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13 pages, 816 KB  
Systematic Review
Reduced Versus Full-Dose Direct Oral Anticoagulants for Long-Term Management of Venous Thromboembolism: A Systematic Review
by Manar Al Arifi, Walaa A. Alshahrani, Abdulmajeed M. Alshehri and Majed S. Al Yami
J. Clin. Med. 2026, 15(2), 770; https://doi.org/10.3390/jcm15020770 (registering DOI) - 17 Jan 2026
Abstract
Background: Venous thromboembolism (VTE) is still a serious clinical problem because many patients still have a significant chance of having it happen again after their first course of anticoagulation is over. In recent years, reduced-dose direct oral anticoagulants (DOACs) have been investigated as [...] Read more.
Background: Venous thromboembolism (VTE) is still a serious clinical problem because many patients still have a significant chance of having it happen again after their first course of anticoagulation is over. In recent years, reduced-dose direct oral anticoagulants (DOACs) have been investigated as a means to ensure prolonged protection while diminishing the risk of bleeding complications. This systematic review aims to summarize the available evidence comparing reduced-dose and full-dose DOAC regimens during the extended phase of VTE treatment. Methods: A systematic search of PubMed and the Cochrane Library (January 2010–November 2025) identified randomized trials and one ambispective cohort study evaluating reduced-dose apixaban (2.5 mg BID), rivaroxaban (10 mg OD), dabigatran (110 mg BID), or edoxaban (30 mg OD). Methodological quality was assessed using RoB-2 for trials and the Newcastle–Ottawa Scale for observational data. Because of differences in study designs and outcome definitions, a narrative synthesis was applied. Results: Five studies met the inclusion criteria. Across trials, reduced-dose DOACs maintained consistently low rates of recurrent VTE: 1.7% in AMPLIFY-EXT versus 8.8% with placebo; 1.2–1.5% in EINSTEIN CHOICE versus 4.4% with aspirin; 2.2% in RENOVE versus 1.8% with full-dose therapy; and 1.3% in HI-PRO versus 10% with placebo. Real-world data from Valeriani et al. showed only a single recurrence (0.7%) over nearly three years. Major bleeding remained uncommon, ranging from 0.1 to 0.5% in randomized trials and 2.1–2.9% in longer-term observational cohorts. Conclusions: In summary, reduced-dose DOACs appear to offer a favorable balance of safety and efficacy, providing durable protection against recurrence with a lower bleeding burden. These findings support their role as a practical extended-treatment strategy in clinical practice. Full article
(This article belongs to the Section Vascular Medicine)
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31 pages, 538 KB  
Review
Bispecific T-Cell Engagers, Cell Therapies, and Other Non-Checkpoint Immunotherapies for Metastatic Uveal Melanoma: A Narrative Review
by Jakub Kleinrok, Weronika Pająk, Joanna Pec, Kamil Rusztyn, Joanna Dolar-Szczasny, Alicja Forma, Grzegorz Teresiński and Jacek Baj
J. Clin. Med. 2026, 15(2), 641; https://doi.org/10.3390/jcm15020641 - 13 Jan 2026
Viewed by 131
Abstract
Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and [...] Read more.
Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events. Full article
(This article belongs to the Section Ophthalmology)
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30 pages, 1761 KB  
Review
Harnessing Optical Energy for Thermal Applications: Innovations and Integrations in Nanoparticle-Mediated Energy Conversion
by José Rubén Morones-Ramírez
Processes 2026, 14(2), 236; https://doi.org/10.3390/pr14020236 - 9 Jan 2026
Viewed by 236
Abstract
Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions [...] Read more.
Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions can achieve >96% absorption across 250–2500 nm and photothermal efficiencies exceeding 98% under one-sun illumination (1000 W·m−2, AM 1.5G). Next, we highlight advances in solar steam generation and desalination: floating photothermal receivers on carbonized wood or hydrogels reach >95% efficiency in solar-to-vapor conversion and >2 kg·m−2·h−1 evaporation rates; three-dimensional architectures recapture diffuse flux and ambient heat; and full-spectrum nanofluids (LaB6, Au colloids) extend photothermal harvesting into portable, scalable designs. We then survey photothermal-enhanced thermal energy storage: metal-oxide–paraffin composites, core–shell phase-change material (PCM) nanocapsules, and MXene– polyethylene glycol—PEG—aerogels deliver >85% solar charging efficiencies, reduce supercooling, and improve thermal conductivity. In biomedicine, gold nanoshells, nanorods, and transition-metal dichalcogenide (TMDC) nanosheets enable deep-tissue photothermal therapy (PTT) with imaging guidance, achieving >94% tumor ablation in preclinical and pilot clinical studies. Multifunctional constructs combine PTT with chemotherapy, immunotherapy, or gene regulation, yielding synergistic tumor eradication and durable immune responses. Finally, we explore emerging opto-thermal nanobiosystems—light-triggered gene silencing in microalgae and poly(N-isopropylacrylamide) (PNIPAM)–gold nanoparticle (AuNP) membranes for microfluidic photothermal filtration and control—demonstrating how nanoscale heating enables remote, reversible biological and fluidic functions. We conclude by discussing challenges in scalable nanoparticle synthesis, stability, and integration, and outline future directions: multicomponent high-entropy alloys, modular photothermal–PCM devices, and opto-thermal control in synthetic biology. These interdisciplinary innovations promise sustainable solutions for global energy, water, and healthcare demands. Full article
(This article belongs to the Special Issue Transport and Energy Conversion at the Nanoscale and Molecular Scale)
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13 pages, 1711 KB  
Review
Chronic Kidney Disease in Metabolic Disease: Regulation of SGLT2 and Transcriptomic–Epigenetic Effects of Its Pharmacological Inhibition
by Chiara Salvà, Susanne Kaser and Matteo Landolfo
Int. J. Mol. Sci. 2026, 27(2), 589; https://doi.org/10.3390/ijms27020589 - 6 Jan 2026
Viewed by 173
Abstract
Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have revolutionized the management of type 2 diabetes mellitus, heart failure, and chronic kidney disease (CKD), providing cardiorenal and metabolic benefits that extend beyond glycemic control. While their clinical efficacy is well established, the underlying molecular mechanisms remain [...] Read more.
Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have revolutionized the management of type 2 diabetes mellitus, heart failure, and chronic kidney disease (CKD), providing cardiorenal and metabolic benefits that extend beyond glycemic control. While their clinical efficacy is well established, the underlying molecular mechanisms remain only partially understood. This review focuses on current knowledge of SGLT2 expression and regulation in health and metabolic diseases, as well as transcriptional and epigenetic consequences of pharmacological SGLT2 inhibition. Human and experimental studies demonstrate that SGLT2 expression is confined to proximal tubular cells and regulated by insulin, the renin–angiotensin–aldosterone system, the sympathetic nervous system, oxidative stress, and transcriptional and epigenetic pathways. SGLT2 expression follows a biphasic pattern in metabolic disorder-associated CKD: upregulation in early phases and reduction in advanced stages. Evidence from animal models and single-cell transcriptomic studies indicates that SGLT2is normalize metabolic and inflammatory gene networks. To our knowledge, a recent single-cell RNA sequencing study provides the only currently available human dataset linking SGLT2i therapy with tubular metabolic rewiring and suppression of the energy-sensitive mechanistic target of rapamycin complex 1. Collectively, these findings support a model in which SGLT2 inhibition mitigates metabolic stress by restoring energy homeostasis across multiple nephron segments. Full article
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13 pages, 260 KB  
Review
Health-Related Quality of Life in the Era of Immune Checkpoint Blockade: What Do Patient-Reported Outcomes Reveal?
by Alexandra M. Dunker, Neha Malik, Kathryn J. Krause, Emily Z. Keung, Jason B. Liu, Elise F. Nassif Haddad, Neeta Somaiah, Heather G. Lyu and Christina L. Roland
Cancers 2025, 17(24), 3917; https://doi.org/10.3390/cancers17243917 - 7 Dec 2025
Viewed by 714
Abstract
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical. Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical. Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken from original protocols or primary manuscripts. Results: ICIs generally preserved or improved HRQL in patients with various malignancies compared with chemotherapy, targeted therapies, or observation. PD-1/PD-L1 inhibitors maintained global health and function and delayed symptom progression in patients with lung cancer, melanoma, and renal cell carcinoma. Regimens combining CTLA-4 blockade and PD-1/PD-L1 inhibition (e.g., nivolumab + ipilimumab, durvalumab + tremelimumab) are associated with HRQL outcomes similar or superior to those of targeted therapies. Overall, most immune-related adverse effects were short-term and did not diminish HRQL benefits. Conclusions: ICIs extend survival while preserving, and often enhancing, patient HRQL. These medications represent a shift in oncology, offering not just longer life but also better daily well-being. Continued long-term patient-reported outcome monitoring is essential to guide survivorship care in the immunotherapy era. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)
17 pages, 1142 KB  
Article
Rifampicin/Quercetin Nanoemulsions: Co-Encapsulation and In Vitro Biological Assessment Toward Tuberculosis Therapy
by Frank do Carmo Guedes Júnior, Gabriela Hädrich, Camila de Oliveira Vian, Gustavo Richter Vaz, Virginia Campello Yurgel, Daniela Pastorim Vaiss, Gabriela Alves Felício da Costa, Marcelle Oliveira Garcia, Wanessa Maria dos Santos, Beatriz Sodré Matos, Lara Cristina dos Santos Teodoro, João Victor Villa Real, David Nascimento da Silva Teixeira, Alexandre de Paula Rogério, Sergiane Caldas Barbosa, Ednei Gilberto Primel, Pedro Eduardo Almeida da Silva, Daniela Fernandes Ramos and Cristiana Lima Dora
Pharmaceuticals 2025, 18(12), 1829; https://doi.org/10.3390/ph18121829 - 1 Dec 2025
Viewed by 410
Abstract
Background: Tuberculosis (TB) remains a leading cause of global mortality, with 1.25 million deaths reported in 2023. Extended treatment duration contributes to poor patient adherence and treatment failure. Innovative drug delivery platforms are needed to improve therapeutic outcomes. Objective: This study [...] Read more.
Background: Tuberculosis (TB) remains a leading cause of global mortality, with 1.25 million deaths reported in 2023. Extended treatment duration contributes to poor patient adherence and treatment failure. Innovative drug delivery platforms are needed to improve therapeutic outcomes. Objective: This study aimed to develop nanoemulsions co-encapsulating quercetin and rifampicin and evaluate their physicochemical properties and in vitro biological activity relevant to TB therapy. Methods: Nanoemulsions (NEs) were prepared via hot solvent diffusion and phase inversion temperature techniques. Physicochemical characterization, stability, anti-inflammatory effects in BEAS-2B cells, and antimycobacterial activity against Mycobacterium tuberculosis H37Rv and resistant strains were assessed in vitro. Results: The quercetin-rifampicin nanoemulsion (QUE-RIF-NE) showed an average size of 24 nm, zeta potential of −27 mV, and drug recovery rates of 77% (quercetin) and 75% (rifampicin). The formulation was stable and non-cytotoxic at 10−8 M, reducing IFN-γ production by half and reactive oxygen species production by almost 75% in BEAS-2B cells. It also exhibited antimycobacterial activity against both susceptible and resistant M. tuberculosis strains (MIC ≤ 0.015 µg/mL). Conclusions: QUE-RIF-NE exhibits promising physicochemical stability and dual anti-inflammatory and antimicrobial activity in vitro, demonstrating potential for optimized pulmonary or systemic TB therapy that integrates both anti-inflammatory and antimicrobial effects. Full article
(This article belongs to the Special Issue Application of Nanotechnology in Drug Delivery)
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32 pages, 481 KB  
Review
Emerging and Investigational Systemic Therapies in Recurrent/Metastatic Head and Neck Cancer After Progression on Immunotherapy
by Freya F. Abraham and Ricklie Julian
Cancers 2025, 17(23), 3817; https://doi.org/10.3390/cancers17233817 - 28 Nov 2025
Viewed by 1473
Abstract
Background: Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) progression represents a major clinical challenge. Between 60 and 80% of patients develop resistance, and historical salvage regimens like cytotoxic chemotherapy or chemotherapy plus cetuximab rarely [...] Read more.
Background: Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) progression represents a major clinical challenge. Between 60 and 80% of patients develop resistance, and historical salvage regimens like cytotoxic chemotherapy or chemotherapy plus cetuximab rarely extend median overall survival (mOS) beyond one year. Scope of Review: This review examines systemic therapies evaluated specifically in the post-ICI setting, emphasizing agents advancing to Phase II and III trials. Classes include chemotherapy combinations, ICI-based approaches, small-molecule targeted combinations, bispecific antibodies, antibody-drug conjugates (ADCs), and next-generation vaccines. Results: Promising signals have emerged across multiple therapeutic modalities. Targeted combination strategies have demonstrated encouraging response rates and survival outcomes in difficult-to-treat, PD-1-resistant disease. Antibody-based platforms, including antibody-drug conjugates and bispecific antibodies, continue to show consistent clinical activity across diverse patient populations, offering disease control and prolonged survival. Novel immunotherapies and therapeutic vaccines are also generating durable responses, particularly in biologically defined subgroups, highlighting the potential of immune-based precision treatments in R/M HNSCC. Conclusions: Comparative analysis highlights distinct advantages and limitations: chemotherapy ensures rapid shrinkage but poor durability; biomarker-driven small molecules achieve strong survival gains in narrow niches; ADCs and bispecifics offer balanced efficacy in unselected patients; and vaccine platforms deliver durable benefit in defined subsets. Together, these data signal a paradigm shift toward biomarker-guided, mechanism-driven strategies as the path to closing the post-ICI therapeutic gap in R/M HNSCC. Full article
25 pages, 5741 KB  
Article
Stabilizing the Localized Surface Plasmon Resonance (LSPR) of Citrate-Synthesized Metal Nanoparticles in Organic Solvents
by Jacob P. Magdon, Matthew J. Jasienski, Madison R. Waltz, Gabrielle A. Grzymski, Calvin Chen, Arion M. Solomon, Minh Dang Nguyen, Jong Moon Lee, John C. Deàk, T. Randall Lee and Riddhiman Medhi
Materials 2025, 18(22), 5246; https://doi.org/10.3390/ma18225246 - 20 Nov 2025
Viewed by 870
Abstract
Gold–silver nanoshells (GS-NSs) are hollow spherical nanoparticles with an alloyed Ag-Au shell. GS-NSs exhibit a tunable localized surface plasmon resonance (LSPR) in the visible to near-IR wavelengths as a function of composition and shell thickness and offer greater stability across pH ranges compared [...] Read more.
Gold–silver nanoshells (GS-NSs) are hollow spherical nanoparticles with an alloyed Ag-Au shell. GS-NSs exhibit a tunable localized surface plasmon resonance (LSPR) in the visible to near-IR wavelengths as a function of composition and shell thickness and offer greater stability across pH ranges compared to other metal nanoparticles. These properties make GS-NSs promising materials for diagnostics, photothermal therapy, and photocatalysis. However, current research has explored GS-NSs only in aqueous systems, since they immediately aggregate in other solvents, limiting their utility. This paper provides an in-depth study of the choice and effect of non-thiol ligands on the stability and phase-transfer of GS-NSs from aqueous to non-aqueous solvents, such as ethylene glycol, tetrahydrofuran, dichloromethane, and toluene. Ligand exchange for functionalization of GS-NSs was performed with Triton X-100 (TX100), sodium stearate (NaSt), polyvinylpyrrolidone (PVP), and hydroxypropyl cellulose (HPC), prior to phase-transfer. The nanoparticles were phase-transferred to the non-aqueous solvents, and the stability of the colloids in the various solvents before and after functionalization was recorded with UV–visible spectroscopy, dynamic light scattering (DLS), zeta potential (ζ), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The study was also extended to include silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) to evaluate broad-range applicability. Among the ligands studied, HPC functionalization demonstrated the widest range of phase-transfer stability across 21 days for all three particle systems studied. UV–vis spectroscopy demonstrated sustained LSPR integrity after HPC functionalization in EG, THF, and DCM. SEM, TEM, and hydrodynamic size measurements by DLS further confirmed no aggregation in EG, THF, and DCM but suggested possible twinning or clustering in the solution. Overall, this work successfully identified non-toxic alternatives to expand the LSPR stability of citrate-synthesized metal nanoparticles in organic solvents. Full article
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26 pages, 566 KB  
Review
Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders
by Ralf Weiskirchen and Amedeo Lonardo
Med. Sci. 2025, 13(4), 265; https://doi.org/10.3390/medsci13040265 - 12 Nov 2025
Viewed by 3173
Abstract
Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly [...] Read more.
Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article
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24 pages, 2524 KB  
Article
Phenotype-First Diagnostic Framework for Tracking Fluoroquinolone Resistance in Escherichia coli
by Eman Marzouk and Abdulaziz M. Almuzaini
Diagnostics 2025, 15(22), 2831; https://doi.org/10.3390/diagnostics15222831 - 7 Nov 2025
Viewed by 726
Abstract
Background: Fluoroquinolone (FQ) resistance in Escherichia coli (E. coli) undermines empiric therapy and often coincides with multidrug resistance (MDR). Because sequencing is not routinely available in many laboratories, we evaluated a phenotype-first, sequencing-independent diagnostic framework deployable on standard platforms. Methods: We [...] Read more.
Background: Fluoroquinolone (FQ) resistance in Escherichia coli (E. coli) undermines empiric therapy and often coincides with multidrug resistance (MDR). Because sequencing is not routinely available in many laboratories, we evaluated a phenotype-first, sequencing-independent diagnostic framework deployable on standard platforms. Methods: We profiled 45 archived E. coli isolates for susceptibility (Clinical and Laboratory Standards Institute [CLSI]-guided), extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC) phenotypes, MDR, and multiple-antibiotic resistance (MAR) indices. Ten founders (five FQ-susceptible [FQ-S], five low-level resistant [LLR]) seeded 20 parallel lineages exposed to stepwise ciprofloxacin. We tracked minimum inhibitory concentrations (MICs), collateral resistance, growth kinetics, and biofilm biomass using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification, automated and reference antimicrobial susceptibility testing (AST), growth-curve analysis, and crystal violet microtiter assays. The intended use is a sequencing-independent workflow for routine laboratories—especially where whole-genome sequencing is not readily available—working with archived or prospective clinical E. coli. This workflow is best applied when local FQ nonsusceptibility threatens empiric reliability; inputs include standard ID/AST with simple growth and biofilm assays. Primary outputs include: (i) MIC trajectories with time to high-level resistance (HLR), (ii) ΔMAR-summarized collateral resistance with class-level susceptible-to-resistant conversions, and (iii) concise fitness/biofilm summaries to guide empiric-policy refresh and early de-escalation. Results: At baseline, ciprofloxacin nonsusceptibility was 40.0%; ESBL and AmpC phenotypes were confirmed in 28.9% and 15.6%, respectively; 46.7% met the MDR definition; and the median MAR index was 0.29. During evolution, 70% of lineages reached HLR (MIC ≥ 4 μg/mL), with earlier conversion from LLR versus FQ-S founders (median 7 vs. 11 passages). Collateral resistance emerged most often to third-generation cephalosporins (3GCs), trimethoprim–sulfamethoxazole, and tetracyclines, while carbapenem activity was preserved. MAR increased in parallel with rising MICs. Resistance acquisition imposed modest fitness costs (slightly reduced growth rates and longer lag phases) that were partly offset under subinhibitory ciprofloxacin, whereas biofilm biomass changed little. Conclusions: this phenotype-first, routine-laboratory workflow rapidly maps FQ resistance and clinically relevant co-selection in E. coli. In high-resistance settings, empiric FQ use is difficult to justify, and MAR trends provide practical co-selection signals for stewardship. This reproducible framework complements genomic surveillance and is directly applicable where sequencing is unavailable. Full article
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22 pages, 757 KB  
Review
Beyond Lipids and Platelets: A Review of Anti-Inflammatory Strategies in Secondary Prevention of Acute Coronary Syndromes
by Girish Pathangey, Mohamed N. Allam, Mahmoud H. Abdelnabi, Dan Sorajja, Floyd David Fortuin, Kwan S. Lee and Mayurkumar D. Bhakta
J. Clin. Med. 2025, 14(22), 7910; https://doi.org/10.3390/jcm14227910 - 7 Nov 2025
Viewed by 1025
Abstract
Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, [...] Read more.
Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments. Full article
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34 pages, 7924 KB  
Systematic Review
Efficacy, Safety and Predictive Biomarkers of Oncolytic Virus Therapy in Solid Tumors: A Systematic Review and Meta-Analysis
by Mohamed El-Tanani, Syed Arman Rabbani, Mohamed Anas Patni, Rasha Babiker, Shakta Mani Satyam, Imran Rashid Rangraze, Adil Farooq Wali, Yahia El-Tanani and Thantrira Porntaveetus
Vaccines 2025, 13(10), 1070; https://doi.org/10.3390/vaccines13101070 - 20 Oct 2025
Cited by 2 | Viewed by 1331
Abstract
Background: Oncolytic virus (OV) therapy couples direct tumor lysis with systemic immune priming, yet clinical benefit remains heterogeneous and the predictive biomarker landscape is poorly defined. We undertook a systematic review and meta-analysis to quantify the efficacy and safety of OV therapy in [...] Read more.
Background: Oncolytic virus (OV) therapy couples direct tumor lysis with systemic immune priming, yet clinical benefit remains heterogeneous and the predictive biomarker landscape is poorly defined. We undertook a systematic review and meta-analysis to quantify the efficacy and safety of OV therapy in solid tumors and to synthesize current evidence on response-modulating biomarkers. Methods: Following PRISMA 2020 guidelines, MEDLINE, Embase, Cochrane CENTRAL, ProQuest and Scopus were searched from inception to May 2025. Phase II–III randomized trials of genetically engineered or naturally occurring OV reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS) or biomarker data were eligible. Hazard ratios (HRs) or odds ratios (OR) were pooled with random-effects models; heterogeneity was assessed with I2 statistics. Qualitative synthesis integrated genomic, immunologic and microbiome biomarkers. Results: Thirty-six trials encompassing around 4190 patients across different tumor types met inclusion criteria. Compared with standard therapy, OV-based regimens significantly improved ORR nearly three-fold (pooled OR = 2.77, 95% CI 1.85–4.16), prolonged PFS by 11% (HR = 0.89, 95% CI 0.80–0.99) and reduced mortality by 16% (OS HR = 0.84, 95% CI 0.72–0.97; I2 = 59%). Benefits were most pronounced in melanoma (ORR 26–49%; OS HR 0.57–0.79) and in high-dose vaccinia virus for hepatocellular carcinoma (HR = 0.39). Grade ≥ 3 adverse events were not increased versus control (risk ratio 1.05, 95% CI 0.89–1.24); common toxicities were transient flu-like symptoms and injection-site reactions. Biomarker synthesis revealed that high tumor mutational burden, interferon-pathway loss-of-function mutations, baseline CD8+ T-cell infiltration, post-OV upregulation of IFN-γ/PD-L1, and favorable gut microbial signatures correlated with response, whereas intact antiviral signaling, immune-excluded microenvironments and myeloid dominance predicted resistance. Conclusions: OV therapy confers clinically meaningful improvements in tumor response, PFS and OS with a favorable safety profile. Integrating composite genomic–immune–microbiome biomarkers into trial design is critical to refine patient selection and realize precision viro-immunotherapy. Future research should prioritize biomarker-enriched, rational combination strategies to overcome resistance and extend benefit beyond melanoma. Full article
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16 pages, 647 KB  
Article
Implementation of a Generative AI-Powered Digital Interactive Platform for Clinical Language Therapy in Children with Language Delay: A Pilot Study
by Chia-Hui Chueh, Tzu-Hui Chiang, Po-Wei Pan, Ko-Long Lin, Yen-Sen Lu, Sheng-Hui Tuan, Chao-Ruei Lin, I-Ching Huang and Hsu-Sheng Cheng
Life 2025, 15(10), 1628; https://doi.org/10.3390/life15101628 - 18 Oct 2025
Viewed by 1517
Abstract
Early intervention is pivotal for optimizing neurodevelopmental outcomes in children with language delay, where increased language stimulation can optimize therapeutic outcomes. Extending speech–language therapy from clinical settings to the home is a promising strategy; however, practical barriers and a lack of scalable, customizable [...] Read more.
Early intervention is pivotal for optimizing neurodevelopmental outcomes in children with language delay, where increased language stimulation can optimize therapeutic outcomes. Extending speech–language therapy from clinical settings to the home is a promising strategy; however, practical barriers and a lack of scalable, customizable home-based models limit the implementation of this approach. The integration of AI-powered digital interactive tools could bridge this gap. This pilot feasibility study adopted a single-arm pre–post (before–after) design within a two-phase, mixed-methods framework to evaluate a generative AI-powered interactive platform supporting home-based language therapy in children with either idiopathic language delay or autism spectrum disorder (ASD)-related language impairment: two conditions known to involve heterogeneous developmental profiles. The participants received clinical language assessments and engaged in home-based training using AI-enhanced tablet software, and 2000 audio recordings were collected and analyzed to assess pre- and postintervention language abilities. A total of 22 children aged 2–12 years were recruited, with 19 completing both phases. Based on 6-week cumulative usage, participants were stratified with respect to hours of AI usage into Groups A (≤5 h, n = 5), B (5 < h ≤ 10, n = 5), C (10 < h ≤ 15, n = 4), and D (>15 h, n = 5). A threshold effect was observed: only Group D showed significant gains between baseline and postintervention, with total words (58→110, p = 0.043), characters (98→192, p = 0.043), type–token ratio (0.59→0.78, p = 0.043), nouns (34→56, p = 0.043), verbs (12→34, p = 0.043), and mean length of utterance (1.83→3.24, p = 0.043) all improving. No significant changes were found in Groups A to C. These findings indicate the positive impact of extended use on the development of language. Generative AI-powered digital interactive tools, when they are integrated into home-based language therapy programs, can significantly improve language outcomes in children who have language delay and ASD. This approach offers a scalable, cost-effective extension of clinical care to the home, demonstrating the potential to enhance therapy accessibility and long-term outcomes. Full article
(This article belongs to the Section Medical Research)
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15 pages, 2912 KB  
Article
Extended Real-World Efficacy of Faricimab in Therapy-Resistant Macular Edema Due to Retinal Vein Occlusion: 9-Month Follow-Up Results
by Michael Hafner, Tina R. Herold, Alexander Kufner, Franziska Eckardt, Ben Asani, Siegfried G. Priglinger and Johannes Schiefelbein
J. Clin. Med. 2025, 14(20), 7197; https://doi.org/10.3390/jcm14207197 - 13 Oct 2025
Viewed by 1536
Abstract
Background: Macular edema (ME) secondary to retinal vein occlusion (RVO) is a significant cause of vision impairment. Many patients show suboptimal responses to anti-vascular endothelial growth factor (anti-VEGF) monotherapy, prompting the exploration of alternative treatments. Faricimab is a bispecific antibody that targets VEGF-A [...] Read more.
Background: Macular edema (ME) secondary to retinal vein occlusion (RVO) is a significant cause of vision impairment. Many patients show suboptimal responses to anti-vascular endothelial growth factor (anti-VEGF) monotherapy, prompting the exploration of alternative treatments. Faricimab is a bispecific antibody that targets VEGF-A and angiopoietin-2. We report 9-month real-world outcomes of switching to faricimab in therapy-resistant RVO-associated ME. Methods: In this retrospective study at a single tertiary center, patients with persistent or recurrent ME despite prior treatments (ranibizumab, aflibercept, or dexamethasone implant) were switched to faricimab. All eyes received a loading phase of four monthly faricimab injections, followed by a treat-and-extend regimen individualized per response. Key outcomes included best-corrected visual acuity (BCVA, logMAR), the central subfield thickness (CST, μm), and the intraretinal fluid (IRF) status on optical coherence tomography, assessed from the baseline (month 0, mo0) through the loading phase (mo1–mo3) and at month 9 (mo9). Results: Nineteen eyes (19 patients, mean age 64.8 years) were analyzed. The median BCVA improved from 0.20 to 0.00 logMAR by month 3 (p < 0.01) and was maintained at month 9. The median CST decreased from 325 μm at the baseline to 285 μm at month 3 (p < 0.01) and remained at 285 μm at month 9. IRF was present in 100% of eyes at the baseline, 26% at month 3, and 26% at month 9 (p < 0.01 for the baseline vs. month 9). Among eyes previously on anti-VEGF therapy (n = 14), the median treatment interval increased from 45.50 days at the baseline to 56.50 days at month 9 (p = 0.01; δ = 0.86). No intraocular inflammation or other adverse events were observed in this cohort over nine months. Conclusions: In this retrospective series, switching to faricimab was associated with improvements in vision and retinal anatomy that were maintained over 9 months; injection intervals were extended in a subset of eyes. These exploratory findings warrant confirmation in larger, controlled studies to define long-term effectiveness, safety, and dosing strategies. Full article
(This article belongs to the Special Issue Causes and Advanced Treatments of Macular Edema)
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42 pages, 3246 KB  
Review
Wound Healing: Molecular Mechanisms, Antimicrobial Peptides, and Emerging Technologies in Regenerative Medicine
by Ana Paula de Araújo Boleti, Ana Cristina Jacobowski, Breno Emanuel Farias Frihling, Maurício Vicente Cruz, Kristiane Fanti Del Pino Santos, Ludovico Migliolo, Lucas Rannier Melo de Andrade and Maria Ligia Rodrigues Macedo
Pharmaceuticals 2025, 18(10), 1525; https://doi.org/10.3390/ph18101525 - 10 Oct 2025
Cited by 3 | Viewed by 5131
Abstract
Wound healing is a dynamic process involving distinct phases that are regulated by cellular and molecular interactions. This review explores the fundamental mechanisms involved in wound healing, including the roles of cytokines and growth factors within the local microenvironment, with a particular focus [...] Read more.
Wound healing is a dynamic process involving distinct phases that are regulated by cellular and molecular interactions. This review explores the fundamental mechanisms involved in wound healing, including the roles of cytokines and growth factors within the local microenvironment, with a particular focus on antimicrobial peptides (AMPs) as immune modulators and therapeutic agents in chronic wounds. Notably, AMPs such as LL-37 have been shown to reduce biofilm density by up to 60%, highlighting their dual role in both modulating host immune responses and combating persistent bacterial infections. It further examines emerging technologies that are transforming the field, extending beyond traditional biological mechanisms to innovations such as smart dressings, 3D bioprinting, AI-driven therapies, regenerative medicine, gene therapy, and organoid models. Additionally, the review addresses strategies to overcome bacterial biofilms and highlights promising approaches including biomaterials, nanomedicine, gene therapy, peptide-loaded nanoparticles, and the application of organoids as advanced platforms for studying and enhancing wound repair. Full article
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