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14 pages, 1046 KB  
Article
Effects of Cryotherapy and Thermotherapy Using an E-TEET on Pain, Stress, and Satisfaction Among Patients and Healthcare Providers During Intravenous Catheterization: A Randomized Controlled Trial
by Bosong Kim, Soukyoung Kim, Jihoo Her, Yu Jin Lee and Myung-Haeng Hur
Nurs. Rep. 2026, 16(1), 17; https://doi.org/10.3390/nursrep16010017 - 7 Jan 2026
Viewed by 68
Abstract
Background: Intravenous catheterization is a common nursing procedure, although it is invasive and may cause pain and stress. Non-pharmacological interventions such as cryotherapy and thermotherapy have been explored, but practical and effective options remain limited. Purpose: This study aimed to evaluate [...] Read more.
Background: Intravenous catheterization is a common nursing procedure, although it is invasive and may cause pain and stress. Non-pharmacological interventions such as cryotherapy and thermotherapy have been explored, but practical and effective options remain limited. Purpose: This study aimed to evaluate the effects of cryotherapy and thermotherapy using the Enhanced Thermoelectric Element Tourniquet (E-TEET) a device equipped with a temperature-controlled plate and wireless charging on pain, stress, and patient satisfaction during intravenous catheterization. Methods: A randomized controlled trial was conducted involving 128 adult inpatients scheduled for preoperative intravenous catheterization. Participants were randomly assigned to one of four groups: cryotherapy (n = 31), thermotherapy (n = 31), control (E-TEET without temperature, n = 33), or comparison (latex tourniquet, n = 33). Pain and stress levels were measured using- the Numeric Rating Scale (NRS), along with pulse rate and oxygen saturation. Post-procedure satisfaction was also evaluated. Results: No significant differences were observed among the groups in terms of pain, pulse rate, or oxygen saturation. However, the cryotherapy group exhibited significantly lower stress levels and higher satisfaction compared to the comparison group (p < 0.05). Furthermore, Healthcare provider Satisfaction was significantly higher in the cryotherapy group than in the control group (p < 0.05). Conclusions: Cryotherapy using the E-TEE Tourniquet effectively reduced stress and improved satisfaction during intravenous catheterization, supporting its use as a feasible non-pharmacological intervention. Further studies are needed to standardize intervention parameters and validate findings across populations. Full article
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11 pages, 482 KB  
Article
Efficacy and Safety of Pirfenidone in Patients with Progressive Pulmonary Fibrosis: A Retrospective Single-Center Study
by Ju Hyun Oh, Jin Han Park, Ji Hoon Jang, Minyoung Her, Een Young Cho and Jae Ha Lee
Life 2026, 16(1), 11; https://doi.org/10.3390/life16010011 - 21 Dec 2025
Viewed by 474
Abstract
Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone [...] Read more.
Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone remains insufficient. In this study, we aimed to evaluate the efficacy and safety of pirfenidone in treating PPF. In this retrospective single-center study, we analyzed clinical data from patients with PPF who were treated with pirfenidone. Lung function data from six months before and after pirfenidone treatment were collected to assess changes over time. Missing values were imputed using a general linear mixed model (GLMM) for longitudinal data analysis. Of 33 subjects, the median age was 65.0 years, and 51.5% were female. Rheumatoid arthritis-related ILD was the most common subtype (45.5%). The median daily dose of pirfenidone was 600 mg, with a median treatment duration of 7.3 months. GLMM analysis showed a significant forced vital capacity (FVC) improvement, from −114 mL in the 6 months before treatment to +47.3 mL in the 6 months after treatment (p = 0.001). All adverse events related to pirfenidone were mild. In conclusion, the use of pirfenidone in PPF can potentially reduce the rate of FVC decline in real clinical practice. Full article
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24 pages, 1308 KB  
Article
Population Mobility in the Wake of COVID-19 in the US Northeast Region: Lessons for Regional Planning
by Omur Damla Kuru, Elisabeth Infield, Henry Renski, Paromita Shome and Emily Hodos
Land 2026, 15(1), 3; https://doi.org/10.3390/land15010003 - 19 Dec 2025
Viewed by 279
Abstract
Environmental factors motivate migration across the globe, calling for better planning. Although the US experienced such movements during the COVID-19 pandemic, literature on population mobility and outcomes for receiving communities in the US is scarce. We use a mixed-methods case study approach to [...] Read more.
Environmental factors motivate migration across the globe, calling for better planning. Although the US experienced such movements during the COVID-19 pandemic, literature on population mobility and outcomes for receiving communities in the US is scarce. We use a mixed-methods case study approach to explore the COVID-era population movement trends in the US Northeast (NE) Region and their outcomes for receiving communities to draw lessons for strategic regional planning aiming to achieve sustainable and equitable outcomes of disaster-induced movements. Utilizing the Statistics of Income data and focus group data collected from 27 local experts in 22 rural counties of NE, which experienced the highest relative numbers of in-movers between 2016 and 2020, the findings revealed the top receiving counties were predominantly rural areas where urbanites moved from within NE. This movement challenged the housing market and services, disproportionately burdening socioeconomically disadvantaged groups in receiving communities. The COVID-19 experience opened a window of opportunity for regional planning to prepare desirable outcomes of such mobilities by addressing existing issues in receiving communities while incorporating pulse and slow population movements into the agenda. The right policy timing and communication among communities are keys to building trust and ensuring integration of newcomers into receiving communities. Full article
(This article belongs to the Special Issue Strategic Planning for Urban Sustainability (Second Edition))
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30 pages, 1002 KB  
Review
Immunopathogenic Mechanisms in Connective Tissue Disease-Associated Interstitial Lung Disease: Incessant Loop of Immunity to Fibrosis
by Jae Ha Lee, Ji Hoon Jang, Sunggun Lee and Minyoung Her
Int. J. Mol. Sci. 2025, 26(24), 12126; https://doi.org/10.3390/ijms262412126 - 17 Dec 2025
Viewed by 623
Abstract
Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a significant cause of morbidity and mortality. It is characterized by the progressive convergence of chronic inflammation, immune dysregulation, and fibrotic remodeling in the lung parenchyma. While often conceptualized through a model of idiopathic pulmonary [...] Read more.
Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a significant cause of morbidity and mortality. It is characterized by the progressive convergence of chronic inflammation, immune dysregulation, and fibrotic remodeling in the lung parenchyma. While often conceptualized through a model of idiopathic pulmonary fibrosis (IPF), CTD-ILD is fundamentally an immune-driven pathology with distinct inflammatory mechanisms in which adaptive immunity plays a profound role. This narrative review explores the “inflammation–immunity–fibrosis continuum” in CTD-ILD, elaborating the intricate cellular and molecular pathways that distinguish it from IPF. We highlight the central role of persistent T-cell responses and B-cell dysregulation, which often occur within organized tertiary lymphoid structures in the lung. This review examines how these immune processes are propagated by multiple cytokine pathways, including the TGF-β/SMAD, JAK/STAT, and phosphodiesterase-4 signaling pathways, which serve as crucial links between inflammation and fibrosis. This distinct immune mechanism in CTD-ILD explains why immunomodulatory agents are a cornerstone of CTD-ILD treatment, in contrast to their limited efficacy in IPF, and emphasizes the current paradigm of combining immunosuppression with antifibrotic drugs to target the dual drivers of the disease. Full article
(This article belongs to the Special Issue New Advances in Autoimmune Diseases)
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24 pages, 15012 KB  
Article
A New Way to Engineer Cell Sheets for Articular Cartilage Regeneration
by Ta-Lun Tan, Yuan Tseng, Jia-Wei Li, Cheng-Tse Yang, Hsuan-Yu Chen, Her-I Lee, Jun-Jen Liu, Yi-Yuan Yang and How Tseng
J. Funct. Biomater. 2025, 16(12), 437; https://doi.org/10.3390/jfb16120437 - 25 Nov 2025
Viewed by 1119
Abstract
Background: Articular cartilage has limited self-repair capacity. While thermoresponsive poly N-isopropyl acrylamide (pNIPAAm)-based Cell Sheet Engineering (CSE) is a promising scaffold-free strategy, its inherent material properties pose limitations. This study developed and validated a novel, non-thermoresponsive CSE platform for functional cartilage regeneration. [...] Read more.
Background: Articular cartilage has limited self-repair capacity. While thermoresponsive poly N-isopropyl acrylamide (pNIPAAm)-based Cell Sheet Engineering (CSE) is a promising scaffold-free strategy, its inherent material properties pose limitations. This study developed and validated a novel, non-thermoresponsive CSE platform for functional cartilage regeneration. Methods: A culture platform was fabricated by grafting the biocompatible polymer poly gamma-glutamic acid (γ-PGA) and a disulfide-containing amino acid onto porous PET membranes. This design enables intact cell sheet detachment with its native extracellular matrix (ECM) via specific cleavage of the disulfide bonds by a mild reducing agent. Results: The hydrated substrate exhibited a biomimetic stiffness (~16.2 MPa) that closely mimics native cartilage. The platform showed superior biocompatibility and supported the cultivation of multi-layered rabbit chondrocyte sheets rich in Collagen II and Glycosaminoglycans. Critically, in a rabbit full-thickness defect model, transplanted autologous cell sheets successfully regenerated integrated, hyaline-like cartilage at 12 weeks, as confirmed by MRI, CT, and histological analyses. Conclusions: This novel CSE platform, featuring highly biomimetic stiffness and a gentle, chemically specific detachment mechanism, represents a highly promising clinical strategy for repairing articular cartilage defects. Full article
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22 pages, 10322 KB  
Article
Biochars Derived from Diverse Local Tunisian Feedstocks for Environmental Remediation: Physicochemical Properties and Adsorption Behaviour
by Asma Hmaied, Aïda Ben Hassen Trabelsi, Fethi Lachaal, Sandrine Negro and Claude Hammecker
Land 2025, 14(11), 2224; https://doi.org/10.3390/land14112224 - 10 Nov 2025
Viewed by 785
Abstract
Water resource management and agricultural practices in the Mediterranean region, characterised by the excessive use of pesticides, pose significant environmental and human health challenges. As they can be easily and inexpensively produced from various biomass sources, biochars are frequently recommended as a low-cost [...] Read more.
Water resource management and agricultural practices in the Mediterranean region, characterised by the excessive use of pesticides, pose significant environmental and human health challenges. As they can be easily and inexpensively produced from various biomass sources, biochars are frequently recommended as a low-cost secondary decontamination strategy to address soil contamination problems. This study investigates the properties and sorption behaviours of biochars produced in a low-cost metallic kiln using local rosemary, giant reed, St. John’s wort, olive, cypress, and palm tree biomass residues to evaluate their potential for environmental remediation, with a special focus on the mobility and retention of contaminants. Analytical and experimental techniques were employed to characterise the biochars’ physicochemical attributes and sorptive capacities. The core analyses included measurement of basic physicochemical properties, including pH, electrical conductivity, functional group identification via Fourier transform infrared (FTIR) spectroscopy, and the molarity of ethanol droplet (MED) test to assess the surface hydrophobicity. Batch sorption experiments were conducted using methylene blue (MB) and two fluorescent tracers—uranine (UR) and sulforhodamine-B (SRB)—as proxies for organic contaminants to assess the adsorption efficiency and molecule–biochar interactions. Furthermore, the adsorption isotherms at 20 °C were fitted to different models to assess the biochars’ specific surface areas. Thermodynamic parameters were also evaluated to understand the nature and strength of the adsorption processes. The results highlight the influence of feedstock type on the resulting biochar’s properties, thus significantly affecting the mechanism of adsorption. Rosemary biochar was found to have the highest specific surface area (SSA) and cation exchange capacity (CEC), allowing it to adsorb a wide range of organic molecules. Giant reed and palm tree biochars showed similar properties. In contrast, wood-derived biochars generally showed very low SSA, moderate CEC, and low hydrophobicity. The contrasting properties of the three dyes—MB (cationic), UR (anionic), and SRB (zwitterionic)—enabled us to highlight the distinct interaction mechanisms between each dye and the surface functional groups of the different biochars. The reactivity and sorption efficiency of a biochar depend strongly on both the nature of the target molecule and the intrinsic properties of the biochar, particularly its pH. The findings of this study demonstrate the importance of matching biochar characteristics to specific contaminant types for optimised environmental applications, providing implications for the use of tailored biochars in pollutant mitigation strategies. Full article
(This article belongs to the Section Land, Soil and Water)
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32 pages, 2601 KB  
Review
Consensus Statement on Drug-Coated Balloons in Coronary Artery Disease from the Cardiovascular Intervention Association of Thailand
by Pannipa Suwannasom, Korakoth Towashiraporn, Worawut Roongsangmanoon, Wiwat Kanjanarutjawiwat, Purich Surunchupakorn, Muenpetch Muenkaew, Ply Chichareon, Pisit Hutayanon, Anek Kanoksilp and Mann Chandavimol
J. Clin. Med. 2025, 14(21), 7505; https://doi.org/10.3390/jcm14217505 - 23 Oct 2025
Cited by 1 | Viewed by 3534
Abstract
Background: Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs without leaving a permanent scaffold. DCB is initially indicated for in-stent restenosis (ISR) and now has expanded indication for treating small vessel disease and bifurcation lesions. However, there [...] Read more.
Background: Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs without leaving a permanent scaffold. DCB is initially indicated for in-stent restenosis (ISR) and now has expanded indication for treating small vessel disease and bifurcation lesions. However, there is a heterogeneity in the patient and lesion selection, lesion preparation techniques, and the optimal duration of dual antiplatelet therapy after DCB angioplasty. The Cardiovascular Intervention Association of Thailand (CIAT) developed a consensus statement on DCB use in coronary interventions. Methods: The CIAT expert panel systematically reviewed randomized controlled trials, meta-analyses, and real-world studies evaluating DCB therapy. Procedural strategies, imaging guidance, physiologic assessment, and antiplatelet therapy protocols were appraised. The recommendations were developed and put to an online vote. Consensus was defined when the recommendation reached 80% of votes in support of “agree” or “neutral”. Results: Clinical evidence demonstrates that DCBs achieve comparable outcomes to drug-eluting stents (DESs) in selected lesions while enabling shorter durations of dual antiplatelet therapy (DAPT), particularly beneficial for high-bleeding-risk patients. Optimal outcomes require meticulous lesion preparation, appropriate balloon sizing, and controlled vessel dissection. Intravascular imaging and physiologic assessment further refine procedural precision, while hybrid strategies combining DCBs and DESs address complex lesions and multivessel disease. The final document presents 15 consensus statements addressing indications, procedural techniques, imaging and physiologic guidance, and antiplatelet therapy recommendations. Conclusions: DCB angioplasty can be an alternative or complement to therapeutic options to DESs across multiple clinical and anatomical scenarios. The CIAT consensus provided structured recommendations to support DCB therapy in contemporary practice. Full article
(This article belongs to the Section Cardiology)
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13 pages, 884 KB  
Article
Comparison of the Prognostic Performance of Various Machine Learning Models in Patients with Acute Myocardial Infarction: Results from the COREA-AMI Registry
by Ji-Hoon Jung, Kyusup Lee, Kiyuk Chang, Youngkeun Ahn, Sung-Ho Her and Sangin Lee
Medicina 2025, 61(10), 1783; https://doi.org/10.3390/medicina61101783 - 2 Oct 2025
Viewed by 834
Abstract
Background and Objectives: To date, several machine learning (ML) prognostic prediction models have been investigated for patients with acute myocardial infarction (AMI). However, few studies have compared the prognostic performance of ML techniques in AMI patients who underwent percutaneous coronary intervention (PCI). [...] Read more.
Background and Objectives: To date, several machine learning (ML) prognostic prediction models have been investigated for patients with acute myocardial infarction (AMI). However, few studies have compared the prognostic performance of ML techniques in AMI patients who underwent percutaneous coronary intervention (PCI). We sought to compare the prognostic performance among various machine learning techniques to determine which one showed the best prediction ability. Materials and Methods: Using data from the large, multicenter COREA-AMI registry, this study analyzed 10,172 patients to predict major adverse cardiac events (MACEs) at 1 and 5 years. MACE was defined as a composite of cardiac death, myocardial infarction, or cerebrovascular accident. Results: Compared with the four other ML techniques and traditional logistic regression, the random forest (RF) model consistently demonstrated the highest predictive performance. At 5 years, the RF model achieved a superior area under the curve (AUC) of 0.822, an accuracy of 0.804, and an F1 score of 0.870. To ensure clinical interpretability, a SHapley Additive exPlanations analysis was performed on the RF model. It identified key independent predictors for MACEs. The top nonmodifiable predictors included age, renal function, and left ventricular ejection fraction, whereas modifiable risk factors included dual antiplatelet therapy, statin therapy, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy, and adherence to these optimal medical therapy. Conclusions: In this real-world patient cohort, the RF model provided modest improvements in long-term risk stratification, and our findings highlight the continuing importance of guideline-directed medical therapy in determining patient prognosis. Full article
(This article belongs to the Section Cardiology)
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30 pages, 5419 KB  
Article
MIL-100(Fe)-Enabled Oral Delivery of Syringic Acid with Enhanced Pharmacokinetics
by Joshua H. Santos, Hannah Jean Victoriano, Mary Sepulveda, Hung-En Liu, Shierrie Mae N. Valencia, Rikkamae Zinca Marie L. Walde, Emelda A. Ongo and Chia-Her Lin
Pharmaceutics 2025, 17(10), 1282; https://doi.org/10.3390/pharmaceutics17101282 - 1 Oct 2025
Viewed by 1013
Abstract
Background/Objectives: Plant-derived bioactive compounds like syringic acid, a phenolic acid from the shikimic acid pathway, have shown potential against chronic diseases, including diabetes, cardiovascular disorders, cancer, and cerebral ischemia. However, its poor water solubility and rapid systemic elimination result in low oral bioavailability, [...] Read more.
Background/Objectives: Plant-derived bioactive compounds like syringic acid, a phenolic acid from the shikimic acid pathway, have shown potential against chronic diseases, including diabetes, cardiovascular disorders, cancer, and cerebral ischemia. However, its poor water solubility and rapid systemic elimination result in low oral bioavailability, limiting therapeutic potential. This study aimed to enhance its oral bioavailability using MIL-100(Fe), a metal–organic framework (MOF) known for high surface area and drug-loading capacity. Methods: MIL-100(Fe) was synthesized using an optimized method and loaded with syringic acid through impregnation at 12, 24, 36, and 48 h. Characterization included PXRD, FTIR, BET, SEM, and DLS. Acute oral toxicity was evaluated following OECD 423 guidelines, and bioavailability was assessed in Sprague Dawley rats. Results: The 1:2 MIL-100(Fe) to syringic acid ratio achieved the highest drug loading at 64.42 ± 0.03% (12 h). PXRD and FTIR confirmed successful loading (notably at 1239.2 cm−1), and TGA indicated thermal stability at ~350 °C. SEM revealed octahedral particles with an average size of 270.67 ± 2.60 nm. BET showed reduced surface area post-loading. In vitro drug release exhibited media-dependent profiles. Toxicity tests indicated no adverse effects at 2000 mg/kg. Oral administration of SYA@MIL-100(Fe) resulted in a 10.997-fold increase in relative bioavailability versus oral syringic acid and a 12.82-fold increase compared to intraperitoneal administration. Conclusions: MIL-100(Fe) is a safe and effective oral carrier for syringic acid, significantly enhancing its bioavailability. This platform shows strong potential for delivering phenolic compounds in pharmaceutical applications. Full article
(This article belongs to the Special Issue Novel Drug Delivery Systems for Natural Extracts)
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21 pages, 1271 KB  
Article
Feasibility and Limitations of Generalized Grover Search Algorithm-Based Quantum Asymmetric Cryptography: An Implementation Study on Quantum Hardware
by Tzung-Her Chen and Wei-Hsiang Hung
Electronics 2025, 14(19), 3821; https://doi.org/10.3390/electronics14193821 - 26 Sep 2025
Viewed by 1243
Abstract
The emergence of quantum computing poses significant threats to conventional public-key cryptography, driving the urgent need for quantum-resistant cryptographic solutions. While quantum key distribution addresses secure key exchange, its dependency on symmetric keys and point-to-point limitations present scalability constraints. Quantum Asymmetric Encryption (QAE) [...] Read more.
The emergence of quantum computing poses significant threats to conventional public-key cryptography, driving the urgent need for quantum-resistant cryptographic solutions. While quantum key distribution addresses secure key exchange, its dependency on symmetric keys and point-to-point limitations present scalability constraints. Quantum Asymmetric Encryption (QAE) offers a promising alternative by leveraging quantum mechanical principles for security. This paper presents the first practical implementation of a QAE protocol on IBM Quantum devices, building upon the theoretical framework originally proposed by Yoon et al. We develop a generalized Grover Search Algorithm (GSA) framework that supports non-standard initial quantum states through novel diffusion operator designs, extending its applicability beyond idealized conditions. The complete QAE protocol, including key generation, encryption, and decryption stages, is translated into executable quantum circuits and evaluated on both IBM Quantum simulators and real quantum hardware. Experimental results demonstrate significant scalability challenges, with success probabilities deteriorating considerably for larger systems. The 2-qubit implementation achieves near-perfect accuracy (100% on the simulator, and 93.88% on the hardware), while performance degrades to 78.15% (simulator) and 45.84% (hardware) for 3 qubits, and declines critically to 48.08% (simulator) and 7.63% (hardware) for 4 qubits. This degradation is primarily attributed to noise and decoherence effects in current Noisy Intermediate-Scale Quantum (NISQ) devices, highlighting the limitations of single-iteration GSA approaches. Our findings underscore the critical need for enhanced hardware fidelity and algorithmic optimization to advance the practical viability of quantum cryptographic systems, providing valuable insights for bridging the gap between theoretical quantum cryptography and real-world implementations. Full article
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15 pages, 1824 KB  
Article
Differential Associations Between Adaptability and Mental Health Symptoms Across Interpersonal Style Groups: A Network Comparison Study
by Shixiu Ren
Behav. Sci. 2025, 15(10), 1307; https://doi.org/10.3390/bs15101307 - 25 Sep 2025
Viewed by 874
Abstract
The university period is a transitional stage during which students develop heterogeneous interpersonal styles to navigate complex social demands. While prior studies have linked interpersonal functioning to adaptability and mental health, structural differences across interpersonal style groups remain underexplored. Therefore, the current research [...] Read more.
The university period is a transitional stage during which students develop heterogeneous interpersonal styles to navigate complex social demands. While prior studies have linked interpersonal functioning to adaptability and mental health, structural differences across interpersonal style groups remain underexplored. Therefore, the current research was designed to examine whether and how adaptability is differentially related to mental health symptoms when considered within the framework of distinct interpersonal style profiles. Using K-means clustering, we identified three distinct interpersonal profiles: the withdrawn and avoidant type, the overinvolved and compliant type, and the well-adjusted interpersonal type. Based on this classification, network analyses were conducted to examine how six dimensions of adaptability related to three core mental health symptoms within each group. The results showed a consistent pattern across all profiles, with emotional adaptability negatively associated with depression, anxiety, and stress. Subsequent network comparison analyses demonstrated that the withdrawn and avoidant group differed significantly in structure from the well-adjusted interpersonal group, particularly in the connections involving emotional, interpersonal, and economic adaptability. By uncovering meaningful differences in adaptability-mental health associations across interpersonal style, this study provides a foundation for designing targeted strategies that address the unique adaptabilities and mental health problems of distinct interpersonal profiles. Full article
(This article belongs to the Section Health Psychology)
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18 pages, 817 KB  
Review
BK Polyomavirus-Associated Nephropathy and Hemorrhagic Cystitis in Transplant Recipients—What We Understand and What Remains Unclear
by Tang-Her Jaing, Yi-Lun Wang and Tsung-Yen Chang
Viruses 2025, 17(9), 1256; https://doi.org/10.3390/v17091256 - 17 Sep 2025
Viewed by 2020
Abstract
The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review [...] Read more.
The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review aims to summarize the current understanding and lingering ambiguity by looking at three primary questions: (1) In cases with BKPyV-related illnesses in transplant patients, which diagnostic methods have the best track record of accuracy and success? (2) Which therapy approaches have the best track records of safety and efficacy in real-world clinical settings? (3) What can immunological research teach us about the development of future tailored treatments? Diagnosis involves the patient’s appearance, ruling out other potential causes, and employing quantitative PCR to identify active viral replication in urine or plasma. BKPyV-HC can vary from self-limited hematuria to potentially fatal bleeding, while BKPyVAN may lead to loss and dysfunction of the allograft. Reducing immunosuppression remains the key aspect of treatment. However, the effectiveness of antivirals (such cidofovir and leflunomide) is not always the same, and supporting measures depend on the syndrome. Researchers are looking into new immunotherapies, such as virus-specific cytotoxic T cells. Due to the intricate viro-immunopathology and lack of defined treatment regimens, future initiatives should focus on prospective studies to establish validated thresholds, enhance management algorithms, and integrate immune surveillance into individualized therapy. Full article
(This article belongs to the Special Issue Viral Immunology in Transplant Patients)
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23 pages, 1508 KB  
Review
Richter Transformation in Chronic Lymphocytic Leukemia: Current Treatment Challenges and Evolving Therapies
by Zi-Chi Lin, Ming-Jen Chan, Tang-Her Jaing, Tung-Liang Lin, Yu-Shin Hung and Yi-Jiun Su
Int. J. Mol. Sci. 2025, 26(17), 8747; https://doi.org/10.3390/ijms26178747 - 8 Sep 2025
Viewed by 2883
Abstract
Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, [...] Read more.
Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20–30% and median overall survival of 6–12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton’s tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60–65%, though relapses remain frequent. Bispecific antibodies (e.g., CD3×CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma. Full article
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18 pages, 2476 KB  
Article
Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway
by Tsung-Hsun Hsieh, Jar-Yi Ho, Chih-Chien Wang, Feng-Cheng Liu, Chian-Her Lee, Herng-Sheng Lee and Yi-Jen Peng
Cells 2025, 14(15), 1208; https://doi.org/10.3390/cells14151208 - 6 Aug 2025
Cited by 1 | Viewed by 1162
Abstract
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. [...] Read more.
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article
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11 pages, 1605 KB  
Article
Year-Long Antibody Response to the EuCorVac-19 SARS-CoV-2 Vaccine in Healthy Filipinos
by Jonathan F. Lovell, Kazutoyo Miura, Yeong Ok Baik, Chankyu Lee, YoungJin Choi, Jeong-Yoon Lee, Carole A. Long, Michelle Ylade, Roxas Lee-Llacer, Norman De Asis, Mitzi Trinidad-Aseron, Jose Manuel Ranola, Loreta Zoleta De Jesus and Howard Her
Vaccines 2025, 13(8), 776; https://doi.org/10.3390/vaccines13080776 - 22 Jul 2025
Cited by 1 | Viewed by 1042
Abstract
Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELDTM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: [...] Read more.
Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELDTM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: Healthy adults over 18 years of age received two injections of ECV-19 or CS vaccines, with 4 weeks between prime and boost. Analysis was carried out in individuals with immunogenicity measurements available at all 4 timepoints (weeks 0, 6, 30, and 56; n = 535 for ECV-19 and n = 260 for CS). Results: 2 weeks after boosting (week 6), ECV-19 elicited higher median anti-RBD IgG (1512 vs. 340 BAU/mL, p < 0.001) and neutralizing antibodies (1280 vs. 453 median microneutralization (MN) titer, p < 0.001) compared to CS. Anti-RBD IgG remained higher for ECV-19 compared to CS through week 30 (412 vs. 238 BAU/mL, p < 0.001) and 56 (425 vs. 260 BAU/mL, p < 0.001). MN titers remained higher for ECV-19 compared to CS through week 30 (640 vs. 453, p < 0.001) and 56 (453 vs. 320, p < 0.001). Correlation between anti-RBD IgG and neutralization titers persisted throughout the study. Women generally exhibited greater antibody responses than men. In the first six months following immunization, the ECV-19 group had a median antibody half-life of 80 days for anti-RBD IgG and 112 days for MN titer. In the subsequent six months, antibody half-life increased to 237 days for anti-RBD IgG and 168 days for MN titer. Conclusions: Following initial prime-boost vaccination, ECV-19 maintained higher anti-RBD IgG and neutralizing antibody titers relative to the CS comparator over a full-year period. Full article
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