Tag: statistics

Brain Behav Immun. 2023 Oct 24:S0889-1591(23)00319-7. doi: 10.1016/j.bbi.2023.10.019. Online ahead of print.

ABSTRACT

BACKGROUND: Neuroinflammation and aberrant immune regulation are increasingly implicated in the pathophysiology of white matter hyperintensities (WMH), an imaging marker of cerebrovascular pathologies and predictor of cognitive impairment. The role of human leukocyte antigen (HLA) genes, critical in immunoregulation and associated with susceptibility to neurodegenerative diseases, in WMH pathophysiology remains unexplored.

METHODS: We performed association analyses between classical HLA alleles and WMH volume, derived from MRI scans of 38 302 participants in the UK Biobank. To identify independent functional alleles driving these associations, we conducted conditional forward stepwise regression and lasso regression. We further investigated whether these functional alleles showed consistent associations with WMH across subgroups characterized by varying levels of clinical determinants. Additionally, we validated the clinical relevance of the identified alleles by examining their association with cognitive function (n = 147 549) and dementia (n = 460 029) in a larger cohort.

FINDINGS: Four HLA alleles (DQB1*02:01, DRB1*03:01, C*07:01, and B*08:01) showed an association with reduced WMH volume after Bonferroni correction for multiple comparisons. Among these alleles, DQB1*02:01 exhibited the most significant association (β = -0.041, 95 % CI: -0.060 to -0.023, p = 1.04 × 10^-5). Forward selection and lasso regression analyses indicated that DQB1*02:01 and C*07:01 primarily drove this association. The protective effect against WMH conferred by DQB1*02:01 and C*07:01 persisted in clinically relevant subgroups, with a stronger effect observed in older participants. Carrying DQB1*02:01 and C*07:01 was associated with higher cognitive function, but no association with dementia was found.

INTERPRETATION: Our population-based findings support the involvement of immune-associated mechanisms, particularly both HLA class I and class II genes, in the pathogenesis of WMH and subsequent consequence of cognitive functions.

PMID:37884160 | DOI:10.1016/j.bbi.2023.10.019

Sci Total Environ. 2023 Oct 24:168065. doi: 10.1016/j.scitotenv.2023.168065. Online ahead of print.

ABSTRACT

Thorium-232 (Th-232), a naturally-occurring radioactive element with high potential of nuclear fuel is now being utilized in advanced nuclear reactors for CO₂-free energy generation. To achieve all-round capability in Th-fuel cycle for health and environment, understanding the biological effects of Th-232 at cellular and molecular level are extremely important. The present study investigated long-term effects (6 and 12 months) of Th-232 (4, 10 and 20 mg/kg) on gene expression in mice liver (major target organ). Analysis of differentially expressed genes (DEGs, ≥2.0 folds, p < 0.05) showed that with the increase of Th dose (4 to 20 mg/kg), the number of upregulated DEGs increased and the number of downregulated DEGs decreased significantly. A significant number of upregulated DEGs (10 genes in 6 months and 14 genes in 12 months) were found common between 4 and 20 mg/kg. Gene Ontology analysis revealed significant (P_adj ~ 10^-6-10^-28) enrichment of upregulated DEGs for metabolic process, signal transduction, cell death, cell cycle and cell proliferation. KEGG pathway analysis showed DEGs significantly enriched in several cancer-related pathways including hepatocellular carcinoma (HCC). Protein-protein interaction analysis further revealed statistically significant functional interaction (p-value ~10-6-10-10) among the proteins of HCC, which identified β-catenin as one of the most significant signaling nodes in association with myc, an oncogene and p53, a tumor suppressor. Importantly, these results were corroborated by quantitative real time-polymerase chain reaction and western blotting in liver tissues of animals exposed to Th-232. This study insights Wnt/β-catenin signaling network attributable to drive Th-induced liver carcinogenesis, which may have significant implications for management of long-term effects of Th-232.

PMID:37884152 | DOI:10.1016/j.scitotenv.2023.168065

Indian Heart J. 2023 Oct 24:S0019-4832(23)00167-0. doi: 10.1016/j.ihj.2023.10.003. Online ahead of print.

ABSTRACT

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with development of left ventricular (LV) dysfunction and heart failure (HF). The study aimed to determine the prevalence of LV dysfunction and HF in unselected out-patients with T2DM with no previous cardiac history and to correlate LV dysfunction and HF with demographic and comorbid characteristics.

METHODS: This cross-sectional study conducted at 27 centers in India captured demographic and clinical data through electronic case record forms. B-type natriuretic peptide of >105 pg/mL was used to diagnose HF and two-dimensional echocardiography was used to assess LV dysfunction.

RESULTS: Of the 615 patients, 54.3 % (n = 334) were males; mean age was 57.4 ± 10.48 years. More than one-third of the patients had T2DM duration of >10 years (n = 238; 38.7 %), with hypertension as the most prevalent comorbidity (n = 372, 78.6 %). Approximately 61.3 % of the patients had LV hypertrophy. The mean LV mass was 135.0 ± 56.16 g (95 % CI 130.28, 139.70). The prevalence of any type of LV dysfunction, including systolic or diastolic dysfunction and HF was 55 % (95 % CI 51.0, 59.0) and 10 % (95 % CI 7.0, 12.0), respectively. A negligible but statistically significant correlation was observed between LV dysfunction and T2DM duration (p = 0.011), alongside HF and age (p < 0.0001).

CONCLUSION: Real-world data from this registry from India demonstrates a substantial burden of LV dysfunction and HF in individuals with T2DM in India. It is imperative to formulate strategies for early identification of LV dysfunction in individuals with T2DM for prevention and consequent management of HF.

PMID:37884126 | DOI:10.1016/j.ihj.2023.10.003

Ann Endocrinol (Paris). 2023 Oct 24:S0003-4266(23)00714-X. doi: 10.1016/j.ando.2023.10.006. Online ahead of print.

ABSTRACT

Goals： The goal of this study was to use meta-analysis to compile information from various studies to investigate the existence and severity of cognitive impairment in elderly diabetes patients who have hypoglycemic episodes. Materials and techniques: For research studies on the relationship between hypoglycemia and cognitive decline or dementia in persons older than 45 years, we searched the PubMed, EMBASE, Cochrane Library, CNKI, WanFang, CBM and VIP databases for the period 1989 to 2022. We conducted random effects inverse variance on the meta-analysis and used the I² statistic to assess heterogeneity. Result: We selected 44 of the 518 studies we retrieved, 7 being appropriate for meta-analysis. 6,045 individuals were involved in total. Both types of older diabetic patients with hypoglycemia performed considerably worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized mean difference, 0.19; 95% CI, 0.29-0.09). Additionally, we found that older type-2 diabetes patients with hypoglycemia had significantly poorer psychomotor function than those without hypoglycemia (standardized mean difference, 0.51; 95% CI, 0.38-0.63).

PMID:37884125 | DOI:10.1016/j.ando.2023.10.006

Am J Cardiol. 2023 Oct 24:S0002-9149(23)01209-2. doi: 10.1016/j.amjcard.2023.10.059. Online ahead of print.

ABSTRACT

We aimed to assess the overall clinical impact of cardiac myosin inhibitors in hypertrophic cardiomyopathy (HCM). We performed a meta-analysis of published trials assessing the effect of cardiac myosin inhibitors (Mavacamten and Aficamten) on resting and Valsalva LVOT gradients and functional capacity in symptomatic HCM. The co-primary outcomes were mean percent change (mean difference, MD) from baseline in resting LVOT gradient and Valsalva LVOT gradient, as well as proportion of patients achieving NYHA Class improvement ≥ 1. Secondary outcomes included mean percent change from baseline NT ProBNP, Troponin I, and left ventricular ejection fraction (LVEF). Four studies (all randomized-control trials, including 3 Mavacamten-focused and 1 Aficamten-focused trials) involving 463 patients were included in the meta-analysis. Compared to placebo, the cardiac myosin inhibitor group demonstrated statistically significant differences in baseline percent change in mean resting LVOT gradient (MD -62.48, CI -65.44, -59.51, p <0.00001) and Valsalva LVOT gradient (MD -54.21, CI -66.05, -42.36, p <0.00001), as well as proportion of patients achieving NYHA Class improvement ≥ 1 (OR 3.43, CI 1.90, 6.20, p <0.0001). Regarding secondary outcomes, the intervention group demonstrated statistically significant reductions in mean percent change from baseline in NT-proBNP (MD -69.41, CI -87.06, -51.75, p < 0.00001), Troponin I (MD, -44.19, CI -50.59, -37.78, p < 0.00001), and LVEF (MD -6.31, CI -10.35, -2.27, p = 0.002). In conclusion, cardiac myosin inhibitors may confer clinical and symptomatic benefits in symptomatic HCM, at the possible expense of LVEF. Further trials with large sample sizes are needed to confirm our findings.

PMID:37884110 | DOI:10.1016/j.amjcard.2023.10.059

Clin Biochem. 2023 Oct 24:110680. doi: 10.1016/j.clinbiochem.2023.110680. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aβ42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

METHODS: 900 plasma specimens from male and female participants aged 3-79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aβ42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression.

RESULTS: For discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aβ42/40: 3-<55y = 0.053-0.098, 55-<80y = 0.040-0.090; p-tau-181: 3-<12y = 1.4-5.6 pg/ml, 12-<60y = 0.8-3.1 pg/ml, 60-<80y = 0.9-4.0 pg/ml; NfL: 3-<40y = 2.6-11.3 pg/ml, 40-<60y = 4.6-17.7 pg/ml, 60-<80y = 8.1-47.1 pg/ml; GFAP; 3-<10y = 47.0-226 pg/ml, 10-<60y = 21.2-91.9 pg/ml, 60-<80y = 40.7-228 pg/ml. Continuous RIs produced smooth centile curves across the age range, from which point estimates for each year of age were calculated.

CONCLUSIONS: Discrete and continuous RIs for neurological plasma biomarkers will help refine normative cut-offs across the lifespan and improve the precision of interpretating biomarker levels. Continuous RIs are recommended for use in age groups, such as pediatrics and older adults, that experience rapid concentration changes by age.

PMID:37884086 | DOI:10.1016/j.clinbiochem.2023.110680

J Neurosci Methods. 2023 Oct 24:109991. doi: 10.1016/j.jneumeth.2023.109991. Online ahead of print.

ABSTRACT

BACKGROUND: Mixed-effects models are the current standard for the analysis of behavioral studies in psycholinguistics and related fields, given their ability to simultaneously model crossed random effects for subjects and items. However, they are hardly applied in neuroimaging and psychophysiology, where the use of mass univariate analyses in combination with permutation testing would be too computationally demanding to be practicable with mixed models.

NEW METHOD: Here, we propose and validate an analytical strategy that enables the use of linear mixed models (LMM) with crossed random intercepts in mass univariate analyses of EEG data (lmeEEG). It avoids the unfeasible computational costs that would arise from massive permutation testing with LMM using a simple solution: removing random-effects contributions from EEG data and performing mass univariate linear analysis and permutations on the obtained marginal EEG.

RESULTS: lmeEEG showed excellent performance properties in terms of power and false positive rate.

COMPARISON WITH EXISTING METHODS: lmeEEG overcomes the computational costs of standard available approaches (our method was indeed more than 300 times faster).

CONCLUSIONS: lmeEEG allows researchers to use mixed models with EEG mass univariate analyses. Thanks to the possibility offered by the method described here, we anticipate that LMM will become increasingly important in neuroscience. Data and codes are available at osf.io/kw87a. The codes and a tutorial are also available at github.com/antovis86/lmeEEG.

PMID:37884082 | DOI:10.1016/j.jneumeth.2023.109991

Environ Res. 2023 Oct 24:117491. doi: 10.1016/j.envres.2023.117491. Online ahead of print.

ABSTRACT

Seasonal variations in cardiorespiratory diseases may be influenced by air pollution and meteorological factors. This work aims to highlight the relevance of a complete seasonal characterization of pollutant-meteorological factors and cardio-respiratory mortality in Portugal and the relationships between health outcomes and environmental risk factors. To this end, air pollution and meteorological variables along with health outcomes were analyzed at national level and on a monthly basis for the period 2011-2020. It was found that cardiorespiratory mortality rates during winter were 44% higher than during the summer. Furthermore, particulate matter with aerodynamic diameters of 10 and 2.5 μm (μm) or smaller (PM₁₀ and PM_2.5), carbon monoxide (CO) and nitrogen dioxide (NO₂) showed a seasonal variability, with the highest concentrations during winter while ozone (O₃) presented higher concentrations during spring and summer. PM₁₀, PM_2.5 and NO₂, showed a positive correlation between seasons, indicating similar patterns of behavior. Canonical correlation analysis (CCA) applied to pollutant-meteorological and cardiorespiratory mortality data indicates a strong linear correlation between pollutant-meteorological factors and health outcomes. The first canonical correlation was 0.889, and the second was 0.545, both statistically significant (p-value < 0.001). The CCA results suggest that there is a strong association between near-surface temperature, relative humidity, PM₁₀, PM_2.5, CO and NO₂ and health outcomes. The results of this study provide important information of the seasonal variability of air pollutants and meteorological factors in Portugal and their associations with cardiorespiratory mortality.

PMID:37884072 | DOI:10.1016/j.envres.2023.117491

Diabetes Res Clin Pract. 2023 Oct 24:110972. doi: 10.1016/j.diabres.2023.110972. Online ahead of print.

ABSTRACT

AIMS: To investigate the association between organic food consumption and the incidence of type 2 diabetes mellitus.

METHODS: Among 41,286 cohort participants, aged 50-65 years, organic food consumption of vegetables, fruits, dairy products, eggs, meat, and cereal products, was summarized into an organic food score evaluated as never, low, medium and high consumption and as continuous intake. During follow-up, 4,843 cases were identified in the National Diabetes Register. Organic food consumption was associated to the disease incidence in Cox regression models.

RESULTS: Organic food consumption was linearly associated with a lower incidence of type 2 diabetes mellitus (Women, HR: 0.94, 95% CI: 0.89-1.00, Men, HR: 0.95, 95% CI: 0.90-1.00). Organic food consumption frequency, compared to never consumption, showed HRs below 1.00 for both women (medium intake HR: 0.96, 95% CI: 0.84-1.10, high intake HR: 0.88, 95% CI: 0.74-1.05) and men (low intake, HR: 0.95, 95% CI: 0.85-1.05, medium intake, HR: 0.92, 95% CI: 0.83-1.03, high intake, HR: 0.89, 95% CI: 0.75-1.05) but were not statistically significant. Similar patterns were observed with consumption of the specific organic food groups for women, but not for men.

CONCLUSIONS: Organic food consumption was associated with a suggested lower incidence of type 2 diabetes mellitus.

PMID:37884066 | DOI:10.1016/j.diabres.2023.110972

Ann Med. 2023;55(2):2272711. doi: 10.1080/07853890.2023.2272711. Epub 2023 Oct 26.

ABSTRACT

Objective: To realize the changes in pulmonary hypertension (PH) patients’ right ventricular function.Methods: A total number of 74 patients with PH were included, and the parameters of standard echocardiographic were measured as well as the strain of peak longitudinal of each segment during the systole of the right ventricle to calculate the global longitudinal strain (LS) during systole of the right ventricular free wall.Results: ① As pulmonary arterial pressure increased, the right ventricular area gradually increased, and the case group showed the decreased right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and tricuspid annular peak systolic velocity (S’) (p < 0.05). They, RVFAC, and TAPSE depicted significant differences that were statistical (p < 0.05) from the other groups. ② With increasing pulmonary arterial pressure, the right ventricular free wall’s LS gradually reduced (p < 0.05).Conclusion: ① LS right ventricular free wall is useful in detecting changes in right ventricular systolic function early on with greater sensitivity than RVFAC, TAPSE, and S’. In addition, increased right ventricular pressure loading can result in a subsequent impairment of right ventricular myocardial mechanics. ② As right ventricular pressure loading increases, right ventricular strain decreases. ③ In mild PH, the right ventricular free wall’s. LS is more sensitive than standard measures in spotting early alterations in myocardial mechanics.

PMID:37883811 | DOI:10.1080/07853890.2023.2272711