Objectives/Goals: This research develops a Ruthenium (III)–Fruquintinib complex for lung cancer treatment. Goals include structural characterization using MALDI-TOF and UV–Vis spectroscopy, synthesis optimization, and antitumor activity assessment comparing efficacy against Fruquintinib alone through cell studies. Methods/Study Population: The Ruthenium(III)–Fruquintinib complex is synthesized through an optimized coordination chemistry protocol ensuring reproducibility. Small-scale reactions defined baseline conditions, monitored by UV–Vis spectroscopy for ligand–metal charge transfer. After successful crystallization, the method was scaled up consistently. Structural characterization using MALDI-TOF mass spectrometry will be performed in collaboration with the MSRC, University of Puerto Rico, with infrared spectroscopy as a complementary validation. Biological evaluation will use NSCLC cell lines to compare cytotoxic efficacy against Fruquintinib alone, employing MTT assays to determine IC50 and potential synergistic effects. Results/Anticipated Results: Lung cancer remains the leading cause of cancer-related mortality, with 125,070 projected deaths in 2024. Current treatments for metastatic disease include surgery, chemotherapy, radiation, and targeted therapy. Fruquintinib (FQ), a VEGFR inhibitor, showed promise in early NSCLC trials but limited efficacy in advanced stages. Ruthenium (III) complexes, based on the hard–soft acid–base principle, offer potential anticancer properties. Combining FQ with Ruthenium (III) may enhance therapeutic outcomes. Preliminary synthesis yielded reproducible crystals confirmed by UV–Vis signals. Future MALDI-TOF characterization and biological assays will assess structural validity and antitumor potential. Discussion/Significance of Impact: The Ruthenium (III)–Fruquintinib complex could enhance Fruquintinib efficacy in advanced NSCLC. This approach demonstrates the potential of metal-based drug design to improve cancer therapies, offering insights into combinatorial strategies and advancing coordination chemistry in medicinal research.

Although temperamental negative affectivity has been identified as a developmental mechanism mediating the link between perinatal risk and internalizing problems in early childhood, its role in predicting broader behavioral and emotional problems across childhood remains understudied. We examined the longitudinal relations among perinatal complications (i.e., prenatal maternal depression and cardiometabolic complications, preterm birth, and low birth weight), children’s negative affectivity (Mage = 2.76; SD = 2.32; range = 0.24–12.46 years), and children’s internalizing, externalizing, and total problems (Mage = 5.12; SD = 2.63; range = 1.50–16.85 years) in the Environmental influences on Child Health Outcomes (ECHO) program (N = 3070; 47% females). Results support child negative affectivity as a mechanism in the developmental pathway linking perinatal maternal depressive symptoms and preterm birth to future emotional and behavioral problems, underscoring the importance of early prevention and intervention efforts to promote psychological well-being of at-risk children.

Socioeconomic disadvantage has been established as a key risk factor for adverse child behavioral outcomes. Understanding how individual components of socioeconomic status (SES) interact with each other can elucidate protective factors and inform interventions and policies to promote positive developmental outcomes. This study examined the interactive effects of prenatal household income and neighborhood deprivation on child externalizing and internalizing problems (N = 793; Mage = 8.37 years; 51.2% females; 81.5% White). Results revealed an interaction effect between prenatal household income levels and neighborhood deprivation on child externalizing problems. Higher neighborhood deprivation was associated with higher child externalizing outcomes only at lower household income levels per person. Although no interaction between household income and neighborhood deprivation on child internalizing problems was observed, lower household income levels were independently associated with higher child internalizing problems. These findings underscore how prenatal individual- and neighborhood-level SES factors interact to shape children’s behavioral outcomes across childhood.

Nearly 80% of the world’s population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7–13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.

Inhibitory control plays an important role in children’s cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents’ psychopathology are associated with children’s inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children’s behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; Mage = 7.13 years; Rangeage = 4–11 years). Results showed that theta power, which was positively predicted by prenatal SES and was negatively related to children’s externalizing problems, mediated the longitudinal and negative relation between them. ERP amplitudes and latencies did not mediate the longitudinal association between prenatal risk factors (i.e., prenatal SES and maternal psychopathology) and children’s internalizing and externalizing problems. Our findings increase our understanding of the neural pathways linking early risk factors to children’s psychopathology.

In this paper, we prove that the lower triangular matrix category $\Lambda =\left [ \begin{smallmatrix} \mathcal{T}&0\\ M&\mathcal{U} \end{smallmatrix} \right ]$, where $\mathcal{T}$ and $\mathcal{U}$ are $\textrm{Hom}$-finite, Krull–Schmidt $K$-quasi-hereditary categories and $M$ is an $\mathcal{U}\otimes _K \mathcal{T}^{op}$-module that satisfies suitable conditions, is quasi-hereditary. This result generalizes the work of B. Zhu in his study on triangular matrix algebras over quasi-hereditary algebras. Moreover, we obtain a characterization of the category of the $_\Lambda \Delta$-filtered $\Lambda$-modules.

Recent models of psychopathology suggest the presence of a general factor capturing the shared variance among all symptoms along with specific psychopathology factors (e.g., internalizing and externalizing). However, few studies have examined predictors that may serve as transdiagnostic risk factors for general psychopathology from early development. In the current study we examine, for the first time, whether observed and parent-reported infant temperament dimensions prospectively predict general psychopathology as well as specific psychopathology dimensions (e.g., internalizing and externalizing) across childhood. In a longitudinal cohort (N = 291), temperament dimensions were assessed at 4 months of age. Psychopathology symptoms were assessed at 7, 9, and 12 years of age. A bifactor model was used to estimate general, internalizing, and externalizing psychopathology factors. Across behavioral observations and parent-reports, higher motor activity in infancy significantly predicted greater general psychopathology in mid to late childhood. Moreover, low positive affect was predictive of the internalizing-specific factor. Other temperament dimensions were not related with any of the psychopathology factors after accounting for the general psychopathology factor. The results of this study suggest that infant motor activity may act as an early indicator of transdiagnostic risk. Our findings inform the etiology of general psychopathology and have implications for the early identification for children at risk for psychopathology.

Identifying early risk factors for the development of social anxiety symptoms has important translational implications. Accurately identifying which children are at the highest risk is of critical importance, especially if we can identify risk early in development. We examined continued risk for social anxiety symptoms at the transition to adolescence in a community sample of children (n = 112) that had been observed for high fearfulness at age 2 and tracked for social anxiety symptoms from preschool through age 6. In our previous studies, we found that a pattern of dysregulated fear (DF), characterized by high fear in low threat contexts, predicted social anxiety symptoms at ages 3, 4, 5, and 6 years across two samples. In the current study, we re-evaluated these children at 11–13 years of age by using parent and child reports of social anxiety symptoms, parental monitoring, and peer relationship quality. The scores for DF uniquely predicted adolescents’ social anxiety symptoms beyond the prediction that was made by more proximal measures of behavioral (e.g., kindergarten social withdrawal) and concurrent environmental risk factors (e.g., parental monitoring, peer relationships). Implications for early detection, prevention, and intervention are discussed.

Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for ‘sticking to healthful foods’ and who ‘felt weird if [they] didn’t eat healthily’. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions of Bocconia frutescens L. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects of B. frutescens L. in an experimental model. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7–13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20. Bocconia frutescens L. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption of B. frutescens L. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.

The current study had three goals. First, we replicated recent evidence that suggests a concurrent relation between attention bias to reward and externalizing and attention problems at age 7. Second, we extended these findings by examining the relations between attention and behavioral measures of early exuberance (3 years), early effortful control (4 years), and concurrent effortful control (7 years), as well as later behavioral problems (9 years). Third, we evaluated the role of attention to reward in the longitudinal pathways between early exuberance and early effortful control to predict externalizing and attention problems. Results revealed that attention bias to reward was associated concurrently and longitudinally with behavioral problems. Moreover, greater reward bias was concurrently associated with lower levels of parent-reported effortful control. Finally, attention bias to reward moderated the longitudinal relations between early risk factors for behavioral problems (gender, exuberance, and effortful control) and later externalizing and attention problems, such that these early risk factors were most predictive of behavioral problems for males with a large attention bias to reward. These findings suggest that attention bias to reward may act as a moderator of early risk, aiding the identification of children at the highest risk for later behavioral problems.

Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.

Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.

The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AAv. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (P trend=0·028) and 3·1 cm greater WC (P trend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.

An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0·001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson’s correlation between the measured values and the predicted values was r 0·65, and the sd of their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.