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30 pages, 5074 KB  
Article
Vitamin D Modulates Humoral Responses to SARS-CoV-2 Vaccination in Autoimmune Thyroiditis: An Endocrine–Immune Perspective Supported by Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations
by Nawel Zerouak, Salma Hentabli, Abderrahmane Zitouni, Mouna Lehassani, Hamza Hentabli, Mohamed Anis Haroun, Mammar Khames, Karine Benachour, Yassine Amrani and Mustapha Oumouna
Int. J. Mol. Sci. 2026, 27(5), 2208; https://doi.org/10.3390/ijms27052208 - 26 Feb 2026
Abstract
Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine–immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with [...] Read more.
Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine–immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti–spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D3 related molecular targets were integrated with AIT-associated genes, followed by protein–protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D3 (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D3 to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine–immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance. Full article
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15 pages, 580 KB  
Article
Chronic Low-Grade Inflammation: A Possible Link Between COVID-19 and New-Onset Atrial Fibrillation
by Ciprian Ilie Roșca, Daniel Florin Lighezan, Daniel-Dumitru Nișulescu, Nilima Rajpal Kundnani, Romina Georgiana Bita, Ariana Violeta Nicoras, Christian Banciu and Andreea Munteanu
J. Clin. Med. 2026, 15(5), 1750; https://doi.org/10.3390/jcm15051750 - 25 Feb 2026
Abstract
Background: Persistent inflammation and endothelial dysfunction have been proposed as key mechanisms of post-COVID cardiovascular sequelae and may contribute to atrial fibrillation (AF). We examined whether inflammatory/prothrombotic biomarkers and endothelial function differ between post-COVID patients and controls, and whether baseline inflammation/endothelial dysfunction relates [...] Read more.
Background: Persistent inflammation and endothelial dysfunction have been proposed as key mechanisms of post-COVID cardiovascular sequelae and may contribute to atrial fibrillation (AF). We examined whether inflammatory/prothrombotic biomarkers and endothelial function differ between post-COVID patients and controls, and whether baseline inflammation/endothelial dysfunction relates to AF burden at 12 months. Methods: In this single-center, retrospective observational study, 198 outpatients were enrolled: 99 post-COVID patients evaluated 3–6 months after documented SARS-CoV-2 infection (Group 1) and 99 age- and sex-matched controls without prior COVID-19 (Group 2). At baseline (t0), clinical characteristics, inflammatory/prothrombotic biomarkers, brachial artery flow-mediated dilation (FMD), and 24 h Holter ECG were assessed in both groups. Univariable linear regression tested associations between baseline variables and FMD in Group 1. At 12 months (t1), 24 h Holter ECG was repeated in both groups. Quartile analyses were performed according to baseline neutrophil-to-lymphocyte ratio (NLR) to explore AF distribution across inflammatory strata. Results: At baseline, post-COVID patients had higher inflammatory and prothrombotic markers than controls (ESR, CRP, fibrinogen, and D-dimer; all p < 0.0001) and markedly lower FMD (7.72 vs. 13.72; p < 0.0001). In Group 1, FMD was inversely associated with multiple inflammatory/prothrombotic markers (all p < 0.0001), with the strongest association for ESR (R2 = 0.6297). Holter-detected AF prevalence at baseline did not differ significantly between groups (25/99 [25.3%] vs. 18/99 [18.2%]). At 12 months, AF prevalence was numerically higher in the post-COVID group (32/99 [32.3%] vs. 21/99 [21.2%]); on two-sided testing, this difference was borderline (p = 0.047) and should be interpreted cautiously. Across increasing baseline NLR quartiles, AF prevalence increased stepwise in both groups (post-COVID: 2/25, 5/25, 10/24, 15/25; controls: 1/25, 3/25, 7/24, 10/25), consistent with the enrichment of AF in higher-inflammatory strata. Conclusions: Post-COVID patients exhibited a persistent inflammatory–prothrombotic profile and pronounced endothelial dysfunction at baseline. At 12 months, AF burden was numerically higher post-COVID, and AF clustered in strata characterized by higher baseline NLR and lower FMD, consistent with an inflammation–endothelial dysfunction axis associated with subsequent AF burden. Prospective studies with standardized rhythm monitoring and comprehensive multivariable adjustment are warranted. Full article
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23 pages, 10908 KB  
Article
MSF: Multi-Level Spatiotemporal Filtering for Event Denoising via Motion Estimation
by Jiuhe Wang, Kun Yu, Xinghua Xu and Nanliang Shan
Sensors 2026, 26(5), 1437; https://doi.org/10.3390/s26051437 - 25 Feb 2026
Abstract
Event cameras provide microsecond-level temporal resolution, low latency, and high dynamic range, enabling robust perception under fast motion and challenging lighting conditions. Nevertheless, event streams are susceptible to background activity, thermal noise, and hot pixels. Their sparse and irregular patterns can corrupt event [...] Read more.
Event cameras provide microsecond-level temporal resolution, low latency, and high dynamic range, enabling robust perception under fast motion and challenging lighting conditions. Nevertheless, event streams are susceptible to background activity, thermal noise, and hot pixels. Their sparse and irregular patterns can corrupt event structures and degrade downstream tasks. We propose MSF, a multi-level spatiotemporal filtering framework that couples motion-compensated aggregation with neighborhood-level verification. In each temporal window, MSF estimates a constant 2D optical flow by maximizing a robust, density-normalized contrast objective on the image of warped events (IWE). We further incorporate polarity–gradient decorrelation to suppress mixed-polarity noise and an explicit peak-suppression regularizer to avoid hot-pixel-induced degeneracy. The motion parameters are optimized via coarse grid initialization followed by gradient-ascent refinement. Based on the estimated motion, MSF performs hierarchical event selection: central events are extracted from high-confidence aggregated regions, local events are recovered through joint spatial–temporal–directional–polarity consistency, and weak border events are identified using a density-normalized probabilistic support model that rewards support from reliable structures while penalizing self-clustering. Experiments on four public benchmarks (DVSNOISE20, DVSMOTION20, DVSCLEAN, and E-MLB) show that MSF consistently improves the Event Structural Ratio (ESR) and outperforms representative baselines across diverse motion regimes and severe low-light noise. Full article
(This article belongs to the Special Issue Event-Driven Vision Sensor Architectures and Application Scenarios)
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12 pages, 295 KB  
Article
Role of Serum Inflammatory Biomarkers in Risk Stratification of Hospitalized Children with Macrolide-Non-Responsive Mycoplasma pneumoniae Pneumonia
by Jin-Sung Park and Hyo-Bin Kim
Children 2026, 13(3), 313; https://doi.org/10.3390/children13030313 - 24 Feb 2026
Viewed by 31
Abstract
Background/Objectives: Macrolide is the first-line treatment in children with Mycoplasma pneumonia; however, macrolide-non-responsive Mycoplasma pneumoniae pneumonia (MNMP) has been increasing recently. We aimed to investigate serum inflammatory biomarkers that could identify children at risk of clinically defined macrolide non-responsiveness as early as possible. [...] Read more.
Background/Objectives: Macrolide is the first-line treatment in children with Mycoplasma pneumonia; however, macrolide-non-responsive Mycoplasma pneumoniae pneumonia (MNMP) has been increasing recently. We aimed to investigate serum inflammatory biomarkers that could identify children at risk of clinically defined macrolide non-responsiveness as early as possible. Methods: This retrospective cohort study included 93 children hospitalized with Mycoplasma pneumonia between September 2019 and January 2020. Patients were classified into macrolide-sensitive MP (MSMP) and MNMP groups based on clinical response to treatment. Clinically defined MNMP was defined as persistent fever and lack of clinical improvement after at least 3 days of macrolide therapy, reflecting macrolide non-responsiveness in routine clinical practice. By reviewing medical records, we compared laboratory findings at admission, including serum procalcitonin (PCT), C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and erythrocyte sedimentation rate (ESR), between the two groups to identify potential predictive biomarkers. Multivariable logistic regression analysis was used to estimate the risk for MNMP based on serum inflammatory biomarkers. Results: CRP, ferritin, and ESR levels at admission were higher in the MNMP group than the MSMP group. By multivariate analysis, elevated ferritin levels were significantly associated with an increased risk of macrolide non-responsiveness. In addition, when serum inflammatory biomarkers were elevated simultaneously at admission, the risk of MNMP was higher. Conclusions: Serum inflammatory biomarkers may assist in early risk stratification of children with clinically defined macrolide non-responsiveness following macrolide therapy. Furthermore, combined assessment of multiple inflammatory biomarkers may improve early risk evaluation. Full article
(This article belongs to the Section Pediatric Infectious Diseases)
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20 pages, 3646 KB  
Article
Distinct Expression Patterns and Clinical Associations of the IRX Gene Family Across Hormone-Sensitive Cancers
by Amali Thennakoon, Achala Fernando and Jyotsna Batra
Cancers 2026, 18(5), 726; https://doi.org/10.3390/cancers18050726 - 24 Feb 2026
Viewed by 84
Abstract
Background/Objectives: The Iroquois (IRX) family of homeobox genes regulates critical developmental processes, and emerging evidence suggests that their dysregulation contributes to cancer progression, particularly in relation to cancer stemness. Although their expression appears to be influenced by hormonal regulation, their potential [...] Read more.
Background/Objectives: The Iroquois (IRX) family of homeobox genes regulates critical developmental processes, and emerging evidence suggests that their dysregulation contributes to cancer progression, particularly in relation to cancer stemness. Although their expression appears to be influenced by hormonal regulation, their potential roles in hormone-sensitive cancers remain incompletely understood. Methods: In this study, we performed a comprehensive, exploratory analysis of all six Iroquois genes (IRX1IRX6) across prostate, breast, ovarian, and endometrial cancers. Using large-scale publicly available transcriptomic datasets, we systematically examined IRX gene expression patterns and their associations with tumour progression, prognosis, hormone regulation, drug response, and cancer stemness. Results:IRX3 and IRX5 were consistently elevated in estrogen-dependent tumours and IRX2 and IRX4 were notably upregulated in prostate cancer. Despite evidence of estrogen receptor 1 (ESR1) and androgen receptor (AR) binding near several IRX promoters, estrogen treatment assays showed that ESR1 binding at promoters alone was insufficient to induce IRX transcription. Clinically, IRX2 expression was associated with favourable outcomes in breast, endometrial, and ovarian cancers and showed correlations with stemness-related signatures in prostate cancer. Similarly, IRX4 expression was associated with stemness features in prostate and endometrial cancers. In addition, IRX6 expression showed associations with reduced sensitivity to abiraterone, suggesting a potential link with therapeutic resistance in these tumours. Conclusions: Collectively, these findings highlight the context-dependent expression patterns and clinical associations of IRX genes across hormone-driven cancers. While largely correlative, this study provides a framework for future functional investigations and suggests that selected IRXs may have potential utility as biomarkers for disease stratification and treatment response in hormone-sensitive cancers. Full article
(This article belongs to the Section Molecular Cancer Biology)
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21 pages, 1386 KB  
Article
Comparison of Severe COVID-19 Outcomes in Vaccinated and Unvaccinated Patients, with and Without Diabetes Mellitus in a Romanian Tertiary Healthcare Pneumology Hospital—A Retrospective Study
by Ioana-Mădălina Moşteanu, Adela Gabriela Ştefan, Beatrice Mahler, Adina Mitrea, Ionela Mihaela Vladu, Oana-Andreea Parliţeanu, Diana Clenciu, Eugen Moţa, Maria Magdalena Roşu, Delia-Viola Reurean Pintilei, Beatrice Elena Vladu, Alexandru Stoichiță, Diana Cristina Protasiewicz-Timofticiuc, Theodora Claudia Radu-Gheonea, Ion-Cristian Efrem, Anca Maria Amzolini and Maria Moţa
Int. J. Mol. Sci. 2026, 27(4), 2082; https://doi.org/10.3390/ijms27042082 - 23 Feb 2026
Viewed by 161
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on public health. In the present study, we aimed to analyze the association of certain inflammatory biomarkers with severe COVID-19 and to explore the role of diabetes mellitus (DM) and vaccination status [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on public health. In the present study, we aimed to analyze the association of certain inflammatory biomarkers with severe COVID-19 and to explore the role of diabetes mellitus (DM) and vaccination status in relation to COVID-19 severity, intensive care need and mortality. Associated comorbidities (DM, obesity, cardiovascular, neurological, endocrine, hepatic, renal, pulmonary, rheumatological, psychiatric, hematological diseases, cancer and HIV), as well as inflammatory biomarkers, like ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were analyzed in 866 subjects, according to vaccination status. In unvaccinated subjects, the highest AUROC curve for severe COVID-19 was recorded for CRP (0.668), and in the vaccinated group, the highest was recorded for SII (0.694). In age- and comorbidity-adjusted analyses, diabetes mellitus was associated with higher odds of severe COVID-19, ICU admission, and mortality among unvaccinated patients. This analysis was not feasible in the vaccinated group because of the very low number of unfavorable outcomes. These findings emphasize the potential role of vaccination in attenuating the excess risk linked to comorbidities—particularly diabetes mellitus—and support the use of accessible inflammatory biomarkers for early risk stratification. The results should be interpreted within the specific epidemiological phases of the pandemic and in the context of the observational study design. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)
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18 pages, 221265 KB  
Article
ESR2 Regulates Granulosa Cell Proliferation and Steroidogenesis via the PI3K/AKT/mTOR Signaling Pathway in Wuding Chickens
by Chen Li, Wei Zhu, Xinyu Ma, Xinyang Fan, Fu Ha and Yongwang Miao
Biology 2026, 15(4), 370; https://doi.org/10.3390/biology15040370 - 22 Feb 2026
Viewed by 122
Abstract
The Wuding chicken, a renowned indigenous breed in Yunnan Province, is prized for its superior meat quality; however, its economic potential is limited by pronounced broodiness and suboptimal egg production. Central to alleviating these constraints is the precise regulation of ovarian granulosa cell [...] Read more.
The Wuding chicken, a renowned indigenous breed in Yunnan Province, is prized for its superior meat quality; however, its economic potential is limited by pronounced broodiness and suboptimal egg production. Central to alleviating these constraints is the precise regulation of ovarian granulosa cell (GC) proliferation and steroidogenic processes that dictate follicular development and laying performance. While Estrogen Receptor 2 (ESR2) is a known transcription factor implicated in follicular maturation, its spatiotemporal dynamics within the hypothalamic-pituitary-ovarian (HPO) axis and its specific regulatory mechanisms in Wuding chicken remain elusive. This study characterizes ESR2 expression across the HPO axis during the laying and broody periods and functionally validates its role in GCs. We observed that ESR2 expression was significantly higher throughout the HPO axis during the laying period compared to the broody period, with the most pronounced differential expression occurring in the ovary. Notably, subcellular localization analysis revealed that ESR2 is distributed in both the nucleus and the cytoplasm, indicating involvement in both nuclear transcriptional regulation and cytoplasmic signaling. Functional assays demonstrated that ESR2 modulates the expression of genes associated with GC proliferation, steroidogenesis, and apoptosis, involving the PI3K/AKT/mTOR signaling pathway. Our findings indicate that this process involves a synergistic interplay between genomic and potential non-genomic actions. Specifically, ESR2 overexpression upregulates the expression of key signaling components and steroidogenic genes, including CYP19A1, STAR, PTGS2, and FSHR, while its cytoplasmic localization suggests a role in non‑genomic interactions. Together, these coordinated mechanisms synergistically maintain GC functional homeostasis. Collectively, these results prove that ESR2 plays an important role in regulating GC homeostasis and follicular development through genomic and non-genomic modes of action. These findings provide a molecular basis for the role of ESR2 in avian follicular development and offer potential targets for improving the reproductive efficiency of Wuding chickens. Full article
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12 pages, 885 KB  
Article
Short-Term Metabolic and Inflammatory Effects of Upadacitinib in Biologic-Refractory Spondyloarthritis: Real-World Evidence on Lipid Paradox and Safety
by Zeynel Abidin Akar, Dilan Yıldırım, Ömer Karakoyun and Mehmet Çağlayan
Pharmaceutics 2026, 18(2), 272; https://doi.org/10.3390/pharmaceutics18020272 - 22 Feb 2026
Viewed by 129
Abstract
Background: Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, is an established therapeutic option for spondyloarthritis (SpA). Although its clinical efficacy has been demonstrated in randomized trials, real-world evidence regarding its early metabolic effects—particularly in the context of the inflammatory “lipid paradox”—remains [...] Read more.
Background: Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, is an established therapeutic option for spondyloarthritis (SpA). Although its clinical efficacy has been demonstrated in randomized trials, real-world evidence regarding its early metabolic effects—particularly in the context of the inflammatory “lipid paradox”—remains limited. This study aimed to evaluate the short-term impact of UPA on inflammatory, hematologic, and metabolic parameters in a biologic-refractory SpA cohort. Methods: This retrospective cohort study included 61 patients (51 with ankylosing spondylitis and 10 with psoriatic arthritis) who had an inadequate response to tumor necrosis factor inhibitors (TNFi-IR). The study evaluated the short-term effects of UPA treatment on disease activity, inflammatory markers, and lipid-related atherogenic risk, as assessed using the LDL/HDL ratio, over a three-month period. Demographic characteristics, disease activity (BASDAI), inflammatory markers (CRP, ESR), safety parameters (creatine kinase [CK], ALT, AST), and lipid profiles were assessed at baseline, Month 1, and Month 3. Results: The mean age was 42.6 ± 10.8 years. By Month 3, UPA treatment resulted in significant reductions in BASDAI (5.8 ± 1.4 to 3.6 ± 1.2, p < 0.001), CRP (11.4 ± 10.2 to 6.9 ± 5.8 mg/L), and ESR (p < 0.01). Hemoglobin and albumin levels increased significantly (p < 0.05), while liver enzymes remained stable. CK levels demonstrated a modest but statistically significant increase without exceeding three times the upper limit of normal and without clinical evidence of myopathy. Total cholesterol, LDL-C, and HDL-C increased significantly (p ≤ 0.003); however, triglycerides and the LDL/HDL ratio remained unchanged (p > 0.05). No significant differences in inflammatory or metabolic responses were observed between ankylosing spondylitis and psoriatic arthritis subgroups (p > 0.05). Conclusions: In biologic-refractory SpA patients, upadacitinib provides rapid anti-inflammatory and clinical benefits. Although quantitative increases in lipid subfractions were observed, the stability of the LDL/HDL ratio suggests a balanced metabolic recalibration consistent with inflammation control rather than an immediate pro-atherogenic shift. These findings highlight the importance of early lipid monitoring and individualized cardiovascular risk assessment while maintaining the therapeutic advantages of JAK1 inhibition in complex SpA populations. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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22 pages, 8223 KB  
Article
Tribological Properties of AISI 420 ESR Stainless Steel Modified by Sequential Boriding and Nitriding
by Melvyn Alvarez Vera, Rafael Carrera Espinoza, Valeria López López, Marc Wettlaufer, Stefan Barth, Juan Carlos Díaz Guillén, Héctor Manuel Hernández García, Rita Muñoz Arroyo, Javier A. Ortega, Pablo Moreno Garibaldi and Marco A. Cruz-Gómez
Coatings 2026, 16(2), 263; https://doi.org/10.3390/coatings16020263 - 21 Feb 2026
Viewed by 175
Abstract
This study investigates the effects of surface thermochemical treatments using boriding, nitriding, and boronitriding on the microstructure and mechanical properties of martensitic stainless steel AISI 420 ESR. Powder-pack boriding, gas nitriding, and sequential boronitriding processes were applied to enhance surface hardness, wear resistance, [...] Read more.
This study investigates the effects of surface thermochemical treatments using boriding, nitriding, and boronitriding on the microstructure and mechanical properties of martensitic stainless steel AISI 420 ESR. Powder-pack boriding, gas nitriding, and sequential boronitriding processes were applied to enhance surface hardness, wear resistance, and adhesion. The microstructural and mechanical properties of the surface samples were analyzed using scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, microhardness, and nanoindentation testing. Tribological behavior was analyzed using a pin-on-disk tribometer under dry-sliding wear conditions, with applied normal loads of 5 N and 10 N and a sliding distance of 1000 m. The results showed that the borided samples exhibited the highest surface hardness, up to 1182 HV0.05, as well as brittle fracture and spallation with poor adhesion, while the boronitrided layer offered excellent adhesion. The boronitriding condition demonstrated a synergistic balance, combining high wear resistance (5.92 × 10−7 mm3N−1m−1 and 4.96 × 10−7 mm3N−1m−1) and reduced friction (~0.78 and ~0.67) for loads of 5 N and 10 N, respectively, without brittle fractures on the coating layer. These results confirm that duplex coating treatment is an effective strategy for improving the surface performance of AISI 420 ESR components subjected to severe operating conditions. Full article
(This article belongs to the Special Issue Advances in Protective Coatings for Metallic Surfaces)
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11 pages, 597 KB  
Article
Evaluation of Serum Calprotectin Levels and Their Relationship with Disease Activity in Psoriatic Arthritis and Axial Spondyloarthritis
by Emre Ali Acar, Sadettin Uslu, Semih Gülle, Muhammet Nurullah Yiğit, Cevval Ulman and Timur Pırıldar
Medicina 2026, 62(2), 406; https://doi.org/10.3390/medicina62020406 - 20 Feb 2026
Viewed by 168
Abstract
Background and Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by marked clinical heterogeneity and variable disease trajectories, underscoring the need for robust biomarkers of inflammatory burden. Serum calprotectin, a neutrophil- and monocyte-derived protein, has been proposed as a surrogate [...] Read more.
Background and Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by marked clinical heterogeneity and variable disease trajectories, underscoring the need for robust biomarkers of inflammatory burden. Serum calprotectin, a neutrophil- and monocyte-derived protein, has been proposed as a surrogate marker of active inflammation in inflammatory arthritis due to its close association with innate immune activation. In this study, we compare serum calprotectin levels among patients with PsA, axial spondyloarthritis (AxSpA), and healthy controls and evaluate their association with disease activity. Materials and Methods: This single-center, cross-sectional study included 123 patients with PsA, 119 patients with AxSpA, and 77 healthy controls. Serum calprotectin levels were measured by enzyme-linked immunosorbent assay, and their associations with disease activity were evaluated using correlation, multivariable regression, and receiver operating characteristic analyses. Results: Serum calprotectin levels were significantly higher in PsA and AxSpA patients compared with healthy controls (p < 0.001 for both) and were higher in PsA than in AxSpA (p = 0.022). In PsA, serum calprotectin levels showed significant correlations with ASDAS-CRP, DAS28-CRP, and DLQI, but not with CRP or ESR. In contrast, in AxSpA, calprotectin showed only a weak association with CRP and was not related to disease activity indices. In multivariable analysis, serum calprotectin was independently associated with ASDAS-CRP in PsA (B = 0.704, p = 0.003), but not in AxSpA. Receiver operating characteristic analysis demonstrated that serum calprotectin discriminated high disease activity in PsA with an area under the curve of 0.669 (95% CI: 0.563–0.775; p = 0.003). Conclusions: Serum calprotectin levels are elevated in patients with PsA and are associated with disease activity, supporting its potential role as a biomarker in this condition. In contrast, serum calprotectin does not appear to reflect disease activity in AxSpA, suggesting disease-specific differences in its clinical utility. Full article
(This article belongs to the Section Hematology and Immunology)
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17 pages, 590 KB  
Article
The Association Between Neuropathic Pain, Pain Intensity, and Inflammatory Activity in Rheumatoid Arthritis
by Zeynel Abidin Akar, Dilan Yıldırım, Ömer Karakoyun, Kadir Kaya, Mehmet Çağlayan, Pelin Oktayoğlu and Remzi Çevik
J. Clin. Med. 2026, 15(4), 1601; https://doi.org/10.3390/jcm15041601 - 19 Feb 2026
Viewed by 146
Abstract
Background: Nociplastic-like pain features are increasingly recognized as significant contributors to chronic pain and reduced quality of life in patients with rheumatoid arthritis (RA). However, their clinical correlates and relationship with disease activity remain incompletely understood. Objective: To evaluate the prevalence [...] Read more.
Background: Nociplastic-like pain features are increasingly recognized as significant contributors to chronic pain and reduced quality of life in patients with rheumatoid arthritis (RA). However, their clinical correlates and relationship with disease activity remain incompletely understood. Objective: To evaluate the prevalence of nociplastic-like pain features in patients with RA and to investigate their associations with disease activity, pain intensity, fatigue, sleep quality, and health-related quality of life. Methods: In this cross-sectional study, 160 patients with RA were enrolled. Nociplastic-like pain features were assessed using the PainDETECT questionnaire. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28). Pain intensity, fatigue, sleep quality, and health-related quality of life were assessed using the visual analog scale (VAS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Short Form-36 (SF-36), respectively. Continuous variables were compared using t-tests or Mann–Whitney U tests according to data distribution. Stepwise multivariate linear regression analysis was performed to identify independent factors associated with PainDETECT scores. Results: Pain patterns suggestive of nociplastic-like features were identified in 22.5% of patients. These patients had significantly higher pain intensity, greater fatigue (lower FACIT-F scores), poorer sleep quality (higher PSQI scores), and lower SF-36 scores across all domains compared with patients without these features (all p < 0.001). PainDETECT scores showed a strong positive correlation with VAS pain intensity (r = 0.679, p < 0.001) and a moderate correlation with DAS28 (r = 0.536, p < 0.001). PainDETECT scores were negatively correlated with FACIT-F (r = −0.512, p < 0.001) and several SF-36 domains. In stepwise multivariate regression analysis, pain intensity, tender joint count, and education level emerged as independent predictors of nociplastic-like pain features, whereas inflammatory markers (CRP, ESR) and DAS28 were excluded from the model. Conclusions: Nociplastic-like pain features are common in RA and are independently associated with pain intensity, joint tenderness, and psychosocial factors rather than inflammatory activity alone. Routine assessment of these features is essential for personalized pain management and underscores the importance of considering potential central sensitization mechanisms in addition to traditional anti-inflammatory therapies. Full article
(This article belongs to the Section Immunology & Rheumatology)
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43 pages, 4356 KB  
Review
A Systematic Review of Major Advances in Breast Cancer Therapeutics in 2025: Synthesis of Conference and Published Evidence
by Nabil Ismaili
Int. J. Mol. Sci. 2026, 27(4), 1971; https://doi.org/10.3390/ijms27041971 - 19 Feb 2026
Viewed by 288
Abstract
The year 2025 has been transformative in breast oncology, marked by the maturation of pivotal adjuvant trials, the introduction of novel ADCs, and the validation of proactive biomarker-driven strategies across all molecular subtypes. ASCO, ESMO, and SABCS contributed pivotal updates that further refined [...] Read more.
The year 2025 has been transformative in breast oncology, marked by the maturation of pivotal adjuvant trials, the introduction of novel ADCs, and the validation of proactive biomarker-driven strategies across all molecular subtypes. ASCO, ESMO, and SABCS contributed pivotal updates that further refined treatment paradigms. This systematic review synthesizes and critically evaluates pivotal Phase II/III clinical trials presented at major oncology conferences (ASCO 2025, ESMO 2025, SABCS 2025) and published in high-impact journals during 2025. A curated selection of pivotal Phase II/III trials, and major prospective trials published or presented in 2025 was performed. Data extraction focused on trial design, population, interventions, efficacy endpoints, and safety outcomes. Narrative synthesis was organized by disease stage and molecular subtype. Key 2025 findings (50 clinical trials) include: (1) confirmation of overall survival benefit with adjuvant CDK4/6 inhibitors in HR+/HER2− early breast cancer (monarchE: HR = 0.842, p = 0.0273); (2) establishment of trastuzumab deruxtecan (T-DXd) as a new standard in high-risk HER2+ early disease (DESTINY-Breast05: IDFS HR = 0.47) and first-line metastatic settings (DESTINY-Breast09: PFS HR = 0.58); (3) validation of TROP2-directed ADCs as first-line therapy for metastatic triple-negative breast cancer (ASCENT-03: PFS HR = 0.62; BEGONIA: ORR 79%); (4) paradigm shift to proactive, liquid biopsy-guided therapy switching (SERENA-6: PFS HR = 0.44); (5) updated efficacy and safety of the oral SERD imlunestrant from the EMBER-3 trial, supporting its role in ESR1-mutated advanced breast cancer and in combination with abemaciclib; (6) confirmation of long-term survival benefit for neoadjuvant carboplatin in early TNBC and new positive adjuvant data; (7) pivotal advances in HER2+ metastatic disease sequencing with tucatinib and T-DXd; (8) evidence supporting optimized adjuvant endocrine therapy in HER2+/HR+ early disease; and (9) emergence of novel agents with improved therapeutic indices, including PROTAC degraders, oral SERDs, and mutant-selective PI3K inhibitors. The 2025 evidence base has fundamentally reshaped breast cancer management, establishing new standards of care across all subtypes. Unifying themes include biomarker-driven personalization, strategic treatment sequencing, management of unique toxicities, and emphasis on patient-reported outcomes. Future challenges include optimizing treatment integration, managing financial toxicity, and ensuring equitable global access. Full article
(This article belongs to the Special Issue Advances in Molecular Pathology and Treatment of Breast Cancer)
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17 pages, 653 KB  
Article
Diagnostic Value of Mean Platelet Volume and Hematological Inflammatory Ratios in Brucellosis: A Case–Control Study
by Enes Dalmanoğlu, Yeşim Çağlar and Gülce Eylül Aldemir
Life 2026, 16(2), 352; https://doi.org/10.3390/life16020352 - 18 Feb 2026
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Abstract
Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital [...] Read more.
Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital in Turkey (2015–2018). Complete blood count parameters, hematological ratios (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured at diagnosis. Receiver operating characteristic (ROC) curve analysis evaluated diagnostic performance; multivariate logistic regression developed a combined model. Brucellosis patients showed significantly lower MPV (8.04 ± 0.95 vs. 8.56 ± 0.69 fL, p = 0.002), higher platelet counts (305.0 ± 116.0 vs. 246.0 ± 55.2 × 103/μL, p = 0.002), lower NLR (median: 1.69 vs. 2.07, p = 0.013), and higher LMR (median: 5.28 vs. 4.12, p = 0.008). ESR demonstrated the best individual diagnostic performance (area under the curve [AUC] = 0.842). The combined model (MPV + ESR + CRP) achieved superior performance (AUC = 0.891, sensitivity 84%, specificity 86%). Limitations include the single-center retrospective design, lack of internal validation, and comparison with healthy controls only. Notably, healthy controls were deliberately selected to establish baseline hematological profiles associated with brucellosis rather than to differentiate it from other infections. Brucellosis presents a unique hematological profile with decreased MPV and altered inflammatory ratios. The combined model offers a potentially cost-effective screening approach for endemic settings, pending external validation. Full article
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25 pages, 1248 KB  
Guidelines
Romanian Consensus Statement for Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer (HR+/HER2– mBC) and Triple-Negative Metastatic Breast Cancer (mTNBC)
by Mircea Dragoș Median, Nicoleta Zenovia Antone, Simona Volovăț, Laura Mazilu, Șerban Mircea Negru, Răzvan Ovidiu Curcă, Amedeia Niță, Raluca Ileana Pătru, Andrei Ungureanu, Vlad Lupu and Cristina Marinela Oprean
Curr. Oncol. 2026, 33(2), 120; https://doi.org/10.3390/curroncol33020120 - 17 Feb 2026
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Abstract
Breast cancer (BC) is the most common malignant disease in women in Romania, with incidence and mortality rates among the highest in Europe. This consensus statement aims to ensure equitable access to care for human epidermal growth factor receptor 2-negative metastatic BC (HR+/HER2– [...] Read more.
Breast cancer (BC) is the most common malignant disease in women in Romania, with incidence and mortality rates among the highest in Europe. This consensus statement aims to ensure equitable access to care for human epidermal growth factor receptor 2-negative metastatic BC (HR+/HER2– mBC) and triple-negative mBC (mTNBC) in Romania. Between December 2024 and June 2025, a scientific board of 11 oncologists, in collaboration with the Romanian National Society for Medical Oncology (SNOMR), developed national recommendations based on ESMO/NCCN/ABC guidelines, clinical expertise, and local conditions. A modified Delphi survey was conducted among medical oncologists to evaluate acceptance of recommendations with greatest clinical impact. Key recommendations included: mandatory biopsy at metastasis with ER/PgR/HER2 retesting, HER2-low assessment, and molecular profiling (BRCA, PIK3CA, AKT1/PTEN, ESR1, plus PD-L1 testing in mTNBC); for HR+/HER2– mBC, first-line endocrine therapy plus CDK4/6 inhibitor, followed by targeted agents, chemotherapy, or antibody–drug conjugates based on progression and visceral crisis; for mTNBC, first-line immune checkpoint inhibitor plus chemotherapy in PD-L1-positive, PARP inhibitors in BRCA-positive patients, and sacituzumab-govitecan or trastuzumab-deruxtecan later; systematic toxicity monitoring; and integrated supportive and palliative care. Sixty-one oncologists completed the survey, with >90% overall agreement, suggesting broad acceptance of recommendations as Romania’s national standard for mBC care. Full article
(This article belongs to the Section Breast Cancer)
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25 pages, 3543 KB  
Article
B-Doped ZnO Nanoparticles: Defect Chemistry, Tensile Strain, and Tunable Optical Response
by Lütfi Arda, Merve Mine Seker Perez, Ersin Ozugurlu and Ilke Tascioglu
Inorganics 2026, 14(2), 60; https://doi.org/10.3390/inorganics14020060 - 16 Feb 2026
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Abstract
ZnO and ZnO:5%B nanoparticles produced by sol–gel synthesis exhibit a single-phase wurtzite structure. X-ray diffraction (XRD) investigation reveals crystallite sizes in the range of 32.3739.63 nm and microstrain values on the order of [...] Read more.
ZnO and ZnO:5%B nanoparticles produced by sol–gel synthesis exhibit a single-phase wurtzite structure. X-ray diffraction (XRD) investigation reveals crystallite sizes in the range of 32.3739.63 nm and microstrain values on the order of (1.988.03)×104, despite the Uniform Stress Deformation Model (USDM) indicating the presence of considerable tensile stress. Significant band-tail states are introduced via boron doping, resulting in Urbach energies ranging from 110 to 193 meV and a narrowed optical band gap of 3.216 eV. With a refractive index range of 2.052.71, the material exhibits tunable optical characteristics. Violet and blue emissions originating predominantly from zinc interstitials (Znᵢ) and zinc vacancies (VZn) dominate the photoluminescence spectra, while oxygen interstitial-related contributions remain relatively weak. A high spin density is confirmed by electron spin resonance measurements, which reveal a strong defect-related signal at g2.294. The formation of Znᵢ/VZn defect centers due to charge compensation and ionic size mismatch induced by B3+ substitution for Zn2+ significantly modifies the band-edge states and optical constants. These defect-engineered properties render the material promising for applications in ultraviolet (UV) photodetectors, transparent conducting oxides, and electron transport layers in organic photovoltaic devices. Full article
(This article belongs to the Special Issue Mixed Metal Oxides, 3rd Edition)
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