bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–12–14
forty-two papers selected by
Luca Bolliger, lxBio
  1. [Phage therapy for respiratory infections: from experimental evidence to clinical challenge].
  2. Hard to jump: host shifts appear unlikely in a T4-like phage evolved in the lab.
  3. Phage therapy and the microbiome in hematologic malignancies: opportunities, mechanisms, and early evidence.
  4. Harnessing phages to tackle antimicrobial resistance: a Saudi Arabian perspective.
  5. Phage Cocktails: State-of-the-Art Technologies and Strategies for Effective Design.
  6. Steering the course: targeting and exploiting surface receptors in phage therapy.
  7. PBIP: a deep learning framework for predicting phage-bacterium interactions at the strain level.
  8. Comprehensive analysis of phage genomes from diverse environments reveals their diversity, potential applications, and interactions with hosts and other phages.
  9. A bacteriophage genus infects carbapenem resistant Acinetobacter baumannii via a non-capsular receptor and provides protection in vivo.
  10. Phage-mediated control of melioidosis in Southern China: molecular insights and therapeutic potential of N4-like viruses from Hainan.
  11. Extensive cultivation of human gut phages revealing undescribed Bacteroidaceae phages.
  12. Managing malodorous wounds in the community using a structured approach for practice.
  13. Choosing the right wound dressing in community nursing.
  14. Identification of multi-drug resistant Acinetobacter baumannii phage YZ2 and evaluation of its therapeutic efficacy in vivo and in vitro.
  15. Implementation and comparison of two concentration methods to detect and characterize bacteriophages and bacterial hosts from large drinking water samples.
  16. Isolation and characterization of two novel phages with lytic activity against multidrug-resistant Acinetobacter baumannii strains: potential for phage therapy.
  17. Minimal PEGylation Improves Pharmacokinetics, Immunocompatibility, and Efficacy of a Lytic Bacteriophage against Multidrug-Resistant Acinetobacter baumannii.
  18. Characterization and genome analysis of jumbo Escherichia phage UE-S1 and the antibacterial potential of its lysozyme against uropathogenic E. coli.
  19. Bacteriophage genome-wide transposon mutagenesis.
  20. Biological characterization and genome analysis of Pseudomonas phage ZAM-Pa99 as a promising anti-biofilm agent.
  21. Postbiotics as Emerging Therapeutics for Skin Wound Healing and Dermatological Care: Clinical Trends and Mechanistic Insights.
  22. Multifaceted mesoporous silica-based nanoplatform to co-deliver honokiol and baicalin for integrative therapy of drug-resistant bacteria infection.
  23. Emerging antimicrobial hydrogel dressings based on bacterial cellulose-chitosan composites: A review.
  24. What drives bacterial extinction? The role of bacteriophages.
  25. Advances in diabetic wound healing: from pathophysiology to emerging therapies.
  26. Research progress on the use of polyphenols in the treatment of Crohn's disease.
  27. Wounds and the Microbiota: The Healing Interplay Between Host and Microbial Communities.
  28. Exploring Global Research Status and Trends in Necrotizing Fasciitis: A Bibliometric Analysis.
  29. Pediatric saprochaete infections: insights from case reports.
  30. Broad-Spectrum Antimicrobial Treatment Targeted Through Drug Conjugation to Vancomycin.
  31. A Scoping Review of Clinical Trials on the Efficacy of Curcumin and Its Formulations for Wound Healing.
  32. Gut microbiota dysbiosis drives stroke-associated pneumonia: mechanisms and targeted therapeutic strategies.
  33. Educational Perspectives on Compassionate Concussion Care: A Scoping Review.
  34. Ecological strategies of bacteria shape inherent phage diversity in Atlantic salmon gut microbiomes.
  35. Transforming Care Models in Cystic Fibrosis: A Review.
  36. Increased abundance of actinobacteria and upregulation of primary bile acid biosynthesis in diabetic foot ulcers.
  37. Purple Urine Bag Syndrome Caused by Klebsiella pneumoniae in an Elderly Patient: A Case Report.
  38. The Role of the Oral Microbiome in Periodontal Disease: A Systematic Review of Microbial Associations and Therapeutic Implications.
  39. Early shift to oral antibiotic treatment for pyogenic vertebral osteomyelitis (SAVE): study protocol for an open label, non-inferiority, nation-wide randomized controlled clinical trial.
  40. Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon.
  41. An Expert Knowledge Algorithm and Model Predicting Wound Healing Trends for a Decision Support System for Pressure Injury Management in Home Care Nursing: Development and Validation Study.
  42. Digital technology for monitoring adherence to inhaled therapies in people with cystic fibrosis.
  1. Zhonghua Jie He He Hu Xi Za Zhi. 2025 Dec 12. 48(12): 1203-1206
    [Phage therapy for respiratory infections: from experimental evidence to clinical challenge].
    R Y Wang, J Wang, F W Jiao.
      The global rise in antibiotic resistance has created an urgent need for novel antimicrobial strategies. Although phage therapy has recently demonstrated significant potential for treating respiratory infections, yet its widespread adoption remains limited by technical and practical hurdles. This review synthesizes recent advances in phage therapy protocols, evaluates clinical efficacy through case studies, and discusses current challenges. By consolidating the latest evidence, it provides actionable guidance to advance the safe and effective integration of phage therapy into clinical practice.
    DOI:  https://doi.org/10.3760/cma.j.cn112147-20250623-00349
  2. Front Cell Infect Microbiol. 2025 ;15 1597805
    Hard to jump: host shifts appear unlikely in a T4-like phage evolved in the lab.
    Yu Ning, Enrique González-Tortuero, Jeroen Wagemans, Flor I Arias-Sánchez.
       Introduction: Bacteriophage therapy is emerging as a promising alternative to antibiotics, particularly in the face of rising antimicrobial resistance. However, concerns remain regarding host shifts, where therapeutic phages could evolve to infect and harm beneficial commensal bacteria. Understanding how frequently host shifts occur and what evolutionary constraints shape them is critical to assessing the safety of phage therapy.
    Methods: We investigated the evolutionary potential for host shifts using Escherichia coli-infecting phage BW-1. Experimental evolution was conducted under controlled conditions that favored adaptation, using both non-permissive (unable to infect) and semi-permissive (low infectivity) bacterial strains. Virulence was assayed across hosts, and whole-genome sequencing was used to identify mutations associated with adaptation.
    Results: Host shifts were found to be rare, with no significant increases in virulence observed in non-permissive hosts. In contrast, adaptation occurred in semi-permissive hosts and was linked to trade-offs, where increased virulence in one host reduced infectivity in others. Whole-genome sequencing revealed a single convergent regulatory SNP across all phages adapted to the semi-permissive host, indicating constrained evolutionary pathways during host adaptation.
    Discussion: Our findings suggest that phages exhibit high host specificity, which limits the risk of host shifts to commensal bacteria. Although adaptation to semi-permissive hosts is possible, it is constrained and associated with fitness trade-offs across host ranges. These results indicate that therapeutic phages are unlikely to negatively impact intestinal microbiota, supporting their potential as safe and effective alternatives to antibiotics.
    Keywords:  host shifts; infection; phage therapeutics; phage therapy; virulence
    DOI:  https://doi.org/10.3389/fcimb.2025.1597805
  3. J Cancer Res Clin Oncol. 2025 Dec 12. 152(1): 8
    Phage therapy and the microbiome in hematologic malignancies: opportunities, mechanisms, and early evidence.
    Juanwen Zhang, Jin Liu, Alireza Bayani.
      Hematologic malignancies remain among the most difficult cancers to treat, challenged by profound heterogeneity, treatment-induced immune dysfunction, and the frequent emergence of drug resistance. Beyond tumor-intrinsic mechanisms, dysbiosis of the gut microbiome is increasingly recognized as a critical determinant of therapeutic outcomes, shaping hematopoiesis, immune responses, and drug metabolism. Bacteriophage (phage) therapy has re-emerged as a precision tool capable of selectively eradicating pathogenic taxa while preserving commensal short-chain fatty acid-producing communities. Preclinical and early human studies demonstrate that phages can recalibrate microbial ecosystems, disrupt antibiotic-tolerant biofilms, and enrich metabolites such as butyrate that support mucosal integrity and immune balance. Mechanistically, phage DNA enriched with CpG motifs engages Toll-like receptor 9, activating dendritic cells and enhancing cytotoxic T lymphocyte responses, suggesting dual benefits in infection control and anti-tumor immunity. Emerging applications extend further, with engineered phages serving as vectors for CRISPR-Cas gene editing, targeted cytokine delivery, and nanocarrier platforms for leukemia therapy. Despite translational promise, major hurdles persist, including immunogenicity, horizontal gene transfer, resistance evolution, and regulatory uncertainty. Addressing these challenges through GMP-compliant manufacturing, metagenomics-guided personalization, and AI-optimized cocktail design could establish phage therapy as a microbiome-informed adjunct to overcome drug resistance in blood cancers. However, direct clinical evidence of phage therapy efficacy in hematologic malignancies remains limited, and current data are largely derived from preclinical and compassionate-use contexts.
    Keywords:  CRISPR–Cas gene delivery; Gut microbiome dysbiosis; Hematologic malignancies; Phage therapy; Short-chain fatty acids (SCFAs)
    DOI:  https://doi.org/10.1007/s00432-025-06393-6
  4. Front Cell Infect Microbiol. 2025 ;15 1702890
    Harnessing phages to tackle antimicrobial resistance: a Saudi Arabian perspective.
    Alhassan Alrafaie.
      The worldwide antimicrobial resistance (AMR) threat continues to grow, causing an estimate of 4.71 million deaths during 2021. Scientists predict it could lead to 10 million deaths each year by 2050 unless effective solutions are developed. The government of Saudi Arabia implemented the AMR Action Plan (2022-2025) and participated in the 4th Global High-Level Ministerial Conference on AMR (2024) to address this issue. However, ESBL-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii remain major threats in Saudi Arabia. Bacteriophage therapy offers a promising additional treatment approach as phages specifically attack bacteria. They also evolve and demonstrate effectiveness against bacteria that form biofilms. This review evaluates Saudi Arabia's readiness for phage-based therapy implementation through an analysis of both local and worldwide antibiotic resistance data.
    Keywords:  Saudi Arabia; antibiotic; antimicrobial resistance; bacteriophage; phage therapy
    DOI:  https://doi.org/10.3389/fcimb.2025.1702890
  5. FEMS Microbiol Rev. 2025 Dec 08. pii: fuaf061. [Epub ahead of print]
    Phage Cocktails: State-of-the-Art Technologies and Strategies for Effective Design.
    Tomoyoshi Kaneko, Kanata Nakatsuka, Satoshi Tsuneda.
      With the growing severity of antimicrobial resistance (AMR), phage therapy has garnered attention as a novel therapeutic alternative. In particular, phage cocktails, which combine multiple phages, potentially offer broader antimicrobial spectra than single-phage applications and may suppress the emergence of resistant bacteria. This comprehensive review systematically examines cutting-edge technologies and effective strategies for designing phage cocktails. Special attention was given to the combination of phages recognizing different receptors, designs based on phage-bacteria infection network analysis, and synergistic effects with antibiotics. Additionally, the analysis of large-scale clinical studies has identified challenges in practical implementation, including ensuring cocktail stability and addressing immune responses. These insights are expected to contribute to the design of more effective phage cocktails and the establishment of novel therapeutic strategies to address AMR.
    Keywords:  AMR; Bacteriophage; Clinical application; ESKAPE; Phage cocktail; Phage resistance; Phage therapy
    DOI:  https://doi.org/10.1093/femsre/fuaf061
  6. J Bacteriol. 2025 Dec 08. e0037525
    Steering the course: targeting and exploiting surface receptors in phage therapy.
    Veronica N Tran, Lori L Burrows.
      The global rise of antibiotic resistance highlights the urgent need for alternative therapeutics such as bacteriophages (phages). Phages exert selective pressure that can "steer" bacteria toward reduced pathogenicity, increased antibiotic susceptibility, or immune clearance. A receptor-focused steering strategy is especially powerful since many phage receptors are also critical for bacterial fitness and virulence. Effective therapy requires identifying these receptors during characterization and combining phages that target distinct, conserved structures to minimize resistance. We review the current state of phage steering research and highlight guidelines emphasizing receptor identification for rational, durable therapeutic design. While this review focuses on P. aeruginosa, the findings and implications can be extended to other multi-drug resistant pathogens.
    Keywords:  Pseudomonas aeruginosa; bacteriophage; cell surface
    DOI:  https://doi.org/10.1128/jb.00375-25
  7. Brief Bioinform. 2025 Nov 01. pii: bbaf656. [Epub ahead of print]26(6):
    PBIP: a deep learning framework for predicting phage-bacterium interactions at the strain level.
    Lijia Ma, Peng Gao, Gufeng Liu, Yuan Bai, Qiuzhen Lin, Jianqiang Li, Minfeng Xiao.
      Phage therapy has received great attention as a promising antimicrobial treatment, and its core technique, namely predicting phage-bacterium interactions (PBIs), is crucial for understanding infection mechanisms and optimizing therapeutic strategies. However, existing computational methods mainly focus on the species or higher taxonomic levels, and usually neglect the potential of deep embedding representations, limiting their ability to capture complex biological patterns inherent in sequences. This hinders the discovery of rich sequence features, and restricts the clinical application of phage therapy. To address these limitations, we propose a novel deep learning framework (called PBIP) for strain-level PBI prediction. In PBIP, we first identify strain-level interactions through biological infection experiments and sequencing of Klebsiella pneumoniae isolated from the clinical environment of Xiangya Hospital. Then, we utilize a pretrained unified representation model to convert protein sequences of phages and bacteria into deep embeddings. Next, we apply the synthetic minority oversampling technique to generate positive interactions in the embedding space to address the data imbalance issue. Subsequently, we design a deep neural network that uses a convolutional neural network to extract local features, a bi-directional gated recurrent unit to capture global features, and an attention module to highlight significant features. Finally, a fully connected layer integrates this information for PBI prediction. Experimental results show the superiority of PBIP over the state-of-the-art methods in predicting PBIs. The code and datasets are available at https://github.com/a1678019300/PBIP.
    Keywords:  attention mechanism; deep learning; phage–bacterium interactions; protein representation learning
    DOI:  https://doi.org/10.1093/bib/bbaf656
  8. Front Microbiol. 2025 ;16 1686402
    Comprehensive analysis of phage genomes from diverse environments reveals their diversity, potential applications, and interactions with hosts and other phages.
    Chao Wei, Zhe Chen.
      Phages are ubiquitous and diverse, playing a key role in maintaining microbial ecosystem balance. However, their diversity, potential applications, and their interactions with hosts and other phages remain largely unexplored. To address this, we collected 59,652,008 putative viral genomes from our laboratory, 45 public viral datasets, and an integrated public viral genome database (IGN), covering seven habitats. We obtained 741,692 phage genomes with completeness ≥50% (PGD50), and most (93.83%, 695,938/741,692) of these phage genomes were classified into the Caudoviricetes class. We found that 158,522 species-level viral clusters that contained 28.96% (214,814/741,692) phage genomes without any known phage genomes in the IGN, indicating substantial novelty. Global phylogenetic trees for five iterations based on complete phage genomes significantly expanded the known diversity of the virosphere. Genome analysis revealed phage potential divergence with habitat types and highlighted the utilization of alternative genetic codes. Furthermore, 3D structural similarity searches demonstrated significant potential for annotating previously uncharacterized viral proteins. Analysis of CRISPR spacer inferred potential hosts of phages and competitive networks among phages, highlighting virulent phages as promising candidates for phage therapy against pathogenic bacteria. Intriguingly, diverse CRISPR-Cas systems were detected within phage genomes themselves, suggesting their enormous potential as novel gene editing tools. Collectively, this study provides a comprehensive phage genome resource, foundational for future research into phage-host and phage-phage interactions, phage therapy development, and the mining of next-generation genetic tools.
    Keywords:  diverse CRISPR-Cas systems; diverse environments; phage diversity; phage–phage interactions; potential applications
    DOI:  https://doi.org/10.3389/fmicb.2025.1686402
  9. iScience. 2025 Dec 19. 28(12): 114026
    A bacteriophage genus infects carbapenem resistant Acinetobacter baumannii via a non-capsular receptor and provides protection in vivo.
    Patrick O Kenney, Krushe Mundru, Hakimuddin Sojar, Nelli Kisliuk, Roy Miller, John Richter, Ulrike Carlino-MacDonald, Ting L Luo, Francois Lebreton, Patrick T McGann, Oscar G Gómez-Duarte, Thomas A Russo.
      Extensive drug resistance (XDR) in Acinetobacter baumannii and other pathogens has revitalized bacteriophage as a therapeutic consideration. Six phages (AB1I1L, AB1I1M, AB1I1P, AB1I1T, AB2I2, and AB2I3) targeting A. baumannii were isolated from wastewater. These represent a previously undescribed phage genus with rapid adsorption and potent lysis. 18/40 A. baumannii clinical isolates, including 11/27 carbapenem-resistant isolates, were susceptible to one of the isolated phages. Importantly, in vitro-derived, phage resistant bacteria were killed in human ascites, demonstrating decreased biofitness. In contrast to most described phages that target A. baumannii, the bacterial capsule is not the primary receptor. Capsule impedes phage activity in vitro. The treatment of an XDR isolate using phage monotherapy in a rat subcutaneous abscess model showed dose-dependent efficacy, though a higher sustained concentration of phage was needed when compared with in vitro conditions. These phages are potential candidates for phage therapy, warranting additional preclinical evaluation as adjunctive treatment for A. baumannii infections.
    Keywords:  Microbiology; Virology
    DOI:  https://doi.org/10.1016/j.isci.2025.114026
  10. BMC Microbiol. 2025 Dec 11.
    Phage-mediated control of melioidosis in Southern China: molecular insights and therapeutic potential of N4-like viruses from Hainan.
    Shen Tian, Jiaxin Deng, Dai Kuang, Meiping Lv, Qiao Zhu, Nan Zhang, Wei Liu, Jiling Yi, Qianfeng Xia, Yanshuang Wang.
       BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, is a tropical disease that poses a serious risk of fatal sepsis and imposes a substantial financial burden on healthcare systems, driven by its complicated antibiotic resistance profile. With the successful isolation of vB_BpP_HN01 in Hainan, a theoretical basis for phage therapy has been established. Whilst the observation of certain clinical isolates non-susceptible to its infection, along with concerns about the potential emergence of tolerance during monophage treatment, highlights the urgent need to develop a broader and more diverse phage arsenal.
    METHODS: Phage screening was performed on environmental samples collected at sites geographically distinct from the original isolation location via B. pseudomallei HNBP001, a Hainan representative strain previously employed as the isolation host. Candidates characterized by host range and plaque properties were subjected to assays assessing environmental stability, infection and proliferation traits. Genetic features were analyzed by sequencing and comparative bioinformatics, followed by efficacy evaluation in A549 cell infection assays and Galleria mellonella larvae. Statistical analyses included one-way ANOVA and Kaplan-Meier survival curves with log-rank tests.
    RESULTS: A total of four podoviruses (vB_BpP_HN02 - HN05), with highly efficient (≥ 92%) and complementary lytic activities, were recovered from natural sources in Wenchang and Qiongzhong. Each exhibited distinct plaque morphology and robust viability, although compromised by exposure to high temperatures (≥ 60 °C) or extremely acidic conditions (pH ≤ 3). Highest titer production was demonstrated in vB_BpP_HN02 and vB_BpP_HN05 (2.5 × 10¹⁰ and 1.0 × 10¹¹ PFU/mL at optimal multiplicities of infection of 0.1 and 1, respectively), whilst complete bacterial clearance was achieved by the former. Genomic analysis classified them into the Schitoviridae family, sharing conserved N4-like architecture. Phage treatments restored the viability of infected A549 cells from 29.29% to 60.07-75.81%, with vB_BpP_HN02 displaying superior bactericidal capacity, even against the ceftazidime-resistant strain, further supported in the G. mellonella model, albeit modestly under single-dose administration.
    CONCLUSIONS: As a continuation of our previous work, the identification of these phages addresses the natural occurrence of vB_BpP_HN01-insensitive strains and enhances understanding of B. pseudomallei phage diversity in Hainan. However, owing to close genetic similarity, cocktail formulation remains unfeasible, warranting further efforts to isolate more diverse novel phages.
    Keywords:  Burkholderia pseudomallei; Melioidosis; N4-like podovirus; Phage
    DOI:  https://doi.org/10.1186/s12866-025-04588-y
  11. Gut Microbes. 2025 Dec 31. 17(1): 2597614
    Extensive cultivation of human gut phages revealing undescribed Bacteroidaceae phages.
    Zhe Liu, Yaoyu Yang, Sihong Mao, Zhaoqi Wang, Qiheng Zhu, Yuyu Yuan, Ye Xiang.
      The isolated and characterized gut phages remain rare. Most of the gut phages that have been isolated and propagated thus far are lytic phages, leaving significant gaps in the study of gut temperate phages. In this study, we successfully isolated a large-scale collection of gut bacteria and phages, containing 1,679 bacterial strains from 86 species and 79 phages that infect bacteria from 26 different species. Among the phage isolates, 32 are temperate phages and two of these temperate phages were directly isolated from faecal samples of healthy human donors. Sequence comparisons and analysis show that the isolated temperate phages are characterized with highly diverse genomes and significantly higher prevalence in the human gut when compared with these characterised lytic gut phages. Further analysis shows that most of these temperate phages contain unique diversity-generating retroelements (DGRs) and may have a broad host range. Additionally, by combining sequence and structural similarity we developed a pipeline that can significantly enhance the annotation rate of our gut phage genomes. The annotation pipeline helps to identify a candidate phage family, "Bacteroiduroviridae", that diverged from other bacteriophages early in the evolutionary process.
    Keywords:  Gut bacteria; diversity-generating retroelements (DGRs); genome annotation; gut phage; temperate phage
    DOI:  https://doi.org/10.1080/19490976.2025.2597614
  12. Br J Community Nurs. 2025 Dec 01. 30(Sup12): S22-S30
    Managing malodorous wounds in the community using a structured approach for practice.
    Jackie Stephen-Haynes.
      Malodour is a potentially distressing complication of chronic wounds, and it is one that is frequently managed within community settings. Malodorous wounds are primarily caused by anaerobic bacterial colonisation and sloughy or necrotic tissue. Malodorous wounds are frequently a challenge to the clinician as well as the patient, their family members and carers. They have a significant impact on overall wellbeing, sleep, social interactions, diet and, potentially, wound healing. Understanding the cause of malodorous wounds, alongside developing assessment and management skills, can improve care for clinical and psychological patients, as well as being clinically cost effective. The author offers a structured approach for assessing and managing malodorous wounds in the community setting. It outlines the importance of holistic assessment, antimicrobial stewardship, psychological support and emerging innovations. The article also highlights the limitations in current assessment tools and the need for validated quality of life measures specific to malodorous wounds.
    Keywords:  antimicrobial stewardship; chronic wounds; community nursing; malodorous wounds; odour control; quality of life; wound infection; wound odour
    DOI:  https://doi.org/10.12968/bjcn.2025.0189
  13. Br J Community Nurs. 2025 Dec 01. 30(Sup12): S32-A34
    Choosing the right wound dressing in community nursing.
    Selma Maloumi.
      Wound care is estimated to cost £8.3 billion annually and takes up to 50% of community nurse time. Thorough wound assessments followed by selecting the best wound dressing for the patient, taking into consideration wound severity (acute or chronic), depth, location, treatment duration and ease of application will help to improve wound healing rates and patient quality of life while saving on healthcare resources. This article discusses synthetic dressings, which make up most modern dressings, and include moist, absorbent, and non-adherent dressings that are further broken down into different products. This article explores the mode of action of each dressing, their recommended indications, and summarises their strengths and limitations for ease of reference. Healthcare professionals should continue to keep up to date with the current research and guidelines in order to provide care that optimises wound healing.
    Keywords:  biological dressings; quality of life; synthetic dressings; wound care; wound dressing
    DOI:  https://doi.org/10.12968/bjcn.2025.0213
  14. Front Microbiol. 2025 ;16 1657539
    Identification of multi-drug resistant Acinetobacter baumannii phage YZ2 and evaluation of its therapeutic efficacy in vivo and in vitro.
    Yaru Zhi, Dongmei Yan, Qinfang Tang, Lihua Xiao, Aiting Cai, Mingzhong Sun, Hongmei Chen, Yungang Wang, Qingping Fu.
       Introduction: Carbapenem-resistant Acinetobacter baumannii (CRAB) has recently become an important pathogen in clinically acquired infections, making treatment more challenging.
    Methods: The treatment of bacterial infections may improve with the development of phage therapy and phage-antibiotic combination therapy. Here, we reported a novel phage YZ2 that has a double-stranded DNA genome of 40,181 bp with 37.93% GC content. A total of 46 open reading frames (ORFs) and no virulence or antimicrobial resistance genes were annotated in the genome of phage YZ2. Phage YZ2 is a novel member of the Autographiviridae, with a latency period of approximately 20 min and a burst size of approximately 134 phage particles per infected host cell.
    Results: The in vitro antibacterial results demonstrated that YZ2 could rapidly eliminate host bacteria at a low multiplicity of infection, showing strong bactericidal efficacy. In vivo, YZ2 significantly increased the survival rate of A. baumannii-infected Galleria mellonella larvae from 10 to 100% within 72 h.
    Discussion: Moreover, compared with the use of phage or polymyxin B alone, the combined use of phage YZ2 and polymyxin B can significantly increased the survival rate of G. mellonella larvae and had a synergistic effect. These results imply that phage YZ2 has the potential for development as an antimicrobial agent.
    Keywords:  Acinetobacter baumannii; biological characteristics; genome analysis; multidrug resistant; phage YZ2; phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2025.1657539
  15. Environ Microbiome. 2025 Dec 11.
    Implementation and comparison of two concentration methods to detect and characterize bacteriophages and bacterial hosts from large drinking water samples.
    Mathilde Duvivier, Bouziane Moumen, Yann Héchard, Laurent Moulin, Vincent Delafont, Sébastien Wurtzer.
      Drinking water distribution systems (DWDS) are low biomass biomes harboring a large variety of microorganisms. Much of the attention has been focused on bacteria, whose diversity and abundance in DWDS were repeatedly shown to be influenced by abiotic factors such as pH, temperature, growth inhibitors and water sources. However, little is known about biotic factors, such as bacteriophage presence, even though they are known to be present in DWDS and to influence bacterial dynamics. While bacteriophage impact has been assessed in natural environments such as oceans, little is known about the way they shape DWDS bacterial communities. To fill this knowledge gap and accessing bacteriophage diversity from such low biomass environment, the present study aimed to propose and compare two methods based on ultrafiltration and adsorption/elution methods, already used for the concentration of bacteria and virus from water. To this end, both methods were compared with a weekly sample collection, for one month, on the DWDS of Paris, France. Metagenomic sequencing was performed on concentrated samples to investigate the presence and diversity of bacteriophages, using a coupling of complementary bioinformatic prediction tools. Though viral fractions represented a minority of recovered contigs (1.5 to 2.5%), most were associated with Caudoviricetes class. The predicted bacterial hosts matched with the observed bacterial diversity, highlighting the robustness of host prediction tool. A total of 437 putative phages were present in all samples, constituting a core phage diversity. Among those, 380 viral contigs contained sequences showing significant non-viral matches. We leveraged this information to further refine the inference of bioinformatics pairs of bacterial hosts and their phages. In conclusion, we propose a method to simultaneously concentrate bacteriophages with bacteria from low-biomass environment. Through metagenomics, this study showed that an optimized bioinformatic pipeline could provide an overview of DWDS phage diversity. Moreover, this method allowed to detect sequence similarities between phages and bacteria, suggesting potential genetic exchanges and providing clues for host spectrum. Altogether, this study highlights the tight interactions between bacteria and bacteriophages in drinking water and the possibility to study both phages and potential hosts to better grasp their intricate interplay.
    Keywords:  Bacteriophages; Diversity; Drinking water; Filtration; Metagenomics; Microbiome
    DOI:  https://doi.org/10.1186/s40793-025-00818-y
  16. Sci Rep. 2025 Dec 10. 15(1): 43520
    Isolation and characterization of two novel phages with lytic activity against multidrug-resistant Acinetobacter baumannii strains: potential for phage therapy.
    Xi Chen, Zimeng Ma, Gege Feng, Zhirou Sun, Yating Zeng, Dan Li, Yingqi Qian, Qin Peng.
      The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB) has raised concerns regarding the lack of effective treatment options, prompting interest in phage therapy. In this study, two phages, designated vB_MZM_2AB-P and vB_MZM_4AB-P, were isolated and characterized for their lytic activity against MDR-AB strains. vB_MZM_2AB-P demonstrated considerable stability, retaining activity at 70 °C and pH 11.00, with over 37.10% survival rate after three months of storage. It displayed a 10-min latent period and a burst size of 39.72 PFU/cell. vB_MZM_4AB-P was stable at 50 °C and pH 7.00, but lost activity after three months of storage. Its latent period was also 10 min, with a burst size as high as 746.70 PFU/cell. Transmission electron microscopy revealed that phage vB_MZM_2AB-P has an icosahedral head with a diameter of 55.00 nm and a non-contractile tail that is 121.00 nm long, while phage vB_MZM_4AB-P has an icosahedral head with a diameter of 75.36 nm and a non-contractile tail that is 19.44 nm long. Genomic analysis showed that vB_MZM_2AB-P (43,664 bp) shared 94.18% and 92.80% similarity with phages DMU1 and SH-Ab15497, respectively, while vB_MZM_4AB-P (42,975 bp) shared 73.82% similarity with phage vB_AbaP_Acibel007. Phylogenetic analysis indicated that vB_MZM_2AB-P may represent a new genus within the order Caudoviricetes, and vB_MZM_4AB-P a new species within the genus Daemvirus. No antibiotic resistance or virulence genes were detected. These findings demonstrate that vB_MZM_2AB-P and vB_MZM_4AB-P are novel phages with distinct genomic features and favorable lytic activity against MDR-AB strains, highlighting their value for expanding phage diversity and for future fundamental research.
    Keywords:   Acinetobacter baumannii ; Phage; Phage therapy
    DOI:  https://doi.org/10.1038/s41598-025-27600-x
  17. ACS Infect Dis. 2025 Dec 10.
    Minimal PEGylation Improves Pharmacokinetics, Immunocompatibility, and Efficacy of a Lytic Bacteriophage against Multidrug-Resistant Acinetobacter baumannii.
    Yoon-Jung Choi, Shukho Kim, Ji Yun Jeong, Chaewon Park, Cheol-Am Hong, Jungmin Kim.
      Multidrug-resistant (MDR) Acinetobacter baumannii presents a critical therapeutic challenge due to its extensive antibiotic resistance and the paucity of effective alternatives. This study evaluated whether minimal PEGylation could enhance the pharmacokinetic performance, immune compatibility, and antibacterial efficacy of the lytic phage vB_AbaSt_W16 in an immunocompetent murine model of systemic infection. The phage vB_AbaSt_W16 was conjugated with methoxy polyethylene glycol succinimidyl ester (mPEG-S-NHS, MW 5000) at a low concentration (4.2 pM), experimentally defined as the minimal PEGylation level. PEGylation efficiency, infectivity, adsorption, and replication kinetics were characterized in vitro, and serum and intracellular stability were assessed using mouse or human serum and RAW 264.7 macrophages. In vivo pharmacokinetics and therapeutic efficacy were examined in BALB/c mice challenged intraperitoneally with MDR A. baumannii KBN10P02782, while immune responses were profiled by cytokine quantification and antiphage IgG enzyme-linked immunosorbent assay (ELISA). PEGylated vB_AbaSt_W16 retained infectivity and adsorption capacity while markedly improving pharmacokinetics, showing a 2.7- to 3.7-fold increase in half-life, a >200-fold reduction in systemic clearance, and a >1000-fold increase in the area under the plasma concentration (AUC0-t) relative to the wild-type (WT) phage. The PEGylated phage remained detectable for up to 96 h and achieved complete bacterial clearance within 72-96 h. Immune profiling revealed attenuated proinflammatory cytokine responses and reduced antiphage IgG titers, indicating diminished Th1/Th2 activation. These effects were phage-specific, as the structurally related vB_AbaSi_W9 (a siphovirus) exhibited no comparable improvements following PEGylation. Collectively, minimal PEGylation of vB_AbaSt_W16 enhanced circulation time, immune evasion, and infection control without impairing infectivity. This strategy offers a phage-compatible, structure-informed approach to overcoming key translational barriers in systemic phage therapy and establishes a quantitative framework for optimizing PEGylation in future bacteriophage therapeutics.
    Keywords:  Acinetobacter baumannii; PEGylation; bacteriophage therapy; multidrug-resistant bacteria; systemic delivery
    DOI:  https://doi.org/10.1021/acsinfecdis.5c00755
  18. BMC Microbiol. 2025 Dec 11.
    Characterization and genome analysis of jumbo Escherichia phage UE-S1 and the antibacterial potential of its lysozyme against uropathogenic E. coli.
    Hira Niaz, Anza Abbas, Aqsa Ayub, Abdur Rahman, Fazal Adnan.
       BACKGROUND: Every year, millions of individuals worldwide are affected by urinary tract infections (UTIs), one of the most frequent bacterial infections. Uropathogenic Escherichia coli strains (UPEC) are the main cause of both complicated and uncomplicated UTIs. In addition, uropathogens are becoming progressively more resistant to commonly prescribed antibiotics. As a result, new strategies for the prevention and treatment of UTIs must be developed, and the use of bacteriophages and their enzymes are potential options to eliminate uropathogens from the urinary tract.
    RESULTS: The present study aimed to investigate the therapeutic efficiency of a UE-S1 phage and its lysozyme (LysUE1) against the MDR UPEC strain PSU-5266 (UE-17). The phage UE-S1 was isolated from sewage water and exhibited potent lytic activity against the UPEC strain. Biological characterization revealed that phage UE-S1 was stable over a wide range of temperatures (4 °C to 55 °C) and pH values (3 to 11) with an adsorption time of 15 min. The phage was able to lyse 31% (27/86) of the assessed bacterial strains and significantly inhibited bacterial growth without inducing phage resistance. TEM micrographs revealed that the phage had a Myoviridae morphology with an icosahedral head and long contractile tail. The genomic analysis of phage UE-S1 revealed that it is a jumbo phage with a 358 kb genome encoding 595 putative open reading frames. Among these, 108 predicted genes with putative functions were primarily associated with nucleotide metabolism, DNA replication, and recombination. Additionally, no antibiotic resistance, virulence, or lysogenic genes were detected. Phylogenetic analysis revealed that the new phage UE-S1 belongs to the genus Asteriusvirus. Moreover, the phage lysozyme LysUE1 was cloned, expressed, and purified. LysUE1 demonstrated lytic activity against Gram-negative (pathogenic E. coli strains) and Gram-positive (S. aureus) strains.
    CONCLUSION: Overall, the results indicated that phage UE-S1 and its lysozyme LysUE1 might be promising therapeutic agents for combating multidrug-resistant UPEC in UTIs.
    Keywords:  Antibiotic resistance; Jumbo phage; Lysozyme; Phage therapy; Urinary tract infections
    DOI:  https://doi.org/10.1186/s12866-025-04513-3
  19. bioRxiv. 2025 Nov 24. pii: 2025.11.23.690004. [Epub ahead of print]
    Bacteriophage genome-wide transposon mutagenesis.
    Alex Chan, Wearn-Xin Yee, Deepto Mozumdar, Claire Kokontis, Matias Rojas-Montero, Li Yuping, Ying Yang, Joseph Bondy-Denomy.
      Bacteriophages have genomes that span a wide size range, are densely packed with coding sequences, and frequently encode genes of unknown function. Classical forward genetics has defined essential genes for phage replication in a few model systems but remains laborious and non-scalable. Unbiased functional genomics approaches are therefore needed for phages, particularly for large lytic phages. Here, we develop a phage transposon sequencing (TnSeq) platform that uses the mariner transposase to insert an anti-CRISPR selectable marker into phage genomes. CRISPR-Cas13a-based enrichment of transposed phages followed by pooled sequencing identifies both fitness-conferring and dispensable genes. Using the Pseudomonas aeruginosa -infecting nucleus-forming jumbo phage ΦKZ (280,334 bp; 371 predicted genes) as a model, we show that ~110 genes are fitness-conferring via phage TnSeq. These include conserved essential genes involved in phage nucleus formation, protein trafficking, transcription, DNA replication, and virion assembly. We also isolate hundreds of individual phages with insertions in non-essential genes and reveal conditionally essential genes that are specifically required in clinical isolates, at environmental temperature, or in the presence of a defensive nuclease. Phage TnSeq is a facile, scalable technology that can define essential phage genes and generate knockouts in all non-essential genes in a single experiment, enabling conditional genetic screens in phages and providing a broadly applicable resource for phage functional genomics.
    DOI:  https://doi.org/10.1101/2025.11.23.690004
  20. Mol Biol Rep. 2025 Dec 10. 53(1): 175
    Biological characterization and genome analysis of Pseudomonas phage ZAM-Pa99 as a promising anti-biofilm agent.
    Zahra Baniamerian, Ameneh Elikaei, Mahshid Khazani Asforooshani, Milad Gharedaghi, Morvarid Shafiei, Hamid Solgi.
       BACKGROUND: The increasing prevalence of highly antibiotic-resistant pathogen Pseudomonas aeruginosa, necessitates the exploration of novel therapeutic alternatives. This study aimed to isolate and characterize a bacteriophage with potential applications against P. aeruginosa wound infection.
    METHODS AND RESULTS: The lytic phage ZAM-Pa99 was isolated from hospital sewage and subjected to comprehensive analysis, including morphological characterization, physicochemical properties, growth dynamics, biofilm degradation, genome sequencing, and bioinformatics analysis. ZAM-Pa99 was classified as a newly characterized isolate within the Pbunavirus genus, demonstrating a broad lytic host range (80% efficacy) against the tested clinical strains. This result aligns with in silico host-range predictions, which reflect the high sequence similarity of its receptor-binding proteins with those of relatedPbunavirus phages. Genomic analysis (65,139 bp) was crucial for identifying its therapeutic safety profile, confirming the absence of virulence factors or antimicrobial resistance genes. Importantly, multi-tool proteomic analysis resolved a canonical lysis cassette including a confirmed endolysin, a holin candidate and an identified tailspike-like receptor-binding protein with strong putative depolymerase activity. This mechanism correlated with functional results: ZAM-Pa99 achieved up to 95% degradation of 1-day-old P. aeruginosa biofilms, maintaining high efficacy against 3- and 5-day-old mature structures, results that were quantified and visually confirmed.
    CONCLUSION: ZAM-Pa99's promising characteristics, including its broad host range, biofilm-degrading ability, and lack of harmful genes, make it a promising candidate for phage-based therapy against P. aeruginosa infections. These findings contribute to a growing body of evidence supporting the potential of bacteriophages as valuable nature's weapons for combating antibiotic-resistant pathogens.
    Keywords:   Pseudomonas aeruginosa ; Biofilm; Genome analysis; Phage therapy
    DOI:  https://doi.org/10.1007/s11033-025-11322-4
  21. Int Wound J. 2025 Dec;22(12): e70799
    Postbiotics as Emerging Therapeutics for Skin Wound Healing and Dermatological Care: Clinical Trends and Mechanistic Insights.
    Seyedeh-Sara Hashemi, Alireza Rafati, Shahin Roohinejad, Fatemeh Yaghoobi, Alireza Salehi.
      Postbiotics, non-viable microbial components or metabolites derived from probiotics, represent a promising new class of therapeutic agents in dermatological and wound-healing science. This review highlights the bioactive potential of postbiotics in modulating inflammation, enhancing tissue regeneration, and restoring microbiota balance in skin wounds. Through analysis of recent experimental and clinical studies, postbiotics were found to accelerate wound closure, stimulate collagen synthesis, and improve barrier integrity while providing antimicrobial and immunomodulatory benefits. Their incorporation into topical formulations and wound dressings has shown to regulate moisture, prevent infection, and support optimal healing conditions. In contrast to live probiotics, postbiotics are stable, safe, and free from viability-related limitations, making them ideal for cosmetic and medical use. Overall, postbiotics represent an innovative, next-generation strategy for skin regeneration and wound management.
    Keywords:  dermatological care; postbiotics; skin microbiota; topical therapy; wound healing
    DOI:  https://doi.org/10.1111/iwj.70799
  22. J Control Release. 2025 Dec 05. pii: S0168-3659(25)01116-2. [Epub ahead of print] 114502
    Multifaceted mesoporous silica-based nanoplatform to co-deliver honokiol and baicalin for integrative therapy of drug-resistant bacteria infection.
    Biao Li, Yan Liao, Junfeng Huang, Baode Shen, Xiaowen Zhang, Fangwen Chen, Zihong Xie, Hao Song, Pengfei Yue.
      Bacterial infections and excessive inflammation are the main factors that hinder chronic wound healing. The current research mainly focused on killing wound bacteria, but ignoring the excessive inflammation caused by lipopolysaccharide (LPS) released by dead bacteria. Meanwhile, the bacterial cell wall and the bacterial biofilm as a natural barrier for bacteria can strongly block the penetration of antimicrobial drugs. In this study, we designed a multifaceted smart nanoplatform to co-deliver the antibacterial molecule honokiol (HK) as well as the anti-inflammatory molecule baicalin (BA) for synergistic eradication of wound infection. And this multifaceted nanoplatform was composed of fractal mesoporous silica nanoparticles (FSNs) with spiky structure capped by chitosan (CS) as a pH-responsive valve and grafted with folic acid (FA) to achieve specific binding to folate receptors overexpressed on the surface of the bacterial biofilms. Notably, this integrated fractal mesoporous silica-based nanoplatform played a prominent role in enhancing antimicrobial action as well as eliminating the mature biofilm. And under the acidic microenvironment of bacterial infection, this smart nanoplatform could specifically adhere to bacteria, and responsively release both HK and BA. As compared to free drugs (HK and BA) or unmodified FSNs, the fractal mesoporous silica-based nanoplatforms for co-delivery of HK and BA exhibited stronger capacity of biofilm eradication and killing the multidrug-resistant bacteria, and stimulated macrophage polarization toward the M2 phenotype and promote wound healing. Therefore, this multi-stimuli-responsive smart nanoplatform capable of co-delivering dual drugs appears to be a highly promising strategy for integrative therapy, offering efficient antibacterial and long-term anti-inflammatory effects in the treatment of chronic wounds.
    Keywords:  Fractal mesoporous silica nanoparticles; Infected wound healing; Integrative therapy; Multidrug-resistant bacteria; Smart nanoplatform
    DOI:  https://doi.org/10.1016/j.jconrel.2025.114502
  23. Int J Biol Macromol. 2025 Dec 10. pii: S0141-8130(25)10127-X. [Epub ahead of print] 149570
    Emerging antimicrobial hydrogel dressings based on bacterial cellulose-chitosan composites: A review.
    Danica Zmejkoski, Dijana Mitić, Zoran Marković, Natalia O Kozyrovska, Biljana Todorović Marković.
      Wounds result from disruptions in the tightly regulated wound healing process, which is often complicated by comorbidities, infections, and biofilm formation. Advancing therapeutic strategies relies on a comprehensive understanding of cellular and molecular mechanisms, with particular emphasis on host-pathogen interactions. Early intervention can prevent biofilm maturation through antioxidant and anti-inflammatory treatments administered within 24 h post-debridement. Furthermore, growth factors can promote angiogenesis and tissue regeneration. The escalating challenge of antibiotic resistance highlights the critical need to develop effective alternative therapies. Antimicrobial hydrogel wound dressings composed of nanomaterials represent a promising strategy that integrates effective infection control with accelerated tissue regeneration. This review focuses on composite materials composed solely of bacterial cellulose and chitosan, which exhibit excellent antibacterial, antibiofilm, and antioxidant activities along with high porosity, superior fluid absorption capacity, and strong support for cell migration. The originality of this work lies in its detailed discussion of the influence of these composites on the molecular mechanisms underlying angiogenesis. Preclinical and clinical studies support their potential in promoting wound healing. Future advancements are likely to involve the development of smart hydrogels incorporating pH- and temperature-responsive sensors and controlled-release systems, leading to more effective and sustainable approaches to wound care.
    Keywords:  Angiogenesis; Antimicrobial hydrogel; Bacterial cellulose; Chitosan; Oxidative stress; Wound healing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.149570
  24. Theor Popul Biol. 2025 Dec 10. pii: S0040-5809(25)00069-3. [Epub ahead of print]
    What drives bacterial extinction? The role of bacteriophages.
    Mark M Tanaka, Lindi M Wahl.
      Bacterial lineages are relatively short-lived on geological timescales, according to phylogenetic analyses, implying that bacterial extinction occurs at high rates. Since the vast majority of bacteria live in large populations in oceans and soils, many well-studied extinction mechanisms, such as demographic or environmental stochasticity, seem unlikely to drive this pattern. We outline mechanisms for the extinction of large bacterial populations, and discuss the emergence of a new virus as a possible cause of extinction. We use deterministic and stochastic models to characterise the persistence of a bacterial population, demonstrating that when resistance to a new virus does not emerge, large populations are more likely to go extinct than small populations, which contrasts with classically studied extinction mechanisms. When they go extinct, large populations also reach extinction more quickly. When phage-resistant bacteria appear, extinction is rare but its probability increases with population size in some parameter regimes. We also quantify bacterial extinction in spatially distinct subpopulations. We conclude that large bacterial populations are robust to many extinction mechanisms, and typically evolve resistance to new phages, as observed empirically. For bacterial lineages that have gone extinct, however, the failure to evolve resistance to a novel phage is a likely underlying mechanism.
    Keywords:  Bacterial evolution; Bacteriophage; Evolutionary rescue; Extinction; Mathematical model; Predation
    DOI:  https://doi.org/10.1016/j.tpb.2025.12.001
  25. Acta Diabetol. 2025 Dec 10.
    Advances in diabetic wound healing: from pathophysiology to emerging therapies.
    Swati Swagatika Swain, Veera Venkata Satyanarayana Reddy Karri, Md Ekhtiar Uddin, Kuppuswamy Gowthamarajan, Manimaran Bhaskaran, Vetriselvan Subramaniyan.
      Diabetic wounds (DWs), particularly those affecting the lower extremities, represent a significant clinical challenge due to their chronic nature and high risk of complications, including infection and amputation. Despite advances in diabetes management, conventional wound care strategies often fail to achieve satisfactory healing outcomes, largely due to the complex pathophysiology of DWs, are involving impaired angiogenesis, chronic inflammation, and compromised immune responses. The data on the conventional and emerging therapies used in the management of DWs were searched using PubMed, Scopus, and Web of Science databases to locate literature published. Studies have shown that conventional wound care interventions like debridement, dressing, and infection control mostly provide symptomatic treatment without eliminating underlying cellular and molecular diabetic wound pathophysiology. Recent years have witnessed the emergence of novel therapeutic approaches, including stem cell therapy, gene therapy, nanotechnology-based interventions, and tissue engineering. These strategies improve angiogenesis, alter the polarization of macrophages, and stimulate tissue repair, which can offer new hope for enhancing wound healing in diabetic patients. This review synthesizes current literature on the pathophysiology of diabetic wound healing, evaluates the limitations of traditional therapies, and provides a comprehensive overview of cutting-edge treatments that holds an effective diabetic wound management.
    Keywords:  Diabetic wound healing; Gene therapy; Nanotechnology; Novel therapeutics; Stem cell therapy
    DOI:  https://doi.org/10.1007/s00592-025-02629-6
  26. Front Pharmacol. 2025 ;16 1704901
    Research progress on the use of polyphenols in the treatment of Crohn's disease.
    Xianmei Zhong, Qian Dai, Jing Li, Jie Yang, Xi Zheng.
      Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD), and its specific etiology is still unclear. However, it is currently widely believed that this disease is the result of interactions among four main factors: host genetic factors, environmental factors, dysbiosis of the gut microbiota, and an abnormal immune system response. In recent years, polyphenolic compounds have become a research hotspot due to their anti-inflammatory, antioxidant, and microbial regulatory properties, demonstrating potential application value in the treatment of CD. This review aimed to explore the mechanism of action of polyphenolic compounds in the treatment of CD, as well as their progress in animal model research and clinical practice.
    Keywords:  anti-inflammatory; antioxidant; crohn’s disease; inflammatory bowel disease; polyphenols
    DOI:  https://doi.org/10.3389/fphar.2025.1704901
  27. Int J Mol Sci. 2025 Nov 24. pii: 11365. [Epub ahead of print]26(23):
    Wounds and the Microbiota: The Healing Interplay Between Host and Microbial Communities.
    Raghad Al-Taweel, Ayat S Hammad, Ali Tajammul, Sergio Crovella, Maha Al-Asmakh.
      Chronic, non-healing wounds represent a major global health challenge, often aggravated by microbial dysbiosis and impaired host responses. Wound healing progresses through four overlapping phases-hemostasis, inflammation, proliferation, and remodeling-yet recent findings reveal that the skin microbiota actively participates in each step through immune, metabolic, and signaling mechanisms. Beneficial microorganisms such as Staphylococcus epidermidis and Lactobacillus plantarum promote tissue repair by inducing antimicrobial peptides and modulating cytokine production, whereas opportunistic pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis) delay closure via biofilm formation and proteolytic activity. This review integrates current molecular insights and bibliometric trends to highlight advances and remaining challenges in understanding the wound-microbiome axis. A deeper grasp of these interactions can inform next-generation, microbiome-targeted therapies for chronic wounds.
    Keywords:  biofilm; chronic wounds; commensal bacteria; host–microbe interaction; skin microbiota; wound healing
    DOI:  https://doi.org/10.3390/ijms262311365
  28. J Craniofac Surg. 2025 Dec 12.
    Exploring Global Research Status and Trends in Necrotizing Fasciitis: A Bibliometric Analysis.
    Xiuqi Li, Peihua Sun, Xiaoqian Li, Min Du.
      Necrotizing fasciitis (NF) is a rare and extremely destructive soft tissue infection characterized by rapid progression and severe clinical manifestations. It can lead to serious complications and even death without prompt diagnosis and treatment. Despite advances in medical science, NF remains a major clinical challenge. This study analyzed 3381 NF-related research papers from the Web of Science Core Collection (WoSCC) database (1977-2024). We used text mining and bibliometric methods to research the number of papers, publishing institutions and countries, key authors, research hotspots, evolving trends, and other information, and to visualize the results. The analysis revealed a significant increase in publications, from fewer than 10 per year before 1990 to 228 in 2023. The United States, China, and Canada were the leading contributors, with the United States forming a core research network with Canada and the UK, while Chang Gung University in Taiwan, China, emerged as a key research hub in Asia. Early studies primarily focused on pathogens, whereas recent research has shifted toward treatment techniques and outcome prediction. High-frequency keywords like "mortality" and "diagnosis" reflect ongoing clinical challenges. Key unresolved issues include the diagnostic accuracy of the LRINEC score, optimal debridement timing, and health care disparities in resource-limited regions. The findings indicate a shift in NF research focus from etiology to clinical management and technological innovation. Future research should aim to refine diagnostic criteria, explore personalized treatments, and improve diagnostic capabilities in underserved areas. Interdisciplinary approaches, including information technology and materials science, are expected to drive NF research toward precision medicine.
    Keywords:  Bibliometric; citespace; necrotizing fasciitis; visualization; wound management
    DOI:  https://doi.org/10.1097/SCS.0000000000012206
  29. Eur J Clin Microbiol Infect Dis. 2025 Dec 12.
    Pediatric saprochaete infections: insights from case reports.
    Sevgi Aslan Tuncay, Gulsen Akkoc, Zeynep Ergenc, Seyhan Yılmaz, Burcu Parlak, Aylin Dizi Isik, Pinar Canizci Erdemli, Didem Buyuktas Aytac, Meryem Cagla Abaci Capar, Rabia Emel Senay, Burcu Tufan Tas, Nursah Eker, Ahmet Koc, Eda Kepenekli, Sevliya Ocal Demir.
      Saprochaete species are emerging fungal pathogens, particularly affecting immunocompromised individuals, with clinical manifestations ranging from superficial to invasive infections. We present three cases of pediatric Saprochaete spp. infections, detailing clinical presentation, diagnostic workup, and treatment strategies. Two patients with acute myeloid leukemia developed bloodstream infections with Saprochaete clavata; both required prolonged antifungal therapy due to deep organ involvement, and one experienced relapse after treatment discontinuation. The third case involved a patient with cystic fibrosis, in whom Saprochaete capitata was isolated from sputum; she improved with antifungal therapy and had no relapse. Saprochaete spp. infections in pediatric populations present diagnostic and therapeutic challenges. Further research is needed to optimize management strategies and improve patient outcomes.
    Keywords:  Fungal infection; Immunocompromised; Neutropenia; Parenchymal nodules
    DOI:  https://doi.org/10.1007/s10096-025-05378-0
  30. Adv Healthc Mater. 2025 Dec 08. e03932
    Broad-Spectrum Antimicrobial Treatment Targeted Through Drug Conjugation to Vancomycin.
    Magnus Schou Dybtved, Maiken E Petersen, Alif Firman Firdausy, Mikkel Illemann Johansen, Emma Faddy, Christoffer Gadeberg, Lars Østergaard, Nis Pedersen Jørgensen, Lærke N Glud, Ane Bretschneider Søgaard, Rikke Louise Meyer, Alexander N Zelikin.
      Antimicrobial resistance, microbial persister cells, and microbial biofilms represent some of the most pressing, unresolved issues and healthcare challenges. To tackle these, we develop targeted delivery of antimicrobial compounds. The drug of choice is mitomycin C, which has documented activity against persister cells. For targeting, we use vancomycin, a compound that binds the bacterial cell wall. The linker between the two contains a scissile disulfide bond for drug release. The conjugate is optimized as regards the site of drug attachment to vancomycin. The lead conjugate is shown to be a broad-spectrum antibacterial agent with activity against Gram-positive strains, including vancomycin intermediate and resistant ones, as well as Gram-negative strains and the bacterial biofilm. In vitro, antimicrobial effects of the targeted mitomycin treatment are shown to be significantly more potent compared to the free drug; at the same time, the non-specific cytotoxicity to mammalian cells is significantly decreased. In vivo evaluation in the implant-associated osteomyelitis model in mice reveals robust targeting and good tolerance to the treatment with no signs of toxicity. However, the limited therapeutic efficacy indicates that more work is needed to match the developed treatment to an appropriate disease model.
    Keywords:  antibiotics; broad spectrum antimicrobial; drug conjugation; drug targeting; mitomycin; vancomycin
    DOI:  https://doi.org/10.1002/adhm.202503932
  31. J Cosmet Dermatol. 2025 Dec;24(12): e70615
    A Scoping Review of Clinical Trials on the Efficacy of Curcumin and Its Formulations for Wound Healing.
    Mohammad Mahdi Parvizi, Ali Arefkia, Yasamin Dehghan, Mohammad Ali Salimi, Negin Fazelzadeh Haghighi.
       BACKGROUND: Curcumin, the main component of turmeric, may be effective in wound healing due to its anti-inflammatory and antibacterial effects. Although pre-clinical studies are promising, a comprehensive clinical review is lacking. This scoping review examines clinical trials on the efficacy of curcumin in wound healing.
    METHOD: This study was conducted in accordance with the PRISMA-ScR guidelines and involved a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library databases for clinical trials on various forms of curcumin for wound healing in humans, from January 1, 2000 to May 31, 2025.
    RESULTS: A total of 920 results were retrieved through the search, of which 19 clinical trials met the predefined inclusion and exclusion criteria and were included in our study. Most studies (14 out of 19) were randomized controlled trials. Curcumin was used in various dosages and treatment durations, and in multiple forms, including topical and oral formulations. Curcumin improved wound healing compared to placebo or conventional care in 89% of the studies. Additionally, no adverse events were reported in 84% of the studies, with minor and temporary side effects observed in the remaining cases.
    CONCLUSIONS: According to the findings of the current study, curcumin is a safe and effective adjuvant for improving wound healing. However, the significant heterogeneity observed among clinical trials limits the ability to develop consistent treatment guidelines. Future studies should focus on large-scale, standardized trials to better define the role of curcumin in wound care.
    Keywords:  Persian medicine; complementary therapies; curcumin; plant extracts; wound healing
    DOI:  https://doi.org/10.1111/jocd.70615
  32. Front Neurosci. 2025 ;19 1677744
    Gut microbiota dysbiosis drives stroke-associated pneumonia: mechanisms and targeted therapeutic strategies.
    Jun Xiao, Jing Xia, Zhiying Chen, Weiwei Zha, Tian Xu, Xulong Chen, Xiaoping Yin.
      The gut microbiota has been increasingly recognized as a central regulator of immune function, with growing research highlighting its association with the development of stroke-associated pneumonia (SAP). This review provides an overview of current research on the correlation between SAP and alterations in gut microbial composition and metabolism, with a focus on microbial imbalance, changes in key metabolites, and relevant biological mechanisms. Clinical and preclinical studies consistently report a decline in short-chain fatty acids (SCFAs)-producing bacteria, an increase in potentially harmful microbial species, reduced SCFAs levels, and elevated lipopolysaccharide (LPS) concentrations. These disturbances appear to be associated with SAP progression through the microbiota-gut-brain and microbiota-gut-lung axes by affecting immune regulation and inflammatory responses. The review also examines microbiota-targeted treatment approaches, including dietary modification, antibiotic therapy, probiotics, microbiota-regulating compounds, fecal microbiota transplantation (FMT), and respiratory microbiota transfer. A deeper understanding of how microbial disturbances are correlated with SAP may help explain the increased vulnerability to pulmonary infections following stroke and support the design of more effective, microbiota-based therapeutic strategies.
    Keywords:  gut microbiota dysbiosis; microbiota gut brain axis; microbiota- gut lung axis; microecological therapy; stroke-associated pneumonia
    DOI:  https://doi.org/10.3389/fnins.2025.1677744
  33. Clin Teach. 2026 Feb;23(1): e70296
    Educational Perspectives on Compassionate Concussion Care: A Scoping Review.
    Alice Sau Han Kam, Farida Roy, David Wiljer, Nicolas Fernandez, Denyse Richardson.
       BACKGROUND: Teaching compassionate concussion care, particularly by engaging patients and caregivers as partners in education, is a complex and evolving field. Clinician-educators are now expected to move beyond traditional methods and draw on diverse approaches to understand how people learn. Yet, many current teaching practices lack clear theoretical grounding, limiting their ability to prepare physicians to address patients' individual needs. Despite growing interest in compassion education, little is known about how paradigms shape postgraduate concussion-care training and assessment. This scoping review aimed to (1) explore the educational paradigms and learning theories underpinning postgraduate concussion-care education and (2) contrast the paradigms guiding assessment of and for learning.
    METHODS: Following Arksey and O'Malley's scoping review framework, we searched MEDLINE, Embase, ERIC, Cochrane, and CINAHL. Eligible articles described full-length postgraduate concussion-care educational interventions. Extracted data included intervention design, educational paradigm, learning theory and reported outcomes.
    FINDINGS: Of the 1574 articles screened, 9 met inclusion criteria. Identified paradigms included behaviourism, positivism, cognitivism and constructivism. Social-cultural learning theory (a form of Constructivism) appeared in six of nine studies. Most studies did not explicitly state their guiding paradigm or align assessment with compassionate outcomes.
    CONCLUSION: This review highlights the implicit paradigms shaping concussion-care education and their limitations for cultivating compassion. Constructivism offers the most promise for advancing compassionate practice by fostering collaboration, reflection, and learner agency. Given the interpersonal, cognitive and contextual demands of concussion care, adopting a constructivist orientation may better prepare physicians to meet patient and caregiver needs.
    Keywords:  clinical assessment; compassionate care; concussion‐care; constructivism; curriculum design; educational research paradigms; postgraduate medical education
    DOI:  https://doi.org/10.1111/tct.70296
  34. ISME J. 2025 Dec 08. pii: wraf272. [Epub ahead of print]
    Ecological strategies of bacteria shape inherent phage diversity in Atlantic salmon gut microbiomes.
    Caroline S Winther-Have, Jacob A Rasmussen, Xichuan Zhai, Dennis S Nielsen, Thomas Sicheritz-Pontén, Shyam Gopalakrishnan, Martha R J Clokie, Mathias Middelboe, Morten T Limborg.
      Understanding host-specific phage diversity is essential for deciphering the complex dynamics shaping microbial ecology and evolution. However, the lack of inherent host associations between uncultivated bacteria and their viruses remains a major limitation to understanding the drivers of viral diversity and its role in bacterial ecology, particularly given the intricate specificity of phage-host interactions. The naturally low complexity of the gut microbiota within piscivorous fish, such as Atlantic salmon (Salmo salar), makes it a valuable model for unravelling ecological patterns of viral diversity in the context of a limited bacterial species composition, and to explore the impact of an invading pathogen on the "steady-state" viral community. The intestinal microbiota of the salmon studied here, was in some cases dominated by a salmon-associated Mycoplasma or increasing levels of an opportunistic Aliivibrio, the latter observed in response to a disease outbreak. The two bacteria are distinctively different in their ecological strategies and their overall genomic and functional properties. A pronounced difference was observed in the gut viral communities and diversity, depending on whether it was dominated by a commensal or an invading bacterial species. Samples dominated by Mycoplasma sp. had few to no viruses, whereas samples dominated by Aliivibrio sp. had viral communities comprising up to 22 viral taxonomic operational units. This study provides unique insights into the significance of bacterial ecological trade-offs linked to niche adaptation and how these affect the associated viral communities in a natural host-controlled environment.
    Keywords:  Aliivibrio; Mycoplasma; Salmo salar; intracellular bacteria; microbial ecology; microbiota dysbiosis; phage diversity; virome; virus ecology
    DOI:  https://doi.org/10.1093/ismejo/wraf272
  35. Healthcare (Basel). 2025 Nov 22. pii: 3022. [Epub ahead of print]13(23):
    Transforming Care Models in Cystic Fibrosis: A Review.
    Barry Lawrence Diener, Maria Berdella, Joan DeCelie-Germana, Teresa Stables-Carney, Catherine Kier.
      Cystic fibrosis (CF) is a multisystemic, chronic disease that requires a large multidisciplinary team for effective treatment. Over the past 20 years, the landscape of cystic fibrosis care has evolved from an almost exclusively pediatric disease to both a pediatric and adult condition. The median age of cystic fibrosis patients is rising, and the number of adults with CF is also increasing. With new developments in cystic fibrosis care, patients' health and needs have changed, and therefore the care model of the cystic fibrosis team has also changed. The introduction of highly effective CFTR modulator therapy, the COVID-19 pandemic, and the partnership of people with CF (PwCF) and their families have catalyzed the transformation of the CF care model, which includes the growth and evolution of the CF care team given the changes in the demographics of CF patients and the incorporation of telehealth and remote patient monitoring, shared decision-making, and coproduction of care. This narrative review, focusing on the United States (US) experience, explores the transformation of CF care, highlighting demographic changes, medical breakthroughs, and systemic adaptations.
    Keywords:  coproduction; cystic fibrosis; model of care; shared decision-making; telehealth
    DOI:  https://doi.org/10.3390/healthcare13233022
  36. Front Cell Infect Microbiol. 2025 ;15 1651828
    Increased abundance of actinobacteria and upregulation of primary bile acid biosynthesis in diabetic foot ulcers.
    Mi Zhou, Han Zhang, Rui Zhang, Tianshu Wei, Xiaojun Zhou.
       Background: Vascular microbial imbalance may disrupt homeostasis and impair wound healing by triggering local and systemic inflammation. Diabetic foot (DF), a severe complication of diabetes, is frequently associated with bacterial infections. However, the arterial microbiota in DF remains unexplored. This study characterizes the arterial microbiota in DF patients and investigates its potential role in disease progression.
    Methods: A total of 22 patients were recruited, including those undergoing surgery for DF, patients with lower limb atherosclerosis (AS) requiring surgery, and trauma patients who underwent amputation as healthy controls (C). Samples were obtained under sterile conditions, and 16S rRNA sequencing was performed. Microbial diversity and functional pathways were analyzed using QIIME2.
    Results: Alpha diversity analysis revealed a progressive decline in microbial diversity from the C group to the AS and DF groups. Beta diversity analysis demonstrated that the DF and AS groups clustered closely, while both exhibited significant microbial compositional differences compared to the C group (ANOSIM, P < 0.01). At the phylum level, Actinobacteria was significantly enriched in the DF and AS groups, whereas TM6 was reduced in the DF group and Proteobacteria was reduced in the AS group. LEfSe analysis identified Corynebacterium, Streptophyta_Group, Caulobacter, Hydrogenophaga, and Diaphorobacter as key representative genera in the DF group. Furthermore, KEGG analysis revealed metabolic alterations in both the DF and AS groups, including upregulated metabolism and organismal system pathways. At level 3, the DF group exhibited significant downregulation of amino sugar and nucleotide sugar metabolism, whereas primary bile acid biosynthesis was markedly upregulated, suggesting a potential role in DF progression.
    Conclusion: DF is associated with distinct alterations in arterial microbiota composition and metabolic pathways. Alterations in Actinobacteria and primary bile acid biosynthesis may be relevant to DF progression and could serve as potential therapeutic targets.
    Keywords:  16S rRNA sequencing; actinobacteria; atherosclerosis; diabetic foot; microbiota; primary bile acid biosynthesis
    DOI:  https://doi.org/10.3389/fcimb.2025.1651828
  37. Clin Med Insights Case Rep. 2025 ;18 11795476251401715
    Purple Urine Bag Syndrome Caused by Klebsiella pneumoniae in an Elderly Patient: A Case Report.
    Sreeja Botuku, Sai Mouli Krishna Garre, Ramya Sree Muppavarapu, Nagateja Yedida, Sumanth Gundraju, Tarun Kumar Suvvari, Tejinder Singh.
      Purple Urine Bag Syndrome (PUBS) is an uncommon but notable clinical phenomenon primarily observed in patients with long-term indwelling catheters. This syndrome is characterized by a striking purple discoloration of the urine collection bag, often indicative of an underlying urinary tract infection (UTI) and associated metabolic processes. PUBS occurs due to the breakdown of indoxyl sulfate, a tryptophan metabolite, by specific bacteria present in the urinary tract. In this report, we present the case of a 73-year-old female with a chronic Foley's catheter, later developed PUBS, accompanied by symptoms of lower abdominal pain, fever, and reduced urine output. Urine culture identified Klebsiella pneumoniae, a common uropathogen, as the causative organism. This case highlights the clinical presentation, pathophysiology, and management of PUBS in a patient with long-standing catheterization, along with a brief review of existing literature on the condition. Prompt recognition and targeted antibiotic therapy, alongside supportive measures, were essential in managing the infection and alleviating symptoms.
    Keywords:  Klebsiella pneumoniae; catheters; purple urine bag syndrome; urinary tract infection
    DOI:  https://doi.org/10.1177/11795476251401715
  38. Curr Microbiol. 2025 Dec 09. 83(1): 64
    The Role of the Oral Microbiome in Periodontal Disease: A Systematic Review of Microbial Associations and Therapeutic Implications.
    Seyed Ebrahim Alavi, Hasan Ebrahimi Shahmabadi, Lavanya A Sharma, Ajay Sharma.
      Periodontitis is a chronic inflammatory disease driven by bacterial pathogens. This meta-analysis aimed to quantitatively assess the association between nine bacterial strains and periodontitis across 11 studies. We extracted odds ratios (ORs) and 95% confidence intervals (CIs) from studies evaluating Streptococcus mutans, Lactobacillus, Fusobacterium nucleatum, Prevotella intermedia, Staphylococcus aureus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Treponema denticola. Heterogeneity was evaluated using Cochran's Q and I2 tests. We systematically searched PubMed, Scopus, and Web of Science up to March 2024, following PRISMA guidelines, to identify studies investigating the association between oral bacterial species and periodontitis. Porphyromonas gingivalis was identified as a significant risk factor for periodontitis in all eight studies (ORs: 4.17-97, I2 = 85.99%). Tannerella forsythia (ORs: 2.75-36.88, I2 = 85.39%) and Treponema denticola (ORs: 3.12-24.5, I2 = 85.54%) were also significantly associated with periodontitis. Prevotella intermedia showed a significant association in three out of four studies, despite high heterogeneity (I2 = 79.82%). Fusobacterium nucleatum and Staphylococcus aureus were not found to be significant risk factors. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are key bacterial risk factors for periodontitis. The findings highlight the importance of microbial screening in clinical practice, while the heterogeneity suggests the need for standardized research. Future studies should focus on longitudinal assessments and microbial interactions.
    DOI:  https://doi.org/10.1007/s00284-025-04648-6
  39. Trials. 2025 Dec 10.
    Early shift to oral antibiotic treatment for pyogenic vertebral osteomyelitis (SAVE): study protocol for an open label, non-inferiority, nation-wide randomized controlled clinical trial.
    Zahra Persson Theilgaard, Nina Weis, Pernille Ravn, Peter Haahr Bernhard, Nis Pedersen Jørgensen, Jesper Andreas Knudsen, Kristina Öbrink-Hansen, Iben Ørsted, Kristian Schønning, Isik Somuncu Johansen, Anne-Mette Lebech.
       BACKGROUND: The current Danish National Guideline (DNG) for treatment of pyogenic vertebral osteomyelitis (PVO) recommends 6 weeks antibiotic (AB) treatment, with a 2-week intravenous (IV) AB lead-in followed by 4 weeks oral AB for uncomplicated PVO, and 12 weeks AB treatment with a 4-week IV AB lead-in followed by 8 weeks oral AB for complicated PVO. The primary objective of the current study is to investigate whether shortening the duration of IV AB to one week is non-inferior to the current DNG.
    METHODOLOGY: The SAVE trial is an investigator initiated, randomized (1:1), controlled, non-inferiority, parallel group, open-label trial. Patients will be included at departments of infectious diseases in Denmark. All adult patients diagnosed with and treated for PVO will be assessed for eligibility. Patients will be eligible for inclusion if they fulfill all the inclusion and none of the exclusion criteria. Exclusion criteria include among others previous episodes of PVO within the past 24 months, spinal implants inserted prior to current episode of PVO, other infectious foci necessitating >7 days of IV AB, identification of selected bacteria as well as fungi as the etiology and severe immunocompromise. Patients will be randomized if their C-reactive protein (CRP) has decreased to <75% of peak value or to <20 mg/l by day 7 of appropriate IV AB. Five-hundred thirty patients will be included and randomized. The primary endpoint is a composite of all-cause mortality, unplanned surgical intervention in relation to the spine and related to PVO, relapse of bacteremia with the primary pathogen, relapse of bacteria by culture with the initial pathogen being cultured from relevant material from infected areas in relation to the spine or iliopsoas muscle (detected by culture), renewed course of IV ABs given for >7 days for treatment of PVO. The primary endpoint will be adjudicated by a blinded end-point committee.
    DISCUSSION: If early transition to oral therapy is found non-inferior to the current DNG, it will provide the basis for shortening hospitalization, reducing costs, and increasing patient autonomy.
    TRIAL REGISTRATION: European Union Clinical Trials - EU CT Number 2023-507617-96-01: First approval 27/11/2023. Link: https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-507617-96-01.
    DOI:  https://doi.org/10.1186/s13063-025-09316-5
  40. AAPS PharmSciTech. 2025 Dec 12. 27(1): 55
    Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon.
    Vaibhavi Srivastava, Pragya Yadav, Abhishek Yadav, Poonam Parashar.
       BACKGROUND: Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.
    AREA COVERED: This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.
    EXPERT OPINION: AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.
    Keywords:  bionic eye; machine learning; neural network; ocular delivery; personalized therapy
    DOI:  https://doi.org/10.1208/s12249-025-03271-9
  41. JMIR Nurs. 2025 Dec 09. 8 e65716
    An Expert Knowledge Algorithm and Model Predicting Wound Healing Trends for a Decision Support System for Pressure Injury Management in Home Care Nursing: Development and Validation Study.
    Aya Kitamura, Aruto Ando, Gojiro Nakagami, Hiromi Sanada.
       Background: Home-visiting nurses have difficulty selecting appropriate pressure injury (PI) management despite using clinical practice guidelines in various home-visiting settings. Clinical decision support systems can help home-visiting nurses' decision-making.
    Objective: This study aimed to develop a care algorithm reflecting the expertise of a wound expert nurse and a predictive model for the change of PI severity to inform home-visiting nurses to receive actual consultation.
    Methods: First, an existing algorithm was modified by semistructured interviews with a certified wound expert nurse. Case information was input into both base and high-expertise algorithms, which provided care recommendations across 9 fields: (1) pressure relief; (2) nutritional management; (3) shear relief; (4) moisture management; (5) wound dressing use; (6) care for physical factors including bone prominence, obesity, joint contractures, and periwound edema; (7) care for systemic disorder; (8) selection of wound dressings, ointments, and negative pressure wound therapy; and (9) wound cleansing. An expert interviewee assessed the high-expertise algorithm's recommendations on a 5-point scale, comparing them to the base algorithm and their own clinical judgment. To measure the algorithm's applicability, agreement proportions were calculated as the number of vignettes where the care recommendation was considered appropriate or total number of vignettes. To measure the algorithm's alignment, improvement proportions were calculated as the number of vignettes where the care recommendation improved or total number of vignettes excluding vignettes when the existing and high-expertise algorithm both showed an appropriate recommendation. Expected healing levels were evaluated by a 4-point scale where 4 indicates the high-expertise algorithm can "much improve" the case. Second, predictive distributions of changes in DESIGN-R 2020 score, PI severity score, were estimated with a hierarchical Bayesian model. The best model determined using training data (n=42) calculated coverage probabilities of 90% prediction interval in test data (n=34). The coverage probability of a 90% prediction interval was defined as follows: the number of times when actual scores were within the 90% prediction interval or the number of assessments when the prediction was conducted.
    Results: The agreement proportions were 0.92 (33/36), 0.75 (27/36), and 0.89 (32/36) for each round. The improvement proportions were 0.73 (8/11), 0.25 (3/12), and 0.76 (13/17), respectively. The expected healing level was 2.67, 3.00, and 3.25, respectively. Coverage probabilities of 90% prediction interval in the test data were 0.67 (4/6), 0.83 (5/6), 0.86 (6/7), and 0.80 (8/10), respectively.
    Conclusions: This study developed an algorithm reflecting the expertise and a model to estimate predictive distributions of changes of DESIGN-R 2020 score for developing clinically applicable clinical decision support systems for home-visiting nurses providing appropriate PI management.
    Keywords:  algorithm; care recommendation; clinical decision support system; home care; pressure injury
    DOI:  https://doi.org/10.2196/65716
  42. Cochrane Database Syst Rev. 2025 Dec 10. 12 CD013733
    Digital technology for monitoring adherence to inhaled therapies in people with cystic fibrosis.
    supported by the Cochrane Cystic Fibrosis Review Group
       RATIONALE: Improved understanding and treatment of cystic fibrosis (CF) has led to longer life expectancy, which is accompanied by an increasingly complex regimen of treatments. Suboptimal adherence to the treatment plan, in the context of respiratory disease, is associated with poorer health outcomes. With digital technology being more accessible, it can be used to monitor adherence to inhaled therapies via chipped nebulisers, mobile phone applications and web-based platforms. This technology can allow monitoring of adherence, as well as clinical outcomes, and allow feedback to both the person with CF and their healthcare team.
    OBJECTIVES: To assess the effects of using digital technology to monitor adherence to inhaled therapies and health status in adults and children with CF.
    SEARCH METHODS: We searched the Cochrane CF Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched Embase and three clinical trial registries, and checked the references of included studies. The date of last search was 27 February 2025.
    ELIGIBILITY CRITERIA: We searched for randomised controlled trials (RCTs) looking at the effects of digital technology for monitoring adherence to inhaled therapies of children and adults with CF.
    OUTCOMES: We assessed available data (at up to three months in one study, and up to 12 months in the second) for adherence to the inhaled treatment, treatment burden, quality of life (QoL) and the change from baseline in forced expiratory volume in one second (FEV1). We assessed the number of pulmonary exacerbations by the end of each study.
    RISK OF BIAS: Using Cochrane's Risk of Bias 2 tool, we assessed the risk of bias within each of the included trials and for each outcome from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome and selection of the reported result.
    SYNTHESIS METHODS: Two review authors screened the search results for studies eligible for inclusion in the review and extracted their data. Due to the difference in the studies' interventions, we analysed the data separately. We assessed the overall certainty of the evidence using GRADE.
    INCLUDED STUDIES: We included two studies with 628 participants aged five to 41 years. There was one study in each of two different comparisons.
    SYNTHESIS OF RESULTS: Nebuliser target inhalation mode versus standard inhalation mode One parallel study was carried out over 10 weeks after a run-in period of four to six weeks. The study compared the effects of a digitally enhanced inhalation mode (target inhalation mode) for nebulised antibiotics compared to standard mode in children attending a regional CF clinic in the UK. The primary outcome was the time taken to complete the inhaled treatment, but the study authors also reported on adherence to therapy. The results showed that adherence may improve when using the target inhalation mode (mean difference (MD) 24.0%, 95% confidence interval (CI) 2.95 to 45.05; 1 study, 20 participants; low-certainty evidence). The target inhalation mode may make little or no difference to FEV1 % predicted (MD 1.00%, 95% CI -9.37 to 11.37; 1 study, 20 participants; low-certainty evidence). The study did not report on treatment burden, QoL or pulmonary exacerbations. We downgraded the certainty of the evidence for imprecision due to the small sample size, and for indirectness as the study was carried out in children and the results may not be applicable to adults. eNebuliser with digital support versus eNebuliser without support One large multicentre RCT monitored adherence via data-tracking nebulisers for 12 months. The intervention group also received access to an online web-based platform, CFHealthHub, which offered tailored, flexible support from the study authors as well as access to their adherence data, educational and problem-solving information. Compared to usual care, the digital intervention probably improves adherence to inhaled therapy (MD 18%, 95% CI 12.90 to 23.10; 1 study, 588 participants; moderate-certainty evidence); probably leads to slightly reduced treatment burden (MD 5.10, 95% CI 1.79 to 8.41; 1 study, 539 participants; moderate-certainty evidence); and may lead to slightly improved FEV1 % predicted (MD 3.70%, 95% CI -0.23 to 7.63; 1 study, 556 participants; low-certainty evidence). There is probably little or no difference in the incidence of pulmonary exacerbations or QoL between the two groups. We downgraded the certainty of the evidence for indirectness as the intervention was only assessed in an adult population and therefore may not apply to children.
    AUTHORS' CONCLUSIONS: Digital monitoring plus tailored support via an online platform probably improves adherence to inhaled therapies and reduces treatment burden (but without a corresponding change in QoL) in the medium term (low- and moderate-certainty evidence). In a shorter timeframe, technological enhancement of inhaling antibiotics may improve adherence to treatment (low-certainty evidence). There may be little or no effect on lung function with either intervention, and online monitoring probably makes no difference to pulmonary exacerbations. Future research should assess the effect of digital technology on adherence to inhaled therapies in both children and adults. Consideration of adherence to the total treatment regimen is also important, as improved adherence to inhaled therapies could come at the cost of adherence to other parts of the treatment regimen.
    FUNDING: The original review was supported by Cochrane Infrastructure funding from the National Institute for Health Research (NIHR). The review was updated with Cochrane CF funding from the CF Foundation and the UK CF Trust.
    REGISTRATION: Protocol (2020) DOI: 10.1002/14651858.CD013733 Original review (2023) DOI: 10.1002/14651858.CD013733.pub2.
    DOI:  https://doi.org/10.1002/14651858.CD013733.pub3
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