Type 2 diabetes mellitus (T2DM) is a major disease worldwide, causing significant mortality and morbidity. Currently, in Aotearoa, New Zealand, there is a high prevalence of T2DM, with a disproportionate impact on Māori and Pacific populations(1). Moreover, it has been predicted that the prevalence will continually increase. Research has shown that insulin resistance (IR) has been reported to play a critical role in the development of T2DM and other related cardiometabolic diseases(2). Therefore, managing IR is crucial to reducing the development of T2DM. Notably, bioactive compounds in various diets are known to modify the risk of T2DM by regulating IR. Among such dietary compounds include kawakawa (Piper excelsum), an indigenous species used by Māori in traditional medicine (Rongoā). Kawakawa is shown to contain several bioactive compounds that are shown to have insulin-sensitising effects. Research by our group has recently shown kawakawa to have potential anti-diabetic and anti-inflammatory effects in healthy human volunteers(3,4). However, how Kawakawa exerts these effects on insulin signalling and glucose uptake remains unknown. We hypothesise that kawakawa will enhance the glucose uptake in the treated cells and will differentially regulate key genes involved in insulin signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, across various tissues. To test our hypothesis, we aim to investigate the mechanistic action of kawakawa extract on insulin signalling pathways in different cell models from metabolically active organs. We will use the same kawakawa powder sample shown to improve postprandial insulin in a healthy population. Cell models representing different insulin-responsive organs: liver (HepG2), skeletal muscle (L6-GLUT4myc), pancreas (MIN6), and adipose (3T3-L1) will be used. The cells will be treated with different doses of kawakawa extract, and glucose uptake will be measured. Key signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, will be monitored using western blot and quantitative polymerase chain reaction (qPCR) analysis. The findings of this study have the potential to identify key targets of kawakawa action on insulin signalling in metabolically active organs. These outcomes will inform future research with kawakawa in clinical settings in people with cardiometabolic diseases such as T2DM and can form the basis for developing a dietary intervention for individuals at risk of these diseases. Additionally, Rongoā is an acceptable intervention by Māori, integrating this knowledge with evidence-based scientific interventions would aid in creating a holistic health paradigm that resonates within Māori communities.

Astrobiology is a scientific field that is very interdisciplinary and developing very fast, with many new discoveries generating a high level of attention in both the scientific community and the public. A central goal of astrobiology is to discover life beyond Earth which is, with our current instrumentation and knowledge, arguably within our reach. However, knowledge exchange crossing disciplinary boundaries is becoming increasingly challenging due to different usage of nomenclature and scientific controversies often limited to subdisciplines. There have been some efforts to compile organized databases of terms, concepts and other relevant material within some of the subfields contributing to astrobiology, for example through manually curated online portals designed to benefit students, teachers and practitioners of astrobiology-related research. However, the developments within the subfields and the potentially premature communication of research findings are too fast for objective research portals to remain reliable and up-to-date enough to enable well-informed scientific discussions. We suggest here a novel strategy for developing an online tracers portal as a self-maintaining and self-updating information platform, that would allow not only for a relatively unbiased selection of research results, but also provide fast access to latest scientific discoveries together with potential controversies, such that users of the tracers portal can form their own opinion on all available data rather than obtaining an already filtered and potentially biased selection of information.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

Hospital food service quality significantly impacts patient satisfaction with overall care(1) and can influence food intake, thereby increasing the risk of malnutrition(2). By contrast, meals tailored to patients’ needs result in lower complications and hospitalisation costs(3). With Australia’s ageing population and projected increases among racial and ethnic minority migrants, service delivery must adapt to promote equity and inclusion in the healthcare system. However, data is lacking on the lived experience, preferences, and acceptance of hospital food service and meal quality among older patients from culturally and linguistically diverse (CALD) backgrounds. This study aimed to bridge this gap by investigating the differences in hospital food services related to cultural and ethnic backgrounds. Semi-structured qualitative interviews were planned among 15 Australian-born and 15 CALD-background patients, aged 65 years or over, admitted to the Department of General Medicine at Flinders Medical Centre. Patients admitted with a highly contagious infectious disease (e.g., COVID-19), those referred for palliative care, receiving parenteral or enteral nutrition, or on nil-by-mouth orders were excluded. Translators were available to participants upon request. With participants’ consent, all interviews were audio recorded and transcribed verbatim. Transcripts were analysed thematically using Braun and Clarke’s six-phase process(4). Data was inductively coded with a phenomenological perspective to explore participants’ experiences with hospital food services. Similar codes were grouped together and further developed into themes through iterative discussions with the research team. The current analysis involved six participants from each group to present preliminary results. Among the 12 participants, the mean age was 82 years, ranging from 72–92 in the Australian-born group and 68–92 in the CALD group. Five primary themes emerged: (1) No Complaints—participants did not want to complain about their meals, preferring staff to focus on their healthcare. This attitude was compounded for CALD participants who lacked the language to voice complaints; (2) Food and Identity—CALD participants viewed themselves separately from Australian-born patients, with the lack of culturally familiar food contributing to a feeling of being the minority; (3) Acceptance—the food service was viewed in the context of the overall hospital system, with participants accepting that meals may not suit their preference; (4) Experiences of the Food Service—influenced by participant’s individual preferences for meal quality, menu options, and staff interactions; and (5) Nutrition and Health—All participants had a preference for smaller portions due to their perception of reduced nutritional needs, yet meals were also valued for enjoyment. These preliminary results indicate that hospital food services should offer culturally familiar options, improve patient-staff communication, and provide personalised, smaller portions to enhance patient experience. Addressing the enablers and barriers to meeting cultural and individual dietary needs in hospitals will promote equity, diversity, and inclusion in healthcare.

Objectives/Goals: We assessed the feasibility of using a large language model (LLM) to create lay language descriptions of study protocols for recruitment, which has the potential to improve accessibility and transparency of clinical studies and enable participants to make informed decisions. Methods/Study Population: All studies from a clinical research recruitment platform were included, which features human-written lay descriptions and titles for study recruitment. Corresponding protocol summaries in the IRB system were extracted and translated into lay language using a LLM (gpt-35-turbo-0613). A subset was used to develop prompt variations through an iterative process. Prompt strategies evaluated include chain-of-thought and few-shot prompting techniques. LLM-generated and human-written descriptions were compared for readability using Flesch–Kincaid and Simple Measure of Gobbledygook (SMOG) reading grade levels and information completeness using Word Movers’ Distance (WMD). Results/Anticipated Results: A total of 55 study descriptions were included – 10 were used to develop prompts and 45 were used for evaluation. The final LLM instructions included multistep prompts. The LLM was first instructed to produce a two- to three-sentence long description without using scientific jargon and included two pairs of examples. The LLM was then asked to shorten the description and finally to provide an engaging title. LLM-generated and human-written summaries were similar in length (median (IQR) 328 (278.5–360.5) vs. 342 (203–532.5) characters, respectively). LLM-generated summaries had lower Flesch-Kincaid grade level (5.15 vs. 8.28, p Discussion/Significance of Impact: An LLM can be used to generate lay language summaries that are readable at a lower grade level while maintaining semantic similarity. This approach can be used to improve the drafting of summaries for recruitment, thereby improving accessibility to potential participants. Future work includes human evaluation and implementation into practice.

Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.

Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell-free DNA and rejection parameters to help elucidate this further. Methods/Study Population: Lung transplant candidacy prioritizes patients who have a high mortality risk within 2 years and will likely survive beyond 5 years. We stratified patients who died within 2 years of transplant as early death (n = 50) and those who survived past 5 years as long-term survivors (n = 53). Lung transplant recipients had serial blood collected as part of two prospective cohort studies. Cell-free DNA (cfDNA) was quantified using relative (% donor-derived cfDNA {%ddcfDNA}) and absolute (nuclear-derived {n-cfDNA}, mitochondrial-derived {mt-cfDNA}) measurements. As part of routine posttransplant clinical care, all patients underwent pulmonary function testing (PFT), surveillance bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy (TBBx), and donor-specific antibody testing (DSA). Results/Anticipated Results: Over the first 2 years after transplant, the number of episodes of antibody-mediated rejection (p) Discussion/Significance of Impact: Clinically, early-death patients perform worse on routine surveillance PFTs and experience a worse degree of CLAD. These patients also have higher levels of cfDNA as quantified by n-cfDNA and mt-cfDNA. These results provide preliminary evidence that early-death patients have worse allograft rejection, dysfunction, and molecular injury.