Tag: statistics

Geroscience. 2026 May 11. doi: 10.1007/s11357-026-02314-8. Online ahead of print.

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a cardiometabolic syndrome strongly associated with aging, systemic inflammation and endothelial dysfunction, in which impaired endothelial nitric oxide synthase (eNOS) signaling plays a central role. This study aimed to identify circulating proteins associated with HFpEF and to explore their relationship with endothelial alterations under metabolic stress. A total of 109 HFpEF patients and 49 control subjects underwent clinical, laboratory, and echocardiographic assessment. HFpEF patients exhibited a high burden of cardiometabolic comorbidities and significantly increased NT-proBNP (2851.2 ± 1565.5 vs 156.0 ± 85.2 pg/mL) and C-reactive protein levels (2.9 ± 4.5 vs 0.31 ± 0.33 mg/dL). Echocardiography revealed elevated filling pressures (E/e’ 16.5 ± 3.8 vs 7.0 ± 1.9), a higher prevalence of high-probability pulmonary hypertension, and impaired right ventricular-pulmonary artery coupling. Exploratory proteomic profiling identified galectin-3 binding protein (LGALS3BP) as increased in plasma from HFpEF patients, a finding confirmed by ELISA showing significantly higher circulating levels compared with controls (8.65 ± 0.66 vs 2.36 ± 0.26 ng/mL, p < 0.001). Pathway analysis suggested a potential association between LGALS3BP and activation of nitric oxide synthase 2 (NOS2)-related inflammatory pathways. In vitro, metabolic stress conditions increased LGALS3BP expression in murine endothelial cells, with a more pronounced response in eNOS⁻/⁻ cells. In addition, eNOS deficiency was associated with the appearance of a lower-molecular weight LGALS3BP form and with increased markers of endothelial senescence and autophagy. LGALS3BP is elevated in HFpEF and is associated with endothelial alterations linked to impaired eNOS signaling under metabolic stress. These findings suggest a potential connection between endothelial stress responses and LGALS3BP expression in HFpEF, supporting further investigation of this protein as a biomarker of endothelial dysfunction in age-related cardiometabolic disease.

PMID:42113325 | DOI:10.1007/s11357-026-02314-8

Inflamm Res. 2026 May 11;75(1):113. doi: 10.1007/s00011-026-02268-9.

ABSTRACT

BACKGROUND: Ulcerative colitis (UC) patients carry a 2.5-fold increased risk of colorectal cancer (CRC), yet the shared multi-scale genetic architecture remains poorly understood. We constructed an integrative framework across tissue, cellular, and variant levels to systematically dissect the pathogenic evolution of this comorbidity across spatiotemporal dimensions.

METHODS: We integrated GWAS data from 100,204 CRC cases and 12,160 UC patients with tissue-specific MAGMA enrichment, embryonic spatial mapping (gsMap), and multidimensional single-cell prioritization (ECLIPSER, CELLECT, scDRS). We further resolved cell-specific co-expression patterns using hdWGCNA and identified high-confidence causal variants and genes through Bayesian fine-mapping (eCAVIAR, fastenloc) and Open4Gene analysis.

RESULTS: Genetic susceptibility for both diseases was significantly enriched in the terminal ileum and transverse colon, anchored to E16.5 embryonic gut programs. CD4 + T cells emerged as the core immune hub in UC, exhibiting profound immunometabolic polarization (Th17/IL-17 axis and Warburg effect), while progenitors were identified as the primary cellular origin for CRC malignancy. Pathological progression was characterized by a transition from chronic inflammatory stress toward p53-mediated genomic instability, epithelial-mesenchymal transition (EMT), and vascular remodeling. We prioritized Tier 1 candidate genes-ARPC5, PTGER4, CIB1, PREX1, and S100A10-as key mediators of the comorbidity association between inflammation and cancer.

CONCLUSIONS: These findings partially support a “genetic programming-microenvironment triggering” hypothesis, where regional vulnerabilities established by embryonic developmental programs are activated by postnatal insults, though its broad applicability warrants caution. This study provides a comprehensive multi-scale molecular framework for understanding UC-CRC comorbidity, offering potential targets for risk stratification and therapeutic intervention.

PMID:42113310 | DOI:10.1007/s00011-026-02268-9

Int J Health Econ Manag. 2026 May 11;26(2):11. doi: 10.1007/s10754-026-09415-z.

ABSTRACT

Economic shocks have been shown to affect social and political outcomes. Here, I show that U.S. counties that faced greater economic shocks within the last 30 years were less likely to comply with the advice/orders of public health officials during the COVID-19 pandemic. Analyzing county-level vaccination rates and then compliance rates with stay-at-home orders, I show that compliance with these initiatives was lower in counties that had experienced trade exposure to China, excess unemployment from the Great Recession, and a greater risk of job automation. These shocks are comparable in importance to factors such as income, age, and education.

PMID:42113308 | DOI:10.1007/s10754-026-09415-z

Anim Cogn. 2026 May 11. doi: 10.1007/s10071-026-02062-4. Online ahead of print.

ABSTRACT

Experiencing environmental complexity during early life is fundamental for vertebrate neural development, with profound and often irreversible effects on later behavioural and cognitive outcomes. However, studies on the early stages of invertebrate development are scanty. European lobsters (Homarus gammarus) are routinely reared in captivity for subsequent release in the context of restocking and stock-enhancement. The impoverished captive conditions they experience may exert long-term effects on their development, ultimately impairing their success after release. Here we tested the effects of environmental complexity during early life on learning (N = 38) and personality (N = 132) of juvenile lobsters. Lobsters experienced a full enrichment (with both substrate and shelter), a partial enrichment (either substrate or shelter), or bare standard conditions as a control. We assessed lobsters’ exploration and activity patterns via repeated open field tests, quantified their learning in a double T-maze, and investigated the possible presence of a speed-accuracy/flexibility trade-off in decision-making. We found that juvenile lobsters raised in enriched environments were more active compared to lobsters raised in control conditions. They were also faster in taking decisions and in correcting erroneous ones compared to controls, while decision speed did not predict the accuracy of its outcome. Finally, while all lobsters reached the learning criterion, the effects of environmental treatment on learning speed were only detectable in individuals that developed a wild-type morphological phenotype (i.e. asymmetrical claws), who showed a higher information-seeking tendency and required more trials. Overall, these results indicate a key role of early-life experience of environmental complexity in the development of behavioural and cognitive traits that can drive success in the wild.

PMID:42113306 | DOI:10.1007/s10071-026-02062-4

Int J Biometeorol. 2026 May 11;70(5):159. doi: 10.1007/s00484-026-03222-4.

ABSTRACT

Recently, pregnant women have been identified as susceptible to the effects of high ambient temperature. Evidence suggests that high temperature increases the risk of stillbirth, however, how this association differs by social disadvantage remains unclear. The aim of this study is to investigate the effect of maternal exposure to high ambient temperature on the risk of stillbirth, overall, and by social disadvantage. Maternal and birth information from 1 January 2000 to 31 December 2021 were obtained from the South Australian Perinatal Statistics Collection. We implemented a cohort study design of 417,207 births including 2,776 (0.7%) stillbirths. Mixed-effect logistic regression models with odds ratios (OR) and 95% confidence intervals (95% CI) were used to examine the effect of maternal exposure to daily maximum temperature at birth (lag day 0), and for each individual day in the week preceding delivery (lag days 1-7). Adjustments for low, medium or high disadvantage were considered in our models. Maternal exposure to high temperature ≥ 95th percentile (36.1 °C) in the week before delivery slightly increased the risk of stillbirth on lag day 2 (aOR: 1.10, 95%CI: 0.93-1.30, p = 0.26) and slightly decreased risk on lag day 3 (aOR: 0.90, 95%CI: 0.75-1.08, p = 0.26); however, the confidence intervals were wide and included 1, consistent with a null effect. Social disadvantage made negligible difference to the estimated odds of stillbirth associated with maximum temperature ≥ 95th percentile in the week before delivery. We recommend pregnant women consider adaptation strategies during periods of high temperature to minimise the risk of stillbirth.

PMID:42113305 | DOI:10.1007/s00484-026-03222-4

Bioprocess Biosyst Eng. 2026 May 11. doi: 10.1007/s00449-026-03343-5. Online ahead of print.

ABSTRACT

Ammonia is an essential nutrient for anaerobic digestion (AD) but becomes inhibitory at elevated concentrations, leading to process instability. Although numerous microbial taxa and functional genes have been proposed as indicators of ammonia stress, most lack systematic validation across defined inhibitory thresholds. In this study, batch anaerobic digestion assays were conducted under increasing total ammonia nitrogen concentrations to experimentally characterize ammonia-induced inhibition. Methane yields obtained from batch tests were fitted using a Hill model to define non-inhibitory, inhibitory, and minimum inhibitory ammonia levels. Shotgun metagenomic sequencing was applied to samples representative of each inhibition level, and a statistical framework integrating differential abundance analysis, network topology, redundancy analysis, and metabolic relevance was used to identify robust microbial indicators. Key taxa, including Anaerolinea, Methanomassiliicoccus, and Syntrophobacter, along with functional genes involved in acetate and propionate metabolism (e.g., acs and fhs), showed consistent and threshold-dependent responses to ammonia stress. These microbial indicators provide mechanistic insight into ammonia-induced AD instability and offer a promising basis for early-warning monitoring and microbial management strategies to improve the operational stability of anaerobic digesters treating food waste.

PMID:42113294 | DOI:10.1007/s00449-026-03343-5

Neuroradiol J. 2026 May 11:19714009261450379. doi: 10.1177/19714009261450379. Online ahead of print.

ABSTRACT

BackgroundThis study aims to assess whether T2 relaxometry can distinguish tissue characteristics between high-grade gliomas and non-infiltrative lesions.MethodsWe report our initial experience using the Relaxo LNI software to analyze multi-echo T2 relaxometry magnetic resonance imaging in patients with high-grade gliomas. For comparison, peritumoral T2-hyperintense areas in meningiomas and metastases were used as reference regions for vasogenic edema, based on the established concept that these tumor types typically do not infiltrate adjacent tissue. In contrast, peritumoral hyperintensity observed in high-grade gliomas may represent either vasogenic edema or tumor infiltration.ResultsData from 30 patients were analyzed, including 20 with high-grade gliomas and 10 with metastasis or meningiomas. A statistically significant difference was observed in multi-echo T2 relaxation values between the glioma and non-glioma groups (p < 0.05). Mean T2 relaxation times were longer in the high-grade glioma group than in the non-glioma group (p < 0.05). Within the high-grade glioma group, central regions showed significantly longer mean relaxation times than peripheral regions (p < 0.05).ConclusionOur preliminary findings suggest that T2 relaxometry identifies differences in relaxation profiles between tumor tissue and control edema, indicating potential value in detecting variations in peritumoral tissue composition in high-grade gliomas. However, these results are exploratory and hypothesis-generating, lack histopathological validation, and require further investigation to clarify the role of T2 mapping in preoperative planning.

PMID:42109220 | DOI:10.1177/19714009261450379

Adv Sci (Weinh). 2026 May 11:e75533. doi: 10.1002/advs.75533. Online ahead of print.

ABSTRACT

Spatial multi-omics technologies enable in situ molecular profiling but face challenges in integrating multi-modal data for spatial domain identification and cell heterogeneity analysis. We propose SOTMGF, a self-supervised, goal-directed multi-view graph fusion framework for spatial multi-omics data. SOTMGF includes five modules: pre-clustering, sparse feature processing, multi-view feature extraction and fusion (integrating molecular expression, spatial location, disease microenvironment, and molecular associations), and multi-modality integration. The self-training process and graph embedding are optimized iteratively within a unified framework, enabling mutual benefits across several components. SOTMGF outperformed existing methods in spatial domain identification, data denoising, and detection of spatially variable molecular features. Innovatively, it jointly analyzes spatial transcriptomics (ST) and proteomics (SP) from the same tissue, computationally generates spatial ATAC-seq via Tangram, reconstructs spatial pseudo-expression to identify spatial dark genes/proteins (SDGs/SDPs), and iteratively optimizes self-training and graph embedding in a unified framework. SOTMGF outperforms existing methods in spatial domain detection and denoising, reveals mRNA-protein discordance, predicts key transcription factors, and aids biomarker and therapeutic target discovery, advancing spatial biology research, molecular regulatory mechanisms, and therapeutic discovery.

PMID:42109219 | DOI:10.1002/advs.75533

J Med Internet Res. 2026 May 11. doi: 10.2196/93349. Online ahead of print.

ABSTRACT

BACKGROUND: Artificial intelligence (AI)-themed delusions are increasingly observed in psychotic-spectrum disorders, reflecting the incorporation of contemporary sociotechnical elements into delusional systems. While prior research has examined the phenomenology of technology-related delusions, it remains unclear whether the structural role of AI within these belief systems (particularly when AI occupies a central, organizing function) is associated with increased violence risk or more restrictive forensic outcomes. Given the importance of dynamic clinical factors such as insight and treatment adherence in forensic risk assessment, clarifying the role of AI centrality has clinical and legal relevance.

OBJECTIVE: This study aimed to examine whether centrality of AI within psychotic delusional systems is associated with (1) violence toward others and (2) judicial findings of significant public safety risk in forensic psychiatric decisions.

METHODS: We conducted a retrospective observational study using jurisprudential data from the Société québécoise d’information juridique (SOQUIJ) database, including all publicly available Quebec tribunal and court decisions up to December 31, 2025. Eligible cases involved psychotic-spectrum disorders with explicit AI-related delusional content and judicial consideration of dangerousness or disposition. The unit of analysis was the judicial decision. A total of 29 judgments were included. AI centrality was coded as central (n=15) or non-central (n=14) using a structured, text-based framework. Primary outcome was documented violence toward others; secondary outcomes included direct AI-violence attribution and judicial findings of significant public safety risk. Covariates included lack of insight, treatment nonadherence, substance use disorder, and prior violence history. Data were extracted through full-text review using a standardized coding grid. Bivariate associations were analyzed using Fisher exact tests (α=.05), and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Exploratory logistic regression models were performed to assess adjusted associations.

RESULTS: Violence toward others was documented in 20/29 cases (69.0%; 95% CI 50.3-83.1). AI centrality was not significantly associated with violence (12/15 [80.0%; 95% CI 54.8-93.0] vs 8/14 [57.1%; 95% CI 32.6-78.6]; OR 2.91, 95% CI 0.63-13.45; P=.26). However, AI centrality was strongly associated with direct AI-violence attribution (9/15 [60.0%] vs 2/14 [14.3%]; OR 9.00, 95% CI 1.48-54.6; P=.014). Judicial findings of significant public safety risk were more frequent in AI-central cases (13/15 [86.7%] vs 9/14 [64.3%]; OR 3.60, 95% CI 0.63-20.5; P=.24), although not statistically significant. AI-central cases demonstrated higher prevalence of impaired insight (13/15 [86.7%] vs 8/14 [57.1%]; OR 4.89, 95% CI 0.79-30.1) and treatment nonadherence (9/15 [60.0%] vs 4/14 [28.6%]; OR 3.75, 95% CI 0.74-18.9).

CONCLUSIONS: AI centrality within delusional systems appears to be not independently associated with increased violence toward others but was strongly associated with AI-based attribution of behavior and markers of epistemic vulnerability, including impaired insight and treatment nonadherence. This study is innovative in operationalizing the structural role of AI within delusions using real-world forensic data, rather than focusing solely on thematic content. Unlike prior phenomenological or case-based research, it integrates jurisprudential analysis with quantitative risk modeling. These findings suggest that AI-themed delusions function as structural organizers of meaning and agency rather than novel criminogenic risk factors. Clinically and legally, this underscores the importance of prioritizing dynamic risk variables over thematic novelty, informing more proportionate forensic decision-making and risk assessment in an era of rapidly evolving digital environments.

PMID:42109215 | DOI:10.2196/93349

Eur J Pain. 2026 May;30(5):e70291. doi: 10.1002/ejp.70291.

ABSTRACT

BACKGROUND: Spinal disorders are associated with substantial healthcare costs, but prognostic factors associated with high spine-related healthcare expenditures remain insufficiently understood. Therefore, this study aimed to identify prognostic factors associated with spine-related healthcare costs among patients with spinal disorders.

METHODS: A prognostic factor study using data from the Norwegian Neck and Back Registry was conducted. Thirty-four potential prognostic factors were considered. Spine-related healthcare costs were analyzed as a continuous outcome. Continuous predictors were modelled using restricted cubic splines to account for potential non-linear associations. Univariable and multivariable adjusted models were fitted, with priori defined covariate adjustments.

RESULTS: The study included 7877 patients with spinal pain. In adjusted models, healthcare region (patients from the Mid-Norway, West and Southeast regions incurred 69.1%, 44.5% and 29.6% higher costs, respectively, compared with those in the North), disability (90th vs. 10th percentile: +29.2%; CI +11.9% to +49.2%), pain during activity (90th vs. 10th percentile: +23.4%; CI +7.6% to +41.6%), health-related quality of life (90th vs. 10th percentile: -21.3%; CI -31.1% to -10.0%), job satisfaction (90th vs. 10th percentile: +14.7%; CI +2.3% to +28.7%), and opioid use (+15.3%; CI +5.7% to +26.2%) were associated with healthcare costs.

CONCLUSIONS: This set of identified prognostic factors may be useful for characterizing patient subgroups, developing prognostic models to identify individuals at risk of high healthcare expenditures, and informing strategies to improve the efficiency and equity of healthcare resource allocation.

SIGNIFICANCE: This study identifies clinical and societal determinants of health associated with high spine-related healthcare costs, highlighting how these factors jointly drive resource use. These findings help clarify mechanisms underlying cost variation and support the future development of prognostic tools and targeted strategies to improve efficiency and equity in spine care.

PMID:42109197 | DOI:10.1002/ejp.70291