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Nevin Manimala Statistics

The implementation of a robotic surgical platform for the treatment of patients with malignant or pre-malignant pancreatic tumors at the University Medical Center Ljubljana

Radiol Oncol. 2025 Sep 5;59(3):425-434. doi: 10.2478/raon-2025-0051. eCollection 2025 Sep 1.

ABSTRACT

BACKGROUND: Robotic platforms are increasingly employed in the field of minimally invasive pancreatic surgery. It is essential to develop an innovative method that ensures both safety and efficacy, producing outcomes comparable to those of established treatment modalities. Implementation process should incorporate surgical science, education, local implementation, and non-technical skills. In our study, we describe the safe implementation of a robotic platform in pancreatic surgery within our medical institution.

PATIENTS AND METHODS: We analysed prospectively collected data from the first ten consecutive robotic-assisted distal pancreatectomies (RDP) and pancreatoduodenectomies (RPD). Due to nature of the study basic statistical analysis were performed.

RESULTS: The mean operating time was 211minutes (±49.4) for RDP and 365 minutes (±69.6) for RPD, with blood loss 330 mL for RDP and 195 mL for RPD. Hospital stay was 8.7 days (±3.9) in RDP and 7.9 days (±3.9) in RPD. One patient (10%) in the RDP group developed clinically relevant postoperative pancreatic fistula (CR-POPF) and delayed gastric emptying (DGE). The mean tumour size was 31 mm (±9.8) in the RDP and 27 mm (±7.5) in the RPD. The mean number of lymph nodes harvested was 6 (0-24) in the RDP and 15 (6-22) in the RPD. The R0 resection rate was 60% in the RDP and 70% in the RPD.

CONCLUSIONS: Robotic surgical technology can be safely and effectively integrated into a clinical setting. This integration should be facilitated through a well-established training program and curriculum. Nonetheless, patient selection is important, especially in the early phases of robotic program development.

PMID:40959923 | DOI:10.2478/raon-2025-0051

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Polygenic risk score of Alzheimer’s disease is associated with cognitive trajectories and phenotypes of cerebral organoids

Alzheimers Dement. 2025 Sep;21(9):e70660. doi: 10.1002/alz.70660.

ABSTRACT

INTRODUCTION: Polygenic risk score (PRS) identifies individuals at high genetic risk for Alzheimer’s disease (AD), but its utility in predicting cognitive trajectories and AD pathologies remains unclear. We optimized PRS (optPRS) for AD, investigated its association with cognitive trajectories and AD phenotypes of cerebral organoids.

METHODS: Using genome-wide association study (GWAS) summary statistics from a European population, we developed optPRS to predict AD in Korean individuals (n = 1634). We analyzed the association between optPRS and cognitive trajectories (n = 771). We generated induced pluripotent stem cell-derived cerebral organoids from patients with high (n = 3) and low (n = 4) optPRS to evaluate amyloid beta (Aβ) and phosphorylated tau (p-tau) levels.

RESULTS: OptPRS predicted AD dementia and Aβ positivity, independent of apolipoprotein E (APOE). Higher optPRSs correlated with rapid cognitive decline. Cerebral organoids from the high optPRS group exhibited increased Aβ insolubility and p-tau levels.

CONCLUSION: OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug-screening platform.

HIGHLIGHTS: Optimized polygenic risk scores (optPRSs) improve the prediction of Alzheimer’s disease (AD) dementia and amyloid beta positivity (Aβ+). High optPRS is associated with faster cognitive decline, particularly in Aβ+. Induced pluripotent stem cell (iPSC)-derived cerebral organoids from high optPRSs show high Aβ insolubility and phosphorylated tau (p-tau). PRS genetic risk stratification provides insight into AD progression and pathology.

PMID:40959898 | DOI:10.1002/alz.70660

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Five-year change in sleep duration and incident Alzheimer’s Disease and Related Dementias among lower-income older adults

Alzheimers Dement. 2025 Sep;21(9):e70678. doi: 10.1002/alz.70678.

ABSTRACT

INTRODUCTION: Little is known about change in sleep duration over time and Alzheimer’s Disease and Related Dementias (ADRD) risk.

METHODS: ADRD cases were identified among Southern Community Cohort Study participants enrolled in Medicare. Sleep duration was reported at enrollment and first study follow-up and categorized (short (< 7 hours), recommended (7-9) and long (> 9)), change was calculated between timepoints. Adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD.

RESULTS: We identified 2,093 ADRD cases among 17,945 participants. Compared to maintaining optimal sleep duration (7-9 hours) over 5 years, suboptimal changes were associated with 20-69% greater ADRD risk: adjusted HR (95% CI) was 1.50 (1.23-1.82) for long-recommended, 1.56 (1.21-2.01) for long-long, 1.69 (1.25-2.27) for long-short, 1.49 (1.16-1.91) for short-long, and 1.20 (1.06-1.36) for short-short.

DISCUSSION: Suboptimal 5-year change in sleep durations were associated with ADRD risk among lower-income adults underrepresented in ADRD research.

HIGHLIGHTS: The study calculated 5-year change in sleep duration in a large community-based cohort of predominately lower-income adults. Cases of Alzheimer’s Disease and Related Dementias (ADRD) were ascertained from Medicare claims data among 17,945 participants with up to 12 years of follow-up. Compared to maintaining 7-9 hours of sleep, older adults with suboptimal sleep categories were consistently at a greater risk of ADRD.

PMID:40959862 | DOI:10.1002/alz.70678

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Nevin Manimala Statistics

Equity reporting in systematic reviews and meta-analysis for geographic atrophy: a PROGRESS-Plus assessment

J Osteopath Med. 2025 Sep 8. doi: 10.1515/jom-2025-0107. Online ahead of print.

ABSTRACT

CONTEXT: As systematic reviews and meta-analyses (SRMAs) are crucial for treatment development, they must provide guidelines that represent diverse patient demographics to promote equitable health care. As new research and treatment modalities are being developed for geographic atrophy (GA), establishing an equitable research foundation is becoming vitally important to physicians as they personalize their treatment plans.

OBJECTIVES: This analysis aims to determine whether SRMAs pertaining to GA are reporting equity-related items utilizing the PROGRESS-Plus framework.

METHODS: We conducted a cross-sectional analysis by searching databases for systematic reviews and meta-analyses concerning GA from the year 2000 to November 2023. From this search, 176 articles returned, but only 57 of them met all the inclusion criteria. After screening the articles for inclusion, data pertaining to PROGRESS-Plus items were extracted. All analyses were conducted in a masked and duplicative fashion. χ 2 tests were employed to determine whether associations existed between the variables.

RESULTS: From the initial search, 176 articles returned, of which 119 were excluded due to duplication, data unrelated to GA, or because it was animal-based research. Of the remaining 57 studies, 26 (45.6 %) included zero PROGRESS-Plus items. Fewer articles from the US-reported equity items (31.3 %, 5/16) compared to other countries (63.4 %, 26/41), which held statistical significance (p=0.028).

CONCLUSIONS: The American Academy of Ophthalmology has created initiatives to increase diversity, equity, and inclusion within the subspecialty. By using the PROGRESS-Plus framework, this study concluded that the majority of the articles pertaining to GA do not meet equity item objectives. As these documents aid physicians in developing treatment plans, these findings are concerning as physicians may find it more difficult to individually tailor treatment plans according to each patient’s holistic needs. Limitations in this study included unintentional omission or misclassification of research documents despite the comprehensive search string and double-blinded analysis. Furthermore, the results of this study cannot be generalized to other areas of research.

PMID:40959859 | DOI:10.1515/jom-2025-0107

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Differential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns

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

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State of Art of Dose Individualization to Support tacrolimus drug monitoring: What’s Next?

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

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Mining for gene-environment and gene-gene interactions: parametric and non-parametric tests for detecting variance quantitative trait loci

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

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A Comparative Analysis of Diagnostic Performance and Cytomorphologic Features Between Newly Developed WellPrep® and SurePath™ in Serous Effusion Cytology

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

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Dual improvement of cognitive function and auditory ability in elderly patients with hearing impairment by transcranial direct current stimulation-assisted auditory rehabilitation training

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

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Accuracy of AI chatbots in answering frequently asked questions on cervical cancer

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