Longitudinal Analysis Research Articles

Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study

BackgroundBoth the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population.MethodsThis study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses.ResultsThe mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (< 8.6 [median level]) and hsCRP < 1 mg/L, those concurrently with a higher TyG and hsCRP had the highest risk of overall cardiovascular disease (adjusted hazard ratio [aHR], 1.300; 95% CI 1.155–1.462), coronary heart disease (aHR, 1.294; 95% CI 1.130–1.481) and stroke (aHR, 1.333; 95% CI 1.093–1.628), which were predominant among those aged 70 years or below. High hsCRP significantly mediated 13.4% of the association between the TyG index and cardiovascular disease, while TyG simultaneously mediated 7.9% of the association between hsCRP and cardiovascular risk.ConclusionsThe findings highlight the coexposure effects and mutual mediation between the TyG index and hsCRP on cardiovascular diseases. Joint assessments of the TyG index and hsCRP should be underlined for the residual risk stratification and primary prevention of cardiovascular diseases, especially for middle-aged adults.

Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study.

Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population-based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th-75th percentiles, 0.6-3.1 ng/L), median age was 52 years (39.1-65.6 years), and 57% were female subjects. Cross-sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross-sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations

BackgroundInfections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking.MethodsWe present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates.ResultsWe show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development.ConclusionsOur data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

A longitudinal analysis of soil salinity changes using remotely sensed imageries

Soil salinization threatens agricultural productivity, leading to desertification and land degradation. Given the challenges of conducting labor-intensive and expensive field studies and laboratory analyses on a large scale, recent efforts have focused on leveraging remote sensing techniques to study soil salinity. This study assesses the importance of soil salinity indices’ derived from remotely sensed imagery. Indices derived from Landsat 8 (L8) and Sentinel 2 (S2) imagery are used in Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Decision Tree (DT), and Support Vector Machine (SVR) are associated with the electrical (EC) conductivity of 280 soil samples across 24,000 hectares in Northeast Iran. The results indicated that the DT is the best-performing method (RMSE = 12.25, MAE = 2.15, R2 = 0.85 using L8 data and RMSE = 10.9, MAE = 2.12, and R2 = 0.86 using S2 data). Also, the results showed that Multi-resolution Valley Bottom Flatness (MrVBF), moisture index, Topographic Wetness Index (TWI), and Topographic Position Indicator (TPI) are the most important salinity indices. Subsequently, a time series analysis indicated a reduction in salinity and sodium levels in regions with installed drainage networks, underscoring the effectiveness of the drainage system. These findings can assist decision-making about land use and conservation efforts, particularly in regions with high soil salinity.

Associations between dietary diversity and dyslipidemia among Japanese workers: cross-sectional study and longitudinal study findings.

The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. The cross-sectional study included 1399 participants aged 20-63years and the longitudinal study included 751 participants aged 20-60years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.

The causal associations between interoception, self-regulation, non-purposeful eating behaviors, and weight status in college women: a longitudinal cross-lagged model analysis

Aims Excessive weight gain has led to increased obesity and mortality risk among college students. Issues with maintaining a healthy weight may be attributed to poor internal awareness and unhealthy eating behaviors. The study’s purpose was to determine the longitudinal effects among interoception, self-regulation, nonpurposeful eating behaviors, and weight status (BMI) among college women. Methods Data from 103 females were collected via Qualtrics over 3 timepoints (T1, T2, T3) during an academic semester. Repeated measures ANOVA and cross-lagged model analyses were used. Significant changes were found in interoceptive responsiveness, external, and uncontrolled eating throughout 3 timepoints. Results Longitudinally, significant causal effects were found among the study measures. Among all models, higher interoceptive responsiveness (T1) predicted increased self-regulation (T2). Higher non-purposeful eating behaviors (T1) predicted reduced self-regulation (T2). Higher BMI (T1) predicted reduced non-purposeful eating behaviors (T2), however higher BMI (T2) predicted increased non-purposeful eating (T3) and reduced interoceptive responsiveness (T3). Significant causal effects were found within each non-purposeful eating behavior models. Conclusion Overall, the research study provided foundational evidence of the importance of self-regulatory skills to help prevent unhealthy eating behaviors and increased weight status in college women. Future interventions educating college women to become more internally aware and better self-regulate are needed.

Challenges and directions for digital twin implementation in otorhinolaryngology.

Digital twin technology heralds a transformative era in Otorhinolaryngology (ORL), merging the physical and digital worlds to offer dynamic, virtual models of physical entities or processes. These models, capable of simulating, predicting, and optimizing real-world counterparts, are evolving from static replicas to intelligent, adaptive systems. Fueled by advancements in communication, sensor technology, big data analytics, Internet of Things (IoT), and simulation technologies, artificial intelligence (AI), digital twins in ORL promise personalized treatment planning, virtual experimentation, and therapeutic intervention optimization. Despite their potential, the integration of digital twins in ORL faces challenges including data privacy and security, data integration and interoperability, computational demands, model validation and accuracy, ethical and regulatory considerations, patient engagement, and cost and accessibility issues. Overcoming these challenges requires robust data protection measures, seamless data integration, substantial computational resources, rigorous validation studies, ethical transparency, patient education, and making the technology accessible and affordable. Looking ahead, the future of digital twins in ORL is bright, with advancements in AI and machine learning, omics data integration, real-time monitoring, virtual clinical trials, patient empowerment, seamless healthcare integration, longitudinal data analysis, and collaborative research. These developments promise to refine diagnostic and treatment strategies, enhance patient care, and facilitate more efficient and tailored ORL research, ultimately leading to more effective and personalized ORL management.

CSR in the banking industry: A longitudinal analysis of the impact on financial performance and risk-taking

Building on the stakeholder influence capacity theory we propose a non-linear relationship between CSR investments and financial performance and between CSR investments and risk-taking behavior in financial firms. We study the impact of ESG scores on both the financial performance and risk-propensity of European banks using panel data from 2005 to 2022. Given the role of Swiss banks as frontrunners regarding the implementation of CSR-related regulations in the financial industry, we also shed light on the Swiss case. Controlling for bank and time fixed effects we confirm a U-shaped relationship between ESG and financial performance, and an inverted U-shaped relationship between ESG and risk for Swiss banks. Remarkably, we find no relationship between CSR initiatives and financial performance for European banks and find a direct negative effect of CSR on risk density. These results indicate the need to consider institutional differences in the CSR debate. Moreover, we show that promoting ESG initiatives in the financial industry might lead to adverse effects (i.e. lower financial performance and higher risk) if banks do not commit sufficiently to those CSR investments.

Shaping down syndrome brain cognitive and molecular changes due to aging using adult animals from the Ts66Yah murine model

Down syndrome (DS) is the most common condition with intellectual disability and is caused by trisomy of Homo sapiens chromosome 21 (HSA21). The increased dosage of genes on HSA21 is associated with early neurodevelopmental changes and subsequently at adult age with the development of Alzheimer-like cognitive decline. However, the molecular mechanisms promoting brain pathology along aging are still missing. The novel Ts66Yah model represents an evolution of the Ts65Dn, used in characterizing the progression of brain degeneration, and it manifest phenotypes closer to human DS condition. In this study we performed a longitudinal analysis (3–9 months) of adult Ts66Yah mice. Our data support the behavioural alterations occurring in Ts66Yah mice at older age with improvement in the detection of spatial memory defects and also a new anxiety-related phenotype. The evaluation of hippocampal molecular pathways in Ts66Yah mice, as effect of age, demonstrate the aberrant regulation of redox balance, proteostasis, stress response, metabolic pathways, programmed cell death and synaptic plasticity. Intriguingly, the genotype-driven changes observed in those pathways occur early promoting altered brain development and the onset of a condition of premature aging. In turn, aging may account for the subsequent hippocampal deterioration that fall in characteristic neuropathological features. Besides, the analysis of sex influence in the alteration of hippocampal mechanisms demonstrate only a mild effect. Overall, data collected in Ts66Yah provide novel and consolidated insights, concerning trisomy-driven processes that contribute to brain pathology in conjunction with aging. This, in turn, aids in bridging the existing gap in comprehending the intricate nature of DS phenotypes.

Longitudinal Analysis of Overlapping Psychosocial Factors Predicting Incident Hospitalization Among Mixed HIV Serostatus Men who have Sex with Men in the Multicenter AIDS Cohort Study.

Men who have sex with men (MSM) are at increased risk for certain types of chronic diseases and mental health problems. Despite having extended survival in the highly active antiretroviral therapy (HAART) era, MSM living with HIV contend with aging-related diseases and complications with treatment. Consequent hospitalizations incur high costs, fear, low quality of life, and frailty. Unlike heterosexual men, MSM experience more structural violence and "syndemics" of psychosocial factors that not only accelerate HIV acquisition and transmission risk but also may increase morbidity, leading to greater rates of hospitalization. We aim to examine the impact of "syndemic" psychosocial factors on the incidence of hospitalization among geographically diverse MSM in the US. Participants were 1760 MSM from the Multicenter AIDS Cohort Study (MACS) between 2004 and 2019. We examined the relationship between six psychosocial factors (depression, stimulant use, smoking, heroin use, childhood sexual abuse, and intimate partner violence) and incident hospitalization (admission to a hospital for treatment). We found a positive dose-response relationship between the number of syndemic factors and hospitalization. MSM reporting five or more syndemic factors had over twice the risk of hospitalization compared to MSM without syndemic factors [aRR = 2.14 (95% CI = 1.56, 2.94)]. Psychosocial factors synergistically increased hospitalizations over time. The positive dose-response relationship between the number of syndemic factors and hospitalization and the synergistic effects of these factors underscore the need for interventions that disentangle the syndemics to reduce hospitalization and related costs and improve the quality of life among MSM.

Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults

Many epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood. To examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aβ) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults. This was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aβ deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aβ deposition were included. Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Baseline levels and longitudinal changes of global Aβ and AD-signature region tau deposition measured by PET scans. Among the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aβ deposition (β = -0.04; 95% CI, -0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (β = -0.02; 95% CI, -0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (β = -0.06; 95% CI, -0.11 to -0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aβ deposition (β = 0.006; 95% CI, 0.00-0.02; P = .27). The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aβ and tau deposition.

Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities

BackgroundOrganophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. MethodsIn 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. ResultsThe organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (βboys = 5.88% [1.21%, 10.78%], βgirls = 4.10% [-0.02%, 8.39%]), and cortisol (βboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β2boys = −0.17 (−0.33, −0.003), p = 0.04) and DHEA (β2boys = −0.49 (−0.80, −0.19), p = 0.001) in boys. The neonicotinoid summary score (βboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (βboys = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. ConclusionsWe observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Gut microbiome and resistome characterization of pigs treated with commonly used post-weaning diarrhea treatments

BackgroundThe global burden of antimicrobial resistance demands additional measures to ensure the sustainable and conscious use of antimicrobials. For the swine industry, the post-weaning period is critical and for many years, antimicrobials have been the most effective strategy to control and treat post-weaning related infections. Among them, post-weaning diarrhea causes vast economic losses, as it severely compromises piglets’ health and growth performance. In this study, 210 piglets were transferred from a farm with recurrent cases of post-weaning diarrhea to an experimental farm and divided into six different treatment groups to determine the effect of the different treatments on the growth performance and survival, the microbiome, and the resistome in a cross-sectional and longitudinal study. The different treatments included antimicrobials trimethoprim/sulfamethoxazole, colistin, and gentamicin, an oral commercial vaccine, a control with water acidification, and an untreated control. An extra group remained at the farm of origin following the implemented amoxicillin routine treatment. A total of 280 fecal samples from pigs at four different sampling times were selected for metagenomics: before weaning-treatment at the farm of origin, and three days, two weeks, and four weeks post-treatment.ResultsThe control group with water acidification showed a reduced death risk in the survival analyses and non-significant differences in average daily weight gain in comparison to the antibiotic-treated groups. However, the growth-promoting effect among antibiotic-treated groups was demonstrated when comparing against the untreated control group at the experimental farm. After four weeks of treatment, diversity indexes revealed significantly decreased diversity for the untreated control and the group that remained at the farm of origin treated with amoxicillin. For this last group, impaired microbial diversity could be related to the continuous amoxicillin treatment carried out at the farm. Analysis of the resistome showed that both gentamicin and amoxicillin treatments significantly contributed to the emergence of resistance, while trimethoprim/sulphonamide and colistin did not, suggesting that different treatments contribute differently to the emergence of resistance.ConclusionsOverall, this shotgun longitudinal metagenomics analysis demonstrates that non-antibiotic alternatives, such as water acidification, can contribute to reducing the emergence of antimicrobial resistance without compromising pig growth performance and gut microbiome.

Inside Airbnb’s performance and adaptive strategies in Barcelona using artificial neural networks: A longitudinal, spatial, and multi-host perspective

This research explores the Airbnb platform's performance and adaptive strategies by analysing its spatial, temporal, and multi-host patterns. A three-layer model based on machine learning and neural networks, compared with a multiple linear regression, Random Forest Regression (RFR), and Support Vector Regression (SVR) methods, is used to conduct a longitudinal analysis of three representative months for tourism each year from 2016 to 2022. The study reveals the importance of “minimum nights”, active price management and professionalization, coupled with the potential transfer of accommodations in the medium- and long-term residential markets, as the platform's adaptive strategies. The findings also suggest a shift towards more professional host profiles and the consolidation of new tourist hubs in the city in post-Covid period. The study contributes to the understanding of Airbnb's performance and impact on global urban dynamics and demonstrates an application of machine learning to tourism and hospitality research. Theoretical and practical implications are discussed.

Background TV and infant-family interactions: Insights from home observations.

Background television has been found to negatively impact children's language development and self-regulatory skills, possibly due to decreased parent-child interactions. Most of the research on the relationship between background TV and caregiver-child interactions has been conducted in laboratory settings. In the current study, we conducted home observations and investigated whether infants engage in fewer interactions with family members in homes where background TV is more prevalent. We observed 32 infants at the ages of 8, 10, and 18months in their home environments, coding for dyadic interactions (e.g., parent talking to and/or engaging with the child), triadic interactions (e.g., parent and infant play with a toy together), and infants' individual activities. Our findings revealed that background TV was negatively associated with the time infants spent in triadic interactions, positively associated with time spent engaging in individual activities, and not significantly related to the time spent in dyadic interactions. Apart from the relationship between background TV and individual activity time at 8months, these associations remained significant even after accounting for families' socioeconomic status. These findings imply a correlation between background TV exposure and caregiver-infant-object interactions, warranting a longitudinal analysis with larger sample sizes.

Longitudinal Analysis of Predictive Factors for Stroke and Bleeding Events in Atrial Fibrillation Patients: Insights From a Tertiary Care Center Cohort.

Atrial fibrillation (AF) represents a prevalent cardiac arrhythmia associated with increased risks of stroke and bleeding events, necessitating comprehensive risk assessment and management strategies. This retrospective cohort research aimed to longitudinally analyze risk factors associated with stroke and bleeding incidents in patients diagnosed with AF, focusing on identifying predictive factors and their impact on patient outcomes. The research enrolled 480 AF patients from a tertiary care center over an 18-month period (2021-2022). Baseline demographic, clinical, and medication data were collected from electronic health records. Patients were monitored for occurrences of stroke and bleeding events during follow-up. Cox proportional hazards models and Kaplan-Meier estimates were utilized to assess risk factor associations and cumulative event incidences, respectively. A cohort of 480 AF patients, with a meanage of 65.4 years, wasobserved over 18 months. Stroke patients tended to be older (72.1 years),and bleeders slightly younger (68.8 years). Cox models revealed higher stroke risk in >70-year-olds (hazard ratio (HR): 1.85, 95% confidence interval (95% CI): 1.21-2.78, p < 0.001) and with prior stroke history (HR: 2.13, 95% CI: 1.45-3.12, p < 0.001). Prior stroke linked to bleeding risk (HR: 1.88, 95% CI: 1.26-2.81, p = 0.003). At six months, stroke incidence was 5.2%, bleeding 3.8%; at 18 months, 12.5% experienced strokes, 9.3% bleeding. These findings underscore age and prior stroke as vital predictors of adverse outcomes in AF patients. This research reaffirms age and prior stroke as pivotal risk factors for adverse outcomes in AF patients. The findings emphasize the necessity for tailored risk stratification and interventions to mitigate stroke and bleeding risks, thereby enhancing patient care and prognosis in AF management.

Abstract PO5-23-10: Development of a long-term in vitro assay able to identify compounds that can overcome resistance to CDK4/6 inhibitor plus endocrine therapy in ER+ HER2- breast cancer

Abstract CDK4/6 inhibitor plus endocrine therapy (ET) has emerged as the standard of care first line therapy in ER+ HER2- breast cancer. While this combination has shown the ability to extend overall survival, nearly all patients acquire resistance and progress after 2-3 years. Subsequently, interest has turned to identifying a third partner compound that can be integrated into the CDK4/6i plus ET backbone regimen with the goal of overcoming resistance and driving a deeper response. However, a comprehensive assay-based workflow proficient in identifying compounds with the most promising potential is lacking. To fill this need, we set out to develop a high-throughput in vitro assay with relevant multi-faceted readouts to assess the efficacy of potential triplet combinations using 12 human ER+ breast cancer lines. For this assay, cells were engineered to express nuclear RFP to enable accurate cell counting using basic imaging techniques in 384 well plates. Each third partner compound was tested at two different doses and, in addition to the triplet combination (CDK4/6i + ET + third partner), single agent as well as double agent combinations were investigated. The assay was imaged and re-dosed every 5 days until day 15. On day 15, the compounds were washed out and the cells underwent a 25-day drug holiday to monitor relapse. Duplicate plates of all conditions were monitored and imaged every two hours for 24 hours for live cell staining of apoptosis markers. Additional duplicate plates were fixed and stained on days 5 and 15 for markers of senescence and cell cycle. Images were subsequently fed into a python-based algorithm to determine the percentage of cell population expressing the various markers and phenotypic correlates were extracted. We are looking for triplet combinations that induce a deeper cell cycle arrest, senescence, and/or cell death compared with the CDK4/6 inhibitor plus ET only treatment. Our drug holiday results will help elucidate the treatments able to continue to induce suppression once washed out, indicating treatment options that may induce long-lasting, possibly irreversible effects on the cells. Finally, by extracting phenotypic correlates from brightfield images we hope to cluster the various compounds in their effects across cell lines of diverse backgrounds to help understand the best way to benefit multiple patient populations. Overall, the assay will be able to identify and differentiate various therapeutic combinations based on cell count, senescence, and cell death. The format of this assay enables depth of analysis not accessible using other techniques such as FACS, including full dose-response curves, combination matrices, and longitudinal analyses. Additionally, the assay can be modified to evaluate any number of cellular markers and can be useful across a number of applications. The approach developed here will be foundational in discovering next-step strategies for patients with therapy resistance. Citation Format: Stephanie Kronstadt, Neil Umbreit, Matt Niederst, Rens Janssens. Development of a long-term in vitro assay able to identify compounds that can overcome resistance to CDK4/6 inhibitor plus endocrine therapy in ER+ HER2- breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-10.

The Impact of the COVID-19 Pandemic on Physical Activity and Quality of Life Among Ukrainian Students

The COVID-19 pandemic continues to pose serious challenges to society. Strategies such as social distancing are employed to reduce its spread; however, this can lead to a sedentary lifestyle. Many people report difficulties in maintaining a healthy level of physical activity during the pandemic. The aim of this study was to examine the levels of physical activity and quality of life among Ukrainian university students during the COVID-19 pandemic. A diagnostic questionnaire was used, and the International Physical Activity Questionnaires (IPAQ) were employed to assess participants' physical activity levels. The study involved 662 students from three Ukrainian universities. A significant decrease in physical activity and an increase in sleep duration were observed during the COVID-19 pandemic. One of the main advantages of this study was the use of both cross-sectional and longitudinal analyses. The study also allowed for the evaluation of two types of behavior: physical activity and sleep. The conclusions. After the onset of the COVID-19 pandemic, physical activity was low in 90% of students, amounting to 791±7.3 MET, with a significant amount of time (8.6±1.2 hours) spent on sleep, while less than half of the participants (40.2%) met the recommended physical activity guidelines.

Social connectedness and diabetes self-management across the COVID-19 pandemic: A mixed methods study.

Structural social connectedness is the structure and size of a person's social network, including whether persons live with or have regular contact with others. The COVID-19 pandemic disrupted structures that facilitate social connectedness. This study investigated how a person's structural social connectedness influenced diabetes self-management strategies through the COVID-19 pandemic. The study followed an explanatory sequential mixed methods design. First, quantitative data were collected via surveys of 54 patients living with diabetes (67% female, Mage of 60 [12] years) in 2021. Then in 2022, we interviewed 25 patients (64% female, Mage of 62 [9] years) as a follow-up to the survey to help explain quantitative findings. Longitudinal mixed methods analysis integrated both phases to offer a holistic view of the factors influencing diabetes self-management. A full-factorial analysis of covariance tested home and workplace social connectedness effects onto glycemic control and four self-management measures. In integrated analysis, researchers categorized patients into four groups by level of home and workplace social connectedness. Individuals with home social connectedness were more likely to overcome pandemic-related self-management challenges than those without home social connectedness. Although the workplace provided social connectedness, it imposed structural barriers to self-management. Structural social connectedness influenced how patients navigated diabetes self-management challenges through the COVID-19 pandemic. Results suggest clinicians should consider how home and workplace connectedness interact to facilitate or impede patient self-management. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract PO3-10-08: Long-term uptake rate of a breast cancer screening program in Fukushima, Japan, following the 2011 Triple Disaster: a retrospective observational study

Abstract Introduction There has been a growing concern over the past few years about the effects of disasters and crises on breast cancer screening, an argument that has been further enhanced by the novel coronavirus disease 2019 (COVID-19) pandemic. However, little is known about how crises might affect the long-term uptake of breast cancer screening programs. This study aimed to clarify the long-term trend of breast cancer screening program uptake in Minamisoma City following the 2011 Triple Disaster in Fukushima, Japan (earthquake, tsunami, and nuclear disaster), and to evaluate the factors associated with this uptake. Material and Methods This study retrospectively analyzed data from the Basic Resident Registry and Breast Cancer Screening Program in Minamisoma City following the Triple Disaster. We calculated the annual breast cancer screening uptake rate for women aged 40–74 years who were of an even-numbered age at the end of each fiscal year and the incidence of at least one instance of uptake of the breast cancer screening initiative during the biennial intervals. We further performed cross-sectional and longitudinal regression analyses for the biannual screening uptake and investigated its associated factors. Results Breast cancer screening participation rates were 19.8% and 18.2% in 2009 and 2010, respectively. They decreased to 4.2% in 2011, and gradually increased thereafter, reaching the pre-disaster level of 20.0% in 2016. Similar but longer decrease of the uptake was observed in the biannual screening uptake rate. No pre-disaster screening uptake between 2009 and 2010, those living alone, or those who were evacuated, were factors that were found to be associated with non-uptake of the breast cancer screening program following the 2011 disaster. Conclusion This study showed a long-term decline in breast cancer screening uptake in the area affected by the Triple Disaster, which was the most severe among those under evacuation, those who were isolated, and those without previous uptake. The insights emerging from this study could be used to increase awareness of this issue and establish potential countermeasures. Nonetheless, we lack a complete understanding of the effects and variations of disasters on cancer screening in the affected areas. Therefore, global efforts should be intensified to conduct further studies on this topic. Citation Format: Kenji Gonda, Akihiko Ozaki, Kazunoshin Tachibana, Masahiro Wada, Hiroaki Saito, Yudai Kaneda, Yoshitaka Nishikawa, Michio Murakami, Kei Hirai, Hiromichi Ohira, Toyoaki Sawano, Tomohiro Kurokawa, Masaharu Tsubokura, Koji Kono, Thoru Ohtake, Seiichi Takenoshita. Long-term uptake rate of a breast cancer screening program in Fukushima, Japan, following the 2011 Triple Disaster: a retrospective observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-08.