Category: Statistics

Toxicol Lett. 2026 Aug 15:113179. doi: 10.1016/j.toxlet.2026.113179. Online ahead of print.

ABSTRACT

Higenamine is a catecholic benzyltetrahydroisoquinoline alkaloid occurring in plant-derived foods and food supplements, the latter potentially resulting in substantially higher exposure levels than conventional foods. Because of its catechol and alkylphenol structures, oxidative conversion to electrophilic quinone or quinone methide intermediates is plausible, raising concern about a potential genotoxic hazard. However, experimental data on the genotoxic potential of higenamine are lacking. The present study, therefore, investigated its potential to induce gene mutations and chromosomal damage in cultured V79 cells. Gene mutations were examined at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus after 24hours treatment without metabolic activation and after 4hours in the absence or presence of rat liver S9-mix. Clastogenicity and aneugenicity were assessed using in vitro micronucleus assay with CREST staining after 4hours of treatment, followed by compound-free postincubation periods of 16 and 24hours. Proliferation and mitotic activity were monitored, and higenamine stability was analyzed by HPLC-UV. Higenamine caused a statistically significant increase in the frequency of micronuclei at 300-510µM, reaching maxima of 51 and 73 micronucleated cells per 1,000 cells without and with metabolic activation, respectively. Micronuclei mainly contained chromosomal fragments, indicating a prevalent clastogenic mode of action, although a smaller increase in micronuclei containing whole chromosomes was also observed. Mutant frequencies in the HPRT assay were not significantly increased under any condition tested, despite concentration-dependent cytotoxicity. During incubation, higenamine concentrations decreased while only minor formation of O-methylated metabolites was detected, suggesting conversion into additional reactive products. Overall, these findings provide the first experimental evidence that higenamine exhibits clastogenic potential in vitro and support the hypothesis that oxidative activation of its catechol and/or alkylphenol moiety to electrophilic intermediates capable of reacting with cellular nucleophiles might contribute to its genotoxic activity.

PMID:42603655 | DOI:10.1016/j.toxlet.2026.113179

Crit Rev Oncol Hematol. 2026 Aug 15:105547. doi: 10.1016/j.critrevonc.2026.105547. Online ahead of print.

ABSTRACT

OBJECTIVE: The prognostic value of circulating tumor cells (CTCs) in colorectal cancer (CRC) remains debated. This meta-analysis evaluates their role in monitoring treatment response and predicting survival.

METHODS: We systematically searched multiple databases up to November 2025. Inclusion criteria comprised cohort studies involving CRC patients that assessed peripheral blood CTCs and reported outcomes such as CTC positivity/levels before and after treatment, progression-free survival (PFS), and overall survival (OS). Two reviewers independently extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale. The meta-analysis was performed using Stata 18.0, with pooled odds ratios (ORs), standardized mean differences (SMDs), and hazard ratios (HRs) calculated using fixed- or random-effects models based on heterogeneity assessed by the I² statistic. This study was registered in PROSPERO.

RESULTS: A total of 18 studies involving 2,838 CRC patients were included. The meta-analysis demonstrated a significant decrease in both the CTC-positive rate (OR=0.52, 95% CI 0.31-0.87) and CTC count (SMD=-0.32, 95% CI -0.42 to -0.21) following therapy. Compared to patients without CTC reduction, those with reduced CTCs exhibited significantly better progression-free survival (HR=2.41, 95% CI 1.75-3.31) and overall survival (HR=3.29, 95% CI 1.99-5.45). Furthermore, CTC-positive status, both before and after treatment, was consistently associated with inferior PFS and OS (all p < 0.0001).

CONCLUSIONS: CTCs can serve as a biomarker for monitoring CRC therapeutic efficacy, predicting prognosis, and guiding subsequent treatment.

PMID:42603643 | DOI:10.1016/j.critrevonc.2026.105547

Cardiovasc Pathol. 2026 Aug 15:107854. doi: 10.1016/j.carpath.2026.107854. Online ahead of print.

ABSTRACT

Aortic aneurysms have traditionally been studied as a single pathological entity, with emphasis on valve morphology. While histopathological differences between bicuspid (BAV) and tricuspid (TAV) aortopathy are well documented, less is known about how these mechanisms interact with aneurysm location within the ascending aorta. This gap complicates risk assessment and surgical planning beyond diameter-based criteria. We aimed to evaluate histopathological features of ascending aortic aneurysms across three topographical subgroups-root, tubular, and combined involvement-and assess modification by valve cuspidity. Using systematic criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on medial degeneration, adventitial alterations and atherosclerosis in patients undergoing ascending aortic surgery at a Finnish tertiary care center. The cohort comprised 296 patients with aneurysms located in the sinus of Valsalva (n = 122), tubular part (n = 130), and both regions (n = 44). Medial degeneration was present in all samples and predominantly moderate, with comparable median severity score of 2 (range 1-3, P = 0.829) across groups. In the overall cohort, no statistically significant differences were observed between topographical groups. Among TAV patients, tubular aneurysms demonstrated significantly higher histopathological scores for medial degeneration, elastic fiber fragmentation and loss, elastic fiber disorganisation, smooth muscle cell disorganization and nuclei loss, laminar medial collapse, medial fibrosis, adventitial fibrosis and atherosclerosis (all P < 0.05). In BAV patients, no statistical differences were found. Tubular aneurysms are characterized by more extensive wall remodeling and adventitial changes compared to root aneurysms, particularly in TAV patients. Notably, female sex emerged as a strong independent predictor of advanced medial and adventitial pathology. These findings underscore the importance of considering anatomical location, valve morphology, and sex in risk stratification and may inform surgical decision-making beyond diameter-based criteria.

PMID:42603640 | DOI:10.1016/j.carpath.2026.107854

Radiother Oncol. 2026 Aug 15:111743. doi: 10.1016/j.radonc.2026.111743. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Preoperative stereotactic body radiotherapy (SBRT) has emerged as a precision locoregional strategy for early luminal breast cancer, yet no quantitative meta-analysis exists in this subtype. We aimed to estimate the pooled pathological complete response (pCR) rate, identify its predictors through meta-regression, and characterise safety and cosmetic outcomes.

MATERIALS AND METHODS: A systematic review and meta-analysis of prospective trials of preoperative SBRT in patients with clinical stage T1-T2 N0-N1 luminal (ER-positive, HER2-negative) breast cancer was conducted following PRISMA 2020 guidelines. Random-effects models with REML estimation were fitted on logit-transformed proportions. Univariable meta-regression analyses examined absorbed dose (BED_4), irradiation-to-surgery interval, fractionation, technique, and biological tumor characteristics as covariates.

RESULTS: Eleven prospective studies (428 patients) were included. Eight trials (N = 277) reported pCR data, yielding a pooled pCR rate of 21.4 % (95 % CI: 12.1-35.1 %; I² = 77.0 %). The irradiation-to-surgery interval was the sole statistically significant predictor of pCR (β = +0.045 per week; p < 0.001; R² = 98.9 %), whilst BED_4, fractionation, and technique showed no independent association. Pooled late grade ≥ 3 toxicity was 5.9 % (95 % CI: 3.7-9.1 %) and excellent or good cosmesis was achieved in 88.3 % of patients (95 % CI: 79.4-93.6 %).

CONCLUSION: Preoperative SBRT achieves a clinically meaningful pCR rate in early luminal breast cancer, with acceptable toxicity and preserved cosmesis. The irradiation-to-surgery interval is the dominant modifiable predictor of pathological response. Randomized trials prospectively optimizing this interval in the luminal subtype are warranted.

PMID:42603618 | DOI:10.1016/j.radonc.2026.111743

Am J Med Sci. 2026 Aug 15:S0002-9629(26)00313-7. doi: 10.1016/j.amjms.2026.08.005. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVE: Malignant pleural effusion and tuberculous pleurisy may both present with elevated levels, making their differential diagnosis challenging. Although an ADA level ≥ 40 U/L increases the likelihood of both conditions, additional biomarkers are needed for better discrimination. Therefore, we aimed to evaluate clinical and biochemical markers that could aid in differentiating these two conditions in patients with high ADA levels.

MATERIALS AND METHODS: This retrospective cohort study included patients with pleural effusion and pleural fluid ADA levels ≥ 40 U/L who were evaluated between 2014 and 2024. The cancer ratio (serum LDH/pleural ADA) and the pleural LDH/ADA ratio, previously described in the literature, were calculated. Multivariable regression analysis was performed to identify independent predictors of malignant pleural effusion.

RESULTS: A total of 294 patients constituted the study cohort. In multivariable regression analysis, cancer ratio was not statistically significant in differentiating malignant pleural effusion from tuberculous pleurisy. In contrast, the pleural LDH/ADA ratio, pleural protein level and age were identified as independent predictors of malignant pleural effusion. The LAPAGE index, derived from these variables [(pleural LDH / ADA) × age / pleural protein], demonstrated superior diagnostic performance in predicting malignant pleural effusion compared with individual parameters.

CONCLUSION: In patients with pleural effusion and ADA levels ≥ 40 U/L, neither the cancer ratio nor the pleural LDH/ADA ratio alone provided sufficient discriminatory power between malignant pleural effusion and tuberculous pleurisy. The LAPAGE index may serve as a useful adjunctive tool in the differential diagnosis of tuberculosis and malignancy in pleural effusions with high ADA levels.

PMID:42603615 | DOI:10.1016/j.amjms.2026.08.005

Neuroscience. 2026 Aug 15:S0306-4522(26)00559-2. doi: 10.1016/j.neuroscience.2026.08.024. Online ahead of print.

ABSTRACT

Early and objective screening of Autism Spectrum Disorder (ASD) remains challenging because conventional diagnosis primarily relies on behavioural assessment and clinical observation. To address this limitation, this study proposes a dual-domain computational framework for automated EEG-based ASD classification by integrating complementary time-frequency analysis with Horizontal Visibility Graph (HVG)-based network modelling. Four time-frequency decomposition techniques, namely the Short-Time Fourier Transform (STFT), Discrete Wavelet Transform (DWT), Wigner-Ville Distribution (WVD), and Superlet Transform (SLT), were employed to characterise the non-stationary dynamics of resting-state EEG signals. The resulting time-frequency representations were transformed into HVG networks, from which 17 graph-theoretic descriptors were extracted and evaluated using conventional machine learning classifiers, including a Soft Voting Ensemble. Among the investigated methods, the DWT-HVG framework combined with the Soft Voting Ensemble achieved the best performance, yielding an accuracy of 93.54%, sensitivity of 94.32%, specificity of 92.76%, F1-score of 93.62%, balanced accuracy of 93.54%, and an Area Under the Curve (AUC) of 98.17% using stratified 10-fold cross-validation. Statistical analysis using the Wilcoxon signed-rank test further confirmed the superiority of the DWT-based representation over the STFT, WVD, and SLT-based approaches. These findings demonstrate that integrating multiresolution time-frequency analysis with HVG-based graph-theoretic feature extraction provides an accurate, interpretable, and computationally efficient framework for objective EEG-based ASD screening.

PMID:42603613 | DOI:10.1016/j.neuroscience.2026.08.024

Arch Phys Med Rehabil. 2026 Aug 15:S0003-9993(26)00882-8. doi: 10.1016/j.apmr.2026.08.007. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the effectiveness of a 12-week complementary and alternative medicine (CAM) program for people with multiple sclerosis (pwMS) delivered by a therapist in a clinic (DirectCAM) versus self-initiated at home (TeleCAM).

DESIGN: Pragmatic cluster-randomized controlled trial.

SETTING: Forty-three clinics across Alabama, Mississippi, and Tennessee.

PARTICIPANTS: A total of 759 adults with MS were enrolled (DirectCAM, n=382; TeleCAM, n=377). Eligible participants were aged 18-70 years, self-reported a diagnosis of MS, had a Patient-Determined Disease Steps (PDDS) score between 0 and 7, were able to use their arms or legs for exercise, and had physician clearance.

INTERVENTIONS: Participants received the same 12-week CAM exercise program delivered either onsite by a therapist (DirectCAM) or at home using preloaded exercise videos (TeleCAM).

MAIN OUTCOME MEASURE(S): Patient-reported outcomes included the Modified Fatigue Impact Scale (MFIS), the 36-Item Short Form Health Survey (SF-36) Pain domain, the SF-36 physical and mental component scores, and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Performance-based outcomes included the Berg Balance Scale (BBS), the Five Times Sit-to-Stand Test (FTSST), the Timed Up and Go (TUG) test, the Timed 25-Foot Walk (T25-FW), the six-minute walk test (6MWT), and grip strength. Outcomes were assessed at baseline and 3, 6, and 12 months.

RESULTS: Of the 759 participants across 43 clinics, 382 were assigned to DirectCAM and 377 to TeleCAM. No statistically significant between-group differences were observed for patient-reported outcomes at 3, 6, or 12 months. For performance-based outcomes, improvement in BBS from baseline to 12 months was greater in DirectCAM than TeleCAM (2.1 [95% CI, 1.4-2.9], adjusted P<.001). No statistically significant between-group differences were observed for changes in 6MWT, FTSST, or T25-FW.

CONCLUSIONS: DirectCAM and TeleCAM produced comparable improvements in patient-reported outcomes. DirectCAM was superior only for BBS. Therefore, the hypothesis that TeleCAM would be superior to DirectCAM was not supported.

PMID:42603596 | DOI:10.1016/j.apmr.2026.08.007

Int J Radiat Oncol Biol Phys. 2026 Aug 15:S0360-3016(26)04147-7. doi: 10.1016/j.ijrobp.2026.07.051. Online ahead of print.

ABSTRACT

PURPOSE: Lattice radiation therapy is an innovative three-dimensional implementation of spatially fractionated radiation therapy. This study aimed to develop a novel lattice-based proton arc therapy (PAT) technique to deliver a highly modulated peak-valley spatial dose distribution and a modulated linear energy transfer (LET) distribution.

METHODS AND MATERIALS: We introduced a PAT lattice algorithm that optimizes three key components, including energy-layer selection, spot assignment, and LET optimization (PAT_LESL). A simulated annealing algorithm was used to select the optimal energy layers. Meanwhile, an adaptive spot assignment strategy was implemented using a spot-sparsity optimization algorithm based on the primal-dual active set with continuation to achieve an improved peak-to-valley dose ratio (PVDR). Subsequently, LET optimization was achieved using the alternating direction method of multipliers with a minimum monitor unit constraint. Eighteen patients were selected to evaluate plan quality and delivery efficiency compared with the lattice technique based on the previously reported spot-scanning proton arc therapy energy sequence optimization algorithm (PAT_seq). Feasibility and dosimetric accuracy were further validated using clinical phantom measurements.

RESULTS: Compared with PAT_seq, the PAT_LESL plan exhibited improved dose and LET distributions with higher delivery efficiency. More specifically, PAT_LESL achieved steeper dose gradients, improving the PVDR from 16.90 ± 18.04 to 41.85 ± 29.69 (p < 0.01), shortening the beam delivery time by 37.43%, and increasing the target spot coverage by 44.12% while reducing the spot number by 93.78%. It also increased the mean LET in the LTV from 2.84 ± 0.38 to 3.59 ± 0.26 keV/μm (p < 0.01), on average. Meanwhile, the phantom measurement confirmed high agreement between the planned and delivered results.

CONCLUSIONS: A novel PAT lattice technique using adaptive spot assignment and LET optimization could deliver an enhanced peak-valley spatial dose distribution. Experimental validation on a clinical proton system confirmed deliverability and dosimetric accuracy, which may facilitate future clinical translation of proton lattice radiotherapy.

PMID:42603564 | DOI:10.1016/j.ijrobp.2026.07.051

Int J Radiat Oncol Biol Phys. 2026 Aug 15:S0360-3016(26)04154-4. doi: 10.1016/j.ijrobp.2026.07.063. Online ahead of print.

ABSTRACT

PURPOSE: Significant advancements in external beam radiotherapy (RT) over the past 20+ years have occurred with evolution from 2D techniques based on plain film x-rays to three-dimensional (3D) conformal and intensity modulated photon techniques. Likewise, proton radiotherapy (PRT) was also introduced and has become more widely available. Each advance in radiation technique improves targeting and has the potential to mitigate late effects associated with RT. In this study, we use metadata from past and present Children’s Oncology Group (COG) trials that included RT to describe the evolution of different RT modalities across time and disease sites.

METHODS: Imaging and Radiation Oncology Core (IROC) database was queried for protocols with at least one patient receiving RT during 1998-2025. Protocol metadata including primary disease site, study timeline and quality assurance (QA) was extracted, as was non-identifiable patient-level variables including age, institution, year of enrollment, and RT modality utilized. Descriptive statistics were used for downstream analysis.

RESULTS: The study population comprised 8,898 patients, including 7,881 from the USA and 1,017 from other countries. The median age at enrollment was 9 years; California, Texas, Florida and New York were among the top contributing states. Of the 83 included COG trials, 48 included at least one patient receiving PRT. The number of trials allowing PRT peaked in 2010 with 17 protocols. Trials involving central nervous system (CNS) tumors and rhabdomyosarcoma soft tissue sarcomas (RST) dominated both in the number of trials and enrollment. They were also among the earliest to incorporate PRT into treatment protocols. From 1998 to 2025, 3D photon-based treatments declined from 73% to 15%, while IMRT/VMAT usage rose from 26% to 89% over the same interval. The use of PRT increased from 2% pre-2000 to nearly 40% in 2021, which has since stabilized. QA review demonstrated >90% protocol compliance across all RT modalities both nationally and internationally.

CONCLUSIONS: Over 25 years of COG experience, photon therapy has transitioned from 3D conformal to IMRT/VMAT, while PRT use has continued to expand, particularly in CNS and RST trials. These trends highlight how pediatric cooperative-group studies continue to shape national standards and underscore the need for future work linking modality adoption with toxicity, survivorship, and access across diverse treatment settings.

PMID:42603563 | DOI:10.1016/j.ijrobp.2026.07.063

J Affect Disord. 2026 Aug 15:122364. doi: 10.1016/j.jad.2026.122364. Online ahead of print.

ABSTRACT

BACKGROUND: This post-hoc analysis examined the effect of sustained psychiatric medication on suicide reattempt risk among Korean patients with depression following an initial attempt.

METHODS: Using the Korean Health Insurance Review and Assessment Service (HIRA) database, we identified adults aged 18 years and older diagnosed with depressive disorder who attempted suicide in 2014 (N = 4925; mean age 47.4 ± 17.3 years, range 19-96). Sustained psychiatric medication was defined as receiving antidepressant or antipsychotic treatment for ≥75% of the six months after the index attempt. Stabilized inverse-probability-of-treatment weighting (IPTW) based on propensity scores addressed baseline imbalances. Logistic regression assessed one-year reattempt risk; survival analyses examined long-term risk over up to seven years (from index through August 31, 2020; median follow-up 5.9 years, maximum 6.7 years). Exploratory subgroup analyses compared patients <65 and ≥ 65 years.

RESULTS: After IPTW, baseline characteristics were balanced. The one-year reattempt rate was 5.3% with medication versus 7.9% without (OR:0.65, 95% CI:0.504-0.846, P = 0.001). Survival analyses over the seven-year follow-up showed no significant long-term difference (IPTW-adjusted log-rank P = 0.886). The protective effect was evident only in patients <65 years (OR:0.621, 95% CI:0.471-0.822, P < 0.001), with no significant effect in those ≥65 years.

CONCLUSIONS: Sustained psychiatric medication after a suicide attempt reduces one-year reattempt risk in patients with depression, in particular in those aged under 65 years. The benefit of initial treatment did not persist over seven years, suggesting that the effect of continued treatment beyond six months warrants future investigation.

PMID:42603561 | DOI:10.1016/j.jad.2026.122364