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Results for “Restricted cubic spline”

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At least 19 recordsLinked to original sources

PubMed2002

Assessing time-by-covariate interactions in relative survival models using restrictive cubic spline functions.

BACKGROUND: The Cox model is widely used in the evaluation of prognostic factors in clinical research. However, in population-based studies, which assess long-term survival of unselected populations, relative-survival models are often considered more appropriate. In both approaches, the validity of proportional hazards hypothesis should be evaluated. METHODS: We propose a new method in which restricted cubic spline functions are employed to model time-by-covariate interactions in relative survival analyses. The method allows investigation of the shape of possible dependence of the covariate effect on time without having to specify a particular functional form. Restricted cubic spline functions allow graphing of such time-by-covariate interactions, to test formally the proportional hazards assumption, and also to test the linearity of the time-by-covariate interaction. RESULTS: Application of our new method to assess mortality in colon cancer provides strong evidence against the proportional hazards hypothesis, which is rejected for all prognostic factors. The results corroborate previous analyses of similar data-sets, suggesting the importance of both modelling of non-proportional hazards and relative survival approach. We also demonstrate the advantages of using restricted cubic spline functions for modelling non-proportional hazards in relative-survival analysis. The results provide new insights in the estimated impact of older age and of period of diagnosis. DISCUSSION: Using restricted cubic splines in a relative survival model allows the representation of both simple and complex patterns of changes in relative risks over time, with a single parsimonious model without a priori assumptions about the functional form of these changes.

Aged↗

PubMed2001

Analysis of ambulatory blood pressure monitor data using a hierarchical model incorporating restricted cubic splines and heterogeneous within-subject variances.

Hypertensive disorders of pregnancy are associated with significant maternal and foetal morbidity. Measurement of blood pressure remains the standard way of identifying individuals at risk. There is growing interest in the use of ambulatory blood pressure monitors (ABPM), which can record an individual's blood pressure many times over a 24-hour period. From a clinical perspective interest lies in the shape of the blood pressure profile over a 24-hour period and any differences in the profile between groups. We propose a two-level hierarchical linear model incorporating all ABPM data into a single model. We contrast a classical approach with a Bayesian approach using the results of a study of 206 pregnant women who were asked to wear an ABPM for 24 hours after referral to an obstetric day unit with high blood pressure. As the main interest lies in the shape of the profile, we use restricted cubic splines to model the mean profiles. The use of restricted cubic splines provides a flexible way to model the mean profiles and to make comparisons between groups. From examining the data and the fit of the model it is apparent that there were heterogeneous within-subject variances in that some women tend to have more variable blood pressure than others. Within the Bayesian framework it is relatively easy to incorporate a random effect to model the between-subject variation in the within-subject variances. Although there is substantial heterogeneity in the within-subject variances, allowing for this in the model has surprisingly little impact on the estimates of the mean profiles or their confidence/credible intervals. We thus demonstrate a powerful method for analysis of ABPM data and also demonstrate how heterogeneous within-subject variances can be modelled from a Bayesian perspective.

Bayes Theorem↗

PubMed1995

The restricted cubic spline as baseline hazard in the proportional hazards model with step function time-dependent covariables.

We incorporate a cubic spline function where the tails are linearly constrained, as the baseline hazard, into the proportional hazards model. We show estimation of covariable coefficients and survival probabilities with this model to be as efficient statistically as with the Cox proportional hazards model when covariables are fixed. Examples show that the inclusion of time-dependent covariables defined as step functions into the restricted cubic spline proportional hazards model reduces computation time by a factor of 213 over the Cox model. Advantages of the spline model also include flexibility of the hazard, smooth survival curves, and confidence limits for the survival and hazard estimates when there are time-dependent covariables present.

Coronary Artery Bypass↗

PubMed1994

On prediction of future observation in growth curve model.

Rao proposed and compared several approaches for predicting future observations in a growth curve model. The assessment of associated prediction efficiency for different prediction methods were evaluated by Cross-Validation Assessment Error (CVAE). He used three data sets, each with a limited number of subjects (13-27) and also with a limited number of repeated measurements (4-7) per subject, to illustrate the prediction methods. In the present paper, we applied four of the prediction methods discussed by Rao, on a data set with a relatively large number of subjects (174) and also with a larger number of measurements (21) per subject, using the polynomial function and log-linear function. We propose to use the restricted cubic spline function as an alternative growth curve model and compare its performance with the polynomial function and log-linear function. It turns out that, at least for larger data sets such as that used in this paper, the prediction methods perform somewhat better when the growth is described by restricted cubic spline function than when the growth is described by polynomial function and log-linear function.

Calibration↗

PubMed2026

Association between hepatic steatosis index and female infertility: a cross-sectional study using NHANES 2013-2018.

Female infertility is a major reproductive health concern. Hepatic steatosis index (HSI), a non-invasive marker of liver-related metabolic burden, has not been well studied in relation to infertility across its distribution. We analyzed women aged 20-49 years from three NHANES cycles (2013-2018). HSI was examined as both a continuous variable and in quartiles, and restricted cubic spline models were used to assess potential nonlinearity. Sensitivity analyses using alternative infertility definitions and exploratory interaction analyses were also performed. Among 3,007 women, 416 (13.8%) were classified as having infertility. In the fully adjusted model, women in the highest HSI quartile had higher odds of infertility than those in the lowest quartile (OR 1.66, 95% CI 1.08-2.57; P = 0.031), with a significant trend across quartiles (P for trend = 0.010). Restricted cubic spline analysis showed a nonlinear association between HSI and infertility (P for overall association = 0.005), which was more evident at higher HSI levels. Higher HSI was associated with greater odds of infertility among reproductive-aged women.

Humans↗

PubMed2026

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (≥15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans↗

PubMed2006

Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study.

Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

Carcinoma, Squamous Cell↗

PubMed2026

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72 h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR = 5.12; 95% CI: 2.57-12.24; p < 0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity < 0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p = 0.045) and significantly improved risk reclassification (cNRI = 0.4778, p < 0.001; IDI = 0.0240, p = 0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗

PubMed1989

Flexible regression models with cubic splines.

We describe the use of cubic splines in regression models to represent the relationship between the response variable and a vector of covariates. This simple method can help prevent the problems that result from inappropriate linearity assumptions. We compare restricted cubic spline regression to non-parametric procedures for characterizing the relationship between age and survival in the Stanford Heart Transplant data. We also provide an illustrative example in cancer therapeutics.

Adult↗

PubMed2026

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans↗

PubMed1998

Standards of birth weight in twin gestations stratified by placental chorionicity.

OBJECTIVE: To establish fetal growth nomograms for twin gestations, categorized by placental chorionicity, and to compare them with those of published singleton and twin nomograms. METHODS: Computerized data files of live births of all twins delivered between January 1990 and October 1996 at Saint Peter's Medical Center were used. Birth weight curves corresponding to the fifth, tenth, 50th, 90th, and 95th percentiles were derived separately for twins with monochorionic and dichorionic placentation. We generated the curves by applying the method of generalized estimating equations, after adjusting for the potential intracluster correlation due to twinning. The curves were then smoothed on the basis of nonparametric restricted cubic splines to derive (smoothed) birth weight percentiles. We then compared our twin birth weight nomogram to six previously published singleton and two twin nomograms published previously for predicting small for gestational age infants (defined as birth weight below the tenth percentile). RESULTS: Among 1302 twin fetuses, 272 (21%) were monochorionic. Twins from monochorionic gestations weighed, on average, 66.1 g (standard deviation 28.4 g, P = .02) less than twins from dichorionic gestations after correcting for gestational age. Twin curves based on parity (nulliparity versus multiparity) were not different from each other. Analyses indicate that all previously published singleton nomograms approximate twin growth reasonably well between 32 and 34 weeks, but they underestimate twin growth at earlier gestational ages (between 25 and 32 weeks) and overestimate twin growth beyond 34 weeks' gestation. Similarly, a comparison of previously published twin nomograms with those of ours indicates that the growth standards in our population were similar to those in other published twin nomograms. CONCLUSION: We recommend that future epidemiologic and clinical studies use twin nomograms to identify growth-restricted twin fetuses. Moreover, because fetal growth is influenced by placental chorionicity, we recommend that fetal growth assessment in twin gestations consider placental chorionicity, whenever the information is available.

Birth Weight↗

PubMed2026

Separate and joint associations of morning plasma cortisol and aldosterone with Cardiovascular - Kidney - Metabolic syndrome in Chinese Hakka adults.

BACKGROUND: Advanced stages of cardiovascular-kidney-metabolic syndrome (CKMs) are associated with a markedly increased risk of mortality. However, the individual and combined effects of cortisol (COR) and aldosterone (ALD) on CKMs remain unclear. We aimed to investigate their separate and joint associations with CKMs stages and major components. METHOD: This cross-sectional study included 8,781 participants to investigate the separate and joint associations of COR and ALD with CKMs and its components, using linear regression, logistic regression, restricted cubic spline analyses (RCS), interaction analyses, and stratified analyses. RESULT: Beyond associations with CKMs staging-related continuous indicators and key components, higher quartiles of COR (Q4 vs. Q1, OR = 1.56, 95%CI, 1.26–1.95) and ALD (Q4 vs. Q1, OR = 1.33, 95%CI, 1.07–1.64) were independently associated with higher odds of advanced CKMs. RCS revealed significant nonlinear associations between log-transformed COR and ALD levels and advanced CKMs. A significant additive interaction was observed between COR and ALD on advanced CKMs (RERI = 0.94, 95%CI, 0.35–1.52; AP = 0.41, 95%CI, 0.30–0.52; S = 3.75, 95%CI, 1.84–7.63). Co-exposure analyses showed a 46% higher odds of advanced CKMs in the “High COR, High ALD” group (OR = 1.46, 95%CI, 1.19–1.80, P < 0.001) compared to the “Low COR, Low ALD” group, with consistent trends across most subgroups. CONCLUSION: Both COR and ALD show significant associations with advanced CKMs. The joint assessment of COR and ALD improves the identification of high-risk individuals, underscoring the value of adrenal hormone profiling in CKMs risk stratification.

Adult↗

PubMed2026

Prognostic modeling of overall survival in metastatic pancreatic cancer: an inflammation-based tool validated in PANTHEIA-SEOM cohort.

PURPOSE: To develop and internally validate the PANTHEIA-SIRI prognostic model, which integrates log-transformed systemic inflammation response index (SIRI) with clinical predictors, to estimate overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line chemotherapy. METHODS: We used data from the multicenter PANTHEIA-SEOM registry. OS was defined from chemotherapy start. The model was fitted as a Weibull accelerated failure time model in the survival-analysis population with multiple imputation. Predictors were log-transformed baseline SIRI, modeled with restricted cubic splines, ECOG, tumor burden, chemotherapy regimen, and anorexia-cachexia syndrome. Internal validation used a separate, non-overlapping cohort from the same registry; the centers contributing to each cohort are listed in a supplementary annex. TRIPOD was followed. Discrimination was assessed with Harrell´s C-index and calibration with IPCW Brier scores and IPA. RESULTS: The derivation cohort comprised 672 patients with SIRI data (593 analyzed for survival) across 22 Spanish hospitals (2015-2025); 80.1% had died after a median OS of 9.9 months. The imputation-pooled derivation C-index was 0.654 (95% CI, 0.627-0.681); optimism-corrected, 0.629. Internal validation used 62 separate patients from the same registry; 96.8% had died after a median OS of 9.2 months. The validation C-index was 0.603 (95% CI, 0.518-0.687). Calibration was adequate at 6 and 12 months. CONCLUSIONS: The PANTHEIA-SIRI model provides individualized OS estimates in mPDAC with routine clinical predictors. Its open-access calculator ( https://pantheia-siri.shinyapps.io/calc/ ) may support prognostic communication, treatment-intensity selection, and supportive-care planning. Routine clinical implementation will require further validation in larger, fully independent cohorts.

Cachexia↗

PubMed2026

One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

BACKGROUND: One-carbon metabolism (OCM) is a target of the chemotherapeutic agent capecitabine. OBJECTIVES: We investigated OCM biomarker concentrations in relation to capecitabine-induced toxicities in patients with stage II-III colorectal cancer. METHODS: Within a prospective cohort, 297 patients receiving adjuvant capecitabine-based chemotherapy were included. Pretreatment plasma concentrations of the OCM biomarkers folate, vitamin B2, vitamin B6, vitamin B12, total homocysteine, methionine, serine, and glycine were determined. We also investigated whether associations differed according to methylenetetrahydrofolate reductase (MTHFR) C677T genotypes. Chemotherapy-induced toxicities were defined as toxicity-induced modifications of capecitabine treatment. To allow for inspection of shapes of the associations, restricted cubic splines and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: In total, 156 (53%) patients experienced toxicity-induced modifications of capecitabine treatment. Folate was not associated with toxicities in the overall population. Higher folate concentrations were associated with a lower risk of toxicities in patients with MTHFR C677T CT/TT genotype (HRperdoubling: 0.75; 95% CI: 0.57, 0.98) but not in patients with CC genotype (HRperdoubling: 1.17; 95% CI: 0.84, 1.63). Higher concentrations of vitamin B2 were associated with a lower risk of toxicities (HRperdoubling: 0.81; 95% CI: 0.67, 0.99), whereas higher glycine concentrations were associated with a higher risk of toxicities (HRperdoubling: 1.87; 95% CI: 1.18, 2.94). The association between vitamin B6 and vitamin B12 and toxicities appeared nonlinear. Homocysteine, methionine, and serine were not associated with toxicities. CONCLUSIONS: Future studies investigating whether nutrition-guided optimization of OCM biomarkers will result in improved treatment tolerance are warranted.

Humans↗

PubMed2026

Association of long-term exposure to ambient air pollution and myopia in Chinese children.

Ambient air pollution is recognized as a major global health concern, but evidence on its association with childhood myopia remains limited, particularly under multi-pollutant exposure conditions. A school-based study was conducted in Tianjin, China, including 212,566 students in grades 4-6. The 3-yr mean concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), its major components (sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM), and black carbon (BC)), and ozone (O3) were estimated using machine-learning exposure models and linked to school locations. Restricted cubic splines and quartile-based modified Poisson models were used to assess single-pollutant exposure-response relationships, and quantile-based g-computation was applied to estimate joint pollutant associations. In single-pollutant models, the highest quartile of SO42- was associated with higher myopia prevalence compared with the lowest quartile (PR = 1.10; 95% CI, 1.07-1.13). O3 showed weaker and non-monotonic positive patterns (Q4 vs Q1: PR = 1.03; 95% CI, 1.00-1.05). In mixture analyses, a one-quartile increase in joint exposure was associated with higher myopia prevalence (PR = 1.017; 95% CI, 1.007-1.027). Sensitivity analyses generally supported the direction of the main findings. These findings suggest that long-term exposure to specific ambient air pollutants may be associated with myopia in school-aged children.

Chemical components↗

PubMed2026

Chronic heart failure and GPX3 promoter methylation: A clinical-epigenetic analysis.

BACKGROUND: Selenoprotein GPX3 is linked to Chronic Heart Failure (CHF), but its promoter methylation patterns in CHF remain unclear. OBJECTIVE: To explore CpG methylation in the GPX3 promoter region and its association with clinical parameters in CHF. METHODS: Twenty CHF patients and twenty healthy controls were included. Methylation levels of CpG sites within the GPX3_FA28 promoter region were quantified. Group differences were assessed using appropriate statistical tests. Restricted cubic spline (RCS) models were applied to explore dose-response associations between differentially methylated CpG sites and clinical indicators across multiple physiological systems. RESULTS: Significant locus-specific methylation alterations were identified in CHF patients. CpG_5 showed hypermethylation (P = 0.017), while CpG_9 (P = 0.045) and CpG_19 (P = 0.008) were hypomethylated compared with controls. Patients with NYHA class I/II exhibited higher methylation at CpG_1 (P = 0.028) and CpG_2 (P = 0.040). CpG_5 methylation displayed nonlinear associations (P < 0.05) with total bilirubin (inverted U-shape), carbon dioxide (triphasic), total cholesterol (U-shape), and plateletcrit (wave-like). CpG_9 correlated with activated partial thromboplastin time and hematopoietic markers, while CpG_19 was linked to eosinophil percentage and erythrocyte parameters. CONCLUSIONS: GPX3 promoter methylation displays apparent locus specificity in CHF. Different CpG sites may contribute to CHF pathophysiology through distinct epigenetic mechanisms. These findings highlight the potential of GPX3 methylation as a stratified biomarker in CHF.

Humans↗

PubMed2025

Association between residential greenness and coronary heart disease: A proteomics and miRNA microarray analysis.

Greenness has been linked to cardiovascular disease. However, the specific biological mechanisms through which greenness impacts coronary heart disease (CHD) remain unclear. We aim to explore the underlying epigenetic mechanisms linking greenness and CHD by using proteomics and miRNA microarray. A total of 2387 participants were included in the population study, 816 of whom were diagnosed with CHD. Residential greenness exposure was characterized using the normalized difference vegetation index (NDVI). Generalized additive models and restricted cubic splines investigated the association between greenness and CHD. Mediation analysis examined whether cardiovascular metabolic risk factors (blood pressure, inflammation indicators, and glucose) mediated the association. After proteomics and miRNA microarray screening, Elisa and qRT-PCR validated selected proteins (THBS1, FCN3, and LTBP1) and miRNAs (miR-671-5p, miR-124-3p, and miR-379-5p) in CHD. Among these, LTBP1 and miR-379-5p showed significant differential expression (P < 0.05) and were examined as potential molecular mediators. Higher greenness exposure within a 1000-m area was associated with a lower risk of CHD (OR: 0.86, 95 % CI: 0.81, 0.92). Systolic blood pressure (6.32 % [95 % CI: 1.49 %, 13.12 %]), lymphocyte (10.98 % [95 % CI: 3.76 %, 22.00 %]), monocyte (9.94 % [95 % CI: 3.42 %, 20.87 %]), and fasting blood glucose (3.41 % [95 % CI: 0.56 %, 7.84 %]) mediated this association. LTBP1 and miR-379-5p were differentially expressed in CHD and mediated 7.19 % [95 % CI: 0.01 %, 23.37 %] and 20.03 % [95 % CI: 2.85 %, 69.71 %] of greenness effect on CHD, respectively. Combining the population study and experiments, we found that miR-379-5p and LTBP1 may jointly modulate vascular constriction and immune inflammation in the association between greenness and CHD.

Humans↗

PubMed2026

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41 ± 0.24 vs. 2.35 ± 0.06, P < 0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans↗