic CRC (mCRC) identified enrichment of pathways related to cell–cell recognition, calcium signaling, transcription regulation, and metalloexopeptidase activity in Tie2+/CD14+ tumors. Subsequent qRT-PCR validation on FFPE primary CRC samples confirmed significant upregulation of C-C chemokine receptor 7 (CCR7), platelet-derived growth factor A (PDGFRA), CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), and carboxypeptidase E (CPE) in TEMs+ regions. Notably, angiopoietin1 (Ang1), but not angiopoietin2 (Ang2), was significantly elevated in TEMs+ primary tumors. Kaplan–Meier analysis on 1336 CRC patients indicated that high expression of CITED2, CPE, and Ang2 is associated with reduced overall survival. Collectively, these findings suggest that TEM infiltration is linked to transcriptional regulation, biological processes, and enzymatic programs in CRC, potentially contributing to tumor progression and poor prognosis, and highlight CCR7, PDGFRA, CITED2, CPE, and Ang1 as candidate biomarkers for further mechanistic exploration. Full article
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23 pages, 868 KB  
Article
Radiomic Features of MRI Subcompartments Associate with Angiogenic and Inflammatory Transcriptomic Programs in Glioblastoma: An IvyGAP Exploratory Analysis
by Daniele Piccolo and Marco Vindigni
Cancers 2026, 18(8), 1293; https://doi.org/10.3390/cancers18081293 - 19 Apr 2026
Viewed by 155
Abstract
Background: Glioblastoma exhibits profound intratumoral heterogeneity, with anatomically distinct tumor zones characterized by divergent molecular programs that drive therapy resistance. Whether magnetic resonance imaging (MRI)-derived radiomic features can capture these regional transcriptomic differences remains unknown. We aimed to determine whether subcompartment-level radiomic features [...] Read more.
Background: Glioblastoma exhibits profound intratumoral heterogeneity, with anatomically distinct tumor zones characterized by divergent molecular programs that drive therapy resistance. Whether magnetic resonance imaging (MRI)-derived radiomic features can capture these regional transcriptomic differences remains unknown. We aimed to determine whether subcompartment-level radiomic features associate with transcriptomic pathway enrichment scores derived from biologically approximate tumor zones. Methods: We matched 28 patients (mean age 58.5 years; 13/28 MGMT methylated) across the IvyGAP RNA-seq atlas and the IVYGAP-RADIOMICS datasets. Single-sample GSEA (ssGSEA) pathway scores were computed for 24 gene sets. Radiomic features (3920 per subcompartment) were reduced to 597. Nested leave-one-patient-out cross-validation (LOPO-CV) with Elastic Net served as the primary predictive analysis; linear mixed-effects models (LMM) provided exploratory associational analysis. Analyses used a biologically motivated but spatially non-co-registered zone-to-subcompartment mapping; all reported associations are zone-approximate. Results: Twenty-one of 24 pathways showed no predictive signal (R2cv ≤ 0). Inflammatory Response (R2cv = 0.185, 95% CI [0.071, 0.355], p = 0.008) was the only pathway supported by both the nested CV (FDR = 0.096) and the exploratory LMM (FDR = 0.024, ΔR2 = 0.214 beyond subcompartment effects) analyses; the LMM association was robust to clinical covariate adjustment (likelihood ratio test p = 0.004). Angiogenesis (R2cv = 0.209, 95% CI [0.028, 0.353], p = 0.006) reached nested CV significance (FDR = 0.096) but was not corroborated by the LMM (FDR = 0.445); it is therefore reported as a tentative single-framework signal requiring independent validation. T2-derived texture features were selected in 100% of folds for both pathways. Conclusions: Inflammatory Response is the only pathway supported by both analytical frameworks; Angiogenesis is a tentative nested-CV-only signal pending independent validation. The absence of signal for 21 of 24 pathways should not be interpreted as evidence of biological inaccessibility: at N = 28 (vs. N ≈ 240 required by Riley criteria), severe underpowering, attenuation from the non-spatial zone-to-subcompartment mapping, and methodological constraints each independently suffice to suppress real associations. Five of the 24 gene sets (the IvyGAP zone modules) are non-independent from the outcome data and cannot be interpreted as discovery. All reported associations are zone-approximate and may partly reflect macro-compartment (between-subcompartment) effects; validation in larger cohorts with spatially precise co-registration is essential. Full article
(This article belongs to the Section Molecular Cancer Biology)
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24 pages, 564 KB  
Review
Honey and Beehive Products in Oncology: A Comprehensive Review
by Pauline Celine Raoul, Gabriele Egidi, Marta Palombaro, Ilaria Romeo, Ginevra Del Borrello, Marco Cintoni, Esmeralda Capristo, Emanuele Rinninella, Antonio Gasbarrini and Maria Cristina Mele
Appl. Sci. 2026, 16(8), 3959; https://doi.org/10.3390/app16083959 - 19 Apr 2026
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Abstract
Background: Bee-derived products are rich in bioactive compounds with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Interest is growing in their potential role as adjuncts in supportive nutritional oncology, particularly for preventing and managing treatment-related toxicity symptoms in patients receiving chemotherapy and/or radiotherapy. Methods: [...] Read more.
Background: Bee-derived products are rich in bioactive compounds with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Interest is growing in their potential role as adjuncts in supportive nutritional oncology, particularly for preventing and managing treatment-related toxicity symptoms in patients receiving chemotherapy and/or radiotherapy. Methods: A systematic search of human and preclinical studies was conducted in PubMed/MEDLINE, Web of Science, and Scopus from January 2000 to December 2025. Search terms combined bee-related product keywords with oncology-related keywords. Eligible studies included in vitro and in vivo preclinical models as well as clinical studies assessing biological properties, clinical outcomes, safety, and issues of product standardization. Results: Preclinical and clinical studies indicate that beehive products reduce oxidative stress, modulate inflammatory signaling pathways, exhibit antimicrobial activity against wound pathogens, and promote tissue repair. Results are most consistent for oral mucositis and for symptom management in head and neck cancer, where some studies report reduced pain, improved mucosal healing, and better nutritional status. Conclusions: This literature review identifies honey and beehive products as promising functional foods for improving oncological patient care. Further large studies are needed, as the evidence is heterogeneous across sample size, product composition, outcome measures, and therapeutic preparations. Full article
(This article belongs to the Special Issue New Advances in Functional Foods and Nutraceuticals: 2nd Edition)
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13 pages, 2935 KB  
Article
Pilot Assessment of RNA Stabilization Methods for Influenza A Virus in Swine Oral Fluids
by Berenice Munguía-Ramírez, Betsy Armenta-Leyva, Luis Giménez-Lirola, Yanqi Zhang, Bailey Arruda, Giovana Ciacci-Zanella and Jeffrey Zimmerman
Pathogens 2026, 15(4), 439; https://doi.org/10.3390/pathogens15040439 - 18 Apr 2026
Viewed by 190
Abstract
Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% [...] Read more.
Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% trehalose, sorbitol, sucrose, and mannitol) and two commercial nucleic acid stabilizers (PrimeStore® MTM and RNAlater®) to preserve RT-qPCR-detectable IAV RNA in swine oral fluids exposed to field-relevant stress conditions. Oral fluid samples collected from pigs experimentally infected with H1N2 (Study 1: n = 150; DPIs 2, 3, 4) or with H1N2 and H3N2 (Study 2: n = 58; DPI 5) were subjected to storage at 25 °C for up to 144 h (Study 1) or 2, 5, 10, or 15 freeze–thaw cycles (Study 2), with DPIs (Study 1) or subtypes (Study 2) serving as biological replicates, given the limited sample size. IAV detection was quantified as efficiency standardized Cq values (ECq) and analyzed using a linear mixed-effects model. Overall, both carbohydrates (trehalose, sorbitol, sucrose) and commercial stabilizers maintained higher ECq values than untreated oral fluids under both thermal and freeze–thaw stress conditions. Due to the limited sample size, these findings should be interpreted cautiously, yet they demonstrate the potential utility of carbohydrates as a low-cost, non-inactivating alternative for stabilizing IAV RNA in field-collected oral fluids. Full article
(This article belongs to the Section Viral Pathogens)
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