bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–06–21
57 papers selected by
Luca Bolliger, lxBio
  1. Phage Therapy at a Turning Point: Convergence, Customisation, and Clinical Promise.
  2. Systematic combinatorial optimization of three-phage cocktails against multidrug-resistant Pseudomonas aeruginosa.
  3. When bacteriophages encounter macrophages during their journey through the human body.
  4. The biology of jumbo phages.
  5. Microbial and host innate immune factors affecting the persistence of Staphylococcus aureus in cystic fibrosis airways.
  6. Comparison and correlation of in vitro and in vivo approaches for determining Pseudomonas aeruginosa bacteriophages activity.
  7. The role of the gut microbiome in antibiotic-driven antimicrobial resistance.
  8. Preclinical Research on Bacteriophage Therapy for Carbapenem-Resistant Klebsiella Pneumoniae: A Systematic Review.
  9. Efficacy and Safety Outcomes of Bacteriophage Therapy for Resistant Bacterial Infections.
  10. Deciphering skin architecture, wound pathophysiology and molecular mechanisms of healing: insights into immune response and therapeutic strategies.
  11. Bacteriophage therapy against American foulbrood in honey bees: a PRISMA-guided systematic review.
  12. Vancomycin and phage COP-80B combination therapy for Staphylococcus epidermidis periprosthetic joint infections: a preclinical mouse study.
  13. Intravesical therapies for catheter-associated urinary tract infections: current approaches and future directions.
  14. Pseudomonas aeruginosa in Ventilator-Associated Pneumonia: A Comprehensive Review of Resistance and Clinical Outcomes.
  15. Periodontal status, oral inflammatory biomarker, and relative expression of red complex bacteria in periodontitis-rheumatoid arthritis: a cross-sectional preliminary study.
  16. The gut microbiome in preterm infants: development, dysbiosis, and disease implications.
  17. An AI-driven framework for diabetic foot ulcer classification, segmentation, and depth estimation.
  18. Diabetic Foot Ulceration in Dialysis-Dependent End-Stage Kidney Disease: A Systematic Review of Epidemiology, Clinical Outcomes and Mortality Risk.
  19. Rapid Quantification of Bacteriophages of Mycobacterium spp. and Related Genera in Aquatic Systems.
  20. The STEADY diabetic foot ulcer registry: methods, insights, and future directions.
  21. From screening to treatment: in vitro and in vivo efficacy of phage-meropenem combination against highly virulent Carbapenem-resistant Acinetobacter baumannii.
  22. INTERLEUKIN-1 GENE POLYMORPHISMS AND SUSCEPTIBILITY TO PERIODONTITIS ACROSS ETHNICITIES AND POPULATIONS: A LITERATURE REVIEW.
  23. Application of Digital Twin Technology to Enhance Chronic Diseases Management: A Systematic Review.
  24. Mapping the knowledge landscape of Pseudomonas aeruginosa biofilm-mediated drug resistance: a bibliometric analysis and clinical trial landscape overview.
  25. Test, Treat, Repopulate™ method reduces red complex bacteria and stabilizes the oral microbiome.
  26. Management of Infected Wounds: A Wound Healing Foundation Consensus Statement.
  27. Volatile organic compound profiling for tracking clinical Pseudomonas aeruginosa isolates.
  28. Surfactant-driven quorum sensing of Pseudomonas aeruginosa in cystic fibrosis.
  29. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus: A Comprehensive Phenotypic and Genotypic Review.
  30. Deep3D-DTA: A Tri-Modal Deep Learning Framework for Binding Affinity Prediction Leveraging 3D Structural Representations of Drugs and Targets.
  31. Factors associated with foot self care behavior among older adults with recurrent diabetic foot ulcer: a cross-sectional study.
  32. Chitosan-Based Wound Dressings: Property Modulation, Fabrication Strategies, and Emerging Applications in Tissue Regeneration.
  33. Clinical challenges and solutions in wound care.
  34. Bacterial Infections in Decompensated Cirrhosis: Clinical Profile, Microbiology, and Antimicrobial Resistance Patterns.
  35. Microbial Dysbiosis in Oral Potentially Malignant Disorders: A Systematic Review.
  36. A scoping review of computational models of the diabetic foot.
  37. Predictive variables for early detection of sepsis in adults admitted to intensive care units: protocol for a systematic review.
  38. Machine learning assisted classification of periodontal health and periodontitis using alveolar bone loss measurements on bitewing radiographs.
  39. Emergence, evolution, and global dissemination of antimicrobial resistance: A One Health review.
  40. Remodeling the pathological airway: advanced nanotechnology for diagnostics and therapeutics in cystic fibrosis.
  41. Machine learning-driven identification of virulence determinants in Borrelia burgdorferi associated with human dissemination.
  42. Heterogeneous Systemic IgG Responses to Porphyromonas gingivalis Gingipains in Advanced Periodontitis.
  43. Helicobacter pylori phages: resource landscape, translational challenges, and engineered antibacterial strategies.
  44. A selective deep learning framework for pressure injury staging with calibrated confidence and automated clinical documentation.
  45. Synergistic effects of two bacteriophages with distinct infection patterns and broad host specificity against multidrug-resistant Salmonella Typhimurium and their potential applications in the poultry industry.
  46. Hospital-Based Robotic Applications in Nursing Practice: A Scoping Review.
  47. Burn Wound Infections With Staphylococcus aureus: Clinical Characteristics and Risk Factors for Methicillin-Resistant Strains.
  48. Uropathogenic profiles and antibiotic resistance in gynecological cases: a microbial surveillance study from Northeast India.
  49. Engineered bacteria in disease diagnosis and therapy: A synthetic biology perspective.
  50. From Health to Disease: A Comprehensive Review of Ocular Surface Microbiota and Detection Methods in Dry Eye.
  51. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.
  52. Barriers to Self-Management of Patients with Diabetic Foot Ulcers: A Systematic Review and Qualitative Meta-Synthesis.
  53. Sinuhe Classification for Pretibial Injuries: Categorising Dermatoporotic Wounds.
  54. Immunomodulation as a novel treatment strategy for periodontal disease: a systematic review.
  55. The Impact of Dental Prostheses in Patients With Cardiovascular Disease: A Scoping Review With Exploratory Analysis.
  56. Er:YAG laser Therapy for Diabetic Foot Ulcers: A Pilot Study with Hyperspectral Imaging Assessment.
  57. The predictive value of the ratio of multi-dimensional inflammatory biomarkers in pediatric diseases from the perspective of pro-inflammatory/anti-inflammatory balance: a systematic review.
  1. Int J Antimicrob Agents. 2026 Jun 15. pii: S0924-8579(26)00102-0. [Epub ahead of print] 107813
    Phage Therapy at a Turning Point: Convergence, Customisation, and Clinical Promise.
    Prof Ruby Lin, Dr Gina Suh.
      
    DOI:  https://doi.org/10.1016/j.ijantimicag.2026.107813
  2. Microbiol Spectr. 2026 Jun 15. e0409625
    Systematic combinatorial optimization of three-phage cocktails against multidrug-resistant Pseudomonas aeruginosa.
    Meshack Tweya Omwega, Moses Gachoya, Justin Nyasinga, Martin Georges, Collins Kigen, Kevin Kamanyi, Samuel Nyamweya, Erick Odoyo, Lillian Musila.
      Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a significant global health threat, necessitating alternative therapeutic strategies. Bacteriophage therapy shows promise, but single-phage use is prone to resistance. Bacteriophage cocktails can address this issue, but they are typically formulated empirically without a systematic evaluation of constituent phage interactions. We employed a comprehensive combinatorial approach to optimize three-phage cocktails against clinical P. aeruginosa isolates. From 25 candidate bacteriophages, 5 were selected based on a broad host range (≥60% of 51 MDR P. aeruginosa clinical isolates). Ten possible three-phage cocktail combinations were systematically generated and evaluated using real-time Omnilog phenotypic microarray analysis. Phage interactions were quantified using the Highest Single Agent independence model to classify synergistic (Δ > +5%), neutral (-5% ≤ Δ ≤ +5%), or antagonistic (Δ < -5%) effects. Individual phage inhibition efficiencies ranged from 35.4% to 75.4%. Cocktail performance varied dramatically (16.1%-84.1% inhibition). Only one cocktail exhibited synergy, achieving 84.1% inhibition, an 8.7% improvement over the best individual phage. Four cocktails (40%) showed neutral interactions, while five (50%) demonstrated antagonistic effects. The optimal cocktail (Phages 1 + 3 + 4) demonstrated efficacy across six of eight diverse clinical isolates in biofilm inhibition assays (29%-63% biomass reduction, 2.7-3.6 log10 colony-forming unit reduction) and achieved 80% survival in Galleria mellonella versus 10% in infected controls. These findings demonstrate that phage cocktail optimization requires rational validation, as antagonistic interactions can occur, establishing a critical validation step before committing resources to in vivo efficacy studies.
    IMPORTANCE: Bacteriophage cocktails are increasingly proposed as alternatives to antibiotics against multidrug-resistant bacteria, yet their development remains largely empirical. This study challenges the assumption that the combination of effective phages yields additive or synergistic benefits. Through systematic evaluation of all possible three-phage combinations from five phages, we discovered that antagonistic interactions (50%) predominated over synergistic effects (10%), with some cocktails performing worse than individual phages. Using the Highest Single Agent independence model, we established a quantitative framework for rational cocktail design that identified a therapeutically superior formulation. This approach is generalizable across bacterial pathogens and provides a critical validation step for phage therapy development. Our findings demonstrate that rational testing of phage interactions is essential before in vivo or clinical translation, potentially preventing costly failures and accelerating the development of effective phage-based therapeutics against multidrug-resistant infections.
    Keywords:  Galleria mellonella; Highest Single Agent independence model; Pseudomonas aeruginosa; antimicrobial resistance; bacteriophage therapy; biofilm; combinatorial optimization; invertebrate infection model; phage cocktail design; phage cocktails; phage interactions; synergy
    DOI:  https://doi.org/10.1128/spectrum.04096-25
  3. Front Cell Infect Microbiol. 2026 ;16 1857968
    When bacteriophages encounter macrophages during their journey through the human body.
    Martyna Cieślik, Magdalena Gębicka, Michał Wójcicki, Andrzej Górski, Ewa Jończyk-Matysiak.
      The increasing problem of antibiotic resistance is one of the most significant threats to global public health, contributing to higher mortality rates, prolonged hospitalizations, and rising healthcare costs. As a response to this challenge, phage therapy - based on the use of bacteriophages (phages), viruses that selectively infect and lyse bacteria - has emerged as a promising alternative. In recent years, increasing interest in phage therapy has been observed in both preclinical and clinical research. Accordingly, increasing attention is being directed toward investigating potential interactions between phages and mammalian cells. Bacteriophages, like other exogenous particles introduced into the human body, are subject to innate and adaptive immune mechanisms. This review places particular emphasis on interactions between phages and macrophages. On the one hand, their significant participation in the clearance of therapeutic phages is described, which may reduce the effectiveness of antibacterial treatment; nevertheless, this mechanism is considered to be an indirect way of autotolerance of intestinal phages. From another perspective, bacteriophages, as nucleoprotein molecules, can induce various immunomodulation mechanisms, which may find clinical applications in the future. Their involvement in macrophage polarization, induction of the secretion of pro- and anti-inflammatory cytokines, and modulation of phagocytic functions are briefly discussed. Apart from their therapeutic importance, studying the interactions of phages with eukaryotic cells, such as immunocompetent cells including macrophages, may also help explain their indisputable role in maintaining homeostasis as integral components of the human microbiota.
    Keywords:  antibiotic resistance; bacteriophage; immunomodulation; macrophage; mononuclear phagocyte system; phagocytosis
    DOI:  https://doi.org/10.3389/fcimb.2026.1857968
  4. Nat Commun. 2026 Jun 19. pii: 5458. [Epub ahead of print]17(1):
    The biology of jumbo phages.
    Sam P B van Beljouw, Li Yuping.
      Jumbo bacteriophages are bacterial viruses with double-stranded DNA genomes exceeding 200 kb. These viral giants feature exceptionally large virions, expansive genetic repertoires, and in some cases, remarkable eukaryotic-like traits. Jumbo phages challenge long-standing notions of phage simplicity, redefining the boundaries of what a phage can be. In this Review, we examine the biology of jumbo bacteriophages, highlighting their diversity, evolutionary origins, distinctive morphologies and lifecycles, complex interactions with bacterial hosts, and their potential for biotechnology and therapy, with a focus on, but not limited to, the Chimalliviridae phages.
    DOI:  https://doi.org/10.1038/s41467-026-74333-0
  5. Front Cell Infect Microbiol. 2026 ;16 1797869
    Microbial and host innate immune factors affecting the persistence of Staphylococcus aureus in cystic fibrosis airways.
    Jacob D Fairholm, Gavin Thomas Paul, Susan Birket, Balázs Rada.
      Chronic bacterial respiratory infections by Staphylococcus aureus are a hallmark of cystic fibrosis (CF) lung disease, affecting up to 80% of all people with CF by their mid-teens. S. aureus is able to survive and persist in the CF lung despite robust neutrophilic inflammation. As neutrophils are the immune system's front line of defense against bacteria, the persistent nature of S. aureus infections in CF indicates both a defect in the ability of neutrophils to kill S. aureus and an enhanced ability of the bacteria to survive. S. aureus persistence in the CF lung is driven by both microbial and host, genetic and microenvironmental, factors. There doesn't seem to be one unifying feature that makes S. aureus more virulent in the CF lung as several factors have been proposed to aide its survival. These include increased resistance to antibiotics, the ability to form small colony variants, biofilm formation, co-infection with Pseudomonas aeruginosa, and several virulence factors such as the accessory gene regulatory system, leukocidins, and staphylococcal protein A. A variety of host factors also affect the ability of neutrophils to kill S. aureus in the CF lung. Defects in the function of the cystic fibrosis transmembrane conductance regulator, the genetic cause of CF, affect phagolysosomal killing and lead to increased formation of neutrophil extracellular traps, which are less effective at killing S. aureus. Additionally, data suggest that factors within the CF lung microenvironment also affect neutrophilic killing of S. aureus. However, more research is needed to clearly identify what these environmental factors may be. This review article summarizes the current knowledge on the clinical relevance of S. aureus lung infections in CF, on microbial and host mechanisms promoting S. aureus survival in the CF lung, and on details of neutrophil-S. aureus interactions in CF. By understanding how S. aureus is able to survive in the CF lung and why neutrophils are unable to kill this bacterium, it could be possible to identify potential therapeutic targets to alleviate the consequences of S. aureus respiratory infection in CF.
    Keywords:  Staphylococcus aureus; biofilm; cystic fibrosis - CF; neutrophil extracellular trap; neutrophils; persistence; small-colony variant (SCV); virulence factors
    DOI:  https://doi.org/10.3389/fcimb.2026.1797869
  6. BMC Microbiol. 2026 Jun 13.
    Comparison and correlation of in vitro and in vivo approaches for determining Pseudomonas aeruginosa bacteriophages activity.
    Pedro Henrique Takata, Giovana Nicolete Pereira, Jhonatan Macedo Ribeiro, Laura Pierobão, Gabriel Henrique Maximino Santos, Bruna Carolina Gonçalves, Pedro Ademário Lima E Silva, Mariana Marques Bertozzi, Rafael Reis de Rezende, Giarlã Cunha da Silva, Ruither Arthur Loch Gomes, Waldiceu A Verri, Poliane Alfenas-Zerbini, Renata Katsuko Takayama Kobayashi, Gerson Nakazato.
      The rise of infections caused by multidrug-resistant bacteria has driven the search for alternative therapies, with Pseudomonas aeruginosa representing a major target. Among these alternatives, the use of bacteriophages (phage therapy) employs these viruses that specifically infect bacteria to fight infections. Although phage efficacy has been demonstrated both in vitro and in vivo, few studies have directly correlated these two dimensions. This study aimed to evaluate, compare, and correlate in vitro and in vivo phage activity. For this, three strictly lytic bacteriophages (ph9027, ph1461, and ph3678) were isolated and tested against 15 clinical isolates and three reference strains of P. aeruginosa. Their in vitro activity was assessed through Spot-Test, Efficiency of Plating, Local Virulence, and Virulence Index assays, followed by in vivo assays in Galleria mellonella larvae and Balb/C mice in a peritonitis model with bacteremia induction. Virulence Index and animal treatments were performed using a phage cocktail (1:1:1 ratio, 1.0 × 10⁹ PFU/mL). In vitro assays revealed varying phage activity, with the Virulence Index showing the strongest correlation with in vivo results in G. mellonella (rs = 0.7648). Larval treatment achieved up to 100% survival, significantly different (p < 0.05) from bacteria-only controls. In mice, phage therapy reduced bacterial loads by up to 3 logs in blood, spleen, peritoneal lavage, liver, and lung (p < 0.05) in comparison with control groups. Therefore, the present study, in addition to reiterating the safety and therapeutic efficacy of phage therapy in animal models, presents evidence that Virulence Index techniques, associated with the survival results of G. mellonella larvae, can be excellent tools for directing preclinical assays due to the strong statistical correlation observed between these data and those obtained in mouse experiments.
    Keywords:   Galleria mellonella ; Correlation coefficient; Host range; Mice model; Multidrug-resistant bacteria; Peritonitis; Phage therapy
    DOI:  https://doi.org/10.1186/s12866-026-05289-w
  7. Front Microbiol. 2026 ;17 1856738
    The role of the gut microbiome in antibiotic-driven antimicrobial resistance.
    Gargi Joshi, Smriti Rani, Dipti Bharti, Namrata Panda, Prerana Chavan, Shalini Mathpal, Sudha Ramaiah, Anand Anbarasu.
      Antimicrobial resistance (AMR) is one of the most pressing threats to global health system. The human gut harbors a complex microbial ecosystem coordinated through mechanisms of metabolic interdependence. The gut microbiota plays a vital role in normal growth and physiological processes of the human body. It serves both as a target of antibiotic-mediated disruption and as a reservoir for the propagation of antimicrobial resistance genes. Although antibiotics remain indispensable for the treatment of bacterial infections, their broad ecological impact on the gut microbiota can undermine the microbial balance that protects the host against pathogen invasion and metabolic dysfunction. The gut microbiome also functions as a reservoir of antimicrobial resistance genes collectively termed the "resistome," which can be mobilised and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms such as conjugation, transformation, and transduction. This review examines the composition and functions of the human gut microbiota, the mechanism of antibiotic-induced gut dysbiosis, and the role of host factors like age, genetics, diet and immune status, on microbiome dynamics and AMR development. We further evaluate emerging methods for resistome characterisation, which include PCR, next-generation sequencing, functional metagenomics and artificial intelligence-driven tools. Finally, we discuss microbiome-targeted therapeutic strategies such as faecal microbiota transplantation (FMT), phage therapy, CRISPR-based therapies, and antimicrobial peptides for combating AMR and restoring gut microbial homeostasis. Overall, this review highlights that maintaining and re-establishing the integrity of the gut microbiome should be considered a fundamental component of antimicrobial stewardship strategies aimed at controlling AMR worldwide.
    Keywords:  antimicrobial resistance; dysbiosis; gut microbiome; gut resistome; horizontal gene transfer
    DOI:  https://doi.org/10.3389/fmicb.2026.1856738
  8. Comb Chem High Throughput Screen. 2026 Jun 10.
    Preclinical Research on Bacteriophage Therapy for Carbapenem-Resistant Klebsiella Pneumoniae: A Systematic Review.
    Xiexue Liu, Ye Liang, Yu Li, Xinhua Qiang, Yibin Lin, Jie He.
       INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a substantial threat to global health. As the effectiveness of first-line antibiotics like tigecycline and polymyxins wanes, bacteriophage therapy, including phage cocktails and integrated approaches, has emerged as a feasible alternative. This systematic review evaluated the bactericidal efficacy of bacteriophages against carbapenem-resistant K. pneumoniae in preclinical studies.
    METHODS: A comprehensive search of PubMed, Web of Science, and Embase databases was conducted for records published between January 2010 and December 2024. Risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE tool). Primary endpoints were animal mortality and tissue bacterial burden, reported as pooled Risk Ratios (RRs) and mean differences using random-effects models. The study was registered with PROSPERO (CRD420251018670).
    RESULTS: Of 191 screened references, 18 studies met the selection criteria and were assessed as having low to moderate risk of bias. In animal infection models, subgroup analyses demonstrated a statistically significant association between bacteriophage therapy and reduced mortality in both murine (RR 0.30 (95% CI 0.22, 0.41), I2= 0.0%) and Galleria mellonella larva models (RR 0.36 (95% CI 0.16,0.81), I2= 23.7%), with no significant difference between subgroups (p= 0.689). The overall pooled analysis confirmed a significant reduction in mortality (RR 0.32 (95% CI 0.24,0.42), I2= 0.0%), indicating substantial improvement in infection outcomes. Bacteriophage therapy remained non-inferior to conventional antibiotic therapy for CRKP.
    DISCUSSION: The findings substantiate the potent bactericidal activity of bacteriophage therapy against CRKP in preclinical settings, highlighting its feasibility and safety profile. The consistency of results across different animal models strengthens the evidence base. However, the translation of these promising results into clinical practice requires further validation. Limitations of this review include the relatively small number of available studies and occasional missing experimental details.
    CONCLUSION: Bacteriophage therapy exhibits significant potential as an effective intervention against CRKP infections in preclinical models. Future research should focus on expanding the sample size and rigor of preclinical studies to corroborate these findings and provide a robust foundation for clinical application.
    Keywords:  Carbapenem-resistant klebsiella pneumoniae; animal models; bacteriophage therapy; meta-analysis; phage efficacy; preclinical studies.
    DOI:  https://doi.org/10.2174/0113862073443395260418195524
  9. Cureus. 2026 May;18(5): e108749
    Efficacy and Safety Outcomes of Bacteriophage Therapy for Resistant Bacterial Infections.
    Luke Cho, Hannah Chang, Evan Cho, Thiru Rajagopal.
      Phage therapy, the therapeutic use of bacteriophages for multi-drug resistant bacterial infections, is an understudied treatment approach that has been receiving increased interest in recent years. With multiple different treatment strategies (e.g., oral vs. intravenous (IV)) as well as varying types of bacteriophage combinations (phage cocktails) that are possible, the effectiveness of these phage cocktails on certain bacterial infections, as well as overall safety, is in question. This systematic review aims to analyze current evidence on the efficacy and safety outcomes of bacteriophage therapy for resistant bacterial infections. A systematic search of PubMed, Embase, and Scopus was conducted to investigate clinical studies following guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Included studies addressed the efficacy of phage cocktails in bacterial-resistant infections with a secondary focus on safety and adverse events. Two independent reviewers assessed randomized controlled studies using the Cochrane Risk-of-Bias 2 (ROB-2) tool and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. The three randomized controlled studies demonstrated low risk of bias, while the non-randomized controlled study showed a serious risk of bias. Patient outcomes and adverse events were narratively synthesized due to heterogeneity across study populations, pathogens, and treatment protocols. In total, only four studies met the scope of this review, which significantly limits the interpretation of the results. Two studies focused on Pseudomonas aeruginosa infections, while one study looked at Mycobacterium spp., and another study examined Helicobacter pylori infections known to hold some antibiotic resistance. Phage administration ranged from topical/aerosol for the P. aeruginosa infections, IV/aerosol for Mycobacterium spp., and oral for H. pylori. The two studies on P. aeruginosa demonstrated statistically significant reductions in bacterial presence, while the other two studies did not demonstrate statistically significant results. Regarding safety, no study reported any statistically significant severe adverse events. Two trials provided data on less severe adverse events, which were not statistically significant compared to the comparison groups. The trends synthesized from this study are limited by disease and therapeutic heterogeneity, sample size, and different treatment durations. Phage therapy shows early promise for drug-resistant infections, particularly P. aeruginosa, with a favorable safety profile. However, due to therapeutic and disease heterogeneity, small sample sizes, and variable treatment durations, larger dedicated trials are needed.
    Keywords:  antibiotic-resistant bacterial infection; bacteriophage; management; outcomes; phage therapy; therapy
    DOI:  https://doi.org/10.7759/cureus.108749
  10. Front Bioeng Biotechnol. 2026 ;14 1812108
    Deciphering skin architecture, wound pathophysiology and molecular mechanisms of healing: insights into immune response and therapeutic strategies.
    Mayank Maan, Shubhi Joshi, Avneet Saini.
      Skin not only serves as a protective barrier, but also as a dynamic immunological and sensory organ responsible for complex physiological processes. Disruption through trauma, surgery, burns or chronic metabolic disease initiates a tightly regulated healing cascade involving inflammatory signaling, extracellular matrix remodeling, angiogenesis and coordinated cellular responses. While acute wounds generally progress through orderly phases of repair, chronic wounds such as diabetic foot ulcers, venous ulcers and pressure injuries become arrested in persistent inflammatory states characterized by protease imbalance, senescent cell accumulation, impaired vascularization and colonization of microbial biofilms, contributing to significant global morbidity and healthcare burden. This review integrates structural biology, immune mechanisms and molecular signaling pathways that govern wound repair, clearly delineating the differences between acute and chronic healing. Particular emphasis is placed on inflammation-driven dysregulation, extracellular matrix dynamics and defective angiogenesis that underpin chronic wound pathology. Rare and often underrepresented wound types, including radiation-induced and autoimmune-associated lesions, are also discussed to provide a broader and clinically relevant perspective. Importantly, the review highlights translational and technological advances transforming wound management, including self-healing hydrogels, nanofiber scaffolds, bioactive and stimuli-responsive dressings, biosensor-integrated platforms, cellular and molecular therapies and AI-assisted diagnostic systems. These innovations exemplify a shift from passive wound coverage toward biointeractive, precision-guided and microenvironment-responsive therapeutic strategies. By bridging immunopathology, regenerative medicine, nanobiotechnology and digital health platforms within a single cohesive narrative, this review serves as a comprehensive and integrative resource for academicians, clinicians, translational researchers and pharmaceutical innovators seeking a mechanistically grounded yet application-oriented understanding of modern wound care.
    Keywords:  advanced wound dressings; chronic wounds; regenerative medicine; wound healing; wound therapeutics
    DOI:  https://doi.org/10.3389/fbioe.2026.1812108
  11. Front Microbiol. 2026 ;17 1816537
    Bacteriophage therapy against American foulbrood in honey bees: a PRISMA-guided systematic review.
    Nike Walter, Aaron Teja Bolte, Mohammadali Khan Mirzaei, Li Deng, Markus Rupp.
      American foulbrood (AFB), caused by the spore-forming bacterium Paenibacillus larvae, is the most destructive bacterial brood disease of Apis mellifera. Control is challenging because endospores persist for decades and antibiotic use is restricted by regulations, resistance, and residue concerns. Bacteriophages have re-emerged as a species-specific, residue-free strategy for AFB prevention and treatment. A PRISMA-guided systematic review was conducted searching PubMed, Embase, and Web of Science using the terms (bacteriophage OR phage) AND (honeybee OR Apis mellifera). A total of 90 records were retrieved; after deduplication (19 removed), 71 titles and abstracts were screened. Eleven full texts were assessed for eligibility. Nine studies met inclusion criteria: three in adult bees or colonies, four in larvae, and two in vitro. Across studies, 27 P. larvae phages were characterized in vitro, 18 tested in larval assays, and nine evaluated at the hive level, mainly via oral delivery. In a controlled hive trial, a three-phage cocktail provided complete protection from natural AFB (100% protected vs. 80% infection in controls; p < 0.05) and enabled full recovery within 2 weeks, performing comparably to or better than prophylactic antibiotics. Larval studies generally showed significantly improved survival with prophylactic or therapeutic dosing, though efficacy varied by phage. A biodistribution study found limited indirect larval exposure after adult feeding (~32 PFU/larva at 24 h), indicating hive-mediated inactivation as a key translational barrier. One phage bound both vegetative cells and spores while retaining ~93% in-vitro infectivity. Overall, phage cocktails show strong proof-of-concept, with formulation, delivery, and rational cocktail design as key translational priorities.
    Keywords:  American foulbrood; Paenibacillus larvae; antimicrobial resistance; bacteriophage; honey bee
    DOI:  https://doi.org/10.3389/fmicb.2026.1816537
  12. Eur J Clin Microbiol Infect Dis. 2026 Jun 16.
    Vancomycin and phage COP-80B combination therapy for Staphylococcus epidermidis periprosthetic joint infections: a preclinical mouse study.
    Vida Štilec, Monika Marušić, Helena Motaln, Klara Gregorič, Urška Draksler, Maša Čater, Jani Izlakar, Nika Janež, Rihard Trebše, Simon Horvat, Matjaž Peterka.
      The increasing number of joint replacement surgeries has led to an increase in periprosthetic joint infections (PJI). Chronic PJI caused by Staphylococcus epidermidis is very common and challenging to treat, prompting interest in bacteriophage therapy. Preclinical studies are essential for optimizing phage administration routes and dosages. Here, phage replication and bacterial growth inhibition using phage and vancomycin were first assessed in vitro. Then, chronic PJI was induced in mice using biofilm-coated titanium implants inoculated with S. epidermidis COB-SE3 to evaluate the efficacy of phage COP-80B and vancomycin therapy. Mice received one intra-articular and two intraperitoneal phage doses over three days, along with vancomycin administered twice daily for five days. Four weeks after implantation, we quantified and compared bacterial loads in periarticular tissues and implants across four groups: untreated controls, phage monotherapy, vancomycin monotherapy, and phage-vancomycin combination. Infection persistence was lower than expected, limiting the ability to detect treatment effects and assess therapeutic efficacy in this low-virulence model. Intra-articular administration of 1010 PFU of COP-80B did not alter plasma alanine aminotransferase levels, indicating no hepatotoxicity. Bacterial isolates remained susceptible to both phage and vancomycin, while phage-neutralizing antibodies developed during treatment. Overall, this study evaluates phage-vancomycin therapy while also contributing a murine model that advances methodological development for chronic S. epidermidis PJI research, with additional refinement of infection kinetics needed to reliably assess therapeutic efficacy.
    Keywords:   Staphylococcus epidermidis ; Infection models; Mouse; Periprosthetic joint infection; Phage therapy; Vancomycin
    DOI:  https://doi.org/10.1007/s10096-026-05561-x
  13. Clin Microbiol Rev. 2026 Jun 17. e0038225
    Intravesical therapies for catheter-associated urinary tract infections: current approaches and future directions.
    Chloe Linham, Mark Webber, Sheng Qi.
      SUMMARYUrinary tract infections (UTIs) are among the most common bacterial infections worldwide, with catheter-associated UTIs (CAUTIs) representing a major subset in healthcare settings. CAUTIs significantly increase patient morbidity, mortality, hospital stays, and healthcare costs, while driving antibiotic overuse and antimicrobial resistance (AMR). Systemic antibiotics often fail due to poor biofilm penetration, localized infection sites, and rising multidrug resistance, highlighting the urgent need for alternative, targeted therapies. This review discusses the role of intravesical therapies in both the treatment and prevention of CAUTIs, with a primary emphasis on therapeutic applications. The bladder is an accessible target for local treatment, as catheters can be repurposed for drug delivery. These devices are frequently colonized by biofilm-forming bacteria that contribute to persistent infection and treatment failure. This review explores intravesical therapy, the direct instillation of antimicrobial agents into the bladder, as a promising strategy to improve CAUTI management and mitigate AMR. We examine CAUTI pathogenesis, biofilm development, and current clinical approaches, including antimicrobial stewardship, catheter management, and coating technologies. Evidence for intravesical antibiotics such as gentamicin, amikacin, colistin, fosfomycin, and trimethoprim is reviewed alongside limited data from clinical trials, and applications in other urological disorders. Non-antibiotic alternatives, including sterile saline, antiseptic solutions, bacteriophages, antimicrobial peptides, natural bioactives, probiotics, and silver nanoparticles, are also discussed, particularly for their potential synergistic use with antibiotics to reduce resistance emergence. Despite encouraging results, intravesical therapy faces challenges such as limited clinical data, lack of standardized protocols, and delivery barriers. This review summarizes current evidence, identifies research gaps, and proposes directions to advance this underused strategy against CAUTIs amid escalating antibiotic resistance.
    Keywords:  antimicrobial resistance (AMR); catheter-associated UTIs (CAUTIs); intravesical drug delivery; urinary tract infections (UTIs)
    DOI:  https://doi.org/10.1128/cmr.00382-25
  14. Cureus. 2026 May;18(5): e108901
    Pseudomonas aeruginosa in Ventilator-Associated Pneumonia: A Comprehensive Review of Resistance and Clinical Outcomes.
    Sneha D Parit, Priyanka M Mane, Satish R Patil.
      Ventilator-associated pneumonia (VAP) remains one of the most common and serious healthcare-associated infections in intensive care units (ICUs), contributing significantly to patient morbidity and mortality among patients on mechanical ventilation. Due to its virulence and increasing antimicrobial resistance, Pseudomonas aeruginosa poses a significant clinical challenge. This review provides a comprehensive analysis of the epidemiology, pathogenesis, resistance mechanisms, and clinical outcomes associated with P. aeruginosa-induced VAP. Among the most notable virulence mechanisms are quorum sensing, biofilm formation, type III secretion systems, and host immune defence resistance. Current therapeutic options, such as piperacillin-tazobactam, meropenem, and newer β-lactam/β-lactamase inhibitor combinations, are reviewed in the context of emerging resistance. Preventive strategies such as antimicrobial-coated endotracheal tubes, cuff pressure adjustment, and subglottic secretion drainage are also discussed. The rising incidence of multidrug-resistant P. aeruginosa indicates the critical requirement for enhanced antimicrobial stewardship and novel therapeutic approaches to lessen the impact of VAP in critically ill patients. Additionally, this review addresses intrinsic, acquired, and adaptive resistance mechanisms, the clinical burden associated with multidrug-resistant and extensively drug-resistant strains, including increased mortality and prolonged ICU stay, advancements in rapid diagnostic techniques such as molecular assays and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and emerging therapeutic strategies, including cefiderocol, bacteriophage therapy, and anti-biofilm approaches.
    Keywords:  antimicrobial resistance; biofilm formation; esbl; intensive care unit (icu); metallo-beta-lactamase; multidrug resistance; pseudomonas aeruginosa; ventilator-associated pneumonia (vap)
    DOI:  https://doi.org/10.7759/cureus.108901
  15. Front Cell Infect Microbiol. 2026 ;16 1824946
    Periodontal status, oral inflammatory biomarker, and relative expression of red complex bacteria in periodontitis-rheumatoid arthritis: a cross-sectional preliminary study.
    Minessa Mahardika, Widya Rakhmawati, Benso Sulijaya, Sandra Olivia Kuswandani, Natalina Haerani, Suryo Anggoro Kusumo Wibowo, Yuniarti Soeroso, Sri Lelyati C Masulili, Fatimah Maria Tadjoedin, Herlis Rahdewati, Cut Intan Safitri, Ines Augustina Sumbayak, Koichi Tabeta, Naoki Takahashi.
       Objectives: To determine the differences in periodontal status-Probing Depth (PD), Clinical Attachment Loss (CAL), Bleeding on Probing (BOP); oral inflammatory biomarkers-Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1 Beta (IL-1β), Prostaglandin E2 (PGE2); and the relative expression of red complex bacteria-Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf) among groups with periodontitis and periodontitis accompanied by rheumatoid arthritis (RA).
    Materials and methods: A cross-sectional preliminary study by exploring periodontal clinical parameters, gingival crevicular fluid (GCF) inflammatory biomarker levels, and subgingival plaque relative expression of red complex bacteria. A total of 21 subjects, samples were taken one-time from patients with periodontitis (n=12) and periodontitis with RA (n=9). Biomarker levels were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) and bacterial expression was measured using real-time polymerase chain reaction (RT-PCR). All periodontal parameters, GCF biomarkers, and bacterial expression were then analyzed accordingly.
    Results: No statistically significant differences (p > 0.05) were found for PD and CAL. BOP ​​was significantly higher in the periodontitis group than periodontitis+RA group. All biomarker levels were significantly increased in the periodontitis+RA group compared to periodontitis group. No significant difference in total bacterial expression (16sRNA) among groups. Pg and Td expression were significantly higher in the periodontitis group compared to periodontitis+RA group.
    Conclusions: In this exploratory study, patients with periodontitis and RA exhibited significantly higher inflammatory biomarkers levels, indicating an amplified inflammatory response. This exploratory study identifies numerical trends suggesting that systemic condition may be associated with a suppressed red complex profile in Indonesian RA patients.
    Keywords:  dentistry; inflammatory biomarker; periodontal parameter; periodontitis; red complex bacteria; rheumatoid arthritis
    DOI:  https://doi.org/10.3389/fcimb.2026.1824946
  16. Clin Microbiol Rev. 2026 Jun 15. e0008826
    The gut microbiome in preterm infants: development, dysbiosis, and disease implications.
    Enfu Tao, Lizhen Wang, Tianming Yuan.
      SUMMARYPreterm infants face a unique trajectory of gut microbiome assembly, shaped by the convergence of physiological immaturity, necessary clinical interventions, and the neonatal intensive care unit environment. This dysbiotic ecosystem-characterized by low diversity, depletion of beneficial commensals such as Bifidobacterium, and expansion of pathobionts, including Enterobacteriaceae-is increasingly recognized as a central mediator of neonatal morbidity. This review synthesizes current evidence on preterm microbiome development, its role in necrotizing enterocolitis through mechanisms involving Toll-like receptor 4 signaling, bile acid dysmetabolism, and immune dysregulation, and its systemic impact via gut-organ axes linking the intestine to the brain, lung, eye, and systemic circulation. We critically evaluate microbiome-targeted interventions across the translational spectrum, from foundational practices such as human milk feeding and antibiotic stewardship to active modulation with probiotics and prebiotics, and emerging precision strategies, including postbiotics, phage therapy, and fecal microbiota transplantation. Methodological advances in multi-omics, machine learning, and digital twin modeling are paving the way for personalized, predictive microbiome-mediated care. We also address the hidden burden of antimicrobial resistance in the preterm gut and the challenges of translating mechanistic insights into clinical practice. Looking forward, embracing the complexity of the preterm microbiome as a dynamic, multi-kingdom ecosystem is essential for developing holistic interventions that improve both short-term survival and long-term neurodevelopmental, respiratory, and metabolic outcomes.
    Keywords:  dysbiosis; gut microbiome; gut-organ axes; multi-omics; necrotizing enterocolitis; neurodevelopment; preterm infant; probiotics
    DOI:  https://doi.org/10.1128/cmr.00088-26
  17. Sci Rep. 2026 06 17. pii: 18861. [Epub ahead of print]16(1):
    An AI-driven framework for diabetic foot ulcer classification, segmentation, and depth estimation.
    Saswati Debnath, Daniel Willson, Renukadevi M N, Shreenidhi H S, Jaydeep Kishore, Rohit Singh.
      Diabetic Foot Ulcers are a severe complication of diabetes that can lead to infection, amputation, and increased mortality, making timely and objective assessment essential. Conventional evaluation relies primarily on visual inspection and manual measurements, which are often subjective and inconsistent. This paper presents a comprehensive automated deep learning-based framework for DFU assessment that integrates classification, segmentation, relative depth estimation, and explainability. An EfficientNet-B0 model is employed for binary classification of ulcerated versus healthy skin. At the same time, a U-Net with an EfficientNet-B0 encoder is used for precise delineation of ulcer boundaries, enabling quantitative morphometric analysis such as area and width estimation. Model interpretability is incorporated through Gradient-weighted Class Activation Mapping and Local Interpretable Model-Agnostic Explanations, providing visual insights into the decision-making process. To characterize wound topology, relative pseudo-depth maps are generated from single RGB images using a MiDaS-based monocular depth estimation approach. Finally, an automated reporting module synthesizes outputs from all components into structured, clinician-friendly summaries. Experimental results demonstrate strong classification performance, accurate segmentation, and meaningful characterization of relative depth, highlighting the potential of the proposed framework as a research-oriented AI-assisted decision-support tool for DFU assessment. However, further clinical validation involving expert clinicians and prospective studies is required before real-world clinical deployment.
    Keywords:  Computer-aided diagnosis; Deep learning; Diabetic foot ulcer; Explainable AI; Hybrid model; Medical imaging; Multi-class classification; Transformer
    DOI:  https://doi.org/10.1038/s41598-026-52864-2
  18. Diabetes Metab Res Rev. 2026 Jul;42(5): e70189
    Diabetic Foot Ulceration in Dialysis-Dependent End-Stage Kidney Disease: A Systematic Review of Epidemiology, Clinical Outcomes and Mortality Risk.
    J Z M Lim, D Selvarajah, S Mitra, N S L Ng, G Rayman, L Vileikyte, F L Game, A J M Boulton.
       BACKGROUND: Diabetic foot ulceration (DFU) and lower limb complications are highly prevalent in people with end-stage kidney disease (ESKD), particularly those receiving dialysis; however, the overall burden and outcomes remain incompletely characterised. This systematic review with narrative synthesis aimed to summarise study characteristics and evidence on the epidemiology of DFU in ESKD, including incidence, prevalence, wound healing outcomes, and associations with lower-extremity amputation (LEA) and mortality.
    METHODS: MEDLINE (via PubMed), EMBASE and the Cochrane Database of Systematic Reviews were searched from inception to 31 January 2026 for longitudinal and cross-sectional studies, including registry data, in adults with ESKD or on dialysis. Outcomes included DFU epidemiology, wound healing, revascularisation, LEA and mortality.
    RESULTS: The review included 64 observational studies. In dialysis-dependent populations, DFU incidence is high and increases with advancing renal impairment, often preceding dialysis initiation. Evidence on whether dialysis initiation itself increases DFU risk is limited and heterogeneous, although observational cohorts suggest a temporal association with haemodialysis initiation, particularly within the first 2 years. Data comparing haemodialysis and peritoneal dialysis are scarce. Wound healing outcomes were variable, with earlier recurrence observed, although multidisciplinary care improved healing, largely driven by perfusion and ulcer severity rather than renal function alone. Although based on observational and heterogeneous data, dialysis-dependent ESKD was frequently identified as an independent predictor of LEA after adjustment for confounders, with coexisting peripheral arterial disease, a key determinant of adverse limb outcomes. Mortality risk appeared to compound following amputation, with observational data suggesting high post-amputation mortality (approaching 50% at 2 years and 70% at 5 years), consistent with a shift towards limb loss rather than increased DFU occurrence. Interpretation is limited by study heterogeneity, observational design, limited long-term data on healing and recurrence, and inadequate stratification by dialysis modality.
    CONCLUSIONS: Current evidence underscores substantial gaps in understanding the natural history and optimal management of diabetic foot disease in dialysis-dependent ESKD. Future research should prioritise well-designed prospective studies to delineate dialysis-specific risk pathways, incorporate robust stratification by dialysis modality, and evaluate interventions targeting ischaemia and limb preservation. Standardisation of outcome reporting, particularly for healing durability and recurrence, will be essential to enable meaningful comparisons and guide the development of tailored multidisciplinary care models for this high-risk population.
    Keywords:  diabetic foot ulcer; dialysis; end‐stage kidney disease; lower‐extremity amputation; mortality; wound healing
    DOI:  https://doi.org/10.1002/dmrr.70189
  19. Environ Microbiol. 2026 Jun;28(6): e70352
    Rapid Quantification of Bacteriophages of Mycobacterium spp. and Related Genera in Aquatic Systems.
    Hanieh Shakeri Moghaddam, S Jane Fowler.
      Viruses shape microbial communities but remain underexplored in aquatic systems. Most studies target specific viruses as contamination indicators, while the potential of phages to reflect microbial dynamics is often overlooked. We designed and optimised two qPCR assays to quantify specific phages from the order Caudoviricetes-some of the most abundant in aquatic environments-infecting Mycobacterium, Rhodococcus and Gordonia spp. Major capsid protein (MCP) sequences were retrieved from the NCBI Viral Database and degenerate and non-degenerate primers, along with a TaqMan probe, were developed targeting the MCP gene. SYBR Green and TaqMan assays were optimised, validated using an MCP sequence and applied to samples from a drinking water treatment plant (DWTP), urban lakes and activated sludge. Both assays showed strong linearity with efficiencies of 95% (TaqMan) and 94% (SYBR Green). Viral gene copies decreased across the DWTP, indicating up to four-log phage removal during treatment. Phage counts in source water paralleled bacterial counts, especially in the cold season, suggesting a potential correlation between phages and bacterial hosts. Lake samples had higher phage concentrations (up to 106 copies/L), while only two wastewater treatment plants showed phage presence. These assays offer sensitive tools for monitoring phage abundance and microbial dynamics in freshwater environments.
    Keywords:   Caudoviricetes ; Mycobacterium spp.; bacteriophage; major capsid protein; qPCR; water
    DOI:  https://doi.org/10.1111/1462-2920.70352
  20. Wounds. 2026 Apr;38(4): 97-106
    The STEADY diabetic foot ulcer registry: methods, insights, and future directions.
    Jared R Adams, Jennifer N Lannon, Vickie R Driver, David Alper, Cyaandi R Dove, John C Lantis, Joseph Rolley, Robert Snyder.
       BACKGROUND: Diabetic foot ulcers (DFUs) are a major cause of morbidity, amputation, and mortality among individuals with diabetes, with disproportionate impact on underserved populations. Comprehensive real-world data on DFU management and outcomes are lacking.
    OBJECTIVE: To describe the design and methodology of the STEADY (Structured Evaluation and Analysis of Diabetic Foot Ulcers in the US) registry, a national prospective cohort study of patients with DFUs in the United States whose objective is to evaluate DFU treatment patterns, outcomes, and health care resource utilization in real-world settings, to assess comparative effectiveness, cost effectiveness, and safety of DFU therapies and therapy combinations, and to advance disease management through risk- and site-stratified treatment optimization models.
    METHODS: STEADY is a 10-year prospective multicenter observational study with an aim of enrolling 5000 adults with active DFUs in the United States. Data sources include electronic case report forms, electronic medical records (EMRs), patient-reported outcomes via mobile app, and optional insurance claims. Primary and secondary end points will include time and incidence of partial and complete wound closure; wound and disease characteristics; rates of recurrence, infection, ischemic events, and amputation; health care utilization, including surgical procedures; health-related quality of life; work productivity; and additional patient reported outcomes. Descriptive, survival, and comparative effectiveness analyses will be performed. Data governance ensures full regulatory compliance and robust data security and integrity, supporting the potential use of the registry dataset as a synthetic control arm in future clinical research.
    CONCLUSION: STEADY leverages an artificial intelligence (AI)-enabled platform to integrate multisource data, including wound photography, social determinants of health, patient reported outcomes and caregiver information. The platform uses AI for transcription and interpretation of patient and provider dictation, supports patient-controlled EMR synchronization for comprehensive longitudinal tracking across providers, offers participant incentives to enhance engagement, and ensures rigorous, automated data quality assurance at all stages.
    Keywords:  artificial intelligence; diabetic foot ulcer; machine learning; registry; wound management
    DOI:  https://doi.org/10.25270/wnds/26010
  21. Microbiol Spectr. 2026 Jun 15. e0396225
    From screening to treatment: in vitro and in vivo efficacy of phage-meropenem combination against highly virulent Carbapenem-resistant Acinetobacter baumannii.
    Lan Liao, Shanchen Yang, Gang Luo, Ruidong Wu, Rongjing Lu, Yushan Huang, Guanfeng Wu, Wei Yi, Zhu Zeng, Zhilang Qiu, Jian Peng.
      Carbapenem-resistant Acinetobacter baumannii (CRAB) is a hospital-acquired pathogen of significant clinical importance. Given the slow progress in antibiotic development, phages have emerged as a novel therapeutic strategy against CRAB infections due to their synergistic effects with antibiotics. This study aims to explore phage-antibiotic combination therapy targeting CRAB, thereby providing a theoretical foundation for its clinical translation. Through virulence assessments in Galleria mellonella larvae and mice, CRAB110 was identified as the most virulent strain among 199 clinical CRAB isolates. Transcription analysis revealed that its enhanced pathogenicity may be associated with dysregulated pro-inflammatory responses. Using CRAB110 as the host bacterium, the newly isolated phage, P2, was selected for further study due to its high lytic efficiency and broad host range. The CRAB110 mutant strain CRAB110-2N, treated with P2, exhibited increased drug susceptibility and attenuated virulence compared to the wild-type strain. Both in vitro and in vivo experiments demonstrated that the combination of P2 with antibiotics achieved superior bacterial clearance compared to phage therapy alone. Furthermore, whole-genome analysis of CRAB110-2N revealed a mutation in its ugd. The constructed CRAB110Δugd showed tolerance to P2; the quorum-sensing gene abaI was associated with phage susceptibility, with the CRAB110ΔabaI strain displaying insensitivity to P2. These findings provide experimental evidence supporting the clinical application of phage-antibiotic combination therapy.
    IMPORTANCE: This study focused on phage-antibiotic combination therapy targeting carbapenem-resistant Acinetobacter baumannii (CRAB), a priority pathogen designated by the World Health Organization (WHO). A highly virulent strain, CRAB110, was screened from 199 clinical isolates, and a novel, highly lytic phage, P2, was isolated from sewage samples. CRAB110-2N, a mutant strain induced by P2 exposure, displayed increased antibiotic susceptibility and attenuated virulence. Key findings showed that the combination of P2 and meropenem achieved a 99% bacterial clearance rate in vitro and exerted significant synergistic effects in vivo. Genomic analysis identified mutations in the ugd gene, and knockout experiments confirmed its correlation with phage susceptibility. Additionally, the quorum-sensing gene abaI was found to be associated with phage susceptibility in CRAB. Collectively, these results provide critical experimental evidence for the clinical translation of this phage-antibiotic combination therapy.
    Keywords:  CRAB; phage therapy; quorum sensing; virulence
    DOI:  https://doi.org/10.1128/spectrum.03962-25
  22. Georgian Med News. 2026 Apr; 50-60
    INTERLEUKIN-1 GENE POLYMORPHISMS AND SUSCEPTIBILITY TO PERIODONTITIS ACROSS ETHNICITIES AND POPULATIONS: A LITERATURE REVIEW.
    E Jahja, A Koçi, I Nakashidze.
      Periodontitis is a multifactorial inflammatory disease of the tooth-supporting tissues caused by dental biofilm and mediated by the host immune response. Interleukin-1 is a key pro-inflammatory cytokine implicated in periodontal inflammation, connective tissue breakdown, and disease progression. Beyond microbial and environmental factors, genetic polymorphisms affecting interleukin-1 activity contribute to interindividual variability in disease susceptibility, progression, and treatment response. This review examines the association between interleukin-1 gene polymorphisms and periodontitis risk across different populations, ethnic groups, clinical conditions and demographics. Data were retrieved from the PubMed database, covering publications from 2007 to 2024, using the following search strategy: ("periodontitis" OR "periodontal disease") AND ("interleukin-1" OR "IL-1") AND "polymorphism". Only human studies investigating the association between interleukin-1 polymorphisms and susceptibility to periodontal diseases were selected. Exclusion criteria included animal studies, meta-analyses and review articles. Although results are sometimes conflicting, most studies identify interleukin-1 polymorphisms as significant genetic risk factors for periodontal diseases, suggesting-at least to some extent-shared genetic susceptibility across populations or among different ethnic groups within a given population. Understanding population- and ethnicity-related genetic influences may improve risk assessment, enable early identification of susceptibility, and support the development of personalized preventive and therapeutic strategies.
  23. Int J Telemed Appl. 2026 ;2026 2299762
    Application of Digital Twin Technology to Enhance Chronic Diseases Management: A Systematic Review.
    Amirhossein Zarei, Marsa Gholamzadeh, Fatemeh Asadi.
       Background: Given that chronic diseases account for a considerable proportion of preventable deaths globally, the adoption of innovative technologies for disease management and prevention is crucial. Digital twins (DTs), representing one of the most advanced technological solutions, enable real-time simulation and monitoring of chronic disease progression, facilitating personalized treatment strategies and early intervention. This systematic review examines current research on DT applications in chronic disease management to evaluate their potential impact.
    Methods: A systematic search was conducted in four databases including PubMed, Scopus, Web of Science, and IEEE from inception to the date of the last search. The research question was formulated using PICO framework. Next, all articles were screened following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select eligible articles based on inclusion criteria. The extracted information was analyzed to determine the main applications, domains, and employed technologies using quantitative and qualitative techniques.
    Results: Out of 298 citations, 20 studies met our inclusion criteria after duplicate removal and screening. Most studies (45%, n = 10) were published between 2023 and 2024, indicating an increasing trend in this area. Geographically, the United States contributed the most studies (25%, n = 5), followed by Switzerland (15%, n = 3). Our analysis revealed that primary applications of DT in chronic disease management included medical training and education (65%, n = 13), personalized medicine and patient care (45%, n = 9), and drug discovery and clinical trials (35%, n = 7). Target groups comprised clinicians (42.11%), patients (31.58%), and medical students (15.79%). Key enabling technologies in this subject were data analytics (65%), artificial intelligence and machine learning (60%), computational physiological modeling (30%), and IoT sensors (25%).
    Conclusions: Our findings demonstrate that DT technology has evolved from theoretical models to integrated clinical applications, with the potential to revolutionize healthcare through personalized medicine, continuous monitoring, and AI-driven decision support.
    Keywords:  artificial intelligence; chronic disease management; digital twins; healthcare technology; personalized medicine; systematic review
    DOI:  https://doi.org/10.1155/ijta/2299762
  24. Front Cell Infect Microbiol. 2026 ;16 1830404
    Mapping the knowledge landscape of Pseudomonas aeruginosa biofilm-mediated drug resistance: a bibliometric analysis and clinical trial landscape overview.
    Peng Zhao, Zejia Wang, Nan Jia, Xin Wang, Jingyu Liu, Yuanqi Zhu.
       Background: Pseudomonas aeruginosa is a major opportunistic pathogen whose ability to form biofilms greatly enhances antimicrobial tolerance and contributes to persistent infection. Although increasing attention has been paid to biofilm-mediated drug resistance, the overall knowledge structure and translational development of this field remain unclear.
    Methods: A bibliometric analysis was performed using publications retrieved from the Web of Science Core Collection and Scopus on December 20, 2025. The search covered the period 2014-2025 and focused on P. aeruginosa, antimicrobial resistance, and biofilms, resulting in 6,537 publications for bibliometric analysis. To complement the bibliometric findings, a supplementary narrative review of published clinical studies and a separate registered trial landscape overview were conducted. After screening, 6 published clinical studies and 18 registered interventional trials were included.
    Results: Global research output on P. aeruginosa biofilm-mediated resistance increased steadily from 2014 to 2025. China, the United States, and India were the most productive countries, while the United States showed the leading role in the international collaboration network. Keyword clustering and temporal analyses indicated three major research directions: multidrug resistance evolution and pathogenic synergy, novel antibacterial interventions and functional materials, and clinical translation and efficacy evaluation. The supplementary clinical component showed growing interest in adjunctive and mechanistically targeted strategies, particularly in chronic airway and wound-associated infections, although mature efficacy data remain limited.
    Conclusions: Research on P. aeruginosa biofilm-mediated drug resistance is shifting from mechanistic exploration toward translational application. This study provides a data-driven overview of the field's intellectual structure, research hotspots, and emerging trends, and may help guide future anti-biofilm and anti-resistance research.
    Keywords:  Pseudomonas aeruginosa; anti-biofilm strategies; antimicrobial resistance; bibliometric analysis; biofilm-mediated drug resistance; clinical trials
    DOI:  https://doi.org/10.3389/fcimb.2026.1830404
  25. Front Dent Med. 2026 ;7 1839034
    Test, Treat, Repopulate™ method reduces red complex bacteria and stabilizes the oral microbiome.
    Rachelle Beattie McAliley, Lora Hooper, Kami Hoss, David J Vigerust.
      Despite advances in dental hygiene and clinical interventions, preventable conditions such as tooth decay and gum disease remain widespread public health concerns. Recent research implicates complex, polymicrobial interactions as central drivers of disease pathogenesis, which often limits the effectiveness of traditional therapeutic approaches. Here, researchers evaluate the effectiveness of the Test, Treat, Repopulate method, a multi-phase oral health protocol combining scaling and root planing, targeted antibiotic therapy, use of a pH-balanced, prebiotic containing toothpaste and rinse, and daily oral probiotic use on the health of the oral microbiome. Retrospective analysis of RT-qPCR salivary diagnostic data from 38 de-identified U.S. patients, collected before and after treatment during routine care, demonstrated significant and sustained reductions in key oral pathogens following the combined treatment approach. Seven bacterial species were significantly reduced post-treatment, including Treponema denticola, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Fusobacterium nucleatum, Fusobacterium nucleatum subsp. animalis, and Streptococcus mutans. Additional pathogens, including Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were also reduced. The protocol had minimal impact on the fungal species Candida albicans, highlighting an area for potential optimization. Additionally, four viral targets were assessed pre- and post-protocol, making this one of the first studies to evaluate a dental intervention's effects on oral viruses. Comparison of the cohort with 35,570 pre-treatment salivary diagnostic tests across the United States shows that baseline pathogen distributions reflect national patterns, supporting the generalizability of the protocol. A structured protocol for patients with elevated red complex bacteria is detailed, providing clinicians with a data-driven, reproducible framework for precision oral healthcare. These findings underscore the potential for microbiome-focused interventions to achieve measurable, lasting improvements in oral health across diverse populations.
    Keywords:  dental caries; oral microbiome; periodontitis; probiotics; salivary diagnostics
    DOI:  https://doi.org/10.3389/fdmed.2026.1839034
  26. Adv Wound Care (New Rochelle). 2026 Jun 16. 21621918261459794
    Management of Infected Wounds: A Wound Healing Foundation Consensus Statement.
    Nicolás Cortés-Penfield, Benjamin A Lipsky, Elof Eriksson, Meghan B Brennan, Martin Clauss, Catherine Dunyach-Remy, Sue Gardner, Roman Hayda, Lindsay Kalan, Paul Kim, Klaus Kirketerp-Møller, Paul Liu, Samuel Mandell, Oscar Murillo, Gojiro Nakagami, Laura K S Parnell, Edgar J G Peters, Parham Sendi, Gary Sibbald, Terry Swanson, Rica Tanaka, Tze-Woei Tan, Ilker Uçkay, Dot Weir.
      The Wound Healing Foundation (WHF) previously organized consensus panels on the management of chronic wounds (2022), acute wounds (2024), and diabetic wounds (2025). This WHF consensus statement, authored by a global interdisciplinary panel of clinicians and researchers, focuses on the management of infected wounds. The panel members reviewed the literature and reached consensus on elements of an evidence-based approach to infected wounds. Using a structured format, this statement progresses from discussing how wound infections develop, how to diagnose them, how to provide the most appropriate antimicrobial and surgical treatment, how to assess response to treatment, and how to further investigate instances of unsuccessful treatment.
    Keywords:  treatment consensus; wound infection; wound infections; wounds
    DOI:  https://doi.org/10.1177/21621918261459794
  27. Sci Rep. 2026 Jun 18.
    Volatile organic compound profiling for tracking clinical Pseudomonas aeruginosa isolates.
    M Trinidad García-Barceló, Biel Martorell, Alexandre González-Alsina, Antonio Doménech-Sánchez, Rosa M Gomila, Sebastián Albertí, Margalida Mateu-Borràs.
      Pseudomonas aeruginosa is an opportunistic respiratory pathogen frequently affecting hospitalized patients and individuals with chronic lung diseases such as cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD). Current diagnostic methods for airway infection are often invasive or lack sensitivity, highlighting the need for non-invasive approaches. Volatile organic compounds (VOCs) released by microbes represent promising candidates for non-invasive detection of respiratory pathogens. In this study we characterized the volatilome of clinical P. aeruginosa isolates and identified candidate VOC markers associated with bacterial metabolism. An untargeted volatilomics workflow based on gas chromatography-mass spectrometry (GC-MS) was applied to profile the in vitro VOCs produced by 48 clinical P. aeruginosa isolates associated with acute and chronic respiratory infections. We identified three previously unrecognized VOCs consistently produced by all isolates, suggesting conserved metabolic features of P. aeruginosa. Comparative analysis revealed marked metabolic differences between infection phenotypes: chronic isolates produced higher levels of aliphatic volatiles, whereas acute isolates were enriched in aromatic compounds, particularly acetophenone. Longitudinally sampled clonally related isolates from CF patients exhibited distinct and evolving volatilomic signatures, indicating metabolic adaptation over the course of chronic infection. Because LasR dysfunction is common during chronic airway colonization, we further assessed its impact on VOC production. LasR-functional isolates produced elevated levels of sulfur-containing VOCs and specific ketones, while LasR-deficient isolates displayed increased alcohol production. Overall, our findings show that isolates from chronic infections are associated with a shift from aromatic to aliphatic VOCs compared to acute isolates, and highlight volatilomics as a powerful tool for probing metabolic adaptation in P. aeruginosa and for identifying candidate VOC markers associated with infection-related phenotypes.
    DOI:  https://doi.org/10.1038/s41598-026-58199-2
  28. AMB Express. 2026 Jun 16.
    Surfactant-driven quorum sensing of Pseudomonas aeruginosa in cystic fibrosis.
    Prathibha Selvamani, James John, Janaki Devi Kumar, Sangeetha Gopalakrishnan, Jagadish Chandra Kumar Mangu, Priyatharshini Thangaraj, Krupakar Parthasarathy.
      Cystic fibrosis (CF) is a genetic lung disease in which thick mucus builds up in the airways, making patients highly vulnerable to chronic bacterial infections. One of the most problematic bacteria in these infections is Pseudomonas aeruginosa, an adaptable microbe that can survive antibiotics and persist in the lungs for many years. This bacterium uses a communication system called "quorum sensing (QS)" to coordinate group behaviors. Through this system, bacterial cells sense their population density and collectively switch on genes that control toxin production, biofilm formation, and resistance to treatment. In cystic fibrosis lungs, the protective lung surfactant layer, especially a major lipid component called dipalmitoylphosphatidylcholine (DPPC), becomes altered due to chronic inflammation. Emerging evidence suggests that altered surfactant lipids may influence bacterial behavior in addition to reflecting lung damage. Instead, they may actively signal to P. aeruginosa, triggering its QS system earlier than expected. This early activation promotes virulence, biofilm persistence, and long-term infection. This review highlights how host lung lipids interact with bacterial communication networks and discuss how targeting QS using surfactant-inspired molecules may offer new therapeutic strategies. Understanding this host-pathogen interaction could lead to innovative anti virulence treatments that weaken the bacteria without directly killing them, potentially reducing antibiotic resistance.
    Keywords:   Pseudomonas aeruginosa ; Anti virulence therapy; Cystic fibrosis (CF); Dipalmitoylphosphatidylcholine (DPPC); Lung surfactant; Quorum sensing (QS)
    DOI:  https://doi.org/10.1186/s13568-026-02083-9
  29. Cureus. 2026 May;18(5): e108813
    Biofilm-Forming Methicillin-Resistant Staphylococcus aureus: A Comprehensive Phenotypic and Genotypic Review.
    Sejal R Bhujugade, Harsha V Patil, Satish R Patil.
      Methicillin-resistant Staphylococcus aureus (MRSA) is a major global pathogen, capable of forming biofilms that confer enhanced antimicrobial tolerance, virulence, and persistence in both hospital and community settings. Biofilms are structured microbial communities encased in extracellular polymeric substances, composed of polysaccharides, proteins, and extracellular DNA. Complex genetic networks, including the ica operon, the agr quorum-sensing system, the sarA regulatory system, and stress-response genes such as sigB, regulate MRSA biofilm formation. Phenotypic methods (Congo red agar, microtiter plate, and tube test) and genotypic assays (PCR-based detection of ica, fnbA/B, clfA/B, sarA, and agr) provide insights into biofilm capacity and virulence potential. Clinically, MRSA biofilms contribute to device-related infections, chronic wounds, and recurrent infections, challenging conventional therapies such as vancomycin, daptomycin, and rifampicin. Emerging strategies, including enzymatic matrix degradation, bacteriophage therapy, quorum-sensing inhibitors, and nanoparticle-based drug delivery, offer potential alternatives. This review synthesizes current knowledge on MRSA biofilm phenotypes and genotypes, highlighting molecular mechanisms, clinical significance, and therapeutic approaches.
    Keywords:  agr system; antimicrobial resistance; biofilm; genotypic analysis; ica operon; mrsa; phenotypic detection; sara
    DOI:  https://doi.org/10.7759/cureus.108813
  30. Interdiscip Sci. 2026 Jun 15.
    Deep3D-DTA: A Tri-Modal Deep Learning Framework for Binding Affinity Prediction Leveraging 3D Structural Representations of Drugs and Targets.
    Han Zhou, Xiumin Shi, Lu Wang.
      Predicting drug-target affinity (DTA) plays a pivotal role in drug discovery and repurposing. While existing computational approaches predominantly rely on 1D sequences or 2D structural data, they often fail to fully capture the intricate nature of molecular interactions. To address this limitation, we propose Deep3D-DTA, a novel tri-modal deep learning framework that integrates 1D sequence semantics, 2D graph topology, and 3D spatial geometry complementary representations for both drugs and target proteins. The proposed architecture offers three key advancements: First, it employs a pre-trained protein language model to encode amino acid sequences, effectively capturing long-range sequential dependencies. Second, it constructs precise 3D structural representations by computing interatomic distances and bond angles, enabling accurate modeling of the spatial conformations of both proteins and compounds. Third, it leverages a hybrid feature extraction module that combines graph neural networks with multi-head attention mechanisms to learn hierarchical structural patterns. Extensive experiments on three widely used benchmark datasets (Davis, KIBA, and Metz) demonstrate that Deep3D-DTA significantly outperforms state-of-the-art methods in DTA prediction. These results highlight its potential as a robust and reliable computational tool for accelerating drug discovery and reducing development costs through more accurate affinity prediction.
    Keywords:  Attention mechanism; DTA prediction; Drug 3D structure; Graph neural network; Protein 3D structure
    DOI:  https://doi.org/10.1007/s12539-026-00839-2
  31. Front Endocrinol (Lausanne). 2026 ;17 1856183
    Factors associated with foot self care behavior among older adults with recurrent diabetic foot ulcer: a cross-sectional study.
    Liping Lin, Jianbing He, Hongjian Zhang, Aiwen Yang, Qiuni Cai.
       Background: Diabetic foot ulcers (DFU) are a severe complication of diabetes, with high recurrence rates and substantial clinical burden. Foot self-care behavior is essential for preventing ulcer recurrence, yet evidence specifically targeting older adults with recurrent DFU remains limited. This study aims to identify the factors associated with foot self-care behavior among older adults with recurrent diabetic foot ulcers.
    Methods: A cross-sectional study was conducted using a purposive sampling technique among 170 older adults (≥60 years) with recurrent DFU recruited from the multidisciplinary diabetic foot clinics of three general hospitals in China between January 2023 and December 2024. The study adhered to the STROBE guidelines for cross-sectional studies. Data were collected using structured questionnaires, including the Nottingham Foot Care Assessment (NAFF), Foot Care Confidence Scale, Multidimensional Scale of Perceived Social Support, and Geriatric Depression Scale (GDS-15). Clinical characteristics were extracted from medical records. Multiple linear regression analysis was performed to identify factors associated with foot self-care behavior.
    Results: The mean total NAFF score was 48.5 ± 10.2, indicating a moderate level of foot self-care. Foot care self-efficacy (β = 0.41, P < 0.001), receipt of foot care health education (β = 0.25, P = 0.001), perceived social support (β = 0.19, P = 0.008), and depressive symptoms (β = -0.17, P = 0.021) were factors associated with foot self-care behavior, collectively explaining 47.2% of the variance in foot self-care behavior (adjusted R² = 0.472).
    Conclusion: Foot self-care behavior among older adults with recurrent DFU is moderate and is associated with modifiable psychosocial factors. Interventions targeting self-efficacy, health education, social support, and depressive symptoms may contribute to improved self-care and potentially reduce ulcer recurrence. Longitudinal and interventional studies are warranted to confirm these associations and evaluate clinical effectiveness.
    Keywords:  aged; cross-sectional studies; diabetes mellitus; diabetic foot; health behavior; recurrence; self-care
    DOI:  https://doi.org/10.3389/fendo.2026.1856183
  32. Int J Nanomedicine. 2026 ;21 607257
    Chitosan-Based Wound Dressings: Property Modulation, Fabrication Strategies, and Emerging Applications in Tissue Regeneration.
    Mingjie Fan, Xinmu Zhang, Longfei Lin, Ruying Tang, Hui Li, Yuling Liu.
      Chronic wounds are often difficult to heal because of multiple pathological barriers, including infection, vascular insufficiency, and immune imbalance, and therefore require highly effective dressings to promote repair. Chitosan (CS), a cationic polysaccharide derived from the deacetylation of chitin, has attracted broad attention in wound management because of its favorable biocompatibility, biodegradability, chemical modifiability, and intrinsic hemostatic and antibacterial activities. The therapeutic value of CS-based dressings does not depend solely on CS itself, but rather on their ability to target the dominant pathological barriers of different wound types through structural modification and formulation design. This review links the key pathological features of various chronic wounds with the functional requirements of CS-based dressings, and systematically summarizes how modification strategies such as catechol grafting, quaternization, carboxymethylation, and dynamic covalent crosslinking regulate the properties of CS, as well as the major fabrication platforms and formulation types, including crosslinked hydrogels, freeze-dried sponges, electrospun nanofibers, phase-inversion membranes, and solvent-cast films. Their effects on porosity, mechanical strength, moisture retention, and permeability are also analyzed. Finally, the review discusses the challenges facing CS-based dressings in standardization, scalable manufacturing, clinical translation, and regulatory evaluation, and highlights the need for greater emphasis on multifunctional smart design and the improvement of evidence quality in future research.
    Keywords:  chitosan; hydrogel; polymer composites; wound dressings; wound healing
    DOI:  https://doi.org/10.2147/IJN.S607257
  33. Br J Nurs. 2026 Jun 18. 35(12): S3
    Clinical challenges and solutions in wound care.
    Jackie Stephen-Haynes.
      
    DOI:  https://doi.org/10.12968/bjon.2026.0257
  34. Cureus. 2026 May;18(5): e108810
    Bacterial Infections in Decompensated Cirrhosis: Clinical Profile, Microbiology, and Antimicrobial Resistance Patterns.
    Anubhav Dabas, Mohmad Sejarali Sayeed, Praful Kumar Chavhan, Tehsin Saiyad, Jaskirat K Hundal, Tazean Zahoor Malik, Sajidali S Saiyad, Gajendra Anuragi, Avinash Kumar Sudan.
      Background Hospitalised patients with decompensated cirrhosis face a high risk of bacterial infections. Antimicrobial resistance (AMR) is increasing globally, yet prospective data from the Indian subcontinent - a recognised AMR hotspot - remain limited. Methods This prospective observational study enrolled 176 consecutively hospitalised adults with decompensated cirrhosis over 18 months (September 2022 to February 2024). We analysed clinical profiles, infection prevalence, microbiological isolates, antimicrobial susceptibility patterns, and in-hospital outcomes. Multivariate logistic regression identified independent predictors of infection and mortality. Results Bacterial infections were documented in 82 patients (46.6%). Infected patients were younger (mean age, 48.5 vs. 53.8 years) and predominantly male (76.8%), with higher disease severity (93.9% Child-Turcotte-Pugh (CTP) class C; 79.3% Model for End-Stage Liver Disease-sodium (MELD-Na) >21). In-hospital mortality was significantly higher in infected patients (31/82, 37.8%) compared with non-infected patients (3/94, 3.2%; p < 0.001). Culture positivity was 48.8% (40/82), with Escherichia coli (27.5%) and Klebsiella spp. (17.5%) predominating. Overall, drug resistance was 57.5%, comprising 45.0% multidrug-resistant (MDR) and 12.5% extensively drug-resistant (XDR) organisms. MDR prevalence was highest in urinary tract infections (UTIs) (72.7%), while XDR was most frequent in spontaneous bacterial peritonitis (SBP) (33.3%). Susceptibility of E. coli to ceftriaxone was only 27.3%. Elevated international normalised ratio (INR) and hypoalbuminemia independently predicted infection, whereas hyperbilirubinemia predicted mortality. Conclusion Bacterial infections affect nearly half of hospitalised patients with decompensated cirrhosis in North India and are associated with markedly poor outcomes. The alarmingly high prevalence of MDR and XDR organisms renders conventional empirical antibiotics inadequate. Region-specific antibiograms, enhanced antimicrobial stewardship, and infection prevention strategies are urgently needed in this vulnerable population.
    Keywords:  antibiotic stewardship; antimicrobial resistance; bacterial infections; clinical outcomes; decompensated cirrhosis; india; multidrug-resistant organisms; spontaneous bacterial peritonitis
    DOI:  https://doi.org/10.7759/cureus.108810
  35. J Stomatol Oral Maxillofac Surg. 2026 Jun 17. pii: S2468-7855(26)00172-2. [Epub ahead of print] 102876
    Microbial Dysbiosis in Oral Potentially Malignant Disorders: A Systematic Review.
    Keerthika R, Akhilesh Chandra, Subhadeep Pal, Harshita Tiwari, Amlendu Shekhar, Rahul Agarwal.
       BACKGROUND: Oral potentially malignant disorders (OPMDs) including oral leukoplakia (OLK), proliferative verrucous leukoplakia (PVL), and oral verrucous hyperplasia (OVH) pose variable malignant transformation risk to oral squamous cell carcinoma (OSCC), yet the role of microbial dysbiosis in their progression remains ambiguous.
    OBJECTIVES: To elucidate microbial shifts in OPMDs, their association with dysplasia progression and malignant transformation, highlighting prospects for early detection and risk stratification.
    MATERIAL AND METHODS: A comprehensive literature search was conducted across scientific databases up to May 2025. Studies investigating microbial dysbiosis in OLK, PVL, or OVH using 16S rRNA sequencing, metagenomic, or transcriptomic analyses were included. Risk of bias was assessed using the modified Newcastle-Ottawa scale.
    RESULTS: OPMDs showed inconsistent alpha diversity and distinct beta diversity compared to controls. Microbial composition differed by lesion type: OLK was enriched with Fusobacterium periodonticum, Porphyromonas pasteri, Streptococcus, and Haemophilus; PVL with Campylobacter concisus, Leptotrichia, and Haemophilus parainfluenzae; and OVH with Porphyromonas gingivalis, Tannerella forsythia, and Saccharibacteria TM7. High-risk OLK showed reduced diversity and enrichment of Fusobacterium nucleatum, Parvimonas, and Streptococcus infantis. Malignant transformation revealed lesion-specific shifts, including increased Fusobacterium, Capnocytophaga and Porphyromonas in OLK-OSCC, while Neisseria was specifically enriched in progressive OLK lesions, Treponema and Campylobacter in PVL-OSCC, and Capnocytophaga sputigena and Prevotella oris in OVH-OSCC.
    CONCLUSION: This review highlights the pivotal role of microbial dysbiosis in the evolution of OPMDs to malignancy. Distinct microbial signatures across OLK, PVL, and OVH may serve as biomarkers for disease stratification and early detection of high-risk lesions.
    Keywords:  16S rRNA sequencing; Malignant transformation; Metagenomics; Microbial dysbiosis; Oral leukoplakia; Oral microbiome; Oral potentially malignant disorders; Oral squamous cell carcinoma; Oral verrucous hyperplasia; Proliferative verrucous leukoplakia
    DOI:  https://doi.org/10.1016/j.jormas.2026.102876
  36. PLoS One. 2026 ;21(6): e0351638
    A scoping review of computational models of the diabetic foot.
    Yufeng Li, Athia Haron, Chaofan Lin, Yuan Tang, Andrew Weightman, Glen Cooper.
      The prevalence of diabetes is expected to be 650 million people by 2030, and diabetic foot ulceration (DFU) is one of its most severe complications. It poses a significant challenge to global health and brings substantial social and economic burdens. Although many studies have explored the mechanisms of DFU development, they are still not fully understood. Due to the high cost of the experimental research, many recent studies have employed the computational modelling approaches to simulate the effects of diabetes on foot tissues from mechanical, thermal, fluid, and cellular perspectives. This study aims to provide a comprehensive review of computational modelling approaches used to investigate various factors influencing DFU, discuss current knowledge gaps and limitations, and outline future research directions. A systematic search was conducted in Web of Science, Scopus, and PubMed databases, identifying a total of N = 1631 records up to March 2025, 31 of which studies met the inclusion criteria and were analysed in this study. Results showed that DFU-related computational models can be categorized into five types: mechanical stress models, thermal models, vascular and nerve system models, multiphysics models, and cellular-based models. These models explore the formation mechanisms of DFU from different perspectives, including biomechanics, temperature, fluid dynamics, HHμm neural signalling, and cellular responses. However, except for mechanical stress models, the other approaches remain in the early stages of development, and the single physics modelling strategies are unable to provide understanding on the coupled processes with the foot and their effect on DFU. Future research should further develop modelling approaches and couple these together to develop comprehensive understanding of DFU pathogenesis.
    DOI:  https://doi.org/10.1371/journal.pone.0351638
  37. BMJ Open. 2026 Jun 16. 16(6): e109036
    Predictive variables for early detection of sepsis in adults admitted to intensive care units: protocol for a systematic review.
    Zahra Keshavarz, Farid Zand, Naeimehossadat Asmarian, Mahkameh Rafiee, Roghayeh Ershad Sarabi.
       INTRODUCTION: Sepsis is a life-threatening condition in intensive care units (ICUs), where any delay in diagnosis and treatment can lead to organ dysfunction, prolonged hospital stay and increased mortality. Early identification of sepsis prior to its clinical manifestation may enable timely intervention and improve outcomes. This review aims to identify, synthesise and categorise predictor variables assessed in adult ICU patients prior to sepsis diagnosis.
    METHODS/DESIGN: This protocol, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline, will involve a comprehensive search of PubMed/Medline, Scopus, Embase, Web of Science, IEEE Xplore and Cochrane Library for English-language studies from database inception. The search is planned to be conducted between March 2026 and June 2026. We will include prospective, retrospective, cohort, case-control and cross-sectional studies, and both randomised and non-randomised designs. Additionally, we will consider secondary analysis of electronic health records, clinical registries and routinely acquired clinical data that determine risk factors and predictive variables that will help in the early identification of sepsis using machine learning, artificial intelligence, computational or statistical methods. Two independent reviewers will perform title and abstract screening followed by full-text review and data extraction. The risk of bias will be evaluated using appropriate tools depending on study design: the Newcastle-Ottawa Scale for observational studies, Cochrane Risk of Bias tool for randomised trials and PROBAST for prediction model studies. We will perform a narrative synthesis structured by variable-type, timing and performance metrics (area under the curve, sensitivity, ORs). Subgroup analyses will be conducted based on study design, sepsis definition, type of ICU (medical, surgical, mixed) and geographic area (high-income and low- and middle-income countries).
    ETHICS AND DISSEMINATION: Findings from this systematic review will be disseminated through publication in a peer-reviewed journal and/or presentation at scientific conferences. The data used will not include individual patient data, so ethical approval is not required.
    PROSPERO REGISTRATION NUMBER: CRD420251113781.
    Keywords:  Artificial Intelligence; Intensive Care Units; Machine Learning; Risk Factors; Sepsis
    DOI:  https://doi.org/10.1136/bmjopen-2025-109036
  38. Front Oral Health. 2026 ;7 1814025
    Machine learning assisted classification of periodontal health and periodontitis using alveolar bone loss measurements on bitewing radiographs.
    Sunaina Shetty Yadadi, Raghavendra M Shetty, V Sowmya, Wael Bakie, Karim Jaziri, Hamza Alsaraierh, Hisham Abu Hijazi, Gadila Siri Reddy, Subhashini Sudhakar, Vineet Vinay, Vijay B Desai.
       Background: Periodontitis is a prevalent inflammatory disease characterized by progressive loss of periodontal attachment and alveolar bone. Conventional diagnostic approaches, including periodontal probing and radiographic interpretation, are influenced by examiner variability, limiting consistency in large-scale and community-based assessments. Machine learning-driven models may support standardized screening for periodontal health and periodontitis.
    Aim: To develop and validate a machine learning algorithm to classify periodontal health and periodontitis using clinician-measured and validated radiographic alveolar bone loss obtained from bitewing radiographs, aligned with the 2018 American Academy of Periodontology/European Federation of Periodontology (AAP/EFP) classification of periodontal and peri-implant diseases and conditions.
    Methods: In this retrospective study, 1,537 of 2,162 bitewing radiographs were included. Alveolar bone loss was measured from the cemento-enamel junction to the alveolar crest using MiPACS software and validated by calibrated examiners (κ=0.94). Data were preprocessed, balanced, and split into training, validation, and test sets. Multiple classifiers were benchmarked, with Random Forest (RF) selected after hyperparameter tuning. Performance was assessed using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC).
    Results: The RF model achieved 96.4% accuracy on the validation dataset and 92% on the independent, previously unseen test dataset. Sensitivity was 100% for periodontitis and 93% for healthy cases in the validation set, with an AUC of 0.99. On the unseen test dataset, sensitivity was 94% for healthy and 92% for periodontitis, with an AUC of 0.97.
    Conclusions: The machine learning algorithm accurately classified periodontal health and periodontitis from bitewing radiographs, providing an automated assessment aligned with the 2018 AAP/EFP classification. It may improve diagnostic consistency, support early intervention, and enable community-based screening and triage for large-scale periodontal assessment.
    Clinical relevance: Automated classification of periodontal status from bitewing radiographs may improve diagnostic consistency and facilitate efficient screening and triage in large-scale and community-based dental care.
    Keywords:  2018 AAP/EFP world workshop classification; alveolar bone loss; artificial intelligence; automated assessment; bitewing radiographs; machine learning; periodontitis
    DOI:  https://doi.org/10.3389/froh.2026.1814025
  39. Arch Microbiol. 2026 Jun 19. pii: 447. [Epub ahead of print]208(9):
    Emergence, evolution, and global dissemination of antimicrobial resistance: A One Health review.
    Rashid Ahmad, Zakir Ullah, Mengzhe Li, Yigang Tong.
      Antimicrobial resistance (AMR) is a critical global health threat that undermines the treatment of infections and compromises medical interventions. AMR develops when microorganisms evolve mechanisms to survive antimicrobial exposure, a process accelerated by misuse and overuse of antibiotics in human medicine, agriculture, and veterinary settings. Bacterial resistance poses the greatest immediate concern, contributing to an estimated 1.27 million deaths in 2019 and nearly 5 million deaths associated with resistant infections worldwide. Without urgent intervention, Projections suggest that AMR could cause up to 10 million deaths annually by 2050, potentially surpassing cancer as a leading cause of mortality although these estimates remain subject to uncertainty. This review examines key biological mechanisms of resistance, including enzymatic degradation, target modification, efflux pumps, porin loss, and horizontal gene transfer. It highlights global hotspots and emerging resistance determinants such as NDM-1 and mcr-1, as well as antibiotic usage trends across human and animal sectors. Unlike acute pandemics such as COVID-19, AMR progresses silently but persistently, earning recognition as a "slow pandemic." Its spread involves interconnected human, animal, and environmental reservoirs, necessitating a One Health approach. The review also summarizes current global responses, including the WHO Global Action Plan, surveillance platforms such as GLASS, and ECDC, and research initiatives like CARB-X and GARDP. Despite progress, significant gaps remain in policy, surveillance, and antimicrobial stewardship, particularly in low- and middle-income countries, underscoring the urgent need for coordinated multisectoral action. However, the conclusions drawn are limited by variability in global surveillance data, differences in reporting standards, and reliance on previously published studies, which may not fully capture regional disparities.
    Keywords:  Antimicrobial resistance (AMR); Antimicrobial stewardship; ESKAPE pathogens; Multidrug resistant bacteria; One Health approach
    DOI:  https://doi.org/10.1007/s00203-026-04997-1
  40. J Nanobiotechnology. 2026 Jun 16.
    Remodeling the pathological airway: advanced nanotechnology for diagnostics and therapeutics in cystic fibrosis.
    Ying Zou, Hang Zhao, Mengyi Feng, Zhaoqi Wu, Zhongping Cao, Zhonghao Fan, Martin Gluchman, Huazhe Yang, Chenyu Zhao, Peng Yu, Xudong Zhang.
      Cystic fibrosis (CF) constitutes a prototypical lethal genetic disorder characterized by profound pathophysiological barriers that severely compromise both diagnostic performance and targeted therapeutic efficacy. Although the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has revolutionized disease management, the critical clinical imperatives for ultra-sensitive diagnostic modalities and deep pulmonary delivery systems remain largely unmet. This comprehensive review critically evaluates the transformative potential of nanotechnology in remodeling the dual diagnostic and therapeutic landscapes of CF. Initially, we highlight the integration of advanced nanoscale sensors for the real-time and ultra-sensitive profiling of sweat biomarkers, specific genetic mutations, and respiratory metabolites. These innovations fundamentally elevate early diagnostic precision and continuous disease monitoring capabilities. Concurrently, we systematically elucidate how precision-engineered nanocarriers circumvent formidable mucosal and extracellular polymeric substance biofilms. These vehicles facilitate the targeted pulmonary delivery of diverse pharmacological payloads, including CFTR modulators, mucolytics, complex nucleic acid therapeutics and antimicrobial agents. Ultimately, transitioning from engineering conceptualization to clinical application, we dialectically analyze the multifaceted translational hurdles. This review establishes a rigorous roadmap for propelling diagnostic and therapeutic nanomedicine toward clinical accessible realities.
    Keywords:  Biosensor; Clinical translation; Cystic fibrosis; Drug delivery system; Nanomedicine
    DOI:  https://doi.org/10.1186/s12951-026-04689-4
  41. PLoS Comput Biol. 2026 Jun 17. 22(6): e1014407
    Machine learning-driven identification of virulence determinants in Borrelia burgdorferi associated with human dissemination.
    Hoa Thanh Nguyen, Catherine A Brissette.
      Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992-2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér's V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.
    DOI:  https://doi.org/10.1371/journal.pcbi.1014407
  42. Clin Exp Dent Res. 2026 Jun;12(3): e70391
    Heterogeneous Systemic IgG Responses to Porphyromonas gingivalis Gingipains in Advanced Periodontitis.
    Steffen Büttner, Sonja H M Derman, Alexander Simonis, Alicia M Meyer-Hofmann, Max von Kohout, Manuel Koch, Anna Greta Barbe.
       OBJECTIVES: To evaluate serum IgG responses against Porphyromonas gingivalis gingipains RgpB and Kgp in patients with stage III and IV periodontitis and examine associations with clinical periodontal parameters.
    MATERIALS AND METHODS: This exploratory cross-sectional study included participants with advanced periodontitis (Stage III and IV). Clinical periodontal parameters (number of teeth, bleeding on probing in percent [BoP%], probing pocket depth [PPD], bone loss-to-age ratio, periodontal inflamed surface area [PISA] per tooth) were recorded. Blood samples were collected and serum IgG responses against recombinant RgpB and Kgp were analyzed. Serum IgG signals were quantified using enzyme-linked immunosorbent assay (ELISA).
    RESULTS: All 42 participants (mean age 62 years) exhibited measurable serum IgG responses against P. gingivalis gingipains. IgG signals (optical density) ranged from 0.13 to 1.46 for RgpB and 0.34 to 1.51 for Kgp. RgpB-specific IgG levels were higher in Stage IV versus Stage III periodontitis (p = 0.023), whereas Kgp-specific IgG levels showed no significant difference between stages (p = 0.249). Anti-RgpB IgG levels correlated positively with age (ρ = 0.362, p = 0.019) and inversely with the number of teeth (ρ = -0.372, p = 0.015), whereas anti-Kgp IgG showed no statistically significant correlations with the assessed clinical parameters.
    CONCLUSIONS: Serum IgG binding signals to RgpB and Kgp were measurable by ELISA and showed substantial heterogeneity among patients with advanced periodontitis, with considerable overlap between disease stages. Anti-RgpB IgG was associated with age and tooth loss, whereas inflammatory measures showed no significant correlations and anti-Kgp IgG showed only weak trend-level associations. Overall, total gingipain-specific IgG appears to reflect cumulative periodontal disease burden and exposure history more clearly than current inflammatory activity in this cohort, with limited value as a standalone marker for differentiating Stage III and Stage IV periodontitis.
    Keywords:  Porphyromonas gingivalis; gingipains; host immune response; immunoglobulin G; periodontitis; systemic inflammation
    DOI:  https://doi.org/10.1002/cre2.70391
  43. Arch Microbiol. 2026 Jun 16. pii: 441. [Epub ahead of print]208(9):
    Helicobacter pylori phages: resource landscape, translational challenges, and engineered antibacterial strategies.
    Zhenkai Li, Ling Chen, Shixuan Huang, Ying Zhang, Fei Yao, Peihao Huang, Yanyan Shang, Xiaoming Yuan, Xinqiang Xie, Ying Li, Qingping Wu.
      Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen whose increasing antimicrobial resistance has reduced the efficacy of conventional eradication regimens. Bacteriophages and phage-derived products have therefore attracted growing interest as alternative antimicrobial strategies against H. pylori. However, progress in this field remains constrained by the limited availability of cultivated phages, the underexplored reservoir of prophages and uncultivated phages, narrow host range, and poor stability under gastric conditions. In this review, we summarize the current landscape of H. pylori phage research, including both virulent and temperate phages, and discuss how genome-based mining is expanding access to previously inaccessible phage resources. We further examine recent application-oriented advances, including artificial intelligence-assisted endolysin discovery, receptor-binding protein engineering for host-range expansion, and targeted delivery platforms designed to improve phage stability and site-specific activity in the stomach. Finally, we highlight key translational barriers, including biosafety evaluation, functional validation, and in vivo efficacy. Together, these advances provide a framework for evaluating phage-based and phage-derived antimicrobial strategies for H. pylori control, while highlighting the need for rigorous functional validation, biosafety assessment, and in vivo efficacy testing.
    Keywords:   Helicobacter pylori ; Bacteriophage; Endolysin; Host range engineering; Prophage; Targeted delivery
    DOI:  https://doi.org/10.1007/s00203-026-04996-2
  44. Intensive Crit Care Nurs. 2026 Jun 18. pii: S0964-3397(26)00134-5. [Epub ahead of print]97 104466
    A selective deep learning framework for pressure injury staging with calibrated confidence and automated clinical documentation.
    Jack Lott, David McShannon, Nicholas Dietrich.
       OBJECTIVES: Pressure injuries are common chronic wounds that require accurate staging to guide management. Deep learning has shown promise for automated staging from clinical photographs, but most prior studies report classification accuracy alone without accounting for prediction uncertainty. We developed and evaluated a selective deep learning framework that calibrates prediction confidence, defers low-confidence cases for clinician review, and generates structured clinical documentation.
    METHODS: We trained a ConvNeXt-V2-Tiny classifier on 763 images labeled across four National Pressure Injury Advisory Panel (NPIAP) pressure injury stages. Post-hoc temperature scaling was applied to improve probability calibration. A selective prediction framework deferred low-confidence cases to clinician review. Structured wound documentation was generated by a large language model using NPIAP guideline-based staging definitions. External validation was performed on an independent dataset of 159 pressure injury images.
    RESULTS: The classifier achieved 74.4% overall accuracy, 73.7% balanced accuracy, and a macro-AUC-ROC of 0.929. Temperature scaling reduced test expected calibration error from 0.101 to 0.063. At an 85% confidence threshold, classification accuracy on retained predictions reached 90.8%, while deferral captured 83.3% of all baseline errors. The documentation module generated structured wound notes for all test images. External validation yielded macro-AUC-ROC of 0.809 and macro F1 score of 0.590. At the same 85% threshold, accuracy on retained predictions was 72.7%.
    CONCLUSIONS: Selective deep learning with calibrated confidence improved the reliability of automated pressure injury staging by deferring uncertain predictions while generating structured wound documentation. Future work should evaluate prospective clinical deployment to better assess generalizability and workflow integration.
    IMPLICATIONS FOR CLINICAL PRACTICE: A selective deep learning system that reports calibrated confidence and defers uncertain cases may support clinicians in pressure injury staging while maintaining human oversight. Automated generation of structured wound documentation may also help standardize reporting and reduce documentation burden.
    Keywords:  Artificial intelligence; Calibration; Clinical decision support; Deep learning; Pressure injury; Selective prediction; Wound documentation
    DOI:  https://doi.org/10.1016/j.iccn.2026.104466
  45. Poult Sci. 2026 Jun 12. pii: S0032-5791(26)00920-X. [Epub ahead of print]105(9): 107289
    Synergistic effects of two bacteriophages with distinct infection patterns and broad host specificity against multidrug-resistant Salmonella Typhimurium and their potential applications in the poultry industry.
    Youbin Choi, Jeongkuk Park, Anna Kang, Eunsol Seo, Daniel Junpyo Lee, Seon-Hui Son, Ki Beom Jang, Woo Kyun Kim, Darae Kang, Younghoon Kim.
      Controlling Salmonella Typhimurium in poultry requires effective alternatives to conventional antimicrobials. This study evaluated the efficacy of a two-phage cocktail composed of S. Typhimurium-infecting phages SLAM_phiST45 and SLAM_phiST56 and investigated its mechanistic basis. Host-range profiling of 61 phages against 10 S. Typhimurium strains revealed two major host-associated clusters (swine-human vs. poultry). Notably, the cocktail exhibited broad host ranges that crossed these clusters. The cocktail showed clear synergy, supported by complementary receptor usage and reduced emergence of phage-resistant mutants. In egg-based food application assays, the cocktail achieved rapid bacterial suppression even at an MOI of 1 and fully eliminated S. Typhimurium under refrigerated conditions. In a chick infection model, the cocktail improved growth performance, reduced intestinal and systemic bacterial loads, alleviated intestinal lesions, and restored inflammatory and barrier-related gene expression. While the overall gut microbiota structure remained stable, subtle alterations in low-abundance taxa indicated that phage treatment may cause minor off-target shifts. Overall, this study demonstrates that the phage cocktail is a potent and practical biocontrol tool capable of reducing Salmonella in both food matrices and live birds. These findings support its application in poultry production and highlight the importance of monitoring microbiome-level impacts in future phage-based interventions.
    Keywords:  Bacteriophage cocktail; Broad host range; Distinct infection mechanisms; Poultry industry; Salmonella Typhimurium
    DOI:  https://doi.org/10.1016/j.psj.2026.107289
  46. J Nurs Scholarsh. 2026 Jul;58(4): e70106
    Hospital-Based Robotic Applications in Nursing Practice: A Scoping Review.
    Yebin Kim, Su In Jung, Seonyeong Woo, Earom Lim.
       INTRODUCTION: The integration of robots into clinical practice requires careful consideration of their alignment with nursing workflows, patient needs, and clinical contexts. This scoping review aimed to support effective technology adoption by systematically identifying and classifying how robots are used in hospital-based nursing practice using standardized nursing terminology.
    DESIGN: A scoping review following Arksey and O'Malley's five-stage framework.
    METHODS: A structured search was conducted in five peer-reviewed databases (PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE) for studies published between January 2019 and July 24, 2025. The data were analyzed to classify the types of nursing tasks supported by the robots. Robotic functions were classified into direct care, indirect care, and associated work using standardized nursing terminology, Hurst's framework, and the Clinical Care Classification system to provide a codified and structured analysis of nursing tasks.
    RESULTS: A total of 40 studies were included in the final review. Thirty-three focused on direct care with robots, primarily supporting psychological, physiological, and functional care. The key interventions included coping support, emotional support, infection control, and vital sign monitoring. Only one study involved indirect care, and nine focused on associated work, such as errands and cleaning.
    CONCLUSIONS: Robots are primarily used for direct care, such as emotional support and monitoring, while their role in indirect care-requiring professional judgment including documentation-remains limited. This suggests that future development should prioritize user-centered designs and ethical guidelines aligned with actual clinical needs. Properly implemented robotic technology will serve as a strategic tool to enhance nursing efficiency and improve practice environments amidst chronic workforce shortages.
    CLINICAL RELEVANCE: By categorizing robotic functions using standardized nursing terminology, this review offers a structured understanding of how robots can support nursing. These insights help identify tasks that can be delegated to robots during crises, such as pandemics or staffing shortages, allowing nurses to focus on essential patient care.
    Keywords:  nursing; nursing informatics; nursing intervention; robotics; standardized nursing terminology; technology implementation; workload
    DOI:  https://doi.org/10.1111/jnu.70106
  47. Int Wound J. 2026 Jun;23(6): e70978
    Burn Wound Infections With Staphylococcus aureus: Clinical Characteristics and Risk Factors for Methicillin-Resistant Strains.
    Xiaolan Hong, Shaobo Zhou, Qinghua Cai, Yuanyuan Cai, Zhaohong Chen, Wanting Zhao, Yongjian Ye, Xubo Dai.
      This study aimed to systematically delineate the clinical characteristics and identify the key risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) infections in burn patients, thereby informing targeted preventive measures and therapeutic strategies. This retrospective study included 270 burn patients with Staphylococcus aureus (S. aureus) infections at a Chinese centre (2019-2022), comprising 127 MRSA and 143 methicillin-susceptible S. aureus (MSSA) cases. Clinical data were analysed to assess infection profiles, resistance patterns and MRSA risk factors. Amongst the infections, 68.1% (184/270) were caused by multi-drug resistant S. aureus, specifically 47.0% (127/270) by MRSA and 21.1% (57/270) by MSSA. The predominant resistance pattern (penicillin, oxacillin, gentamicin, clindamycin, erythromycin, ciprofloxacin, levofloxacin, tetracycline) accounted for 23.9% (44/184) of multidrug-resistant cases. The overall MRSA detection rate was 47.0% (127/270). Univariate analysis identified multiple factors significantly associated with MRSA infection (p < 0.05). Multivariate analysis identified the use of ≥ 3 types of antibiotics as an independent risk factor for MRSA infection in burn wounds. The detection rate of multi-drug resistant S. aureus (including MRSA) infections in burn wounds is relatively high. A number of variables are the influencing factors for MRSA infections. Medical personnel should adopt infection control measures to block the transmission of multi-drug resistant bacteria (including MRSA).
    Keywords:  burn wound infection; infection control; methicillin‐resistant S. aureus; multidrug‐resistant; risk factors
    DOI:  https://doi.org/10.1111/iwj.70978
  48. Sci Rep. 2026 Jun 18.
    Uropathogenic profiles and antibiotic resistance in gynecological cases: a microbial surveillance study from Northeast India.
    Julie Bania, Vishal Chakraborty, Archita Limboo, Ritusmita Deori, Amlan Das, Rupesh Kumar.
      Urinary tract infection (UTI) is one of the most common bacterial infections affecting women worldwide. This study investigated bacterial diversity, associated risk factors, and multidrug resistance (MDR) patterns among Gynecological patients in the northeastern region of India. A total of 896 participants were enrolled in the study. Midstream urine specimens were collected and processed using standard microbiological procedures to confirm infection. Antimicrobial susceptibility testing was performed in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines, 2022. Of the 896 participants, 278 (31.02%) were microbiologically confirmed as UTI-positive. Significant associations were observed between UTI prevalence and several risk factors, including age 18-39 years (OR 2.14, p < 0.001), previous history of UTI (OR 7.81, p < 0.001), hypertension (OR 2.75, p < 0.001), prior antibiotic use (OR 2.99, p < 0.001), and pregnancy (OR 1.96, p < 0.001). The most prevalent pathogens were Escherichia coli (62.5%) and Klebsiella pneumoniae (16.9%). Notably, E. coli, K. pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa demonstrated high resistance to fluoroquinolones, nalidixic acid, ampicillin, and cephalosporins. In contrast, these isolates showed higher susceptibility to fosfomycin, amikacin, gentamicin, ertapenem, and piperacillin/tazobactam. The findings highlight region-specific antimicrobial resistance trends and underscore the need for targeted antibiotic stewardship policies, continuous surveillance, and routine integration of microbiological testing into Gynecological practice to optimize treatment outcomes and curb the spread of resistant pathogens.
    Keywords:  Antibiotic resistance; Gynecological infections; Northeast India; Pathogens; Urinary tract infection; Urinary tract infections (UTIs); Uropathogenic
    DOI:  https://doi.org/10.1038/s41598-026-57947-8
  49. Synth Syst Biotechnol. 2026 Dec;14 459-470
    Engineered bacteria in disease diagnosis and therapy: A synthetic biology perspective.
    Yan Shen, Si-Ming Lu, Long Yang, Yang Li, Yu Zhang, Li-Guo Liang.
      Synthetic biology is an interdisciplinary field that integrates knowledge and techniques from modern biology and many other disciplines to design and construct novel biological systems or to modify existing life forms. Its core technologies include gene editing (e.g., CRISPR/Cas9), DNA assembly, in vivo directed evolution, and integration with artificial intelligence. The development of these technologies has greatly advanced the application of synthetic biology in medicine. In disease diagnosis, engineered bacteria have shown considerable promise. They can be designed to sense disease-specific signals and produce detectable reporter outputs, thereby establishing new paradigms for early diagnosis and real-time disease monitoring. For example, bacteria engineered via synthetic biology have been developed as "living sensors" to detect disease biomarkers. In therapeutic applications, synthetic biology offers a fresh perspective on using microorganisms to treat diseases. Researchers can design and construct microorganisms with tailored functions for targeted drug delivery, immunotherapy, and microbiome modulation. These applications not only improve the precision and efficacy of treatments but also offer innovative solutions to overcome the limitations of conventional therapeutic approaches. However, despite their considerable potential, the clinical translation of engineered bacteria still faces numerous challenges, such as ensuring stable in vivo colonization, controlling immunogenicity, standardizing large-scale production, and establishing robust regulatory and ethical frameworks. This review summarizes engineering strategies aimed at enhancing the safety and efficacy of bacterial therapies, with the goal of optimizing bacterial functions and expanding their potential in diagnostics and precision medicine.
    Keywords:  CRISPR-Cas systems; Disease diagnosis; Engineered bacteria; Microbial therapeutics; Synthetic biology
    DOI:  https://doi.org/10.1016/j.synbio.2026.04.028
  50. Curr Microbiol. 2026 Jun 19. pii: 439. [Epub ahead of print]83(8):
    From Health to Disease: A Comprehensive Review of Ocular Surface Microbiota and Detection Methods in Dry Eye.
    Mengzhen Xie, Ying Jie.
      Dry eye disease (DED) is a prevalent and multifactorial condition that significantly impacts the ocular surface, characterized by symptoms of discomfort, visual disturbance, and tear film instability. Recent research has increasingly focused on the ocular surface microbiome (OSM) and its potential role in the pathogenesis and progression of DED. The OSM consists of a diverse community of microorganisms, including bacteria, fungi, and viruses, that interact with the host to maintain ocular surface health. Dysbiosis, or the imbalance of these microbial communities, has been linked to various ocular surface disorders, including DED. This review comprehensively summarizes the current understanding of the differences in OSM between healthy individuals and patients with different types of DED, such as aqueous-deficient dry eye, evaporative dry eye, and DED associated with autoimmune conditions. Additionally, it explores the detection methods used to study the OSM, highlighting the strengths and limitations of culture-based approaches, 16 S rRNA sequencing, metagenomic shotgun sequencing, and emerging technologies like 2bRAD-M. The review also outlines future research directions, emphasizing the need for advanced multi-omics approaches, personalized microbiome-based therapies, and longitudinal studies to further elucidate the role of the OSM in DED. By enhancing our understanding of the OSM composition and function, these insights may lead to innovative diagnostic and therapeutic strategies for managing DED.
    DOI:  https://doi.org/10.1007/s00284-026-05011-z
  51. BioDrugs. 2026 Jun 15.
    Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.
    Matthew J Slarve, Christine Tkaczyk, Michael P Doyle, Timothy J Break, Alexander B Smith, Galit Alter, Brian Luna, Brad Spellberg, Antonio DiGiandomenico.
      The ever-increasing trend of antibiotic resistance necessitates new therapeutic strategies for fighting infection. Standing on decades of extensive research and development, monoclonal antibodies have great promise for treating antibiotic-resistant bacterial infections. In this comprehensive review of the field, we summarize the rapidly emerging field of monoclonal therapeutics that offer alternative approaches to target bacterial pathogens that pose critical concern to human health. Organizing the findings by species and by molecular target, we discuss antibodies that have demonstrated therapeutic potential as well as those that did not provide efficacy, highlighting new insights for the design and discovery of highly effective therapeutics for the future. Furthermore, we discuss the latest advances in molecular biology that have revolutionized the implementation, efficacy, and utility of monoclonal antibodies as therapeutics, and that continues to drive what will be an exciting era for antibacterial monoclonal antibodies.
    DOI:  https://doi.org/10.1007/s40259-026-00787-9
  52. Adv Skin Wound Care. 2026 Jul 01. 39(6): E276-E285
    Barriers to Self-Management of Patients with Diabetic Foot Ulcers: A Systematic Review and Qualitative Meta-Synthesis.
    Qin Liu, Lei Shi, Jin Wang, Huiren Zhuang.
       OBJECTIVE: To synthesize qualitative research on self-management among patients with diabetic foot ulcers (DFUs) to provide insights and recommendations for enhancing self-management interventions.
    DATA SOURCES: A comprehensive search of PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, WanFang, and VIP databases was conducted through August 15, 2024.
    STUDY SELECTION: Studies were selected based on the PICo-D model; P (Population) was patients with DFUs, I (Interest) was barriers to self-management, Co (Context) was the patient's life following a DFU diagnosis, and D (Design) was qualitative or mixed-method studies. Exclusion criteria included duplicate publications, unavailable full text, and literature published in languages other than Chinese or English.
    DATA EXTRACTION: Two researchers independently screened, assessed quality, and extracted data. Discrepancies were resolved by discussion or a third reviewer. Extracted data included authors, year, country, methodology, sample size, phenomenon of interest, and key findings.
    DATA SYNTHESIS: A meta-synthesis approach integrated findings from 14 studies with 256 participants. Barriers to DFU self-management were grouped into eight themes: (a) cognitive factors (eg, lack of knowledge, information processing, decision-making abilities, self-efficacy); (b) emotional factors; (c) behavioral factors (eg, behavioral habits, adherence); (d) social factors (eg, social resources, social support); (e) economic factors; (f) environmental factors (eg, living environment, environmental support); (g) policy factors (eg, policy support, resource allocation, regulatory restrictions); and (h) cultural factors (eg, cultural identity, traditional beliefs).
    CONCLUSIONS: Patients with DFUs face multiple barriers to effective self-management. Health care providers should focus on enhancing health education, providing psychological support, fostering a supportive environment, and implementing personalized interventions to improve patients' self-management abilities and strengthen their overall prognosis.
    Keywords:  diabetes; diabetic foot ulcers; meta-synthesis; qualitative research; self-management
    DOI:  https://doi.org/10.1097/ASW.0000000000000469
  53. Int Wound J. 2026 Jun;23(6): e70981
    Sinuhe Classification for Pretibial Injuries: Categorising Dermatoporotic Wounds.
    Toni Seppälä, Vahur Grünthal, Virve Koljonen.
      Pretibial injuries manifest as lacerations or haematomas. Despite differences in pathogenesis and treatment, these entities have been mixed together in previous classifications. No classification for pretibial haematomas exists, and the Modified Dunkin Classification includes a Type V category that conflates lacerations with haematomas. To present the Sinuhe Classification-a comprehensive system categorising pretibial lacerations and haematomas with evidence-based treatment recommendations-and propose the umbrella term 'dermatoporotic wounds' to encompass the full spectrum of cutaneous injuries arising from chronic skin fragility. A narrative literature review of PubMed, MEDLINE and EMBASE was conducted. Treatment recommendations and clinical findings were synthesised from the available literature, including a doctoral thesis on pretibial injuries. The Sinuhe Classification categorises pretibial lacerations into linear lacerations; flap lacerations (vital, i.e., with adequate perfusion and non-vital, i.e., with flap necrosis); and total skin loss. Pretibial haematomas are classified into open (ruptured), closed and necrotic haematomas. Each subtype is paired with specific treatment guidance. The classification eliminates the Modified Dunkin Type V category and provides a classification framework for pretibial haematomas. The Sinuhe Classification offers a unified yet distinct framework for diagnosing and treating pretibial injuries. Adoption into clinical practice and medical education is recommended.
    Keywords:  chronic leg ulcers; classification; dermatoporosis; dermatoporotic wounds; pretibial haematomas; pretibial injuries; pretibial lacerations; wound management
    DOI:  https://doi.org/10.1111/iwj.70981
  54. BMC Oral Health. 2026 Jun 15.
    Immunomodulation as a novel treatment strategy for periodontal disease: a systematic review.
    Fariad Akbar, Marta Czesnikiewicz-Guzik.
       BACKGROUND: Periodontal diseases (PDs) are globally prevalent and are associated with reduced quality of life and systemic health complications. Conventional therapy, involving professional mechanical plaque removal (PMPR) and oral hygiene instruction, faces limitations involving disease recurrence and patient factors. This systematic review explores immunomodulatory therapies as alternative or adjunctive treatments.
    METHOD: MEDLINE (Ovid), EMBASE (Ovid), Cochrane Database of Systematic Reviews and MEDLINE (Web of Science) databases were searched on 9 June 2024. Two authors independently screened the articles using pre-specified inclusion and exclusion criteria, and findings were grouped by immunomodulatory agent.
    RESULTS: The search retrieved 2363 records, and 42 were included. Thirteen types of immunomodulatory agents were evaluated across cell lines, animal models of PD, and observational studies and clinical trials in humans. Several agents showed evidence of effects on inflammation and alveolar bone loss; however, the quality and consistency of evidence varied. Limited data suggest that longer treatment duration, alternative delivery methods, or combination approaches may enhance therapeutic outcomes.
    CONCLUSION: Immunomodulatory agents show promise for the management of PD, including in patients with co-morbidities. However, clinical evidence in the context of conventional therapy and safety data remain limited. Further rigorous trials are needed to confirm efficacy, optimise treatment, and evaluate long-term safety before these therapies can be incorporated into routine clinical practice.
    Keywords:  Gingivitis; Immunomodulation; Periodontal Diseases; Periodontal therapy; Periodontitis
    DOI:  https://doi.org/10.1186/s12903-026-08120-0
  55. Int Dent J. 2026 Jun 19. pii: S0020-6539(26)00284-4. [Epub ahead of print]76(4): 109691
    The Impact of Dental Prostheses in Patients With Cardiovascular Disease: A Scoping Review With Exploratory Analysis.
    Monika Werdiningsih, En-Chih Weng, Yoko Hasegawa, Ma Therese Sta Maria, Kazuhiro Hori, Yasuyuki Nagasawa, Ken Shinmura.
      Dental prostheses not only restore oral function but may also impact systemic health outcomes. This scoping review sought to synthesize evidence on the association between dental prostheses, hypertension, and physical function, including frailty, in adults with established cardiovascular disease (CVD) or elevated cardiovascular risk. This review was conducted following the PRISMA-ScR guidelines and Joanna Briggs Institute methodology. Literature searches were performed in PubMed and Google Scholar up to November 10, 2024. Eligible studies were observational investigations involving adults with established CVD or elevated cardiovascular risk who used dental prostheses. An exploratory quantitative approach was used to summarize the direction and patterns of association. Seven studies met the inclusion criteria: 5 assessed hypertension and 2 examined physical function. Exploratory pooled analysis based on unadjusted data indicated that individuals with dental prostheses had a lower odds of hypertension (odds ratio = 0.69; 95% confidence interval, 0.52-0.91), although substantial heterogeneity (I² = 95%) and the use of unadjusted estimates imply a high risk of residual confounding. Limited evidence suggests that dental prosthesis use may help preserve mobility and mitigate frailty in patients with CVD; however, differences in frailty definitions and limited adjustment for confounding factors reduce comparability and indicate that these findings should be interpreted as exploratory and hypothesis-generating. Current evidence suggests that dental prosthesis use may offer benefits beyond oral rehabilitation, potentially linked to better hypertension-related outcomes and physical function in adults with CVD or elevated cardiovascular risk, but certainty is limited by the small number of studies and methodological heterogeneity. These exploratory, hypothesis-generating findings highlight the need for well-designed longitudinal studies to clarify potential associations and underlying mechanisms. Beyond restoring oral function, prosthodontic rehabilitation may have broader systemic implications, contributing to better cardiovascular-related outcomes in aging populations.
    Keywords:  Cardiovascular disease; Dental prostheses; Frailty; Hypertension; Physical function
    DOI:  https://doi.org/10.1016/j.identj.2026.109691
  56. Int J Low Extrem Wounds. 2026 Jun 16. 15347346261459556
    Er:YAG laser Therapy for Diabetic Foot Ulcers: A Pilot Study with Hyperspectral Imaging Assessment.
    Sebastián Flores-Escobar, Francisco Javier Álvaro-Afonso, Yolanda García-Álvarez, Mateo López-Moral, Irene Sanz-Corbalán, José Luis Lázaro-Martínez.
      Diabetic foot ulcers (DFU) are associated with impaired wound healing and high morbidity. Er:YAG laser therapy has been proposed as an adjunctive treatment due to its ablative and biostimulatory properties. The aim of this study was to explore the feasibility and preliminary clinical and physiological responses to adjunctive Er:YAG laser therapy in DFUs using hyperspectral imaging (HSI). A pilot study including five patients with DFU was conducted. All patients received Er:YAG laser therapy once weekly for 8 weeks in addition to standard of care. Clinical outcomes included wound area and wound-bed quality assessed using the Wollina wound score. Physiological responses were evaluated using HSI-derived parameters, including tissue oxygen saturation, oxyhemoglobin, deoxyhemoglobin, and total hemoglobin, measured before and after laser treatment sessions. Wound area showed a progressive reduction during follow-up, with a mean percentage wound area reduction of 33.06 ± 44.9% at week 8. Wound-bed condition improved significantly over time, with the Wollina wound score increasing from a median of 5 at baseline to 7 at week 8 (p = 0.024). HSI analysis demonstrated significant and sustained increases in THb and OxyHb at weeks 4 and 8 compared with baseline values (p < 0.05), indicating improved tissue perfusion and oxygen delivery. These preliminary findings suggest that adjunctive Er:YAG laser therapy was feasible and showed promising improvements in wound-bed quality and perfusion-related HSI parameters, alongside clinically meaningful wound size reduction. HSI appears to be a promising tool for the objective assessment of physiological responses to therapy.
    Keywords:  diabetic foot ulcer; hyperspectral imaging; laser therapy; wound healing
    DOI:  https://doi.org/10.1177/15347346261459556
  57. Transl Pediatr. 2026 May 31. 15(5): 197
    The predictive value of the ratio of multi-dimensional inflammatory biomarkers in pediatric diseases from the perspective of pro-inflammatory/anti-inflammatory balance: a systematic review.
    Xuepeng Chen, Bo Ding, Zixuan Shen, Weicheng Han, Yi Li, Yilu Xie, Kaijing Wang, Yazhou Wang.
       Background: Imbalance of immune homeostasis, particularly the dysregulation of pro-inflammatory/anti-inflammatory balance, is a core pathological mechanism in many acute and chronic pediatric diseases. Traditional single inflammatory biomarkers have limitations in disease prediction, clinical evaluation, and prognostic stratification, as they cannot reflect the overall dynamic balance of the immune network. This systematic review aimed to evaluate the predictive value of multi‑dimensional inflammatory biomarker ratios centered on pro‑inflammatory/anti‑inflammatory balance in pediatric inflammatory diseases, and to clarify their classification and clinical application strategies.
    Methods: We performed this systematic review in accordance with the PRISMA guidelines. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Science and Technology Journal Database databases from database inception to December 31, 2025. Eligible studies were original studies that focused on multi-dimensional inflammatory biomarker ratios in children aged ≤18 years. We excluded animal studies, studies involving only adult populations, low-quality studies, conference abstracts, case reports, and irrelevant correspondence. Two independent reviewers conducted literature screening, data extraction, and methodological quality assessment using standard tools, with 32 articles finally included in this systematic review.
    Results: We categorized multi-dimensional inflammatory biomarker ratios into two classes: Class A [cytokine-based ratios, e.g., interleukin (IL)-6/IL-10, tumor necrosis factor-α (TNF-α)/IL-10, IL-17A/IL-10, IL-1β/IL-1 receptor antagonist (IL-1Ra)], which have high specificity for reflecting molecular immune balance; and Class B (systemic inflammatory ratios derived from routine laboratory tests, e.g., neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Systemic Immune-Inflammation Index, C-reactive protein-to-albumin ratio), which have high accessibility in clinical practice for rapid screening. Compared with single inflammatory biomarkers, these multi-dimensional ratios demonstrated superior predictive performance in disease prediction, severity assessment, and prognosis of pediatric sepsis, Kawasaki disease, juvenile idiopathic arthritis, and pediatric multisystem inflammatory syndrome.
    Conclusions: Multi-dimensional inflammatory biomarker ratios, centered on the pro-inflammatory/anti-inflammatory balance, overcome the limitations of single inflammatory markers. In clinical practice, Class A ratios facilitate precise immune subtyping and targeted therapy, while Class B ratios facilitate early screening and severity stratification of pediatric inflammatory diseases. The combined application of both classes can establish a stratified and precise diagnosis and treatment framework for pediatric inflammatory diseases. Future research should establish pediatric reference ranges for these ratios, conduct large-scale prospective validation studies, and integrate artificial intelligence and point-of-care testing (POCT) technologies to promote the advancement of individualized pediatric care.
    Keywords:  Children; biomarker; cytokine ratio; predictive value; systemic immune-inflammatory index
    DOI:  https://doi.org/10.21037/tp-2026-0189
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