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17 pages, 3205 KiB  
Review
Microbiome–Immune Interaction and Harnessing for Next-Generation Vaccines Against Highly Pathogenic Avian Influenza in Poultry
by Yongming Sang, Samuel N. Nahashon and Richard J. Webby
Vaccines 2025, 13(8), 837; https://doi.org/10.3390/vaccines13080837 (registering DOI) - 6 Aug 2025
Abstract
Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating [...] Read more.
Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8+ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article
(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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16 pages, 1504 KiB  
Article
Tuning the Activity of NbOPO4 with NiO for the Selective Conversion of Cyclohexanone as a Model Intermediate of Lignin Pyrolysis Bio-Oils
by Abarasi Hart and Jude A. Onwudili
Energies 2025, 18(15), 4106; https://doi.org/10.3390/en18154106 - 2 Aug 2025
Viewed by 143
Abstract
Catalytic upgrading of pyrolysis oils is an important step for producing replacement hydrocarbon-rich liquid biofuels from biomass and can help to advance pyrolysis technology. Catalysts play a pivotal role in influencing the selectivity of chemical reactions leading to the formation of main compounds [...] Read more.
Catalytic upgrading of pyrolysis oils is an important step for producing replacement hydrocarbon-rich liquid biofuels from biomass and can help to advance pyrolysis technology. Catalysts play a pivotal role in influencing the selectivity of chemical reactions leading to the formation of main compounds in the final upgraded liquid products. The present work involved a systematic study of solvent-free catalytic reactions of cyclohexanone in the presence of hydrogen gas at 160 °C for 3 h in a batch reactor. Cyclohexanone can be produced from biomass through the selective hydrogenation of lignin-derived phenolics. Three types of catalysts comprising undoped NbOPO4, 10 wt% NiO/NbOPO4, and 30 wt% NiO/NbOPO4 were studied. Undoped NbOPO4 promoted both aldol condensation and the dehydration of cyclohexanol, producing fused ring aromatic hydrocarbons and hard char. With 30 wt% NiO/NbOPO4, extensive competitive hydrogenation of cyclohexanone to cyclohexanol was observed, along with the formation of C6 cyclic hydrocarbons. When compared to NbOPO4 and 30 wt% NiO/NbOPO4, the use of 10 wt% NiO/NbOPO4 produced superior selectivity towards bi-cycloalkanones (i.e., C12) at cyclohexanone conversion of 66.8 ± 1.82%. Overall, the 10 wt% NiO/NbOPO4 catalyst exhibited the best performance towards the production of precursor compounds that can be further hydrodeoxygenated into energy-dense aviation fuel hydrocarbons. Hence, the presence and loading of NiO was able to tune the activity and selectivity of NbOPO4, thereby influencing the final products obtained from the same cyclohexanone feedstock. This study underscores the potential of lignin-derived pyrolysis oils as important renewable feedstocks for producing replacement hydrocarbon solvents or feedstocks and high-density sustainable liquid hydrocarbon fuels via sequential and selective catalytic upgrading. Full article
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29 pages, 3958 KiB  
Article
Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy
by Somaiyeh Azmoun, Freeman C. Lewis, Daniel Shoieb, Yan Jin, Elena Colicino, Isha Mhatre-Winters, Haiwei Gu, Hari Krishnamurthy, Jason R. Richardson, Donatella Placidi, Luca Lambertini and Roberto G. Lucchini
Brain Sci. 2025, 15(8), 829; https://doi.org/10.3390/brainsci15080829 (registering DOI) - 31 Jul 2025
Viewed by 297
Abstract
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on [...] Read more.
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m3 (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article
(This article belongs to the Special Issue From Bench to Bedside: Motor–Cognitive Interactions—2nd Edition)
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21 pages, 471 KiB  
Review
Role and Contribution of Serological Surveillance in Animals and Exposed Humans to the Study of Zoonotic Influenza Disease Epidemiology: A Scoping Review
by Rebecca Badra, Wenqing Zhang, John S. L. Tam, Richard Webby, Sylvie van der Werf, Sergejs Nikisins, Ann Cullinane, Saad Gharaibeh, Richard Njouom, Malik Peiris, Ghazi Kayali and Jean-Michel Heraud
Pathogens 2025, 14(8), 739; https://doi.org/10.3390/pathogens14080739 - 27 Jul 2025
Viewed by 477
Abstract
Background: Zoonotic influenza viruses pose a significant and evolving public health threat. In response to the recent rise in H5N1 cross-species transmission, the World Health Organization (WHO) R&D Blueprint for Epidemics consultations have prioritized strengthening surveillance, candidate vaccines, diagnostics, and pandemic preparedness. Serological [...] Read more.
Background: Zoonotic influenza viruses pose a significant and evolving public health threat. In response to the recent rise in H5N1 cross-species transmission, the World Health Organization (WHO) R&D Blueprint for Epidemics consultations have prioritized strengthening surveillance, candidate vaccines, diagnostics, and pandemic preparedness. Serological surveillance plays a pivotal role by providing insights into the prevalence and transmission dynamics of influenza viruses. Objective: This scoping review aimed to map the global research landscape on serological surveillance of zoonotic influenza in animals and exposed humans between 2017, the date of the last WHO public health research agenda for influenza review, and 2024, as well as to identify methodological advancements. Methods: Following PRISMA-ScR guidelines, we searched PubMed for English-language peer-reviewed articles published between January 2017 and March 2024. Studies were included if they reported serological surveillance in wild or domestic animals or occupationally exposed human populations, or novel methodologies and their technical limitations and implementation challenges. Results: Out of 7490 screened records, 90 studies from 33 countries, covering 25 animal species, were included. Seroprevalence studies were in domestic poultry and swine. Surveillance in companion animals, wild mammals, and at the human–animal interface was limited. Emerging serological methods included multiplex and nanobody-based assays, though implementation barriers remain. Conclusions: The review is limited by its restriction to one database and English-language articles, lack of quality appraisal, and significant heterogeneity among the included studies. Serological surveillance is a critical but underutilized tool in zoonotic influenza monitoring. Greater integration of serological surveillance into One Health frameworks, especially in high-risk regions and populations, is needed to support early detection and pandemic preparedness. Full article
(This article belongs to the Section Emerging Pathogens)
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11 pages, 810 KiB  
Article
Pediatric Hematology–Oncology Provider Attitudes and Beliefs About the Use of Acupuncture for Their Patients
by Holly L. Spraker-Perlman, Kenneth M. Busby, Amy Ly, Maggi Meyer, Justin N. Baker and Deena R. Levine
Children 2025, 12(8), 961; https://doi.org/10.3390/children12080961 - 22 Jul 2025
Viewed by 335
Abstract
Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation [...] Read more.
Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation of acupuncture for symptom management for their patients. Methods: A cross-sectional survey instrument was created, formatted, and delivered to physicians and advanced practice providers (APPs) at a single US pediatric cancer center. Survey responses were summarized by descriptive statistics. Results: A total of 78 PHO clinicians participated (response rate 29%). Most participants were interested in learning more about acupuncture (n = 42, 56.0%), yet rarely (n = 17, 22.7%) or never (n = 46, 61.3%) recommend acupuncture to patients. Most (n = 51, 73.9%) noted that they would support institutional development of an acupuncture program. Over half (n = 37, 52.2%) indicated their threshold for minimum hematologic indices for acupuncture includes a platelet count greater than 20,000 and absolute neutrophil count (ANC) greater than 500 (n = 37, 54.4%). Approximately two-thirds (n = 52, 66.7%) of participants noted that acupuncture could improve their patient’s quality of life, and most (n = 46, 67.6%) were not worried about harm. Conclusions: Acupuncture for symptom management is an evidenced-based, guideline-concordant recommendation for adults with cancer, but robust data in the pediatric oncology population are lacking. PHO providers do not routinely recommend acupuncture for patients but note that it may improve quality of life. Given their high symptom burden, rigorous studies of non-pharmacologic strategies for pediatric symptom management are vital. Acupuncture should be examined as a potential beneficial adjunct. Full article
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16 pages, 417 KiB  
Review
Potential Biological and Genetic Links Between Dementia and Osteoporosis: A Scoping Review
by Abayomi N. Ogunwale, Paul E. Schulz, Jude K. des Bordes, Florent Elefteriou and Nahid J. Rianon
Geriatrics 2025, 10(4), 96; https://doi.org/10.3390/geriatrics10040096 - 20 Jul 2025
Viewed by 342
Abstract
Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions. Methods: Studies [...] Read more.
Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions. Methods: Studies selected (1) involved clinical research investigating genetic factors or biomarkers associated with dementia or osteoporosis, and (2) were published in English in a peer-reviewed journal between July 1993 and March 2025. We searched Medline Ovid, Embase, PsycINFO, the Cochrane Library, the Web of Science databases, Google Scholar, and the reference lists of studies following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). Results: Twenty-three studies were included in this review. These explored the role of the APOE polymorphism (n = 2) and the APOE4 allele (n = 13), associations between TREM2 mutation and late onset AD (n = 1), and associations between amyloid beta and bone remodeling (n = 1); bone-related biomarkers like DKK1, OPG, and TRAIL as predictors of cognitive change (n = 2); extracellular vesicles as bone–brain communication pathways (1); and the role of dementia-related genes (n = 1), AD-related CSF biomarkers (n = 1), and parathyroid hormone (PTH) (n = 1) in osteoporosis–dementia pathophysiology. Conclusions: Bone-related biomarkers active in the Wnt/β-Catenin pathway (Dkk1 and sclerostin) and the RANKL/RANK/OPG pathway (OPG/TRAIL ratio) present consistent evidence of involvement in AD and osteoporosis development. Reports proposing APOE4 as a causal genetic link for both osteoporosis and AD in women are not corroborated by newer observational studies. The role of Aβ toxicity in osteoporosis development is unverified in a large clinical study. Full article
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11 pages, 370 KiB  
Article
Evaluating the Antibiotic Resistance Patterns in Mycoplasma hominis and Ureaplasma spp. Infections in Salvador, Brazil
by Sofia Lírio Santos Silva, Larissa Vieira do Amaral, Raissa Vieira do Amaral, Maria Isabel Figueiredo Sousa, Mauricio Freitas Batista, Maria Betânia Toralles, Caroline Alves Feitosa, Galileu Barbosa Costa and Viviane Matos Ferreira
Venereology 2025, 4(3), 12; https://doi.org/10.3390/venereology4030012 - 19 Jul 2025
Viewed by 433
Abstract
Background/Objectives: Mycoplasma and Ureaplasma species are pathogens commonly associated with urogenital infections in sexually active individuals. Despite their clinical relevance, these organisms are less frequently studied than other sexually transmitted infections (STIs), leading to limited data on their antimicrobial susceptibility and resistance [...] Read more.
Background/Objectives: Mycoplasma and Ureaplasma species are pathogens commonly associated with urogenital infections in sexually active individuals. Despite their clinical relevance, these organisms are less frequently studied than other sexually transmitted infections (STIs), leading to limited data on their antimicrobial susceptibility and resistance profiles. This study aimed to characterize the antimicrobial susceptibility and resistance patterns of Mycoplasma hominis and Ureaplasma spp. among individuals in Salvador, Bahia, Brazil, and to identify the potential associated risk factors. Methods: We conducted a retrospective descriptive study during 2022–2024 using secondary data obtained from the SMARTLab® diagnostic system. Sociodemographic and epidemiological data, along with results from IST2 and IST3 diagnostic tests, were analyzed. Absolute and relative frequencies were calculated by sex, age group, and antimicrobial susceptibility profile. Results: Our results revealed a predominance of M. hominis and Ureaplasma spp. infection among women (98.5%), and in individuals aged 38 to 47 years. Ureaplasma spp. accounted for the majority of positive cases. High rates of resistance were observed in the IST2 test, with 75.0% of M. hominis and 84.1% of Ureaplasma urealyticum resistant to ciprofloxacin. In the IST3 test, Ureaplasma spp. demonstrated a 7.3% resistance rate to levofloxacin, which increased to 22.2% in cases of co-infection. Conclusions: These findings underscore the growing threat of antimicrobial resistance in Mycoplasma and Ureaplasma species and highlight the need for targeted public health strategies and diagnostic tools to manage infections caused by these organisms, particularly in high-risk populations. Full article
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17 pages, 1035 KiB  
Review
Ancient Grains as Functional Foods: Integrating Traditional Knowledge with Contemporary Nutritional Science
by Jude Juventus Aweya, Drupat Sharma, Ravneet Kaur Bajwa, Bliss Earnest, Hajer Krache and Mohammed H. Moghadasian
Foods 2025, 14(14), 2529; https://doi.org/10.3390/foods14142529 - 18 Jul 2025
Viewed by 781
Abstract
Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum [...] Read more.
Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum of bioactive compounds such as phenolic acids, flavonoids, carotenoids, phytosterols, and betalains, these grains exhibit antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and immunomodulatory properties. Their health-promoting effects are underpinned by multiple interconnected mechanisms, including the reduction in oxidative stress, modulation of inflammatory pathways, regulation of glucose and lipid metabolism, support for mitochondrial function, and enhancement of gut microbiota composition. This review provides a comprehensive synthesis of the essential nutrients, phytochemicals, and functional properties of ancient grains, with particular emphasis on the nutritional and molecular mechanisms through which they contribute to the prevention and management of chronic diseases such as cardiovascular disease, type 2 diabetes, obesity, and metabolic syndrome. Additionally, it highlights the growing application of ancient grains in functional foods and nutrition-sensitive dietary strategies, alongside the technological, agronomic, and consumer-related challenges limiting their broader adoption. Future research priorities include well-designed human clinical trials, standardization of compositional data, innovations in processing for nutrient retention, and sustainable cultivation to fully harness the health, environmental, and cultural benefits of ancient grains within global food systems. Full article
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29 pages, 2426 KiB  
Review
Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases
by Buyan-Ochir Orgil, Mekaea S. Spaulding, Harrison P. Smith, Zainab Baba, Neely R. Alberson, Enkhzul Batsaikhan, Jeffrey A. Towbin and Enkhsaikhan Purevjav
Int. J. Mol. Sci. 2025, 26(14), 6856; https://doi.org/10.3390/ijms26146856 - 17 Jul 2025
Viewed by 317
Abstract
Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction [...] Read more.
Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article
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16 pages, 5794 KiB  
Article
A More Rapid Method for Culturing LUHMES-Derived Neurons Provides Greater Cell Numbers and Facilitates Studies of Multiple Viruses
by Adam W. Whisnant, Stephanie E. Clark, José Alberto Aguilar-Briseño, Lorellin A. Durnell, Arnhild Grothey, Ann M. Miller, Steven M. Varga, Jeffery L. Meier, Charles Grose, Patrick L. Sinn, Jessica M. Tucker, Caroline C. Friedel, Wendy J. Maury, David H. Price and Lars Dölken
Viruses 2025, 17(7), 1001; https://doi.org/10.3390/v17071001 - 16 Jul 2025
Viewed by 370
Abstract
The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated [...] Read more.
The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated to mature neurons. In this paper, we present a new method for differentiating one such model, the Lund human mesencephalic (LUHMES) dopaminergic neurons. This method is two days faster than some established protocols, results in nearly five times greater numbers of mature neurons, and involves fewer handling steps that could introduce technical variability. Moreover, it overcomes the problem of cell aggregate formation that commonly impedes high-resolution imaging, cell dissociation, and downstream analysis. While recently established for herpes simplex virus type 1, we demonstrate that LUHMES neurons can facilitate studies of other herpesviruses, as well as RNA viruses associated with childhood encephalitis and hemorrhagic fever. This protocol provides an improvement in the generation of large-scale neuronal cultures, which may be readily applicable to other neuronal 2D cell culture models and provides a system for studying neurotrophic viruses. We named this method the Streamlined Protocol for Enhanced Expansion and Differentiation Yield, or SPEEDY, method. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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21 pages, 817 KiB  
Article
C3-VULMAP: A Dataset for Privacy-Aware Vulnerability Detection in Healthcare Systems
by Jude Enenche Ameh, Abayomi Otebolaku, Alex Shenfield and Augustine Ikpehai
Electronics 2025, 14(13), 2703; https://doi.org/10.3390/electronics14132703 - 4 Jul 2025
Viewed by 422
Abstract
The increasing integration of digital technologies in healthcare has expanded the attack surface for privacy violations in critical systems such as electronic health records (EHRs), telehealth platforms, and medical device software. However, current vulnerability detection datasets lack domain-specific privacy annotations essential for compliance [...] Read more.
The increasing integration of digital technologies in healthcare has expanded the attack surface for privacy violations in critical systems such as electronic health records (EHRs), telehealth platforms, and medical device software. However, current vulnerability detection datasets lack domain-specific privacy annotations essential for compliance with healthcare regulations like HIPAA and GDPR. This study presents C3-VULMAP, a novel and large-scale dataset explicitly designed for privacy-aware vulnerability detection in healthcare software. The dataset comprises over 30,000 vulnerable and 7.8 million non-vulnerable C/C++ functions, annotated with CWE categories and systematically mapped to LINDDUN privacy threat types. The objective is to support the development of automated, privacy-focused detection systems that can identify fine-grained software vulnerabilities in healthcare environments. To achieve this, we developed a hybrid construction methodology combining manual threat modeling, LLM-assisted synthetic generation, and multi-source aggregation. We then conducted comprehensive evaluations using traditional machine learning algorithms (Support Vector Machines, XGBoost), graph neural networks (Devign, Reveal), and transformer-based models (CodeBERT, RoBERTa, CodeT5). The results demonstrate that transformer models, such as RoBERTa, achieve high detection performance (F1 = 0.987), while Reveal leads GNN-based methods (F1 = 0.993), with different models excelling across specific privacy threat categories. These findings validate C3-VULMAP as a powerful benchmarking resource and show its potential to guide the development of privacy-preserving, secure-by-design software in embedded and electronic healthcare systems. The dataset fills a critical gap in privacy threat modeling and vulnerability detection and is positioned to support future research in cybersecurity and intelligent electronic systems for healthcare. Full article
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17 pages, 3477 KiB  
Article
Breaking Diagnostic Barriers: Vision Transformers Redefine Monkeypox Detection
by Gelan Ayana, Beshatu Debela Wako, So-yun Park, Jude Kong, Sahng Min Han, Soon-Do Yoon and Se-woon Choe
Diagnostics 2025, 15(13), 1698; https://doi.org/10.3390/diagnostics15131698 - 3 Jul 2025
Viewed by 422
Abstract
Background/Objective: The global spread of Monkeypox (Mpox) has highlighted the urgent need for rapid, accurate diagnostic tools. Traditional methods like polymerase chain reaction (PCR) are resource-intensive, while skin image-based detection offers a promising alternative. This study evaluates the effectiveness of vision transformers (ViTs) [...] Read more.
Background/Objective: The global spread of Monkeypox (Mpox) has highlighted the urgent need for rapid, accurate diagnostic tools. Traditional methods like polymerase chain reaction (PCR) are resource-intensive, while skin image-based detection offers a promising alternative. This study evaluates the effectiveness of vision transformers (ViTs) for automated Mpox detection. Methods: By fine-tuning a pre-trained ViT model on an Mpox lesion image dataset, a robust ViT-based transfer learning (TL) model was created. Performance was assessed relative to convolutional neural network (CNN)-based TL models and ViT models trained from scratch across key metrics: accuracy, precision, recall, F1-score, and area under the receiver operating characteristic curve (AUC). Furthermore, a transferability measure was utilized to assess the effectiveness of feature transfer to Mpox images. Results: The results show that the ViT model outperformed a CNN, achieving an AUC of 0.948 and an accuracy of 0.942 with a p-value of less than 0.05 across all metrics, highlighting its potential for accurate and scalable Mpox detection. Moreover, the ViT models yielded a better hypothesis margin-based transferability measure, highlighting its effectiveness in transferring useful learning weights to Mpox images. Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations also confirmed that the ViT model attends to clinically relevant features, supporting its interpretability and reliability for diagnostic use. Conclusions: The results from this study suggest that ViT offers superior accuracy, making it a valuable tool for Mpox early detection in field settings, especially where conventional diagnostics are limited. This approach could support faster outbreak response and improved resource allocation in public health systems. Full article
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38 pages, 3240 KiB  
Review
Beyond the Limits: How Is Spectral Flow Cytometry Reshaping the Clinical Landscape and What Is Coming Next?
by Kamila Czechowska, Diana L. Bonilla, Adam Cotty, Amay Dankar, Paul E. Mead and Veronica Nash
Cells 2025, 14(13), 997; https://doi.org/10.3390/cells14130997 - 30 Jun 2025
Viewed by 1012
Abstract
Spectral flow cytometry has revolutionized traditional single-cell profiling to a new era of high-dimensional analysis, allowing for unprecedented deep phenotyping and more precise cell characterization, thereby significantly enhancing our multiplexing capability. The recent application of this technology in clinical settings has been redefining [...] Read more.
Spectral flow cytometry has revolutionized traditional single-cell profiling to a new era of high-dimensional analysis, allowing for unprecedented deep phenotyping and more precise cell characterization, thereby significantly enhancing our multiplexing capability. The recent application of this technology in clinical settings has been redefining the landscape of clinical diagnostic panels and immune monitoring, particularly for hematologic malignancies, immunological disorders, and drug discovery. Emerging technologies like ghost cytometry, LASE, and imaging flow cytometry are advancing cytometry by improving sensitivity, throughput, and spatial resolution. In this review, we discuss the requirements, challenges, and considerations for spectral applications in clinical diagnostic laboratories and pharmaceutical/contract research organization (CRO) settings. We discuss how these recent innovations are set to push the boundaries of diagnostic accuracy and analytical power, heralding a new frontier in clinical cytometry with the potential to dramatically enhance patient care and treatment outcomes. Full article
(This article belongs to the Special Issue Insight into Developments and Applications of Flow Cytometry)
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11 pages, 1628 KiB  
Article
Vitamin D3, 25-Hydroxyvitamin D3, and 1,25-Dihydroxyvitamin D3 Uptake in Cultured Human Mature Adipocytes
by Nazlı Uçar, Richard. T. Pickering, Peter M. Mueller, Jude T. Deeney, María Morales Suárez-Varela, José Miguel Soriano and Michael F. Holick
Nutrients 2025, 17(13), 2107; https://doi.org/10.3390/nu17132107 - 25 Jun 2025
Viewed by 1527
Abstract
Background/Objectives: Vitamin D3 is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D3 and 1,25(OH)2D3, remain [...] Read more.
Background/Objectives: Vitamin D3 is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D3 and 1,25(OH)2D3, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D3 and 1,25(OH)2D3 or the combination of vitamin D3, 25(OH)D3 and 1,25(OH)2D3. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D3 release under basal and isoproterenol-stimulated conditions using 3H-vitamin D3 and scintillation counting. Results: Vitamin D3 uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D3 and 1,25(OH)2D3 peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D3 release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D3 while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Inflammatory Diseases)
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12 pages, 577 KiB  
Article
Validation of the Arabic Version of the Long-Term Conditions Questionnaire (LTCQ): A Study of Factor and Rasch Analyses
by Walid Al-Qerem, Salwa Abdo, Anan Jarab, Alaa Hammad, Judith Eberhardt, Fawaz Al-Asmari, Lujain Al-Sa’di, Razan Al-Shehadeh, Dana Khasim, Ruba Zumot, Sarah Khalil, Ghazal Aloshebe and Jude Aljazazi
Healthcare 2025, 13(13), 1485; https://doi.org/10.3390/healthcare13131485 - 20 Jun 2025
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Abstract
Background: Patient-reported outcome measures (PROMs) are essential for capturing the lived experiences of individuals managing chronic diseases. However, few PROMs have been culturally adapted and validated for Arabic-speaking populations. Aim: This study aimed to translate, culturally adapt, and validate the Long-Term Conditions Questionnaire [...] Read more.
Background: Patient-reported outcome measures (PROMs) are essential for capturing the lived experiences of individuals managing chronic diseases. However, few PROMs have been culturally adapted and validated for Arabic-speaking populations. Aim: This study aimed to translate, culturally adapt, and validate the Long-Term Conditions Questionnaire (LTCQ) for use among Arabic-speaking adults living with chronic diseases in Jordan. Methods: Following forward–backward translation and an expert review, a cross-sectional survey of 1057 adults with chronic illnesses was conducted. The psychometric evaluation involved exploratory and confirmatory factor analyses (EFA and CFA) and Rasch modelling. While the original LTCQ assumed a unidimensional structure, EFA and CFA supported a two-factor solution: Empowerment and Functional Wellbeing, and Health-Related Psychosocial Distress. Results: The Rasch analysis confirmed that the item response thresholds were ordered, with good item targeting, and no differential item functioning (DIF) by gender. The removal of one poorly performing item resulted in a refined 19-item scale with strong reliability and validity. Conclusions: The Arabic LTCQ demonstrated robust psychometric properties and cultural relevance, supporting its use in clinical care, research, and policy initiatives. Future work should examine longitudinal responsiveness and further validate the tool across diverse Arabic-speaking populations. Full article
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