Project description:BackgroundHealthline is one of the 39 free telehealth services that Whakarongorau Aotearoa/New Zealand Telehealth Services provides to New Zealanders. In early 2021, an image upload system for viewing service user-uploaded images was implemented into the Healthline service.AimsThe aim of this research was to understand the utilisation of Healthline's image upload system by clinicians and service users in New Zealand.MethodsThis is a retrospective observational study analysing Healthline image upload data over a two-year period: March 2021 through to December 2022. A total of 40,045 images were analysed, including demographics of the service users who uploaded an image: ethnicity, age group, and area of residence. The outcome or recommendation of the Healthline call was also assessed based on whether an image was included.ResultsImages uploaded accounted for 6.0% of total Healthline calls (n = 671,564). This research found that more service users were advised to go to an Emergency Department if they did not upload an image compared to service users who used the tool (13.5% vs. 7.7%), whereas a higher proportion of service users were given a lower acuity outcome if they included an image, including visiting an Urgent Care (24.0% vs. 16.9%) and GP (36.7% vs. 24.3%).ConclusionService users who did not upload an image had a higher proportion of Emergency Department outcomes than service users who did use the tool. This image upload tool has shown the potential to decrease stress on Emergency Departments around Aotearoa, New Zealand, through increased lower acuity outcomes.
Project description:Uncertainties, such as road restrictions at shipyards and the irregular shape of blocks, pose challenges for transporter scheduling. Efficient scheduling of multiple transporters is critical to improving transportation efficiency. The digital twin (DT) technology offers numerous benefits, enabling interactions between the virtual and real worlds, real-time mapping, and dynamic performance evaluation. Based on DT technology, this study proposes a dynamic scheduling approach for cooperative transportation utilizing multiple transporters. The scheduling problem for multiple transporters is addressed and modeled in this study, considering factors such as block size and transporter loading. To solve this problem, a framework of DT-based multiple transporters system is established in a virtual environment. By inputting block information into this system, a solution is generated using transporter scheduling rules and interference detection methods. Experimental comparisons are conducted in this paper, exploring various scenarios with different number of tasks and the application of DT. The results demonstrate that the proposed approach effectively enhances transportation efficiency and improves ship construction efficiency. Hence, this study expands the application of DT technology in dynamic scheduling of transportation in shipyards and provides new ideas for shipbuilding company managers.
Project description:The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel therapeutic target for osteoarthritis. Here, we use DNA-encoded Library Technology (ELT) to identify novel ADAMTS-4 inhibitors from a DNA-encoded triazine library by affinity selection. Structure-activity relationship studies based on the selection information led to the identification of potent and highly selective inhibitors. For example, 4-(((4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-6-(((4-methylpiperazin-1-yl)methyl)amino)-1,3,5-triazin-2-yl)amino)methyl)-N-ethyl-N-(m-tolyl)benzamide has IC50 of 10 nM against ADAMTS-4, with >1000-fold selectivity over ADAMT-5, MMP-13, TACE, and ADAMTS-13. These inhibitors have no obvious zinc ligand functionality.
Project description:Summary High-power screening (HPS) technologies, such as DNA-encoded library (DEL) technology, could exponentially increase the dimensions of the chemical space accessible for drug discovery. The intrinsic fragile nature of DNA is associated with cumbersome limitations and DNA durability (e.g., depurination, loss of phosphate groups, adduct formation) is compromised in numerous organic chemistry conditions that require empirical testing. An atlas of reaction conditions (temperature, pH, solvent/buffer, ligands, oxidizing reagents, catalysts, scavengers in function of time) that have been systematically tested in multiple combinations, indicates precisely limits useful for DEL construction. More importantly, this approach could be used broadly to effectively evaluate DNA-compatibility of any novel on-DNA chemical reaction, and it is compatible with different molecular methodologies. This atlas and the general approach presented, by allowing novel reaction conditions to be performed in presence of DNA, should greatly help in expanding the DEL chemical space as well as any field involving DNA durability. Graphical abstract Highlights • Comprehensive atlas of numerous reaction conditions compatible with DNA• Molecular approach to test DNA durability in a time-dependent manner• Impact of different treatments (e.g., temperatures, pHs, catalysts, ligands) on DNA• Importance of DNA content (GC %) and DNA nature for stability Organic chemistry; Biochemistry
Project description:The crucial role of VEGF receptor 2 (VEGFR2) signaling in the angiogenesis and metastasis of solid tumors has prompted the development of inhibitors with minimal bystander effects. Recently, Adnectin C has attracted attention for cancer treatment. To overcome the problematic properties of Adnectin, a novel form of Adnectin C has been designed by its fusion to a biodegradable polymeric peptide containing Pro/Ala/Ser (PAS) repetitive residues. E. coli-expressed recombinant fused and unfused proteins were compared in terms of bioactivity, physicochemical, and pharmacokinetic properties using standard methods. Dynamic light scattering (DLS) analysis of PASylated adnectin C revealed an approximate 2-fold increase in particle size with a slight change in the net charge. Additionally, fusion of the PAS sequence improved its stability against the growth of thermo-induced aggregated forms. The high receptor-binding and improved binding kinetic parameters of PASylated Adnectin C was confirmed by ELISA and surface plasmon resonance assays, respectively. Pharmacokinetic studies showed a noticeable increase in the terminal half-life of Adnectin C-PAS#1(200) by a factor of 4.57 after single dose by intravenous injection into female BALB/c mice. The results suggest that PASylation could offer a superior delivery strategy for developing Adnectin-derived drugs with improved patient compliance.
Project description:BackgroundDespite effective therapies for many conditions, patients find it difficult to adhere to prescribed treatments. Technology-mediated interventions (TMIs) are increasingly being used with the hope of improving adherence.ObjectiveTo assess the effects of TMI, intended to enhance patient adherence to prescribed medications, on both medication adherence and clinical outcomes.MethodsA secondary in-depth analysis was conducted of the subset of studies that utilized technology in at least one component of the intervention from an updated Cochrane review on all interventions for enhancing medication adherence. We included studies that clearly described an information and communication technology or medical device as the sole or major component of the adherence intervention.ResultsThirty-eight studies were eligible for in-depth review. Only seven had a low risk of bias for study design features, primary adherence, and clinical outcomes. Eighteen studies used a TMI for education and/or counseling, 11 studies used a TMI for self-monitoring and/or feedback, and nine studies used electronic reminders. Studies used a variety of TMIs, with telephone the most common technology in use. Studies targeted a wide distribution of diseases and used a variety of adherence and clinical outcome measures. A minority targeted children and adolescents. Fourteen studies reported significant effects in both adherence and clinical outcome measures.ConclusionsThis review provides evidence for the inconsistent effectiveness of TMI for medication adherence and clinical outcomes. These results must be interpreted with caution due to a lack of high-quality studies.
Project description:The ultrasound technology was successfully used to improve the mass transfer processes on food. However, the study of this technology on the grain hydration and on its main components properties was still not appropriately described. This work studied the application of the ultrasound technology on the hydration process of mung beans (Vigna radiata). This grain showed sigmoidal hydration behavior with a specific water entrance pathway. The ultrasound reduced ~25% of the hydration process time. In addition, this technology caused acceleration of the seed germination - and some hypothesis for this enhancement were proposed. Moreover, it was demonstrated that the ultrasound did not change both structure and pasting properties of the bean starch. Finally, the flour rheological properties proved that the ultrasound increased its apparent viscosity, and as the starch was not modified, this alteration was attributed to the proteins. All these results are very desirable for industry since the ultrasound technology improves the hydration process without altering the starch properties, accelerates the germination process (that is important for the malting and sprouting process) and increases the flour apparent viscosity, which is desirable to produce bean-based products that need higher consistency.
Project description:Librarians continually integrate new technologies into library services for health sciences students. Recently published data are lacking about student ownership of technological devices, awareness of new technologies, and interest in using devices and technologies to interact with the library. A survey was implemented at seven health sciences libraries to help answer these questions. Results show that librarian assumptions about awareness of technologies are not supported, and student interest in using new technologies to interact with the library varies widely. Collecting this evidence provides useful information for successfully integrating technologies into library services.
Project description:RNA-binding proteins (RBPs) and their RNA ligands play many critical roles in gene regulation and RNA processing in cells. They are also useful for various applications in cell biology and synthetic biology. However, re-engineering novel and orthogonal RNA-RBP pairs from natural components remains challenging while such synthetic RNA-RBP pairs could significantly expand the RNA-RBP toolbox for various applications. Here, we report a novel library-vs-library in vitro selection strategy based on Phage Display coupled with Systematic Evolution of Ligands by EXponential enrichment (PD-SELEX). Starting with pools of 1.1 × 1012 unique RNA sequences and 4.0 × 108 unique phage-displayed L7Ae-scaffold (LS) proteins, we selected RNA-RBP complexes through a two-step affinity purification process. After six rounds of library-vs-library selection, the selected RNAs and LS proteins were analyzed by next-generation sequencing (NGS). Further deconvolution of the enriched RNA and LS protein sequences revealed two synthetic and orthogonal RNA-RBP pairs that exhibit picomolar affinity and >4000-fold selectivity.
Project description:DNA-encoded chemical libraries (DELs) are powerful drug discovery tools, enabling the parallel screening of millions of DNA-barcoded compounds. We investigated how the DEL input affects the hit discovery rate in DEL screenings. Evaluation of selection fingerprints revealed that the use of approximately 105 copies of each library member is required for the confident identification of nanomolar hits, using generally applicable methodologies.