Wald Test Research Articles

Endogenous retroelement expression in the gut microenvironment of people living with HIV-1

Endogenous retroelements (EREs), including human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), comprise almost half of the human genome. Our previous studies of the interferome in the gut suggest potential mechanisms regarding how IFNb may drive HIV-1 gut pathogenesis. As ERE activity is suggested to partake in type 1 immune responses and is incredibly sensitive to viral infections, we sought to elucidate underlying interactions between ERE expression and gut dynamics in people living with HIV-1 (PLWH). ERE expression profiles from bulk RNA sequencing of colon biopsies and PBMC were compared between a cohort of PLWH not on antiretroviral therapy (ART) and uninfected controls. 59 EREs were differentially expressed in the colon of PLWH when compared to uninfected controls (padj <0.05 and FC≤-1 or≥1) [Wald's Test]. Of these 59, 12 EREs were downregulated in PLWH and 47 were upregulated. Colon expression of the ERE loci LTR19_12p13.31 and L1FLnI_1q23.1s showed significant correlations with certain gut immune cell subset frequencies in the colon. Furthermore L1FLnI_1q23.1s showed a significant upregulation in peripheral blood mononuclear cells (PBMCs) of PLWH when compared to uninfected controls suggesting a common mechanism of differential ERE expression in the colon and PBMC. ERE activity has been largely understudied in genomic characterizations of human pathologies. We show that the activity of certain EREs in the colon of PLWH is deregulated, supporting our hypotheses that their underlying activity could function as (bio)markers and potential mediators of pathogenesis in HIV-1 reservoirs. US NIH grants NCI CA260691 (DFN) and NIAID UM1AI164559 (DFN).

Exploring household food security through institutional factors: A statistical and mathematical analysis

Achieving household food security is the tumbling issue of the century. This article explores the factors affecting household food security and solutions by utilizing a synergy of statistical and mathematical models. The methodology section is divided into two portions namely sociological and mathematical methods. Sociologically, 379 household heads were interviewed through structured questions and further analyzed in terms of descriptive and binary logistic regression. The study found that 4 independent variables (poverty, poor governance, militancy, and social stratification) showed a significant association (P = 0.000) to explain variations in the dependent variable (household FS). The Omnibus test value (χ2= 102.386; P = 0.000) demonstrated that the test for the entire model against constant was statistically significant. Therefore, the set of predictor variables could better distinguish the variation in household FS. The Nagelkerke’s R Square (R2 = .333) helps to interpret that the prediction variable and the group variables had a strong relationship. Moreover, 23% to 33% variation in FS was explained by the grouping variables (Cox and Snell R2 = 0.237 and Nagelkerke’s R2 = 0.333). The significant value of Wald test results for each variable confirmed that the grouping variables (poor governance P = 0.004, militancy P = 0.000, social stratification P = 0.021 and poverty P = 0.000) significantly predicted FS at the household level. Mathematically, all the statistics were validated further through the application of spherical fuzzy mathematics (TOPIS and MADM) to explore what factors are affecting household FS. Thus, the study found that F3 (poverty) &gt; F2 (militancy) &gt; F4 (social stratification) &gt; F1 (poor governance) respectively. Thus, it could be concluded from these findings that the prevalence of poverty dysfunctional all the channels of household FS at the macro and micro levels. Therefore, a sound and workable model to eradicate poverty in the study area by ensuring social safety nets for the locals was put forward some of the policy implications for the government are the order of the day.

Bayesian approach to assessing population differences in genetic risk of disease with application to prostate cancer.

Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of genetic risk differences across populations is highly dependent on the GWAS training sample size, the polygenicity (number of causal variants), and genetic distance (FST) between the populations considered. We derive a Wald test for formally assessing the difference in genetic risk across populations, which we show to have calibrated type 1 error rates under a simplified assumption that all SNPs are independent, which we achieve in practise using linkage disequilibrium (LD) pruning. We further provide closed-form expressions for assessing the uncertainty in estimates of relative genetic risk across populations under the special case of an infinitesimal genetic architecture. We suggest that for many complex traits and diseases, particularly those with more polygenic architectures, current GWAS sample sizes are insufficient to detect moderate differences in genetic risk across populations, though more substantial differences in relative genetic risk (relative risk > 1.5) can be detected. We show that conventional approaches that do not account for sampling error from the training sample, such as using a simple t-test, have very high type 1 error rates. When applying our approach to prostate cancer, we demonstrate a higher genetic risk in African Ancestry men, with lower risk in men of European followed by East Asian ancestry.

The overall fractions of coronary heart diseases and depression attributable to multiple dependent psychosocial work factors in Europe.

The literature is nonexistent on the assessment of overall fractions of diseases attributable to multiple dependent psychosocial work factors. The objectives of the study were to calculate the overall fractions of coronary heart diseases (CHD) and depression attributable to multiple dependent psychosocial work factors in 35 European countries. We used already published fractions of CHD and depression attributable to each of the following psychosocial work factors: job strain, effort-reward imbalance, job insecurity, long working hours, and workplace bullying. We took all exposures and their correlations into account to calculate overall attributable fractions. Wald tests were performed to test differences in these overall attributable fractions between genders and between countries. The overall fractions of CHD and depression attributable to all studied psychosocial work factors together were found to be 8.1% [95% CI: 2.0-13.9] and 26.3% [95% CI: 16.2-35.5] respectively in the 35 European countries. There was no difference between genders and between countries. Our study showed that the overall fractions attributable to all studied psychosocial work factors were substantial especially for depression. These overall attributable fractions may be particularly useful to evaluate the burden and costs attributable to psychosocial work factors, and also to inform policies makers at European level.

The Outliers Influence on Adequateness of Classical and Robust Path Analysis

Path analysis is formed from correlation and regression analysis which assumes a normal distribution. This assumption will be disturbed if there are outliers. This research aims to examine the influence of outliers on classical path analysis and robust path analysis. The data used as initial data is secondary data from Badan Pusat Statistik (BPS) publications on Indikator Kesejahteraan Rakyat, Statistik Ketenagakerjaan, Statistik Indonesia, and Survei Sosial Ekonomi Nasional. These data are used to generate data with a simulation scheme for the number of samples or n (20, 30, and 100), percentage of outliers or p (5%, 25% and 45%) and program repetitions or u (25, 50, 75, 100, 500 and 1000). Based on the combination of 3 treatments, the percentage of model adequateness was measured based on the Wald test and then an ANOVA test was carried out with 2-factor factorial design. The percentage of model adequateness of the classical path analysis model is decreasing as the number of samples increasing. In large sample sizes data, the adequateness tends to be different and increases as the percentage of outliers in the sample size data increases. The adequateness of the robust path analysis model is relatively very stable. The robust path analysis is adequate to use on small or large sample data with any percentage of outliers. The percentage of model adequateness being higher at the larger percentage of outliers. The classical path analysis model is influenced by outliers but the robust path analysis model is not influenced by outliers.

Telemedicine-Based Provision of Adolescent Gender-Affirming Medical Care to Promote Equitable Access.

Purpose: To explore transgender and nonbinary (TNB) young adults' (1) interest in receiving gender-affirming medications through telemedicine before age 18 years and (2) willingness to initiate this care with primary care providers (PCPs). Methods: Data were from a survey of TNB young adults who had not received gender-affirming medications before age 18 years. Chi-square and Wald tests identified demographic differences in telemedicine interest and willingness to initiate medications with their PCP as minors. Results: Among 280 respondents, 82.5% indicated interest in telemedicine and 42.0% were willing to initiate medications with their PCP. Black/African American respondents were more likely to indicate interest in telemedicine than White and multiracial respondents. Respondents from rural areas were more likely to indicate willingness to initiate medications with their PCP than those from urban areas. Conclusions: Telemedicine expansion and further support for PCPs may represent critical opportunities to promote equitable access to adolescent gender-affirming care.

Women's empowerment and tourism: Emerging determinants of poverty in low and middle‐income countries

AbstractThis study examines the impact of women's empowerment and tourism on poverty in the developing economies of South Asia, sub‐Saharan Africa and Latin America. Current study formulates a vector autoregression (VAR) model to estimate the long‐run association between emerging determinants of poverty reduction. Our empirical findings show that tourism and women's empowerment have significant and negative long‐term associations with poverty in South Asia, Latin America and Africa. Moreover, this study found that women's empowerment is relatively more important in poverty reduction than tourism in South Asia and Africa, whereas in Latin America, tourism has a relatively greater contribution to poverty. Similarly, the results of the vector error‐correction (VECM) Granger Causality/Block Exogeneity Wald test indicated unidirectional causality between women's empowerment and poverty, tourism and poverty in South Asia. Similarly, unidirectional causality exists between women's empowerment and poverty in Latin America and Africa. Our econometric discussion helps suggest policy suggestions to overcome the challenges of poverty in developing economies.

Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort

Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10–8 and 4.3 × 10–7). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.

Piecewise Linear Multiple Change Point Modelling for Under-Five Child Mortality

Using a piecewise linear multiple change-point model instead of more traditional survival techniques is more beneficial when dealing with mortality data. Utilizing this technique, the hazard model is estimated and the number of cut-point locations is found. Using various covariates, such as sociodemographic, biological, and proximate co-factors, this piecewise hazard model is fitted to the Infant Mortality Data of Bangladesh Demographic and Health Survey 2014. Finding the change point and the impact of covariates on the hazard rate is done using the maximum likelihood estimation process. The parameter&amp;apos;s significance is subsequently supported by the Wald test statistic. It turns out that the mother&amp;apos;s educational status, religion, mother&amp;apos;s age in years, the number of children they have ever had, currently breastfeeding, the size of the child, desire for more children, cesarean delivery, ANC visits, and birth orders are all significant factors. It is also discovered that the detected change point of the hazard rate is extremely important for the child until they reach the age of five. Through the various time cut points, it is found that a piecewise linear multiple change-point model is very important for under-five child mortality. Public health specialists, researchers, and clinicians can all benefit from this piecewise hazard model. One of the most crucial elements in lowering child mortality is time.

188 Timing of Nerve Reconstruction Surgery to Optimize Long-Term Recovery at the Elbow and Forearm in Neonatal Brachial Plexus Palsy

INTRODUCTION: Restoration of elbow flexion is highly prioritized in nerve reconstruction for neonatal brachial plexus palsy (NBPP). Elbow extension and forearm supination are also frequently impacted in NBPP. Timing of surgical reconstruction for optimal outcomes at the elbow and forearm remains unknown. METHODS: We interrogated a prospectively collected database of all children with NBPP who underwent nerve reconstruction at a single center between 2005-2020. AROM was collected for elbow flexion and extension and forearm supination at every clinic visit and normalized between 0 and 1. The cohort was divided into those with surgery =6 months old, 6-9 months old, and &gt;9 months old. We compared elbow and forearm AROM in local age windows between the groups using a regression model expressing the expected AROM as a linear function. Significant differences between the groups were identified using a Wald test. RESULTS: Of 99 included children 28 had surgery =6 months old, 46 had surgery between 6-9 months, and 25 had surgery &gt;9 months. At ∼13 years follow up, there was no difference in recovery of AROM for elbow flexion between the groups. For elbow extension, mean normalized AROM was significantly worse when comparing the &gt;9 month and =6 month group (0.41 vs 0.84, p &lt; 0.001). For forearm supination, the =6 month group had significantly better AROM than the 6-9 month (0.57 vs 0.77, p = 0.02) and &gt;9 month (0.46 vs 0.77, p &lt; 0.001) groups. Children who presented earlier had surgery at a younger age. CONCLUSIONS: Earlier surgery may result in better long-term recovery of elbow extension and surgery =6 months of age may yield the best outcomes for forearm supination. Early referral may help optimize timing of nerve surgery.

Gender differences in the association of dementia symptoms severity and hospital anxiety

IntroductionSymptoms of anxiety can worsen cognitive decline in people with dementia, and symptoms of dementia and fears of further cognitive decline can cause anxiety. Advanced dementia is not necessarily associated with a loss of emotion, which means that people may still experience anxiety, but their ability to cope in a healthy way is reduced. The problem is exacerbated by the fact that hospital care alone can contribute to the severity of anxiety symptoms due to change in routine of daily activities, unfamiliar surroundings, uncertainty about health status, prognosis and various medical procedures. There are differences between women and men in the prevalence, course and manifestation of both dementia and anxiety disorders.ObjectivesTo examine whether there are differences between women and men in the association of hospital anxiety with eight symptoms of dementia: difficulties with memory, orientation, judgement, problem solving, fulfilling social obligations, daily activities at home and with hobbies, or personal care, in patients with mild to moderate dementia.Methods A cross-sectional study was conducted at Sveti Ivan Psychiatric Clinic in Zagreb in June 2023. The target population were hospitalised patients diagnosed with dementia, both genderes, aged 60-90 years, without psychotic disorder. Anxiety during hospitalisation was measured using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), and the severity of dementia symptoms was measured using the Dementia Assessment Instrument (CDR). The hypothesis was tested using Wald test of differences between women and men in unstandardised linear regression coefficients of the HADS-A on individual dementia symptoms, after adjustment for age, education, presence of a married or stable non-marital partner and duration of current hospitalisation.ResultsWe enrolled 65 women and 35 men of comparable age. There were significant gender-related differences in the association between hospital anxiety and difficulties with judgement (P = 0.01), fulfilling social obligations (P &lt; 0.001), difficulties with home and hobbies (P = 0.02), and personal care (P = 0.00). In women, more pronounced difficulties with judgement and with home and hobbies were associated with higher anxiety, and in men the presence of these two symptoms of dementia was associated with lower anxiety. Difficulties with fulfilling social obligations are associated with lower anxiety in women and higher anxiety in men. Difficulties with personal care were associated with lower anxiety in both genders, but this effect was stronger in men.ConclusionsThere are differences between women and men in the association between anxiety during hospital treatment and the severity of individual dementia symptoms. These differences are present in difficulties with judgement, fulfilling social obligations, home, hobbies and personal care.Disclosure of InterestNone Declared

Gender differences in the effect of rtms with the H7-coil on physical and social anhedonia in schizophrenia spectrum disorder; a randomized, sham-controlled trial

IntroductionStudies of differences in the incidence and severity of physical and social anhedonia between women and men diagnosed with schizophrenia spectrum disorder (SSD) are often inconsistent, and gender differences in treatment response have not been well studied. Hormonal factors, such as those related to the menstrual cycle, pregnancy or menopause, as well as social and cultural patterns and roles, may influence treatment response. The incidence of affective or stress-related psychiatric comorbidities may be gender-specific, which could also complicate the treatment of anhedonia and other negative symptoms of SSD. Finally, there is no evidence of sufficient quality on gender differences in the effects of rTMS, but the results are intriguing and point to the need for further research.ObjectivesTo investigate gender differences in the effect of rTMS with the H7-coil on physical and social anhedonia in patients diagnosed with SSD with dominant negative symptoms.MethodsWe conducted a randomized, sham-controlled trial during 2000-2023 in the population of patients diagnosed with SSD with primary negative symptoms defined as PANSS negative symptoms subscale score &gt; 24, and PANSS positive symptoms subscale score &lt; 20. The intervention was HF rTMS H7 coil (Brainsway Ltd. Jerusalem, Israel) once daily for 20 days applied to the prefrontal cortex (mPFC and ACC) at 100% motor threshold with a frequency of 18 Hz, and total of 39600 pulses. The outcomes were Physical and Social Anhedonia Scales (PAS, and SAS). We controlled for the large number of relevant covariates.ResultsWe randomized 49 men and 29 women of similar age. The effect on physical anhedonia was statistically significant in women (b = 9.04; p = 0.016), but not in men (b = 2.87; p = 0.272). The effect on social anhedonia was similar, but the difference was smaller (for men b = 3.71; p = 0.082; for women b = 5.42; p = 0.043). However, the Wald test showed no statistically significant differences between the beta coefficients for women and men.ConclusionsBased on this study, it is not possible to make valid and reliable conclusions about the existence of gender differences in the effects of rTMS treatment of anhedonia with the H7 coil. However, it is possible to claim that the treatment of anhedonia with this protocol is effective in women.Disclosure of InterestNone Declared

The influence of environmental diplomacy, economic determinants and renewable energy consumption on environmental degradation: Empirical evidence of G20 countries.

This study examines how various environmental and economic variables contribute to environmental degradation. Industrialization, trade openness, and foreign direct investment are among the variables, as are environmental diplomacy, environmental diplomacy secure, and renewable energy consumption. Therefore, the data covers the years 1991-2020, and our sample includes all 19 countries and two groups (the European Union and the African Union). The research used the Pesaran CD test to determine cross-section dependency, CIPS and CADF test to determine stationarity, the Wald test for hetrodcedasasticity and the Wooldridge test for autocorrelation; therefore, VIF for multicollinearity, Durbin and Hausman to analyze the endogeneity. It also employed Westerlund's cointegration test to ensure cross-sectional dependence, Wald test for group-wise heteroscedasticity, Wooldridge test for autocorrelation, VIF for multicollinearity, and Durbin and Hausman for endogeneity. The two-step system generalized method of moments (GMM) is used to estimate the results and confirm the relationship between independent variables (Industrialization, trade openness, FDI, environmental diplomacy, secure environmental diplomacy, and renewable energy) and dependent variables (Environmental Degradation) in G20 countries. Therefore, Industrialization, trade openness, foreign direct investment, ecological diplomacy, and renewable energy consumption significantly impact ecological degradation. Environmental diplomacy is crucial to combat degradation and stimulate global collaboration. G20 nations enact strict environmental restrictions to tackle climate change and encourage economic growth.

DETERMINE FACTORS AFFECTING CUSTOMER LOYALTY IN BIMBINGAN BELAJAR PT. FADHIL KREATIF KOMUNIKA/SNS USING BINARY LOGISTIC REGRESSION BINER

One of the problems that are often faced by tutoring institutions is student stop studying. This isi a serious proplem for a tutoring institution, including the Tutoring Institute PT. Fadhil Kreatif Komunika/SNS. This problem is greatly reduces the number of profits. There are factors that influence the studens of these tutoring institutions to stop studying. One of them is to Customer Loyalty. The purpose of thid research is to find the factors that influence customer loyslty in tutoring institute PT. Fadhil Kreatif Komunika/SNS. The research method is the binary logistic regression. The factors examined in this research are Service Quality, Costumer Satisfaction, Price and Tutor Competence. And the result of the analysis with α = 0,05 obtained a chi-square value of 122,802. Based on the the result of the Wald Test, the significant values was obtained greater than 0,05 on the variables of Service Quality and Tutor Competence, and the signigicant values was obtained less than 0,0t on the variables of Customer Satisfaction and Price. This means that there are variables that have a positive anf significant effecr on Customer Loyalty at PT. Fadhil Kreatif Komunika/SNS that is Customer Satisfaction and Price.&#x0D; &#x0D;

Bayesian detection for distributed target with limited training data

The issue of subspace-based distributed target detection with limited training data is addressed in this study. We use the Bayesian method to tackle the issue by assuming that the covariance matrix follows an inverse Wishart distribution. According to the generalized likelihood ratio test, Rao test, and Wald test, three Bayesian detectors are designed. Real data and simulations both attest to the usefulness of the proposed detectors.

Communication from below: Feedback from employees as a tool for their stabilisation

Given the current organisational changes in a turbulent global economic context, is the appropriate setting of the communication process, with an emphasis on feedback from employees to management for organisations to cope with external changes. Following the COVID-19 pandemic, communication from below is required as it is a primary issue in the context of significant organisational change and can help to shape positive perceptions of change. The main aim is to evaluate the relationships between selected organisational variables regarding the use of different forms of employee-to-management communication. A questionnaire survey of Czech organisations (n1 = 183) was conducted, and the data obtained were evaluated using statistical tests (Wald statistic) to determine whether a demonstrable relationship existed between the traits. The results showed a relationship between the application of most types of bottom-up communication and organisation size in terms of the number of employees, majority ownership, and, for selected types of communication forms, annual turnover. However, none of the communication types examined depended on the sector in which an organisation operated. The results of the qualitative research confirmed that grassroots communication was crucial in all the types of organisations examined and helped to improve organisational climate. This study contributes to theory and practice by confirming that feedback from employees is a tool for their stabilisation. The managerial implications include the finding that effective feedback settings help prevent conflicts in organisations. The study contributes significantly to the deepening of knowledge on the issue of systematic communication leading to the sustainability of organisations, which is also demonstrated by the almost zero overlap with previous studies.

Testing Homogeneity of Proportion Ratios for Stratified Bilateral Correlated Data

Intraclass correlation in bilateral data has been investigated in recent decades with various statistical methods. In practice, stratifying bilateral data by some control variables will provide more sophisticated statistical results to satisfy different research proposed in randomized clinical trials. In this article, we propose three test statistics (the likelihood ratio test, score test, and Wald-type test statistics) to evaluate the homogeneity of proportion ratios for stratified bilateral correlated data under an equal correlation assumption. Monte Carlo simulations of Type I error and power are performed, and the score test yields a robust outcome based on empirical Type I error and power. Lastly, two real data examples are conducted to illustrate the proposed three tests.

Abstract 6151: Relationship between polygenic risk score, lifestyle factors, and colorectal cancer risk

Abstract Although heritable factors are estimated to explain up to 35% of colorectal cancers (CRC), most are diagnosed in people without a family history of CRC suggesting that inherited genetic variants, environmental factors, or a combination of both, contribute to CRC risk. We explored the relationship between a polygenic risk score (PRS) for CRC risk and lifestyle risk factors to understand whether individuals with higher genetic risk, who do not develop CRC, engage in healthier lifestyle behaviors, or conversely, whether those with lower genetic risk, who do develop CRC, engage in riskier behaviors in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Using summary statistics obtained from a large independent GWAS meta-analysis of CRC by the GECCO consortium, we developed a genome-wide PRS for CRC using SBayesR and applied it to participants of European ancestry genotyped in the PLCO Trial (n=74,396). For all subjects, we computed an environmental (E) score based on 19 lifestyle risk factors for CRC, a WCRF/AICR score that measured adherence to the 2018 Cancer Prevention recommendations, and a 2015 healthy eating index (HEI) with higher values indicating healthier lifestyle profiles. We used t-tests to evaluate differences in lifestyle scores between CRC-free participants in the highest quartile of PRS and incident CRC cases in the lowest quartile of PRS. To examine the correlations between the PRS and lifestyle scores, we performed multivariable linear regression models regressing PRS on each lifestyle score. We used multivariable Cox hazards regression models to compute hazard ratios and 95% confidence intervals for CRC risk; multiplicative interactions between PRS and lifestyle scores were evaluated using the Wald test for the interaction terms. During the 15 years follow-up period, a total of 1,052 CRC cases were diagnosed. Individuals in the highest quartile of PRS who remained cancer-free were more likely to engage in healthier behaviors than those in the lowest quartile of PRS who were diagnosed with incident CRC (E-score: -0.01 vs. -0.18, WCRF/AICR score: -0.05 vs. -0.32, HEI score: 0.06 vs. -0.13); however, differences were not statistically significant (P value: 0.1 to 0.4). PRS and lifestyle scores were significantly (all P &amp;lt;0.0001), albeit weakly (β: -0.02 to -0.03), associated among participants who remained CRC-free but not among CRC cases (P: 0.1 to 0.3). PRS-lifestyle score interactions were not statistically significant (P: 0.2 to 0.4). Although the differences and multiplicative interaction models were not statistically significant, we found that individuals with a higher PRS who remained CRC-free were slightly more likely to engage in healthier behaviors than those at a lower genetic score who developed CRC. Additional studies with larger sample size are warranted to further explore the interplay between genetic risk and lifestyle factors related to CRC risk. Citation Format: Wen-Yi Huang, Erikka Loftfield, Rebecca Landy, Difei Wang, Hormuzd A. Katki, Jianxin Shi, Lingxiao Wang, Mitchell J. Machiela, Neal D. Freedman, Sonja I. Berndt. Relationship between polygenic risk score, lifestyle factors, and colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6151.

Abstract 5690: Urinary microRNA expression in pancreatic cancer with cachexia

Abstract Background: Cancer cachexia (CC) is a multifactorial syndrome characterized by appetite loss, weight loss and skeletal muscle wasting. It increases functional impairment, treatment-related toxicity, and a lower quality of life. Importantly, CC is one of the leading causes of cancer-related deaths, and its occurrence is particularly prevalent in advanced stages of pancreatic cancer (PC). The syndrome is thought to be associated with systemic inflammation and increased energy expenditure, yet the specific mechanisms remain to be fully understood. Although timely detection and intervention might be crucial in preventing CC’s progression, early diagnosis of this syndrome remains challenging due to the absence of suitable biomarkers. Here, we analyzed urinary microRNAs (miRNAs) as a potential noninvasive biomarkers for detecting CC in patients (pts) with PC. Methods: Clinical information including presence or absence of CC and urine samples were collected from pts with PC treated at National Cancer Center Hospital, Tokyo, Japan from March to October 2022. The diagnosis of CC was made according to the following definitions by Fearon. K et al. (1) weight loss of ≥5% within 6 months; (2) weight loss of ≥2% in pts with a BMI of &amp;lt;20 kg/m2; or (3) weight loss of ≥2% in pts with sarcopenia. In this study, pts who met the definition of CC within 6 months of enrollment were considered to have CC.Urinary miRNA profiles from pts with PC were sequenced by NGS and analyzed using DESeq2 to identify differentially expressed miRNAs (DEMs) between pts with CC and those without. DEMs were further explored for associated pathways and target genes using miRPathDB v.2.0. Results: Of the 64 subjects, 52 pts were included in the analysis after excluding three pts with low urine sample read coverage and nine pts with no information on CC status. Among those, 38 pts were classified as having CC. Patients’ background was as follows (CC/no CC); median age 70 [range: 44-80]/67 [57-74], male and female 19/7 pts, respectively, cStage {I (6/0), II (1/0), III (17/4), IV (14/10)} pts, median BMI (male 22.1 [17.7-27.2]/21.7 [18.2-28.2], female 21.7 [14.6-25.2]/21.9 [16.6-27.4]) kg/m2. Among 307 miRNAs detected in the urine of pts with PC, 49 miRNAs had previously been reported in CC research. The miR-141-5p was differentially expressed between pts with CC and those without CC (Wald test pBH = 0.079). It was down-regulated in pts with CC (Mann-Whitney U test p = 6.4e-4) and most significantly associated with the FoxO signaling pathway (ORA pBH = 1.84e-4), followed by the mTOR signaling pathway (ORA pBH = 0.008). Conclusions: Our study indicates that miR-141-5p holds potential as a noninvasive biomarker for the detection of CC in pts with PC. Although miR-141-5p has not been previously reported in CC, its significant association with the FoxO signaling pathway, which is one of the major pathways regulating skeletal muscle atrophy, underscores the relevance of miR-141-5p in the context of CC. Citation Format: Mao Okada, Shunsuke Kondo, Yukiko Igawa, Tatsuya Yoshida, Milos Havelka, Mika Mizunuma, Yuki Ichikawa, Noboru Yamamoto. Urinary microRNA expression in pancreatic cancer with cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5690.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.