Objectives/Goals: As the aging population increases, maintaining cognitive and physical health becomes crucial. Executive functions (EF), including reaction time, sustained attention, and spatial memory, are essential for daily life and independence in older adults but tend to decline with age, especially in Alzheimer’s disease (AD) patients. Methods/Study Population: Physical balance (PB) impairments further exacerbate this decline, affecting the quality of life and independence. Balance training (BT) emerges as a potential non-pharmacological intervention to enhance EF. This study aims to 1) assess the association between PB impairments and EF deterioration in older adults with AD; 2) evaluate the impact of BT on EF enhancement in this population; and 3) explore changes in brain-derived neurotrophic factor (BDNF) biomarkers before and after physical activity related to BT. This pilot study employs a cross-sectional design with older Hispanic adults (>65 years) in Puerto Rico, comparing a control group without BT intervention to an experimental group with BT intervention. Both groups will be assessed for EF and BDNF biomarkers pre- and post-physical activity. Results/Anticipated Results: Expected outcomes include identifying significant correlations between PB impairment and diminished EF, demonstrating measurable EF improvements following BT, and evidencing sustained BDNF release post-BT despite PB impairments. By understanding the biological mechanisms linking BT and cognitive improvements, particularly the role of BDNF, this research could inform future strategies to mitigate cognitive decline in AD patients through targeted physical interventions. Discussion/Significance of Impact: The findings of this study could provide valuable insights into the development of new preventive interventions, enhancing the quality of life and independence for older adults.

Objectives/Goals: Gait performance (GP) and global cognitive functions (GCF) are both critical for maintaining independence and quality of life in senior adults. Recent studies have explored the potential link between GP and GCF, encompassing executive functions. Methods/Study Population: PRISMA guidelines will govern this systematic review. This systematic review synthesizes published research from 2000 to 2024, including peer-reviewed articles, pilot studies, and randomized controlled trials, to examine the relationship between GP (how a person walks and stands) and GCP in older adults. The exclusion criteria will be based on studies focused on physical activities unrelated to balance, meta-analysis, and systematic reviews and those published in languages other than English or Spanish. Results/Anticipated Results: Our preliminary data indicate that gait, or walking speed, is significantly correlated with GCP in older adults, with slower walking associated with poorer global cognition. Specifically, gait speed during dual-task walking shows a strong correlation with working memory (p < .001) and processing speed (p < .05) in individuals aged over 60 years. Gender differences were observed, with women over 80 walking slower than men over 85 years, who walked faster, and women exhibited poorer global cognition than men. Discussion/Significance of Impact: Overall, a gait slowing between 0.68 and 1.1 m per second could predict a marker for the risk of developing dementia, indicating that monitoring gait speed in older adults may provide early warning signs, allowing for timely interventions. Enhancing GP and GCF can improve the quality of life and independence in older adults. Acknowledgments: Research supported by NIH: Award Number HCTRECD R25MD007607 from the NIMHD.

As one of the most neglected zoonotic diseases, brucellosis has posed a serious threat to public health worldwide. This study is purposed to apply different machine learning models to improve the prediction accuracy of human brucellosis (HB) in Shaanxi, China from 2008 to 2020, under livestock husbandry intensification from a spatiotemporal perspective. We quantitatively evaluated the performance and suitability of ConvLSTM, RF, and LSTM models in epidemic forecasting, and investigated the spatial heterogeneity of how different factors drive the occurrence and transmission of HB in distinct sub-regions by using Kernel Density Analysis and Shapley Additional Explanations. Our findings demonstrated that ConvLSTM network yielded the best predictive performance with the lowest average RMSE of 13.875 and MAE values of 18.393. RF model generated an underestimated outcome while LSTM model had an overestimated one. In addition, climatic conditions, intensification of livestock keeping and socioeconomic status were identified as the dominant factors that drive the occurrence of HB in Shaanbei Plateau, Guanzhong Plain, and Shaannan Region, respectively. This work provided a comprehensive understanding of the potential risk of HB epidemics in Northwest China driven by both anthropogenic activities and natural environment, which can support further practice in disease control and prevention.

Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were −0·70 (–2·49, 1·09) for rarely drinks, −0·82 (–2·62, 0·97) for < 1 cup/week and −0·86 (–2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

OBJECTIVES/GOALS: The 'field effect' is a concept in pathology that pre-malignant tissue changes forecast health. Spatial transcriptomics could detect these changes earlier than histopathology, suggesting new early cancer screening methods. Knowing how normal tissue damage relates to cancer’s origin and progression may improve long-term outcomes. METHODS/STUDY POPULATION: We trained DEGAS, our machine learning framework, with prostate cancer data, combining both general cancer patterns and in-depth genetic information from individual tumors. The Tumor Cancer Genome Atlas (TCGA) shows how gene patterns in tumors relate to patient outcomes, emphasizing the differences between tumors from different patients (intertumor). On the other hand, spatial transcriptomics (ST) shows the genetic variety within a single tumor (intratumor) but has limited samples, making it hard to know which genetic differences are important for treatment. DEGAS bridges these areas by finding tissue sections that resemble those in TCGA profiles and are key indicators of patient survival. DEGAS serves as a valuable tool for generating clinically-important hypotheses. RESULTS/ANTICIPATED RESULTS: DEGAS identified benign-appearing glands in a normal prostate as being highly associated with poor progression-free survival. These glands have transcriptional signatures similar to high-grade prostate cancer. We confirmed this finding in a separate prostate cancer ST dataset. By integrating single cell (SC) data we demonstrated that cells annotated as cancerous in the SC data map to regions of benign glands in the ST dataset. We pinpoint several genes, chiefly Microseminoprotein-β (MSMB, PSP94), where reduced expression is highly correlated with poor progression-free survival. Cell type specific differential expression analysis further revealed that loss of MSMB expression associated with poor outcomes occurs specifically in luminal epithelia, the putative progenitor of prostate cancer. DISCUSSION/SIGNIFICANCE: DEGAS reveals that normal-appearing tissue can be highly-associated with tumor progression and underscores the importance of the 'field effect' in cancer research. Traditional analysis may miss such nuance, hiding key transitional cell states. Validating gene markers could boost early cancer detection and understanding of metastasis.

A low-profile wideband circularly polarized (CP) metasurface antenna is demonstrated for C-band applications. The metasurface consists of 4 × 4 square patches with Z-shaped slots. Characteristic mode analysis is used to investigate the modal behavior of the metasurface, and a pair of degenerate modes is chosen as the operating modes. The CP radiation is realized by exciting a pair of degenerate modes of the metasurface through a slot antenna, which is used as a feed structure with a 90° phase difference. The CP bandwidth is further widened by combining the resonance modes of the metasurface and slot antenna. The measured results show that the −10 dB impedance bandwidth of the antenna is 3.47–4.76 GHz, and the 3 dB axial ratio bandwidth is 3.5–4.9 GHz with a peak gain of 6.9 dBic. Moreover, the antenna exhibits well left-hand CP radiation performances with a low profile of 0.046λ0.

Multilayer dielectric gratings (MLDGs) are crucial for pulse compression in picosecond–petawatt laser systems. Bulged nodular defects, embedded in coating stacks during multilayer deposition, influence the lithographic process and performance of the final MLDG products. In this study, the integration of nanosecond laser conditioning (NLC) into different manufacturing stages of MLDGs was proposed for the first time on multilayer dielectric films (MLDFs) and final grating products to improve laser-induced damage performance. The results suggest that the remaining nodular ejection pits introduced by the two protocols exhibit a high nanosecond laser damage resistance, which remains stable when the irradiated laser fluence is more than twice the nanosecond-laser-induced damage threshold (nanosecond-LIDT) of the unconditioned MLDGs. Furthermore, the picosecond-LIDT of the nodular ejection pit conditioned on the MLDFs was approximately 40% higher than that of the nodular defects, and the loss of the grating structure surrounding the nodular defects was avoided. Therefore, NLC is an effective strategy for improving the laser damage resistance of MLDGs.

OBJECTIVES/GOALS: Single-cell and spatial transcriptomics have revealed high heterogeneity in the tumor and microenvironment. Identifying populations of cells that impact a patient’s prognosis is an important research goal, so researchers can generate hypotheses and clinicians can provide targeted treatment. METHODS/STUDY POPULATION: DEGAS uses deep-transfer-learning to identify patterns between patient tumor RNA-seq and clinical outcomes and map these associations on to higher-resolution data like spatial and single-cell transcriptomics. We apply DEGAS to prostate and pancreatic cancer spatial transcriptomics samples, as well as one normal sample of prostate tissue. We used the TCGA prostate cancer cohort to with the accompanying survival information and publicly accessible prostate cancer ST data from 10X Genomics to predict survival associations in the ST slides derived from the TCGA patients. Based on these survival associations, we identify higher risk subsections of ST slides which can be further studied. RESULTS/ANTICIPATED RESULTS: We were able to validate our method by comparing it to Scissor and were able to show that the number of high-risk regions in prostate cancer slides increased with the stage of disease. Furthermore, we identify transcriptomic signatures enriched for ontology terms associated with growth regulation and apoptosis, inflammation, immune signaling, and autophagy in histologically normal prostate tissues and adjacent normal pancreatic cancer tissues that were identified as high-risk by DEGAS. The regions highlighted by DEGAS could reflect transcriptional precursors to intraepithelial neoplasia–a well-recognized premalignant morphological change in glandular epithelium. DISCUSSION/SIGNIFICANCE: Identifying biomarkers of tissue stress that precede morphologic diagnosis of high-grade pre-malignant lesions by a pathologist may help triage patients at high risk for future development of cancer, or aid in better understanding whether histologically normal pre-malignant tissues at tumor margins contribute to recurrence.

Multilayer dielectric gratings typically remove multiple-grating pillars after picosecond laser irradiation; however, the dynamic formation process of the removal is still unclear. In this study, the damage morphologies of multilayer dielectric gratings induced by an 8.6-ps laser pulse were closely examined. The damage included the removal of a single grating pillar and consecutive adjacent grating pillars and did not involve the destruction of the internal high-reflection mirror structure. Comparative analysis of the two damage morphological characteristics indicated the removal of adjacent pillars was related to an impact process caused by the eruption of localized materials from the left-hand pillar, exerting impact pressure on its adjacent pillars and eventually resulting in multiple pillar removal. A finite-element strain model was used to calculate the stress distribution of the grating after impact. According to the electric field distribution, the eruptive pressure of the dielectric materials after ionization was also simulated. The results suggest that the eruptive pressure resulted in a stress concentration at the root of the adjacent pillar that was sufficient to cause damage, corresponding to the experimental removal of the adjacent pillar from the root. This study provides further understanding of the laser-induced damage behavior of grating pillars and some insights into reducing the undesirable damage process for practical applications.

The mitochondrial genome provides important information for phylogenetic analysis and an understanding of evolutionary origin. In this study, the mitochondrial genomes of Ilisha elongata and Setipinna tenuifilis were sequenced, which are typical circular vertebrate mitochondrial genomes composed of 16,770 and 16,805 bp, respectively. The mitogenomes of I. elongata and S. tenuifilis include 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), two ribosomal RNA (rRNA) genes and one control region (CR). Both two species' genome compositions were highly A + T biased and exhibited positive AT-skews and negative GC-skews. The genetic distance and Ka/Ks ratio analyses indicated that 13 PCGs were affected by purifying selection and the selection pressures were different from certain deep-sea fishes, which were most likely due to the difference in their living environment. Results of phylogenetic analysis support close relationships among Chirocentridae, Denticipitidae, Clupeidae, Engraulidae and Pristigasteridae based on the nucleotide and amino acid sequences of 13 PCGs. Within Clupeoidei, I. elongata and S. tenuifilis were most closely related to the family Pristigasteridae and Engraulidae, respectively. These results will help to better understand the evolutionary position of Clupeiformes and provide a reference for further phylogenetic research on Clupeiformes species.

It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.

This work studies the detachment of a micron-sized spherical particle from a surface with concave roughness in a linear shear flow. The concave roughness is described as regularly spaced hollow hemispheres below a flat surface and is characterised by two dimensionless parameters, i.e. dimensionless asperity distance and asperity size ratio. The hydrodynamic force and torque on the particle are calculated by performing lattice Boltzmann simulations for particle Reynolds numbers ranging from 0.02 to 40. Empirical correlations of the drag, lift and torque coefficients of the particle as functions of the particle Reynolds number and the asperity size ratio are proposed. For detachment by lifting, sliding and rolling, a numerical approach to calculate the critical particle Reynolds number (i.e. above which the particle can detach from the surface) is proposed. It is found that the dimensionless asperity distance and the distribution of asperities on the rough surface have a minor influence on the hydrodynamic force and torque on the particle, and the detachment of the particle becomes more difficult as the particle sits deeper in a larger hole. Both the empirical correlations and the numerical approach can be implemented into Lagrangian particle tracking and can accurately predict the detachment of particles from the surface with concave roughness or the detachment of particles embedded in a flat surface.

The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.

Prospective cohort studies linking organ meat consumption and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15 568 adults who were free of liver disease, CVD and cancer at baseline. Dietary information was collected at baseline using a validated FFQ. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4·2 years of follow-up, we identified 3604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood and red meat consumption, the multivariable hazard ratios (95 % CI) for incident NAFLD across consumption of organ meat were 1·00 (reference) for almost never, 1·04 (0·94, 1·15) for tertile 1, 1·08 (0·99, 1·19) for tertile 2 and 1·11 (1·01, 1·22) for tertile 3, respectively (P for trend < 0·05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.