Background: Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s Disease (AD) are increasingly linked through shared pathophysiological mechanisms, giving rise to the concept of Type 3 Diabetes Mellitus (T3DM). Brain insulin resistance, oxidative stress, and neuroinflammation are central to both conditions, contributing to cognitive decline and AD progression. Aim: This review aims to explore this emerging relationship and its implications for prevention and management. Methods: Using an integrative review, 21 studies were systematically analyzed. The review focused on identifying demographic, genetic, and lifestyle factors contributing to T2DM and AD and examined shared molecular pathways such as insulin dysregulation and amyloid-beta accumulation. Results: The findings reveal that T3DM shares key features with T2DM and AD, including insulin resistance and chronic inflammation. Lifestyle interventions, such as diet and exercise, alongside routine cognitive and metabolic screenings, are critical in mitigating progression. Conclusions: Further research into diagnostic biomarkers and targeted therapies is essential to manage T3DM and its impact on AD. The role of nursing professionals in early detection, education, and holistic management is emphasized as vital in addressing this dual disease burden. This review offers actionable insights into integrated strategies for addressing these interconnected conditions.

Background: Nursing students are exposed to significant stress due to academic and clinical demands, which can adversely affect their mental health, academic performance, and future clinical competence. Despite the global acknowledgment of this issue, limited research has been conducted to explore the prevalence and determinants of stress among nursing students in Bangladesh. Methods: This cross-sectional study was conducted from December 2023 to February 2024 among 372 nursing students enrolled in selected nursing colleges in Bangladesh. A purposive sampling technique was used, and data was collected using a semi-structured questionnaire. The questionnaire assessed socio-demographic characteristics, academic challenges, and psychological symptoms, with mental health stress measured using a Likert scale. Descriptive statistics and Chi-square tests were used to analyze the data, with a 95% confidence interval applied to all analyses. Results: The findings revealed that 31.7% of nursing students experienced severe stress, 23.9% reported moderate stress, and 16.7% had mild stress. Age, academic semester, and course load difficulties were significantly associated with stress levels (p < 0.05). Psychological symptoms such as anxiety, difficulty concentrating, and loss of interest in activities were also significantly linked to higher stress levels. Notably, students in their first semester and those reporting harder course loads were more likely to experience stress. However, gender was not significantly associated with stress levels. Conclusions: This study underscores the high prevalence of stress among nursing students in Bangladesh, driven by academic and clinical challenges and psychological symptoms. The findings highlight the need for targeted interventions, such as stress management training, enhanced mental health support, and policies to alleviate academic pressures. Future research should explore longitudinal trends in stress and evaluate the effectiveness of interventions to support a resilient nursing workforce.

Artificial Immune Systems (AIS) are bio-inspired computational frameworks that emulate the adaptive mechanisms of the human immune system, such as self/non-self discrimination, clonal selection, and immune memory. These systems have demonstrated significant potential in addressing complex challenges across optimization, anomaly detection, and adaptive system control. This paper provides a comprehensive exploration of AIS applications in domains such as cybersecurity, resource allocation, and autonomous systems, highlighting the growing importance of hybrid AIS models. Recent advancements, including integrations with machine learning, quantum computing, and bioinformatics, are discussed as solutions to scalability, high-dimensional data processing, and efficiency challenges. Core algorithms, such as the Negative Selection Algorithm (NSA) and Clonal Selection Algorithm (CSA), are examined, along with limitations in interpretability and compatibility with emerging AI paradigms. The paper concludes by proposing future research directions, emphasizing scalable hybrid frameworks, quantum-inspired approaches, and real-time adaptive systems, underscoring AIS's transformative potential across diverse computational fields.

Background: The COVID-19 pandemic posed significant psychological challenges to frontline healthcare workers (HCWs), including anxiety, stress, and emotional strain. Aim: This study investigates the psychological impact on HCWs during the pandemic and explores coping strategies employed to manage distress. Methods: An integrative review was conducted using 24 studies published between January and December 2020. These studies were analyzed to identify common psychological outcomes and coping mechanisms among HCWs. Results: Healthcare workers experienced significant psychological distress during the COVID-19 pandemic, including anxiety, stress, insomnia, and depression. Anxiety was the most commonly reported issue, particularly among women, younger healthcare workers, and frontline staff. Stress levels were heightened by high workloads, exposure to COVID-19 patients, and inadequate protective measures. Coping strategies and self-care behaviors, such as seeking social support and utilizing institutional resources, varied in effectiveness across populations. Conclusion: The findings highlight the urgent need for targeted mental health support and resilience programs for HCWs, ensuring they are better equipped to face future health crises.

Considering the current climate conjuncture, it is a consensus that green spaces in large contemporary urban areas should be increasingly more numerous and simultaneously more sustainable, being adapted to the edaphoclimatic conditions of the site, and with reduced maintenance costs. In the case of Algarve, where this research is focused, the current and future water availability, assumes a preponderant role in the design of green spaces, where the demands mentioned above can only be achieved if we deviate from conventional landscape practices and develop holistic strategies of management and design of green spaces that integrate different areas of knowledge and not merely aesthetic issues. In this context, this work aims to develop more adapted and resilient landscaping practices to the current and future climatic conditions of the Algarve, thus reinventing the concept of landscaping in the south of Portugal. Thus, it will be of paramount importance to develop more sustainable, resilient and tolerant projects to worsening ecological conditions, particularly limitations associated with water availability. The xeromorphic succulents are a group of plants with mechanisms of tolerance to water stress and with very specific characteristics, being succulence one of the most relevant. Studies on these mechanisms are increasingly frequent, which may prove to be very advantageous in our adaptation to future climatic challenges. In addition, their ornamental potential is enormous, since their bold forms and colours are a veritable sensory explosion, which, combined with their morphological and physiological characteristics, make them the species of choice in the reconversion or creation of xerophytic gardens.

Neurodegeneration and aging are pressing issues with significant personal, economic, ethical, and social consequences. However, the underlying biological mechanisms of these conditions remain largely unknown, making the development of effective treatments challenging. The difficulty in early detection and diagnosis of neurodegenerative diseases further compounds the issue. Recent advancements in genetics, genomics, and brain imaging technology hold great promise for improving our understanding of neurodegeneration and aging, as well as the development of personalized medicine and new drugs and therapies. Addressing these challenges will require a multi-disciplinary and collaborative approach from researchers in various fields. This Special Issue offers valuable insights and perspectives on this critical area of research, which can help advance our understanding and improve the health and well-being of our aging population.

Nicotinic acetylcholine receptor (nAChR) of subtypes said "neuronal" are expressed in epithelial and immune system cells and participate in acetylcholine signaling by neural or non-neural pathways. It has been shown in macrophages that activation of type α7 nAChRs inhibits the release of pro-inflammatory cytokines, but the ion channel function has not been recorded in these cells. The objective of this work was to clarify what are the molecular mechanisms of transduction of α7 nAChRs in macrophages. To this end, RAW 264.7 cells, mouse peritoneal macrophages and rat hippocampal neurons were used. Cells were submitted to electrophysiological studies and stimulated with brief applications of the agonists acetylcholine, choline and nicotine, associated or not with the allosteric modulator PNU-120596. Responses to ATP were recorded as a reference. Furthermore, macrophages were submitted to cytokine quantitation. The electrophysiological results showed that macrophages responded to ATP but did not show whole-cell current by stimulation with nicotinic agonists. However, hippocampal neurons stimulated in the same pharmacological conditions of the macrophages showed ionic currents typical of the α7 nicotinic receptors. No effect of nicotine was observed in the lipopolysaccharide-induced TNF-α release. These results suggest that the α7 nAChR in macrophages do not work as ion channels similar to those expressed in neurons.

Background: Sexual and gender minority (SGM) youth are at elevated risk for adverse mental health and substance use outcomes. Stressors such as family conflict, discrimination, and trauma have been suggested as possible mediators of these disparities. Aims: This study examined whether family conflict, discrimination, and trauma mediate the associations between SGM identity and adverse outcomes, including suicide attempt, major depressive disorder (MDD), nicotine use, and marijuana use. Methods: Participants were children from the Adolescent Brain Cognitive Development (ABCD) study. SGM identity was reported at baseline, while outcomes included past MDD and suicide attempts as well as future nicotine and marijuana use. Structural equation modeling (SEM) was used to test both direct and indirect pathways linking SGM identity to mental health and behavioral outcomes. Results: No significant mediation was found through family conflict, discrimination, or trauma. Instead, effects of SGM identity were primarily direct: SGM youth had higher odds of past suicide attempts and MDD, as well as future marijuana use, but not future nicotine use. Stressor variables, however, were independently associated with outcomes. Discrimination predicted all outcomes; trauma was positively associated with suicide, nicotine, and marijuana use but not MDD; and family conflict predicted all outcomes except MDD. Conclusion: Family conflict, discrimination, and trauma did not mediate SGM disparities in mental health and substance use, but each emerged as an independent predictor of risk. These findings highlight the complexity of mechanisms underlying SGM-related disparities and suggest the need for future research to explore additional pathways and contextual influences.

Background: Hepatocellular carcinoma (HCC) faces significant challenges in early diagnosis and prognostic assessment, necessitating novel molecular biomarkers. The role of GCN1 in tumorigenesis remains unclear, warranting systematic investigation of its clinical value. Methods: Utilizing multi-omics data from 164 HCC patients in the TCGA database, we comprehensively evaluated the diagnostic and prognostic value of GCN1 through differential expression analysis, Cox proportional hazards regression, and gene set enrichment analysis (GSEA). Results: GCN1 expression was significantly upregulated in tumor tissues (P<0.001), with ROC analysis demonstrating an AUC of 0.921 (95% CI: 0.893-0.950) for discriminating tumor from normal tissue. Clinical correlation analysis revealed that high GCN1 expression significantly associated with advanced T stage (OR=1.941, P=0.002) and AFP levels >400 ng/ml (OR=3.697, P<0.001). Multivariate survival analysis confirmed its independent prognostic value (HR=1.454, P=0.038). Functional analysis indicated GCN1 promotes tumor progression by regulating cell cycle (NES=2.385) and axon guidance (NES=2.307) pathways. Conclusion: This study first elucidates the dual clinical value of GCN1 in HCC, providing a theoretical foundation for developing novel diagnostic biomarkers and prognostic evaluation systems. Future research should validate its molecular mechanisms and explore potential targeted therapies.

This study investigated the pedagogical implications of out-of-field teaching in Social Studies. The Out-of-field Social Studies teachers could encounter several challenges in their preparation and the implementation of the integrated Social Studies curriculum. This study sought the lived experiences of the out-of-field teachers concerning the causes of out-of-field teaching in social studies, problems encountered by the out-of-field teachers and the mechanisms they employ to cope with the teaching of Social Studies. The study chose the qualitative phenomenological research design. Data were collected from all the 17 out-of-field Social Studies teachers through in-depth structured interview. Data were transcribed and analysed, through the inductive thematic analysis approach, unveiling of themes and concepts from the narratives of the research participants. The study revealed that out-of-field teaching in Social Studies occurs as a result of teacher shortage in integrated social studies programme. It is also caused by the perception that any teacher could teach Social Studies irrespective of the teachers’ qualification. Out-of-field teacher encounter problems such as inadequate content and pedagogical knowledge, lack of classroom managerial techniques and inability to deliver lessons through the integrated approach. Engaging in professional development courses, peer coaching, in-service training and workshops were some of the mechanisms employed by out-of-field teachers to cope with the teaching of Social Studies. The pedagogical implications of this phenomenon are that when teaching the Social Studies, the out-of-field teachers place more emphasis on aspects of the Social Studies curriculum where they have much knowledge and skip or put less emphasis on other aspects they lack in-depth knowledge, thus, the integrated approach to teaching Social Studies is not adopted effectively by out-of-field teachers. This waters down the content of Social Studies at the Senior High School level. Addressing the problem of out-of-field teaching in Social Studies requires training and recruiting more teachers who have background training and experience in the integrated approach to the teaching of Social Studies.

Background: Minorities’ Diminished Returns (MDRs) theory posits that the health benefits of socioeconomic resources, such as education, are smaller for marginalized and minoritized populations, including immigrants. While MDRs have been extensively documented for racial and ethnic minorities, less is known about whether these diminished returns extend to immigrant populations. This study tested MDRs of education on various health and cognitive outcomes, including self-rated health (SRH), cognitive function, numeracy, number of chronic medical conditions, and limitations in activities of daily living (ADLs) among immigrants compared to non-immigrants in the United States. Objective. To examine whether educational attainment confers weaker protective effects on SRH, cognitive function, numeracy, chronic medical conditions, and ADLs in immigrants compared to non-immigrants, confirming the presence of MDRs across these domains. Methods: We used data from the Understanding America Study (UAS), a nationally representative survey of U.S. adults. We tested the association between educational attainment and five outcomes—SRH, cognitive function, numeracy, number of chronic medical conditions, and limitations in ADLs—across immigrant and non-immigrant groups. Multivariate regression models were employed, adjusting for key sociodemographic covariates. Results: The protective effects of education on a range of health outcomes were significantly weaker for immigrants compared to non-immigrants. Education level showed weaker associations with SRH, cognitive function, numeracy, number of chronic conditions, and ADLs among immigrants. These findings suggest that even at higher levels of educational attainment, immigrants experience poorer health and cognitive functioning than their U.S.-born counterparts. Conclusion: This study offers strong evidence for the MDRs of education on multiple health outcomes among U.S. immigrants. One possible explanation is that, despite achieving higher levels of education, immigrants often face structural barriers—such as discrimination, limited access to resources, and economic inequities—that constrain the health-related benefits typically associated with educational attainment. Additionally, a portion of immigrant education may be acquired outside the United States, where credentials may not be fully recognized or rewarded within the U.S. labor market. These findings highlight the importance of policies aimed at addressing systemic inequities and improving access to healthcare, employment opportunities, and social support for immigrant communities. Future research should further explore the mechanisms underlying these diminished returns and identify policy solutions to reduce their impact. Keywords: Educational Attainment, Immigrants, Nativity, Self-Rated Health, Chronic Disease, Activities of Daily Living (ADL), Cognitive Function

“To Be Twice as Good to Get Half” is a common mindset among high aspiration and ambition Black individuals in the U.S., capturing the lived reality of Minorities’ Diminished Returns (MDRs). This paper explains that MDRs reflect how, even with high levels of ambition, self-efficacy, education, and income, Black individuals and other marginalized groups do not experience the same protective benefits for health and well-being as White populations. Systemic obstacles embedded within U.S. society weaken the expected returns on socioeconomic achievements for racialized individuals, creating a reality where “being twice as good” still results in lesser outcomes. High-SES Black individuals, for instance, continue to face significant risks for adverse outcomes, such as depression and chronic disease, due to structural inequities across domains like labor market discrimination, segregation, and accumulated disadvantage from childhood. Our analysis identifies key mechanisms—including interpersonal discrimination, lower-quality education, and structural racism in sectors like banking, policing, and real estate—that erode the protective effects of SES across racial lines. Mediating factors, such as chronic stress, allostatic load, and epigenetic changes over the life course, further compound these diminished returns, weakening the expected physical and mental health benefits. Drawing on extensive evidence from U.S. national and local datasets and corroborated by international studies, this paper underscores the necessity of policies that dismantle structural barriers rather than relying solely on SES improvements. Recommendations include implementing multi-sectoral policies, recognizing the unique challenges of middle-class non-White populations, and approaching policy with humility, acknowledging that achieving equity is a long-term endeavor. By challenging the “bootstraps” narrative, this paper advocates for structural interventions aimed at genuine health and economic equity for all racial and socioeconomic groups. While we provide an in-depth analysis of MDRs’ phenomena, mechanisms, mediators, and policy implications, the experience is often distilled as, “I have to be twice as good to get half.”

The pharmaceutical industry is undergoing a profound transformation driven by advancements in Information Technology (IT), with Enterprise Resource Planning (ERP) systems playing a pivotal role in reshaping operations. These systems offer integrated solutions that streamline key business processes, such as production, inventory management, supply chain optimization, regulatory compliance, and data integration, contributing significantly to operational efficiency and organizational agility. This paper explores the evolution and impact of ERP systems within the pharmaceutical sector, highlighting their contributions to overcoming the industry’s inherent challenges, including complex regulatory requirements, the need for accurate and real-time data, and the demand for supply chain resilience. The integration of cloud-based ERP solutions, the incorporation of emerging technologies like Artificial Intelligence (AI), Machine Learning (ML), and the Internet of Things (IoT), and enhanced data analytics capabilities have revolutionized pharmaceutical IT. These advancements not only reduce operational costs, improve forecasting accuracy, and enhance collaboration but also ensure compliance with stringent global regulations, such as Good Manufacturing Practices (GMP) and FDA guidelines. Moreover, ERP systems have been instrumental in managing the pharmaceutical supply chain, ensuring product traceability, and improving inventory control and order fulfillment processes. This manuscript examines how ERP systems enable pharmaceutical companies to maintain high standards of product quality, improve decision-making, and ensure the safety and efficacy of drugs through robust tracking and auditing mechanisms. A case study of a pharmaceutical company that implemented an ERP system demonstrates the tangible benefits, including increased operational efficiency, improved compliance rates, and enhanced customer satisfaction. However, despite the clear advantages, challenges such as customization complexities, data integration issues, and resistance to change remain. As the pharmaceutical industry continues to evolve, ERP systems will remain a cornerstone of digital transformation, facilitating smarter decision-making, better resource management, and enhanced collaboration across global operations. This paper also identifies future trends, including the potential of AI and blockchain technologies in further strengthening ERP systems and transforming the pharmaceutical landscape.

Background: Women have consistently shown lower quit rates in tobacco cessation programs compared to men. This gender disparity persists despite comprehensive interventions and access to cessation resources. While prior studies suggest that factors such as social support, chronic disease burden, and socioeconomic status may contribute to these differences, there is limited empirical evidence to confirm these mechanisms. Aims: This study aimed to investigate potential mechanisms underlying gender differences in quit rates in a tobacco cessation program, testing whether demographic, socioeconomic, health, or behavioral factors explain the observed disparities. Methods: Participants were assigned to one of three smoking cessation interventions: an in-person program (CEASE), a self-help approach, or an online/hybrid program. The main outcome measured was smoking abstinence, evaluated three months after the intervention. Secondary analyses explored whether demographic, socioeconomic, health, or tobacco use-related factors mediated the association between gender and quit rates. Results: Women had significantly lower quit rates than men (p < 0.01). This association remained significant after adjusting for demographic, socioeconomic, health, and addiction-related factors. While women reported higher social support and a higher prevalence of chronic cardiometabolic conditions, these factors did not explain the gender disparity in quit rates. Conclusions: Gender differences in quit rates persist despite controlling for known factors that could influence cessation success. Although women had higher social support, they had lower quit rate. Future research should explore unmeasured variables, such as psychological, biological, and structural influences, to develop more effective cessation strategies tailored for women.

Background: The hippocampus plays a critical role in memory and decision-making processes, with its resting-state functional connectivity (rsFC) linked to various behavioral outcomes. This study investigates whether baseline brain-wide rsFC of the hippocampus mediates the relationship between impulsivity and subsequent substance use, specifically tobacco and marijuana use, in adolescents. Methods: Data were drawn from the baseline wave of the Adolescent Brain Cognitive Development (ABCD) study. Resting-state fMRI data were used to evaluate the functional connectivity of the hippocampus with key brain networks, including the cingulo-parietal network, visual network, sensory-motor network, and default mode network (DMN). Impulsivity was assessed using validated self-report measures, and substance use (tobacco and marijuana) was evaluated at follow-up. Mediation models were conducted to examine the extent to which hippocampal rsFC explains the association between impulsivity and substance use. Results: Baseline hippocampal rsFC with the cingulo-parietal network, visual network, sensory-motor network, and DMN showed marginal associations with future tobacco and marijuana use. Additionally, hippocampal rsFC was significantly associated with impulsivity, which, in turn, predicted higher substance use at follow-up. These findings suggest that hippocampal rsFC partially mediates the relationship between impulsivity and substance use behaviors. Conclusions: Hippocampal functional connectivity with brain networks may influence the pathway from impulsivity to future substance use in adolescence. These findings emphasize the importance of hippocampal connectivity in understanding the neural mechanisms underlying risk behaviors and may inform the development of targeted interventions to reduce substance use in this vulnerable population.

Background: Tobacco control policies are implemented globally to reduce tobacco-related morbidity and mortality. Emerging evidence suggests that individual tobacco use may influence the level of support for these policies. However, the extent to which personal use affects policy endorsement remains underexplored, particularly among young adults in academic settings. Aims: This study aimed to examine whether college students who use tobacco exhibit lower support for tobacco control policies compared to their non-user counterparts. Methods: We conducted a multi-center, cross-sectional study involving 2403 college students from various provinces in Iran. Tobacco use was ascertained based on self-reported consumption of cigarettes, electronic cigarettes, and hookah. Attitudes toward tobacco control policies were evaluated using a structured survey instrument, and comparative analyses were performed to assess differences in policy support between tobacco users and non-users. Results: The analysis revealed that tobacco users demonstrated significantly lower support for tobacco control policies compared to non-users. This association was consistently observed across users of cigarettes, electronic cigarettes, and hookah, suggesting a systematic pattern irrespective of the type of tobacco product used. Conclusion: These findings indicated a clear association between tobacco use and reduced endorsement of tobacco control policies among Iranian college students. These results have potential implications for public health policy, emphasizing the importance of addressing individual tobacco use behaviors in the development and implementation of tobacco control strategies. Further research is needed to elucidate the underlying mechanisms of this relationship.

Background: Menthol-flavored tobacco products are disproportionately used in low-income African American communities, a result of decades of targeted marketing and systemic inequities. Menthol use has been associated with lower quit rates, often compounded by factors such as lower trust in healthcare systems, reduced access to cessation programs, and other structural barriers. Despite this, few studies have systematically examined the explanatory mechanisms that might clarify why menthol-flavored tobacco is linked to poorer cessation outcomes among participants in tobacco cessation programs. Aims: This study aimed to investigate the potential mechanisms by which menthol tobacco use is associated with lower quit rates across three types of smoking cessation interventions. Methods: Participants were randomized into one of three smoking cessation interventions: in-person (CEASE), self-help, or online/hybrid programs. Smoking abstinence was assessed three months post-intervention as the primary outcome. Secondary analyses explored whether demographic, socioeconomic, or behavioral factors mediated the association between menthol use and quit rates across the intervention arms. Results: Menthol tobacco use was significantly associated with lower quit rates (p < 0.01). This association was not explained by demographic, socioeconomic, health, or addiction-related factors. While menthol use was associated with lower education and employment levels, demographic characteristics, physical or mental health, or addiction did not explain the effect of menthol on tobacco cessation. These findings suggest that the lower quit rates observed among menthol users cannot be attributed to any third factors assessed in this study. Conclusions: Menthol tobacco use independently predicts lower quit rates, and the mechanisms behind this disparity remain unclear. The consistent findings across different intervention types highlight the need for further research to uncover the underlying pathways and to design targeted strategies to improve cessation outcomes for menthol users.

Background: As a central component of the brain's reward system, nucleus accumbens (NAcc) plays a crucial role in reward salience and substance use behaviors. Changes in the NAcc are also relevant to higher rates of substance use of youth and adults from low-income backgrounds. Although resting-state functional connectivity (rsFC) of the NAcc provides valuable insights into the neural mechanisms underlying reward processing and the propensity for self-reported reward salience and substance use, research exploring the association between NAcc rsFC and brain networks beyond the default mode network (DMN) and prefrontal cortex (PFC) is limited. Objective: To investigate the role of the resting-state functional connectivity of the NAcc with the cingulo-opercular network, sensorimotor mouth network, and sensorimotor hand network in the association between socioeconomic status, self-reported reward salience, and future substance use. Methods: Data were obtained from the Adolescent Brain Cognitive Development (ABCD) study. NAcc rsFC with the cingulo-opercular network, sensorimotor mouth network, and sensorimotor hand network was assessed at baseline. Socioeconomic status was measured using family income. Self-reported reward salience was assessed using validated psychometric scales. Substance use outcomes were tracked longitudinally over the study period. Structural Equation Modeling was employed to examine the covariances between family income, NAcc rsFC, reward salience, and subsequent substance use. Results: Higher baseline family income was positively associated with baseline NAcc rsFC (B = 0.092, p < 0.001) and negatively associated with baseline reward salience (B = -0.040, p = 0.036) and future substance use (B = -0.081, p < 0.001). Baseline NAcc rsFC was strongly and positively associated with reward salience (B = 0.734, p < 0.001) and future substance use up to age 13 (B = 0.124, p < 0.001). Additionally, baseline reward salience was positively associated with future substance use (Covariance = 0.176, p < 0.001). Conclusion: The findings suggest that NAcc rsFC with brain networks beyond the DMN or PFC may contribute to the links between low parental socioeconomic status, reward salience, and substance use risk. Expanding the understanding of NAcc rsFC provides new insights into the neural mechanisms underlying these associations. These results have important implications for developing targeted interventions aimed at preventing substance use, particularly among low-income youth with heightened reward salience. Further research is needed to explore causal pathways and moderating factors influencing these relationships.

Background: The Cingulo-Opercular Network (CON) is a crucial executive control network involved in regulating actions and facilitating higher-order cognitive processes. Resting-state functional connectivity between the CON and the Default Mode Network (DMN) plays a vital role in cognitive regulation, enabling the transition between internally focused and externally directed tasks. This study investigates whether resting-state functional connectivity between the CON and DMN mediates the effects of social determinants, such as educational opportunities and family structure, on cognitive outcomes in youth. Aims: This study aims to explore how CON-DMN connectivity influences the relationship between social gradients and cognition in youth. Specifically, it examines whether resting-state functional connectivity between these networks mediates the effects of educational opportunities and family structure on cognitive outcomes and seeks to uncover the neural mechanisms underlying these social gradients. Methods: Data were derived from the Adolescent Brain Cognitive Development (ABCD) study, a large longitudinal dataset of over 11,000 children aged 9–10 years. Cognitive outcomes were assessed using standardized NIH toolbox measures: Total Composite, Fluid Reasoning, Picture Vocabulary, Pattern Recognition, and Card Sorting. Social determinants were operationalized using indicators such as parental education, family composition, and neighborhood educational opportunities (COI). Resting-state functional connectivity (rsFC) between the CON and DMN was measured using functional magnetic resonance imaging (fMRI). Structural equation modeling (SEM) was employed to test whether CON-DMN rsFC mediated the relationship between social determinants and cognitive outcomes, adjusting for potential confounders such as age, sex, and race/ethnicity. Results: Stable family structure and greater educational opportunities were significantly associated with improved cognitive performance. These relationships were mediated by reduced functional connectivity between the CON and DMN. Conclusion: Reduced functional connectivity between the CON and DMN serves as a neural mechanism linking social gradients, such as educational opportunities and family structure, to better cognitive outcomes in youth.