Interaction Test Research Articles

Prediction of Lung Adenocarcinoma Driver Genes Through Protein-Protein Interaction Networks Utilizing GenePlexus.

Lung adenocarcinoma, a subtype of lung cancer, is produced by uncontrolled proliferation of somatic cells affected by some tumorigenic factors. The origin of this disease can be attributed to the concept of "cancer driver," which links the occurrence of tumor with specific changes in some key genes. These key genes can be identified at various molecular levels. Our innovative method uses a groundbreaking computing technology called GenePlexus to mine new genes related to lung adenocarcinoma. Initially, a vast network was synthesized from protein-protein interactions. Utilizing GenePlexus, we traversed paths interlinking aberrant genes across different layers and pinpointed emerging candidate genes situated on these trajectories. Finally, the candidate genes that were obtained underwent a series of filtering processes, including a permutation test, interaction test, and enrichment test. Compared with the shortest path method, GenePlexus has identified previously neglected genes involved in lung adenocarcinoma. For example, genes such as EGR2, EPHA3, FGFR4, HOXB1, and HEY1 play key roles at multiple molecular levels, including methylation, microRNA, mRNA and mutation, which affect tumorigenesis and lung cancer progression. These genes regulate various processes, from gene expression and cell proliferation to drug resistance to therapeutic drugs and the progress of lung adenocarcinoma.

Relationship Between A Body Shape Index and Self-Reported Stress Urinary Incontinence Among US Women: A Cross-Sectional Analysis.

Stress urinary incontinence (SUI) is common among women, but its link with A Body Shape Index (ABSI) is not well understood. This study investigates the association between ABSI and SUI risk in women, exploring variations across different subgroups. Data from National Health and Nutrition Examination Survey (2001-2020) were analyzed. A weighted multivariable logistic regression was performed to examine the relationship between ABSI and SUI risk, calculating odds ratios and 95% confidence intervals. A restricted cubic spline (RCS) analysis was used to assess any nonlinear associations. Subgroup analyses and interaction tests were conducted to explore the influence of factors on the ABSI-SUI relationship. Sensitivity analyses were also performed to ensure the robustness of the findings. The analysis, after adjusting for potential confounders, showed a significant association between ABSI and SUI risk (p < 0.001). The RCS analysis indicated a nonlinear relationship (p for nonlinear = 0.02) with a turning point at an ABSI of 0.081. Subgroup analyses revealed that the association between ABSI and SUI was stronger in women with lower BMI, non-Mexican ethnicity, and those without hypertension (p for interaction < 0.05). Sensitivity analyses confirmed the consistency of these findings, supporting their robustness. Higher ABSI is associated with an increased risk of SUI in US women, particularly in specific subgroups. This suggests that ABSI could be a valuable measure for identifying women at higher risk of SUI.

Higher remnant cholesterol increases the risk of coronary heart disease and diabetes in postmenopausal women

BackgroundPostmenopausal women represent the demographic increasingly susceptible to cardiovascular and metabolic diseases. Elevated levels of remnant cholesterol (RC) have been implicated in atherosclerosis and insulin resistance.MethodsThis study aimed to investigate the relationship between RC and the prevalence of coronary heart disease (CHD), diabetes, and CHD combined with diabetes in a nationally representative sample of US postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Multivariate logistic regression models were employed to evaluate the association between RC and the outcomes of interest. Nonlinear associations were assessed using restricted cubic splines (RCS), and subgroup analyses, along with interaction tests, were performed.ResultsA total of 1611 participants were included in the final analysis. Higher RC levels were significantly associated with increased risks of CHD [OR=1.67, 95%CI (1.02, 2.74)], diabetes [OR=1.77, 95%CI (1.22, 2.58)], and CHD combined with diabetes [OR=2.28, 95%CI (1.17, 4.42)] (all P&amp;lt;0.05). Compared to the lowest RC quartile (Q1), the highest quartile (Q4) demonstrated elevated incidences of CHD [OR=1.76, 95%CI (1.04, 2.98)], diabetes [OR=1.81, 95%CI (1.30, 2.53)], and CHD combined with diabetes [OR=3.08, 95%CI (1.29, 7.37)] (all P&amp;lt;0.05). RCS curves indicated a nearly linear relationship between RC and the risks of CHD, diabetes, and CHD combined with diabetes.ConclusionOur study reveals a significant positive correlation between RC levels and the prevalence of CHD, diabetes, and CHD combined with diabetes among postmenopausal women. Understanding these associations could potentially inform targeted prevention and management strategies tailored to this vulnerable population.

Association between atherogenic index of plasma and post-stroke depression: a cross-sectional study

ABSTRACT Background: Few studies have established a link between the atherogenic index of plasma (AIP) and post-stroke depression (PSD). This study aims to further investigate the potential relationship between the AIP and PSD, and to provide references for the prevention and prognosis management of patients with PSD. Methods: A cross-sectional study was conducted using data from participants in the National Health and Nutrition Examination Survey from 2005 to 2018. Inclusion criteria required complete data on the AIP, stroke history, and depression status. Weighted logistic regression models and restricted cubic splines (RCS) were employed to examine the association between the AIP and PSD. By subgroup and interaction analyses, the stability associated with AIP and PSD was assessed between different subgroups. Results: Among the 32,364 participants ultimately enrolled in the study, 482 were diagnosed with PSD. In the weighted multivariate logistic regression adjustment model 3, AIP, as a continuous variable, was positively associated with the risk of PSD [odds ratio (OR) = 1.85, 95% confidence interval (CI): 1.18, 2.91; P = 0.007]. After the quartile classification of AIP, the adjusted model 3 showed that the risk of PSD in group Q4 was significantly higher than that in group Q1 (OR = 1.61, 95%CI:1.10, 2.34; P = 0.006). In the RCS linearity test, AIP was positively associated with the risk of PSD (P non-linear = 0.357). The interaction test demonstrated that AIP only had an interaction with gender (P interaction = 0.031) and not with other variables (P interaction > 0.05). Conclusion: AIP was positively associated with the prevalence of PSD, suggesting that AIP may be a promising predictor of the risk of developing PSD. In addition, the interaction of AIP and gender differences combined to influence the incidence of PSD.

A combined association of alanine aminotransferase, aspartate transaminase and bilirubin with sleep duration in aged 16-85 years (2005-2010).

Sleep is a vital restorative process that plays a pivotal role in maintaining the delicate equilibrium of mental and physical well-being. Both short and long sleep duration are associated with a range of adverse health outcomes. Numerous studies have consistently demonstrated a robust association between sleep duration and liver disease. In this study, we conducted statistical tests and performed subgroup analyses to explore potential variations in this association across different contexts, aiming to elucidate the correlation between ALT, AST, and TB with sleep duration. This cross-sectional investigation utilized datasets from the National Health and Nutrition Examination Survey 2005 to 2010. Multivariate linear regression models were used to examine the linear association between ALT, AST, and TB with sleep duration. Test for interaction is commonly conducted using multivariabte models to assess statistically significant subgroup disparities. Fitted smoothied curves and threshold effect analyses were employed to depict nonlinear relationships. The study enrolled 17,491 participants aged 16 to 85 years who met the inclusion and exclusion criteria, with a mean age of the participants was 45.58 ± 19.94 years. Multivariate linear regression analysis showed a significant positive association between sleep duration and ALT [-0.23 (-0.45, -0.00) 0.0455] and AST[-0.20 (-0.38, -0.01) 0.0338] in Model 3. Using a two-segment linear regression model, we found an U-shaped relationship and significant inflection point between between ALT and AST with sleep duration. The present study unveiled a significant inverse correlation between sleep duration and levels of ALT and AST, while no significant association was observed with TB levels. Furthermore, variations in the optimal sleep duration for liver function recovery were identified across diverse populations, thereby offering valuable healthcare recommendations to public.

The association between weight-adjusted-waist index and psoriasis: A cross-sectional study based on NHANES 2009 to 2014.

Weight-adjusted-waist index (WWI) is an anthropometric indicator of central obesity, which is calculated by dividing the waist circumference (WC) by the squared weight. The purpose of this study was to investigate the association between WWI and psoriasis in adults. Multivariate logistic regression and smoothing curve fitting were used to investigate the relationship between WWI and psoriasis based on data from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014. Subgroup analysis and interaction tests were employed to examine the population-level stability of this connection. There was a positive association between WWI and psoriasis in 15,932 participants > 20 years of age. In the fully adjusted model, each 1-unit increase in WWI was associated with a 14% increase in the risk of developing psoriasis [1.14 (1.01, 1.32)]. Participants in the highest quartile of WWI had a 38% higher risk of developing psoriasis than those in the lowest quartile [1.38 (1.01, 1.94)]. This positive association was more pronounced in males. WWI is positively associated with psoriasis in US adults. Our findings imply that WWI has the potential to improve psoriasis prevention in the general population.

Association between C-reactive protein-triglyceride glucose index and depressive symptoms in American adults: results from the NHANES 2005 to 2010

BackgroundThe novel serum C-reactive protein-triglyceride glucose index (CTI) has been identified as an ideal parameter that integrates inflammation and insulin resistance, which are potential mechanisms underlying depressive symptoms. Our research aimed to investigate the association between CTI and depressive symptoms.MethodsOur cross-sectional investigation utilized data from the National Health and Nutrition Examination Survey conducted between 2005 and 2010. The integrated CTI was calculated as 0.412 × Ln (C-reactive protein) (mg/dL) + Ln [triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The severity of depressive symptoms was evaluated through the continuous Patient Health Questionnaire-9 (PHQ-9) scores, and the categorical definition of depressive symptoms (PHQ-9 score ≥ 10) reflected moderate to severe symptoms. Survey-weighted linear and logistic regression models were conducted to establish the correlation between CTI and PHQ-9 scores, and between CTI and depressive symptoms. Moreover, subgroup analyses, interaction tests, and smoothed curve fitting were performed to scrutinize the steadiness of the results.ResultsA total of 5,954 participants were enrolled in our study, including 477 with depressive symptoms and 5,477 without. The results revealed a significant positive relationship between CTI and PHQ-9 scores (β: 0.40, 95% CI: 0.25,0.55, p < 0.001) and depressive symptoms (OR: 1.30, 95% CI: 1.06,1.61, p = 0.02). Additionally, individuals in the fourth quartile of CTI exhibited a higher likelihood of depressive symptoms than those in the first quartile (PHQ-9 score: β: 0.83, 95% CI: 0.39,1.26, p < 0.001; depressive symptoms: OR: 2.00, 95% CI:1.19,3.36, p = 0.01). Smooth curve fitting and subgroup analyses consistently demonstrated the positive relationship.ConclusionsElevated CTI was correlated with a higher risk of depressive symptoms, underscoring CTI as a potential clinical indicator for identifying and stratifying depressive symptoms.Clinical trial numberNot applicable.

Association between the composite dietary antioxidant index and all-cause mortality in individuals with osteoarthritis via NHANES data

The impact of antioxidant intake on the prognosis of osteoarthritis (OA) patients remains unclear. The aim of this study was to investigate the relationship between the composite dietary antioxidant index (CDAI) and all-cause mortality in OA patients. A total of 35,590 participants with OA from the National Health and Nutrition Examination Survey (1999–2020) were included in this study. We analysed the associations between the CDAI and the risk of all-cause mortality in OA patients via a multivariate Cox regression model. Restricted cubic spline regression was used to investigate the dose–response associations between the CDAI and mortality. We also conducted stratified analyses and interaction tests to explore underlying effect modification. After multivariable adjustment, each one-unit increase in the CDAI was associated with a 2.1% reduction in the risk of mortality. Compared with those in the low CDAI group, the multivariate-adjusted hazard ratios (HRs) for mortality for patients in the high CDAI group were lower [Model 1 (HR 0.648, 95% CI 0.557–0.754), Model 2 (HR 0.739, 95% CI 0.627–0.871), and Model 3 (HR 0.788, 95% CI 0.661–0.941)]. We observed a negative nonlinear relationship between the CDAI and all-cause mortality (P < 0.05). Stratification analyses and interaction tests confirmed the robustness of the results. We found a negative nonlinear relationship between the CDAI and all-cause mortality in OA patients. A higher CDAI was significantly associated with a lower risk of mortality. These results highlight the potential advantages of monitoring and evaluating the CDAI status in preventing mortality among patients with OA.

Maternal exposure to buprenorphine, but not methadone, during pregnancy reduces social play behavior across two generations of offspring.

The prevalence of newborns exposed to medications for opioid use disorder (MOUD), such as methadone or buprenorphine, during pregnancy is increasing. The opioid system plays a crucial role in regulating and shaping social behavior, and children prenatally exposed to opioids face an increased risk of developing behavioral problems. However, the impact of prenatal exposure to MOUD on offspring's social behavior during adolescence and adulthood, as well as potential intergenerational effects, remains largely unexplored. Our study employed a translationally relevant animal model to investigate how maternal (F0) exposure to MOUD during pregnancy affects social behavior in young and adult rats across the first (F1) and second (F2) generation of offspring. Female Sprague-Dawley rats were implanted with an osmotic minipump delivering methadone (10mg/kg/day), buprenorphine (1mg/kg/day), or sterile water, prior to mating with drug-naïve males. Adult F1 females were mated with treatment-matched F1 males to generate F2 offspring. We assessed social play behavior in juvenile offspring, and social interaction behavior in a three-chamber social interaction test in young adults of the F1 and F2 generations. Maternal exposure to buprenorphine, but not methadone, during pregnancy reduced social play behavior in both F1 and F2 offspring, expressed by a reduced number of pounces and pins, which are the two most characteristic parameters of social play in rats. Adult social interactions were unaffected by prenatal MOUD exposure across both generations. Maternal exposure to buprenorphine during pregnancy may have adverse effects on social play behavior across two generations of offspring.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and sarcopenia based on NHANES

The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol, or NHHR, has garnered increased attention because of its connection to metabolic diseases. It is yet unknown, nevertheless, how NHHR and sarcopenia relate to one another in the US population. Examining the relationship between NHHR and the prevalence of sarcopenia in the US population is the main goal of this study. Utilizing information gathered from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, a study was conducted to look at the connection between NHHR and sarcopenia in the US population. The individuals’ baseline features were categorized based on whether or not sarcopenia was present. We used subgroup analysis, restricted cubic spline (RCS), and weighted logistic regression to examine the connection between NHHR and sarcopenia prevalence. Sensitivity analysis was used to confirm that the study’s findings were reliable and consistent. R (version 4.2.3) was used for all analyses, and P < 0.05 was used to indicate statistical significance. There were 10,087 individuals in all, 9,187 of whom were not sarcopenic and 900 of whom were. Sarcopenic patients were generally older, predominantly of Mexican American descent, and had lower educational levels. These patients were generally less active and exhibited higher levels of total cholesterol and BMI, along with lower HDL levels. Following complete adjustment, the weighted logistic regression model indicated that a 7% increased risk of sarcopenia was linked to every unit rise in NHHR (OR = 1.07, 95% CI = 1.02–1.13). An inflection point was identified at 2.90 by RCS analysis, which revealed a nonlinear association between NHHR and the prevalence of sarcopenia. Subgroup analysis showed that, regardless of the demographic group, there was a continuous positive correlation between NHHR and the prevalence of sarcopenia. The results of the interaction test provided evidence in favor of NHHR functioning as a stand-alone risk factor for sarcopenia. Our research suggests that a higher prevalence of sarcopenia may be linked to an increase in NHHR. Consequently, NHHR may function as a separate risk factor for sarcopenia.

The relationship between visual impairment and insomnia among people middle-aged and older in India

The correlation between insomnia and visual impairment has not been extensively studied. This study aims to investigate this relationship among individuals aged 45 and above in India. This investigation utilized data from the 2017–2018 Wave 1 of the Longitudinal Aging Study in India (LASI). Visual impairment was self-reported, including presbyopia, cataracts, glaucoma, myopia, and hyperopia. Insomnia symptoms were determined by at least one of the following: difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), or early morning awakening (EMA) occurring three or more times per week. Analytical methods involved multivariate logistic regression, subgroup analyses, and interaction tests to interpret the data. In our cohort of 65,840 participants, 29.6% reporting insomnia symptoms demonstrated a higher risk for visual impairment. There was a significant association between visual impairment and increased risk of insomnia symptoms after adjustment for confounders. Furthermore, age in the relationship between insomnia and cataracts, sex in the relationship between insomnia and myopia, and age, sex, and smoking status in the relationship between insomnia and hyperopia, was found to have a significant interaction effect, respectively. Visual impairment was significantly associated with a higher incidence of insomnia among middle-aged and older adults in India. These findings underscore the importance of timely interventions to improve sleep quality and overall well-being in visually impaired populations.

Influence of extreme light/dark cycles on monoamine levels, physiological indices, and emotional behaviors in rats

ABSTRACT Aberrant light/dark (LD) cycles are prevalent in modern society due to electric light usage, leading to mood disorders from circadian disruption or misalignment. However, research on the physiological and behavioral effects of LD variations on brain neurotransmitters is limited. We investigated the effects of extreme LD cycles on body weight (BW), core body temperature (Tcore), locomotor activity (ACT), emotional behaviors, and monoamine levels (noradrenaline [NA], dopamine [DA], and serotonin [5-HT]) in male Wistar rats that were exposed to 1 month of either long light phase (20 L:4D), long dark phase (4 L:20D), or normal (12 L:12D) LD cycles. The 20 L:4D rats exhibited blunted rhythms, with decreased amplitude and advanced/delayed acrophase in Tcore and ACT, alongside increased BW. The 4 L:20D rats showed circadian misalignment, with increased/decreased amplitude in Tcore or ACT and delayed acrophase in Tcore and ACT, also gaining BW. In the 20 L:4D group, NA and 5-HT levels decreased in the suprachiasmatic nucleus and amygdala, respectively, while the 4 L:20D group had increased DA and 5-HT levels in the caudate putamen and dorsomedial hypothalamus, respectively. Open field and social interaction tests indicated anxiety-like behaviors in both test groups. Overall, each extreme LD cycle affected Tcore, ACT amplitude, acrophase, and monoamine levels differently, inducing anxiogenic responses.

The modified elevated gap interaction test: a novel paradigm to assess social preference.

Social deficits play a role in numerous psychiatric, neurological and neurodevelopmental disorders. Relating complex behaviour, such as social interaction, to brain activity remains one of the biggest goals and challenges in neuroscience. Availability of standardized tests that assess social preference is however, limited. Here, we present a novel behavioural paradigm that we developed to measure social behaviour, the modified elevated gap interaction test (MEGIT). In this test, animals are placed on one of two elevated platforms separated by a gap, in which they can engage in whisker interaction with either a conspecific or an object. This allows quantification of social preference in real interaction rather than just proximity and forms an ideal setup for social behaviour-related neuronal recordings. We provide a detailed description of the paradigm and its highly reliable, deep-learning based analysis, and show results obtained from wild-type animals as well as mouse models for disorders characterized by either hyposocial (autism spectrum disorder; ASD) or hypersocial (Williams Beuren syndrome; WBS) behaviour. Wild-type animals show a clear social preference. This preference is significantly smaller in an ASD mouse model, whereas it is larger in WBS mice. The results indicate that MEGIT is a sensitive and reliable test for detecting social phenotypes.

Genetic machinery which accompanies metaplasticity operates differentially in experimental model of autism

AbstractThe present study investigated metaplasticity‐related mRNA expressions in valproic acid (VPA)‐rats, focusing on the PI3K/AKT pathway. Wistar dams were treated with a single intraperitoneal injection of 600 mg/kg VPA or saline on embryonic day E12.5 or an equal volume of saline solution. Three behavioral tests were conducted on these males' offspring: grid‐walking test, negative geotaxis test, and three‐chamber social interaction test. Metaplasticity was induced in 60‐day‐old male progeny by giving high‐frequency stimulation for 5 minutes following low‐frequency stimulation to the perforant pathway. For the baseline stimulation protocol (n = 6), stimulation was delivered to the dentate gyrus at the previously determined stimulation intensity (0.33 Hz 0.175 msec 30 s) for 75 min. The percent change of slope of field excitatory postsynaptic potential (fEPSP) and amplitude of population spike were calculated 55–60 min after induction protocol. The mRNA levels of PI3K, PTEN, AKT, GSK‐3β, and MAPT were measured in the hippocampus by using quantitative rt‐PCR. We found that offspring of VPA‐treated rats showed significantly impaired sensorimotor coordination, decreased sociability, impaired preference for social novelty, and reduced input–output curve of fEPSP slope, compared to control animals. Despite a similar metaplastic response, mRNA levels of genes of interest were similar but considerably down‐regulated after induction in offspring of VPA‐treated dams. Our study provides evidence that the induced expression of autism‐related genes has evolved to enable an adaptation mechanism during metaplastic control of long‐term potentiation.

Initial attempt: Design and application of microorganism-material interaction test on On-orbit space microgravity conditions

Initial attempt: Design and application of microorganism-material interaction test on On-orbit space microgravity conditions

Modified neuroimmune processes and emotional behaviour in weaned and late adolescent male and female mice born via caesarean section

Elective and emergency Caesarean section (C-section) procedures are on the rise, exceeding the recommended guidelines by the World Health Organization. Higher morbidities and long-term health conditions are correlated to C-section deliveries, including neurodevelopmental disorders. During C-section delivery, newborns are not exposed to the vaginal commensal flora, which impedes the early establishment of the gut microbiota. The latter is essential for adequate neuro-immune processes to take place during infancy. In this study, we used a validated model of mice born by C-section (CSD), which mimics clinical observations of dysregulated gut microbiota. Animals were either born naturally or by CSD, before being adopted by dams who underwent delivery within the 12 preceding hours. Behavioural analyses were conducted at post-natal day (PND) 21 and 55. Our results indicate that animals born by C-section present significantly higher body weight in late (PND40-P53) but not early adolescence (PND21-P27), compared to animals born by vaginal delivery (VD). Male animals delivered by C-section presented significantly lower exploration time of the novel arm in the Y Maze test at PND55. However, at PND21, abnormal social interaction was witnessed in male and female animals born by CSD, with significantly decreased time spent interacting during the social interaction test. At both PND21 and PND55, animals from both sexes born by C-section presented significantly decreased time spent in the open arm of the Elevated Plus Maze test, compared to control animals. We then measured the expression of genes associated to neuroimmune interactions (microglia phenotype), inflammatory mediators and lipids in several brain structures of VD and CSD mice at PND21 and PND55. At weaning, animals born by CSD presented altered microglia, inflammatory and lipid metabolism signatures, with increased expression of Cd36, Csf1r and Tnfα in different brain regions of males, but not in females. At PND64, Csf1r, Tmem119 as well as C3ar1 were significantly increased in males born by C-section, but not in females. In males born by vaginal delivery, the expression of Cd36 at PND64 was correlated to anxiety at PND55, whilst a correlation between the expression of Clec7a and the number of head dippings in the elevated plus maze was also noted in males born by CSD. Altogether, our study shows altered emotional behaviour in animals delivered by CSD, which is likely explained by underlying neuro-inflammatory processes in different brain regions. Our work further supports the long-term consequences of CSD on brain health.

Association of weight-adjusted waist index (WWI) and a body shape index (ABSI) with serum neurofilament light chain levels in a national study of U.S. adults

ObjectiveThis study explored how the weight-adjusted waist index (WWI) and a body shape index (ABSI) are related to serum neurofilament light chain (sNfL) levels among U.S. adults. We aimed to evaluate sNfL, which plays key roles in neuronal injury in neurological diseases, given its understudied connection to obesity.MethodsWe used cross-sectional data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) of people with complete information on the weight-adjusted waist index (WWI), a body shape index (ABSI), and serum neurofilament light chain (sNfL). Multiple linear regression analysis allowed us to investigate the separate connections among the WWI, ABSI, and sNfL. Moreover, interaction testing and subgroup analysis were performed to improve the general validity of our results. To assess any nonlinear correlations, we also performed threshold effect analysis and smoothed curve fitting.ResultsWWI and ABSI were positively linked with sNfL (WWI: β = 0.05, 95% CI 0.01–0.09; ABSI: β = 1.65, 95% CI 3.53–13.72). There was no clear reliance on this association according to subgroup analysis and interaction tests. Smoothed curve fitting and saturation effects also demonstrated nonlinear associations between WWI and ABSI and sNfL, with inflection points of 10.38 and 0.38, respectively.ConclusionIn the adult American population, while the WWI and ABSI are linearly positively correlated with serum neurofilament light protein (sNfL), the effect size is greater for the ABSI. This correlation provides fresh evidence connecting obesity to neurological conditions, deepening our comprehension of the extensive health impacts associated with obesity.Level of Evidence Level I, experimental studies.

Model-based optimal randomization procedure for treatment-covariate interaction tests.

Linear models are extensively used in the analysis of clinical trials. However, required model assumptions (e.g. homoscedasticity) may not be satisfied in practice, resulting in low power of treatment-covariate interaction tests. Various interaction tests have been proposed to improve the efficiency of detecting differences in treatment-covariate interactions. Aiming to fundamentally improve the power of treatment-covariate interaction tests, for heteroscedasticity of treatment responses, we develop a model-based optimal randomization procedure, referred to as model-based Neyman allocation (MNA) in this article. Thederived limiting allocation proportion indicates that the procedure MNA is a generalization of response-adaptive randomization targeting Neyman allocation (RAR-NA). In theory, we demonstrate that the procedure MNA can maximize the power of treatment-covariate interaction tests. The issue of sample size estimation is also addressed. Simulation studies show, in the framework of the heteroscedastic linear model, compared with Pocock and Simon's minimization method and RAR-NA, the procedure MNA has the greatest power of tests for both systematic effects and treatment-covariate interactions, even under model misspecification. Finally, the efficiency of the procedure MNA is illustrated by a hypothetical case study based on a real schizophrenia clinical trial.

The receptor MIK2 interacts with the kinase RKS1 to control quantitative disease resistance to Xanthomonas campestris.

Molecular mechanisms underlying qualitative resistance have been intensively studied. In contrast, although quantitative disease resistance (QDR) is a common, durable and broad-spectrum form of immune responses in plants, only a few related functional analyses have been reported. The atypical kinase Resistance related KinaSe1 (RKS1) is a major regulator of QDR to the bacterial pathogen Xanthomonas campestris (Xcc) and is positioned in a robust protein-protein decentralized network in Arabidopsis (Arabidopsis thaliana). Among the putative interactors of RKS1 found by yeast two-hybrid screening, we identified the receptor-like kinase MDIS1-Interacting Receptor-like Kinase 2 (MIK2). Here, using multiple complementary strategies including protein-protein interaction tests, mutant analysis, and network reconstruction, we report that MIK2 is a component of RKS1--mediated QDR to Xcc. First, by co-localization experiments, co-immunoprecipitation (Co-IP), and bimolecular fluorescence complementation (BiFC), we validated the physical interaction between RKS1 and MIK2 at the plasma membrane. Using mik2 mutants, we showed that MIK2 is required for QDR and contributes to resistance to the same level as RKS1. Interestingly, a catalytic mutant of MIK2 interacted with RKS1 but was unable to fully complement the mik2-1 mutant phenotype in response to Xcc. Finally, we investigated the potential role of the MIK2-RKS1 complex as a scaffolding component for the coordination of perception events by constructing a RKS1-MIK2 centered protein-protein interaction network. Eight mutants corresponding to seven RKs in this network showed a strong alteration in QDR to Xcc. Our findings provide insights into the molecular mechanisms underlying the perception events involved in QDR to Xcc.

Association between serum apolipoprotein B and depression: A cross-sectional and Mendelian randomization analysis study

BackgroundDepression is a pervasive mental illness that has a significant impact on public health globally. This study aimed to identify risk factors for depression and elucidate their causal relationships. MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) and Genome-Wide Association Studies (GWAS). Serum ApoB was log-transformed and further divided into 4 groups. Multifactorial logistic regression analysis was used to assess the relationship between serum ApoB and depression. Subgroup analyses and interaction tests were used to observe the stability of the association between them. Smooth curve fitting was used to investigate nonlinear correlations. The causal effect of serum ApoB on depression was assessed using Mendelian randomization (MR) analysis. ResultsA total of 6531 participated in the study. After adjusting for all covariates, serum ApoB levels were positively associated with depression after adjustment for all covariates (OR = 1.40, 95 % CI = 1.06–1.84; P = 0.0176). Unfortunately, there was no significant causal relationship between serum ApoB and depression (OR = 0.9985,95 % CI = 0.9962–1.0008; P = 0.1923). Sensitivity analysis verified the reliability of the results. ConclusionsSerum ApoB was positively associated with an increased risk of depression, but MR analysis did not show a genetic causal relationship between ApoB and depression. Based on the results of the current study, no indication maintaining high levels of ApoB contributes to the management of depression. LimitationsThe main limitation of this study is the inconsistency of the cross-sectional study and the MR population.