BioMed Research International

Abstract Background: Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives: This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design: The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes: The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions: Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number: ChiCTR2300074147 (www.chictr.org.cn).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved since its emergence in the human population in 2019. As of 1st August 2025, more than 1,700 Omicron subvariants have been designated by the Pango nomenclature system. The Pango nomenclature system designates a new lineage based on genetic and epidemiological information of SARS-CoV-2 strains. However, there is a possibility that strains that have similar genetic backgrounds and the same phenotype are given different Pango lineage names. In this paper, we propose a new algorithm, called FindPart-w, which can identify groups of viral lineages that share the same relative effective reproduction numbers. We introduced a new lineage replacement model, called the constrained RelRe model, which constrains groups of lineages to have the same relative effective reproduction numbers. The FindPart-w algorithm searches the equality constraints that minimise the Akaike Information Criterion of constrained RelRe models. Using hypothetical observation count data created by simulation, we found that the FindPart-w algorithm can identify groups of lineages having the same relative effective reproduction number in a practical computational time. Applying FindPart-w to actual real-world data of time-stamped lineage counts from the United States, we found that the Pango lineage nomenclature system may have given different lineage names to SARS-CoV-2 strains even if they have the same relative effective reproduction number and similar genetic backgrounds. In conclusion, this study showed that viruses that had the same relative effective reproduction number were identifiable from temporal count data of viral sequences. These findings will contribute to the future development of lineage designation systems that consider both genetic backgrounds and transmissibilities of lineages.

Aim: To comprehensively characterize the salivary proteome in periodontitis using Orbitrap Astral data-independent acquisition mass spectrometry (DIA-MS), identify an atlas of differentially expressed proteins (DEPs), and develop a machine learning-derived multi-protein biomarker panel for non-invasive diagnosis of stage III/IV periodontitis. Materials and Methods: Unstimulated saliva samples from 199 participants (periodontal health/gingivitis, n=120; stage III/IV periodontitis, n=79) were analyzed by Orbitrap Astral DIA-MS. DEPs were identified, and pathway enrichment analysis was performed. A two-tier machine learning pipeline, integrating pathway-based feature selection with cross-validated evaluation, was applied to identify the optimal diagnostic panel. Results: Orbitrap Astral DIA-MS quantified 5,597 salivary proteins and 1,966 DEPs (|log2FC|>0.5, FDR<0.05). Pathway analysis identified 14 periodontitis-relevant KEGG pathways, including Th17 cell differentiation, IL-17 signaling, neutrophil extracellular trap formation, and complement and coagulation cascades. A four-protein panel (TEC, RAC1, MAPK14, KRT17) achieved an area under the curve (AUC) of 0.985 plus-or-minus sign 0.010, with 83% sensitivity and 100% specificity. The panel was corroborated using public datasets. Conclusions: To our knowledge, this study represents the first application of Orbitrap Astral DIA mass spectrometry in periodontitis research, establishing a disease-specific DEPs atlas and a salivary biomarker panel with high diagnostic accuracy for stage III/IV periodontitis, providing a foundation for future external validation studies.

Background: Radiographic detection of caries lesions adjacent to restorations is challenging due to limitations of two-dimensional imaging and difficulties distinguishing true lesions from restorative or anatomical radiolucencies. Artificial intelligence (AI)-based clinical decision support systems (CDSSs) have been introduced to assist radiographic interpretation; however, different AI tools may yield variable diagnostic outputs, and their comparative performance remains unclear. Objective: To compare the diagnostic performance of commercial and experimental AI algorithms for detecting secondary caries lesions on bitewings. Methods: This cross-sectional diagnostic accuracy study included 200 anonymized bitewings comprising 885 restored tooth surfaces. A consensus group reference standard identified all surfaces with a caries lesion and classified each lesion by type (primary/secondary) and depth (enamel-only/dentin-involved). Five commercial (Second Opinion, CranioCatch, Diagnocat, DIO Inteligencia, and Align X-ray Insights) and three experimental (Mask R-CNN-based and Mask DINO-based) systems were tested. Diagnostic performance was expressed through sensitivity, specificity, and overall accuracy (95% CI). Comparisons used generalized estimating equations, adjusted for clustered data. Results: Specificity was high across all systems (0.957-0.986), confirming accurate recognition of non-carious surfaces, whereas sensitivity was moderate (0.327-0.487), reflecting frequent missed detections of enamel and dentin lesions. Accuracy ranged from 0.882 to 0.917, with no significant differences among models (p >= 0.05). Confounding factors, such as radiographic overlapping, marginal restoration defects, and cervical artifacts, were the main sources of misclassification. Conclusions: AI algorithms, regardless of architecture or commercial status, showed similar diagnostic capabilities and a conservative detection profile, favoring specificity over sensitivity. Improvements in dataset diversity, labeling precision, and explainability may further enhance reliability for secondary caries detection. Clinical Significance: AI-based CDSSs assist clinicians by providing consistent detection. Their high specificity is particularly valuable in minimizing unnecessary invasive treatments (overtreatment), though they should be used as adjuncts rather than a replacement for expert judgment.

Esophageal squamous cell carcinoma (ESCC) is still lack of clinically molecular subtyping and effective therapeutic strategies. Herein, a total of 46 paired tissue samples of esophageal squamous cell carcinoma (ESCC) were collected and subjected to a systematic proteogenomic evaluation. Consensus assessment of the ESCC-related transcriptomes and TCGA dataset revealed several consensual modes of gene expression related to ESCC specificity, with 8 plasma-detectable hub proteins that could discriminate ESCC from others. Three ESCC molecular subtypes were defined and validated based on proteome data, including pCC1 with activated immune response and best survival outcome, pCC2 as cell cycle subtype with relative worse outcome, and pCC3 with worst outcome that expressed more cell adhesion related proteins. Furthermore, we proposed potential therapeutic strategies for improving survival outcomes in patients with different ESCC molecular subtypes. This integrative proteogenomic analysis provided a novel view of ESCC-dependent molecular information.

Objective To develop and evaluate a novel machine learning (ML) framework tailored to a clinical diabetes dataset and to assess whether demographic stratification enhances model performance and interpretability for multiclass diabetes classification. Methods A clinical dataset of 264 patients records was used to classify individuals into non-diabetic, prediabetic and diabetic categories. Several supervised learning models were trained using 80:20 train-test split and optimized using RandomizedSearchCV Model and 10-fold cross validation. Model performance was evaluated using the metrics accuracy, precision, recall and the F1-score. Area under the receiver operating characteristic curve (AUC) was calculated for the best generalizing model. A structured ML framework was developed for this dataset, incorporating preprocessing, model optimization, age stratification analysis age (<35 vs >35 years) and gender. SHAP was developed for model interpretability. Results Ensemble methods demonstrated superior performance in comparison to linear or single-tree approaches, with Gradient Boosting showing the most stable generalization with a test accuracy of 0.981 and stable cross validation accuracy of 0.972. AUC-ROC analysis using Gradient Boosting yielded good discriminative ability across the three diabetes classes: 0.991 (non-diabetic), 0.986 (prediabetic) and 0.972 (diabetic). Stratified analysis showed improved reliability in individuals aged >;35 years (accuracy = 0.94, F1-score = 0.92), while performance in younger individuals was unstable due to small sample size. SHAP analysis identified HbA1c, BMI, and age as dominant predictors. Conclusion This study presents a ML framework integrating age stratified modelling with explainable ML frameworks to improve interpretability. The findings offer clinically relevant results that can support clinical decision-making systems, individualized risk assessment, and potential applications for targeted intervention in diabetes progression.

Objective: To assess ethnic disparities in time to hospital presentation, use of acute reperfusion therapies, and in-hospital treatment times among patients presenting with stroke in a Dutch emergency department. Methods: In this single-centre observational cohort study, we included patients with a first-ever ischemic stroke between September 2020 and September 2021. Patients were categorized by ethnicity (with or without migration background). Demographic and stroke characteristics were compared between groups. Outcomes included: rates of presentation outside therapeutic time window, acute reperfusion therapy (intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)), and, when applicable, door-to-treatment time (DTTT), with a door-to-needle time (DTNT) and door-to-groin time (DTGT) for IVT and EVT respectively. Univariable and multivariable linear and logistic regression analyses were performed, adjusted for age, sex, and NIHSS at presentation, where appropriate. Results: A total of 232 patients were included, of whom 62 (26.7%) had a migration background. These patients were younger (66.6 vs 71.2 years) and more frequently had diabetes (27.4% vs 15.9%). Sex distribution was similar (59.7% vs 60.6% male). Stroke etiology differed between groups with less cardio-embolism (4.8% vs 15.3%) and more small vessel disease (69.4% vs 48.2%) among patients with a migration background. These latter patients presented more often outside the therapeutic time window (53.2% vs 37.1%; OR 1.90; 95% CI 1.05-3.45). EVT was less frequently performed in patients with a migration background compared to those without (8.1% vs 22.4%; OR 0.28; 95% CI 0.10-0.75). There were no significant differences in treatment times (DTTT 38min vs 30min, DTNT 35min vs 26min, DTGT 64min vs 54min). Conclusion: Patients with a migration background were more likely to present outside the therapeutic time window and had a lower rate of EVT. In order to improve access for these patients, more insight into prehospital and within hospital barriers and facilitators for appropriate management are needed.

BackgroundChemokine receptor type 5 (CCR5) is expressed on hepatic stellate cells (HSCs), which, together with fibroblasts, are major producers of extracellular matrix during liver fibrosis. Leronlimab is a humanized IgG4{kappa} monoclonal antibody that binds to CCR5. The objective of the present study was to evaluate the antifibrotic effects of leronlimab in three independent preclinical studies using two mouse models of liver fibrosis. MethodsIn STAM (Stelic Animal Model) model 1, leronlimab was administered at doses of 5 or 10 mg/kg/week for 3 weeks. STAM model 2 was conducted as a confirmatory study to validate the antifibrotic effect observed with the 10 mg/kg/week dose in STAM model 1. In a third study, a carbon tetrachloride (CCl)-induced liver fibrosis mouse model was used to evaluate leronlimab administered at 10 mg/kg/week for 3 weeks. An isotype-matched control antibody was included in all studies for comparison. Evaluations included liver enzymes and histological assessment of liver fibrosis. ResultsIn STAM model 1, leronlimab at 10 mg/kg/week significantly reduced fibrosis area compared with the isotype control (p = 0.0005). These findings were confirmed in STAM model 2 (p < 0.0001). Consistent antifibrotic effects were also observed in the CCl-induced liver fibrosis model (p = 0.0006). ConclusionsCollectively, these preclinical results demonstrate that CCR5 blockade by leronlimab is associated with a significant reduction of established liver fibrosis in multiple mouse models and support further evaluation of leronlimab as a potential therapeutic option, either as monotherapy or in combination regimens, for chronic liver diseases with fibrosis.

Adenoid cystic carcinoma (ACC) of salivary gland is a "immune-cold" tumour. Annexin A3 (ANXA3) is an apoptotic protein found to be participating in immune cell infiltration in tumour microenvironment (TME) of various cancer cases. Significant low expressions of ANXA3 protein found in adenoid cystic carcinoma. We hypothesized overexpressing ANXA3 transforms ACC "cold" TME to "hot". We cultured UM-HACC-2A and UFH2 spheroids on extracellular matrix and co cultured them with peripheral blood mononuclear cells. We functionalized FDA (The Food and Drug Administration) approved Poly(lactic-co-glycolic acid) PLGA nanoparticles with anti-cMyb antibody and ANXA3 recombinant protein using streptavidin-biotin conjugation. Upon overexpressing ANXA3 in ACC spheroids in immune coculture model using functionalized nanoparticles, significant increase of tumour infiltrating lymphocytes and decrease in the size of the ACC spheroids observed. Apoptotic profiler assay further confirmed significant upregulation of apoptotic proteins, some of them participate in immune infiltration. Overall, this project exhibits promising results showing potential approach to convert ACC into an immune "hot" tumour.

Candidiasis pose a serious health threat, stimulating efforts to develop new antifungal agents and alternative therapies. Given the high mortality of fungal infections and the historical use of natural remedies, there is a growing interest in integrating natural substances into modern treatments. It is particularly important to explore interactions between home remedies and clinically approved antifungals to avoid harmful combinations or enhance beneficial effects. In this study, the chemical composition of the ethanolic extract of propolis (EEP) using UHPLC-DAD-QqTOF-MS was analyzed. The interactions of this extract with several antifungal agents against four yeast pathogens causing candidiasis: Candida albicans, Nakaseomyces glabratus, Pichia kudriavzevii, and Candida auris were investigated using Checkerboard Titration Assay, Growth Kinetics, and Disc-diffusion assay. Also, a novel simulated infection model was proposed. The results showed synergistic interactions between EEP and amphotericin B, and additive effects with nystatin. Synergy and additivity with fluconazole and voriconazole were observed, but limited to C. albicans and N. glabratus. In contrast, antagonistic interactions were noted with caspofungin, clotrimazole, and ketoconazole, which may have clinical relevance. Additionally, positive interactions with 2-phenoxyethanol and silver nanoparticles (AgNPs) suggest potential practical applications. Propoliss synergistic properties could expand antifungal strategies and support the development of multi-target, resistance-preventing therapies.

High level of protein expression is usually welcomed in industry and research, and codon optimization is widely used to achieve high expression. Methods of implementing codon optimization can be divided into two branches, one is classical methods which develop cost functions based on empirical law, another is AI methods which learn the codon choice principles from endogenous genes with neural networks. Here we develop two codon optimization tools based on two branches respectively, namely OptimWiz 2.1 and OptimWiz 3.0. Results of fusion protein fluorescence detection indicate that both OptimWiz 2.1 and OptimWiz 3.0 are superior to all the other commercially available codon optimization tools. Principles of codon optimization are revealed in the process of machine learning on both tools.

Introduction Cervical spondylotic myelopathy (CSM) surgery is frequently associated with residual neurological deficits, partly due to unrecognized dynamic spinal cord compression on conventional MRI. Current static imaging may miss position-dependent stenosis, resulting in insufficient or inappropriate decompression. This study aims to evaluate whether dynamic MRI-guided individualized surgery improves neurological outcomes compared to conventional MRI-based planning. Objectives This study aims to examine the association between dynamic MRI-guided surgical planning and neurological recovery in cervical spondylotic myelopathy, and to evaluate its role in identifying responsible segments, avoiding excessive surgery, and improving clinical outcomes. Methods This single-center retrospective cohort study will include 300 patients who underwent cervical spine surgery between January 2020 and December 2025 at the First Affiliated Hospital of Guangxi University of Chinese Medicine. Patients will be categorized into the dynamic MRI-guided group (n=150) or conventional MRI-based group (n=150) based on preoperative imaging modality. 1:1 propensity score matching will be performed using age, sex, BMI, disease duration, baseline mJOA score, and number of compressed segments. The primary outcome is the rate of improvement in the mJOA score at 6 months postoperatively. Secondary outcomes include VAS, NDI, reoperation rate, and time to first complication. Between-group comparisons will use t-tests/Mann-Whitney U tests for continuous variables, {chi}{superscript 2} tests/Fisher's exact tests for categorical variables, and Kaplan-Meier estimates with the log-rank test for time-to-event outcomes. A two-sided P<0.05 will be considered significant. Analyses will be performed using R software (version 4.4.1). Ethical approval was obtained from the Medical Ethics Committee of the First Affiliated Hospital of Guangxi University of Chinese Medicine (Approval No. 2025-080-KY-01) from February 06, 2026 to February 05, 2027. Expected outcomes We hypothesize that dynamic MRI-guided surgical planning will improve neurological recovery and decompression accuracy in cervical spondylotic myelopathy, providing evidence for optimized preoperative imaging and precision spine surgery.

Abstract Objective: To compare the safety and efficacy of bridging intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus direct EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) treated within the 6- to 24-hour time window. Methods: This is a retrospective analysis of prospective EVT registry from 10 comprehensive stroke centers in China and Singapore between 2019 and 2024. Eligible patients had anterior circulation LVO, underwent EVT within 6-24 hours of onset, had ASPECTS 6, NIHSS 6, and pre-stroke mRS 2. Patients were stratified into bridging IVT + EVT (IVT group) versus direct EVT alone (non-IVT group). Propensity score matching (1:2 ratio) was performed to balance baseline covariates. The primary outcome was 3-month favorable functional outcome (mRS 0-2). Secondary outcomes included successful recanalization (mTICI 2b-3), symptomatic intracranial hemorrhage (sICH), hemorrhagic transformation (HT) and 3-month mortality. In the matched cohort, binary outcomes were compared using the Cochran-Mantel-Haenszel test. Results: Of 772 included patients, 110 (14.2%) received bridging IVT and 662 (85.8%) received direct EVT. After propensity score matching, 202 non-IVT patients were matched to 101 IVT patients, with all covariates well-balanced (absolute SMD <0.10). In the matched cohort, bridging IVT was not associated with a significant difference in 3-month favorable outcome (44.55% vs. 47.03%; common OR 0.91; 95% CI 0.56-1.46), successful recanalization (91.09% vs. 90.10%; OR 1.11; 0.51-2.44), sICH (5.94% vs. 9.41%; OR 0.61; 0.24-1.58), HT (23.76% vs. 23.27%; OR 1.03; 0.57-1.85), or 3-month mortality (15.84% vs. 13.37%; OR 1.22; 0.62-2.37). Conclusion: In this large multicenter propensity score-matched analysis, bridging intravenous thrombolysis before endovascular thrombectomy in the 6- to 24-hour time window was not significantly associated with improved efficacy or increased safety risks compared with direct endovascular therapy alone.

While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

This research demonstrates that the trans-aqueduct approach is a feasible, minimally invasive access pathway to the third ventricle, offering a potential route to the deep brain for therapeutic technologies. Further pre-clinical investigation is required to thoroughly evaluate physiological tolerance, trauma risk, and the long-term implications of intraventricular implantation. The third ventricle is a high-value site for neuromodulation due to its proximity to deep-brain targets, including the subthalamic nucleus (STN) and globus pallidus internus (GPi). This study defined the anatomical pathway; and evaluated the technical feasibility of retrograde access to the third ventricle via the cerebral aqueduct using minimally invasive interventional techniques. Evaluation was conducted in three phases using human MRI datasets (n=16; mean age 48.4 years) and cadaveric specimens (n=6; mean age 88.2 years). Phase 1 involved morphometric MRI analysis of the aqueduct and ventricles. Phase 2 tested trans-aqueduct access on cadaver specimens via fluoroscopically guided guidewires and catheters. Phase 3 utilized direct anatomical dissections on cadaver specimens (n=3) to morphometrically measure the third ventricular cavity and its relationship to deep-brain nuclei. Measurements across the sample groups showed a mean aqueduct diameter of 1.6 mm (SD=0.14). Third ventricle dimensions averaged 27.6 mm (ventral-dorsal), 19.9 mm (caudal-cranial), and 5.7 mm (lateral). Successful access to the third ventricle was achieved in 83% (5/6) of cadaveric specimens. The optimal technical configuration utilized a 0.018'' angled-tip guidewire and 5-6 Fr catheters; the aqueduct accommodated diameters up to 2.0 mm with minimal resistance. The STN and GPi were localized within 5-20 mm of the ventricular volumetric centroid. The trans-aqueduct approach is a technically feasible, minimally invasive pathway for accessing the third ventricle. This route offers a potential alternative for the delivery of therapeutic neurotechnologies. Further research is required to assess physiological tolerance, trauma risk, and the long-term safety of intraventricular implantation.

Gingival inflammation is associated with dysbiotic oral biofilms characterized by reduced nitrate-reducing capacity and diminished nitric oxide (NO) bioavailability. While dietary nitrate has been shown to influence oral microbial activity, the effects of sustained, localized nitrate delivery on oral biofilm ecology and gingival inflammation remain incompletely defined. In this randomized, double-blind, placebo-controlled trial, 30 adults with gingival bleeding were assigned to receive localized prebiotic nitrate (~0.989 mmol per dose) or placebo for 21 days. The primary outcome was mean bleeding on probing (mBOP). Secondary outcomes included modified Gingival Index (mGI), Quigley-Hein plaque index (QHPI), salivary nitrite (as a proxy for NO bioavailability), oral pH, and microbiome composition assessed by 16S rRNA gene sequencing. Prebiotic nitrate supplementation formulation delivered in a slow-release chewing gum significantly reduced mBOP (25.7% to 15.3%; p = 0.0002) compared to placebo chewing gum. Salivary nitrite levels and oral pH increased, indicating enhanced nitrate metabolism. Microbiome analysis demonstrated enrichment of nitrate-reducing taxa, including Rothia mucilaginosa and Neisseria spp., and a relative reduction in inflammation-associated genera such as Prevotella and Porphyromonas. Localized prebiotic nitrate formula delivered in a functional chewing gum was associated with reduced gingival inflammation and shifts in oral microbiome composition consistent with enhanced nitrate-reducing capacity critical in nitric oxide formation. These findings support a role for biofilm-directed nutritional modulation as a non-antimicrobial approach for managing gingival inflammation and improving nitric oxide bioavailability.

Background Inflammatory markers play an important role in the pathophysiology of Lumbar disc herniation (LDH). This study presents a comprehensive multi-assessment of the inflammatory landscape by combining serum inflammatory cytokines quantification, their diagnostic performance, associations with radiological features, and integrating the experimental findings into an in-silico protein-protein interaction network. Methods A multifaceted study design was utilized to quantify and compare the distribution of selected inflammatory cytokines in patients with LDH and control subjects. The diagnostic ability of these cytokines was assessed using receiver operating characteristic curve analysis. The cytokines values were correlated with selected radiological findings including disc herniation subtypes (protrusion, extrusion, and sequestration), and further categorized as contained and non-contained in patients using a Spearmans rank correlation test. Additionally, computational analysis was performed to identify the central hubs and functionally enriched pathways. Results In patients with LDH, IL-6 and IL-1{beta} showed statistically significant (IL-6: p < 0.001; IL-1{beta}: p = 0.001) rise, but IL-6 showed high diagnostic and discriminative power (AUC = 0.99; cut-off: 19.99 pg/mL). Further IL-1{beta} exhibited a positive correlation with non-contained disc herniation (extrusion and sequestration), while displaying a significant (p < 0.05) negative correlation with protrusion. In silico analysis identified IL-1{beta}, IL-8, TNF-, IL-6, IL-1, CSF2, CSF3, and IL-10 as central hubs, with IL-1{beta} being the top ranked hub in determining functionally enriched cytokine-cytokine receptor interaction. Conclusions Study confirmed IL-6 as a powerful diagnostic marker for LDH, while IL-1{beta} aids in determining contained and non-contained disc herniation. Further, IL-1{beta} was identified as the central hub, triggering functionally enriched pathways in the pathogenesis of LDH.

Background: Single-nephron glomerular filtration rate (GFR) represents a nephron-level functional index that may reveal key pathophysiological mechanisms driving progression in patients with diabetic nephropathy. However, its clinical relevance remains incompletely understood. This cross-sectional study assessed single-nephron estimated GFR (eGFR) across different chronic kidney disease (CKD) stages in patients with advanced diabetic nephropathy. Methods: Nephron number was estimated as the number of nonglobally sclerotic glomeruli per kidney using computed tomography-derived cortical volume combined with biopsy stereology. Single-nephron eGFR was calculated by dividing eGFR by the nephron number of both kidneys. Patients were stratified according to CKD stage at kidney biopsy. Associations between CKD stages and single-nephron eGFR were evaluated using multivariable linear regression models adjusted for age, sex, urinary protein excretion, and eGFR. Results: The study included 105 patients with biopsy-proven diabetic nephropathy and overt proteinuria (median age 59 years, 83% male, HbA1c 6.6%, 57% had nephrotic range proteinuria). The percentage of globally sclerotic glomeruli, mesangial expansion score, and prevalence of nodular lesions increased significantly with advancing CKD stage. Median nephron number declined from 529,178 to 224,458 per kidney, whereas glomerular volume remained constant. Single-nephron eGFR decreased markedly with CKD stage and remained significantly inversely associated with CKD stage after adjustment for clinicopathologic covariates (P for trend <0.001). Conclusion: In overt diabetic nephropathy, single-nephron eGFR decreased with advancing CKD stage, despite relatively preserved glomerular volume. At this stage of disease, structural alterations specific to diabetic nephropathy may impair effective single-nephron filtration capacity.

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide, with Escherichia coli being the predominant uropathogen. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains and their association with fluoroquinolone resistance pose a significant challenge to empirical therapy, particularly in community settings. The aim of this study was to determine the epidemiology and predictive factors associated with ESBL-producing E. coli and its concomitant fluoroquinolone resistance in community-acquired clinical isolates. A retrospective cross-sectional study was conducted analyzing 244 clinical E. coli isolates. Demographic and microbiological data were collected, including age, sex, sample type, and antibiotic susceptibility. Associations between variables and ESBL production were assessed using Pearsons chi-squared test, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of the isolates, 165 (68%) were ESBL-producing. A significant association was observed between age group and ESBL production (p < 0.001), with the highest frequency in the 20-39 age group. Most ESBL-positive isolates were obtained from women (73%), although odds ratio (OR) analysis suggested a non-significant trend toward a higher probability in men (OR = 1.29; 95% CI: 0.72-2.31). High rates of fluoroquinolone resistance were identified among the ESBL-producing isolates, with 30% resistance to levofloxacin and 35% to ciprofloxacin (p < 0.001). Urine samples showed the highest concentration of ESBL-positive isolates, with a significant association between sample type and resistance (p < 0.001). The high prevalence of ESBL-producing E. coli and its concomitant resistance to fluoroquinolones highlight a critical challenge for the empirical treatment of urinary tract infections in Mexico, underscoring the need to strengthen antimicrobial use management and local surveillance strategies.

Despite the remarkable progress of artificial intelligence represented by large language models, how AI technologies can contribute to the construction of evidence in evidence-based medicine (EBM) remains an overlooked issue. Now, we need an AI that can be compatible with EBM. In the present paper, we aim to propose an example analysis that may contribute to this approach using variable Vision Transformer.