Search Results (5,590)

Long-term continuous cropping aggravates soil-borne diseases and seriously affects crop growth, yield, and quality. Soil fumigation is an effective approach for reducing soil-borne pathogen pressure before crop planting, but environmentally compatible alternatives to conventional fumigants are still needed. The objective of this study was to evaluate the field efficacy of ethylicin as a soil fumigant for controlling major soil-borne pathogens under organic greenhouse production conditions and to determine its effects on soil physicochemical properties and tomato growth and yield. Two consecutive years of field trials were conducted at Yanqing Organic Park. During fumigation, the maximum soil temperature reached 50.8 °C at the soil surface and 42.6 °C at a depth of 10 cm, which may have contributed to pathogen suppression and enhanced the fumigation effect of ethylicin. Ethylicin markedly reduced the populations of Fusarium spp., Phytophthora spp., and Meloidogyne spp., with control efficacies ranging from 96.44% to 97.73%, 68.12% to 95.30%, and 72.12% to 96.91%, respectively. Fumigation also altered soil physicochemical and nutrient properties, decreasing NO₃⁻–N content and electrical conductivity while increasing NH₄⁺–N, organic matter, and available potassium. Tomato plant height, stem diameter, and chlorophyll content increased by 16.52%, 20.71%, and 6.73%, respectively, and yield increased by 35.28–38.83% over the two years. Phytophthora parasitica-associated root rot was also reduced following ethylicin fumigation, with the disease index decreasing from 3.75 ± 3.23 to 1.25 ± 2.50 in 2023 and from 5.56 ± 1.92 to 0 in 2024; no visible root rot symptoms were observed in the ethylicin treatment in 2024. Overall, ethylicin provided stable suppression of major soil-borne pathogens while improving soil nutrient conditions and tomato performance. These results support the potential of ethylicin as a pre-plant soil fumigant for greenhouse vegetable production, particularly in systems with high requirements for pesticide-residue control and environmental safety. Full article

Idiopathic pulmonary fibrosis (IPF) remains a progressive and fatal disease despite major advances in antifibrotic therapy. Pirfenidone and nintedanib slow lung function decline, and the PDE4B inhibitor nerandomilast and treprostinil have recently shown promise as next-generation treatments. However, current therapies neither halt nor reverse disease progression, and tolerability issues often limit adherence. We compared the antifibrotic activity and plasma levels of nintedanib administered by either oral gavage or dietary supplementation in a rat model of pulmonary fibrosis. Male Sprague-Dawley rats received intratracheal bleomycin (1 U/kg) on days 0 and 4. From day 7 to day 28, animals were treated with nintedanib (100 mg/kg/day) by either oral gavage or medicated chow. Lung weight, fibrosis biomarkers (procollagen-I, metalloproteinase-7 or MMP7, WNT1-inducible signaling pathway protein or WISP-1), epithelial injury marker KL-6, target engagement biomarkers (Fibroblast Growth Factor 2 or FGF-2, Vascular Endothelial Growth Factor or VEGF), plasma drug levels, and histological fibrosis scores were evaluated. Both administration regimens significantly reduced procollagen-I, WISP-1 and KL-6, and histological fibrosis scores. Oral gavage produced approximately fourfold-higher peak plasma concentrations of nintedanib 30 min after dosing, whereas dietary administration resulted in lower, more stable plasma levels with reduced variability while resulting in comparable antifibrotic efficacy. In conclusion, nintedanib retained robust antifibrotic activity when administered via dietary supplementation despite lower, but continuous, active plasma concentrations. Collectively, these findings indicate that optimizing drug delivery and absorption kinetics may achieve sustained therapeutic efficacy while reducing unnecessary exposure to supratherapeutic concentrations, thereby potentially improving tolerability. Full article

Background: Minimal residual disease (MRD) is an established prognostic factor in multiple myeloma (MM), but the significance of dynamic MRD changes before and after autologous stem cell transplantation (ASCT) remains unclear. Methods: We retrospectively analysed 335 newly diagnosed MM patients who underwent upfront ASCT. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI), adjusting for clinical risk factors. Results: Patients were classified as having persistent MRD negativity (n = 82, 24.5%), MRD− to MRD+ conversion (n = 40, 11.9%), MRD+ to MRD− conversion (n = 168, 50.1%), or persistent MRD positivity (n = 45, 13.4%). Median OS was not reached: 105, 131, and 87 months for the groups (p < 0.001); and PFS was not reached: 50, 71, and 38 months (p < 0.001). In multivariable analysis, persistent MRD positivity (HR, 4.762; 95% CI, 2.151–10.546; p < 0.001) and MRD− to MRD+ conversion (HR, 3.925; 95% CI, 1.791–8.598; p < 0.001) were associated with increased mortality risk compared with persistent MRD negativity, whereas MRD+ to MRD− conversion showed a borderline-significant increase (HR, 1.973; 95% CI, 0.963–4.046; p = 0.063). In addition, similar patterns were observed for PFS. In subgroup analyses, late MRD+ to MRD− conversion was associated with inferior PFS (HR, 1.857; 95% CI, 1.136–3.034; p = 0.014), whereas MRD− to MRD+ conversion showed no differences in OS or PFS (all p > 0.05). Among persistent MRD-positive patients, stable or increasing MRD pattern predicted worse outcomes (HR, 4.397; 95% CI, 1.190–16.240; p = 0.026). Conclusions: Longitudinal MRD trajectories provided independent prognostic information beyond static MRD assessment in MM. Subgroup analyses further suggest that dynamic MRD assessment might help refine risk stratification after ASCT. Full article

Microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) define a molecular subtype of colorectal cancer (CRC) and predict benefit from immune checkpoint inhibition. Clinically, MSI/MMR assessment may yield discordant results across assays, anatomic sites, or time points. A challenging scenario occurs when tissue analysis identifies microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) CRC, whereas circulating tumor DNA (ctDNA) analysis indicates MSI-H. This review evaluates evidence for MSI/MMR heterogeneity and subclonality in CRC. We reviewed literature on spatial, temporal and subclonal MSI/MMR heterogeneity across human cancers, focusing on CRC. Explanations for tissue–plasma and tissue–tissue discordance, including assay limitations, sampling bias, lesions misattribution, biological evolution, and treatment-related selection, were assessed. Although discordance more commonly reflects assay limitations, sampling bias, or profiling of different lesions, increasing evidence supports genuine biological heterogeneity. Distinct tumor regions may show retained MMR protein expression in one area and regional loss with MSI in another. Noncanonical MMR defects, epigenetic heterogeneity, post-treatment evolution, adaptive mutator-state, and immune selection may also generate dynamic or subclonal instability. Therapeutic relevance may depend not simply on MSI detection, but on whether the unstable clone is sufficiently dominant to generate broadly shared neoantigens across the disease burden. MSI/MMR discordance requires careful interpretation and should not automatically be considered as true biological heterogeneity. Nevertheless, genuine subclonality occurs in CRC and other cancers and may affect responsiveness to immune checkpoint inhibition. Integrated tissue, plasma, spatial and longitudinal analyses may improve treatment decisions and biomarker development. Full article

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is associated with substantial morbidity and mortality. Lung transplantation remains the definitive therapy for selected patients; however, severe pulmonary vascular dysfunction and hemodynamic instability may complicate transplant candidacy and pre-transplant management. The role of parenteral prostacyclin therapy as a bridge to transplantation in this population remains poorly defined. The primary objective of this retrospective case series was to evaluate the utility of parenteral treprostinil as a bridge therapy for lung transplantation in 14 patients with severe PH-ILD from 2018 to 2025. Secondary objectives were to describe subsequent changes in clinical outcomes, including hemodynamic parameters measured by right heart catheterization, echocardiographic findings, the six-minute walk distance, oxygen requirements, the need for veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and successful lung transplantation. Parenteral treprostinil was associated with significant improvements in pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and BNP levels, while pulmonary capillary wedge pressure, cardiac output, cardiac index, and oxygen requirements remained stable following therapy initiation. Echocardiography demonstrated improvement in right ventricular dilation and right ventricular dysfunction. Most patients were successfully bridged to lung transplantation, while only two patients died prior to transplantation. In selected patients with severe PH-ILD, parenteral treprostinil may improve pulmonary hemodynamics and facilitate a successful bridge to lung transplantation without worsening oxygenation. Full article

Background: Crop fungal diseases cause huge yield losses globally, and the abuse of chemical fungicides has led to severe resistance and environmental risks. Antimicrobial peptides (AMPs) represent ideal green alternatives, but poor salt tolerance and high production costs limit their field application. Results: In this study, we developed a His-tag engineering strategy to enhance salt tolerance of antifungal peptides, and identified a novel peptide Cla-H derived from Styela clava. Cla-H was efficiently expressed via secretory fermentation in Pichia pastoris, and its crude fermentation supernatant could be directly applied to plants. Cla-H exhibited strong and rapid fungicidal activity against Fusarium graminearum and Botrytis cinerea, accompanied by irreversible inhibition of spore germination and observable membrane permeabilization phenotypes. While SYTOX green and PI staining indicated membrane-damaging events, adequate control experiments are still required to firmly establish membrane permeabilization as its primary mode of action. Meanwhile, it showed outstanding thermal and storage stability. Most importantly, His-tag modification significantly improved its salt tolerance, enabling stable activity under high-salt conditions that completely inactivated the parental peptide. In planta assays demonstrated that crude Cla-H fermentation supernatant effectively controlled wheat scab and tomato gray mold. Conclusions: This study provides a promising salt-tolerant antifungal peptide for crop protection and establishes a simple and low-cost technical route for developing next-generation green biofungicides. Full article

Background/Objectives: Eating-related difficulties in people with multiple sclerosis (MS) may reflect different behavioural and psychological processes, including emotional responses to illness-related stress, habitual overeating, attempts to control food intake, and broader self-management routines. Variable-centred analyses may obscure this heterogeneity by examining eating-related tendencies separately. This study aimed to examine whether habitual overeating, emotional overeating, and dietary restraint in adults with MS are better represented as one general continuum of eating-related difficulty or as distinct person-centred profiles that differ in coping styles, health locus of control, and MS self-management. Methods: This cross-sectional secondary analysis included 382 adults with definite MS. Latent class analysis used 30 binary My Eating Habits Questionnaire items. One-step latent class regression models examined coping and health locus of control. Linear regression compared self-management scores. The models were adjusted for sex, age, disease duration, and Expanded Disability Status Scale score. Results: A five-class solution was retained (BIC = 11,067.60; entropy = 0.920), comprising low difficulties, moderate mixed tendencies, two emotional eating/restraint profiles, and dysregulated overeating. Emotional eating with moderate restraint was associated with lower task-oriented coping and internal health control, and with higher emotion-oriented and avoidance-oriented coping and external health-control beliefs. Dysregulated overeating was associated with lower task-oriented coping, higher avoidance-oriented coping, and stronger powerful-others health beliefs. Self-management was higher for emotional eating with moderate restraint (B = 5.3, 95% CI 1.8 to 8.9; p = 0.003) and high emotional eating and restraint (B = 6.0, 95% CI 1.8 to 10.3; p = 0.005), versus low difficulties. Sensitivity analyses gave similar findings. Conclusions: Eating-related tendencies in MS formed distinct profiles rather than a single continuum. These profiles differed in coping and health-control patterns, suggesting that similar eating-related difficulties may occur in different psychological and self-management contexts. The higher self-management scores observed in restraint-related profiles should be interpreted cautiously and should not be taken to indicate that restrictive eating is adaptive. This study does not establish clinical classification or treatment recommendations. Instead, it provides a descriptive empirical basis for future studies testing whether these profiles are stable and whether they predict dietary, nutritional, psychological, and clinical outcomes. Full article

Objective: To evaluate the sustained real-world effectiveness and safety of catechol-O-methyltransferase (COMT) inhibitors added to levodopa in patients with Parkinson’s disease (PD) presenting early motor fluctuations. Methods: REONPARK is an ongoing, multicenter, prospective observational study conducted in Spain. Adult patients with PD and end-of-dose motor fluctuations for <2 years initiating a COMT inhibitor were included. Outcomes assessed at 3, 6, and 12 months included Clinician and Patient Global Impression of Change (CGI-C, PGI-C), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Wearing-off Questionnaire (WOQ-19), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Questionnaire-8 (PDQ-8), and safety. This article presents the 3-, 6-, and 12-month planned interim analysis of the study. Results: A total of 143 patients were included (99.3% treated with opicapone), of whom 138, 131, and 89 patients completed the 3, 6, and 12 months of follow-up, respectively. Levodopa doses remained stable in most patients (73% at 12 months). Significant and sustained improvements were observed in MDS-UPDRS Parts III and IV scores, as well as the total MDS-UPDRS score over 12 months, with greater likelihood of Part IV improvement in patients receiving <4.5 mg/kg/day of levodopa. OFF time decreased by 1.6–2.0 h from baseline. ON-time quality was maintained over time with 97.7% of patients reporting no or minimal functional impact from dyskinesia, while 47.7% of patients had no impact from motor fluctuations and 36.4% of patients no longer experienced OFF periods at 12 months. PDQ-8 scores remained stable and no overall benefit on total non-motor symptoms burden was demonstrated, despite improvements in selected domains among patients with a higher baseline non-motor symptoms burden. WOQ-19 scores improved significantly. Conclusions: In PD patients with early motor fluctuations, opicapone initiation was associated with sustained improvements in motor outcomes and reduced OFF time, and maintained the ON-time quality over 12 months, with stable levodopa dosing. Full article

Background/Objectives: Advanced endometrial cancer (FIGO III–IV) is characterised by poor prognosis and a heterogeneous biological profile, and molecular classification enables treatment personalisation by identifying subtypes with distinct therapeutic targets. We aimed to characterise the molecular and histopathological features of FIGO III–IV cases in a Polish multicentre cohort and to discuss the resulting treatment implications. Methods: This retrospective multicentre study included 915 consecutive patients with endometrial cancer operated on between April 2022 and May 2025 at three oncology centres in south-eastern Poland. Molecular subtyping (POLEmut, p53abn, dMMR/MSI-H, NSMP) was performed using immunohistochemistry (IHC) and next-generation sequencing (NGS). FIGO stage was assigned according to the FIGO 2009 classification. Results: Among 888 patients with a known molecular subtype, FIGO III–IV cases accounted for 15.9% (n = 141). The p53abn subtype predominated (35.5%), followed by dMMR/MSI-H (26.2%), NSMP (24.1%), and POLEmut (5.7%). The proportion of p53abn increased with stage (I–II vs. III–IV, p < 0.001), whereas dMMR/MSI-H remained stable regardless of stage (p = 0.83). POLEmut was absent in FIGO IV (0/16; 95% CI 0.0–19.4%), which should be regarded as an exploratory observation requiring prospective validation. Conclusions: The molecular profile of advanced endometrial cancer may inform treatment strategy; the therapeutic implications presented here are descriptive and hypothesis-generating, as the study did not include survival data. The dMMR/MSI-H subtype identifies patients who may benefit from immunotherapy in accordance with current clinical indications, supporting routine MMR testing regardless of disease stage. Conversely, p53abn tumours point to the need for a more intensive treatment strategy, in line with current guidelines. The absence of POLEmut in FIGO IV is an exploratory observation requiring prospective validation. Treatment de-escalation in POLEmut FIGO IIIC remains subject to further clinical validation and requires individualised assessment after complete staging. Full article

Background/Objectives: A potential association between individualized multimodal immunotherapy (IMI) within a multiphase combined treatment strategy and prolonged survival was explored through retrospective real-world data analysis. Methods: The patient selection criteria were as follows: treatment after 27 May 2015, adults between ages 18 and 70, GB diagnosis and IDH1wt status documented, known MGMT promoter methylation status (methylated versus unmethylated), known status of OS, and no second malignancy. IMI is currently only accessible to patients with a >60 KPI and sufficient financial resources. Results: A total of 104 patients were identified, distributed as per MGMT methylation versus unmethylation status, respectively, as 18% female/25% male versus 23% f/38% m; the median age at intake was 54 y versus 50 y; the resection extent was 12 R0, 28 < R0 and three not documented versus 25, 28 and eight; and the median KPI at intake was 70 overall. Patients received a median of 37 versus 31 modulated electro-hyperthermia sessions, 37 versus 32 NDV injections, and two versus one dendritic cell vaccines. The median OS and percentage 2 y OS were 33.1 months and 69.7% versus 19.0 months and 35.4%. There were no major adverse reactions (ARs), but the AR burden increased with checkpoint inhibitor use. A 33-patient subset was analyzed on health-related quality of life (HRQoL) throughout IMI treatment, based on at least five EQ-5D-5L questionnaires available from intake. Mobility and self-care affected HRQoL less than usual activity, pain/discomfort and anxiety/depression. Throughout IMI, HRQoL remained stable. Before progressive disease, the median health utility index was 0.86, resulting in a median quality-adjusted life-months of 4.6 versus a median of 5.4 calendar months. Conclusions: Real-world observation indicates IMI may prolong GB patient OS while maintaining HRQoL. Full article

Background/Objectives: Reduced physical activity (PA) and increased sedentary behavior (SB) are associated with adverse outcomes in chronic obstructive pulmonary disease (COPD), but the factors underlying their long-term change are unclear; we investigated the baseline factors associated with these changes. Methods: Japanese outpatients with stable COPD co-enrolled in the SPACE (baseline) and E-PAC (follow-up) studies were analyzed retrospectively. Twenty-nine baseline clinical variables were assessed. PA and SB were measured with a waist-worn triaxial accelerometer and expressed in metabolic equivalents (METs). Annualized percentage changes (per year, relative to baseline) were analyzed by Spearman’s rank correlation and multiple linear regression. Results: Thirty-two participants (all men; median age 71.0 years; median follow-up 5.0 years) were analyzed. Lower baseline body weight, BMI, upper arm circumference, FEV1.0, FEV1.0/FVC, and lowest percutaneous oxygen saturation (SpO₂) during the 6 min walk test (6MWT) were correlated with greater annualized declines in PA. For SB, the annualized change was correlated only with the lowest SpO₂ during the 6MWT, FEV1.0/FVC, and the hemoglobin concentration. In multivariable models adjusted for FEV1.0 %pred and the lowest SpO₂ during the 6MWT, BMI remained associated with the declines in total PA and in the duration at ≥3.0 METs; the models for the step count and SB were not significant. Conclusions: In this exploratory analysis, nutrition-related anthropometric measures, poorer pulmonary function, and exercise-induced desaturation were associated with the long-term decline in PA, and a lower BMI remained associated after adjustment. For the change in SB, associations were found only in unadjusted correlation analysis and were not supported by the multivariable model. These hypothesis-generating findings require confirmation in a larger cohort. Full article

This meta-analysis aimed to systematically assess the effects of organic acid supplementation on growth performance and disease-related parameters in broiler chickens challenged with coccidiosis. Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, and Web of Science, yielding 11 controlled experimental studies for quantitative analysis. The outcomes measured were BWG, feed conversion ratio (FCR), lesion score, and oocyst count (OPG). No overall significant effect of organic acid supplementation was detected on body weight gain (BWG) (MD = 49.88 g; 95% CI: −156.94 to 256.70; p = 0.64) and FCR (MD = −0.12 g/g; 95% CI: −0.25 to 0.01; p = 0.08), with high heterogeneity across investigations (I² = 100%) as identified through random-effects meta-analysis. Organic acid supplementation was associated with lower lesion scores (MD = −1.08 score units; 95% CI: −1.39 to −0.77; p < 0.00001; I² = 57%) and reduced oocyst shedding (SMD = −1.25; 95% CI: −2.25 to −0.25; p = 0.01; I² = 93%). Exploratory subgroup analyses suggested possible differences according to study duration, organic acid type, Eimeria species, and measurement time point. However, several subgroup estimates were based on a small number of studies and should therefore be interpreted cautiously rather than as confirmatory evidence of differential efficacy. Leave-one-out sensitivity analyses showed stable conclusions for BWG, FCR, and lesion score, whereas the statistical significance of the OPG effect was sensitive to omission of some studies. Exploratory assessments suggested possible small-study effects for BWG and OPG, but these analyses were underpowered because fewer than 10 studies contributed to each outcome. Using the GRADE framework, the certainty of evidence was rated as very low for BWG, FCR, lesion score, and OPG because of risk-of-bias concerns, inconsistency, and imprecision. Overall, very low-certainty evidence suggests that organic acids may reduce intestinal lesion severity and oocyst shedding, whereas their effects on growth performance remain uncertain. Further well-designed and standardized studies are required to clarify treatment effects and optimal supplementation strategies. Full article

Atopic dermatitis is a common inflammatory skin disease affecting up to 10% of adults. Whether atopic dermatitis exhibits a strong systemic inflammatory signature remains debated. We characterized peripheral whole-blood alterations in adults with moderate-to-severe atopic dermatitis undergoing treatment with dupilumab or baricitinib therapy. Blood samples were collected at weeks 0, 4, and 16. Whole-blood proteins were measured using Olink, transcriptomic profiling was performed by RNA sequencing, and torque teno virus plasma levels were quantified by qPCR. During targeted atopic dermatitis therapy with dupilumab or baricitinib, clustering of samples based on gene expression levels showed no separation by time or treatment, with only a limited number of differentially expressed genes. Proteomic changes were similarly modest; however, treatment was consistently associated with decreased CCL17/TARC levels. Teno torque virus plasma load remained stable throughout therapy, indicating preserved immunocompetence. These findings suggest that the dominant inflammatory processes in atopic dermatitis may be largely tissue-restricted, supporting the use of peripheral biomarkers for pragmatic monitoring rather than mechanistic discovery. Full article

Background: The aim of this study was to assess long-term trends in mortality due to digestive diseases among older adults in Poland. Methods: Mortality data for the years 2000–2022 were analyzed for individuals aged ≥65 years. Age-standardized death rates (SDRs) were calculated. Particular attention was paid to liver cirrhosis-related mortality, operationalized according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) joined categories K70 and K74. Temporal trends were assessed using joinpoint regression to estimate annual percentage change (APC) and average annual percentage change (AAPC) stratified by sex and age groups (65–74 and ≥75 years). The total number of deaths included in the statistical analysis was 6,645,408. Results: In early old age (65–74 years), the proportion of deaths due to digestive diseases increased in both men (from 3.6% to 5.0%) and women (from 4.1% to 4.5%), while a decrease was observed in late old age (≥75 years). The combined K70/K74-coded liver disease category represented an important component of digestive disease mortality. Among women aged 65–74 years, a significant upward trend in SDR was observed after 2015 (APC 3.5%, p < 0.05), with an increase from 54.7 to 70.8. In men of the same age, SDR remained relatively stable overall (160.5 to 171.6), although mortality due to liver-related diseases increased significantly after 2015 (APC 6.7%, p < 0.05). In older age groups, declining trends were observed until the late 2010s, followed by recent non-significant increases. Conclusions: Mortality patterns for alcohol-related liver disease and hepatic fibrosis/cirrhosis showed particularly unfavorable recent trends in adults aged 65–74 years. These findings highlight the need for continued surveillance and prevention of chronic liver disease in ageing populations. Full article

Reliable clinical decision support systems require not only high predictive accuracy but also trustworthy probability estimates and robust uncertainty quantification. However, most medical artificial intelligence (AI) studies primarily emphasize discrimination performance while overlooking systematic reliability evaluation. This study proposes a reliability-aware evaluation framework for Alzheimer’s disease detection that integrates discrimination analysis, statistical validation, probability calibration, uncertainty quantification, robustness assessment, and clinical decision analysis within a unified pipeline. Multiple machine learning classifiers and ensemble configurations were evaluated using repeated stratified cross-validation and assessed through discrimination and calibration metrics. Support Vector Machine achieved the highest ROC-AUC (0.955 ± 0.046), while Extra Trees obtained the highest Accuracy (0.878) and F1-score (0.887). Friedman analysis confirmed statistically significant differences among classifiers ($p<0.001$). Platt scaling consistently improved probabilistic reliability, whereas Beta calibration demonstrated stable performance under noise, feature perturbation, and reduced-data scenarios. Uncertainty-aware selective prediction increased high-confidence diagnostic accuracy by up to 8.1%, and decision curve analysis demonstrated improved clinical utility. The reliability analysis identified calibration-aware stacking as the most reliable ensemble configuration. An independent cross-dataset evaluation on a heterogeneous Alzheimer’s disease clinical dataset with a substantially different feature space yielded stable discrimination (ROC-AUC = 0.858 ± 0.025) and calibration (ECE = 0.132 ± 0.019) after the STACK_CAL architecture was independently retrained from scratch. These findings provide evidence of the cross-dataset applicability of the proposed reliability-aware strategy across different clinical data modalities, while further prospective and independent validation remains necessary before real-world clinical deployment. Full article