The common vole (Microtus arvalis) is one of the most abundant rodent species in Europe and is known for its cyclic population outbreaks, which result in significant crop damage and an increased risk of transmission of zoonotic pathogens to humans. In this study, we confirmed that common voles are an important reservoir of multiple zoonotic pathogens in South Moravia, Czech Republic, with a high prevalence of infection and frequent co-infections. Overall, we found 70 (50%), 72 (51.4%), 50 (35.7%) and 35 (25%) positive voles for Leptospira spp., Bartonella spp., Brucella spp. and TULV, respectively. Our results highlight the significant epidemiological role of this species in agricultural ecosystems. Therefore, further studies are needed to monitor vole populations and other small mammal species in this area to better understand pathogen dynamics and assess potential risks to human and animal health.

We aimed to investigate the activity of aztreonam and aztreonam-avibactam combination against gram-negative bacilli producing different types of β-lactamases. Activity of aztreonam and aztreonam-avibactam against 166 isolates (33 AmpC-producing, 33 ESBL-producing, 66 carbapenemase-producing Enterobacterales, 34 metallo-β-lactamase-producing P. aeruginosa) from four centers in Türkiye was determined using gradient diffusion method. Aztreonam susceptibility rates among AmpC-producing, ESBL-producing and carbapenemase-producing Enterobacterales were 75.8%, 3% and 6.1%, respectively. All AmpC-producing or ESBL-producing Enterobacterales were susceptible to aztreonam-avibactam. ESBL-producing K. pneumoniae had significantly higher aztreonam-avibactam MICs compared with ESBL-producing E. coli. K. pneumoniae carrying blaCTX-M + blaSHV + blaTEM had significantly higher aztreonam-avibactam MICs when compared to those carrying only blaCTX-M. Aztreonam-avibactam susceptibility rate among carbapenemase-producing K. pneumoniae (100%) was significantly higher than that observed for carbapenemase-producing E. coli (65%). Metallo-β-lactamase-producing P. aeruginosa had significantly higher aztreonam-avibactam MICs (MIC50/90: 16/96 mg/L) when compared to metallo-β-lactamase-producing Enterobacterales (MIC50/90: 0.19/8 mg/L). Aztreonam-avibactam may be an option for treatment of infections caused by ESBL-producing or AmpC-producing K. pneumoniae, E. coli and carbapenemase-producing K. pneumoniae. However, aztreonam-avibactam resistance may be encountered in a considerable portion of carbapenem-resistant E. coli isolates. High aztreonam-avibactam MIC values suggest limited in vitro activity of aztreonam-avibactam against MBL-producing P. aeruginosa isolates in this collection.

To map international literature on the extent, nature and standards of evidence on postmortem microbiology (PMM) sampling in paediatric cases. Investigations of sudden unexpected deaths in infancy and childhood warrant high standards due to their public health and legal significance. PMM is an integral component of these investigations. The review aimed to examine paediatric studies; however, only a single study was identified. The review therefore included articles on PMM of all ages and forensic and clinical autopsies. Data sources used were Medline, Embase, Cochrane CENTRAL and Scopus. Primary studies were selected by title and abstract screening using Covidence. Twenty four primary studies covering 2965 postmortems with an age range of 0-90+ years. There was significant heterogeneity in the selection of sampling sites and interpretation, with no consistent definition for contamination or true infection. There were significant gaps in literature, particularly the lack of paediatric studies, standardised techniques for specimen collection and definition of contamination. An interpretation framework for PMM results was proposed by the authors. These gaps warrant immediate attention as inconsistent interpretation of PMM results can lead to low public confidence in mortality statistics, disease surveillance data and public health policy.

This bibliometric analysis reveals a substantial increase in global research on postmortem interval (PMI) estimation over the last decade, reflecting growing scientific interest in molecular, omics-based, and data-driven approaches. The bibliometric findings indicate growing research attention toward advanced analytical techniques and interdisciplinary approaches in forensic science. This bibliometric analysis examined Scopus-indexed literature on postmortem interval estimation published between 2015 and 2025. Using VOSviewer, 643 retrieved records were screened, and 497 eligible research articles were analyzed to evaluate publication trends, leading journals, countries, institutions, authors, and keyword co-occurrence and co-citation networks. The analysis revealed a significant and sustained increase in publications over the last two years, reflecting increasing scientific interest in emerging technologies for PMI estimation research. The co-citation analysis identified foundational works that define modern research trends in PMI estimation. Overall, the bibliometric evidence suggests a growing integration of conventional postmortem examination methods with molecular, omics-based, and computational approaches in the scientific literature on PMI estimation.

Necrotizing granulomatous lung lesions have diverse infectious etiologies, and histology with Ziehl-Neelsen (ZN) staining is often insufficient for definitive diagnosis, particularly in formalin-fixed paraffin-embedded (FFPE) tissue. Among 2025 consecutive autopsy cases examined between 2011 and 2025, five cases showed necrotizing granulomatous lung lesions. DNA extracted from lesion-directed, manually trimmed FFPE tissue underwent PCR analysis targeting IS6110 and hsp65. Additional rpoB-based restriction fragment length polymorphism (RFLP) analysis was performed in suspected nontuberculous mycobacterial (NTM) infections, while one case with suspected parasitic infection underwent cox1 PCR and sequencing. Molecular analysis identified Mycobacterium tuberculosis complex (MTBC) in two cases, NTM in two cases, and Dirofilaria immitis in one case. rpoB-based RFLP demonstrated distinct patterns between the two NTM cases. ZN staining showed abundant bacilli in one MTBC case, rare bacilli in another, and negative results in the remaining cases. Lesion-directed manual trimming enabled successful amplification in all cases despite the use of archival FFPE tissue. Multi-target PCR analysis of lesion-enriched FFPE tissue provides a practical approach for etiological evaluation of necrotizing granulomatous lung lesions and may improve diagnostic characterization of paucibacillary or late-stage infectious lesions.

Ghrelin signaling, mediated by the growth hormone secretagogue receptor (GHS-R1a), has emerged as an important regulator of inflammation and bone metabolism. This study investigated GHS-R1a regulation in periodontal tissues exposed to experimental periodontitis (EP), orthodontic tooth movement (OTM), or both. Human periodontal fibroblasts were stimulated with Fusobacterium nucleatum, static tensile strain, or their combination, and GHS-R1a expression was evaluated by RT-qPCR. In vivo experiments were conducted in rats subjected to EP, OTM, or combined treatment. Gingival GHS-R1a expression was assessed by RT-qPCR and immunohistochemistry, while alveolar bone loss was quantified histometrically. Combined bacterial and mechanical stimulation markedly increased GHS-R1a expression in periodontal fibroblasts, whereas either stimulus alone produced minimal changes. Similarly, combined EP and OTM induced a pronounced early increase in gingival GHS-R1a gene and protein expression, which declined over time. Animals exposed to both conditions also exhibited significantly greater alveolar bone loss. These findings demonstrate that periodontal inflammation and orthodontic loading dynamically regulate GHS-R1a, with early upregulation followed by attenuation during prolonged inflammation. The ghrelin/GHS-R1a system may therefore contribute to the periodontal response to concurrent inflammatory and biomechanical stimuli and participate in maintaining tissue homeostasis under inflammatory stress.

Candida albicans presents a major, yet underestimated challenge in clinical settings due to its increased resistance to treatment. This study intended to focus on the utility of a novel proprietary lactam molecule, a quorum sensing (QS) inhibitor, against C. albicans. We assessed isolate susceptibility to lactam treatment. In addition, RNA-Seq was used to assess lactam-induced transcriptional changes in phenotypically distinct C. albicans strains. The mechanistic basis of these transcriptional responses and a series of biochemical assays were performed using the reference strain SC5314. Our findings show that lactam influences multiple cellular processes, including cell wall integrity, efflux pump activity, oxidative stress responses and biofilm formation, with effects differing markedly between high and low biofilm formers. Vacuolation was observed with prolonged exposure to the lactam, and related genes in this process were identified and the phenotype confirmed. These results, supported by pathway analyses and mechanistic validation experiments, indicate that lactam's antifungal activity does not rely on a single mode of action. Rather, it appears to involve multiple mechanisms that vary across heterogeneous C. albicans isolates. These data indicate the potential therapeutic benefit of a novel fungicidal antifungal agent with broad-spectrum activity.

Graft inflammation and fibrosis are associated with progressive fibrosis and potential graft loss after liver transplantation, but diagnosis relies on invasive biopsies. Torque teno virus (TTV) may be a noninvasive marker of functional immunity, however its association with these changes remains unclear. In this Nordic multicenter cohort study, plasma samples collected with biopsies were analyzed for TTV load, and biopsies were scored for inflammation and fibrosis. Associations and performance of TTV versus tacrolimus were evaluated using logistic regression and ROC curves. TTV was categorized using the Youden Index. Among 287 liver transplant recipients, median age was 55, mean TTV load 5 log10 copies/mL and median time from transplantation to TTV measurement 12 months. Low TTV load was associated with higher odds of fibrosis (aOR 2.96 [95% CI 1.40-6.25], adjusted for time since transplantation). Compared with tacrolimus, TTV load remained associated with fibrosis (2.64 [1.19-5.85]), whereas tacrolimus did not (1.16 [0.95-1.42]). The model including both markers had the highest AUC (0.69 [0.60-0.78]). At the optimal threshold, TTV demonstrated 64% sensitivity and specificity, positive predictive value 20% and negative predictive value 93%. TTV load was not significantly associated with inflammation. In conclusion, TTV load may support risk-stratified biopsy strategies, requiring external validation.

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled malignant plasma cell proliferation. B-cell maturation antigen (BCMA) is an attractive therapeutic target due to its high expression on malignant plasma cells. In this study, BCMA-directed CAR-NK-92 cells were generated via lentiviral transduction of a second-generation CAR construct. CAR expression was confirmed by flow cytometry (81% efficiency). Engineered cells were functionally evaluated against BCMA-positive (U266, RPMI-8226) myeloma cell lines, as well as BCMA-negative control cells (K562, Jurkat). CAR-NK-92 cells demonstrated significantly enhanced cytotoxic activity against BCMA-positive targets compared with parental NK-92 cells (e.g., 87% vs. 54% cytotoxicity at 1:1, p < 0.001). Enhanced antitumor activity was accompanied by increased CD107α surface expression and elevated secretion of perforin, granzyme B, TNF-α, and IFN-γ (p < 0.05). No significant differences in cytotoxicity or cytokine secretion were observed against BCMA-negative control cells (p > 0.05), supporting antigen-specific activity. Importantly, CAR-NK-92 cells also exhibited potent cytotoxicity and significantly elevated cytokine secretion against primary CD138+ myeloma cells isolated from patient bone marrow aspirates. These findings demonstrate that anti-BCMA CAR-NK-92 cells exhibit potent and selective antimyeloma activity in vitro, supporting CAR-NK-92 cells as an off-the-shelf immunotherapeutic platform for multiple myeloma.

Ophthalmic imaging has advanced to a level at which it can closely approximate key histopathological features of certain ocular tissues, changing the way ocular disease is screened for, diagnosed, and monitored. Modalities such as optical coherence tomography (OCT), anterior segment OCT (AS-OCT), OCT angiography (OCTA), and in vivo confocal microscopy (IVCM) capture tissue architecture with high-resolution structural and even microvascular information. In this review, the authors summarize the current evidence on artificial intelligence (AI) based applications that utilize high-resolution ophthalmic imaging and digital pathology to support near-histologic interpretation across a range of ocular diseases. Reported diagnostic performance and concordance with histopathologic findings are examined while describing the technical, biological, and regulatory boundaries of AI-derived inference. While AI supports objective, scalable, and reproducible analyses of ophthalmic imaging data, limitations in resolution, generalizability, and specificity prevent its use as an independent substitute for tissue-based diagnosis where histopathologic confirmation is required.

The sustained increase in antimicrobial resistance among Gram-negative bacilli (GNB) compromises the effectiveness of empirical treatment regimens. This study aims to describe the evolution of the frequency and antimicrobial resistance profiles of the most commonly isolated GNB in urine cultures in our area. A cross-sectional, descriptive, and retrospective study was conducted, analyzing urine cultures from patients with suspected UTIs between 2021 and 2025. Microorganism identification was performed using MALDI Biotyper or MicroScan systems, and antimicrobial susceptibility testing was carried out using MicroScan, interpreted according to EUCAST guidelines. A total of 81,791 urine cultures were analyzed. In E. coli, a significant increase in resistance was observed for amoxicillin-clavulanate, ciprofloxacin, piperacillin-tazobactam, and fosfomycin (from 3.48% in 2021 to 25.31% in 2025). Klebsiella pneumoniae showed a marked increase in resistance to fosfomycin (from 27.25% to 79.73%) and imipenem. Pseudomonas aeruginosa, predominantly hospital-acquired, exhibited a significant increase in resistance to piperacillin-tazobactam, imipenem, and antipseudomonal cephalosporins. The evolution of antimicrobial resistance in uropathogenic GNB in our region is complex and dynamic. The spread of carbapenemases highlights the need for rigorous local epidemiological surveillance and optimization of antimicrobial stewardship programs to guide empirical therapy and infection control measures.

This retrospective study explored the relationship of serum neutrophil-to-lymphocyte ratio (NLR) and fibrinogen-to-albumin ratio (FAR) with disease activity and lupus nephritis (LN) in systemic lupus erythematosus (SLE) and assessed the clinical value of the derived combination model. Patients (N = 147) with SLE were enrolled in the final analysis. Peripheral blood NLR and FAR also differed between subgroups based on LN absence/presence: LN (79 cases) and non-LN groups (68 cases) were independently associated with SLE disease activity and LN onset according to univariate and multivariate logistic regression results. Crucially, the NLR and FAR composite model demonstrated potentially auxiliary performance superior to the conventional indicator composite model (anti-dsDNA, complement C3/C4, 24-h UPr), yielding an area under the ROC curve (AUC) of 0.865 for severe disease activity (95% CI: 0.799-0.915, sensitivity: 0.833, specificity: 0.769) and 0.922 for LN development (95% CI: 0.867-0.962, sensitivity: 0.785, specificity: 0.941). In conclusion, peripheral blood NLR and FAR may serve as potentially useful auxiliary biomarkers for identifying severe disease activity and LN in patients with SLE. These exploratory findings were obtained from a single-center, small-scale population. Therefore, multi-center prospective cohort studies with large-scale populations are needed to confirm their clinical applicability and generalizability.

Bacterial infections present a challenge in clinical settings due, in part, to their remarkable diversity in physiological context and treatment resistance. Bacteriophage viruses (phages) offer renewed therapeutic promise, yet their performance in vivo often differs from expectations based on standard laboratory assays. Biofilms, with their dense extracellular matrix and spatial heterogeneity, restrict phage access, diffusion, and replication. Anaerobic niches and metabolically dormant bacterial subpopulations at the biofilm core pose additional hurdles, often rendering bacteria tolerant to both antibiotics and phages. These physiological constraints are rarely captured during phage isolation, where agar-based plaque assays, oxygen-rich conditions, and rapidly growing hosts inadvertently deselect phages adapted to biofilms, anaerobic zones, or dormant states. Understanding how phage-bacterial interactions vary across these niches and how antibiotics synergize with or antagonize phage activity is essential for designing therapies with improved effectiveness beyond the Petri dish. This TechNote synthesizes key challenges for phage infection dynamics in biofilms, anaerobic environments, and dormant populations, highlighting the need for isolation and screening strategies that better reflect the physiology of clinical infections.