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Nevin Manimala Statistics

Head-to-head Comparison of Fibroblast Activation Protein Inhibitors and 18F-fluorodeoxyglucose in Cervical Cancer: A Systematic Review and Meta-analysis

Acad Radiol. 2026 Mar 24:S1076-6332(26)00170-4. doi: 10.1016/j.acra.2026.03.006. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: This study aims to compare the diagnostic performance of fibroblast activation protein inhibitor (FAPI) and 18F-fluorodeoxyglucose (18F-FDG) in patients with cervical cancer.

METHODS: In this review, we performed a systematic search of studies published in PubMed, Web of Science, and Embase databases up to October 30, 2025. All included studies used radionuclide labeled FAPI and 18F-FDG to evaluate their performance in patients with cervical cancer.

RESULTS: In patient-based analysis (n=109), FAPI showed higher sensitivity than 18F-FDG (0.96 vs 0.77) and greater specificity (0.98 vs 0.86). Lesion-based analysis (n=203 lymph nodes) yielded similar sensitivity patterns (0.99 vs 0.72) but may inflate precision due to within-patient clustering. Semi-quantitative parameters (SUVmax) showed variable patterns across studies (FAPI SUVmax range: 15.1-18.3 for primary lesions; FDG SUVmax range: 13.96-17.1). Descriptive comparison suggests FAPI SUVmax was generally comparable to or higher than FDG values, though formal pooled statistical comparison was not performed due to substantial heterogeneity in PET platforms, tracer variants, and acquisition protocols.

CONCLUSION: Compared with 18F-FDG, FAPI PET/CT and PET/MR are suggested to be promising imaging modalities with favorable sensitivity for cervical cancer. However, these results should be interpreted cautiously due to heterogeneity among studies and potential verification bias. Larger prospective studies are needed to confirm it in the future.

PMID:41881693 | DOI:10.1016/j.acra.2026.03.006

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Expression and Clinical Significance of the Long Non-Coding RNA OIP5-AS1 in Alcohol Use Disorder

Addict Biol. 2026 Apr;31(4):e70146. doi: 10.1111/adb.70146.

ABSTRACT

The present study aimed to investigate the expression of OIP5-AS1 in alcohol use disorder and to explore its potential clinical relevance. A total of 78 patients with alcohol use disorder and 36 healthy controls were enrolled in this study. Clinical data were collected for all participants. The expression levels of OIP5-AS1 were quantified using quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) analysis was subsequently performed to evaluate the diagnostic value of OIP5-AS1. StarBase-based bioinformatics analysis suggested that OIP5-AS1 may function within a miRNA-mediated regulatory network influencing SERPINA3 expression. OIP5-AS1 expression levels, as determined by RT-PCR, were markedly higher in patients with alcohol use disorder than in healthy controls (p < 0.001). Patients were stratified into high- and low-expression groups based on the median OIP5-AS1 level. Comparative analyses of baseline characteristics and clinical parameters showed that body mass index (BMI) was significantly lower in the high-expression group, and this inverse association between OIP5-AS1 expression and BMI remained statistically significant in subsequent logistic regression analyses. ROC analysis demonstrated that OIP5-AS1 had strong diagnostic performance, yielding an area under the curve of 0.9091 (p < 0.0001), with a sensitivity of 100% and a specificity of 75% at the defined cutoff. In conclusion, OIP5-AS1 expression was significantly increased in patients with alcohol use disorder and was inversely associated with BMI. In addition, OIP5-AS1 demonstrated good diagnostic performance in distinguishing patients with alcohol use disorder from healthy controls. These findings suggest that OIP5-AS1 may have potential clinical relevance in alcohol use disorder and merit further investigation.

PMID:41881680 | DOI:10.1111/adb.70146

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Does inflammation explain the association between vitamin D and depression? Results of a cross-sectional study in children and adolescents

Br J Nutr. 2026 Mar 26:1-37. doi: 10.1017/S0007114526106928. Online ahead of print.

ABSTRACT

Vitamin D has been associated with depression, potentially via anti-inflammatory mechanisms, yet data is scarce, particularly in adolescence. We investigated (1) whether lower vitamin D status is associated with greater depression severity and (2) whether this association is statistically moderated by inflammation in patients of a child and adolescent psychiatry department. At admission fasting morning venous blood was drawn. Serum vitamin D (25(OH)D) and C-reactive protein (CRP) were analyzed in all participants [n=465 (64.7%♀; 11.3-18.9 years)]. In a subsample [n=177], we additionally measured tumor necrosis factor-alpha, interferon-gamma and interleukin (IL)-1β, IL-6, IL-8, IL-10. Depression severity was assessed by the Beck Depression Inventory-II (BDI-II) [n=450], the Diagnostic System for Mental Disorders in Childhood and Adolescence via self-assessment (DISYPS Self) [n=441], and parent-assessment (DISYPS Proxy) [n=422]. Overall, 43.2% [n=201] were at risk for vitamin D deficiency (<30nmol/L), and 73.5%-83.2% -depending on assessment tool- showed at least mild depression. Linear regression revealed an inverse association between 25(OH)D and BDI-II in both crude and CRP-adjusted full-sample models. Logistic regressions showed a robust inverse association between 25(OH)D and DISYPS Proxy, but not for DISYPS Self. Although 25(OH)D was inversely correlated with some pro-inflammatory markers, neither their inclusion in regression models nor formal mediation analyses supported inflammation as a mediator of the vitamin D-depression association. Overall, our results suggest that vitamin D relates modestly to both depression and inflammation in adolescence. However, based on the measured parameters, we cannot confirm that anti-inflammatory effects are the link between vitamin D and depression.

PMID:41881679 | DOI:10.1017/S0007114526106928

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Nevin Manimala Statistics

Treatment of Melasma Targeting Dermal-Epidermal Interactions Utilizing High-Intensity, High-Frequency Parallel Ultrasound Beam in Asian Skin

J Cosmet Dermatol. 2026 Apr;25(4):e70820. doi: 10.1111/jocd.70820.

ABSTRACT

BACKGROUND: Melasma is a multifactorial disorder, and while treatments aimed at suppressing melanin production and removing excess melanin have demonstrated some efficacy, no definitive therapy has yet been established. Dermal aging is widely recognized as a contributing factor in melasma, and previous studies have demonstrated that the presence of senescent fibroblasts reduces the efficacy of melasma treatments. Therefore, treatment strategies focused on reactivating fibroblast activity are anticipated to be effective against melasma.

OBJECTIVE: The objective of this study is to investigate the safety and efficacy of the Thermal-Thread Technique, which utilizes high-intensity, high-frequency parallel ultrasound beams for the treatment of melasma among Asian subjects.

STUDY DESIGN/METHODS: Patients diagnosed with melasma, regardless of disease type, duration, or Fitzpatrick skin type, underwent a single treatment session covering the entire face utilizing a high-intensity, high-frequency parallel ultrasound beam with Thermal-Thread Technique. High-resolution skin images were captured using a skin analyzer before treatment and six months after the treatment. Two independent evaluators assessed these images using the modified Melasma Area and Severity Index (mMASI) scoring system to objectively evaluate treatment efficacy. Statistical analyses of the mMASI scores were performed using paired t-tests. All potential side effects were carefully monitored both during and after the procedure.

RESULTS: All patients (n = 20, female, mean age: 50.5 ± 5.7) completed the study. The distribution of Fitzpatrick skin types among participants was as follows: type II (n = 7), type III (n = 11), and type IV (n = 2). The mean mMASI score significantly decreased from 4.63 ± 1.66 at baseline to 1.69 ± 0.90 six months post-treatment (p = 1.53e-9; p < 0.001). No statistically significant difference was observed among FST groups (F(2,17) = 1.68, p = 0.216). No side effects were observed or reported during or after the treatment period.

CONCLUSION: The improvement in mMASI scores observed with the Thermal-Thread Technique, utilizing a high-intensity, high-frequency parallel ultrasound beam, demonstrates its potential as an effective treatment for melasma. Further research is necessary to evaluate its efficacy in more severe cases, extend the observational period, and investigate the potential benefits associated with multiple treatment sessions.

PMID:41881668 | DOI:10.1111/jocd.70820

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Prognostic Value of Microvascular Resistance Reserve in Coronary Artery Disease: A Systematic Review and Meta-Analysis

JACC Cardiovasc Interv. 2026 Mar 23;19(6):740-751. doi: 10.1016/j.jcin.2025.12.022.

ABSTRACT

BACKGROUND: Microvascular resistance reserve (MRR) is a novel index for evaluating coronary microvascular function independently of epicardial disease. Its prognostic significance in coronary artery disease (CAD) remains uncertain.

OBJECTIVES: The aim of this study was to assess the association between MRR and adverse cardiovascular outcomes across various CAD presentations.

METHODS: A systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and Embase were searched from January 2019 to January 2025 for prospective studies reporting HRs for major adverse cardiovascular events in relation to MRR. Risk for bias was assessed using the Quality in Prognosis Studies tool. Pooled HRs were calculated using a random-effects model; heterogeneity was evaluated using the I2 statistic.

RESULTS: Five studies (n = 3,186) were included. Higher MRR was significantly associated with lower risk for adverse events (HR per unit increase: 0.75; 95% CI: 0.64-0.88; I2 = 80.9%). When dichotomized, low MRR conferred a more than 2-fold increased risk for major adverse cardiovascular events (HR: 2.39; 95% CI: 1.66-3.43). Subgroup analysis showed a stronger prognostic effect for ST-segment elevation myocardial infarction (HR: 0.46) vs stable CAD (HR: 0.86; P for interaction < 0.0001). Threshold analysis identified MRR ≥ 3 as optimal for sensitivity (58.9%) and rule-out performance, while lower thresholds improved specificity.

CONCLUSIONS: MRR is a robust, independent predictor of cardiovascular outcomes of both acute and chronic CAD. Its prognostic impact is particularly pronounced for acute coronary syndrome. A threshold of 3 provides the best prognostic balance, supporting its integration into invasive physiological assessment for risk stratification.

PMID:41881651 | DOI:10.1016/j.jcin.2025.12.022

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Nevin Manimala Statistics

Transcatheter Tricuspid Valve Intervention Risk Scores: Assessment in an International Multicenter Cohort

JACC Cardiovasc Interv. 2026 Mar 23;19(6):665-676. doi: 10.1016/j.jcin.2025.12.020.

ABSTRACT

BACKGROUND: Accurate risk stratification is crucial for patients undergoing transcatheter tricuspid valve intervention (TTVI). The performance of existing surgical and TTVI risk scores (TRI-SCORE, STS-TR [Society of Thoracic Surgeons Tricuspid Regurgitation], and TRIVALVE [International Multisite Transcatheter Tricuspid Valve Therapies Registry]) has not been comprehensively evaluated and compared in a contemporary, real-world cohort.

OBJECTIVES: The aim of this study was to assess the discrimination and calibration of these scores in a large international multicenter population of patients undergoing TTVI.

METHODS: This study population included 457 patients from 6 international centers who underwent TTVI (tricuspid transcatheter edge-to-edge repair, transcatheter tricuspid valve replacement, or transcatheter tricuspid annuloplasty) between 2019 and 2024. The performance of the TRIVALVE score was assessed for the 1-year endpoint of death and rehospitalization. The TRI-SCORE and STS-TR scores were assessed for in-hospital and 30-day mortality, respectively. Performance was evaluated using C statistics for discrimination and smoothed calibration plots for calibration.

RESULTS: All 3 scores demonstrated limitations. The TRIVALVE score showed low discrimination (area under the curve: 0.609) and was well calibrated after its endpoint was refined to exclude non-cardiovascular-related hospitalizations. The surgically derived TRI-SCORE and STS-TR scores were miscalibrated and significantly overestimated mortality. The TRI-SCORE showed an observed-to-expected mortality ratio of 0.13 (95% CI: 0.07-0.23), and the STS-TR score had an observed-to-expected mortality ratio of 0.35 (95% CI: 0.19-0.60).

CONCLUSIONS: The currently available TTVI risk scores derived from surgical or early TTVI cohorts may not be well suited for accurate risk assessment in contemporary TTVI. The surgical scores when applied to TTVI are miscalibrated, and the TRIVALVE score lacks discrimination. There is a need for the development of a contemporary dedicated TTVI risk model validated specifically for this population.

PMID:41881641 | DOI:10.1016/j.jcin.2025.12.020

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Nevin Manimala Statistics

Statistical Methods for Understanding Trajectories in Genetic Epidemiology

Annu Rev Biomed Data Sci. 2026 Mar 25. doi: 10.1146/annurev-biodatasci-092724-035434. Online ahead of print.

ABSTRACT

Genetic influences on how human traits change over time remain underexplored and may play an important role in disease processes. In this review, we explore emerging statistical approaches for incorporating longitudinal data on trait trajectories into genetic epidemiology studies, including longitudinal genome-wide association studies, polygenic scores, and Mendelian randomization. We discuss the caution required when analyzing longitudinal data focused on disease progression, where analyses are conducted within a group of patients rather than the general population. Finally, we outline the large longitudinal data resources that are available and discuss future directions in trajectory-based genetic epidemiological studies. Embracing time as a critical dimension of human traits offers deeper insight into disease pathways and intervention opportunities.

PMID:41880638 | DOI:10.1146/annurev-biodatasci-092724-035434

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Nevin Manimala Statistics

Fuzzy Logic Approaches for Causal Inference in Health Care: Systematic Review

JMIR AI. 2026 Mar 25;5:e83425. doi: 10.2196/83425.

ABSTRACT

BACKGROUND: Fuzzy logic has been progressively investigated as a viable alternative to traditional statistical and machine learning methods in health care modeling, especially in environments marked by uncertainty, nonlinearity, and missing information. Although its use in prediction, classification, and risk stratification is well established, its application to explicit causal inference remains limited, varied, and methodologically premature.

OBJECTIVE: This systematic review aimed to examine how fuzzy logic frameworks have been used to address causal questions in health care, focusing on their methodological characteristics, comparative performance, and degree of integration with formal causal inference approaches.

METHODS: A systematic search across 6 databases (PubMed, Web of Science, ScienceDirect, SpringerLink, Scopus, and IEEE Xplore) identified peer-reviewed studies published between 2014 and 2025 that applied fuzzy modeling in health care settings with explicit or implicit causal objectives. The review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines and used a modified PICO (population, intervention, comparator, and outcome) framework for study selection. Data were extracted on the health care domain, fuzzy method, comparator use, and causal framing. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) checklist and the PROBAST+AI tool, according to study design.

RESULTS: A total of 37 studies met the inclusion criteria. The most frequently applied approaches were fuzzy inference systems, fuzzy cognitive maps, and neuro-fuzzy models, with applications spanning infectious diseases, cancer, cardiovascular health, mental health, and occupational health. Fourteen studies included comparator models; among these, 5 reported superior performance of fuzzy approaches, 3 showed comparable results, and 6 lacked sufficient detail for a robust comparison. Only 2 studies explicitly implemented formal causal inference frameworks, while most relied on predictive or associative modeling with implicit causal assumptions. Overall, the risk of bias was moderate to high.

CONCLUSIONS: Fuzzy logic offers interpretability and flexibility well suited to complex health care problems, yet its application to explicit causal inference remains fragmented. Greater methodological transparency, systematic benchmarking, and integration with formal causal designs-such as counterfactual and target trial frameworks-are required to establish fuzzy logic as a robust paradigm for causal inference in health care.

PMID:41880635 | DOI:10.2196/83425

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Nevin Manimala Statistics

Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer

N Engl J Med. 2026 Mar 26;394(12):1155-1166. doi: 10.1056/NEJMoa2507874.

ABSTRACT

BACKGROUND: Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair-deficient (dMMR) status is unclear.

METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with resected stage III dMMR tumors to receive either adjuvant atezolizumab plus mFOLFOX6 for 6 months, with atezolizumab continued as monotherapy (for a total of 12 months of therapy), or mFOLFOX6 alone for 6 months. The primary end point was disease-free survival. Secondary end points were overall survival and the adverse-event profile.

RESULTS: A total of 355 patients were assigned to receive atezolizumab plus mFOLFOX6 and 357 to receive mFOLFOX6 alone. The median age of the patients was 64 years, 55.1% were women, and 53.9% had tumors that were T4, N2, or both (indicating high risk). At a median follow-up of 40.9 months, the 3-year disease-free survival was 86.3% (95% confidence interval [CI], 81.8 to 89.8) in the atezolizumab-mFOLFOX6 group, as compared with 76.2% (95% CI, 70.9 to 80.6) in the mFOLFOX6 group (hazard ratio for disease recurrence or death, 0.50; 95% CI, 0.35 to 0.73; P<0.001). Adverse events of grade 3 or 4 occurred in 84.1% of the patients who received atezolizumab plus mFOLFOX6 and in 71.9% of those who received mFOLFOX6 alone.

CONCLUSIONS: The addition of atezolizumab to mFOLFOX6 significantly improved disease-free survival among patients with stage III dMMR colon cancer. (Funded by the National Cancer Institute of the National Institutes of Health and Genentech; ATOMIC ClinicalTrials.gov number, NCT02912559.).

PMID:41880612 | DOI:10.1056/NEJMoa2507874

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Nevin Manimala Statistics

Determinants of the Uptake and Frequency of Use of a Web Portal Digital Health Intervention in Patients With Type 2 Diabetes and/or Coronary Heart Disease: Secondary Analysis of a Randomized Controlled Trial

J Med Internet Res. 2026 Mar 25;28:e80895. doi: 10.2196/80895.

ABSTRACT

BACKGROUND: The targeted application and design of digital health interventions (DHIs) require an understanding of usage determinants. Usage includes uptake (initial use) and frequency (extent of use), but it is unclear whether both components are driven by the same determinants.

OBJECTIVE: This study aimed to examine the determinants of uptake and frequency of use and assess whether they differ.

METHODS: The investigated DHI was a web portal provided in an intervention for improving disease-related self-management. This study is a secondary analysis of intervention group data from a parallel-group randomized controlled trial. Eligibility criteria were being an adult and being diagnosed with type 2 diabetes and/or coronary heart disease. Sociodemographic, psychological, and health-related variables were examined as determinants. Determinants were analyzed using simple and multiple regression models. Uptake was analyzed using logistic regression, and frequency was analyzed using negative binomial regression with robust SEs. Frequency was analyzed for those who used the DHI at least once. Except for sociodemographic variables, all other variables were standardized to a range from 0 to 1. For simple regression, inflation of the α error due to multiple testing was controlled via the approach of Benjamini and Hochberg, and for multiple regression, it was controlled via the significance of the complete multiple regression model.

RESULTS: Of 462 intervention group members, 199 (43.1%) used the web portal at least once. After controlling for inflation of the α error, simple regression for uptake yielded significant effects for higher education (B=0.56, 95% CI 0.18-0.95; P=.004), openness (B=1.08, 95% CI 0.33-1.83; P=.005), intention regarding physical activity (B=2.28, 95% CI 1.30-3.26; P<.001), and intention regarding healthy nutrition (B=2.30, 95% CI 1.30-3.31; P<.001). The multiple regression model for uptake was highly significant (P<.001), with significant positive associations for intentions regarding physical activity (B=1.86, 95% CI 0.74-2.97; P=.001) and healthy nutrition (B=2.22, 95% CI 1.00-3.44; P<.001), as well as a significant negative association for patient activation (B=-3.20, 95% CI -4.95 to -1.46; P<.001). After controlling for inflation of the α error, simple regression for frequency yielded no statistically significant effect, and the multiple regression model for frequency was not significant (P=.07).

CONCLUSIONS: This study is innovative in jointly examining determinants of the uptake and frequency of use of the same DHI within a single context and sample. By demonstrating that factors driving uptake do not necessarily increase the frequency of use, it advances existing research. The study contributes to a more differentiated understanding of DHI use and shows that distinct strategies are required to promote adoption versus sustained engagement. Applying this approach to other DHIs and settings may support more targeted and equitable digital health implementation in real-world contexts, thereby optimizing digital health deployment strategies overall.

PMID:41880606 | DOI:10.2196/80895