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22 pages, 586 KB  
Article
Onco-Hem Connectome—Network-Based Phenotyping of Polypharmacy and Drug–Drug Interactions in Onco-Hematological Inpatients
by Sabina-Oana Vasii, Daiana Colibășanu, Florina-Diana Goldiș, Sebastian-Mihai Ardelean, Mihai Udrescu, Dan Iliescu, Daniel-Claudiu Malița, Ioana Ioniță and Lucreția Udrescu
Pharmaceutics 2026, 18(2), 146; https://doi.org/10.3390/pharmaceutics18020146 - 23 Jan 2026
Abstract
We introduce the Onco-Hem Connectome (OHC), a patient similarity network (PSN) designed to organize real-world hemato-oncology inpatients by exploratory phenotypes with potential clinical utility. Background: Polypharmacy and drug–drug interactions (DDIs) are pervasive in hemato-oncology and vary with comorbidity and treatment intensity. Methods: We [...] Read more.
We introduce the Onco-Hem Connectome (OHC), a patient similarity network (PSN) designed to organize real-world hemato-oncology inpatients by exploratory phenotypes with potential clinical utility. Background: Polypharmacy and drug–drug interactions (DDIs) are pervasive in hemato-oncology and vary with comorbidity and treatment intensity. Methods: We retrospectively analyzed a 2023 single-center cohort of 298 patients (1158 hospital episodes). Standardized feature vectors combined demographics, comorbidity (Charlson, Elixhauser), comorbidity polypharmacy score (CPS), aggregate DDI severity score (ADSS), diagnoses, and drug exposures. Cosine similarity defined edges (threshold ≥ 0.6) to build an undirected PSN; communities were detected with modularity-based clustering and profiled by drugs, diagnosis codes, and canonical chemotherapy regimens. Results: The OHC comprised 295 nodes and 4179 edges (density 0.096, modularity Q = 0.433), yielding five communities. Communities differed in comorbidity burden (Kruskal–Wallis ε2: Charlson 0.428, Elixhauser 0.650, age 0.125, all FDR-adjusted p < 0.001) but not in utilization (LOS, episodes) after FDR (ε2 ≈ 0.006–0.010). Drug enrichment (e.g., enoxaparin Δ = +0.13 in Community 2; vinblastine Δ = +0.09 in Community 3) and principal diagnoses (e.g., C90.0 23%, C91.1 15%, C83.3 15% in Community 1) supported distinct clinical phenotypes. Robustness analyses showed block-equalized features preserved communities (ARI 0.946; NMI 0.941). Community drug signatures and regimen signals aligned with diagnosis patterns, reflecting the integration of resource-use variables in the feature design. Conclusions: The Onco-Hem Connectome yields interpretable, phenotype-level insights that can inform supportive care bundles, DDI-aware prescribing, and stewardship, and it provides a foundation for phenotype-specific risk models (e.g., prolonged stay, infection, high-DDI episodes) in hemato-oncology. Full article
(This article belongs to the Special Issue Drug–Drug Interactions—New Perspectives)
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12 pages, 1138 KB  
Article
The Role of Homocysteine in Pediatric MASLD: A Bipotential Biomarker of Cardiovascular Risk and Liver Fibrosis
by Antonella Mosca, Nadia Panera, Giulia Andolina, Luca Della Volpe, Anna Pastore, Maria Rita Braghini, Lidia Monti, Paola Francalanci, Giovanna Soglia, Andrea Pietrobattista and Anna Alisi
Life 2026, 16(2), 191; https://doi.org/10.3390/life16020191 - 23 Jan 2026
Abstract
The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. [...] Read more.
The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker. Full article
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13 pages, 316 KB  
Review
Therapeutic Outcomes of Anti-VEGF Agents Versus Corticosteroids in Diabetic Macular Edema: A Comparative Review
by Saranya Sanaka and Minzhong Yu
Int. J. Mol. Sci. 2026, 27(3), 1142; https://doi.org/10.3390/ijms27031142 - 23 Jan 2026
Abstract
This structured narrative review compared the efficacy, durability, and safety of anti-vascular endothelial growth factor (anti-VEGF) agents and intravitreal corticosteroids for the treatment of diabetic macular edema (DME), with the aim of identifying patient- and disease-specific factors to guide individualized therapy. A comprehensive [...] Read more.
This structured narrative review compared the efficacy, durability, and safety of anti-vascular endothelial growth factor (anti-VEGF) agents and intravitreal corticosteroids for the treatment of diabetic macular edema (DME), with the aim of identifying patient- and disease-specific factors to guide individualized therapy. A comprehensive search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted for studies published between January 2009 and November 2025, including randomized controlled trials, meta-analyses, and large observational cohorts with at least six months of follow-up. Visual acuity, anatomical outcomes, treatment burden, durability, and safety were extracted, and evidence quality was assessed using the GRADE framework. Eleven studies encompassing 1341 eyes were included. Anti-VEGF therapy consistently produced greater improvements in best-corrected visual acuity, particularly in treatment-naïve eyes and in patients with worse baseline vision, whereas corticosteroids achieved larger reductions in central macular thickness and significantly reduced injection burden because of longer durability. However, corticosteroid therapy was associated with higher rates of intraocular pressure elevation and cataract progression. In pseudophakic patients and in chronic or refractory DME, functional and anatomical outcomes were generally comparable between the two therapeutic classes. Combination therapy resulted in the greatest anatomical improvement but at the cost of increased ocular adverse events. Overall, anti-VEGF agents remain the preferred first-line treatment for most patients with DME owing to superior visual outcomes and a more favorable safety profile, while corticosteroids represent valuable alternatives in pseudophakic eyes, chronic or anti-VEGF–refractory DME, and cases with prominent inflammatory features, provided that careful monitoring for ocular adverse events is maintained. Full article
(This article belongs to the Special Issue Advances in Retinal Diseases: 3rd Edition)
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24 pages, 1219 KB  
Systematic Review
Challenges and Treatment Strategies in Elderly Patients with Inflammatory Bowel Disease: A Systematic Review and Narrative Synthesis
by John K. Triantafillidis, Konstantinos Malgarinos, Georgia Kontrarou, Emmanouil Kritsotakis, Victoria Polydorou, Konstantinos Pantos, Konstantinos Sfakianoudis, Agni Pantou, Anastasios Karandreas, Manousos M. Konstandoulakis and Apostolos E. Papalois
J. Pers. Med. 2026, 16(2), 59; https://doi.org/10.3390/jpm16020059 (registering DOI) - 23 Jan 2026
Abstract
Introduction: The proportion of elderly patients with IBD is steadily increasing due to the aging population and improved survival. Patients in this age group present specificities in diagnosis and treatment, particularly regarding the use of biological agents, where immunosenescence, multimorbidity, and polypharmacy [...] Read more.
Introduction: The proportion of elderly patients with IBD is steadily increasing due to the aging population and improved survival. Patients in this age group present specificities in diagnosis and treatment, particularly regarding the use of biological agents, where immunosenescence, multimorbidity, and polypharmacy affect the precise assessment of benefit and risk. Aim: This systematic review, which was conducted in accordance with the PRISMA 2020 statement, aims to synthesize available data on the epidemiology, clinical characteristics, and therapeutic management of IBD in the elderly, with emphasis on the most recent data and practical guidelines for the use of biological therapies. Methods: A systematic search of PubMed, Scopus, and Embase was conducted. A total of 40 studies were included, comprising 5 randomized controlled trials, 15 prospective cohort studies, and 20 retrospective observational studies. Eligible studies included randomized controlled trials, observational cohort studies, and population-based analyses. Given substantial clinical and methodological heterogeneity, findings were synthesized narratively. Data on demographics, disease phenotype, comorbidities, and treatment outcomes were extracted and analyzed. In addition, a narrative synthesis of major randomized trials of biologic therapies, recent guidelines, and data from prospective studies and patient registries was performed with a focus on safety and real-world outcomes in the elderly. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) and the Cochrane Risk of Bias tool. Results: The majority of included studies (85%) were found to have a low to moderate risk of bias, providing a reliable basis for the synthesis. Data show an increasing incidence of IBD in the elderly, often with a milder clinical course and a higher ratio of UC to CD. Multimorbidity and polypharmacy are significant challenges that increase the risk of adverse events. Although classic therapies remain effective, in many cases, a lower threshold is required to initiate advanced therapies, such as biologic agents. Anti-tumor necrosis factor (anti-TNF) agents, as well as biologics with alternative mechanisms of action such as vedolizumab (α4β7 integrin antagonist) and ustekinumab (interleukin-12/23 inhibitor), represent key therapeutic options in elderly patients with IBD. These biologic factors have efficacy comparable to that in younger patients and are considered attractive options due to reduced systemic immunosuppression and favorable safety profiles. JAK inhibitors are a practical option but are associated with an increased thromboembolic risk and require careful patient selection. Older age is associated with higher absolute rates of serious infections, hospitalizations, and, in some series, mortality. Individualized decision-making, including frailty assessment, vaccination coverage, infection control, and dose adjustments based on renal and hepatic function, is essential for optimal care. Conclusions: IBD in the elderly is a distinct clinical entity with unique challenges in diagnosis and management. A multidisciplinary approach and individualized treatment strategies are essential to ensure the balance between disease control and minimizing the risks associated with comorbidity and polypharmacy. Further research, including specifically designed clinical trials, is needed to optimize treatment and outcomes in this unique patient group. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
16 pages, 5092 KB  
Article
Evaluating Adjuvant Radiation Therapy Survival Benefit in Early-Stage HER2-Positive Invasive Breast Cancer Following Breast-Conserving Surgery: A National Cohort Aligned with NRG-BR008 HERO Trial
by Jonathon S. Cummock, Ali J. Haider, Mohummad Kazmi, Waqar M. Haque, Andrew M. Farach, E. Brian Butler and Bin S. Teh
Cancers 2026, 18(3), 352; https://doi.org/10.3390/cancers18030352 (registering DOI) - 23 Jan 2026
Abstract
Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with [...] Read more.
Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with the HERO RT de-escalation trial (NRG-BR008). Materials and methods: We queried the National Cancer Database for patients with early-stage HER2-positive invasive breast carcinoma treated with BCS and systemic therapy, stratified into HERO trial-aligned cohorts: Arm 1 (adjuvant systemic therapy) vs. Arm 2 (neoadjuvant systemic therapy, pathologic complete response). Within each cohort, patients receiving adjuvant RT were compared with those omitting RT. In the primary analysis, patients were propensity score matched (PSM) on demographics, diagnosis years, tumor characteristics, and trial stratification variables. Inverse probability of treatment weighting (IPTW) was additionally performed as a sensitivity analysis. Overall survival was evaluated using Kaplan–Meier, Cox regression, and restricted mean survival time (RMST). Results: In Arm 1 (818 patients, 94 deaths), 5-year OS was 96.9% with RT vs. 88.0% without RT, and 10-year OS was 94.3% vs. 68.5% (log-rank p < 0.001). RT omission was associated with higher mortality in the PSM Cox model (HR, 4.78; 95% CI, 2.84–8.02; p < 0.001), with an RMST advantage favoring RT of +2.86 months at 5 years and +12.55 months at 10 years (p < 0.001). In Arm 2 (176 patients, 10 deaths), 5-year OS was 97.6% with RT vs. 91.1% without RT, and OS at 107 months was 94.8% vs. 91.1% (log-rank p = 0.13). RT omission was not statistically significant in the PSM Cox model (HR, 3.40; 95% CI, 0.82–14.05; p = 0.09), though RMST favored RT (+1.83 months at 5 years, p = 0.004; +3.91 months at 107 months, p = 0.03). IPTW analyses were directionally consistent in Arm 1 (HR, 3.26; 95% CI, 2.52–4.21; p < 0.001) and inconclusive in Arm 2 (HR, 1.78; 95% CI, 0.80–3.95; p = 0.16). Conclusions: In this HERO-aligned national cohort, RT omission was associated with inferior OS in patients treated with adjuvant systemic therapy after BCS. Findings in the neoadjuvant pCR cohort were imprecise and hypothesis-generating. Given the retrospective registry design, lack of recurrence-specific endpoints, and potential residual confounding, results should not be interpreted as causal but support continued RT use outside prospective de-escalation trials. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care (2nd Edition))
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16 pages, 1793 KB  
Article
Sedation Strategies for Awake Carotid Endarterectomy: An Exploratory Retrospective Study Comparing Dexmedetomidine and Remifentanil
by Rosanna Carmela De Rosa and Antonio Romanelli
Clin. Pract. 2026, 16(2), 23; https://doi.org/10.3390/clinpract16020023 (registering DOI) - 23 Jan 2026
Abstract
Background: Awake carotid endarterectomy (CEA) under local anesthesia demands an optimal sedation strategy that ensures patient comfort while preserving the ability for real-time neurological assessment. Dexmedetomidine (DEX) and remifentanil (REMI) are widely used agents, but direct comparisons in this setting remain scarce. Methods: [...] Read more.
Background: Awake carotid endarterectomy (CEA) under local anesthesia demands an optimal sedation strategy that ensures patient comfort while preserving the ability for real-time neurological assessment. Dexmedetomidine (DEX) and remifentanil (REMI) are widely used agents, but direct comparisons in this setting remain scarce. Methods: Exploratory, retrospective, single-center study of awake CEA (March–July 2019). DEX or REMI infusions were titrated to a Richmond Agitation–Sedation Scale (RASS) of −1 to −2. Outcomes were sedation failure (RASS ≥ +2 despite maximum infusion rate), bradycardia, hypotension, and neurologic events. Statistical analyses used χ2 test (categorical variables) and Student’s t-test or Mann–Whitney test (continuous variables). Associations were assessed with Firth’s logistic regression (univariable and bivariate models), reporting odds ratios (OR) with 95% confidence intervals (CI95%). Trends in the Bispectral Index (BIS), hemodynamic, and respiratory parameters were assessed using two-way repeated-measures Analysis of Variance (ANOVA). A p-value < 0.05 was considered significant. Results: Fifty-two patients were included (DEX = 25; REMI = 27). DEX group showed more frequent sedation failure (32.0% vs. 3.7%; p = 0.020), bradycardia (36.0% vs. 3.7%; p = 0.009), and hypotension (28.0% vs. 0%; p = 0.011). DEX was associated with increased risk in sedation failure (OR 8.58, CI95% 1.70–85.81), bradycardia (OR 10.17, CI95% 2.05–101.21), and hypotension (OR 22.30, CI95% 2.46–2959.60); the direction of associations remained consistent in bivariate models adjusted for baseline confounders. ANOVA showed group-by-time interactions for BIS, heart rate, mean arterial pressure, and end-tidal CO2. No intraoperative complications or adverse outcomes were observed. Conclusions: In this retrospective cohort of awake CEA, DEX was associated with higher rates of sedation failure and hemodynamic adverse events compared with REMI, without an apparent impact on procedural success. Given non-random allocation and baseline imbalances, these findings are hypothesis-generating and warrant confirmation in larger, robust, and prospective studies. Full article
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23 pages, 497 KB  
Systematic Review
The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers
by Dagmara Cylwik, Roksana Dwornik and Katarzyna Białkowska
Cancers 2026, 18(3), 354; https://doi.org/10.3390/cancers18030354 (registering DOI) - 23 Jan 2026
Abstract
The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease [...] Read more.
The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease penetrance (BRCA1: ~40% and BRCA2: 11–27%), substantial variability in individual risk is observed, suggesting the influence of additional genetic variants. Background: Ovarian cancer is characterized by late detection and high mortality, and a significant portion of risk among BRCA1/2 carriers is shaped by reproductive and environmental factors as well as genetic modifiers. The article emphasizes that carriers of the same BRCA PV can exhibit markedly different risk levels depending on additional variants that modulate key biological processes, such as DNA repair, cell cycle regulation, and apoptosis. Methods: A systematic literature search covering the years 1996–2025 was conducted in the PubMed database. Initially, 734 publications were identified; after removing duplicates, thematically irrelevant articles, non-full-text papers, and studies not meeting the inclusion criteria, 47 articles were included in the review. These studies covered candidate gene analyses, GWAS, and data from the CIMBA consortium, which enables the examination of large cohorts of PV carriers. Results: The review identified numerous variants associated with increased or decreased ovarian cancer risk in BRCA1 carriers, including the following: OGG1, DR4, MDM2, CYP2A7, CASP8, ITGB3, HRAS1, TRIM61, and MTHFR. The reviewed studies also identified both protective and risk-increasing variants among BRCA2 PV carriers: UNG, TDG, and PARP2, and haplotypes in ATM, BRIP1, BARD1, MRE11, RAD51, and 9p22.2. The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP. Protective variants include BNC2 and LINC00824. The only SNP reaching genome-wide significance (p < 5 × 10−8) was in BNC2. Conclusions: The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets. Full article
(This article belongs to the Special Issue Genetics of Ovarian Cancer (2nd Edition))
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10 pages, 419 KB  
Article
Patient Factors Affecting Physicians’ Decision to Add Perineoplasty to Pelvic Organ Prolapse Surgery: A Quantitative Analysis
by Esther C. A. M. van Swieten, Yasmina Chaghouaoui, Karlijn J. van Stralen and Jan-Paul W. R. Roovers
J. Clin. Med. 2026, 15(3), 916; https://doi.org/10.3390/jcm15030916 (registering DOI) - 23 Jan 2026
Abstract
Background/Objectives: Perineoplasty can be performed as an adjunct to native tissue pelvic organ prolapse (POP) surgery; the optimal indication for perineoplasty is unknown due to limited evidence regarding its benefits and the absence of clear clinical guidelines. This study aims to describe patient-related [...] Read more.
Background/Objectives: Perineoplasty can be performed as an adjunct to native tissue pelvic organ prolapse (POP) surgery; the optimal indication for perineoplasty is unknown due to limited evidence regarding its benefits and the absence of clear clinical guidelines. This study aims to describe patient-related factors associated with surgeons’ decisions to add perineoplasty to POP surgery and to quantify the frequency of intraoperative changes from preoperative surgical plans. Methods: In this multicenter observational cohort study, women ≥ 18 years scheduled for primary native tissue POP surgery between April 2023 and November 2024 were included. Baseline characteristics, pelvic floor anatomy (POP-Q), genital hiatus (GH), perineal body (PB) measurements, and surgeon-reported considerations regarding perineoplasty were collected. Surgical plans (“with”, “without”, or “undecided”) were documented and compared with the actual performed procedure. Logistic and linear regression analyses were used to identify factors associated with perineoplasty. Results: Among the 305 enrolled women, 285 underwent surgery, of whom 135 (47%) received perineoplasty. Patients who underwent perineoplasty had a larger GH size (5.2 cm) compared to patients without perineoplasty (4.5 cm). Obesity was associated with an increased rate of perineoplasty compared to normal weight (OR 2.3 95%CI 1.2–4.6). There was a strong exponential association between childbirth and perineoplasty, with a fivefold increase for two children (95%CI 1.3–17.1) and thirtyfold increase for four or more children (95%CI 6.3–142) compared to one child. Nearly all procedures (92%) followed the preoperative plan; surgeons were more likely to omit than add perineoplasty intraoperatively. Surgeons frequently reported GH/PB size and age as key considerations to perform perineoplasty and lack of evidence and fear of dyspareunia as reasons to not perform perineoplasty. Conclusions: Surgeons more often perform perineoplasty in patients with factors that have been associated with a higher risk of recurrent prolapse. Prospective comparative studies are required to determine whether perineoplasty reduces recurrent POP after primary surgical repair. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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13 pages, 1120 KB  
Article
The Role of NLR, PLR, SII and CRP Pre- and Post-Treatment with Infliximab in Rheumatoid Arthritis
by Diellor Rizaj, Avni Kryeziu, Artidon Kelmendi, Behar Raci, Shend Kryeziu and Visar Baftijari
Biomedicines 2026, 14(1), 255; https://doi.org/10.3390/biomedicines14010255 (registering DOI) - 22 Jan 2026
Abstract
Background: Inflammatory activity in rheumatoid arthritis can be determined by normal blood count ratios such as Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammation Index (SII), and C-reactive Protein (CRP). Objective: The aim of this research is to [...] Read more.
Background: Inflammatory activity in rheumatoid arthritis can be determined by normal blood count ratios such as Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammation Index (SII), and C-reactive Protein (CRP). Objective: The aim of this research is to determine how these markers change after therapy and whether their pre- and post-treatment differences follow patterns that allow for simple parametric analyses. Methods: A prospective cohort of 52 RA patients (30 females and 22 males) was examined. The patients’ blood samples were tested at baseline and at the end of their 6-month Infliximab treatment. Hematologic markers such as NLR, PLR, and SII were calculated from the complete blood count (CBC), and CRP levels were measured. The statistical methods of Shapiro–Wilk (SW), Kolmogorov–Smirnov (KS), and Anderson–Darling (AD) were used, and later, paired t-tests were used to generate statistics where necessary. Results: Post-treatment measurements were consistently lower for all four biomarkers. QQ-plots and formal tests revealed that the differences between findings were essentially normal, allowing for paired t-tests. The mean decreases were as follows: NLR −1.10 (95% CI −1.48 to −0.71), PLR −43.0 (−55.4 to −30.7), SII −299 (−388 to −211), and CRP −11.36 (−13.18 to −9.54), all p < 0.001. CRP showed the greatest drop, with significant decreases in PLR and SII and a moderate decline in NLR, indicating therapy-related attenuation of systemic inflammation. Conclusions: The study shows that six months of infliximab therapy results in a consistent post-treatment decrease in all four biomarkers: NLR, PLR, SII, and CRP. Because the pre-post differences were roughly normal, CRP revealed the greatest decrease, with significant decreases in PLR and SII and a moderate decrease in NLR, consistent with systemic inflammation reduction. When combined, the CBC-derived indices track with CRP and can serve as practical, low-cost markers for monitoring therapy response in RA, despite the single-arm design. Full article
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19 pages, 7426 KB  
Article
Promoter Methylation–Expression Coupling of Gliogenesis Genes in IDH-Wildtype Glioblastoma: Longitudinal Analysis and Prognostic Value
by Roxana Radu, Ligia Gabriela Tataranu, Anica Dricu and Oana Alexandru
Int. J. Mol. Sci. 2026, 27(2), 1112; https://doi.org/10.3390/ijms27021112 - 22 Jan 2026
Abstract
Glioblastoma (GBM) shows extensive epigenetic heterogeneity. In IDH-wildtype (IDH-WT) GBM, promoter DNA methylation may regulate lineage programs influencing tumor evolution and prognosis; here, we systematically profiled promoter-level methylation dynamics across longitudinal tumors. Genome-wide DNA methylation data were obtained from the [...] Read more.
Glioblastoma (GBM) shows extensive epigenetic heterogeneity. In IDH-wildtype (IDH-WT) GBM, promoter DNA methylation may regulate lineage programs influencing tumor evolution and prognosis; here, we systematically profiled promoter-level methylation dynamics across longitudinal tumors. Genome-wide DNA methylation data were obtained from the publicly available Gene Expression Omnibus (GEO; GSE279073) dataset, comprising a longitudinal cohort of 226 IDH-wildtype glioblastomas profiled on the Illumina Infinium EPIC 850K array across primary and recurrent stages at the University of California, San Francisco. From 333 Gene Ontology gliogenesis-annotated genes (GO:0042063), a 48-gene promoter panel was derived, with ≥2 probes per gene. Promoter methylation was summarized as the median β-value and tested using one-sample Wilcoxon with FDR correction. Functional enrichment, longitudinal variation, and patient-level methylation burden were assessed. Validation analyses were performed using independent IDH-wildtype GBM datasets from The Cancer Genome Atlas (RNA-seq and 450K methylation; n = 347). Promoter hypomethylation predominated across all stages, with 25 genes consistently hypomethylated and 7 hypermethylated. Functional enrichment highlighted gliogenesis, glial cell differentiation, neurogenesis, and Notch-related signaling. In TCGA, promoter methylation inversely correlated with expression for 11 of 33 genes (FDR < 0.05). An Expression Score contrasting hypomethylated and hypermethylated genes was positively associated with improved overall survival, where higher scores predicted better outcome (HR = 0.87, p = 0.016; Q4 vs. Q1 HR = 0.68, p = 0.025), and a complementary Methylation Score showed that higher promoter hypermethylation predicted poorer outcome (HR = 1.73, p < 0.001). CNTN2 and TSPAN2 were adverse prognostic genes (FDR < 0.05). The Expression Score was highest in Proneural tumors and lowest in Mesenchymal tumors (p < 0.001), reflecting a proneural-like state associated with better prognosis. Promoter methylation within gliogenesis genes defines a stable yet prognostically informative epigenetic signature in IDH-WT GBM. Hypomethylation promotes transcriptional activation and a favorable outcome, whereas hypermethylation represses lineage programs and predicts poorer survival. Full article
(This article belongs to the Special Issue Hallmarks of Cancer: Emerging Insights and Innovations)
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10 pages, 347 KB  
Article
The Role of Prior HBV Infection on the Efficacy of 3TC/DTG as a Maintenance Therapy
by Tommaso Matucci, Sara Occhineri, Alessandra Palomba, Maria Linda Vatteroni, Laura Del Bono, Marina Polidori, Riccardo Iapoce, Alberto Borghetti and Marco Falcone
Viruses 2026, 18(1), 142; https://doi.org/10.3390/v18010142 - 22 Jan 2026
Abstract
Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure [...] Read more.
Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03–22.43; p = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40–161.38; p = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG. Full article
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26 pages, 1611 KB  
Article
Evaluating a Virtual Learning Environment for Secondary English in a Public School: Usability, Motivation, and Engagement
by Myriam Tatiana Velarde Orozco and Bárbara Luisa de Benito Crosetti
Educ. Sci. 2026, 16(1), 169; https://doi.org/10.3390/educsci16010169 - 22 Jan 2026
Abstract
Public schools often operate with shared devices, unstable connectivity, and limited support for digital tools, which can make feature-heavy platforms difficult to adopt and sustain. This study reports the first formal design iteration and formative evaluation of VLEPIC, a school-centred virtual learning environment [...] Read more.
Public schools often operate with shared devices, unstable connectivity, and limited support for digital tools, which can make feature-heavy platforms difficult to adopt and sustain. This study reports the first formal design iteration and formative evaluation of VLEPIC, a school-centred virtual learning environment (VLE) developed to support secondary English as a Foreign Language in a low-resource Ecuadorian public school. Using a design-based research approach with a convergent mixed-methods design, one Grade 10 cohort (n = 42; two intact classes) used VLEPIC for one month as a complement to regular lessons. Data were collected through questionnaires on perceived usability and motivation, platform usage logs, and open-ended feedback from students and the teacher; results were analysed descriptively and thematically and then integrated to inform design decisions. Students reported high perceived usability and strong motivational responses in attention, relevance, and satisfaction, while confidence was more heterogeneous. Usage logs indicated recurrent but uneven engagement, with distinct low-, medium-, and high-activity profiles. Qualitative feedback highlighted enjoyment and clarity alongside issues with progress tracking between missions, navigation on mobile devices, and task submission reliability. The main contribution is a set of empirically grounded, context-sensitive design principles linking concrete interface and task-design decisions to perceived usability, motivation, and real-world usage patterns in constrained school settings. Full article
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14 pages, 1099 KB  
Article
Distinct Gut Microbiome Profiles Underlying Cardiometabolic Risk Phenotypes in Individuals with Obesity
by Iveta Nedeva, Yavor Assyov, Veselka Duleva, Vera Karamfilova, Zdravko Kamenov, Julian Naydenov, Teodora Handjieva-Darlenska, Venelin Denchev, Alexander Kolevski, Victoria Pencheva and Vlayko Vodenicharov
Nutrients 2026, 18(2), 353; https://doi.org/10.3390/nu18020353 (registering DOI) - 22 Jan 2026
Abstract
Background: Obesity-related cardiometabolic disorders have been linked to alterations in selected gut microbiome components, yet clinically relevant microbial signatures remain incompletely defined. Objectives: This study investigated associations between selected gut bacterial taxa and cardiometabolic risk phenotypes in individuals with obesity. Methods: [...] Read more.
Background: Obesity-related cardiometabolic disorders have been linked to alterations in selected gut microbiome components, yet clinically relevant microbial signatures remain incompletely defined. Objectives: This study investigated associations between selected gut bacterial taxa and cardiometabolic risk phenotypes in individuals with obesity. Methods: In this cross-sectional study, 100 adults with obesity were stratified according to metabolic syndrome status. Gut microbiome composition was assessed using targeted multiplex real-time PCR of functionally relevant bacterial taxa. Associations with anthropometric and cardiometabolic parameters were examined using correlation analysis, ROC curves, and multivariable logistic regression models. Results: Reduced relative abundance of Lachnospiraceae was associated with metabolic syndrome, lower Faecalibacterium abundance with arterial hypertension, and increased Prevotella abundance with dyslipidemia. ROC analyses identified cohort-specific discriminative thresholds with moderate accuracy. Conclusions: Selected taxon-specific gut microbiome signatures are associated with cardiometabolic risk phenotypes in obesity. These findings are exploratory and require validation in longitudinal and independent cohorts. Full article
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14 pages, 2173 KB  
Article
Exploring the Role of Skull Base Anatomy in Surgical Approach Selection and Endocrinological Outcomes in Craniopharyngiomas
by Alessandro Tozzi, Giorgio Fiore, Elisa Sala, Giulio Andrea Bertani, Stefano Borsa, Ilaria Carnicelli, Emanuele Ferrante, Giulia Platania, Giovanna Mantovani and Marco Locatelli
J. Clin. Med. 2026, 15(2), 896; https://doi.org/10.3390/jcm15020896 (registering DOI) - 22 Jan 2026
Abstract
Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and [...] Read more.
Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m2; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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16 pages, 1581 KB  
Article
Platelet Recovery and Mortality in Septic Patients with Thrombocytopenia: A Propensity Score-Matched Analysis of the MIMIC-IV Database
by Yi Zhou, Xiangtao Zheng, Yanjun Zheng and Zhitao Yang
J. Clin. Med. 2026, 15(2), 884; https://doi.org/10.3390/jcm15020884 (registering DOI) - 21 Jan 2026
Abstract
Background: Thrombocytopenia (platelet count < 100 × 109/L) occurs in 20–40% of critically ill patients with sepsis and is associated with adverse outcomes. Most prior studies have treated thrombocytopenia as a static risk indicator rather than a dynamic process. We investigated [...] Read more.
Background: Thrombocytopenia (platelet count < 100 × 109/L) occurs in 20–40% of critically ill patients with sepsis and is associated with adverse outcomes. Most prior studies have treated thrombocytopenia as a static risk indicator rather than a dynamic process. We investigated whether platelet recovery within 7 days provides independent prognostic information in patients with sepsis. Methods: We performed a retrospective cohort study using the MIMIC-IV database. Among 22,513 adults with sepsis admitted to intensive care units, 5401 developed thrombocytopenia within 24 h of admission and had sufficient follow-up data. The primary exposure was sustained platelet recovery to ≥100 × 109/L within 7 days. The primary outcomes were 28-day and in-hospital mortality. Propensity-score matching and overlap weighting were used to adjust for demographic characteristics, comorbid conditions, illness severity, and organ-support therapies. Results: Among 5401 septic ICU patients with thrombocytopenia, 3193 (59%) achieved platelet recovery within 7 days. A total of 2056 patients (38%) recovered by day 3, and 1137 (21%) recovered between days 4 and 7. After multivariable adjustment, platelet recovery was independently associated with markedly lower mortality (adjusted risk ratio, 0.56; 95% CI, 0.53–0.67 for in-hospital death; and 0.60; 95% CI, 0.53–0.67 for 28-day death) and more than a doubling of survival time (adjusted ratio, 2.08; 95% CI, 1.65–2.63). Early and intermediate recovery conferred similar benefits. Higher baseline platelet counts, antiplatelet therapy, and heparin use were associated with recovery, whereas cirrhosis, greater illness severity, and continuous renal replacement therapy were associated with non-recovery. Conclusions: In patients with sepsis and thrombocytopenia, platelet recovery within 7 days was a strong and independent predictor of survival. Exploratory timing-stratified analyses yielded similar associations across subgroups. These findings support platelet recovery as a useful prognostic marker reflecting broader physiologic stabilization in sepsis. Full article
(This article belongs to the Section Emergency Medicine)
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