Category: Statistics

Int J Nanomedicine. 2026 Mar 16;21:588259. doi: 10.2147/IJN.S588259. eCollection 2026.

ABSTRACT

INTRODUCTION: To address the poor water solubility and low bioavailability of the curcumin derivative CU1, this study constructed a long-circulating pH-sensitive nanoliposome (CU1-LCpHL) as its delivery system.

METHODS: The physicochemical properties, stability, and anti-lung cancer efficacy of CU1-LCpHL were systematically evaluated, including in vitro cellular assays (cellular uptake, apoptosis, proliferation, and migration), in vivo pharmacokinetics and pharmacodynamics, mechanistic studies, and immunohistochemical analysis.

RESULTS: CU1-LCpHL presented a spherical morphology with uniform particle size. Its lyophilized powder remained stable for at least three months at 25°C and exhibited sustained-release characteristics. In vitro experiments demonstrated that, compared to free curcumin (CU), free CU1, and long-circulating stable nanoliposomes (CU1-LSLN), CU1-LCpHL promoted more efficient cellular uptake, induced apoptosis, and significantly inhibited the proliferation and migration of lung cancer cells. Pharmacokinetic studies revealed that the area under the curve (AUC_0-t) of CU1-LCpHL was 9.52-fold and 9.47-fold higher than that of CU and CU1, respectively, while its mean residence time (MRT_0-t) was 3.37-fold and 7.69-fold longer, respectively. In vivo pharmacodynamic results indicated that the tumor-inhibition rate of CU1-LCpHL was 2.42-, 2.17-, and 1.37-fold higher than those of CU, CU1, and CU1-LSLN, respectively, with no significant organ toxicity or hemolysis observed. Mechanistic studies showed that CU1-LCpHL significantly upregulated Caspase-3, Caspase-9, and Bax, while downregulating the p-AKT/AKT ratio and Bcl-2 levels. Immunohistochemical analysis further confirmed that CU1-LCpHL markedly reduced the positive expression of Ki67, CD34, and VEGFR2, outperforming all other treatment groups.

CONCLUSION: CU1-LCpHL significantly enhances the delivery efficiency and antitumor efficacy of CU1, representing a promising nano-drug delivery system for lung cancer therapy.

PMID:41869398 | PMC:PMC13004129 | DOI:10.2147/IJN.S588259

Front Surg. 2026 Mar 5;13:1730726. doi: 10.3389/fsurg.2026.1730726. eCollection 2026.

ABSTRACT

BACKGROUND: Superior labrum anterior and posterior (SLAP) lesions are a common cause of shoulder pain and instability. Developing accurate, non-invasive diagnostic tools is essential to support clinical decision-making for SLAP lesions. This study aimed to establish an automated diagnostic model for SLAP lesions using a 2.5D deep learning framework combined with ensemble learning and to evaluate its clinical utility.

METHODS: In this retrospective study, 185 patients who underwent shoulder arthroscopy between January 2019 and September 2025 were included (91 SLAP lesions, 94 controls). Preoperative shoulder magnetic resonance imaging (MRI) data were analysed. Images from three consecutive slices, centred on the maximal region of interest (ROI), were processed using a Wide_ResNet101_2 network pre-trained on ImageNet for deep feature extraction and probability prediction. A decision-level fusion strategy integrated the predicted probabilities from all three layers as input features for three ensemble classifiers: AdaBoost, Random Forest, and XGBoost. Model performance was assessed with accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F1-score. The DeLong test and integrated discrimination improvement (IDI) were used to compare models.

RESULTS: All ensemble models exhibited robust diagnostic performance. On the test set, the XGBoost model achieved the highest AUC (0.754) and sensitivity (0.933), though specificity was moderate (0.538). The Random Forest model yielded an AUC of 0.745, while the AdaBoost model achieved an AUC of 0.731. F1-scores ranged from 0.75 to 0.80. There were no statistically significant differences in AUC among the models. Feature importance analysis highlighted the central MRI slice as most contributory. Model interpretability assessments showed that the network focused predominantly on the biceps-labral complex, which is anatomically consistent with SLAP pathology.

CONCLUSIONS: The proposed automated diagnostic model, utilising a 2.5D deep learning and ensemble approach, demonstrated favourable diagnostic performance and clinical applicability for SLAP lesion detection on shoulder MRI. Among the ensemble strategies, the XGBoost model provided the highest sensitivity, rendering it particularly suitable as a clinical decision-support tool. The multi-slice information fusion framework substantially improved diagnostic accuracy, supporting its potential as a novel artificial intelligence solution to assist radiologists in diagnosing shoulder labral injuries.

PMID:41869384 | PMC:PMC12999963 | DOI:10.3389/fsurg.2026.1730726

Front Surg. 2026 Mar 5;13:1737152. doi: 10.3389/fsurg.2026.1737152. eCollection 2026.

ABSTRACT

STUDY DESIGN: Systematic review and update meta-analysis.

PURPOSE: This systematic review and meta-analysis was conducted to determine the effect of preoperative (neoadjuvant) chemotherapy with 5-fluorouracil (intraperitoneal) on the integrity of colorectal anastomoses in an experimental rat model.

OVERVIEW OF LITERATURE: Emergency surgery in cancer patients undergoing chemotherapy is associated with an increased risk of complications, including anastomotic leakage, and worse survival outcomes. 5FU is widely used in the treatment of GI tumors. The effect of 5FU on anastomotic integrity has been demonstrated previously; this meta-analysis provides a quantitative assessment of this effect.

METHODS: A literature search was conducted using PubMed and Google Scholar in MEDLINE up to May 2025. Only experimental studies on rat models were selected, which compared a Control group (no chemotherapy) and a group receiving intraperitoneal 5FU. The following outcomes were extracted: anastomotic bursting pressure, severity of adhesion formation, and hydroxyproline levels.

RESULTS: Six studies were included in the meta-analysis. Statistically significant results demonstrated the superiority of the Control group over the 5FU group in terms of hydroxyproline levels (p < 0.00001). The severity of adhesion formation was higher in the group treated with 5FU (p = 0.59). The anastomotic bursting pressure was higher in the Control group (p = 0.36).

CONCLUSIONS: 5FU had a negative impact on the integrity of the anastomotic suture line, as evidenced by lower hydroxyproline levels. Lower bursting pressure and a higher degree of adhesions were found in the 5FU group; however, these results were not statistically significant.

PMID:41869383 | PMC:PMC12999958 | DOI:10.3389/fsurg.2026.1737152

Front Surg. 2026 Mar 6;13:1607136. doi: 10.3389/fsurg.2026.1607136. eCollection 2026.

ABSTRACT

Nonunion (non-osteogenic healing) remains a major challenge in fracture management, particularly due to its diagnostic complexity and unpredictable occurrence in clavicle and femoral fractures. This study aimed to investigate the potential association between plasma fibrinogen concentration and the incidence of nonunion in fracture patients, with the objective of identifying a potential biomarker for clinical prediction. Based on retrospective data from Shandong Provincial Hospital Affiliated to Shandong First Medical University (January 2010 to May 2019), we analyzed a cohort of 338 fracture cases, among which 23 (6.8%) developed nonunion. Fibrinogen concentration (AUC = 0.635, 95% CI 0.517-0.752) showed moderate discriminative capability for nonunion. Using smoothing curve fitting techniques and multivariable logistic regression models, the study systematically assessed the dose-response relationship between fibrinogen levels and the risk of nonunion risk, adjusting for confounding factors such as age, sex, injury mechanism, and ASA classification. The results indicated that for every 1 g/L increase in fibrinogen concentration, the risk of nonunion increased significantly by 48% [adjusted odds ratio [OR] = 1.48, 95% confidence interval [CI] not explicitly reported but implied statistical significance]. This association remained statistically significant even after controlling for traditional risk factors such as trauma severity and baseline patient status, suggesting that fibrinogen may influence bone healing through independent pathways. Smoothing curve fitting revealed a nonlinear, dose-dependent increase in nonunion risk with higher fibrinogen levels, potentially guiding the establishment of clinical threshold settings. The study found that elevated plasma fibrinogen levels are independently associated with an increased risk of nonunion, and routine monitoring of fibrinogen concentrations may serve as a promising adjunct tool for early identification of at-risk patients. Future research should focus on elucidating the underlying mechanisms-such as inflammation regulation and extracellular matrix deposition-and validating the predictive value of fibrinogen across different types of fractures to support the development of personalized treatment strategies.

PMID:41869382 | PMC:PMC13002598 | DOI:10.3389/fsurg.2026.1607136

JSAMS Plus. 2025 Jun 20;6:100108. doi: 10.1016/j.jsampl.2025.100108. eCollection 2025 Dec.

ABSTRACT

BACKGROUND: Isometric resistance training (ISO-RT) has gained renewed attention for its potential to elicit muscular adaptations and enhance athletic performance. Unlike dynamic resistance training (DYN-RT), ISO-RT involves no joint movement or eccentric loading, making it particularly suitable for individuals with joint pathologies or those undergoing rehabilitation. Despite increasing interest, the comparative effectiveness of ISO-RT versus DYN-RT across various outcomes, including strength, hypertrophy, endurance, and recovery, remains inadequately explored.

AIMS: This study aims to evaluate and compare the effects of multi-angle ISO-RT and traditional DYN-RT on muscle performance, body composition, and recovery-related indicators in healthy adults.

METHODS: In this pilot randomised controlled trial, 20 healthy adults (≥18 years) will be randomly assigned to either the ISO-RT or DYN-RT group (n ​= ​10 per group). Both groups will complete a full-body resistance training program twice weekly for six weeks. The key distinction lies in the execution of the chest press and leg press exercises-performed isometrically in the ISO-RT group and dynamically in the DYN-RT group. All outcomes will be assessed at baseline and post-intervention.

ANALYSIS: Primary outcomes include dynamic and isometric strength. Secondary outcomes encompass muscular power, dynamic and isometric endurance, body composition (via dual-energy X-ray absorptiometry), muscle oxygenation (via near-infrared spectroscopy), and subjective recovery indicators such as sleep quality and delayed onset muscle soreness. Between-group comparisons will be conducted using appropriate inferential statistical tests to determine effect estimates and feasibility metrics.

DISCUSSION/IMPLICATIONS: This trial will offer preliminary insights into the physiological and perceptual adaptations elicited by ISO-RT versus DYN-RT. The findings will inform the design of larger-scale trials and contribute to developing tailored, evidence-based resistance training guidelines for both clinical and athletic populations.

PMID:41869367 | PMC:PMC12980634 | DOI:10.1016/j.jsampl.2025.100108

Front Immunol. 2026 Mar 5;17:1783216. doi: 10.3389/fimmu.2026.1783216. eCollection 2026.

ABSTRACT

INTRODUCTION: Chemotherapy remains the standard of care for metastatic soft tissue sarcoma (STS), but clinical benefit is modest. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), have transformed cancer treatment, yet their efficacy in STS is variable and largely confined to undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (LPS). Reliable biomarkers to predict ICI response in STS are understudied and currently lacking.

METHODS: We examined mutation profiles and analysed longitudinal blood samples from STS patients (n=13) treated with anti-PD-1/PD-L1-based therapy to identify molecular features and circulating immune correlates of ICI efficacy. To gain deeper insight, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from a patient with prolonged stable disease (>6 months).

RESULTS: Complete blood counts and PBMC profiling demonstrated that elevated circulating lymphoid cells were associated with response, whereas enrichment of innate immune populations, particularly neutrophils and monocytes, correlated with non-response. Single-cell RNA sequencing of PBMCs from a patient with prolonged stable disease revealed dynamic shifts in monocyte and CD8 T cell phenotypes and inflammatory signalling pathways, which paralleled radiological tumour regression and subsequent progression.

DISCUSSION: Our findings highlight peripheral immune profiles as candidate biomarkers for predicting and monitoring ICI efficacy in STS. Incorporating these immune markers could refine patient selection, reduce unnecessary toxicity, and support adaptive treatment strategies for patients with this rare and heterogenous cancer.

PMID:41869350 | PMC:PMC12999908 | DOI:10.3389/fimmu.2026.1783216

Front Immunol. 2026 Mar 6;17:1741434. doi: 10.3389/fimmu.2026.1741434. eCollection 2026.

ABSTRACT

OBJECTIVE: The objective was to investigate the association between tonsillectomy and subsequent ankylosing spondylitis (AS) risk, with particular emphasis on racial disparities in disease susceptibility.

METHODS: A retrospective cohort study was conducted using de-identified electronic health records from approximately 120 million patients in the collaboration network in the United States. Patients diagnosed with tonsillar and adenoidal diseases between 2005 and 2023 were selected and divided into surgical and non-surgical cohorts. Propensity score matching (PSM) was employed to balance baseline differences and control for confounding factors, and statistical analyses were performed using Kaplan-Meier survival analysis and Cox proportional hazards models.

RESULTS: After PSM, 173,483 individuals were included in each cohort with well-balanced baseline characteristics. Overall, tonsillectomy did not significantly increase AS risk (HR = 1.26, 95% CI: 0.90-1.75, p = 0.210). Age- and sex-stratified analyses yielded consistent results. However, race-stratified analysis revealed that White individuals who underwent tonsillectomy had significantly elevated AS risk (HR = 1.80, 95% CI: 1.19-2.72, p = 0.005) and higher cumulative incidence compared to matched controls, a finding not observed in other racial groups.

CONCLUSION: This large-scale study identifies being of White ancestry as a significant effect modifier in the relationship between tonsillectomy and AS development. These findings warrant closer post-operative surveillance for AS symptoms in White patients undergoing tonsillectomy and further mechanistic research.

PMID:41869336 | PMC:PMC13002431 | DOI:10.3389/fimmu.2026.1741434

Front Immunol. 2026 Mar 6;17:1761515. doi: 10.3389/fimmu.2026.1761515. eCollection 2026.

ABSTRACT

BACKGROUND: Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up.

METHODS: We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated.

RESULTS: PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, P = 0.003), with better renal function and more frequent C1q deposition (38.1% vs. 13.5%, P = 0.016). Serum anti-PLA2R antibodies were detected in 55.3% of patients and strongly correlated with tissue PLA2R positivity (AUC = 0.851; optimal cutoff ≥17.47 RU/mL). Baseline antibody titers were not associated with remission (P = 0.573). During 5-years follow-up, 42.4% achieved CR, 36.4% PR, and 21.2% had NR, with an estimated 5-year renal survival rate of 81.95%. No malignancy events were observed among the seven THSD7A-positive patients or the single NELL-1-positive patient in this cohort. Statistical power for rare antigen subgroups was limited.

CONCLUSIONS: This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN.

PMID:41869300 | PMC:PMC13002824 | DOI:10.3389/fimmu.2026.1761515

J Am Stat Assoc. 2026 Mar 17. doi: 10.1080/01621459.2026.2637894. Online ahead of print.

ABSTRACT

While deep neural networks (DNNs) are used for prediction, inference on DNN-estimated subject-specific means for categorical or exponential family outcomes remains underexplored. We address this by proposing a DNN estimator under generalized nonparametric regression models (GNRMs) and developing a rigorous inference framework. Unlike existing approaches that assume independence between estimation errors and inputs to establish the error bound, a condition often violated in GNRMs, we allow for dependence and our theoretical analysis demonstrates the feasibility of drawing inference under GNRMs. To implement inference, we consider an Ensemble Subsampling Method (ESM) that leverages U-statistics and the Hoeffding decomposition to construct reliable confidence intervals for DNN estimates. We show that, under GNRM settings, ESM enables model-free variance estimation and accounts for heterogeneity among individuals in the population. Through simulations under nonparametric logistic, Poisson, and binomial regression models, we demonstrate the effectiveness and efficiency of our method. We further apply the method to the electronic Intensive Care Unit (eICU) dataset, a large scale collection of anonymized health records from ICU patients, to predict ICU readmission risk and offer patient-centric insights for clinical decision making.

PMID:41869283 | PMC:PMC13003751 | DOI:10.1080/01621459.2026.2637894

J Am Stat Assoc. 2026 Feb 24. doi: 10.1080/01621459.2025.2587321. Online ahead of print.

ABSTRACT

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. Unlike existing robust MR literature, our framework delivers valid statistical inference on the causal effect without requiring the genetic pleiotropy effects to follow any parametric distribution or relying on perfect instrument screening property. Under appropriate conditions, we demonstrate that our proposed estimator converges to a normal distribution, and its variance can be well estimated. We demonstrate the performance of our proposed estimator through Monte Carlo simulations and two case studies. The corresponding R package MRcare is available at https://chongwulab.github.io/MRcare/. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.

PMID:41869282 | PMC:PMC13004071 | DOI:10.1080/01621459.2025.2587321