BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.
METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.
RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.
CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

UNASSIGNED: Previous studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles.
UNASSIGNED: This study involved 8,516 adult participants (aged 18-74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index.
UNASSIGNED: In this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50-74 (except for hypertriglyceridemia, where the highest risk was among men aged 50-74 years), during winter/spring or under low/middle ultraviolet index environments.
UNASSIGNED: Nonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D <20 ng/ml], a positive association of serum vitamin D levels with the risk for dyslipidemia was observed, which needs a further.

Over the years, obesity has become more commonplace and has had a substantial impact on several medical specialties, including reproductive medicine. The potential correlation between the visceral adiposity index (VAI) and infertility has yet to be determined. Women between the ages of 18 and 45 were included in this cross-sectional study, which was conducted as part of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2020. Three tertiles were used to group VAI levels. Subgroup analysis and weighted binary logistic regression were employed to investigate the independent relationship between VAI and infertility. Smooth curve fitting was used to explore nonlinear relationships. This cross-sectional study followed the criteria of the STROBE guidelines. Of the 1231 participants, 127 were infertile women aged 18-45 years. A higher VAI was associated with a higher prevalence of infertility (OR = 1.22, 95% CI:1.03-1.45), which remained consistent across all subgroups (p > 0.05 for all interactions). We demonstrated a positive nonlinear association between VAI and infertility using a smooth curve fit. A higher visceral adiposity index level is positively correlated with a higher incidence of infertility among women in the United States. Women who are infertile can be identified using the visceral obesity index, and controlling visceral obesity may help lower the chances of becoming infertile.

Mendelian randomisation (MR) is an established technique in epidemiological investigation, using the principle of random allocation of genetic variants at conception to estimate the causal linear effect of an exposure on an outcome. Extensions to this technique include non-linear approaches that allow for differential effects of the exposure on the outcome depending on the level of the exposure. A widely used non-linear method is the residual approach, which estimates the causal effect within different strata of the non-genetically predicted exposure (i.e. the \"residual\" exposure). These \"local\" causal estimates are then used to make inferences about non-linear effects. Recent work has identified that this method can lead to estimates that are seriously biased, and a new method-the doubly-ranked method-has been introduced as a possibly more robust approach. In this paper, we perform negative control outcome analyses in the MR context. These are analyses with outcomes onto which the exposure should have no predicted causal effect. Using both methods we find clearly biased estimates in certain situations. We additionally examined a situation for which there are robust randomised controlled trial estimates of effects-that of low-density lipoprotein cholesterol (LDL-C) reduction onto myocardial infarction, where randomised trials have provided strong evidence of the shape of the relationship. The doubly-ranked method did not identify the same shape as the trial data, and for LDL-C and other lipids they generated some highly implausible findings. Therefore, we suggest there should be extensive simulation and empirical methodological examination of performance of both methods for NLMR under different conditions before further use of these methods. In the interim, use of NLMR methods needs justification, and a number of sanity checks (such as analysis of negative and positive control outcomes, sensitivity analyses excluding removal of strata at the extremes of the distribution, examination of biological plausibility and triangulation of results) should be performed.

Non-linear and dynamic systems analysis of human movement has recently become increasingly widespread with the intention of better reflecting how complexity affects the adaptability of motor systems, especially after a stroke. The main objective of this scoping review was to summarize the non-linear measures used in the analysis of kinetic, kinematic, and EMG data of human movement after stroke. PRISMA-ScR guidelines were followed, establishing the eligibility criteria, the population, the concept, and the contextual framework. The examined studies were published between 1 January 2013 and 12 April 2023, in English or Portuguese, and were indexed in the databases selected for this research: PubMed®, Web of Science®, Institute of Electrical and Electronics Engineers®, Science Direct® and Google Scholar®. In total, 14 of the 763 articles met the inclusion criteria. The non-linear measures identified included entropy (n = 11), fractal analysis (n = 1), the short-term local divergence exponent (n = 1), the maximum Floquet multiplier (n = 1), and the Lyapunov exponent (n = 1). These studies focused on different motor tasks: reaching to grasp (n = 2), reaching to point (n = 1), arm tracking (n = 2), elbow flexion (n = 5), elbow extension (n = 1), wrist and finger extension upward (lifting) (n = 1), knee extension (n = 1), and walking (n = 4). When studying the complexity of human movement in chronic post-stroke adults, entropy measures, particularly sample entropy, were preferred. Kinematic assessment was mainly performed using motion capture systems, with a focus on joint angles of the upper limbs.

UNASSIGNED: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.
UNASSIGNED: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.
UNASSIGNED: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.
UNASSIGNED: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.

There is limited research on the association between the alanine aminotransferase to high-density lipoprotein cholesterol ratio (ALT/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD). The purpose of the current research was to look into the connection between the ALT/HDL-C ratio and the risk of NAFLD in lean Chinese individuals. Between January 2010 and December 2014, 11,975 non-obese people participated in this prospective cohort research. The relationship between the ALT/HDL-C ratio and the risk of developing NAFLD was assessed using the Cox proportional-hazards regression model, Cox proportional hazards regression with cubic spline functions and smooth curve fitting, sensitivity analysis, and subgroup analyses. The ALT/HDL-C ratio\'s potential value as a NAFLD prognostic marker was to be evaluated using the receiver operating characteristic curve analysis. A total of 5419 (45.253%) women comprised the research\'s participant population, and the research participants\' average age was 43.278 ± 14.941 years. The ALT/HDL-C ratio was 11.607 (7.973-17.422) at the median (interquartile ranges). 2087 (17.428%) patients had NAFLD diagnoses throughout a median follow-up of 24.967 months. The study\'s findings demonstrated a positive connection between the ALT/AHDL-C ratio and the incident NAFLD (HR = 1.037, 95% CI: 1.031-1.042) when adjusting for relevant factors. The ALT/HDL-C ratio and NAFLD risk had a nonlinear connection, with 12.963 as the ratio\'s inflection point. Effect sizes (HR) were 1.023 (95% CI: 1.017-1.029) and 1.204 (95% CI: 1.171-1.237), respectively, on the right and left sides of the inflection point. The sensitivity analysis also showed how reliable our findings were. According to subgroup analysis, those with BMI < 24 kg/m2 and DBP < 90 mmHg had a stronger correlation between the ALT/HDL-C ratio and NAFLD risk. The current study shows a positive and non-linear connection between the ALT/HDL-C ratio and NAFLD risk in lean Chinese individuals. When the ALT/HDL-C ratio is less than 12.963, it is significantly linked to NAFLD. Therefore, from a therapy standpoint, it is advised to keep the ALT/HDL-C ratio less than the inflection point.

The global concern surrounding the aging population has brought the well-being of older individuals to the forefront of societal attention. Unfortunately, studies focusing on the well-being of older people residing in rural areas are frequently overshadowed by the developmental disparities between rural and urban regions. Thus, this study aims to delve into the non-linear impact of walking accessibility on the subjective well-being of rural older adults. The goal is to gain a comprehensive understanding of this relationship, ultimately contributing to an improved quality of life and health for older adults in rural areas.
In this study, the Random Forest algorithm was employed to explore the non-linear effects of demographic variables, perceived safety, subjective built environment (including perceptions and preferences of the built environment), and walking accessibility on the subjective well-being of older adults.
The findings of this study underscore the pivotal role of walking accessibility in influencing the well-being of older adults, particularly in terms of access to bazaars and health centers, where non-linear and threshold effects are evident. Furthermore, community safety, road conditions, and walking preferences were identified as positive influencers on the well-being of older adults. Well-being trends varied with age, revealing noteworthy non-linear relationships for certain variables.
The insights gained from this study provide crucial theoretical guidance for the development of policies tailored to the unique context of rural aging. By taking into account factors such as walking accessibility, community safety, health support, and social interaction, we can create an improved living environment for rural older adults, ultimately enhancing their happiness and overall quality of life.

BACKGROUND: Most studies had shown a linear relationship between serum albumin (sALB) and the prevalence of diabetic retinopathy (DR). Thus, the purpose of this study is to investigate whether their relationship is non-linear.
METHODS: We included 426 patients with type 2 diabetes who were hospitalized in Guangdong Provincial People\'s Hospital from December 2017 to November 2018. The outcome was the prevalence of DR. A two-piecewise logistics regression model was performed to identify the non-linear relationship between sALB and the prevalence of DR. The inflection point was calculated to determine the saturation effect through the maximum likelihood ratio and a recursive algorithm.
RESULTS: DR was diagnosed in 167 of 426 type 2 diabetic patients. The relationship between sALB and DR was nonlinear. When sALB was less than 38.10 g/L, a significant negative association was observed (OR = 0.82; 95% CI, 0.72-0.94; P = 0.0037), while no significant association was observed when sALB was greater than 38.10 g/L (OR = 1.12; 95% CI, 0.92-1.35; P = 0.2637).
CONCLUSIONS: The relationship between sALB and the prevalence of DR is non-linear. sALB is negatively associated with the prevalence of DR when sALB is less than 38.10 g/L. Our findings need to be confirmed by further prospective research.

This study aimed to investigate the relationship between platelet count (PC) and mortality in patients with hemorrhagic stroke (HS). The research reviewed data from 10,466 patients hospitalized in 208 hospitals in the United States from January 1, 2014, to December 31, 2015. Of these, 3262 HS patients were included in the primary analysis for those admitted to the intensive care unit (ICU). The average age of these patients was 67.05 years, with 52.79% being male. The median PC was (221.67 ± 73.78) × 109/L. Multivariate logistic regression analysis revealed that PC was a protective factor for mortality in HS patients (OR = 0.98, 95% CI 0.97-1.00, P < 0.05). Additionally, a non-linear association between PC and mortality in HS patients was found using a generalized additive model (GAM) and smooth curve fitting (penalty spline method). For the first time, a recursive algorithm identified the inflection point of platelet count as 194 × 109/L. On the left side of the inflection point, for every increase of 10 units in platelet count, the mortality rate of HS patients decreases by 10%. The study demonstrates a non-linear relationship between PC and the risk of mortality in HS patients. A platelet counts higher than the inflection point (194 × 109/L) may be a significant intervention to reduce mortality in HS patients.