Category: Statistics

BMC Cancer. 2025 Dec 22. doi: 10.1186/s12885-025-15436-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the value of quantitative parameters and radiomic features based on dual-layer spectral detector CT (DLCT) in predicting spread through air spaces (STAS) of lung adenocarcinoma (LUAD).

METHODS: This study analyzed 266 patients with pathologically confirmed LUAD from two medical centers. Patients from center 1 were divided into training (n = 131) and internal validation (n = 57) sets, while center 2 (n = 78) formed the external validation set. Clinical data, conventional imaging features, and DLCT quantitative parameters were analyzed to develop a clinical-radiological model. Radiomic features were extracted from venous-phase images, including conventional images, virtual monoenergetic images (VMI) at 40 keV, 65 keV, and 100 keV, along with iodine density maps, effective atomic number (Zeff) maps, and electron density (ED) maps. The best-performing radiomics model was combined with clinical-radiological predictors to create a nomogram. Model performance was evaluated through ROC analysis, calibration curves, and decision curve analysis.

RESULTS: Multivariate analysis revealed that tumor-lung interface and ED values were independent predictive factors in the clinical-radiological model. The optimal radiomics model was constructed based on VMI 40 keV, demonstrating AUCs of 0.899, 0.835, and 0.828 in the training, internal validation, and external validation sets, respectively. The nomogram, which incorporated the VMI 40 keV radiomics signature along with tumor-lung interface and ED values, outperformed the clinical-radiological model in the training set (AUC = 0.910 vs. 0.870; P = 0.018) and the internal validation set (AUC = 0.868 vs. 0.798; P = 0.046). While the improvement in the external validation set was not statistically significant (AUC = 0.848 vs. 0.819; P = 0.184).

CONCLUSION: The nomogram, which integrates conventional imaging features, DLCT quantitative parameters and VMI 40 keV radiomic features, demonstrates promising performance and represents a potential valuable non-invasive tool for the preoperative assessment of STAS in LUAD.

PMID:41423690 | DOI:10.1186/s12885-025-15436-7

BMC Oral Health. 2025 Dec 22. doi: 10.1186/s12903-025-07526-6. Online ahead of print.

ABSTRACT

BACKGROUND: The complex and irregular morphology of prepared oval root canals poses optimal sealing in oval canals as a key endodontic challenge. To address this, this study utilized five types of standardized 3D-printed models replicating prepared anatomy of extracted teeth with oval canal, to characterize the morphological diversity of oval canals after preparation and evaluate the efficacy of three obturation techniques across different morphologies.

METHODS: Five standardized 3-dimensional printed models replicating prepared oval canal morphology were produced using cone-beam computed tomography (CBCT)-derived data from sixty extracted premolars, which had undergone standardized collection, screening, and in vitro preparation procedures. Three obturation techniques (n = 15 each) were evaluated: (1) lateral condensation with AH-Plus sealer (AHP-LC), (2) continuous wave vertical compaction with AH-Plus sealer (AHP-CWC), and (3) single-cone technique with iRoot SP sealer (SP-SC). Micro-CT scanning and volumetric analyses were employed to quantify the obturation quality. Statistical analysis was performed using Mann-Whitney U test, Kruskal-Wallis H test, Dunn’s test or Spearman rank’s correlation depending on the experimental design.

RESULTS: Micro-CT analysis revealed significant differences in the percentage of void volume (PVV) among the obturation techniques. Over the entire canal length, SP-SC demonstrated significantly lower PVV compared to AHP-LC and AHP-CWC (p < 0.01). In the apical third, canal morphology significantly influenced the PVV of AHP-CWC (p < 0.05), with a more circular cross-section (higher roundness) correlating strongly with a lower PVV (p < 0.001). No significant effects of morphology were observed in other canal segments or with the other obturation techniques.

CONCLUSIONS: SP-SC achieved more complete three-dimensional adaptation regardless of morphological variations in oval canals including varied diameter ratios, isthmus and recess. Conversely, AHP-CWC’s performance was significantly dependent on canal morphology in the apical third, where more circular cross-sections correlated with lower void volumes.

PMID:41423672 | DOI:10.1186/s12903-025-07526-6

Cancer Med. 2025 Dec;14(24):e71487. doi: 10.1002/cam4.71487.

ABSTRACT

BACKGROUND: Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non-cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear.

OBJECTIVES: To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS).

METHODS: AE reports related to ADT drugs were extracted from FAERS (Q1 2004-Q3 2024). Disproportionality analyses-including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)-were conducted to identify significant cardiovascular safety signals.

RESULTS: Different ADT agents exhibited distinct cardiovascular AE profiles. Some drugs were linked to a broader range of CVD-related AEs, while others had more limited associations.

CONCLUSIONS: ADT agents demonstrate heterogeneous cardiotoxicity profiles. These findings emphasize the need for individualized treatment strategies, particularly in patients with pre-existing CVD risks, and may aid clinicians in balancing cancer control with cardiovascular safety.

PMID:41423663 | DOI:10.1002/cam4.71487

Med Phys. 2026 Jan;53(1):e70206. doi: 10.1002/mp.70206.

ABSTRACT

BACKGROUND: Accurate and consistent image segmentation across longitudinal scans is essential in many clinical applications, including surveillance, treatment monitoring, and adaptive interventions. While personalized model adaptation using patient-specific prior scans has shown promise, current approaches typically rely on fixed training durations and lack mechanisms to determine optimal stopping points on a per-patient basis, particularly in the absence of validation labels.

PURPOSE: We propose an uncertainty-guided test-time optimization (TTO) framework that dynamically adjusts the personalization duration for each patient using a validation-free stopping criterion based on predictive uncertainty.

METHODS: Our framework personalizes a generalized segmentation model using patient-specific prior imaging and selects the optimal checkpoint based on the minimum voxel-wise predictive uncertainty, estimated via Monte Carlo Dropout (TTO-MCD) or Deep Ensembling (TTO-DE). We evaluated the approach on three datasets: 214 pancreas (CT) scans, 243 liver (CT) scans, and 175 head-and-neck tumor (MRI) scans, each containing a subset of patients with paired longitudinal scans to enable patient-specific personalization. Each patient’s follow-up scan was held out for testing. As a baseline, we implemented a fixed-epoch personalization strategy (Pre-TTO) using a fivefold cross-test design to emulate deployable model selection without test label leakage.

RESULTS: TTO methods consistently outperformed the Pre-TTO and unpersonalized baseline across standard metrics, including the Dice Similarity Coefficient (DSC), 95th percentile Hausdorff Distance (HD95), Mean Surface Distance (MSD), and the proposed LogPenalty Score (LPS), which provides a bounded, interpretable scale that jointly reflects volumetric and boundary fidelity. Paired t-tests confirmed statistically significant improvements for pancreas and liver datasets (p < 0.05), while favorable trends were observed in the head-and-neck dataset despite greater anatomical variability. Both TTO-MCD and TTO-DE achieved near-optimal performance without requiring access to labels at test time.

CONCLUSION: Uncertainty-guided TTO provides a robust, validation-free strategy for optimizing patient-specific segmentation models in longitudinal medical imaging. By tailoring personalization based on predictive uncertainty, our method improves segmentation quality across a range of imaging modalities and anatomical targets. This framework supports broad clinical deployment of personalized AI and motivates future extensions to contextual integration and multi-label segmentation. Code is publicly available at https://github.com/jchun-ai/uncertainty-tto.

PMID:41423658 | DOI:10.1002/mp.70206

BMC Nurs. 2025 Dec 21. doi: 10.1186/s12912-025-04240-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Working conditions and occupational stress among nurses affect the quality of care and, consequently, patient satisfaction. Moreover, spiritual health among nurses is an essential component of healthcare services in achieving patient satisfaction. Therefore, the present study aimed to examine the relationship between nurses’ spiritual health and patients’ satisfaction with nursing services (PSNS) provided in southwest Iran.

METHODS: This descriptive-analytical, cross-sectional study was conducted among 80 nurses and their corresponding 80 patients in the clinical wards of Imam Khomeini and Razi Hospitals in Ahvaz in 2022. Data were collected using standardized questionnaires assessing spiritual health and PSNS, employing a convenience sampling method. Data analysis was performed using descriptive statistics, Spearman’s correlation test, and multiple linear regression in SPSS version 24. A significance level of p < 0.05 was considered.

RESULTS: The mean score of nurses’ spiritual health was 90.27 ± 15.32, and the mean score of PSNS was 97.23 ± 14.13, both at a moderate level. No significant association was found between spiritual health scores and demographic variables (p > 0.05). A significant association was observed between patient satisfaction scores and the frequency of hospital visits (p = 0.029). No statistically significant relationship was found between nurses’ spiritual health and patients’ satisfaction (p > 0.05). The coefficient of determination (R² = 0.175) indicated that the type of insurance, frequency of hospital visits, and marital status of patients together predicted 17.5% of the variance in patient satisfaction.

CONCLUSION: Spiritual health among nurses had no effect on patients’ satisfaction with nursing care, and no statistically significant relationship was found between these two variables. PSNS was influenced by their demographic characteristics and environmental factors such as frequency of visits, educational level, insurance coverage, and marital status, rather than by the nurses’ spiritual health. By improving service delivery processes, enhancing patients’ awareness of the treatment process, providing financial support for patients, and identifying other contributing factors, patients’ satisfaction can be improved.

PMID:41423647 | DOI:10.1186/s12912-025-04240-0

Sci Rep. 2025 Dec 22. doi: 10.1038/s41598-025-31438-8. Online ahead of print.

ABSTRACT

Histopathological image analysis plays a critical role in modern medical diagnostics, particularly in the detection and classification of various types of cancer. This study proposes a method called HistoDARE (Histopathology-Aware DINO with Attention-based Representation Enhancement), which offers an innovative approach to the attention module used in the Vision Transformers architecture. Unlike conventional attention mechanisms, HistoDARE introduces a novel three-stage AttentionWrapper module that sequentially applies spatial and channel attention followed by a residual refinement stage, enabling the extraction of spatially-aware and semantically distinctive feature representations. HistoDARE is a method integrated into the DINOv2 model, which uses the ViT-L/14 architecture. The obtained features were interpreted using Logistic Regression, and 5-fold stratified cross-validation was applied on the NCT-CRC-HE-100K dataset. The proposed HistoDARE achieved a mean accuracy of 98.03%, precision of 98.03%, recall of 98.02%, F1-score of 98.02%, and specificity of 99.95%, outperforming the baseline DINOv2 and other state-of-the-art methods. The experiments were conducted on a computer with high computational capacity. Based on the DINOv2 architecture, the proposed HistoDARE maintains comparable computational efficiency and resource usage while generating more contextually enriched and discriminative feature representations. During performance measurements, it demonstrated consistent and stable improvements across all stages in all folds. Notably, significant performance improvements were achieved in clinically critical classes such as NORM and STR. These results demonstrate that HistoDARE not only achieves high overall accuracy but also provides superior class-level consistency, making it a robust and generalisable framework for clinical histopathology applications. The developed method has been shared on our GitHub repository. This ensures transparency in terms of reproducibility and supports its usability by other researchers on different datasets in the future. The core contribution of HistoDARE is a three-stage AttentionWrapper (spatial, channel, residual refinement) integrated into the DINOv2 ViT-L/14 backbone to make patch-level representations histopathology-aware. Despite the small numerical gain over a strong self-supervised baseline, this attention-enabled refinement yields statistically consistent improvements on clinically sensitive classes (NORM, STR) and thus strengthens the model’s potential usability in real pathology workflows.

PMID:41423645 | DOI:10.1038/s41598-025-31438-8

Sci Rep. 2025 Dec 21. doi: 10.1038/s41598-025-33097-1. Online ahead of print.

ABSTRACT

Postoperative pulmonary complications, particularly atelectasis, are common after cardiac surgery and may contribute to impaired gas exchange or acute lung injury (ALI). Neurally Adjusted Ventilatory Assist (NAVA) delivers ventilatory support proportional to the patient’s respiratory drive, offering theoretical advantages over Pressure Support Ventilation (PSV), including improved synchrony, enhanced diaphragmatic efficiency, and reduced risk of ventilator-induced lung injury. However, comparative data on gas exchange, dead space, and regional ventilation during weaning after cardiac surgery remain limited. This prospective crossover study evaluated 12 mechanically ventilated patients with mild ALI following cardiac surgery across three ventilation phases: two PSV phases (PSV1 and PSV2) separated by a phase of NAVA. Intrapulmonary shunt fraction was calculated from measurements obtained via a Swan-Ganz catheter. Physiological dead space fraction (V_D/V_T) was assessed using three methods: the Bohr-Enghoff equation, end-tidal CO₂-derived alveolar dead space fraction (AVDSf-ET), and a novel time-to-volume converted capnographic approach (V_CAP-CALC). Regional ventilation was assessed using electrical impedance tomography (EIT), and neuroventilatory efficiency (NVE) was calculated from diaphragmatic electrical activity (EAdi). Data were analyzed using linear mixed-effects models to account for repeated measures and within-subject variability. V_D/V_T was significantly lower during NAVA compared with PSV1 and PSV2 when assessed by V_CAP-CALC (58.5% vs. 63.8% and 61.3%, respectively; p < 0.001). The PaO₂/FiO₂ ratio and NVE were significantly higher during NAVA (p = 0.01 and p = 0.037, respectively). No significant difference in pulmonary shunt fraction was observed. EIT revealed a modest increase in dorsal end-expiratory lung volume during NAVA, without redistribution of tidal volume or Center of Ventilation. The V_CAP-CALC method showed strong agreement with established dead space measures (R2 = 0.77-0.82) and demonstrated high repeatability (mean coefficient of variation 3.5%). NAVA is a safe and feasible ventilatory mode following cardiac surgery, associated with reduced dead space fraction, improved oxygenation and enhanced neuroventilatory efficiency. Given that shunt fraction remained unchanged, the observed improvement in ventilation-perfusion (V/Q) matching reflects a reduction in V_D/V_T. The potential implications for postoperative recovery and long-term outcomes merit evaluation in larger clinical studies.ClinicalTrials.gov: NCT03217305. Initial Release 21/06/2017.

PMID:41423634 | DOI:10.1038/s41598-025-33097-1

Int J Health Geogr. 2025 Dec 21. doi: 10.1186/s12942-025-00441-7. Online ahead of print.

ABSTRACT

BACKGROUND: Suicide remains a major public health concern worldwide, responsible for more than 700,000 deaths in 2021, accounting for approximately 1.1% of all global deaths. While many high-income countries have reported declines in age-standardized suicide rates over the past two decades, recent evidence from Spain indicates increasing mortality among women, whereas suicide rates among men have remained relatively stable. To better understand these patterns and their potential underlying determinants, this study examines the spatial and temporal patterns of age-stratified suicide mortality across Spanish provinces from 2010 to 2022, with particular attention to sex-specific differences.

METHODS: Mixed Poisson models were applied to analyze provincial- and temporal-level suicide mortality rates, stratified by age and sex. The models accounted for spatial and temporal confounding effects and examined associations with various socioeconomic and contextual factors, including rurality and unemployment.

RESULTS: Findings highlight the influence of rurality and unemployment on suicide mortality, with distinct gender-specific patterns. A 10% increase in the proportion of residents living in rural areas was associated with more than a 5% rise in male suicide mortality, while a 1% increase in the annual unemployment rate was linked to a 2.4% increase in female suicide mortality. Although male suicide rates remained consistently higher than female rates, a notable and steady upward trend was observed in female suicide mortality over the study period.

CONCLUSIONS: The use of sophisticated statistical models permits the detection of underlying patterns, revealing both geographic and temporal disparities in suicide mortality across Spanish provinces.

PMID:41423620 | DOI:10.1186/s12942-025-00441-7

Nat Commun. 2025 Dec 21. doi: 10.1038/s41467-025-67800-7. Online ahead of print.

ABSTRACT

The role of the gut microbiota in carcinogenesis is increasingly being acknowledged. Recent studies in multiple breast cancer mouse models have found that antibiotics, by altering the gut microbiota, can accelerate tumour growth. In humans, a recent cohort study restricted to triple negative breast cancer showed that breast cancer patients using a greater number of antibiotics had markedly worse survival. These studies have raised concerns about repeated antibiotic use in breast cancer patients. In this Registered Report, we investigated whether breast cancer patients using oral antibiotics had increased breast cancer-specific mortality. In population-based cohorts (n = 44,452), we did not observe a statistically significant association between antibiotic prescriptions after diagnosis and breast cancer-specific mortality (adjusted HR = 1.07 95% CI 0.87, 1.33) apart from prescriptions of 12 or more antibiotics (adjusted HR = 1.62 95% CI 1.31, 2.01). This association was weaker after adjustment for infections (adjusted HR = 1.44 95% 1.14, 1.81), when restricted to antibiotics within five years (adjusted HR = 1.33 95% 0.95, 1.84), and was similar for deaths from other causes (adjusted HR = 1.69 95% 1.19, 2.41). Frequent antibiotic users had higher cancer-specific mortality but the attenuation of associations in sensitivity analyses, and similar findings for other causes of death, suggest this increase may reflect residual confounding. Protocol registration: The Stage 1 protocol for this Registered Report was accepted in principle on 7 November 2023. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.24746721.v1.

PMID:41423616 | DOI:10.1038/s41467-025-67800-7

Clin Rheumatol. 2025 Dec 22. doi: 10.1007/s10067-025-07861-7. Online ahead of print.

ABSTRACT

BACKGROUND: Fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS) frequently coexist, compounding disease burden and complicating treatment approaches. Despite the prevalence of this comorbidity, evidence on effective management strategies remains scarce.

OBJECTIVE: This systematic review evaluates the efficacy and safety of oral pharmacological and dietary interventions for patients diagnosed with both FMS and IBS, following PRISMA guidelines.

METHODS: A systematic literature search was performed on September 12, 2024, utilizing the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), Web of Science, EMBASE, and Ovid to identifying randomized control trials evaluating interventions for FMS comorbid with IBS. The outcome encompassed pain reduction, global well-being, depressive symptoms, health-related quality of life, and safety profiles.

RESULTS: The initial search yielded 784 studies, with 364 retrieved after applying inclusion criteria. Following duplicate removal and further screening, five randomized control trials met eligibility criteria. Of these, three were included in the meta-analysis. These trials investigated the effects of pharmacological agents, dietary modifications, and probiotics on pain and quality-of-life measures in patients with FMS-IBS comorbidity. Meta-analysis showed a statistically significant reduction in pain Visual Analog Scale (VAS) scores in groups receiving cyclobenzaprine and pregabalin, while probiotics demonstrated no significant benefit over placebo. Dietary interventions showed mixed results, providing symptom relief in selected patients. Adverse effects were highest in the cyclobenzaprine 30 mg group but were generally well tolerated in other interventions.

CONCLUSION: Pharmacological treatments appear effective in reducing pain associated with FMS and IBS. Dietary interventions, such as monosodium glutamate (MSG) elimination, may benefit specific subgroups, while probiotics showed limited efficacy.

PMID:41423615 | DOI:10.1007/s10067-025-07861-7