Bioprocess decision support tool for scalable manufacture of extracellular vesicles.
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ABSTRACT:
SUBMITTER: Ng KS
PROVIDER: S-EPMC6322973 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Heterogeneous nanoscale extracellular vesicles (EVs) are of significant interest for disease detection, monitoring, and therapeutics. However, trapping these nano-sized EVs using optical tweezers has been challenging due to their small size. Plasmon-enhanced optical trapping offers a solution. Nevertheless, existing plasmonic tweezers have limited throughput and can take tens of minutes for trapping for low particle concentrations. Here, we present an innovative approach called geometry-induced electrohydrodynamic tweezers (GET) that overcomes these limitations. GET generates multiple electrohydrodynamic potentials, allowing parallel transport and trapping of single EVs within seconds. By integrating nanoscale plasmonic cavities at the center of each GET trap, single EVs can be placed near plasmonic cavities, enabling instant plasmon-enhanced optical trapping upon laser illumination without detrimental heating effects. These non-invasive scalable hybrid nanotweezers open new horizons for high-throughput tether-free plasmon-enhanced single EV trapping and spectroscopy. Other potential areas of impact include nanoplastics characterization, and scalable hybrid integration for quantum photonics.
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Project description:Appropriate thromboprophylaxis for patients with atrial fibrillation or atrial flutter (AF) remains a national challenge. The recent availability of direct oral anticoagulants (DOACs) with comparable efficacy and improved safety compared with warfarin alters the balance between risk factors for stroke and benefit of anticoagulation. Our objective was to examine the impact of DOACs as an alternative to warfarin on the net benefit of oral anticoagulant therapy (OAT) in a real-world population of AF patients.This is a retrospective cohort study of patients with paroxysmal or persistent nonvalvular AF. We updated an Atrial Fibrillation Decision Support Tool (AFDST) to include DOACs as treatment options. The tool generates patient-specific recommendations based upon individual patient risk factor profiles for stroke and major bleeding using quality-adjusted life-years (QALYs) calculated for each treatment strategy by a decision analytic model. The setting included inpatient and ambulatory sites in an academic health center in the midwestern United States. The study involved 5,121 adults with nonvalvular AF seen for any ambulatory visit or inpatient hospitalization over the 1-year period (January through December 2016). Outcome measure was net clinical benefit in QALYs.When DOACs are a therapeutic option, the AFDST recommends OAT for 4,134 (81%) patients and no antithrombotic therapy or aspirin for 489 (9%). A strong recommendation for OAT could not be made in 498 (10%) patients. When warfarin is the only option, OAT is recommended for 3,228 (63%) patients and no antithrombotic therapy or aspirin for 973 (19%). A strong recommendation for OAT could not be made in 920 (18%) patients. In total, 1,508 QALYs could be gained if treatment were changed to that recommended by the AFDST.Availability of DOACs increases the proportion of patients for whom oral anticoagulation therapy is recommended in a real-world cohort of AF patients and increased projected QALYs by more than 1,500 when all patients are receiving thromboprophylaxis as recommended by the AFDST compared with current treatment.
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Project description:ObjectivesImmunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies.MethodsThe CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas.ResultsThe tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership.ConclusionsPilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.
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Project description:Acute myeloid leukemia (AML) cells can secrete trophic factors, including extracellular vesicles (EVs), instructing the stromal leukemic niche. Here, we introduce a scalable workflow for purification of immunomodulatory AML-EVs to compare their phenotype and function to the parental AML cells and their secreted soluble factors. AML cell lines HL-60, KG-1, OCI-AML3, and MOLM-14 released EVs with a peak diameter of approximately 80 nm in serum-free particle-reduced medium. We enriched EVs >100x using tangential flow filtration (TFF) and separated AML-derived soluble factors and cells in parallel. EVs were characterized by electron microscopy, immunoblotting, and flow cytometry, confirming the double-membrane morphology, purity and identity. AML-EVs showed significant enrichment of immune response and leukemia-related pathways in tandem mass-tag proteomics and a significant dose-dependent inhibition of T cell proliferation, which was not observed with AML cells or their soluble factors. Furthermore, AML-EVs dose-dependently reduced NK cell lysis of third-party K-562 leukemia targets. This emphasizes the peculiar role of AML-EVs in leukemia immune escape and indicates novel EV-based targets for therapeutic interventions.
| S-EPMC8699161 | biostudies-literature
Project description:Diverse bacterial species secrete ~20-300 nm extracellular vesicles (EVs), comprised of lipids, proteins, nucleic acids, glycans, and other molecules derived from the parental cells. EVs function as intra- and inter-species communication vectors while also contributing to the interaction between bacteria and host organisms in the context of infection and colonization. Given the multitude of functions attributed to EVs in health and disease, there is a growing interest in isolating EVs for in vitro and in vivo studies. It was hypothesized that the separation of EVs based on physical properties, namely size, would facilitate the isolation of vesicles from diverse bacterial cultures. The isolation workflow consists of centrifugation, filtration, ultrafiltration, and size-exclusion chromatography (SEC) for the isolation of EVs from bacterial cultures. A pump-driven tangential flow filtration (TFF) step was incorporated to enhance scalability, enabling the isolation of material from liters of starting cell culture. Escherichia coli was used as a model system expressing EV-associated nanoluciferase and non-EV-associated mCherry as reporter proteins. The nanoluciferase was targeted to the EVs by fusing its N-terminus with cytolysin A. Early chromatography fractions containing 20-100 nm EVs with associated cytolysin A - nanoLuc were distinct from the later fractions containing the free proteins. The presence of EV-associated nanoluciferase was confirmed by immunogold labeling and transmission electron microscopy. This EV isolation workflow is applicable to other human gut-associated gram-negative and gram-positive bacterial species. In conclusion, combining centrifugation, filtration, ultrafiltration/TFF, and SEC enables scalable isolation of EVs from diverse bacterial species. Employing a standardized isolation workflow will facilitate comparative studies of microbial EVs across species.
| S-EPMC8729794 | biostudies-literature
Project description:Biomechanical energy harvesting textiles based on nanogenerators that convert mechanical energy into electricity have broad application prospects in next-generation wearable electronic devices. However, the difficult-to-weave structure, limited flexibility and stretchability, small device size and poor weatherability of conventional nanogenerator-based devices have largely hindered their real-world application. Here, we report a highly stretchable triboelectric yarn that involves unique structure design based on intrinsically elastic silicone rubber tubes and extrinsically elastic built-in stainless steel yarns. By using a modified melt-spinning method, we realize scalable-manufacture of the self-powered yarn. A hundred-meter-length triboelectric yarn is demonstrated, but not limited to this size. The triboelectric yarn shows a large working strain (200%) and promising output. Moreover, it has superior performance in liquid, therefore showing all-weather durability. We also show that the development of this energy yarn facilitates the manufacturing of large-area self-powered textiles and provide an attractive direction for the study of amphibious wearable technologies.
| S-EPMC6382889 | biostudies-literature
Project description:Ag-TiO2@polyethylene glycol (PEG) nanoparticles were continuously obtained in a single-pass configuration by appropriately reacting freshly flame-synthesized TiO2 with Ag formed in an ultrasonic aqueous medium containing PEG. When the proposed synthesis was kept constant, the production rate for Ag-TiO2@PEG nanoparticles reached approximately 3 g/h while only using a combination of a lab-scale inverse-diffusion flame (16 mm head diameter) and an ultrasonic Ag(I) cell (50 mL). The synthesized nanoparticles were employed as inducers for in vitro photoinduced therapy to kill cancer cells at different light wavelengths. Measurements of the nanoparticle cytotoxicity revealed that PEG incorporation with the Ag-TiO2 particles significantly decreased the cytotoxicity (cell viability of more than ~91% at 200 μg mL(-1) particle concentration) of Ag, and this was comparable with that of TiO2 particles (cell viability of more than ~90%). When 632 nm and 808 nm light was applied to the nanoparticles in the HeLa cells, the viability of the cells was significantly affected [decreased to ~4% (632 nm) and ~26% (808 nm) at 200 μg mL(-1), 5 min irradiation time] by surface plasmon resonance heating and photothermal therapy.
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Project description:Background and objectiveClinical decision support tools for risk prediction are readily available, but typically require workflow interruptions and manual data entry so are rarely used. Due to new data interoperability standards for electronic health records (EHRs), other options are available. As a clinical case study, we sought to build a scalable, web-based system that would automate calculation of kidney failure risk and display clinical decision support to users in primary care practices.Materials and methodsWe developed a single-page application, web server, database, and application programming interface to calculate and display kidney failure risk. Data were extracted from the EHR using the Consolidated Clinical Document Architecture interoperability standard for Continuity of Care Documents (CCDs). EHR users were presented with a noninterruptive alert on the patient's summary screen and a hyperlink to details and recommendations provided through a web application. Clinic schedules and CCDs were retrieved using existing application programming interfaces to the EHR, and we provided a clinical decision support hyperlink to the EHR as a service.ResultsWe debugged a series of terminology and technical issues. The application was validated with data from 255 patients and subsequently deployed to 10 primary care clinics where, over the course of 1 year, 569 533 CCD documents were processed.ConclusionsWe validated the use of interoperable documents and open-source components to develop a low-cost tool for automated clinical decision support. Since Consolidated Clinical Document Architecture-based data extraction extends to any certified EHR, this demonstrates a successful modular approach to clinical decision support.
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Project description:Heat poses an urgent threat to public health in cities, as the urban heat island (UHI) effect can amplify exposures, contributing to high heat-related mortality and morbidity. Urban trees have the potential to mitigate heat by providing substantial cooling, as well as co-benefits such as reductions in energy consumption. The City of Boston has attempted to expand its urban canopy, yet maintenance costs and high tree mortality have hindered successful canopy expansion. Here, we present an interactive web application called Right Place, Right Tree-Boston that aims to support informed decision-making for planting new trees. To highlight priority regions for canopy expansion, we developed a Boston-specific Heat Vulnerability Index (HVI) and present this alongside maps of summer daytime land surface temperatures. We also provide information about tree pests and diseases, suitability of species for various conditions, land ownership, maintenance tips, and alternatives to tree planting. This web application is designed to support decision-making at multiple spatial scales, to assist city officials as well as residents who are interested in expanding or maintaining Boston's urban forest.
| S-EPMC7544061 | biostudies-literature