Category: Statistics

Biometrics. 2026 Jul 1;82(3):ujag126. doi: 10.1093/biomtc/ujag126.

ABSTRACT

Emerging technologies enable continuous monitoring of temporal exposures to disease risk factors, leading to complex exposure processes characterized by subject-specific numbers and durations of exposure episodes. A key scientific question is how the number and duration of such episodes influence disease risk. Existing methods typically rely on scalar summaries or time-indexed representations and are not naturally suited to model duration-dependent risk accumulation at the episode level. We introduce the FLexible Accumulation ModEl (FLAME), a semiparametric model for risk accumulation at the level of individual exposure episodes, with duration as the primary driver of risk. FLAME is motivated by and applied to quantifying the association between the duration of intraoperative hypotension and acute kidney injury (AKI) following cardiac surgery. The estimated risk accumulation function reveals that, although 60 one-minute hypotensive episodes are associated with an AKI probability of 0.24, a single sustained 60-minute episode increases that probability to 0.33, representing a 38% increase despite identical total duration. These findings provide actionable insights for intraoperative hemodynamic management and demonstrate the importance of accounting for episodic exposure patterns. While motivated by cardiac surgery, FLAME is broadly applicable to other settings involving high-resolution temporal exposures. An R package, flameRisk, is provided to facilitate the application of the method in practice.

PMID:42439082 | DOI:10.1093/biomtc/ujag126

Biometrics. 2026 Jul 1;82(3):ujag125. doi: 10.1093/biomtc/ujag125.

ABSTRACT

Dynamic systems involving a population of subjects often feature significant variability among the individual trajectories. Mixed-effects ordinary differential equations (ODEs) provide a natural modeling framework for such systems, where subjects share the same functional form for the ODEs but have subject-specific parameters. However, inference for nonlinear mixed-effects ODE models remains challenging, particularly in settings where the system is only partially observed or the trajectories are highly sensitive to the model parameters. In pharmacokinetic modeling, for example, the observed data also tend to be sparse and noisy. To address these challenges, we propose an extension of manifold-constrained Gaussian processes for inference of general mixed-effects ODE models within a Bayesian statistical framework. We evaluate our method on simulated examples, demonstrating its ability to provide fast and accurate inference for parameters and trajectories using nested optimization. To illustrate the practical efficacy of the proposed method, we provide a real data analysis of a pharmacokinetic model used for an HIV combination therapy study.

PMID:42439081 | DOI:10.1093/biomtc/ujag125

J Pediatr Gastroenterol Nutr. 2026 Jul 13. doi: 10.1002/jpn3.70497. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe national patterns of management, outcomes, and prognostic factors in infants with biliary atresia (BA) in Italy.

METHODS: This retrospective study used data from the Italian BA Registry from January 2012 to December 2021. Overall, 309 infants with BA were identified. Clearance of jaundice (CoJ) was defined as total bilirubin <1.2 mg/dL within 6 months. Univariate and multivariate analyses were used to identify prognostic factors for native liver and patient survival.

RESULTS: Kasai portoenterostomy (KPE) was performed in 272 infants (88%) at a median age of 68.5 days (interquartile range 52-83). The CoJ rate after KPE was 39%. Multivariate analysis confirmed that CoJ was significantly associated with younger age and lower total bilirubin at referral (p = 0.0446 and p = 0.0144, respectively), younger age at KPE (p = 0.0345), and postoperative corticosteroid use (p = 0.0036). Multiple logistic regression confirmed the major effect of steroid use: the odds ratio for steroid use was 2.51 (95% confidence interval 1.38-4.58; p = 0.0027), whereas the odds ratio for age at KPE was 0.987 (95% CI: 0.975-0.999; p = 0.0371). Liver transplantation was performed in 212/309 patients, and overall 5-year actuarial patient survival was 97.4%.

CONCLUSIONS: This retrospective analysis confirms that age at KPE and postoperative corticosteroid use are key favorable factors for successful CoJ, with steroid use showing the strongest association. The excellent overall patient survival highlights the critical role of management in expert centers, even within a decentralized model.

PMID:42439064 | DOI:10.1002/jpn3.70497

Ann Clin Transl Neurol. 2026 Jul 13. doi: 10.1002/acn3.70479. Online ahead of print.

ABSTRACT

BACKGROUND: Recent randomized trials (CREST-2, SPACE-2, and ECST-2) have compared carotid revascularization (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) plus contemporary medical therapy (CMT) versus CMT alone in asymptomatic carotid stenosis. ECST-2 included both asymptomatic and low-risk symptomatic patients, introducing clinical heterogeneity. Individual trials reported low event rates and limited statistical power.

OBJECTIVE: To evaluate whether carotid revascularization reduces long-term ipsilateral stroke (> 30 days) compared with CMT alone and to assess periprocedural complications.

METHODS: Phase 3/4 randomized controlled trials published after 2020 were included. The primary outcome was long-term ipsilateral stroke excluding periprocedural events. Periprocedural complications (30-day stroke, myocardial infarction, or death) were analyzed separately. Random-effects models were used. Subgroup analyses by modality (CEA vs. CAS) included CREST-2 and SPACE-2. Sensitivity analyses excluding ECST-2 and using split-control methodology for SPACE-2 were performed.

RESULTS: Three trials (5 arms; 3438 patients) were included. Median follow-up was 4.0 years in CREST-2, 5.0 years in SPACE-2, and 2.0 years in ECST-2. In the primary pooled analysis including ECST-2, revascularization showed a nonsignificant reduction in long-term ipsilateral stroke (RR 0.51; 95% CI 0.21-1.29; p = 0.16; I² = 70%) and a borderline increase in periprocedural complications (RR 2.78; p = 0.06). Sensitivity analyses excluding ECST-2 suggested reduced long-term ipsilateral stroke with revascularization (RR 0.35; 95% CI 0.21-0.58; p < 0.0001; I² = 0%; ARR 2.74%; NNT = 37) but increased periprocedural complications (RR 4.54; p = 0.004; I² = 0%; ARI 1.45%; NNH = 69). Subgroup analyses suggested a possible benefit with CAS, whereas CEA showed a nonsignificant trend; however, subgroup analyses were underpowered. Split-control sensitivity analyses for SPACE-2 yielded directionally similar findings with wider confidence intervals.

CONCLUSION: The primary pooled analysis was inconclusive and demonstrated substantial heterogeneity. Sensitivity analyses restricted to purely asymptomatic populations suggested that carotid revascularization may reduce long-term ipsilateral stroke but increase periprocedural complications. Contemporary medical therapy remains the foundation of management for asymptomatic carotid stenosis, while revascularization should be reserved for carefully selected patients after individualized risk assessment and shared decision-making.

PMID:42439053 | DOI:10.1002/acn3.70479

Laryngoscope. 2026 Jul 13. doi: 10.1002/lary.70728. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether compensatory inferior turbinate (CIT) intervention performed during septorhinoplasty (SRP) independently improves postoperative nasal airway function and patient-reported symptoms.

METHODS: Eighty-four patients with nasal obstruction, septal deviation, external nasal deformity, and Grades 2-3 compensatory inferior turbinate hypertrophy were prospectively enrolled. Patients were randomized into two groups: SRP combined with CIT radiofrequency ablation and turbinate lateralization (SRP + IT, n = 42) or SRP alone (SRP, n = 38). Subjective nasal obstruction was evaluated using the Nasal Obstruction Symptom Evaluation (NOSE) scale, while objective nasal airflow was assessed with Peak Nasal Inspiratory Flow (PNIF). Assessments were performed preoperatively and at 6 months postoperatively. Multivariate regression analysis excluding baseline outcome scores was conducted to identify predictors of postoperative improvement.

RESULTS: Both groups demonstrated significant improvement in NOSE scores at 6 months compared with preoperative values (p = 0.001). PNIF values increased postoperatively in both groups. However, no significant differences were observed between the groups in postoperative NOSE score reduction or PNIF gain on the deviated side, turbinate side, or bilateral measurements. When baseline outcome scores were excluded from regression models to avoid floor effect bias, preoperative bilateral PNIF and sex were individually associated with postoperative NOSE improvement, and preoperative NOSE score with PNIF gain; however, neither overall model reached statistical significance (R² = 0.117 and R² = 0.066, respectively). CIT treatment was not an independent predictor of postoperative functional improvement in either model.

CONCLUSION: Concomitant CIT radiofrequency ablation and turbinate lateralization during SRP does not independently improve postoperative nasal airway function or symptom outcomes. Multivariate analysis excluding baseline outcome scores confirmed that CIT treatment was not an independent predictor of functional recovery. Although preoperative bilateral PNIF and sex showed limited associations with postoperative NOSE improvement, and preoperative NOSE score with PNIF gain, overall model fit was limited in both analyses, suggesting that functional recovery after SRP is multifactorial and not driven by any single clinical variable.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07481045. The study was retrospectively registered because trial registration was not required by the institutional ethics committee at the time of study initiation.

PMID:42439048 | DOI:10.1002/lary.70728

Br J Health Psychol. 2026 Sep;31(3):e70093. doi: 10.1111/bjhp.70093.

ABSTRACT

OBJECTIVES: University students regularly report insufficient sleep, with almost one-third of students achieving less than 6.5 hours per night. Social media is one behaviour shown to negatively influence sleep. However, there has been a reliance on self-report measures of both processes, which may not reflect objective behaviour. The aim was to determine if there is a relationship between social media use and sleep outcomes when measured objectively, and if so, which sleep outcomes were associated with social media use.

DESIGN: A longitudinal repeated measures design was used to assess daily social media use and sleep outcomes over 14 days.

METHODS: Participants wore accelerometers to measure their sleep, with total daily social media use derived from smartphone data.

RESULTS: Sixty-two participants (M_age = 22.11 years, SD = 5.82 years) completed the study. Linear mixed models revealed no between or within-participant effects of daily social media on sleep duration, sleep onset latency, sleep efficiency and bedtime. However, TikTok showed a positive between-participants effect on bedtime. A generalized linear mixed model also revealed that Snapchat had a negative between-participants effect on sleep onset latency.

CONCLUSIONS: Findings indicate that the duration of time spent on social media does not impact sleep across this sample. However, interactions with different social media platforms such as TikTok and Snapchat may play an important role in influencing sleep quality. These findings suggest that behavioural measures do not reflect the same pattern of effects observed with self-report, highlighting the need for future research to corroborate findings derived from self-report.

PMID:42439038 | DOI:10.1111/bjhp.70093

J Phys Chem B. 2026 Jul 13. doi: 10.1021/acs.jpcb.6c01785. Online ahead of print.

ABSTRACT

Molecular dynamics (MD) simulations are powerful tools for elucidating the macroscopic physical properties of materials from microscopic atomic behaviors. However, the massive, high-dimensional data sets generated by MD simulations pose a significant challenge for analysis, necessitating efficient dimensionality reduction and feature extraction techniques. While existing methods such as principal component analysis and unsupervised learning have been utilized, issues regarding data efficiency and computational cost remain. In this study, we propose a statistical analysis framework focusing on the analysis of the particle data distributions through their covariance matrices, corresponding to the second-order moments of MD trajectory data. Discrepancies between system states are quantified using statistical distances between these covariance matrices. By applying dimensionality reduction to the resulting distance matrix, we extract lower-dimensional features that characterize the systems’ dynamics. We validate the proposed method using Lennard-Jones (LJ) particle systems under different temperature conditions, as well as separate bulk systems of ice and liquid water. The results of LJ particles demonstrate an approximately linear correlation between the first principal component obtained through dimensionality reduction of the distance matrix and the diffusion coefficient. This suggests that global physical properties can be effectively inferred from local statistical information, such as covariance matrices, offering a data-efficient alternative for analyzing complex molecular systems. Furthermore, in the case of separate bulk systems of ice and liquid water, the method successfully distinguishes between the two phases, highlighting its potential for characterizing phase transitions and structural differences in molecular systems.

PMID:42439028 | DOI:10.1021/acs.jpcb.6c01785

Ginekol Pol. 2026 Jul 13. doi: 10.5603/gpl.109046. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate whether vaginal microbiota (VM) composition is associated with high-risk human papillomavirus (HR-HPV) persistence.

MATERIAL AND METHODS: Ethics committee approval was obtained on March 7, 2024. Following completion of the two-year prospective clinical follow-up, data collection and analysis were performed between March 15, 2024, and August 15, 2024. The study was considered completed upon final data analysis and included a total of 98 women: 49 women who cleared HR-HPV infection at the two-year follow-up and 49 women with persistent HR-HPV infection. Vaginal swab samples were collected, cultured, and analyzed, with particular attention to Lactobacillus species. Vaginal microbiota profiles were evaluated and compared between groups.

RESULTS: There were no statistically significant differences between the groups in terms of sociodemographic characteristics. No statistically significant differences were observed between HPV-negative and HPV-positive women or between HPV 16/18-positive and other HR-HPV positive groups with respect to Community State Types (CSTs) (p > 0.05). Overall vaginal microbiota composition did not differ significantly between HPV-positive and HPV-negative women. However, a statistically significant difference in CST distribution was observed between women with single and multiple HR-HPV infections (p = 0.002).

CONCLUSIONS: Vaginal microbiota composition does not differ significantly between HPV-positive and HPV-negative women. In contrast, significant differences are observed between women with single and multiple HR-HPV infections.

PMID:42439027 | DOI:10.5603/gpl.109046

APMIS. 2026 Jul;134(7):e70236. doi: 10.1111/apm.70236.

ABSTRACT

Serum collagen IV (Col IV) is an important marker for staging liver fibrosis, but histological baselines in healthy tissue are often lacking or biased. This study applied unbiased stereological sampling to quantify liver Col IV in healthy adult Wistar rats and assess sex differences. No significant differences were observed between sampling strategies (simple, systematic, or stratified random) or between males (4.26% ± 0.93%) and females (3.71% ± 1.27%), yielding a pooled mean of 3.96% ± 1.11%. The Col IV-positive area (3.62% ± 1.29%) did not differ significantly from the total collagen area measured by Sirius red (3.06% ± 1.72%), although a statistical trend was noted (R² = 0.5845, p = 0.0767). These data indicate that IHC-based area measurements capture a larger structural footprint of the mesh-like Col IV network than biochemical mass-based methods, and that 58% of the variance in Col IV area is explained by Sirius red-positive area, suggesting a regulated spatial balance. The absence of sex effects on Col IV implies that previously reported sex-related differences in total liver collagen likely involve other collagen types. Unbiased Col IV quantification may support validation of minimally invasive methods for staging liver fibrosis.

PMID:42439020 | DOI:10.1111/apm.70236

ACS Nano. 2026 Jul 13. doi: 10.1021/acsnano.6c07232. Online ahead of print.

ABSTRACT

CrCl₃, a layered van der Waals (vdW) magnet, exhibits in-plane magnetic anisotropy and enhanced interlayer coupling upon stacking, making it an ideal platform to host exotic nanoscale magnetic phenomena such as magnon hydrodynamics and Meron-like topological spin defects. When interfaced with other vdW materials, its antiferromagnetic-to-ferromagnetic and ferromagnetic-to-paramagnetic phase transitions and magnetic anisotropy can be tuned by voltage, strain, and layer stacking. Understanding the spin dynamics of CrCl₃ at its magnetic phase transitions is crucial to its applications in magnonics. Here, we investigate the spin dynamics of CrCl₃ nanoflakes using cryogenic diamond quantum sensing microscopy, based on measuring optically detected magnetic resonance, Rabi oscillations, and spin-lattice relaxation time (T₁) of shallow nitrogen vacancy (NV) centers in diamond. In the ferromagnetic regime, we observe a pronounced reduction in the NV spin resonance contrast, a collapse of the Rabi oscillations, and a strong enhancement by 2 orders of magnitude of the relaxation rate Γ₁ = 1/T₁. These observations indicate intensified spin fluctuations in the gigahertz range. Broadband ferromagnetic resonance spectroscopy on CrCl₃ crystals reveals resonance frequencies in the 4-15 GHz range together with a line width of ∼24 mT, further supporting the NV measurements. A phenomenological model of magnetic-noise-induced NV relaxation reproduces the temperature dependence of Γ₁ by combining antiferromagnetic, ferromagnetic, and paramagnetic fluctuation channels, indicating that magnetic noise is strongest in the ferromagnetic regime and evolves markedly across the phase transition. These results are crucial for using CrCl₃ in 2D magnonics and hybrid quantum-magnon systems.

PMID:42439011 | DOI:10.1021/acsnano.6c07232