Category: Statistics

BMC Urol. 2025 Dec 4. doi: 10.1186/s12894-025-02011-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the ability of the systemic immune-inflammation index (SII), which is tested before transrectal ultrasound-guided systematic prostate biopsy, to predict the histopathology of non-malignant and malignant prostate tissue.

METHODS: Data from 1040 patients who underwent transrectal ultrasound-guided prostate biopsy between June 2019 and January 2023 due to high prostate-specific antigen levels or palpation of suspicious prostate cancer nodules via digital rectal examination were analyzed retrospectively. The patients were divided into two groups as biopsy negative and prostate cancer. The SII, platelet/lymphocyte ratio (PLR), and neutrophil/lymphocyte ratio (NLR) were compared between the two groups. Statistical analyses were performed using Student’s t, Mann-Whitney U, and one-way ANOVA tests, along with ROC curve analysis and DeLong’s test to assess diagnostic performance.

RESULTS: There was no difference between the groups in terms of the SII, PLR, or NLR (p > 0.05). When evaluated according to the European Urology Association risk groups for biochemical recurrence of localized and locally advanced prostate cancer based on systematic biopsy, a significant difference was observed in the SII and PLR markers between the groups with biopsy negative and those with high-risk prostate cancer (p = 0.009, and p < 0.001, respectively). In the ROC analysis, the AUC for the SII was 0.568 (95% CI 0.523-0.628). The best limit value was determined to be 591.4, and for values ≥ 591.4, the sensitivity was determined to be 0.5, and the specificity was 0.571. For the PLR, the AUC was 0.618 (95% CI 0.559-0.676). The best limit value was 139.6, and for values ≥ 139.6, the sensitivity was 0.52, and the specificity was 0.72.

CONCLUSIONS: Hematological inflammatory parameters before prostate biopsy are not effective markers for distinguishing between biopsy negative and malignant pathologies. The inflammatory markers SII and PLR can be used as diagnostic tools in high-risk prostate cancer patients but cannot be used as markers for the detection of pathologies in low- and intermediate-risk patients.

PMID:41345845 | DOI:10.1186/s12894-025-02011-2

Med Phys. 2025 Dec;52(12):e70183. doi: 10.1002/mp.70183.

ABSTRACT

BACKGROUND: Compared to photon therapy (XT), proton therapy (PT) can often reduce normal tissue toxicity for head and neck (HN) cancer patients, despite being a limited resource. On the other hand, clinical decision-making process to select between PT and XT (e.g., treatment planning and then plan evaluation for comparing normal tissue complication probabilities (NTCP) between XT and PT) is time-consuming and resource demanding.

PURPOSE: This study aims to develop and validate the feasibility of an artificial intelligence (AI)-based automated method for efficient patient selection between PT and XT.

METHODS: A heterogeneous cohort of 104 bilateral HN patients with auto-planned PT and XT plans was analyzed, covering diverse tumor subsites and prescription dose levels. To ensure accurate dose and NTCP prediction, a joint-modality prediction framework was developed, incorporating a 3D attention-gated U-net with a multi-constrained loss function. A stratified 10-fold cross-validation strategy was employed to evaluate and compare model performance. The NTCP differences between XT and PT for grade II/III xerostomia/dysphagia exceeding certain thresholds are used to select patients for PT according to the Landelijk Indicatie Protocol Protonentherapie (versie 2.2) (LIPPv2.2).

RESULTS: AI-assisted patient selection process took about 10.1 s per patient. Our method achieved an accuracy of 85.58% and a weighted accuracy of 81.11% in patient selection. For dysphagia grades ≥ 2 and ≥ 3, the predicted results exhibited consistent selection with the ground truth in 86.54% and 89.42% of cases, respectively. Compared to previous models, the average ΔNTCP prediction error (ΔNTCP ground truth-ΔNTCP predicted, mean ± SD) of the proposed method was 1.47 ± 1.80%, statistically lower than U-net (1.67 ± 2.20%) and hierarchically densely connected U-net (2.34 ± 3.25%). Moreover, the joint-modality prediction of PT and XT dose distributions using Attention U-net achieved comparable performance to separate single-modality predictions.

CONCLUSION: This study highlights the potential of a novel AI-assisted framework with joint-modality prediction to enhance efficiency and precision for proton-photon patient selection in the heterogeneous dataset, demonstrating the generalizability and robustness of the proposed approach.

PMID:41345820 | DOI:10.1002/mp.70183

Neurogastroenterol Motil. 2025 Dec 4:e70216. doi: 10.1111/nmo.70216. Online ahead of print.

ABSTRACT

BACKGROUND: The reference standard for the assessment of esophageal motility and sphincter function is high-resolution esophageal manometry (HRM). Diagnostic values for HRM are determined by the Chicago Classification (CC v4.0), which is based almost entirely on distal esophageal function without measures to address the proximal esophageal segment. Therefore, we sought to determine normal HRM values for proximal esophageal function when obtained in the standard HRM positions (supine and upright).

METHODS: Healthy, asymptomatic adults (≥ 18 years) were recruited. All participants completed a standard protocol. CC v4.0 measurements, along with a proximal contractile integral (PCI) (millimeters mercury-seconds-centimeters[mmHg-s-cm]), temporal measures of proximal and distal contractility (seconds), and lengths of proximal and distal esophagus (centimeters), were performed. Summary statistics, tests of normality, and paired two-sided t-tests were performed.

RESULTS: HRM data from 30 participants were included. Mean supine PCI was 423.9 mmHg-s-cm with a mean contraction time of 3.2 s and a mean length of 5.5 cm. The mean upright PCI was 183.9 mmHg-s-cm with a mean contraction time of 2.2 s, and a mean length of 4.5 cm. All proximal values were significantly different comparing the two positions (PCI p < 0.0001; time p < 0.0001; length p < 0.0001). All distal measurements fell within the ranges of normal, and all measures for contractile integral, contraction time, and contraction length were statistically significantly different (p < 0.0001 for all) comparing proximal versus distal measurements.

CONCLUSIONS: These preliminary data represent our first attempt to quantify normal proximal esophageal function using HRM measurements of contractile vigor, contraction length, and time.

PMID:41345798 | DOI:10.1111/nmo.70216

Magn Reson Med. 2025 Dec 4. doi: 10.1002/mrm.70212. Online ahead of print.

ABSTRACT

PURPOSE: Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath-held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free-breathing cardiac MRE.

METHODS: A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k-space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post-processing specialized for cardiac imaging.

RESULTS: Feasibility of free-breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant-specific images, 17-segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin-systole), 5.74 ± 0.94, 5.42 ± 0.87 (end-systole), 3.84 ± 0.71 (begin-diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end-diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one-way, repeated-measures ANOVA (p < 0.001) and Friedman’s test (p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject-specific. Comparison of free-breathing stiffness measurements against reference breath-held measurements yielded similar systolic stiffness estimates.

CONCLUSIONS: This study establishes the feasibility of free-breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject-specific.

PMID:41345797 | DOI:10.1002/mrm.70212

Nat Methods. 2025 Dec 4. doi: 10.1038/s41592-025-02893-y. Online ahead of print.

ABSTRACT

Pose estimation methods and motion capture systems have opened doors to quantitative measurements of animal kinematics. While animal behavior experiments are expensive and complex, tracking errors sometimes make large portions of the experimental data unusable. Here our deep learning method, Deep Imputation for Skeleton data (DISK), uncovers dependencies between keypoints and their dynamics to impute missing tracking data without the help of any manual annotations. We demonstrate the utility and performance of DISK on seven animal skeletons including multi-animal setups. The imputed recordings allow us to detect more episodes of motion, such as steps, and obtain more statistically robust results when comparing these episodes between experimental conditions. In addition, by learning to impute the missing content, DISK learns meaningful representations of the data capturing, for example, underlying actions. This stand-alone imputation package, available at https://github.com/bozeklab/DISK.git/ , is applicable to outputs of tracking methods (marker-based or markerless) and allows for varied types of downstream analysis.

PMID:41345771 | DOI:10.1038/s41592-025-02893-y

Nat Methods. 2025 Dec 4. doi: 10.1038/s41592-025-02896-9. Online ahead of print.

ABSTRACT

We propose a latent space-based statistical network analysis (LatentSNA) method that implements network science in a generative Bayesian framework, preserves neurologically meaningful brain topology and improves statistical power for imaging biomarker detection. LatentSNA (1) addresses the lack of power and inflated type II errors in current analytic approaches when detecting imaging biomarkers, (2) allows unbiased estimation of the influence of biomarkers on behavioral variants, (3) quantifies uncertainty and evaluates the likelihood of estimated biomarker effects against chance and (4) improves brain-behavior prediction in new samples as well as the clinical utility of neuroimaging findings. LatentSNA is broadly applicable across multiple imaging modalities and outcome measures in developing, aging and transdiagnostic cohorts, totaling 8,003 to 11,861 participants. LatentSNA achieves substantial accuracy gains (averaging 110-150%) and replicability improvements (averaging 153%) over existing approaches in moderate to large datasets. As a result, LatentSNA elucidates how network topology is implicated in brain-behavior relationships.

PMID:41345770 | DOI:10.1038/s41592-025-02896-9

Pharmacoeconomics. 2025 Dec 4. doi: 10.1007/s40273-025-01566-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Chimeric antigen receptor T-cell therapies have changed the treatment paradigm of relapsed or refractory large B-cell lymphoma but are among the most expensive treatments. Moreover, their comparative economic value remains uncertain in adults with relapsed or refractory large B-cell lymphoma. The objective of this study was to understand the comparative value of these therapies in this population and the main factors that influenced conclusions on which intervention was considered more cost effective than others.

METHODS: To assess the comparative cost effectiveness of chimeric antigen receptor T-cell therapies and the drivers of cost-effectiveness results, a systematic literature search of Embase, Scopus, and PubMed was conducted from inception to December 2024 and updated in October 2025. Studies were selected if they were full economic evaluations of head-to-head comparisons of chimeric antigen receptor T-cell therapies for relapsed or refractory large B-cell lymphoma. Two reviewers independently extracted data on key information such as population characteristics and model structure. Results were reported in their original format, and conclusions on cost effectiveness were evaluated based on country-specific willingness-to-pay thresholds. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and the Drummond 10-Item Checklist.

RESULTS: Eight full economic evaluations across the USA, Spain, France, and Japan were included in this systematic review. All studies modeled an adult population or patients with relapsed or refractory large B-cell lymphoma who had failed two or more lines of prior therapy, were conducted over a lifetime horizon, and mostly used the payer perspective (n = 6). All studies utilized three-state partitioned survival models but relied heavily on indirect comparison methods such as matching-adjusted indirect comparison. Three chimeric antigen receptor T-cell therapies were evaluated: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel). Axi-cel was the most frequently reported cost-effective option (n = 7) with two studies concluding it was the dominant strategy. There was substantial uncertainty in the model results given the lack of individual patient-level data for each arm and reliance on indirect comparisons.

CONCLUSIONS: In this systematic review of economic evaluations of head-to-head comparisons of chimeric antigen receptor T-cell therapies for relapsed or refractory large B-cell lymphoma, current evidence suggests that axi-cel may be the most cost-effective option. However, given the studies’ reliance on indirect comparisons and the absence of any study conducted in low- to middle-income countries, these results must be carefully interpreted until additional evaluations or clinical trials are conducted.

PMID:41345759 | DOI:10.1007/s40273-025-01566-0

Eur J Pediatr. 2025 Dec 4;184(12):819. doi: 10.1007/s00431-025-06584-w.

ABSTRACT

Research on the infection-related etiologies of neonatal acute respiratory distress syndrome (NARDS) remains limited. This study aimed to investigate mortality risk differences in NARDS attributed to distinct infection origins (sepsis of extrapulmonary origin or pulmonary infection origin). Subjects were derived from a multicenter retrospective study organized by the Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network. It included neonates with NARDS who initiated invasive mechanical ventilation (IMV) within 72 h of birth. A total of 268 from 1275 NARDS cases with infectious etiologies were enrolled. Multivariate Cox regression found a significant difference in the survival prognosis (sepsis of extrapulmonary origin, adjusted hazard ratio (HR): 3.93, 95% CI 1.79-8.62, log-rank test: P < 0.001]. Further multi-model and sensitivity analysis confirmed the robustness. Between early-onset and late-onset NARDS, the subgroup analysis showed no significant differences in the mortality risk, whether it was pulmonary infection origin (HR 1.69, 95% CI 0.61-4.64) or sepsis of extrapulmonary origin (HR 0.50, 95% CI 0.17-1.51). Restricted cubic spline also exhibited that the onset time of NARDS was not related to the mortality risk.

CONCLUSION: This study suggests that for sepsis of extrapulmonary origin, we should be more vigilant about the mortality risk it brings and deal with the risk factors more actively and prudently.

WHAT IS KNOWN: • Limited research has systematically investigated the association between infection origin and mortality risk in neonatal acute respiratory distress syndrome (NARDS).

WHAT IS NEW: • Our study found that sepsis of extrapulmonary origin was associated with an increased mortality risk in neonates with gestational age > 34 weeks, with robust results from multivariate Cox modeling and sensitivity analyses. • It highlights the need for heightened vigilance and proactive management of extrapulmonary sepsis-related NARDS to mitigate mortality risk in neonates.

PMID:41345740 | DOI:10.1007/s00431-025-06584-w

Microbiome. 2025 Dec 4. doi: 10.1186/s40168-025-02291-8. Online ahead of print.

ABSTRACT

BACKGROUND: Aflatoxin B₁ (AFB₁), a highly carcinogenic and hepatotoxic mycotoxin frequently contaminating animal feed, presents serious health risks to both humans and livestock. Although AFB₁‘s hepatotoxicity and other organ damage are extensively characterized, how this mycotoxin influences ruminal microbiota dynamics and functional activities in ruminants remains underexplored. Although some studies suggest that AFB₁ reduces nutrient digestibility and performance in ruminants, the underlying mechanisms are unclear. To aid in developing effective mitigation strategies for aflatoxicosis in ruminants, this study randomly divided Saanen goats into three groups. The CON group received the standard ration without additives, whereas LD and HD groups were provided identical basal diets fortified with 50 or 500 μg/kg AFB₁. Throughout the study, alterations in ruminal fermentation parameters, microbiome, and metabolome profiles were analyzed.

RESULTS: With increasing AFB₁ levels, ruminal pH, the concentration of total volatile fatty acids (VFA), acetate, and propionate decreased quadratically, while butyrate decreased linearly. Metagenomic profiling indicated suppressed populations of Pelagibacter and Flavobacterium following AFB₁ exposure, contrasting with promoted growth of Cryptobacteroides. Additionally, seven carbohydrate-active enzymes (CAZymes), specifically GT92, GT20, CE7, GT32, GT35, GT57, and GT50, were found to be more prevalent in the rumen of the CON group. Statistically higher viral loads characterized the HD group when benchmarked against CON group. Metabolomics analysis identified 1197 differential metabolites among the CON, LD, and HD groups, including cytochalasin Ppho and chrysophanol, both known for their teratogenic properties and their ability to induce cell death.

CONCLUSIONS: This study indicates that dietary AFB₁ exposure can alter the ruminal microbial and metabolomic profiles, induce prophage activation, and impact carbohydrate degradation and microbial protein turnover. These alterations may contribute to reductions in ruminal pH and volatile fatty acid concentrations, thereby impairing feed digestibility and animal performance. The findings provide valuable insights into AFB₁‘s effects on rumen health, and further investigations of these metabolic pathways may help develop precision interventions to mitigate AFB₁-induced rumen dysfunction and productivity losses. Video Abstract.

PMID:41345737 | DOI:10.1186/s40168-025-02291-8

BMC Psychol. 2025 Dec 5. doi: 10.1186/s40359-025-03767-w. Online ahead of print.

ABSTRACT

BACKGROUND: Healthcare workers are often exposed to traumatic events and as a result, they may experience post-traumatic stress disorder (PTSD) and other mental illnesses. The prevalence of these issues is high among healthcare professionals. Positive transformation (i.e., PTG) can emerge after struggles related to a stressful life event.

METHODS: In this cross-sectional study utilizing structural equation modeling (SEM), a sample of Iranian healthcare workers (nurses and pre-hospital emergency personnel from Ardabil) completed a battery of self-report questionnaires. These measures included a demographic information form, the Life Events Checklist (LEC-5), the Core Beliefs Inventory (CBI), the PTSD Checklist for DSM-5 (PCL-5), the Posttraumatic Growth Inventory (PTGI), scales assessing intrusive and deliberate rumination, and a social support questionnaire.

RESULTS: In examining the direct coefficient paths, all paths were statistically significant with the exception of the path of core belief disruption to deliberate rumination, social support to intrusive rumination, and PTSD to PTG. Similarly, in the examination of the coefficient of indirect paths, all paths were not statistically significant except for the paths of intrusive rumination to PTG through deliberate rumination and social support to PTG through deliberate rumination.

CONCLUSION: The study’s findings suggest that disruptions in core beliefs can result in both post-traumatic growth (PTG) and post-traumatic stress disorder (PTSD) and that social support plays a crucial role in promoting PTG. Clinical interventions that address disruptions in core beliefs and promote social support, such as mindfulness practices and purposeful thinking, may be effective in promoting mental health and well-being among healthcare professionals. Based on the results of the study, clinical interventions that address disruptions in core beliefs and promote social support may be effective in promoting mental health and well-being among healthcare professionals who have experienced traumatic events. As such, these findings can inform the development of evidence-based clinical interventions that can improve the mental health outcomes of healthcare professionals and, ultimately, enhance patient care.

PMID:41345734 | DOI:10.1186/s40359-025-03767-w