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26 pages, 3825 KB  
Article
Biogenic Silica as a Direct Sol–Gel Precursor for High-Efficiency MSU-X Mesostructure Assembly: Closing the Loop from Rice Husk Waste to Functional Wormhole Frameworks
by Ngo Ha-Son, Le Van-Duong, Cong Ngoc-Thang and Nguyen Thi-Linh
Nanomaterials 2026, 16(12), 748; https://doi.org/10.3390/nano16120748 - 15 Jun 2026
Viewed by 204
Abstract
Direct utilization of biomass-derived silica in neutral surfactant-templated mesoporous synthesis remains underexplored with respect to mesostructure control and functional integration. High-purity silica extracted from acid-treated rice husk ash (~98.4 wt% SiO2) was employed as the sole precursor in a fluoride-assisted sol–gel [...] Read more.
Direct utilization of biomass-derived silica in neutral surfactant-templated mesoporous synthesis remains underexplored with respect to mesostructure control and functional integration. High-purity silica extracted from acid-treated rice husk ash (~98.4 wt% SiO2) was employed as the sole precursor in a fluoride-assisted sol–gel route to synthesize MSU-X frameworks without chemical modification. Systematic parametric variation—pH, Si/surfactant ratio, hydrothermal temperature, and aging duration—establishes quantitative structure–processing correlations. Under optimized conditions (pH 2, Si/Tergitol = 8, 60 °C, 96 h), the resulting material exhibits a wormhole-like mesoarchitecture with a BET surface area of 816 m2 g−1, mean pore diameter of ~3.6 nm, and three-dimensionally interconnected channels, confirmed by SAXS, TEM, and N2 sorption. EDXRF analysis confirms effective impurity removal and high silica incorporation efficiency (~95–96%); thermal stability persists to 700 °C, with incipient crystallization near 800 °C. As a functional demonstration, MSU-X served as an anti-agglomeration scaffold for ZIF-8 crystallization during DDT adsorption. Despite attenuated kinetics relative to pristine ZIF-8—where severe agglomeration occludes active imidazole nodes—the Z8/MSU-X composite achieved near-quantitative DDT removal (74.10 mg g−1). This performance stems from the mesoporous matrix driving size-confined, highly dispersed ZIF-8 growth, thereby maximizing active-site exposure. Operating within a reagent-limited regime rather than a capacity-saturated boundary, this efficient depletion confirms that the scaffold successfully suppresses site loss. Ultimately, these findings validate biogenic silica as a directly integrable precursor for tailored mesostructure assembly, positioning agricultural waste as a high-performance feedstock for hierarchical adsorption architectures. Full article
(This article belongs to the Section Synthesis, Interfaces and Nanostructures)
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20 pages, 1397 KB  
Review
From Invisible to Visible: Cutting-Edge Ultrasound Insights into Entheses of the Distal Extremities in Rheumatology
by Luis Coronel, Chiara Rizzo, Juan José de Agustin, David Bong, Maribel Miguel-Pérez, Stefano Alivernini, Lene Terslev, Maria Antonietta D’Agostino and Ingrid Möller
J. Clin. Med. 2026, 15(10), 3753; https://doi.org/10.3390/jcm15103753 - 13 May 2026
Viewed by 332
Abstract
Musculoskeletal ultrasound (MSUS) is a well-established and reliable tool for the evaluation of entheses and enthesitis, particularly at larger and accessible sites. Recent technological advances, including high- and ultra-high-frequency transducers, have expanded its potential, enabling detailed assessment of distal extremity entheses. This narrative [...] Read more.
Musculoskeletal ultrasound (MSUS) is a well-established and reliable tool for the evaluation of entheses and enthesitis, particularly at larger and accessible sites. Recent technological advances, including high- and ultra-high-frequency transducers, have expanded its potential, enabling detailed assessment of distal extremity entheses. This narrative review provides a focused and updated perspective on this evolving field, highlighting three key advances. First, the identification and characterization of previously underrecognized entheseal sites in the distal extremities, such as pulley systems, retinacula, novel tendon insertions, and collateral ligaments, broadening the morphological spectrum of entheseal imaging. This is complemented by improved evaluation of vascularization through microvascular imaging and contrast-enhanced US (CEUS). Second, the emergence of interventional approaches, particularly US-guided entheseal biopsy, offers a novel means to investigate entheseal tissue in vivo and may establish a link between imaging and histopathology. Third, the integration of advanced functional imaging modalities, including elastography and multispectral optoacoustic tomography (MSOT), provides preliminary additional insights into the biomechanical and molecular properties of the enthesis beyond conventional structural assessment. Collectively, these developments support new investigational perspectives, positioning MSUS as a dynamic and integrative modality capable of exploring new anatomical territories and biological dimensions, with the potential to reshape the understanding and evaluation of entheseal involvement in rheumatology. Full article
(This article belongs to the Special Issue Clinical Updates in Imaging of Musculoskeletal Diseases)
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8 pages, 1023 KB  
Case Report
Sonographic Diagnosis of Flexor Tendon Incarceration by a Malunited Fracture Fragment: A Case Report
by Yuan-Chen Chang, Yu-Te Lin and Yu-Hsuan Cheng
Diagnostics 2026, 16(9), 1260; https://doi.org/10.3390/diagnostics16091260 - 23 Apr 2026
Viewed by 309
Abstract
Background and Clinical Significance: Post-traumatic finger stiffness is frequently attributed to soft tissue adhesions; however, mechanical obstruction from occult osseous structures remains a rare but critical differential diagnosis in adults. Case Presentation: This report describes a 56-year-old female presenting with severe, [...] Read more.
Background and Clinical Significance: Post-traumatic finger stiffness is frequently attributed to soft tissue adhesions; however, mechanical obstruction from occult osseous structures remains a rare but critical differential diagnosis in adults. Case Presentation: This report describes a 56-year-old female presenting with severe, refractory stiffness of the little finger eight months after a proximal phalanx fracture. Despite extensive conservative therapy, active and passive flexion at the proximal and distal interphalangeal joints remained locked in extension. While conventional radiographs demonstrated bony union, musculoskeletal ultrasonography (MSUS) revealed an occult protruding malunited fragment incarcerating the flexor tendons. Dynamic MSUS provided real-time evidence of mechanical impingement by demonstrating proximal muscle contraction without distal tendon excursion. Intraoperatively, initial soft tissue tenolysis failed to restore motion; further exploration guided by MSUS evidence successfully identified a sharp bone spike. Subsequent ostectomy resulted in immediate restoration of functional range of motion. This case underscores the limitations of static imaging in evaluating the dynamic gliding mechanism and highlights the valuable role of MSUS in identifying mechanical functional obstructions. Conclusions: Early sonographic evaluation should be considered for refractory post-traumatic stiffness to prevent prolonged, ineffective conservative care and to guide definitive surgical management. Full article
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12 pages, 2105 KB  
Article
PSA Density and PIRADS 5 Lesions as Key Determinants of Upstaging After Radical Prostatectomy
by Patryk Patrzałek, Mikołaj Kisiała, Marcel Dawidowicz, Jakub Wieland, Karol Zagórski, Jakub Karwacki, Adam Gurwin, Jan Łaszkiewicz, Wojciech Tomczak, Wojciech Urbański, Dawid Janczak, Wojciech Krajewski, Tomasz Szydełko and Bartosz Małkiewicz
Cancers 2026, 18(8), 1319; https://doi.org/10.3390/cancers18081319 - 21 Apr 2026
Viewed by 532
Abstract
Introduction: Clinical staging based on digital rectal examination is imprecise, leading to pathological upstaging in patients with prostate cancer (PCa). Accurate preoperative assessment remains a challenge despite the use of multiparametric magnetic resonance imaging (mpMRI) and fusion-guided biopsy. This study aims to [...] Read more.
Introduction: Clinical staging based on digital rectal examination is imprecise, leading to pathological upstaging in patients with prostate cancer (PCa). Accurate preoperative assessment remains a challenge despite the use of multiparametric magnetic resonance imaging (mpMRI) and fusion-guided biopsy. This study aims to identify key predictors of upstaging in preoperative patients. Materials and Methods: A retrospective analysis of 924 patients who underwent radical prostatectomy between July 2012 and January 2025 was performed. Variables included prostate-specific antigen, prostate volume, biopsy type, MRI, body mass index and age. Upstaging was defined as ≥pT3 in patients staged clinically as cT1–2. Optimal cut-offs for continuous variables were defined statistically. Multivariable logistic regression was applied to identify independent predictors of upstaging and minor staging upgrading (MSU)—defined as any upward shift in the pathological T stage relative to the clinical T stage. Model performance was evaluated using the area under the Receiver Operating Characteristic (ROC) curve (AUC). Results: Upstaging occurred in 31.9% and MSU in 50.6% of patients. The mean age was 65 years. Cut-off values for PSA density (PSAD) were 0.29 for upstaging and 0.28 for MSU. In the full-cohort model (AUC = 0.628), PSAD (odds ratio (OR) = 2.55), age (OR = 1.04), and hypertension (HT) (OR = 1.47) were associated with upstaging. In PIRADS-based models, PIRADS 5 and PSAD predicted both upstaging (OR = 1.62 and 6.10, respectively; AUC = 0.664) and MSU (OR = 1.75 and 4.67, respectively; AUC = 0.659). MSU was also associated with HT and a lack of fusion biopsy (AUC = 0.622). Conclusions: PSAD and PIRADS 5 lesions are strong determinants of pathological upstaging and MSU in PCa. These factors should be considered in preoperative risk stratification to improve staging accuracy. Despite advances in imaging and biopsy techniques, upstaging remains a common phenomenon, underlining the need for further refinement of diagnostic protocols. Full article
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17 pages, 853 KB  
Systematic Review
Mobile Cancer Screening Programs: A Systematic Review of Implementation Challenges and Population Access
by Safa ElKefi, Roberta Scheinmann, Alicia K. Matthews and Erica Phillips
Int. J. Environ. Res. Public Health 2026, 23(4), 465; https://doi.org/10.3390/ijerph23040465 - 4 Apr 2026
Viewed by 1169
Abstract
Objective: This review aimed to synthesize evidence on the design characteristics, implementation considerations, and operational challenges of mobile cancer screening units. Methods: A PRISMA-guided review was conducted. Data extracted included screening type, target population, program characteristics, mobile unit features, and reported implementation barriers. [...] Read more.
Objective: This review aimed to synthesize evidence on the design characteristics, implementation considerations, and operational challenges of mobile cancer screening units. Methods: A PRISMA-guided review was conducted. Data extracted included screening type, target population, program characteristics, mobile unit features, and reported implementation barriers. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Results: Sixty-four articles published across 13 countries met the inclusion criteria. Most interventions focused on breast cancer screening (n = 37), followed by lung (n = 11), cervical (n = 6), colorectal, skin, prostate, and multi-cancer screening programs. MSUs were most frequently deployed in urban areas (21 urban/18 rural/17 both). Several comparative studies (fixed programs vs. MSUs) reported higher screening uptake in mobile programs, although findings varied substantially by setting, population, and study design. However, adherence and clinical outcomes varied, often reflecting baseline socioeconomic differences in the populations served. Common implementation barriers included follow-up coordination challenges, program costs, equipment and space limitations, and gaps in referral and reimbursement systems. Conclusions: These findings highlight the potential of mobile screening units as public health strategies to expand access to cancer screening while underscoring the need for stronger implementation frameworks and long-term evaluation of program outcomes. Full article
(This article belongs to the Special Issue Advances and Trends in Mobile Healthcare)
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20 pages, 927 KB  
Article
Ultrasound-Detected Salivary Gland and Joint Inflammation Strongly Reflect Patient-Perceived Symptom Burden in Primary Sjögren’s Syndrome: A Cross-Sectional Multicenter Study
by Tanya Sapundzhieva, Lyubomir Sapundzhiev, Plamen Todorov, Martin Mitev and Anastas Batalov
Biomedicines 2026, 14(4), 819; https://doi.org/10.3390/biomedicines14040819 - 3 Apr 2026
Viewed by 608
Abstract
Aims. To investigate the relationship between ultrasound (US)-detected parenchymal abnormalities in the major salivary glands (MSG), joint and tendon inflammation, and systemic disease activity in patients with primary Sjögren’s syndrome (pSS). Patients and methods. This cross-sectional, multicenter study enrolled 60 patients with pSS [...] Read more.
Aims. To investigate the relationship between ultrasound (US)-detected parenchymal abnormalities in the major salivary glands (MSG), joint and tendon inflammation, and systemic disease activity in patients with primary Sjögren’s syndrome (pSS). Patients and methods. This cross-sectional, multicenter study enrolled 60 patients with pSS and 20 healthy controls (HCs). Systemic disease activity was evaluated using the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), while symptom burden was assessed with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). MSG evaluation included bilateral gray-scale (GS) and power Doppler (PDUS) assessment of the parotid and submandibular glands using a semi-quantitative 0–3 scoring system. Musculoskeletal ultrasound (MSUS) assessment comprised bilateral examination of the wrists, second to fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, the fourth extensor wrist compartment, and the flexor tendons of the second to fifth fingers for GS and PD-detected synovitis and tenosynovitis, also scored semi-quantitatively. Recorded outcomes included GS and PD synovitis scores, total synovitis score, tenosynovitis score, GS and PD glandular scores, and total glandular score. Results. Synovitis was most frequently detected in the wrists, followed by the second PIP joint. Subclinical synovitis—defined as a GSUS synovitis score > 0 in a joint without clinical swelling—was detected in 66.7% (n = 28) of patients with pSS. No significant correlations were found between joint US scores and salivary gland US scores. ESSPRI showed moderate positive correlations with both the GS synovitis score (p = 0.002) and the total synovitis score (p = 0.003), as well as significant positive correlations with all salivary gland US scores: GS (p < 0.001), PD (p = 0.002), and total glandular score (p < 0.001). ESSDAI demonstrated only a weak positive correlation with the GS salivary gland score (p = 0.030). Conclusions. In patients with pSS, the extent of US-detected MSG parenchymal abnormalities does not reflect systemic disease activity and does not correlate with US-detected joint synovitis. In contrast, patient-reported symptom burden is associated with both joint inflammation and MSG parenchymal changes on US. Larger studies are needed to further define the role of salivary gland and joint US in evaluating disease activity in pSS. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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28 pages, 2265 KB  
Review
Non-Hyperuricemia Experimental Models of Gout
by Yevetta Xiang, An-Tzu Chien and Christopher Hall
Gout Urate Cryst. Depos. Dis. 2026, 4(1), 8; https://doi.org/10.3390/gucdd4010008 - 16 Mar 2026
Viewed by 1461
Abstract
Gout is the most common form of inflammatory arthritis in men, driven by hyperuricemia and the deposition of monosodium urate (MSU) crystals. The innate immune response to these crystals leads to acute inflammatory episodes, called flares, characterized by intense joint pain, swelling, and [...] Read more.
Gout is the most common form of inflammatory arthritis in men, driven by hyperuricemia and the deposition of monosodium urate (MSU) crystals. The innate immune response to these crystals leads to acute inflammatory episodes, called flares, characterized by intense joint pain, swelling, and temporary disability. Although gout flares are self-limiting, they impose a considerable burden on patients’ quality of life and contribute to increased healthcare utilization. A detailed understanding of the inflammatory processes triggered by MSU crystals is critical for developing targeted therapies to prevent and manage flares effectively. This review provides an overview of experimental models used to study the inflammatory phase of gout, with a focus on both in vivo and in vitro models of MSU crystal-induced inflammation. We concentrate on models that reproduce the acute inflammatory response following MSU crystal deposition, including the air pouch, intraarticular injection, and peritonitis rodent models, alongside the larval zebrafish model. In addition, we discuss in vitro approaches using primary immune cells and cell lines. We discuss the strengths, limitations, and translational relevance of these models and highlight some examples of how they have contributed to our understanding of the etiology of gout. Of note, models of hyperuricemia are not included here as these have been extensively reviewed elsewhere. Full article
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19 pages, 4205 KB  
Article
Three Polyphenolic Compounds from Inonotus obliquus: Antioxidant Activity, Xanthine Oxidase Inhibition, and Regulatory Effects on MyD88/TLR4/NF-κB Pathway in MSU-Induced RAW 264.7 Macrophages
by Yuting Shu, Jiahui Chen, Shuyue Pang, Hongfei Liu, Helong Bai, Lina Chen, Jing Wang and Fanlei Meng
Antioxidants 2026, 15(2), 267; https://doi.org/10.3390/antiox15020267 - 21 Feb 2026
Viewed by 745
Abstract
Background: Inonotus obliquus (Chaga), a medicinal and edible macrofungus abundant in bioactive polyphenols, is a potential source of natural antioxidants and anti-inflammatory agents for functional foods. This study aimed to evaluate the antioxidant capacity of three key polyphenols (osmundacetone [OS], protocatechuic aldehyde [PAH], [...] Read more.
Background: Inonotus obliquus (Chaga), a medicinal and edible macrofungus abundant in bioactive polyphenols, is a potential source of natural antioxidants and anti-inflammatory agents for functional foods. This study aimed to evaluate the antioxidant capacity of three key polyphenols (osmundacetone [OS], protocatechuic aldehyde [PAH], protocatechuic acid [PA]) from I. obliquus and decipher their anti-inflammatory mechanisms via the MyD88/TLR4/NF-κB pathway in a gout-related model. Methods: Antioxidant activity was assessed by xanthine oxidase (XO) inhibition (IC50), superoxide anion (O2) scavenging, and structure–activity relationship (SAR) analysis; in a monosodium urate (MSU)-induced acute gout cell model, reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH), superoxide dismutase (SOD), pro-inflammatory cytokines (TNF-α, IL-1β) were quantified, and MyD88/TLR4/NF-κB pathway proteins were analyzed by Western blot. Results: OS showed the strongest XO inhibition (IC50 = 4.91 mM), followed by PAH (IC50 = 5.92 mM) and PA (IC50 = 26.53 mM); OS exerted dual redox effects by scavenging O2 and suppressing XO-mediated O2 generation, with its conjugated C=C-carbonyl system and PAH’s aldehyde group enhancing XO binding. All polyphenols and I. obliquus crude extract significantly reduced ROS, NO, LDH, and cytokines (p < 0.05), increased SOD, and downregulated TLR4, MyD88, and NF-κB expression. Conclusions: I. obliquus-derived polyphenols exhibit obvious antioxidant and xanthine oxidase inhibitory effects, and regulate oxidative stress, pro-inflammatory mediators, and the MyD88/TLR4/NF-κB signaling pathway in monosodium urate-stimulated RAW 264.7 inflammatory macrophages, supporting their development as natural functional food ingredients and potential candidates for gout-related and oxidative stress-associated inflammatory cellular disorders. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 669 KB  
Review
Exosome-Mediated Intercellular Communication in the Pathological Processes of Gouty Arthritis and Its Treatment
by Wenren Zhao, Wenhao Zhong, Zexuan Wang, Qian Zhou, Yu Wang, Bing Zhang and Zhijian Lin
Int. J. Mol. Sci. 2026, 27(4), 1656; https://doi.org/10.3390/ijms27041656 - 8 Feb 2026
Cited by 1 | Viewed by 1199
Abstract
Gouty arthritis (GA) is a debilitating autoinflammatory disorder precipitated by the deposition of monosodium urate (MSU) crystals, leading to intense, recurrent joint inflammation and systemic metabolic dysregulation. While hyperuricemia is a prerequisite, the transition to clinical gout involves complex intercellular signaling cascades that [...] Read more.
Gouty arthritis (GA) is a debilitating autoinflammatory disorder precipitated by the deposition of monosodium urate (MSU) crystals, leading to intense, recurrent joint inflammation and systemic metabolic dysregulation. While hyperuricemia is a prerequisite, the transition to clinical gout involves complex intercellular signaling cascades that are not fully understood. Emerging evidence has identified exosomes,— nanoscale extracellular vesicles, —as critical mediators in this pathological process. Exosomes function as intercellular carriers, transporting a diverse cargo of bioactive molecules, including proteins, lipids, and nucleic acids (e.g., microRNAs), which profoundly influence immune cell activation, inflammasome regulation, and metabolic pathways. This review provides a critical analysis of the dual role of exosomes in both propagating and potentially resolving inflammation in GA. We delve into the intricate mechanisms of exosome-mediated pathogenesis, including the modulation of purine metabolism, lysosomal function, and complement–inflammasome crosstalk. Furthermore, we explore the burgeoning field of exosome-based therapeutics, critically evaluating strategies such as engineered exosomes for targeted drug delivery, mesenchymal stem cell (MSC)-derived exosomes for immunomodulation, and the development of exosomal biomarkers for diagnostics. Additionally, we examine how chemical drugs and herbal compounds may exert therapeutic effects by modulating exosome pathways, offering new insights into integrative treatment approaches. By synthesizing recent findings from proteomic, transcriptomic, and functional studies, we aim to unravel the complexities of exosome signaling in GA and to propose innovative therapeutic avenues that target these pathways to improve patient outcomes. Full article
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25 pages, 3677 KB  
Review
Gout Inflammation Time Programming: Molecular Clock from Crystal Triggering to Tissue Remodeling
by Xin Chen, Chunyuan Zhang, Hanwen Zheng, Qingping Shi, Beiyan Chen and Jieru Han
Int. J. Mol. Sci. 2026, 27(3), 1523; https://doi.org/10.3390/ijms27031523 - 4 Feb 2026
Cited by 2 | Viewed by 1196
Abstract
This review introduces and elaborates a novel temporal paradigm, the “Gout Inflammation Time Programming” model, conceptualized through the Gout-STAT™ framework. This model redefines gout inflammation as a dynamic continuum progressing through three precisely timed phases: an acute Perception phase (0–24 h) initiated by [...] Read more.
This review introduces and elaborates a novel temporal paradigm, the “Gout Inflammation Time Programming” model, conceptualized through the Gout-STAT™ framework. This model redefines gout inflammation as a dynamic continuum progressing through three precisely timed phases: an acute Perception phase (0–24 h) initiated by monosodium urate (MSU) crystal recognition, triggering the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and neutrophil-driven burst; a critical Adaptation phase (24–72 h) where outcomes are determined by immunometabolic reprogramming of macrophages and synovial fibroblasts; and a chronic Tissue Injury phase (>72 h) driven by epigenetic memory, leading to irreversible osteoarticular destruction. Deciphering this programmed timeline reveals distinct therapeutic windows. We propose a shift towards stage-specific precision interventions, targeting upstream triggers (e.g., mitochondrial reactive oxygen species(ROS), neutrophil extracellular trap formation (NETosis)) in the acute phase, correcting metabolic checkpoints (e.g., succinate accumulation, impaired autophagy) during adaptation, and employing tissue-protective strategies (e.g., epigenetic modulators) in the chronic phase. Furthermore, we highlight the pivotal role of cutting-edge translational technologies, such as intelligent drug delivery systems and digital twin joint models, in achieving spatiotemporal precision. Understanding this intrinsic molecular clock is fundamental for advancing gout management from reactive treatment to a predictive, preventive, and personalized 4P medicine approach. Full article
(This article belongs to the Section Molecular Immunology)
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9 pages, 783 KB  
Review
The Utility of Ultrasound-Guided Synovial Biopsy in the Diagnosis of Crystal-Induced Arthritis
by Arthur M. Mandelin II, Diane Lewis Horowitz, Darren Tabechian and Ami Ben-Artzi
Gout Urate Cryst. Depos. Dis. 2026, 4(1), 2; https://doi.org/10.3390/gucdd4010002 - 27 Jan 2026
Viewed by 1270
Abstract
The diagnosis of crystal-induced arthritis is routinely established by synovial fluid analysis. However, a synovial effusion is not always present, fluid aspiration is not always possible or practical, and synovial fluid analysis is occasionally subject to false negative results. When there is a [...] Read more.
The diagnosis of crystal-induced arthritis is routinely established by synovial fluid analysis. However, a synovial effusion is not always present, fluid aspiration is not always possible or practical, and synovial fluid analysis is occasionally subject to false negative results. When there is a high suspicion of crystal-induced arthritis, but crystals are not identified in the synovial fluid, a biopsy of the synovium in search of crystals can assist in making a diagnosis. In this manuscript, we review the utility of ultrasound-guided needle biopsy of synovial tissue in the identification of crystal-induced arthritis, briefly describe the procedure, and recommend best practices for specimen handling and tissue processing. Full article
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24 pages, 29209 KB  
Article
WSI-GT: Pseudo-Label Guided Graph Transformer for Whole-Slide Histology
by Zhongao Sun, Alexander Khvostikov, Andrey Krylov, Ilya Mikhailov and Pavel Malkov
Mach. Learn. Knowl. Extr. 2026, 8(1), 8; https://doi.org/10.3390/make8010008 - 29 Dec 2025
Viewed by 1188
Abstract
Whole-slide histology images (WSIs) can exceed 100 k × 100 k pixels, making direct pixel-level segmentation infeasible and requiring patch-level classification as a practical alternative for downstream WSI segmentation. However, most approaches either treat patches independently, ignoring spatial and biological context, or rely [...] Read more.
Whole-slide histology images (WSIs) can exceed 100 k × 100 k pixels, making direct pixel-level segmentation infeasible and requiring patch-level classification as a practical alternative for downstream WSI segmentation. However, most approaches either treat patches independently, ignoring spatial and biological context, or rely on deep graph models prone to oversmoothing and loss of local tissue detail. We present WSI-GT (Pseudo-Label Guided Graph Transformer), a simple yet effective architecture that addresses these challenges and enables accurate WSI-level tissue segmentation. WSI-GT combines a lightweight local graph convolution block for neighborhood feature aggregation with a pseudo-label guided attention mechanism that preserves intra-class variability and mitigates oversmoothing. To cope with sparse annotations, we introduce an area-weighted sampling strategy that balances class representation while maintaining tissue topology. WSI-GT achieves a Macro F1 of 0.95 on PATH-DT-MSU WSS2v2, improving by up to 3 percentage points over patch-based CNNs and by about 2 points over strong graph baselines. It further generalizes well to the Placenta benchmark and standard graph node classification datasets, highlighting both clinical relevance and broader applicability. These results position WSI-GT as a practical and scalable solution for graph-based learning on extremely large images and for generating clinically meaningful WSI segmentations. Full article
(This article belongs to the Special Issue Deep Learning in Image Analysis and Pattern Recognition, 2nd Edition)
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21 pages, 3788 KB  
Article
Dose-Sparing Efficacy of d-Limonene with Low-Dose Allopurinol in a Dual Model of Hyperuricemia and Gouty Arthritis in Rats
by Krishnaraju Venkatesan, Pooja Muralidharan, Durgaramani Sivadasan, Manimekalai Pichaivel, Yahya I. Asiri, Khalid A. Asseri, Nizar Sirag, Hassabelrasoul Elfadil, Mahmoud Elodemi, Kousalya Prabahar, Premalatha Paulsamy and Kumarappan Chidambaram
Nutrients 2026, 18(1), 72; https://doi.org/10.3390/nu18010072 - 25 Dec 2025
Cited by 1 | Viewed by 1142
Abstract
Background: d-Limonene (LIM) is a food-derived monoterpenoid phytocompound predominantly found in citrus peels, endowed with potent antioxidant and anti-inflammatory properties, and has been reported to inhibit xanthine oxidase (XO) activity in vitro. This study investigated the dose-sparing efficacy of this dietary [...] Read more.
Background: d-Limonene (LIM) is a food-derived monoterpenoid phytocompound predominantly found in citrus peels, endowed with potent antioxidant and anti-inflammatory properties, and has been reported to inhibit xanthine oxidase (XO) activity in vitro. This study investigated the dose-sparing efficacy of this dietary bioactive compound in combination with low-dose allopurinol (ALP) using a dual rat model combining potassium oxonate (PO)-induced hyperuricemia and monosodium urate (MSU)-triggered gouty arthritis, thereby capturing both metabolic and inflammatory dimensions of gout. Methods: Female Wistar rats were PO-primed and MSU-challenged, then treated with LIM (50 mg/kg), ALP (5 or 10 mg/kg), or LIM + ALP. Outcomes included paw thickness, dysfunction and inflammation indices, serum uric acid, urea, creatinine, AST/ALT, cytokines (IL-1β, TNF-α, IL-6), oxidative stress markers (MDA, SOD, catalase, GSH), and NLRP3 immunoreactivity, supported by radiographic and histopathological analyses. Data were analyzed by one-way ANOVA with Tukey’s post hoc test. Results: LIM improved clinical and biochemical outcomes versus monotherapies. However, LIM + low-dose ALP exhibited the greatest overall efficacy. On Day 30, paw thickness was significantly lower with LIM + ALP than with LIM alone (3.25 ± 0.31 vs. 3.98 ± 0.72 mm; p < 0.001). Serum uric acid and hepatic transaminases declined most with the combination (p < 0.0001 vs. LIM), accompanied by improved renal indices (p < 0.001). Pro-inflammatory cytokines were markedly reduced, NLRP3 immunostaining was minimal, and oxidative balance shifted toward homeostasis (↓ MDA; ↑ SOD, catalase, GSH). Radiographic and histological evaluations corroborated attenuation of joint inflammation and tissue damage. Conclusions: In the PO + MSU gout model, co-administration of the food-derived compound LIM with low-dose ALP achieved additive, dose-sparing benefits across metabolic, inflammatory, and histological endpoints. While in vivo XO activity was not directly assessed, the findings are consistent with XO-pathway modulation, NLRP3–IL-1β suppression, and redox restoration. These results highlight the potential of dietary bioactives such as d-Limonene to complement standard urate-lowering therapy, warranting further pharmacokinetic and safety validation. Full article
(This article belongs to the Special Issue Food-Derived Bioactive Compounds and Their Health Benefits)
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15 pages, 1080 KB  
Article
Achilles Enthesitis in Psoriatic Arthritis: Inter-Observer Reliability of Ultrasound Findings
by Mihaela Agache, Luminita Enache, Claudiu Costinel Popescu, Bianca Dumitrescu, Catalina Elena Ionescu, Denisa Elena Moscalu, Anca Bobirca and Catalin Codreanu
J. Clin. Med. 2025, 14(24), 8738; https://doi.org/10.3390/jcm14248738 - 10 Dec 2025
Viewed by 839
Abstract
Background/Objectives: Enthesitis is a hallmark feature across the spondylarthritis spectrum, including psoriatic arthritis (PsA). In recent years, advanced imaging techniques, particularly musculoskeletal ultrasound (MSUS), have demonstrated higher sensitivity than clinical examination in detecting enthesitis. This study aimed to evaluate the inter-observer agreement [...] Read more.
Background/Objectives: Enthesitis is a hallmark feature across the spondylarthritis spectrum, including psoriatic arthritis (PsA). In recent years, advanced imaging techniques, particularly musculoskeletal ultrasound (MSUS), have demonstrated higher sensitivity than clinical examination in detecting enthesitis. This study aimed to evaluate the inter-observer agreement for the diagnosis of Achilles enthesitis in a cohort of PsA patients. A secondary objective was to explore specific ultrasound diagnostic criteria for identifying active, inflammatory enthesitis in this population. Methods: Adult patients with PsA, all fulfilling CASPAR classification criteria, were recruited and underwent both clinical and ultrasonographic assessment of the bilateral Achilles tendons. Each patient was scanned by 4 rheumatologists in a direct study, followed by a blinded evaluation of static images of the same patients. The examiners assessed the presence of enthesitis components according to the OMERACT criteria. In addition, the images were subsequently evaluated by 10 MSUS-experienced rheumatologists who were asked to classify the enthesitis as inflammatory by selecting one of the following responses: “yes”, “no,” or “possible”. Results: Ten PsA patients, with a median age of 60 and a median DAPSA score of 21, were included. Both direct and image-based inter-observer studies showed high agreement values for enthesophytes (κ > 0.6), erosions (κ > 0.5), and entheseal thickness (κ > 0.5). In both, low agreement was observed for hypoechogenicity (κ between 0.1 and 0.4). Erosions and power Doppler (PD) signal in erosions showed statistically significant differences between the “possible” and definite (“yes”) inflammatory enthesitis groups. A PD signal of grade 2 or 3 within the enthesis or erosions was observed exclusively in cases classified as definite (“yes”) inflammatory enthesitis. Similarly, a grade 3 PD signal in the bursa was found only in patients with definite inflammatory enthesitis. This study proposes a novel ultrasound scoring system for defining inflammatory enthesitis. The score demonstrated overall good diagnostic performance, with a sensitivity of 67% and a specificity of 100%. Conclusions: The relatively low inter-observer agreement regarding hypoechogenicity and the presence of PD highlights the need for targeted educational interventions to improve interpretation in MSUS. Erosions and PD signal within erosions appear to be significant discriminatory features for identifying inflammatory enthesitis. Full article
(This article belongs to the Section Immunology & Rheumatology)
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49 pages, 6957 KB  
Review
Global Trends in Biotic and Abiotic Stress Mitigation Strategies for Common Bean: A Bibliometric Study
by Wagner Meza-Maicelo, César R. Balcázar-Zumaeta, Henry W. Santillan Culquimboz, Manuel Oliva-Cruz and Flavio Lozano-Isla
Int. J. Plant Biol. 2025, 16(4), 135; https://doi.org/10.3390/ijpb16040135 - 3 Dec 2025
Cited by 2 | Viewed by 2382
Abstract
Common bean (Phaseolus vulgaris L.) is a cornerstone of global food security, yet its production is persistently challenged by biotic and abiotic stresses. This study conducted a bibliometric analysis following PRISMA guidelines on 549 documents published between 1971 and mid-2025, using Biblioshiny, [...] Read more.
Common bean (Phaseolus vulgaris L.) is a cornerstone of global food security, yet its production is persistently challenged by biotic and abiotic stresses. This study conducted a bibliometric analysis following PRISMA guidelines on 549 documents published between 1971 and mid-2025, using Biblioshiny, VOSviewer, and CiteSpace. Results reveal a scientific output concentrated in leading institutions such as Michigan State University (MSU, USA) and the International Center for Tropical Agriculture (CIAT, Colombia). Collaboration networks are dominated by influential authors including Beebe, S. and Kelly, J.D., with Euphytica and Crop Science emerging as primary publication outlets. Research trends highlight salinity tolerance, oxidative stress, and chromosomal mapping, where advanced technologies such as SNP chips have supplanted RAPD markers. Critical challenges remain, including limited phenotyping capacity and the complexity of polygenic resistance, with urgent implications for developing countries where beans are vital for food security but face barriers to technology adoption and restricted participation in global research networks. Concurrently, mitigation strategies have shifted toward sustainable approaches, incorporating beneficial microorganisms for biotic stress and bio-stimulants or plant extracts for abiotic stress. Since 2020, the field has increasingly embraced multifunctional strategies leveraging natural mechanisms to enhance crop resilience. This analysis offers a comprehensive knowledge base to guide future research agendas. Full article
(This article belongs to the Topic New Challenges on Plant–Microbe Interactions)
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