Depression, a leading cause of global disability, arises from a multifaceted combination of genetic and environmental components. This study explores the relationship between major depressive disorder (MDD) polygenic scores (PGS), characteristics and symptoms of depression, and community-shared socioeconomic factors derived from postal code data in a cohort of 12,646 individuals from the Australian Genetics of Depression Study (AGDS). Our findings reveal that people living in areas with relatively higher socioeconomic advantages and education/occupation scores are more likely to report experiencing fewer depressive symptoms during their worst depressive period, as well as fewer number of lifetime episodes. Additionally, participants who reported depression onset later in life tend to currently reside in wealthier areas. Interestingly, no significant interaction between genetic and socioeconomic factors was observed, suggesting their independent contribution to depression outcomes. This research underscores the importance of integrating socioeconomic factors into psychiatric evaluation and care, and points to the critical role of public policy in addressing mental health disparities driven by socioeconomic factors. Future research should aim to further elucidate the causal relationships within these associations and explore the potential for integrated genetic and socioeconomic approaches in mental health interventions.

Objectives/Goals: Cognitive decline is a known sequalae of intracranial radiation in the treatment of brain metastases. In this study, we investigate global structural changes in the brain akin to accelerated aging and compare aging kinetics between patients treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). Methods/Study Population: This retrospective study consists of patients with brain metastases treated with WBRT and SRS at our institution. Brain MRI images collected prior to radiation therapy and at approximately three and six months following radiation will be analyzed, excluding patients with evidence of worsening disease burden in the brain. Surface morphology of the cerebral cortex and sub-cortical structures will be extracted using Freesurfer and converted to graphs. Data will then be input into a validated graph convolutional neural network model to estimate brain age at each time point. A generalized linear model will be used to estimate the aging pace between baseline and follow-up for each subject within the whole brain as well as the sub-cortical structures, which will be compared between WBRT and SRS treatment groups. Results/Anticipated Results: We anticipate that intracranial radiation will accelerate brain aging to a greater extent following WBRT compared to SRS. Additionally, this accelerated aging will occur globally in the whole brain as well as within individual substructures, including the cerebral cortex, nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Discussion/Significance of Impact: This study will demonstrate structural changes in the brain analogous to accelerated aging, supporting its potential use as an imaging biomarker to monitor cognitive decline after radiation therapy. Future work will explore the relationship between structural brain aging and assessments of neurocognitive function.

Objectives/Goals: This scoping review examines how socioeconomic status (SES) and sociodemographic status (SDS) disparities are considered in transition interventions for congenital heart disease (CHD) patients. By identifying gaps, it aims to guide future research and interventions to address inequities in transitional care. Methods/Study Population: A systematic search of the literature was performed using PubMed, Scopus, and Web of Science. Literature was searched from January 1990 to October 2024 and revealed 823 articles. Upon initial screening, 71 duplicates, 76 non-SES focused articles, and an additional 128 irrelevant articles were excluded. A total of 548 full-text articles were reviewed. Articles that did not focus on transition interventions for CHD patients were excluded. Studies were analyzed for factors affecting care transitions with special attention to SDS and SES factors. SDS factors were defined as age, gender, race/ethnicity, and geographic location, while SES factors were defined as income level, education, employment status, and access to care. Results/Anticipated Results: Out of 548 articles reviewed, only 18 addressed SES factors, and 10 examined SDS factors in the transition from pediatric to adult care. The most common interventions were patient education (33%), care coordination (29%), and family support (21%), but they lacked tailoring to SES/SDS factors. Patients from low-income households were 50% more likely to experience care discontinuities and 40% less likely to participate in transition programs. Health literacy interventions were generic, overlooking socioeconomic differences. Tailored transition programs are needed to address low health literacy and financial barriers, potentially improving outcomes for disadvantaged patients in rural and underserved areas. Discussion/Significance of Impact: This review exposes the limited focus on SES and SDS disparities in CHD transition interventions. Disadvantaged patients face barriers like limited access to care and low health literacy. Developing tailored programs to address these gaps is crucial for enhancing transitions and improving long-term outcomes for vulnerable CHD patients.

The Ediacaran/Cambrian transition (ECT; ~575–500 Ma) captures the early diversification of animals, including the oldest crown-group taxa of most major animal phyla alive today. Key to understanding the drivers underneath the ECT macroevolutionary patterns are the interactions of animals with one another and their environment, and how these interactions scale up to global diversity patterns. Understanding the ecology of ECT organisms is enabled by the abundance of Lagerstätten over this time period, with a relatively large proportion of soft-bodied organisms preserved, often within the communities in which they lived. Here, we review our understanding of organismal, community, and macroecology of the ECT, and how these different scales of ecological analyses relate to the macroevolutionary diversification patterns we see over this 75 Myr time period. Across all ecological scales, we find clear trends, starting with stochastic ecosystem dynamics dominated by generalist taxa in the first Ediacaran communities, to more structured, niche-driven specialist dynamics by Cambrian Epoch 2. These trends are reflected in organism functional morphology, the complexity and strength of organisms’ interactions within their communities, and large-scale metacommunity, biogeographic, and biodiversity patterns. Yet there is often a time delay between the origination of a new type of ecological interaction and when it is observed to impact the ecosystem as a whole. As such, while many modern ecological innovations were in place by the end of the Cambrian, the knock-on effects and complexity of these interactions continued to build up throughout the Phanerozoic, leading to the complex biosphere we have today.

Marsupials give birth to immunologically naïve young after a relatively short gestation period compared with eutherians. Consequently, the joey relies significantly on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the S100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet, there are numerous additional research opportunities to pursue, including uncovering novel bioactive components and investigating their modes of action, dynamics, stability and ability to penetrate the gut epithelium to facilitate systemic effects.

Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.

Obesity is one of the major contributors to the excess mortality seen in people with severe mental illness (SMI) and in low- and middle-income countries people with SMI may be at an even greater risk. In this study, we aimed to determine the prevalence of obesity and overweight in people with SMI and investigate the association of obesity and overweight with sociodemographic variables, other physical comorbidities, and health-risk behaviours. This was a multi-country cross-sectional survey study where data were collected from 3989 adults with SMI from three specialist mental health institutions in Bangladesh, India, and Pakistan. The prevalence of overweight and obesity was estimated using Asian BMI thresholds. Multinomial regression models were then used to explore associations between overweight and obesity with various potential determinants. There was a high prevalence of overweight (17·3 %) and obesity (46·2 %). The relative risk of having obesity (compared to normal weight) was double in women (RRR = 2·04) compared with men. Participants who met the WHO recommendations for fruit and vegetable intake had 2·53 (95 % CI: 1·65–3·88) times greater risk of having obesity compared to those not meeting them. Also, the relative risk of having obesity in people with hypertension is 69 % higher than in people without hypertension (RRR = 1·69). In conclusion, obesity is highly prevalent in SMI and associated with chronic disease. The complex relationship between diet and risk of obesity was also highlighted. People with SMI and obesity could benefit from screening for non-communicable diseases, better nutritional education, and context-appropriate lifestyle interventions.

The clinical field of depression and other mood disorders is characterised by the vast heterogeneity between those who present for care, and the highly variable degree of response to the range of psychological, pharmacological and physical treatments currently provided. These individual differences likely have a genetic component, and leveraging genetic risk is appealing because genetic risk factors point to causality. The possibility that individual genotyping at entry to health care may be a key way forward is worthy of discussion (Torkamani et al., 2018).

Coconut farming contributes to the livelihoods of millions of people in tropical countries but is less frequently considered as a threat to biodiversity compared to other palm commodities such as oil palm. The expansion of coconut farming alongside other smallholder agriculture in Sulawesi, Indonesia, is of potential concern as the region is a centre of species endemism. We studied bird diversity and community structure in forests, coconut palm plantations and mixed farmland in Gorontalo Province, northern Sulawesi. Forest and non-forest sites supported similar numbers of species overall, but compared to agricultural areas, forest sites had communities that were more diverse and more even (i.e. different species were present at similar abundances). We found far fewer endemic species in agricultural areas compared to forests, and the communities in palm plantations and mixed farmland sites were dominated by generalist birds, with few indicator taxa. Nevertheless, there was a higher number of endemic species in coconut palm plantations than in mixed farmland sites. These findings mirror patterns of biotic homogenization documented elsewhere in the Wallacea centre of endemism, and imply that coconut palm plantations have comparable biodiversity value to other farmland systems. Increased protection of lowland forests and improved management of coconut farms could be important for supporting the conservation of the endemic birds of Sulawesi in the long term, but this warrants further study.

The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD. We use a polygenic risk score (PRS) approach to test to what extent the genetic risk for AD, and related risk factors predict participation in PISA. We did not identify a significant association of genetic risk for AD with study participation, but we did identify significant associations with PRS for key causal risk factors for AD, IQ, household income and years of education. We also found that older and female participants were more likely to take part in the study. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies.

In this paper, we investigate the thermal evolution in a one-dimensional bagasse stockpile. The mathematical model involves four unknowns: the temperature, oxygen content, liquid water content and water vapour content. We first nondimensionalize the model to identify dominant terms and so simplify the system. We then calculate solutions for the approximate and full system. It is shown that under certain conditions spontaneous combustion will occur. Most importantly, we show that spontaneous combustion can be avoided by sequential building. To be specific, in a situation where, say, a $4.7\,$m stockpile can spontaneously combust, we could construct a $3\,$m pile and then some days later add another $1.7\,$m to produce a stable $4.7\,$m pile.

Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.