Category: Statistics

Histol Histopathol. 2025 Sep 17:18988. doi: 10.14670/HH-18-988. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with an incidence projected to rise significantly worldwide. While TNM staging remains the cornerstone of prognosis and treatment decisions, additional biomarkers are needed to enhance predictive accuracy and therapeutic targeting. Ferroptosis, an iron-dependent cell death pathway, has emerged as a key regulator of CRC progression and therapy resistance. Circadian rhythms, KLOTHO, and tumor suppressors, such as p53, CDKN1A (p21), and Rb, also play crucial roles in CRC biology. Integrating TNM staging with molecular markers and patient-specific variables offers a more precise, personalized approach to CRC management. In the present work, we analyze the histopathological expression of KLOTHO, ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian regulators (CLOCK, BMAL1, PER1, and PER2), and classical tumor suppressors (p53, p21, and Rb) in a cohort of 63 patients diagnosed with CRC. Besides, we have considered important clinical variables, like sex, age, and anatomical location, in our statistical analysis; correlation with the protein expression of these markers was also included for each stage (T1, T2, and T3). Our study reveals that advanced CRC stages (primarily T3) exhibit increased expression of ferroptosis markers (TFRC, ALOX5, ACSL4, and GPX4) and tumor suppressors (p53, p21, and Rb), alongside reduced histopathological detection of KLOTHO and circadian markers (BMAL1, CLOCK, PER1, and PER2) compared with earlier stages. Age, but not sex, influenced the expression of several markers. Tumor location also played a role, with right-sided CRCs showing significant stage-related differences in ferroptosis, tumor suppressor, and BMAL1, whereas left-sided tumors exhibited variations primarily in circadian markers (CLOCK, PER1, and PER2). Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.

PMID:40959856 | DOI:10.14670/HH-18-988

Transpl Int. 2025 Sep 1;38:14201. doi: 10.3389/ti.2025.14201. eCollection 2025.

ABSTRACT

Tacrolimus is an immunosuppressant with a narrow therapeutic index and a high intra- and inter-patient variability showing significant challenges in optimal dosing and monitoring. Historically, pre-dose concentration monitoring and simplified area under the curve measurements have been the standard approach. However, recent advances in pharmacokinetic modeling have improved individualized dosing strategies, moving beyond empirical methods. This review explores the evolving landscape of Tacrolimus therapeutic drug monitoring, focusing on advanced modeling techniques that support personalized dosing. Key methodological approaches include Population Pharmacokinetic (PopPK) modeling, Bayesian prediction, Physiologically-Based Pharmacokinetic (PBPK) modeling, and emerging machine learning and artificial intelligence technologies. While no single method provides a perfect solution, these approaches are complementary and offer increasingly sophisticated tools for dose individualization. The review critically examines the potential and limitations of current modeling strategies, highlighting the complexity of translating advanced statistical and mathematical techniques into clinically accessible tools. A significant challenge remains the gap between sophisticated modeling techniques and the practical usability for healthcare professionals. The need for user-friendly platforms is emphasized, with recognition of existing commercial solutions while also noting their inherent limitations. Future directions point towards more integrated, intelligent systems that can bridge the current technological and practical gaps in personalized immunosuppressant therapy.

PMID:40959818 | PMC:PMC12433911 | DOI:10.3389/ti.2025.14201

Front Genet. 2025 Sep 1;16:1617504. doi: 10.3389/fgene.2025.1617504. eCollection 2025.

ABSTRACT

INTRODUCTION: Detection of variance quantitative trait loci (vQTL) can facilitate the discovery of gene-environment (GxE) and gene-gene interactions (GxG). Identifying vQTLs before direct GxE and GxG analyses can considerably reduce the number of tests and the multiple-testing penalty.

METHODS: Despite some methods proposed for vQTL detection, few studies have performed a head-to-head comparison simultaneously concerning false positive rates (FPRs), power, and computational time. This work compares three parametric and two non-parametric vQTL tests.

RESULTS: Simulation studies show that the deviation regression model (DRM) and Kruskal-Wallis test (KW) are the most recommended parametric and non-parametric tests, respectively. The quantile integral linear model (QUAIL, non-parametric) appropriately preserves the FPR under normally or non-normally distributed traits. However, its power is never among the optimal choices, and its computational time is much longer than that of competitors. The Brown-Forsythe test (BF, parametric) can suffer from severe inflation in FPR when SNP’s minor allele frequencies <0.2. The double generalized linear model (DGLM, parametric) is not valid for non-normally distributed traits, although it is the most powerful method for normally distributed traits.

DISCUSSION: Considering the robustness (to outliers) and computation time, I chose KW to analyze four lipid traits in the Taiwan Biobank. I further showed that GxE and GxG were enriched among 30 vQTLs identified from the four lipid traits.

PMID:40959815 | PMC:PMC12434048 | DOI:10.3389/fgene.2025.1617504

J Cytol. 2025 Jul-Sep;42(3):142-150. doi: 10.4103/joc.joc_16_25. Epub 2025 Aug 29.

ABSTRACT

INTRODUCTION: Whereas liquid-based cytology (LBC) is often the preferred method in gynecological and non-gynecological cytopathology compared to conventional preparation, it does have several limitations. This study aims to evaluate the diagnostic accuracy and specific cytomorphologic characteristics of the newly developed WellPrep^® (WP) in comparison with SurePath™ (SP) in serous effusion cytology.

MATERIALS AND METHODS: A total of 178 body cavity effusion samples were collected, which were divided and further processed using both WP and SP methods. The LBC slides of the cases were independently evaluated regarding their cytomorphologic features by three pathologists. Among them, the diagnosis of 66 cases (42.6%) was confirmed as non-neoplastic or malignant using a combination of histopathological, clinical, and/or radiological follow-up. Statistical analysis was conducted to assess the diagnostic concordance and differences in selected cytomorphologic features between the two LBC methods.

RESULTS: WP demonstrated diagnostic performance comparable to SP, with a concordance rate of 75.7% (kappa = 0.659; Spearman’s ρ = 0.920). Furthermore, the diagnostic accuracy measures tested were not different between WP and SP. No case processed with WP or SP showed suboptimal slide quality. For cytomorphologic features, cellular degeneration was less frequently observed in WP than in SP. SP showed more even cellular distribution and better preservation of architectural patterns. SP also more frequently exhibited prominent nucleoli, cytoplasmic vacuoles, and signet ring cell features.

CONCLUSION: WP offers comparable slide quality and diagnostic accuracy with SP in serous effusion cytopathology. However, more research using larger patient cohorts would provide more evidence regarding WP.

PMID:40959810 | PMC:PMC12435873 | DOI:10.4103/joc.joc_16_25

Front Aging Neurosci. 2025 Sep 1;17:1591496. doi: 10.3389/fnagi.2025.1591496. eCollection 2025.

ABSTRACT

OBJECTIVE: To analyze the dual improvement effects of transcranial direct current stimulation (tDCS)-assisted auditory rehabilitation training on cognitive function and auditory ability of elderly patients with hearing impairment.

METHODS: 100 cases of elderly patients with hearing impairment admitted to our hospital between January 2020 and January 2025 were prospectively selected as study subjects. The patients were divided into sham tDCS group (N = 50) and tDCS group (N = 50) according to the randomized numeric table method. All patients received conventional auditory rehabilitation training, and were intervened for 1 month, 3 times/week, 1 h each time. tDCS was given to patients in both groups before conventional auditory rehabilitation training, patients in the tDCS group underwent dual-site sequential high-definition tDCS stimulation, and patients in the sham tDCS group used sham dual-site sequential high definition tDCS stimulation. The main clinical assessments included hearing thresholds, Hearing Handicap Inventory for the Elderly-Screening (HHIE-S), Montreal Cognitive Assessment Scale (MoCA) and Mini-Mental State Examination (MMSE), Communication Performance Assessment (CPA), Personal Report of Communication Apprehension (PRCA-24), and 36-item Short-Form Health Survey (SF-36) scores of the patients in the two groups before and after the treatment. The correlation between hearing threshold, HHIE-S and MoCA and MMSE scores were analyzed by Pearson correlation coefficient.

RESULTS: There were no significant differences between the two groups in terms of age, gender, BMI, degree of hearing loss, education level, smoking and drinking habits, laboratory indicators [FBG, ALP, ALT, AST, TC, TG, HDL-C, LDL-C], comorbidities, and family history of hearing loss (all p > 0.05). The hearing thresholds and HHIE-S scores of patients in both groups after treatment were significantly lower than those before treatment (both p = 0.001), and the hearing thresholds and HHIE-S scores of patients in the tDCS group after treatment were significantly lower than those in the sham tDCS group (p < 0.001 and p = 0.002, respectively). The MoCA and MMSE scores of patients in both groups were significantly higher than those before treatment (both p < 0.001), and the MoCA and MMSE scores of patients in the tDCS group were significantly higher than those in the sham tDCS group after treatment (p = 0.048 and p = 0.038, respectively). Hearing thresholds and HHIE-S were negatively correlated with MoCA and MMSE scores in elderly patients with hearing impairment (all p < 0.05). Bootstrap mediation analysis suggests that changes in hearing impairment may partially mediate improvements in cognitive function. After treatment, the total CPA and SF-36 scores of all patients were higher than before treatment, and the total PRCA-24 score was lower than before treatment (p < 0.05). The CPA and SF-36 total scores of the patients in the tDCS group were higher than those in the sham tDCS group after treatment (p = 0.012 and p = 0.007, respectively), and the differences in the PRCA-24 total scores of the two groups were not statistically significant when compared with each other after treatment (p = 0.248).

CONCLUSION: Transcranial direct current stimulation-assisted auditory rehabilitation training may improve the cognitive and auditory functions of elderly patients with hearing impairment and enhance the quality of life of patients.

PMID:40959794 | PMC:PMC12434129 | DOI:10.3389/fnagi.2025.1591496

Front Artif Intell. 2025 Sep 1;8:1655303. doi: 10.3389/frai.2025.1655303. eCollection 2025.

ABSTRACT

OBJECTIVE: To compare the accuracy of Deepseek and ChatGPT in answering frequently asked questions (FAQs) about cervical cancer.

METHODS: To compile a list of FAQs concerning cervical cancer, a comprehensive search was conducted on social media and community platforms. The answer keys for all the selected questions were created on the basis of the guidelines of the National Comprehensive Cancer Network (NCCN), the International Federation of Gynecology and Obstetrics (FIGO), and the World Health Organization (WHO) for cervical cancer. The answers given by Deepseek-R1 and ChatGPT O1 were scored according to the Global Quality Score (GQS).

RESULTS: A total of 74 FAQs covered a diverse range of topics related to cervical cancer, including diagnosis (n = 16), risk factors and epidemiology (n = 19), treatment (n = 20), and prevention (n = 19). When all the answers provided by DeepSeek to the FAQs about cervical cancer according to the GQS were evaluated, 68 answers were rated as score five, 4 answers were rated as score four, and 2 answers were rated as score three. For ChatGPT’s responses to the same set of FAQs, 67 answers were classified as score five, 6 answers were classified as score four, and 1 answer was classified as score three. There was no statistically significant difference between the two groups (p > 0.05).

CONCLUSION: Both DeepSeek and ChatGPT demonstrated accurate and satisfactory responses to FAQs about cervical cancer when evaluated according to the GQS. However, in regard to treatment issues, a cautious attitude should be maintained. Compared to ChatGPT, DeepSeek stands out for its free availability, which makes it more accessible in resource-limited scenarios to the public.

PMID:40959772 | PMC:PMC12433935 | DOI:10.3389/frai.2025.1655303

Gen Psychiatr. 2025 Sep 14;38(5):e101957. doi: 10.1136/gpsych-2024-101957. eCollection 2025.

ABSTRACT

BACKGROUND: Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied. Currently, suicide risk assessment tools based on objective indicators are limited in China.

AIMS: To examine the value of various biomarkers in suicide risk prediction and develop a risk assessment model with clinical utility using machine learning.

METHODS: This cohort study analysed patients with major depressive disorder (MDD) who were hospitalised for the first time between January 2016 and March 2023 from four specialised mental health institutions. A total of 139 features, including biomarker measurements, medical orders and psychological scales, were assessed for analysis. Their suicide risk was evaluated by qualified nurses using Nurse’s Global Assessment of Suicide Risk within 1 week after admission. Five machine learning models were trained with 10-fold cross-validation across three hospitals and were externally validated in an independent cohort. The primary performance was assessed using the area under the receiver operating characteristic curve (AUROC). The model was interpreted using the SHapley Additive exPlanations (SHAP) analysis. Biomarker importance was evaluated by comparing model performance with and without these biomarkers.

RESULTS: Of 3143 patients with MDD included in this study, the incidence of high suicide risk within 1 week after first admission was 660 (21.0%). Among all models, the Extreme Gradient Boosting can more effectively predict future risks, with an AUROC higher than 0.8 (p<0.001). The SHAP values identified the 10 most important features, including five biomarkers. After clustering analysis, electroconvulsive therapy, physical restraint, β2-microglobulin and triiodothyronine were found to have heterogeneous effects on suicide risk. Combining biomarkers with other data from electronic health records significantly improved the performance and clinical utility of machine learning models based on demographics, diagnosis, laboratory tests, medical orders and psychological scales.

CONCLUSIONS: This study demonstrates the potential for a biomarker-based suicide risk assessment for patients with MDD, emphasising the interaction between biomarkers and therapeutic interventions.

PMID:40959771 | PMC:PMC12434745 | DOI:10.1136/gpsych-2024-101957

Pregnancy (Hoboken). 2025 Jul;1(4). doi: 10.1002/pmf2.70063. Epub 2025 Jun 30.

ABSTRACT

INTRODUCTION: Operative vaginal delivery (OVD) has experienced a decline, primarily driven by decreasing rates of forceps-assisted vaginal delivery (FAVD). FAVD rates have been suspected to be declining to a point where recovery of this skill may be improbable. While there are numerous reasons for this decline ranging from lack of training to patient preferences, the same period has been suspected to have worsening morbidity with FAVD. Concerns have been raised with respect to obstetric anal sphincter injuries (OASIS). To characterize national trends in OVD and risk factors for associated OASIS between 2016 and 2023, assessing changes in OVD utilization and the associated risk of OASIS.

MATERIALS AND METHODS: This is a cross-sectional study using National Vital Statistics System birth certificate data between 2016 to 2023 to identify temporal trends in OVD and OASIS rates. Liveborn deliveries undergoing trial of labor from 34 weeks and 0 days to 42 weeks and 6 days to patients aged 16-50 years of age were included. Pregnancies with multifetal gestations, fetal anomalies, non-vertex presentations, and unknown mode of delivery were excluded. Temporal trends in OVD and OASIS were assessed using Joinpoint regression. Multivariable logistic regression models were fit to assess the association between OASIS and OVD, adjusting for maternal demographics and comorbidities.

RESULTS: Of the 21,191,398 liveborn deliveries identified, 18,054,141 (85.2%) were spontaneous vaginal births, 2,303,168 (10.9%) were cesarean after trial of labor, 136,927 (0.6%) were forceps-assisted vaginal deliveries (FAVD), and 697,162 (3.3%) were vacuum-assisted vaginal deliveries (VAVD) with a OVD composite of 3.9%. OVD rates decreased significantly from 4.6% to 4.1% (annual average percent change (AAPC): -1.6%, 95% CI: -1.9% to -1.4%). Specifically, FAVD rates declined from 0.8% to 0.6% (AAPC: -3.1%, 95% CI: -3.7% to -2.6%) and VAVD rates declined from 3.8% to 3.4% (AAPC -1.4%, 95%CI: -1.7% to 1.1%). OASIS rates in the overall group did not significantly change (AAPC 1.4%, 95%CI: -2.1% to 4.4%), although among FAVD, there was a significant increase in rates of OASIS from 9.3% in 2016 to 14.0% in 2023 (AAPC 4.8%, 95%CI: 2.3% to 7.0%). Adjusted multivariable logistic regression noted higher likelihood of OASIS in FAVD (aOR 9.50, 95%CI: 9.33 to 9.66), and VAVD (aOR 3.90, 95%CI: 3.85 to 3.94) when compared to spontaneous vaginal birth, adjusting for maternal age, maternal BMI, and maternal comorbidities including diabetes and hypertensive disorders.

CONCLUSION: The primary finding in this study was a national decline in OVD with significantly greater declines in FAVD and an increasing rate of OASIS among FAVD. Whether targeted interventions to enhance training in safe FAVD may increase proficiency in this technique remains to be seen.

PMID:40959760 | PMC:PMC12435513 | DOI:10.1002/pmf2.70063

Front Psychol. 2025 Sep 1;16:1567735. doi: 10.3389/fpsyg.2025.1567735. eCollection 2025.

ABSTRACT

This research primarily investigates whether both reward processing and self-processing are aberrant in individuals with methamphetamine use disorder. It also explores whether initiating self-referential processing modulates reward processing abilities in this population, and how this modulation differs from that observed in healthy controls. Experiment 1 employed a two-factor mixed experimental design to compare the performance of addiction groups with varying withdrawal durations (all participants in the addiction groups were methamphetamine users) against healthy control groups in a probabilistic reward learning task. The results indicated that the healthy control group performed better than the addiction group in learning characters associated with high-probability, high-reward outcomes. While the long-term abstinence group outperformed the short-term abstinence group, these differences were not statistically significant. Therefore, the addiction group subjects in Experiments 2 and 3, the addiction group consisted of methamphetamine users with a uniform withdrawal duration of no more than 12 months. Experiment 2 utilized a two-factor mixed design to explore whether self-processing is abnormal in addicted individuals. The results showed that the addiction group had a significantly lower accuracy rate for self-referential characters compared to the healthy control group, while their accuracy for characters associated with acquaintances was significantly higher than that of the healthy control group. Experiment 3 also employed a two-factor mixed design to examine the moderating effect of self-processing on reward learning. The findings revealed that when high-probability reward characters were linked to self-relevance, learning efficiency was superior to that of characters linked to acquaintances. However, this moderating effect was weaker in the addiction group compared to the healthy control group. These results suggest that substance addiction not only impairs individuals’ reward processing abilities but also reduces their sensitivity to self-referential information. Furthermore, the enhancing effect of self-processing on reward learning is significantly diminished in addicted populations, providing new insights into the cognitive mechanisms underlying addiction.

PMID:40959756 | PMC:PMC12434089 | DOI:10.3389/fpsyg.2025.1567735

Front Rehabil Sci. 2025 Sep 1;6:1626051. doi: 10.3389/fresc.2025.1626051. eCollection 2025.

ABSTRACT

INTRODUCTION: Low balance confidence, i.e., low self-perception in ones’ ability to maintain balance while performing activities, is prevalent among lower limb prostheses users (LLPUs) and can affect community participation and quality of life (QoL). Although low balance confidence can manifest from poor function, it also depends on one’s beliefs in their abilities to engage in activities, which need not reflect actual abilities. Increasing low balance confidence and associated participation limitations requires approaches that address its’ physical and psychological underpinnings.

METHODS: A randomized controlled trial was conducted to evaluate the initial effectiveness of a multicomponent intervention to target balance confidence in LLPU. Nineteen adults with ≥6-months experience using a prosthesis for unilateral, transtibial amputation, and with low balance confidence (Activities-specific Balance Confidence (ABC) scale scores ≤ 80) completed up to eight intervention sessions following an established protocol, which integrated physical therapy exercises (primarily virtual reality active gaming) and cognitive behavioral therapy strategies, or eight weeks of at home-seated exercises. Outcome measures, collected before randomization, and 0- and 16- weeks after completing the intervention/at-home exercises, addressed four domains: (i) balance confidence-the ABC scale, modified Gait Self Efficacy scale and the Fear of Falling Avoidance Behavior Questionnaire; (ii) community participation-sections of the 36-Item Short Form Survey, sections of the Community Reintegration of Injured Servicemembers scale, the Frenchay Activity Index and step counts; (iii) QoL-the wellbeing scale of the Prosthetic Evaluation Questionnaire; and (iv) function-the Berge Balance Sale and the L-Test of walking. Statistical tests compared baseline and post-training assessment scores between groups, and individual responsiveness was evaluated by comparing change scores to minimum detectable change (MDC).

RESULTS: Overall, results support the initial efficacy of the intervention, with at least one outcome in 3-of-4 domains (balance confidence, community participation and functional mobility) showing strong, significant group-level effects, or individual-level effects (>30% of participants having changes > MDC). Moreover, semi-structured exit interviews suggest participants perceived benefit from the intervention.

DISCUSSION: Integrating physical therapy exercises with cognitive behavioral therapy strategies to simultaneously address physical underpinnings and maladaptive cognitions around low balance confidence can meaningfully improve balance and walking confidence, as well as community participation. To the best of our knowledge the current study is the first to evaluate an intervention to specifically target balance confidence in LLPUs.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT03411148.

PMID:40959746 | PMC:PMC12434030 | DOI:10.3389/fresc.2025.1626051