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PubMed2026

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate > 81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r = 0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, αVβ3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals↗

PubMed2026

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans↗

PubMed2025

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 ± 12.7 min) than the C group (29.9 ± 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% ± 1.39% vs. 30.0% ± 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 ± 25.3 vs. 63.0 ± 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 ± 9.3 vs. 21.5 ± 12.5, p < 0.01), days of antibiotic use (15.5 ± 8.7 vs. 18.7 ± 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

Humans↗

PubMed2026

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

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PubMed2026

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6 months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12 months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6 months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p = 0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p < 0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p < 0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6 months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans↗

PubMed2026

Single-organ proteomics in Drosophila melanogaster larva.

The combination of genetic accessibility, organ complexity, evolutionary conservation, and cost-efficiency makes Drosophila melanogaster (Dm) a well-known model system for biomedical and fundamental biological research. Proteomic analysis of single organs enables the identification and quantification of proteins expressed in specific organs. This will help to uncover specific biological functions and unique protein profiles that are not detectable in whole-organism analyses. In this study we have isolated single organs form Dm larvae, and we have performed a deep proteomics mapping by following a minimal manipulation preparation procedure. The combined dataset across all organs comprised 9132 identified proteins. As anticipated, principal component analysis (PCA) revealed clear separation between the proteomes of most organs, confirming distinct protein profiles. These findings demonstrate the applicability of the sample preparation strategy for high-resolution proteomic characterization of individual organs in Drosophila. Given the extensive genetic tools available for this model organism, our approach has the potential to open new avenues for proteomic studies in Drosophila melanogaster and any other biological systems where the sample amount is limiting. SIGNIFICANCE STATEMENT: Drosophila melanogaster is a well-known model system for biomedical and fundamental biological research that serves as a valuable in vivo model organism due to its high degree of evolutionary conservation with higher vertebrates, tractable genetics, and logistical efficiency. However, the proteome of Drosophila at single organ level has been elusive to date, due to several factors like low sensitivity of previous generation mass spectrometers and sample preparation procedures, difficult isolation of some organs. In this study we have applied a compilation of advanced methods including minimal sample manipulation together with simple, straightforward and efficient protein extraction and digestion methods. Obtained peptides were minimally handled to be analyzed by applying specific and sensitive nLC methods coupled on-line to state-of-the-art MS/MS system. Altogether, the applied strategy allowed us to get the first single organ study to date for this animal. These datasets represent a significative resource for future genomic, transcriptomic and proteomic studies in Drosophila, as multi-omic integration requires deep proteomics to translate data into functional biochemistry, and serves as a critical bridge and an indispensable standalone resource across the genomic, transcriptomic, and proteomic landscapes.

Animals↗

PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗

PubMed2026

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged ≥50 (hip) or ≥38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64±8 years), baseline NRS was 3.2±2.3 in the CG and 3.5±2.4 in the IG; HOOS/KOOS-ADL was 71.6±17.7 and 69.4±17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans↗

PubMed2026

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31 mm (95% CI -0.63 to 0.02; p = 0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2 = 28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43 mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43 mm; 95% CI -0.70 to -0.16; p = 0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans↗

PubMed2026

The Effect of Robot-Assisted Gait Training on Balance, Gait and Kinesiophobia in Individuals With Post-Stroke Hemiparesis: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Robot-assisted gait training (RAGT) is well established for post-stroke gait rehabilitation, but its potential effects on psychological and behavioral outcomes are less clear. This study investigated the effects of adding RAGT to conventional rehabilitation on balance, gait, kinesiophobia, and movement confidence in individuals with post-stroke hemiparesis. METHODS: This single-blind, parallel-group randomized controlled trial included 60 individuals with post-stroke hemiparesis (50-75 years), randomly allocated to an RAGT group (n = 30) or control group (n = 30). Ethical approval was obtained from the Clinical Research Ethics Committee of Istanbul Yeni Yüzyıl University (Approval No. 20.01.2022/05; approval date: 20 January 2022). Both groups received conventional rehabilitation for 8 weeks; the RAGT group additionally received 24 sessions of RAGT. Kinesiophobia was a prespecified study outcome assessed using the Kinesiophobia Causes Scale (KCS); balance, gait, and balance confidence were also assessed. All 60 randomized participants completed follow-up and were analyzed in their assigned groups. RESULTS: Significant group × time interactions were observed for several outcomes, including BBS, TUG duration, 10MWT walking speed, ABC, and KCS total score (p < 0.05). The between-group difference in change for KCS total score was -0.36 (95% CI: -0.51 to -0.21; partial eta squared = 0.292). In post hoc analyses adjusting each outcome for its baseline value, significant group effects remained for BBS, TUG duration, 10MWT walking speed, ABC, KCS biological domain, and KCS total score (p< = 0.031), whereas 10MWT step count and the KCS psychological domain were no longer statistically significant. DISCUSSION: Adding RAGT to conventional rehabilitation was associated with greater improvements in several balance, mobility, walking-speed, balance-confidence, and kinesiophobia outcomes compared with conventional rehabilitation alone. These findings suggest potential additional physical and psychological benefits of incorporating RAGT into post-stroke rehabilitation. However, because the RAGT group received greater overall treatment exposure, the observed between-group differences cannot be attributed solely to the robotic component. The principal contribution of this study is the concurrent evaluation of kinesiophobia and movement confidence alongside physical outcomes.

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PubMed2026

Impact of PerioperAtive LidocAine Infusions on Enhanced Recovery After Noncardiac Surgery (IMPALA-ERAS) in an inpatient setting: rationale, design and protocol for a sequential, repeated crossover trial.

INTRODUCTION: Multimodal analgesic strategies designed to minimise perioperative opioid exposure are fundamental components of enhanced recovery after surgery (ERAS) pathways. Despite widespread implementation of ERAS protocols, the optimal analgesic regimen remains undefined, as the individual contributions of specific agents to overall analgesic efficacy and opioid-sparing effects are not fully elucidated. Intravenous lidocaine, a widely utilised local anaesthetic, possesses both analgesic and anti-inflammatory properties and has been associated with improved gastrointestinal recovery. This study seeks to pragmatically evaluate the impact of incorporating perioperative intravenous lidocaine infusion into established ERAS pathways on postoperative functional recovery. METHODS AND ANALYSIS: The Impact of PerioperAtive LidocAine Infusions (IMPALA) on ERAS trial is a single-centre, pragmatic, cluster-randomised, double-blinded, placebo-controlled study. A total of 2290 patients undergoing elective colorectal surgery, emergency general surgery, urology, ventral hernia repair, surgical oncology or spine surgery will be randomly assigned to receive either intraoperative and postoperative intravenous lidocaine infusions (administered for up to 48 hours) or placebo as part of a standardised multimodal analgesic regimen integrated into established ERAS pathways. The primary outcome is case mix index-adjusted resource length of stay, defined as the time interval from surgical initiation to hospital discharge adjusted for case mix index. The primary outcome is total inpatient opioid consumption within the first 72 hours, reported in oral morphine milligram equivalents. Secondary outcomes include various in-hospital clinical endpoints derived from the electronic health record. ETHICS AND DISSEMINATION: This protocol and accompanying statistical analysis plan outline the study design, primary and secondary endpoints and analytic methodology. The IMPALA-ERAS trial has received ethical approval from the Vanderbilt University Institutional Review Board (IRB: 250617). The findings will be disseminated via peer-reviewed publications and presentations at national conferences. Results from this trial are expected to inform evidence-based practices regarding perioperative lidocaine infusion and its potential contributions to enhanced postoperative recovery in surgical patients. TRIAL REGISTRATION NUMBER: NCT07224711.

Humans↗

PubMed2026

Evaluation of three Aspergillus antibody assays for screening of chronic pulmonary aspergillosis: prospective diagnostic accuracy study.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a frequent complication of pulmonary tuberculosis (PTB), particularly in high-burden settings where access to reliable serological diagnostics remains limited. We evaluated the diagnostic performance of two immunochromatographic technology (ICT) lateral flow assays (LFAs) and an ELISA for CPA screening among patients with active or previously treated PTB. METHODS: In this two-year prospective multicentre diagnostic evaluation, serum from adults with prior or active PTB was tested using the Era Biology Aspergillus IgG ICT LFA, LDBio Aspergillus IgG/IgM ICT LFA, and Bordier Aspergillus fumigatus IgG ELISA. CPA diagnosis was established using a consensus composite reference standard incorporating clinical, immunological, radiological, and microbiological criteria. The Bordier ELISA was used as part of the immunological component of the consensus CPA diagnosis, with a cutoff optical density of ≥1.0. Diagnostic accuracy, agreement statistics, receiver operating characteristic analysis, and latent class analysis (LCA) were performed. RESULTS: Among 340 participants, 24 (7.06%) had CPA. Proportion of participants with positive antibody tests among all tested individuals were 6.76% for LDBio ICT LFA, 20.0% for Era Biology ICT LFA, and 11.47% for Bordier ELISA. Against consensus CPA diagnosis, Bordier ELISA showed 87.50% sensitivity and 94.30% specificity, LDBio ICT LFA 58.33% sensitivity and 97.15% specificity, and Era Biology LFA 66.67% sensitivity and 83.54% specificity. LCA estimated CPA prevalence at 7.72%. LCA-derived sensitivities and specificities were 86.58% and 99.92% for LDBio ICT LFA, 83.39% and 85.31% for Era Biology LFA, and 79.10% and 94.19% for Bordier ELISA. CONCLUSIONS: The Bordier ELISA showed high sensitivity and specificity, while the LDBio ICT LFA demonstrated very high specificity with strong LCA-derived performance. These findings support the use of ELISA for laboratory diagnosis and ICT as a point-of-care screening tool for CPA in resource-limited settings. Era Biology Aspergillus IgG LFA demonstrated moderate sensitivity and acceptable diagnostic performance, indicating its potential utility as a supplementary screening assay for CPA in settings where rapid, point-of-care testing is required.

Humans↗

PubMed2026

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber↗

PubMed2026

Malnutrition and adverse outcomes after spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Malnutrition is linked to adverse surgical outcomes, but its impact in spine surgery remains unclear due to inconsistent findings and heterogeneous definitions, including use of serum albumin, prealbumin, lymphocyte count, the Geriatric Nutritional Risk Index, and the Prognostic Nutritional Index. We conducted a systematic review and meta-analysis to evaluate the relationship between malnutrition and postoperative outcomes in spine surgery. PURPOSE: To systematically evaluate the association between preoperative malnutrition and postoperative outcomes in patients undergoing spine surgery. STUDY DESIGN: Systematic review and meta-analysis. PATIENT SAMPLE: Patients undergoing elective or urgent spine surgery across included observational studies comparing malnourished vs well-nourished cohorts. OUTCOME MEASURES: Primary outcomes included postoperative mortality and overall surgical complications. Secondary outcomes included infectious complications (sepsis, urinary tract infection, wound complications), delirium, reoperation, 30-day and 90-day readmission, and prolonged length of hospital stay. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed on April 7, 2025, following PRISMA guidelines. Studies directly comparing postoperative outcomes in malnourished vs well-nourished spine surgery patients were included. A random-effects model generated pooled odds ratios for complications. Outcomes assessed included mortality, surgical complications, infectious outcomes, readmission, reoperation, delirium, prolonged length of stay, and wound complications. RESULTS: Of 2,851 screened articles, 37 met the inclusion criteria, encompassing 16,987 malnourished patients. Malnutrition was associated with significantly increased odds of mortality (OR: 4.05, 95% CI [2.97-5.54]), delirium (OR: 3.95, 95% CI [2.49-6.27]), sepsis (OR: 2.77, 95% CI [2.31-3.33]), surgical complications (OR: 1.79, 95% CI [1.57-2.04]), urinary tract infection (OR: 1.81, 95% CI [1.59-2.06), wound complications (OR: 2.10, 95% CI [1.80-2.45]), reoperation (OR: 1.70, 95% CI [1.46-1.97]), prolonged length of hospital stay (OR: 3.46, 95% CI [2.57-4.65]), 30-day readmission (OR: 1.59, 95% CI [1.36-1.86]), and 90-day readmission (OR: 2.13, 95% CI [1.67-2.71]). CONCLUSIONS: Malnutrition was consistently associated with adverse outcomes after spine surgery. Routine nutritional assessment and targeted preoperative optimization should be considered a standard component of perioperative spine care to help reduce postoperative complications and improve recovery.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Translating single-cell RNA sequencing into monocyte direct leukocyte subpopulation-transcript abundance assay ratio-based biomarkers (IFI27/PSAP or IFI27/CTSS) for clinical detection of viral infection.

A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.

Humans↗

PubMed2026

Temporal proteomic analysis reveals a three-phase adaptation strategy in Phytophthora cinnamomi during salinity stress.

Phytophthora cinnamomi, a highly invasive hemibiotrophic oomycete, threatens global agriculture, forestry, and native ecosystems. Although drought and temperature effects on P. cinnamomi-host interactions are well studied, current knowledge of abiotic stress responses in P. cinnamomi remains largely centered on infection and phytopathology, with limited molecular insight into the pathogen's direct response to salinity independent of its host. To address this gap, we combined growth assays, time-resolved proteomics, and network analysis to define how P. cinnamomi responds and adapts to salinity exposure. Growth assays showed that NaCl-modified agar enhanced mycelial expansion in a concentration-dependent manner, with 100 mM NaCl significantly increasing growth at 48, 72, and 96 h compared with controls, while 50 mM NaCl remained comparable to control conditions. Temporal proteomic analysis of 100 mM NaCl treatment at 0, 1, 6, 12, and 24 h post treatment revealed dynamic shifts in protein abundance. Early induction of ROS (Reactive Oxygen Species)-detoxifying enzymes, including glutathione S-transferases and peroxidases, was consistent with ROS-specific staining assays. Network analysis identified modules enriched for redox regulation, ATP generation, ion transport, and translational control, highlighting multi-layered adaptation to elevated NaCl levels. Notably, clusters of conserved hypothetical proteins were strongly upregulated, indicating unexplored stress tolerance components in Phytophthora species. Here, we propose that P. cinnamomi rapidly activates a three-phase strategy involving metabolism readjustments, redox defenses, and cellular structure alterations under salinity conditions. With increasing soil salinization due to climate change, our study provides first mechanistic insights into P. cinnamomi's adaptive plasticity and ecological resilience to abiotic stress. SIGNIFICANCE: This study represents the first temporal proteomic analysis of salinity stress adaptation in Phytophthora cinnamomi, revealing a sophisticated three-phase adaptation strategy. This research fundamentally advances our understanding of how this globally destructive plant pathogen, P. cinnamomi, maintains environmental resilience. Our findings reveal proteome remodelling as a mechanistic framework for understanding stress tolerance in oomycetes, a group of microorganisms responsible for some of the world's most destructive agricultural and forest diseases. Our results show proteins involved in emergency damage control through metabolic recalibration to sustained adaptation. These findings have relevance for predicting pathogen behavior under climate change scenarios, where increasing soil salinity threatens agricultural productivity while simultaneously enhancing pathogen survival and virulence. Understanding how P. cinnamomi responds to prolonged salinity exposure may inform targeted biocontrol strategies and improve predictive models of disease pressure in salt-affected agricultural regions. The temporal analysis framework we present offers a broadly applicable approach for understanding microbial stress adaptation, with implications extending beyond plant pathology to environmental microbiology and biotechnology applications where stress tolerance is paramount.

Phytophthora↗

PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗