Tag: statistics

Discov Oncol. 2025 Nov 11;16(1):2090. doi: 10.1007/s12672-025-03932-y.

ABSTRACT

Osteosarcoma (OS) is an exceptionally aggressive bone cancer, and the identification of blood-based biomarkers for early detection and prognosis remains a significant challenge. This study aimed to investigate the causal relationships between circulating plasma proteins and OS risk using Mendelian randomization (MR). We utilized genome-wide association study (GWAS) summary statistics, which included 3,282 plasma protein traits from the IEU Open GWAS Project and the FinnGen consortium. Our MR analysis identified 59 proteins positively associated with OS risk, while 66 proteins were inversely associated. Notably, Lactoylglutathione lyase, also known as Glyoxalase 1 (GLO1), showed a significant protective effect on OS risk (IVW OR = 0.2871, 95% CI: 0.1602-0.5145, P = 2.7580 × 10^{– 5}). After false discovery rate (FDR) correction, this association remained significant (FDR_pavl < 0.1). These findings emphasize the potential of circulating proteins, particularly GLO1, as biomarkers for OS, reflecting its role in oxidative stress and inflammation regulation. The study underscores the importance of proteomic analysis in OS pathogenesis and suggests the need for further investigation to validate these associations and explore potential therapeutic targets, thereby providing new insights into the biological mechanisms of OS.

PMID:41217734 | DOI:10.1007/s12672-025-03932-y

Infection. 2025 Nov 11. doi: 10.1007/s15010-025-02665-y. Online ahead of print.

ABSTRACT

BACKGROUND: The detection of pathogens causing infections by conventional diagnostic methods can be challenging and next-generation sequencing (NGS) technology offers a promising alternative method. In this study, we evaluated the performance of real-time metagenomic next-generation sequencing (rt-mNGS) for the detection of pathogens in respiratory samples.

METHOD: We used rt-mNGS, using the Seqstant LiveGene Analysis platform, on 335 respiratory samples in comparison to conventional culture results.

RESULTS: We observed an overall good concordance in 71.64% (240/335) of the methods. The rt-mNGS outperformed the gold standard culture in 16.12% (54/335) of the samples, while the culture was superior in detecting the clinically relevant pathogen in 12.24% (41/335) of the samples. The non-inferiority of rt-mNGS was statistically significant (δ = 10, α = 0.05, 1 – β = 0.8). We also observed that the real-time analysis of NGS data is beneficial in obtaining reliable, timely results, as the initial report at cycle 46 exhibits a Positive Predictive Value (PPV) of 93.75% at the species-level with a sensitivity of 32.09%.

CONCLUSION: Overall, our study showed the non-inferiority of rt-mNGS compared to the standard-of-care microbiology for respiratory samples with statistical significance. Moreover, the rt-mNGS method exhibited superior sensitivity and superior overall performance. It also uniquely detected certain organisms that are typically hard to culture. However, rt-mNGS reported a higher number of false positives and faced limitations in detecting Aspergillus spp. In conclusion, the study highlights the potential of rt-mNGS as a powerful tool in clinical diagnostics of respiratory infections and beyond.

PMID:41217732 | DOI:10.1007/s15010-025-02665-y

Ir J Med Sci. 2025 Nov 11. doi: 10.1007/s11845-025-04145-6. Online ahead of print.

ABSTRACT

BACKGROUND: Aging challenges healthcare globally. Fish and shellfish (fish-shellfish) are substantial providers of omega-3 fatty acids, which may mitigate multiple aging-related diseases. However, the relationship between fish-shellfish consumption and biological aging (BA) remains incompletely elucidated.

AIMS: To explore potential relationships between total fish-shellfish consumption (status/frequency) and BA assessed via Phenotypic age (PhenoAge) and risk of PhenoAge acceleration (PhenoAgeAccel), with a focus on examining the mediation role played by inflammatory/antioxidant biomarkers.

METHODS: The cross-sectional study was executed using weighted data from 27,801 American adults who participated in the National Health and Nutrition Examination Survey (1999-2020). To assess the total fish-shellfish consumption-BA relationship, multivariable linear and logistic regression, restricted cubic spline (RCS), threshold effect analysis, mediation analysis, and subgroup analysis were used.

RESULTS: Total fish-shellfish consumption inversely associated with BA. Specifically, fish consumers had significantly lower PhenoAge (β = -1.01, 95% CI: -1.41, -0.62) and reduced PhenoAgeAccel risk (OR = 0.84, 95% CI: 0.77, 0.92; both P < 0.001) versus non-consumers. Higher fish consumption frequency also associated with attenuated BA (β_PhenoAge = -0.38, 95% CI: -0.57, -0.19; OR_{PhenoAgeAccel} = 0.94, 95% CI: 0.90, 0.99; P < 0.05), with RCS and threshold analyses revealing an L-shaped negative relationship. Inflammatory and antioxidant biomarkers mediated 7.98%-27.37% of the fish consumption-BA association. However, shellfish consumption showed no significant link to BA.

CONCLUSIONS: Our study demonstrated a negative correlation between total fish-shellfish consumption and BA, with a potential primary contributor of fish consumption to this association. Inflammatory/antioxidant biomarkers may mediate the relationship.

PMID:41217697 | DOI:10.1007/s11845-025-04145-6

Ultrasound J. 2025 Nov 11;17(1):58. doi: 10.1186/s13089-025-00466-w.

ABSTRACT

BACKGROUND: Medical education commonly utilizes the “see one, do one” two-step approach for teaching psychomotor skills; however, recent evidence suggests that Peyton’s four-step method leads to superior learning. There is limited evidence, and almost no high-quality studies, specifically evaluating the effect of Peyton’s Four‑Step method on long-term retention of ultrasound/POCUS procedural skills. The purpose of this research project was to evaluate the effectiveness of Peyton’s four-step method on teaching the POCUS psychomotor skills of image acquisition to novice learners. Additionally, this research project assessed the influence of Peyton’s four-step method at three different points in time during the skill acquisition phase, in the setting of ongoing deliberate skill practice.

METHODS: A single-blinded, repeated measures interventional study based on experimental design was completed. Physician Assistant students from one large academic medical center were randomized into a control group (using the two-step method) and intervention group (using Peyton’s four-step method). Students were taught POCUS of the aorta, bladder, heart, lungs, and kidneys. Students’ POCUS skills were assessed during the immediate, intermediate, and delayed learning phases. At each assessment, an organ-specific score and a total score were obtained. Scores were compared using a Wilcoxon rank sum test. An ordinal logistic regression analysis was performed using a generalized linear mixed model with a multinomial distribution and cumulative logit link function to assess the overall effect of Peyton’s four-step method.

RESULTS: Students who were taught using Peyton’s method were found to have an increased likelihood of higher total scores compared to those taught using usual instruction (OR = 4.2, p = 0.003). Peyton’s method was found to have increased likelihood of higher scores for cardiac (OR = 2.3, p = 0.032), lung (OR = 2.5, p = 0.034), and kidney (OR = 3.0, p = 0.015). Student performance statistically improved with Peyton’s four-step method during the immediate (p = 0.031) and delayed (p = 0.011) skill acquisition phases, but not in the intermediate phase.

CONCLUSION: Peyton’s four-step method improves overall psychomotor skill acquisition for POCUS. Peyton’s four-step method specifically improved psychomotor skills in the immediate skill acquisition phase and the delayed skill acquisition phase. The benefit of Peyton’s four-step method was more prominent in POCUS applications with higher complexity.

PMID:41217693 | DOI:10.1186/s13089-025-00466-w

Odontology. 2025 Nov 11. doi: 10.1007/s10266-025-01253-8. Online ahead of print.

ABSTRACT

Oral squamous cell carcinoma (OSCC), comprising 90% of oral malignancies, poses a global health challenge due to late detection and aggressive progression. Circulating tumor DNA (ctDNA), detectable via liquid biopsy, offers a non-invasive alternative for monitoring, prognosis, and treatment response in OSCC. To evaluate ctDNA as a prognostic biomarker in OSCC, the levels of ctDNA with tumor stage, treatment response, survival rates, and demographic characteristics were monitored. A 3-year follow-up study recruited 94 OSCC patients from four hospitals in Peshawar, Pakistan. Blood samples were collected at four time intervals i.e., diagnosis, post-surgery, post-treatment, and during follow-up. ctDNA was extracted and quantified. Statistical analyses, including one-way ANOVA, Kaplan-Meier survival analysis, and Cox proportional hazards model, were conducted to assess the association of ctDNA levels with clinical and demographic variables and treatment response. The mean ctDNA level of the whole cohort was highest before surgery (37.52 ± 8.71 ng/ml) and decreased significantly after surgery (31.93 ± 8.46 ng/ml), post-treatment (25.89 ± 8.38 ng/ml), and at follow-up (20.37 ± 10.31 ng/ml; p < 0.001). Overall survival of patients with high ctDNA levels had poorer survival (median: 15 months) compared to those with low levels (median: 25 months; p = 0.025). Cox regression analysis showed low ctDNA levels were associated with a 66% reduced risk of mortality (HR: 0.34, p = 0.031). ctDNA levels correlated significantly with metastasis and treatment type, but not with tumor grade, stage, or demographics. We believe this study is the largest cohort of OSCC patients from Pakistan with follow-up and treatment data. ctDNA serves as a valuable non-invasive prognostic biomarker for monitoring tumor burden, assessing treatment response, and predicting survival in OSCC patients.

PMID:41217672 | DOI:10.1007/s10266-025-01253-8

Geroscience. 2025 Nov 11. doi: 10.1007/s11357-025-01990-2. Online ahead of print.

ABSTRACT

Epigenetic clocks are increasingly proposed as surrogate endpoints in aging trials, yet their short-term behavior in healthy older adults is not well characterized. We analyzed DNA methylation at baseline, year 1, and year 2 in 899 COSMOS-Blood participants (mean age 70.0; 50% women), deriving Horvath, Hannum, PhenoAge, and GrimAge clocks (original and principal component [PC] versions) and DunedinPACE. Epigenetic age acceleration was computed by regressing each clock on chronological age. Chronological age was independent of epigenetic age acceleration and DunedinPACE. PC clocks exhibited substantially smaller 2-year change variance than original clocks, indicating greater measurement stability. Linear mixed-effects models showed statistically detectable but numerically small annual epigenetic age acceleration increases for several PC clocks (e.g., PC Horvath + 0.14 year/year; PC GrimAge + 0.16 year/year), whereas DunedinPACE did not change significantly. Baseline values strongly predicted the same measure at years 1 and 2 (R² ≈ 0.71-0.88 for PC clocks). Tertile trajectories were largely stable, and first-year increases tended to be followed by second-year decreases, consistent with regression to the mean. Overall, current epigenetic measures, particularly PC clocks, appear stable on average and highly predictable over 2 years in generally healthy older adults, implying limited sensitivity to short-term change. These empirical SDs and strong baseline-follow-up correlations support ANCOVA-based analytic methods for future trials, and the study provides information for the power calculation.

PMID:41217671 | DOI:10.1007/s11357-025-01990-2

J Robot Surg. 2025 Nov 11;20(1):7. doi: 10.1007/s11701-025-02960-8.

ABSTRACT

Intraoperative hypothermia (IOH) is a prevalent perioperative complication.Although the use of robotic surgery in addressing colorectal cancer has seen a notable upward trend in recent clinical practice, its particularity increases the risk of IOH. Therefore, it is particularly important to study the relationship between robotic colorectal cancer surgery (RCRC) and IOH. We retrospectively collected data from patients who underwent RCRC at Jiangsu North People’s Hospital from October 2019 to February 2025. Data regarding intraoperative core temperature and potential influencing factors was collected to probe into the risk factors of IOH in patients undergoing RCRC surgery. Statistical analyses were performed using weighted logistic regression and linear models, with restricted cubic splines (RCS) adopted to detect possible non-linear associations, and subgroup analyses carried out as well. A total of 452 patients were included; IOH was observed in 218 patients (incidence rate, 0.48). Results from univariate and multivariate analyses showed that higher BMI and preoperative body temperature were protective factors against IOH (OR = 0.834, 95% CI: 0.657-0.952, P = 0.012; OR = 0.632, 95% CI: 0.432-0.858, P = 0.018). ASA physical status and operative time were risk factors for IOH (OR = 5.359, 95% CI: 1.680-9.378, P = 0.044; OR = 2.132, 95% CI: 1.123-6.230, P = 0.038). Upon analyzing preoperative body temperature through quartiles, a significant negative correlation was identified between preoperative body temperature and IOH in Quartile 4 (36.6-37.5 ℃). The odds ratio (OR) values were 0.80 (95% CI: 0.65-0.97), 0.64 ((95% CI: 0.53-0.83), and 0.69 (95% CI: 0.55-0.85) for Models 1, 2, and 3, respectively, with corresponding P-values of 0.024, 0.028, and 0.018. RCS highlighted a significant negative non-linear association (nonlinear test P = 0.017, consistent with the described P = 0.019). Below 36.5 ℃, for every 0.1 ℃ decrease, the risk of IOH increased by 13.5% (OR = 1.365, 95% CI: 1.021-1.430). No significant interaction phenomena were detected in any of the subgroups. In the present study focusing on patients who underwent RCRC surgery, there was an L-shaped non-linear relationship between preoperative body temperature and IOH, with the inflection point approaching 36.5 ℃. The integration of RCS and subgroup analyses enhances the depth of our findings, providing valuable insights for preventing perioperative IOH in patients undergoing RCRC.

PMID:41217660 | DOI:10.1007/s11701-025-02960-8

Methods Mol Biol. 2025 Nov 12. doi: 10.1007/7651_2025_676. Online ahead of print.

ABSTRACT

High-throughput drug testing combined with synergy evaluation in patient-derived tumor organoids (PDOs) represents a robust methodological approach to identify effective therapeutic combinations. PDOs retain tumor heterogeneity and the three-dimensional microenvironment, offering a physiologically relevant platform for rational drug testing. In this chapter, we provide a methodological guide to synergy testing in PDOs, including experimental design, statistical frameworks, and troubleshooting strategies. Emphasis is placed on practical aspects of drug combination screening, interpretation of synergy scores, and considerations for reproducibility. This practical guide aims to support researchers in applying organoid-based synergy assays as a translational tool in oncology.

PMID:41217623 | DOI:10.1007/7651_2025_676

Cardiovasc Drugs Ther. 2025 Nov 11. doi: 10.1007/s10557-025-07807-w. Online ahead of print.

ABSTRACT

PURPOSE: Anemia is common among women undergoing elective percutaneous coronary intervention (PCI), yet remains under-addressed in contemporary ACC/AHA guidelines. We evaluated the association between baseline anemia and short- and long-term outcomes after PCI.

METHODS: Using the TriNetX federated electronic health record network, we identified women undergoing first-time elective PCI and compared anemic vs. non-anemic patients. One-to-one propensity score matching yielded N = 1,153 per group, balancing demographics, comorbidities, medications, and labs. Clinical outcomes were assessed at 7 days, 30 days, 6 months, and 12 months, and included major adverse cardiovascular events (MACE), acute coronary syndrome (ACS), acute kidney injury (AKI), stroke or transient ischemic attack (TIA), major bleeding, transfusion requirements, all-cause hospitalization, in-stent restenosis, stent thrombosis, and all-cause mortality. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models.

RESULTS: At 7 days post-procedure, baseline anemia was significantly associated with an increased risk of AKI (HR 2.2; 95% confidence interval [CI], 1.1-4.5; p = 0.03), major bleeding events (HR 3.2; 95% CI, 1.4-7.5; p < 0.01), and transfusion requirements (HR 9.1; 95% CI, 2.1-39.2; p < 0.01). Notably, all 7-day mortality events occurred in the anemic cohort (0.9% vs. 0.0%). By 30 days, patients with anemia continued to demonstrate higher rates of AKI, major bleeding, and transfusion needs. At 12 months, these risks persisted and, in some cases, widened. Anemia was independently associated with increased rates of major adverse cardiovascular events (MACE) (HR 1.4; 95% CI, 1.1-1.8; p = 0.01), AKI (HR 1.9; 95% CI, 1.5-2.5; p < 0.01), all-cause hospitalization (HR 1.3; 95% CI, 1.1-1.5; p < 0.01), and all-cause mortality (HR 2.3; 95% CI, 1.4-3.8; p < 0.01). Differences in stroke or TIA rates were not statistically significant, and the incidence of stent thrombosis or restenosis was comparable between anemic and non-anemic groups.

CONCLUSIONS: Among women undergoing elective PCI, baseline anemia emerged as a strong predictor of adverse outcomes, spanning early kidney/bleeding complications and sustained increases in MACE, hospitalizations, and mortality over one year, without clear differences in stent-related events. These data support integrating anemia into pre-PCI risk assessment and motivate randomized trials of pre-procedural anemia optimization.

PMID:41217611 | DOI:10.1007/s10557-025-07807-w

J Racial Ethn Health Disparities. 2025 Nov 11. doi: 10.1007/s40615-025-02727-9. Online ahead of print.

ABSTRACT

BACKGROUND: The specific association between arthritis and kidney stones was still indistinct and lacked comprehensiveness. The study was to explore this association between them, including racial-ethnic disparities.

METHODS: This cross-sectional study included 26,442 participants (unweighted) from 2007 to 2020 National Health and Nutrition Examination Survey. The main outcome was the risk of kidney stones. Arthritis and its types were the exposure. The outcome and exposures were based on self-report questionnaire. Specific associations were assessed by weighted logistic regression and sensitivity analyses based on complex sample designs. The subgroup and interaction analysis were performed to probe differences in the races/ethnicities (non-Hispanic Whites, non-Hispanic Blacks, Mexican American, Other Hispanics, and other races).

RESULTS: This study recruited 26,442 participants (unweighted), of which 2,526 participants (unweighted) had kidney stone (weighted, 9.9%) while 23,916 participants (unweighted) did not, and 7,284 participants (unweighted) had arthritis (weighted, 25.9%) while 19,158 participants (unweighted) did not. In all models, individuals with arthritis tend to have a higher risk of kidney stone. In fully adjusted models, a positive association was suggested between the risk of kidney stone and arthritis (OR:1.61, 95%CI:1.40-1.86), rheumatoid arthritis (OR:1.93, 95%CI:1.54-2.43), osteoarthritis/degenerative arthritis (OR:1.55, 95%CI:1.29-1.86), and other arthritis (OR:1.56, 95%CI:1.30-1.88). These associations had interactive effects in different races/ethnicities (P for interaction < 0.01). In the races/ethnicities subgroups, though there are positive associations in all groups, only the non-Hispanic Whites had a significant positive association between the risk of kidney stone and rheumatoid arthritis (OR:2.04, 95%CI:1.54-2.70). Other races had the highest positive association between the risk of kidney stone and arthritis (OR:3.32, 95%CI:1.94-5.69), osteoarthritis (OR:3.47, 95%CI:1.98-6.09), and other arthritis (OR:3.77, 95%CI:1.88-7.55), followed by the non-Hispanic Blacks.

CONCLUSIONS: Arthritis, rheumatoid arthritis, osteoarthritis/degenerative arthritis, and other arthritis were significantly and positively associated with kidney stone risk. These associations existed in interactive effects on different races/ethnicities. Cross-sectional nature prevents causal inference in this study.

PMID:41217608 | DOI:10.1007/s40615-025-02727-9