Category: Statistics

Front Neurol. 2025 Sep 17;16:1622941. doi: 10.3389/fneur.2025.1622941. eCollection 2025.

ABSTRACT

BACKGROUND: Carotid plaque thickness and BRI are each associated with an increased risk of stroke. However, the value of their interaction in predicting stroke remains unclear. This study aimed to investigate the predictive performance of maximum carotid plaque thickness, BRI, and their interaction for the occurrence of stroke or TIA.

METHODS: In this prospective cohort study, 230 elderly Chinese adults were enrolled. Baseline measurements included maximum carotid plaque thickness and BRI, and an interaction term was calculated. Participants were followed for 1 year, during which the incidence of stroke or TIA was recorded. Multivariable logistic regression was used to assess the predictive value of each variable. Receiver operating characteristic curve analysis with 95% confidence intervals was conducted to determine the area under the curve (AUC) for model performance, and internal validation using bootstrap resampling (B = 1,000) was performed to correct for potential optimism.

RESULTS: Both maximum plaque thickness (3.305 ± 0.515 mm vs. 2.245 ± 0.820 mm, p < 0.001) and BRI (4.872 ± 1.240 vs. 3.751 ± 0.916, p < 0.001) were significantly higher in the stroke group than in the non-stroke group. Logistic regression analysis showed that maximum plaque thickness (Full multivariable adjustment: OR = 3.619, 95%CI: 1.781-7.355, p = 0.00038) and BRI (Full multivariable adjustment: OR = 3.116, 95% CI: 1.784-5.444, p = 0.00006) were both independent predictors. ROC analysis revealed that the interaction term yielded the highest AUC (0.9192, 95% CI: 0.8772-0.9612), compared with maximum plaque thickness (0.8819, 95% CI: 0.8353-0.9285) and BRI (0.7632, 95% CI: 0.6266-0.8997). Statistical comparisons indicated that the interaction model significantly outperformed BRI, while its advantage over maximum plaque thickness was numerically higher but did not reach statistical significance, likely due to the limited number of events. After bootstrap correction (B = 1,000), the optimism-corrected AUC of the interaction model was 0.897 (95% CI: 0.788-0.954).

CONCLUSION: Both maximum carotid plaque thickness and BRI independently predict the risk of stroke and TIA after adjusting for confounders. Their interaction further improves predictive performance. Combined assessment of these indicators may optimize early stroke risk stratification and warrants further validation in clinical practice.

PMID:41041669 | PMC:PMC12483859 | DOI:10.3389/fneur.2025.1622941

Front Neurol. 2025 Sep 17;16:1641820. doi: 10.3389/fneur.2025.1641820. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aims to investigate gray matter (GM) and white matter (WM) changes in early Parkinson’s disease (PD) patients with mild cognitive impairment (PD-MCI) using high-resolution T1-weighted and diffusion-weighted MR images.

METHODS: We recruited 40 PD-MCI patients, 26 PD patients with normal cognition (PD-NC), and 40 healthy controls (HC). Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were performed to assess the relationship between gray matter volume, cortical thickness, and cognitive ability. Microstructural white matter changes were evaluated using tract-based spatial statistics (TBSS) with diffusion tensor imaging measures.

RESULTS: White matter structural abnormalities were widespread in PD-MCI patients (corpus callosum, corona radiata, superior longitudinal fasciculus, left cerebral peduncle, and left corticospinal tract), with more pronounced involvement in the left cerebral hemisphere compared to healthy controls. Additionally, PD-MCI patients exhibited localized cortical atrophy in the left parieto-occipital region (calcarine, lingual gyrus, and precuneus), left parahippocampal gyrus, fusiform gyrus and entorhinal cortex. A significant positive correlation was observed between reduced gray matter volume (GMV) in the left parieto-occipital region and lower MoCA scores in the PD-MCI group (p < 0.001, R = 0.565).

CONCLUSION: Even in early-stage disease, our study demonstrates widespread WM microstructural damage but only subtle GM atrophy in PD-MCI, particularly in the left hemisphere. These findings provide new evidence to enhance our understanding of the pathogenic mechanisms and pathological basis underlying cognitive impairment in Parkinson’s disease.

PMID:41041668 | PMC:PMC12483916 | DOI:10.3389/fneur.2025.1641820

Transbound Emerg Dis. 2025 Sep 24;2025:5542740. doi: 10.1155/tbed/5542740. eCollection 2025.

ABSTRACT

Autochthonous cases of dengue in Europe are increasing. In 2023 (Lodi province) and 2024 (Fano, Pesaro and Urbino province), Italy saw the largest modern dengue outbreaks to date. Public health measures were adopted to mitigate transmission. The efficacy of these measures is unknown. We model the 2023 and 2024 dengue outbreaks to estimate the likely date of introduction of the primary case and efficacy of control measures, exploring explanations for the patterns of dengue cases for the two outbreaks. We apply a climate-driven mathematical model for Aedes albopictus and dengue virus transmission to the 2023 and 2024 outbreaks, comparing outputs to case data. The model accurately predicts the initial timeline of the Lodi dengue outbreak (R ² = 0.83), with a peak in cases in late August 2023, after which the control efforts reduced transmission. The model also accurately predicts the Fano dengue outbreak (R ² = 0.65), showing an increase in cases, peaking in mid-September 2024, after which there was an abrupt fall in cases. Our results suggest this can be attributed to substantial rainfall, and that public health measures may have latterly prevented a second peak in cases. The high predictive and explanatory ability of the model when applied to the Lodi and Fano outbreaks indicates that this framework may be of high value for public health decision-making for predicting the frequency and magnitude of future dengue outbreaks when coupled with real-time case data.

PMID:41041651 | PMC:PMC12488316 | DOI:10.1155/tbed/5542740

Front Pharmacol. 2025 Sep 17;16:1644029. doi: 10.3389/fphar.2025.1644029. eCollection 2025.

ABSTRACT

BACKGROUND: Opioid-induced respiratory depression (OIRD) is a critical safety concern during ambulatory percutaneous liver tumor thermal ablation. Esketamine has been shown to offer a promising opioid-sparing alternative with the potential to provide respiratory stability benefits. We hypothesize that hepatic hilar nerve block (HHNB) combined with esketamine will reduce the incidence of respiratory depression when compared to HHNB in conjunction with fentanyl in this particular context.

METHODS: This single-center, prospective, double-blind, randomized controlled trial (RCT) will enroll patients undergoing ambulatory ultrasound-guided percutaneous liver thermal ablation. Patients will be randomly assigned to receive either intravenous esketamine 0.37 mg kg^-1 (Intervention group) or intravenous fentanyl 1 μg·kg^– (Control group). All subjects will receive a standardized premedication consisting of midazolam 0.03 mg kg^-1 IV, followed by ultrasound-guided HHNB.

RESULTS AND ANALYSIS: The primary outcome is the incidence of respiratory depression, defined as SpO₂ <90% or EtCO₂ >55 mmHg. Secondary outcomes include the rate of anesthesia success, postoperative pain scores, and the consumption of remedial analgesia at 2, 6, and 24 h post-surgery. Additionally, satisfaction scores from both the sonographer and the patient are considered, along with any adverse events that may occur. The statistical analysis will utilize appropriate parametric/non-parametric tests for continuous data and chi-square/Fisher’s exact tests for categorical data (significance p < 0.05), using SPSS (v20.0) and R (v4.4.3; R Foundation) within the RStudio environment (v2024.12.1 + 563).

CONCLUSION AND DISCUSSION: This trial aims to provide Level I evidence comparing the respiratory depression risk between esketamine-based and fentanyl-based analgesia during HHNB-guided liver ablation. Should esketamine prove to be demonstrably superior in terms of respiratory safety, HHNB-esketamine has the potential to be a viable treatment option.

PMID:41041639 | PMC:PMC12487020 | DOI:10.3389/fphar.2025.1644029

Interv Pain Med. 2025 Jul 24;4(3):100618. doi: 10.1016/j.inpm.2025.100618. eCollection 2025 Sep.

ABSTRACT

SUMMARY OF BACKGROUND DATA: The risk of a symptomatic epidural bleed in patients continuing anticoagulation during most types of spinal injection procedures is extremely low. Cervical epidural steroid injections involve a unique risk of a catastrophic complication if an epidural hematoma is to occur secondary to spinal cord compression due to the anatomic confines of the cervical spinal canal. There is minimal research on the risk of cervical transforaminal epidural steroid injections (CTFESI) with anticoagulation.

OBJECTIVE: Evaluate the risk of performing CTFESI with patients continuing prescribed anticoagulation medication.

METHODS: A retrospective review was performed at two practice settings, a community-based outpatient practice and an academic practice, to identify all CTFESI performed between June 2018 through November 2023. Patient medical records were reviewed for the presence of anticoagulation and NSAID medication the day of the CTFESI. Data analysis used descriptive statistics to summarize the distribution of anticoagulants, NSAIDs, and cervical levels across practices, along with medication frequencies and percentages.

RESULTS: A total of 2792 CTFESIs were performed across both settings between June 2018 and November 2023. Of those, 1040 CTFESIs (37.2 %) were performed on patients taking some form of anticoagulant medication. 277 CTFESI were performed on patients taking anticoagulants or aspirin or a combination of anticoagulants and ASA. 763 were performed on patients taking NSAIDs. There were no reported cases of symptomatic epidural hematomas or other bleeding complications in the immediate post-procedural period or up to 1 week following the procedure.

CONCLUSION: It is likely that CTFESI can be safely performed in patients continuing anticoagulation, aspirin (ASA), or NSAIDs. Discontinuing anticoagulants or NSAIDs for CTFESIs may not be necessary. Further studies are warranted to confirm these results.

PMID:41041612 | PMC:PMC12486170 | DOI:10.1016/j.inpm.2025.100618

Res Sq [Preprint]. 2025 Sep 23:rs.3.rs-7665795. doi: 10.21203/rs.3.rs-7665795/v1.

ABSTRACT

Multi-omics integration faces several challenges, including heterogeneity across platforms, high dimensionality, and reduced effective sample size when all omics types are not available for every participant. We propose the AI-based Network Integration approach, which models connectivity within each omics layer as shaped by the broader biological system, including structured influences from other omics layers.We conducted a cross-sectional multi-omics study of genetic, glycomic, and lipidomic profiles related to immune and inflammatory pathways. We integrated N-glycans of immunoglobulin G (glycans) and specialized pro-resolving lipid mediators (SPMs) to advance the understanding of immune regulation and inflammation resolution, analyzing 24 glycans and 14 SPMs. The sample size decreased from N = 456 (with glycomics) to 368 (with both lipidomics and glycomics), and further to 266 (with genetic data, lipidomics, and glycomics). Pairwise association analysis revealed 10 statistically significant glycan-SPM associations (FDR < 0.05). Using the AI-based Network Integration, we found that these associations disappeared when conditioned on two bridging molecules, 5-Hydroxyeicosapentaenoic acid (5-HEPE) SPM and a glycan peak (GP 21) corresponding to disialylation, suggesting they may be mediated or confounded by a subset of these two molecules.Principal component analysis was applied to the previously identified associated genetic variants within each omics layer to derive polygenic factors, composite components summarizing shared genetic variation across variants. These polygenic factors were used in the Granularity Directed Acyclic Graph (G-DAG) algorithm to identify valid instrumental variables for the identification of molecular causal networks based on the principles of Mendelian randomization. This approach improved robustness and also identified polygenic molecules. Both bridging molecules, 5-HEPE and the GP21 glycan, were under polygenic control. 5-HEPE acted as a receiver (influenced by other SPMs), while GP21 acted as a broadcaster (influencing other glycans). The results suggest that variations in SPM lipidomics are linked to changes in glycosylation. These findings highlight a potential biological link between lipid mediators and glycan-mediated immune regulation and inflammation resolution.The AI-based Network Integration approach turns noisy associations into a small, interpretable, and biologically meaningful connectivity that cannot be explained by any other component in the study.

PMID:41041566 | PMC:PMC12486090 | DOI:10.21203/rs.3.rs-7665795/v1

Res Sq [Preprint]. 2025 Sep 25:rs.3.rs-7485455. doi: 10.21203/rs.3.rs-7485455/v1.

ABSTRACT

Background Periodontal disease (PD) is a common chronic inflammatory condition that progresses severely in people living with HIV (PLWH). Although human leukocyte antigen (HLA) class I molecules, including HLA-A alleles, are key to immune function, their role in PD susceptibility among PLWH is poorly understood. Objective To identify the most frequent HLA-A alleles associated with PD in PLWH and determine those independently linked to PD status. Methods A case-control genetic association study was conducted using buffy coat samples from 156 HIV-positive individuals enrolled at the MJAP-ISS Clinic. DNA was extracted, amplified via PCR, and sequenced using the Oxford Nanopore MinION platform. Due to sequencing throughput limitations, only 64 samples yielded usable sequence data. Allele frequencies were compared between PD cases and periodontally healthy controls. Statistical analyses included logistic regression, and ROC curve analysis. Results Thirteen HLA-A alleles were identified. HLA-A11 was the most common allele among PD cases (48.4%) compared to controls (7.8%). A11 showed a significant association with PD (adjusted odds ratio [AOR] = 12.8; 95% CI: 3.36-61.6; p < 0.001). A sex-stratified analysis showed that the association was significant among females (AOR = 14.3), but not in males. Other alleles, such as A02 and A03 were not significantly associated. The model combining A11 and sex achieved the best performance (AUC = 0.867). Conclusion HLA-A11 is significantly associated with PD in PLWH, especially among females, suggesting a gene-sex interaction. Further studies are needed to explore the immunological basis and validate findings across diverse populations. Clinical trial Number: Not applicable.

PMID:41041565 | PMC:PMC12486094 | DOI:10.21203/rs.3.rs-7485455/v1

Res Sq [Preprint]. 2025 Sep 24:rs.3.rs-7643216. doi: 10.21203/rs.3.rs-7643216/v1.

ABSTRACT

Background: Substantial variability in individual responses to intermittent theta-burst stimulation (iTBS) limits its clinical efficacy, yet neurophysiological predictors underlying this variability remain unclear. While most machine-learning (ML) studies have focused on modeling behavioral or clinical effects of repetitive transcranial magnetic stimulation (rTMS), the few studies examining neurophysiological outcomes have typically utilized limited feature sets in single-visit settings, which captured only inter-subject variability and most importantly lacked independent validation sets. Methods: To address these gaps, we first employed statistical and reliability analysis to understand the statistical relationship between resting state EEG and responses to iTBS. Next, we employed supervised machine learning models that integrated baseline resting-state EEG (rsEEG) features and transcranial magnetic stimulation (TMS)-evoked measures, including motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs), to predict neurophysiological responses to a single iTBS session applied over the primary motor cortex in two independent test-retest studies of healthy adults. Results: Internal cross-validation within the training cohort yielded promising performance (accuracy: 81%), identifying coarse-grained multiscale distribution entropy of rsEEG as the most robust predictor of local cortical excitability changes indexed by the 100-131ms window of TEPs. However, predictive performance markedly declined upon external validation (accuracy: 69%), reflecting unstable relationships between predictors and outcomes likely driven by substantial intra- and inter-individual variability of iTBS-induced changes in neurophysiological outcomes. Conclusions: These findings emphasize that while EEG complexity measures can capture baseline brain states relevant for neuromodulation to a certain degree, the inherent instability of single-session iTBS effects significantly constrains model generalizability and underscores the necessity of test-retest paradigm to avoid overly optimistic performance estimates. Future studies with multi-session and individualized stimulation protocols are urgently needed to better characterize neurophysiological mechanisms underlying rTMS effects and ultimately enhance its therapeutic potential.

PMID:41041549 | PMC:PMC12486114 | DOI:10.21203/rs.3.rs-7643216/v1

Can J Infect Dis Med Microbiol. 2025 Sep 24;2025:8860382. doi: 10.1155/cjid/8860382. eCollection 2025.

ABSTRACT

Objective: Aimed to analyze the relationship between air pollution and Mycoplasma pneumoniae (MP) infection in children in Chengdu. Method: Data on outpatient and inpatient cases of MP infection among children at Chengdu Women and Children’s Central Hospital from 2019 to 2023 were retrospectively collected. Air pollution and meteorological data from the same period were also obtained. A generalized additive model (GAM) was established using R statistical software to examine the impact of different air pollutant concentrations on MP infection incidence in children. The relationship between pollutant concentrations and MP infection rates was further analyzed by stratifying data by age, sex, and season. Results: From 2019 to 2023, a total of 21,075 outpatient and emergency cases and 6964 inpatient cases of MP infection were reported among children at Chengdu Women and Children’s Central Hospital. A 10-μg/m³ increase in the daily concentration of particulate pollutants (PM_2.5, PM₁₀) had the most significant delayed effect on outpatient MP infection incidence at a 6-day lag (lag 06), although the cumulative lag effect was not statistically significant. When the average daily concentration of gaseous pollutants (SO₂) increased by 10 μg/m³, the strongest lag effects on outpatient and inpatient MP infections were observed at 7-day lags (lag 07 and lag 7, respectively). In the single air pollutant model, age-stratified analysis showed that SO₂ concentration had the most significant correlation with the incidence of outpatient and inpatient MP infections in children under 6 years of age, while nitrogen dioxide (NO₂) concentration had the most significant correlation in children over six. Sex-stratified analysis indicated that SO₂ levels were most significantly associated with MP infection in males, whereas NO₂ were most strongly correlated in females. Among outpatients, SO₂ had the most substantial effect on MP infection incidence across sexes. Seasonal stratification revealed that the impact of air pollution on MP infection was greater in autumn and winter than in spring and summer. Conclusion: Increased air pollution levels in Chengdu from 2019 to 2023 had a measurable impact on MP infection incidence in both inpatient and outpatient children, with notable lag and cumulative lag effects. These effects were more pronounced in autumn and winter, highlighting the need for targeted early warning systems to monitor air pollutant concentrations. Such efforts could play a crucial role in protecting vulnerable populations and reducing MP infection risks in children.

PMID:41041510 | PMC:PMC12488315 | DOI:10.1155/cjid/8860382

Phys Imaging Radiat Oncol. 2025 Aug 21;35:100827. doi: 10.1016/j.phro.2025.100827. eCollection 2025 Jul.

ABSTRACT

BACKGROUND AND PURPOSE: Subcutaneous implantable cardioverter defibrillators (S-ICDs) are increasingly used to prevent sudden cardiac death. Due to their placement near the left lateral and apical myocardium, S-ICDs can present technical challenges for stereotactic arrhythmia radioablation (STAR) of ventricular tachycardia. This study aimed to evaluate the feasibility of STAR in patients with S-ICDs.

MATERIALS AND METHODS: Previously acquired cardiac computed tomography data from ten S-ICD patients were retrospectively analyzed. Organs at risk, S-ICD components, and hypothetical planning target volumes (PTV) for segments 8 (septal), 11 (lateral), and 17 (apical) were contoured. For each patient and segment, two treatment plans were calculated with a prescribed PTV dose of 25 Gy: one plan sparing the S-ICD from the primary radiotherapy beam (‘spared’) and one without this constraint (‘non-spared’).

RESULTS: The S-ICD was successfully spared from the primary beam in 27 out of 30 plans, with D _0.035cm ³ < 1 Gy. In three spared plans (PTV segment 11) with a distance between PTV and S-ICD <4 cm, D _0.035cm ³ exceeded 1 Gy. Spared plans for PTV segment 11 showed significant higher dose/volume metrics and reduced plan quality compared to non-spared plans (p < 0.05), although 9/10 plans remained clinically acceptable. For PTV segment 8 and segment 17, no clinical or statistical differences were observed.

CONCLUSIONS: The presence of an S-ICD is not a contraindication for STAR, although plan quality may decrease with PTVs in lateral segments. Rare cases with a distance between PTV and S-ICD <4 cm may complicate radiation treatment planning.

PMID:41041508 | PMC:PMC12486173 | DOI:10.1016/j.phro.2025.100827