PubMed

Introduction Two severe acute respiratory infection (SARI) case definitions (CDs) are often used in test-negative design (TND) hospital-based vaccine effectiveness (VE) studies. SARI-CD1 requires ≥1 symptom (cough, fever, shortness of breath, anosmia, ageusia, or dysgeusia); SARI-CD2 requires both fever and cough. Using VEBIS hospital network end-of-season 2023/24 data, we compared the effect of these CDs on influenza and COVID-19 VE estimates in Europe. Methods Using the TND, we restricted analysis to seven countries recruiting patients using SARI-CD1; we created a subset of SARI patients also meeting SARI-CD2. Cases were RT-PCR-positive for influenza A(H1N1)pdm09, A(H3N2), or SARS-CoV-2; controls were influenza or SARS-CoV-2 RT-PCR-negative. We estimated VE among patients ≥65 years using logistic regression adjusted for country, onset date, age, sex, and chronic conditions. We estimated VE overall, by age group (65–79, ≥80 years) and time since vaccination (14–59, 60–119, ≥120 days). Absolute VE differences ≥10% were considered relevant. Results Patient characteristics and outcomes were similar across CDs. SARI-CD1 had slightly more vaccinated cases, with little difference in controls between the two CDs. For influenza, the absolute VE difference between SARI-CD1 and SARI-CD2 was 10% for influenza A(H1N1)pdm09 (34% vs 44%), 19% among those aged ≥80 years (21% vs 40%) and 18% at 60–119 days post-vaccination (4% vs 22%). For SARS-CoV-2, absolute VE differences were 11% overall (29% vs 40%), 11% among ≥80 years (33% vs 44%), and 12% at 60–119 days (34% vs 46%). All other absolute VE differences were < 10%. Conclusions VE was similar for influenza A(H3N2), adults 65–79 years and 14–60 days post-vaccination. We observed signals of higher VE with SARI-CD2 for influenza A(H1N1)pdm09 and SARS-CoV-2, particularly among adults ≥80 years and ≥ 60 days post-vaccination, although 95% CIs overlapped. These signals suggest CDs may contribute to VE variability and VE studies should clearly indicate CDs used.

Background/Aim: Osteosarcoma (OS) treatment consists of chemotherapy with methotrexate, adriamycin (doxorubicin) and platinol (MAP) combined with intercalated surgery, resulting in a 5-year survival rate of 50–60%. We recently demonstrated that local delivery of doxorubicin via a microparticulate hydroxyapatite-based biomaterial (DASH) could efficiently impede tumor growth in subcutaneous OS; however, its effect in an orthotopic intraosseous OS remains unknown, particularly in conjunction with systemic MAP treatment. In this study, we performed two separate mouse model studies with the aim of (1) evaluating the effect of DASH in an orthotopic osteosarcoma model and (2) evaluating the efficacy and tolerability of DASH in conjunction with systemically administered MAP in a subcutaneous osteosarcoma model. Methods: In the first study, 56 mice were inoculated with human OS cells (i.e., h143B cells) in the proximal tibia. After 10 days, the mice were divided into seven treatment groups, of which group G2 (systemic DOX) was compared with groups G5–G7, which were treated with increasing doses of DOX delivered via DASH. The tumor-impeding response was evaluated via micro-CT (day 14), PET-CT (day 21) and tumor measurements (post-mortem). In the second study, 45 mice were inoculated subcutaneously with 143B cells and, 10 days later, groups G2–G5 were treated locally with increasing DASH doses, followed by two cycles of systemic MAP for all groups. On day 31, the animals underwent PET-CT examination followed by euthanasia and tumor measurements. Results: In both experiments, DASH treatment resulted in significantly lower tumor activity, tumor volume and weight. Micro-CT examination in the orthotopic model demonstrated that DASH treatment protected the bone from osteolysis. The subcutaneous study revealed that the mice were able to tolerate DASH, even in conjunction with systemically administered MAP. Conclusions: Intratumoral administration of DASH impeded OS growth in both animal models and protected bone against tumor-induced osteolysis. Furthermore, DASH was well-tolerated when administered in conjunction with systemic MAP therapy, indicating its potential therapeutic neo-adjuvant value in poor responders.

Background/Aim Avulsion of a permanent tooth is a critical dental emergency requiring rapid intervention to optimize replantation outcomes and minimize complications. Conventional storage media maintain periodontal ligament cell viability but often lack sufficient antimicrobial protection and mechanical stabilization during transport. Hydrogels, specifically those combining gellan gum and natural additives like propolis, offer promising improvements by providing enhanced antimicrobial activity and mechanical cushioning. The aim of this study was to systematically evaluate a hydrogel-based transport medium supplemented with propolis and optimized gellan gum concentration for its ability to preserve cell viability, inhibit microbial growth, and confer mechanical stability to avulsed teeth during simulated transport.

Various Spirulina species and their major pigment, Cyano-phycocyanin (C-PC), have been shown to exhibit antioxidant, anti-inflammatory, and anticancer properties, and are used in various skincare products. Spirulina platensis is rich in nutrients, proteins, and antioxidants, with therapeutic potential for skin protection and regeneration. Aqueous Spirulina extracts have gained increasing attention in recent years due to their biocompatibility; however, comparative assessment of aqueous extract and C-PC responses across non-malignant and malignant skin cells remains limited. This study aimed to evaluate the effects of S. platensis aqueous extract and C-PC on the cellular metabolic activity and wound healing of human skin cell lines—melanoma cells, keratinocytes, and fibroblasts—using a 24 h PrestoBlue assay and time-resolved scratch assays. The results demonstrated a concentration- and cell-type-dependent response to both preparations: at selected concentrations, S. platensis aqueous extract and C-PC reduced melanoma cellular metabolic activity while increasing it in keratinocytes and fibroblasts. Notably, both S. platensis aqueous extract and C-PC significantly accelerated wound closure at selected concentrations in keratinocytes and fibroblasts but not in melanoma cell cultures. Additionally, the S. platensis extract exhibited strong antioxidant activity, which correlated with its phenolic and flavonoid content. In conclusion, S. platensis aqueous extract and C-PC exhibit concentration- and cell-type-dependent effects on skin cell metabolic activity and scratch closure, supporting further investigation of their potential for skin-repair applications.

Background/Objectives: The complex nature of endodontic/periodontal lesions complicates treatment prognosis, making long-term tooth survival challenging to predict. Identifying key prognostic factors can facilitate evidence-based clinical decision-making. This systematic review aims to evaluate the available evidence on factors associated with treatment outcomes in endodontic/periodontal lesions and to identify potential prognostic indicators. Methods: PubMed/MEDLINE, Embase, Web of Science and Cochrane Library were searched from 1 June to 1 July 2026 with no restrictions. Observational studies investigating associations between baseline prognostic factors and treatment outcomes in adults with endodontic/periodontal lesions were eligible for inclusion. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence was evaluated using GRADE. Due to substantial methodological heterogeneity, the findings were synthesized narratively rather than through meta-analysis. Results: Four retrospective studies comprising 501 teeth were included. Risk of bias was predominantly moderate to high, and certainty of evidence was low. No single factor demonstrated directionally consistent independent association across the available adjusted analyses. Conclusions: Despite limited evidence, an overall pattern suggests that endodontic/periodontal lesion prognosis may be most frequently associated with the extent of periodontal tissue destruction and the amount of remaining periodontal support. Prospective studies using standardized endodontic/periodontal lesion definitions, outcomes and appropriately adjusted multivariable prognostic models are needed.

Background and Objectives: The Canadian Occupational Performance Measure (COPM) is a widely used client-centered outcome measure designed to evaluate individuals’ self-perceived occupational performance and satisfaction with performance. Although an official Lithuanian version is available, its psychometric properties have not previously been evaluated in individuals undergoing poststroke rehabilitation. This study aimed to examine the test–retest reliability, concurrent validity, and responsiveness of the Lithuanian version of the COPM. Materials and Methods: Thirty-one individuals with subacute stroke participated in this prospective validation study. Test–retest reliability was assessed over a three-day interval using the intraclass correlation coefficient (ICC). Concurrent validity was examined by correlating COPM Performance and Satisfaction scores with the Functional Independence Measure (FIM). Responsiveness was evaluated by comparing baseline and discharge COPM scores following inpatient rehabilitation. Additional exploratory analyses assessed whether demographic or clinical characteristics were associated with COPM scores. Results: The Lithuanian version of the COPM demonstrated high test–retest reliability, with ICC values of 0.974 (95% CI: 0.947–0.988) for Occupational Performance and 0.956 (95% CI: 0.911–0.979) for Occupational Satisfaction (both p < 0.001). Concurrent validity was partially supported by weak-to-moderate correlations between the COPM and the FIM at both the initial and final evaluations. Both COPM subscales showed significant improvements following inpatient rehabilitation (p < 0.001), with a mean change of 2.37 and 2.18 points for Occupational Performance and Occupational Satisfaction, respectively. Improvements of at least 2 points, a commonly used threshold for minimal important change in COPM scores, were observed in 51.6% and 41.9% of participants, respectively. Exploratory analyses showed no significant differences according to sex, stroke type, or affected body side. Conclusions: The Lithuanian version of the COPM demonstrated high test–retest reliability, evidence partially supporting concurrent validity, and responsiveness to change in individuals undergoing poststroke rehabilitation. These findings support its use as a client-centered outcome measure for evaluating occupational performance and satisfaction alongside standardized functional assessments.

Glioblastoma (GBM) remains highly lethal despite early therapeutic responses, as resistance inevitably emerges. While clinical studies show improvements in progression-free survival (PFS) during the early response (ER) phase, the molecular trajectory bridging ER and recurrent resistance (RR)-and the adaptive resistance programs temporally engaged during this transition- remain poorly understood. To dissect the dynamic molecular evolution underlying therapy resistance, patient-derived xenograft (PDX) models were treated with anti-VEGF therapy. Longitudinal proteogenomic profiling across multiple time points was performed to capture time-resolved molecular changes associated with the tumor response to the therapy. Longitudinal analyses revealed a dynamic, temporally evolving response trajectory, with an initial response phase (IRP) marked by neuronal-like remodeling, and a late response phase (LRP) characterized by mesenchymal transdifferentiation and metabolic adaptation. Proteomic and phosphoproteomic analyses identified the CTNNB1-NRG3-ERBB4 signaling axis as a key driver of neuronal-like remodeling during the IRP. Mechanistically, β-catenin activation upregulated NRG3, promoting postsynaptic scaffold remodeling, while pharmacological inhibition of β-catenin/CBP with PRI-724 disrupted this neuronal program and significantly extended survival in vivo. These findings place neuronal-like remodeling within a time-resolved framework of tumor adaptation to anti-VEGF therapy in GBM and highlight the CTNNB1-NRG3-ERBB4 axis as a tractable therapeutic target, providing a rationale for combination strategies to overcome anti-VEGF therapy failure.

Periprosthetic joint infection (PJI) remains one of the most devastating complications following total joint arthroplasty (TJA). Nevertheless, a universally accepted definition of treatment success and failure has not been described to date. Current definitions each carry major limitations that fail to account for the full spectrum of clinical scenarios encountered in practice and do not adequately reflect the evolving understanding of PJI pathogenesis. Consequently, reported treatment success rates vary widely across the literature, ranging from 54.2 to 88.9%. The purpose of this initiative was to engage the orthopaedic and infectious disease communities to establish a revised, practical, and consensus-driven definition for PJI treatment outcomes. The 2025 International Consensus Meeting convened a multidisciplinary international workgroup, which defined treatment success as the absence of clinical failure following reimplantation, no revision surgery or reoperation attributable to PJI, no requirement for suppressive antibiotics beyond one year from surgical intervention, and no PJI-related mortality. Outcomes assessment initiates at the time of index surgical intervention, regardless of the procedure performed, and all subsequent revision arthroplasty must be adequately investigated to rule out an infectious etiology. The extent of this evaluation should include serologic markers, joint aspiration, and intraoperative cultures, in accordance with validated diagnostic criteria. It is hoped that adoption of this standardized definition will reduce reporting variability, facilitate more accurate assessment of emerging surgical interventions, and enable meaningful comparison of treatment efficacy across institutions and future studies.

Cognitive impairment in cirrhosis is associated with an altered gut‒liver‒brain axis, but geographic variations in diet and clinical practices may limit generalizability. We investigated consistency of microbial signatures for cirrhosis-related cognitive impairment across four countries. We enrolled outpatients with cirrhosis from USA, Denmark, Lithuania, and Mexico who underwent Psychometric Hepatic Encephalopathy Score (PHES) testing for covert hepatic encephalopathy (CHE), and stool shotgun metagenomic sequencing. Taxonomic and functional associations with PHES were evaluated after adjustment for MELD, country, demographics, sex, proton pump inhibitor (PPI), lactulose, and rifaximin use. We enrolled 221 patients (median age 58 y, 57.9% men, median MELD 12). Cognitive performance varied by country despite adjustment for clinical covariates. Lithuania demonstrated greater microbial richness and better cognition despite higher MELD, accompanied by distinct dietary patterns including greater yogurt and tea consumption. In the entire cohort, increasing MELD was associated with reduced microbial richness and depletion of commensals. Worse PHES performance, however, showed a distinct microbiome signature with increased Streptococcus abundance independent of MELD, country, PPI use, and HE therapies. Twenty-two microbial pathways were associated with PHES, mostly related to amino-acid biosynthesis and nitrogen metabolism. Of these, ornithine degradation and heme B biosynthesis II were uniquely enriched with worse PHES and CHE, which mapped onto Enterobacteriaceae. We conclude that across four geographically and culturally disparate countries, cirrhosis-related cognitive impairment was associated with consistent microbial compositional and functional alterations distinct from advancing liver disease. These findings support a consistent gut‒liver‒brain axis signature involving oral–gut translocation and altered nitrogen metabolism.

Colorectal cancer (CRC) encompasses biologically diverse cellular phenotypes with distinct microRNA (miRNA) expression patterns. Assessing whether cell-model-derived alterations recur in extracellular vesicles (EVs) and human tumors may help prioritize candidates with broader relevance to CRC. We performed small RNA sequencing of non-malignant HCoEpiC cells, differentiated enterocyte-like Caco-2 cells, less differentiated HCT116 cells, and their corresponding EVs. miRNAs showing concordant dysregulation in both CRC cell lines relative to HCoEpiC, with greater absolute log2 fold changes in HCT116, were prioritized and evaluated in human colorectal tissues and TCGA-COAD/READ. Seven of 29 prioritized cellular miRNAs met the EV selection criteria. Of the 26 candidates measurable in the patient-tissue dataset, eight showed FDR-significant, directionally concordant differences between CRC and healthy colorectal tissues, including five concordantly dysregulated across cells, EVs, and patient tissues. Analysis of 11 matched TCGA tumor–non-tumor pairs reproduced reduced miR-30a-3p, miR-30c-2-3p, and miR-1271-5p and increased miR-140-5p expression. Target-based enrichment and exploratory miRNA-mRNA correlation analyses identified associations with CRC-relevant signaling and MYC-related, cell-cycle, DNA-repair, and metabolic programs. No significant associations with the evaluated clinicopathological features or overall survival were detected. Collectively, these findings identify a reproducible subset of CRC-associated miRNA alterations and highlight reduced miR-30a-3p and miR-30c-2-3p expression as a recurrent family-level pattern warranting mechanistic investigation.