A reconfigurable microfluidics platform for microparticle separation and fluid mixing

Microfluidics is an engineering tool used to control and manipulate fluid flows, with practical applications for lab-on-a-chip, point-of-care testing, and biological/medical research. However, microfluidic platforms typically lack the ability to create a fluidic duct, having an arbitrary flow path, and to change the path as needed without additional design and fabrication processes. To address this challenge, we present a simple yet effective approach for facile, on-demand reconfiguration of microfluidic channels using flexible polymer tubing. The tubing provides both a well-defined, cross-sectional geometry to allow reliable fluidic operation and excellent flexibility to achieve a high degree of freedom for reconfiguration of flow pathways. We demonstrate that microparticle separation and fluid mixing can be successfully implemented by reconfiguring the shape of the tubing. The tubing is coiled around a 3D-printed barrel to make a spiral microchannel with a constant curvature for inertial separation of microparticles. Multiple knots are also made in the tubing to create a highly tortuous flow path, which induces transverse secondary flows, Dean flows, and, thus, enhances the mixing of fluids. The reconfigurable microfluidics approach, with advantages including low-cost, simplicity, and ease of use, can serve as a promising complement to conventional microfabrication methods, which require complex fabrication processes with expensive equipment and lack a degree of freedom for reconfiguration.ope

A cell rolling cytometer reveals the correlation between mesenchymal stem cell dynamic adhesion and differentiation state

This communication presents quantitative studies of the dynamic adhesion behavior of mesenchymal stem cells (MSCs) enabled by the combination of cell-surface receptor–ligand interactions and three-dimensional hydrodynamic control by microtopography.National Institutes of Health (U.S.) (Grant HL-095722)National Institutes of Health (U.S.) (Grant HL-097172)National Science Foundation (U.S.) (CAREER Award 0952493)Korea (South). Ministry of Science, ICT and Future Planning (National Research Foundation of Korea. Pioneer Research Center Program 2013M3C1A3064777)National Research Foundation of Korea (Framework of International Cooperation Program 2013K2A1A2053078

Ultra-High Throughput Synthesis of Nanoparticles with Homogeneous Size Distribution Using a Coaxial Turbulent Jet Mixer

High-throughput production of nanoparticles (NPs) with controlled quality is critical for their clinical translation into effective nanomedicines for diagnostics and therapeutics. Here we report a simple and versatile coaxial turbulent jet mixer that can synthesize a variety of NPs at high throughput up to 3 kg/d, while maintaining the advantages of homogeneity, reproducibility, and tunability that are normally accessible only in specialized microscale mixing devices. The device fabrication does not require specialized machining and is easy to operate. As one example, we show reproducible, high-throughput formulation of siRNA-polyelectrolyte polyplex NPs that exhibit effective gene knockdown but exhibit significant dependence on batch size when formulated using conventional methods. The coaxial turbulent jet mixer can accelerate the development of nanomedicines by providing a robust and versatile platform for preparation of NPs at throughputs suitable for in vivo studies, clinical trials, and industrial-scale production.Prostate Cancer Foundation (Award in Nanotherapeutics)National Institutes of Health (U.S.) (Grant EB015419)National Institutes of Health (U.S.) (Grant CA119349

WISARD: workbench for integrated superfast association studies for related datasets

Background: A Mendelian transmission produces phenotypic and genetic relatedness between family members, giving family-based analytical methods an important role in genetic epidemiological studies—from heritability estimations to genetic association analyses. With the advance in genotyping technologies, whole-genome sequence data can be utilized for genetic epidemiological studies, and family-based samples may become more useful for detecting de novo mutations. However, genetic analyses employing family-based samples usually suffer from the complexity of the computational/statistical algorithms, and certain types of family designs, such as incorporating data from extended families, have rarely been used. Results: We present a Workbench for Integrated Superfast Association studies for Related Data (WISARD) programmed in C/C++. WISARD enables the fast and a comprehensive analysis of SNP-chip and next-generation sequencing data on extended families, with applications from designing genetic studies to summarizing analysis results. In addition, WISARD can automatically be run in a fully multithreaded manner, and the integration of R software for visualization makes it more accessible to non-experts. Conclusions: Comparison with existing toolsets showed that WISARD is computationally suitable for integrated analysis of related subjects, and demonstrated that WISARD outperforms existing toolsets. WISARD has also been successfully utilized to analyze the large-scale massive sequencing dataset of chronic obstructive pulmonary disease data (COPD), and we identified multiple genes associated with COPD, which demonstrates its practical value. Electronic supplementary material The online version of this article (10.1186/s12920-018-0345-y) contains supplementary material, which is available to authorized users

Cell sorting by deterministic cell rolling

Authors Manuscript 2013 April 21.This communication presents the concept of “deterministic cell rolling”, which leverages transient cell-surface molecular interactions that mediate cell rolling to sort cells with high purity and efficiency in a single step.National Institutes of Health (U.S.) (Grant HL-095722)National Institutes of Health (U.S.) (Grant HL-097172)National Science Foundation (U.S.) (CAREER Award 0952493)Deshpande Center for Technological InnovationNational Science Foundation (U.S.). Chemical and Biological Separation

Smartphone App for Improving Self-Awareness of Adherence to Edoxaban Treatment in Patients With Atrial Fibrillation (ADHERE-App Trial): Randomized Controlled Trial

Background: Adherence to oral anticoagulant therapy is essential to prevent ischemic stroke in patients with atrial fibrillation (AF). Objective: This study aimed to evaluate whether smartphone app–based interventions improve medication adherence in patients with AF. Methods: This open-label, multicenter randomized controlled trial (ADHERE-App [Self-Awareness of Drug Adherence to Edoxaban Using an Automatic App Feedback System] study) enrolled patients with AF treated with edoxaban for stroke prevention. They were randomly assigned to app-conditioned feedback (intervention; n=248) and conventional treatment (control; n=250) groups. The intervention group received daily alerts via a smartphone app to take edoxaban and measure blood pressure and heart rate at specific times. The control group received only standard, guideline-recommended care. The primary end point was edoxaban adherence, measured by pill count at 3 or 6 months. Medication adherence and the proportion of adequate medication adherence, which was defined as ≥95% of continuous medication adherence, were evaluated. Results: Medication adherence at 3 or 6 months was not significantly different between the intervention and control groups (median 98%, IQR 95%-100% vs median 98%, IQR 91%-100% at 3 months, P=.06; median 98%, IQR 94.5%-100% vs median 97.5%, IQR 92.8%-100% at 6 months, P=.15). However, the proportion of adequate medication adherence (≥95%) was significantly higher in the intervention group at both time points (76.8% vs 64.7% at 3 months, P=.01; 73.9% vs 61% at 6 months, P=.007). Among patients aged >65 years, the intervention group showed a higher medication adherence value and a higher proportion of adequate medication adherence (≥95%) at 6 months. Conclusions: There was no difference in edoxaban adherence between the groups. However, the proportion of adequate medication adherence was higher in the intervention group, and the benefit of the smartphone app–based intervention on medication adherence was more pronounced among older patients than among younger patients. Given the low adherence to oral anticoagulants, especially among older adults, using a smartphone app may potentially improve medication adherence

Towards Smart Homes Using Low Level Sensory Data

Ubiquitous Life Care (u-Life care) is receiving attention because it provides high quality and low cost care services. To provide spontaneous and robust healthcare services, knowledge of a patient’s real-time daily life activities is required. Context information with real-time daily life activities can help to provide better services and to improve healthcare delivery. The performance and accuracy of existing life care systems is not reliable, even with a limited number of services. This paper presents a Human Activity Recognition Engine (HARE) that monitors human health as well as activities using heterogeneous sensor technology and processes these activities intelligently on a Cloud platform for providing improved care at low cost. We focus on activity recognition using video-based, wearable sensor-based, and location-based activity recognition engines and then use intelligent processing to analyze the context of the activities performed. The experimental results of all the components showed good accuracy against existing techniques. The system is deployed on Cloud for Alzheimer’s disease patients (as a case study) with four activity recognition engines to identify low level activity from the raw data captured by sensors. These are then manipulated using ontology to infer higher level activities and make decisions about a patient’s activity using patient profile information and customized rules

The ReInforcement of adherence via self-monitoring app orchestrating biosignals and medication of RivaroXaban in patients with atrial fibrillation and co-morbidities: a study protocol for a randomized controlled trial (RIVOX-AF)

BackgroundBecause of the short half-life of non-vitamin K antagonist oral anticoagulants (NOACs), consistent drug adherence is crucial to maintain the effect of anticoagulants for stroke prevention in atrial fibrillation (AF). Considering the low adherence to NOACs in practice, we developed a mobile health platform that provides an alert for drug intake, visual confirmation of drug administration, and a list of medication intake history. This study aims to evaluate whether this smartphone app-based intervention will increase drug adherence compared with usual care in patients with AF requiring NOACs in a large population.MethodsThis prospective, randomized, open-label, multicenter trial (RIVOX-AF study) will include a total of 1,042 patients (521 patients in the intervention group and 521 patients in the control group) from 13 tertiary hospitals in South Korea. Patients with AF aged ≥19 years with one or more comorbidities, including heart failure, myocardial infarction, stable angina, hypertension, or diabetes mellitus, will be included in this study. Participants will be randomly assigned to either the intervention group (MEDI-app) or the conventional treatment group in a 1:1 ratio using a web-based randomization service. The intervention group will use a smartphone app that includes an alarm for drug intake, visual confirmation of drug administration through a camera check, and presentation of a list of medication intake history. The primary endpoint is adherence to rivaroxaban by pill count measurements at 12 and 24 weeks. The key secondary endpoints are clinical composite endpoints, including systemic embolic events, stroke, major bleeding requiring transfusion or hospitalization, or death during the 24 weeks of follow-up.DiscussionThis randomized controlled trial will investigate the feasibility and efficacy of smartphone apps and mobile health platforms in improving adherence to NOACs.Trial registrationThe study design has been registered in ClinicalTrial.gov (NCT05557123)

The telomere maintenance mechanism spectrum and its dynamics in gliomas

Background : The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Methods : Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. Results : We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. Conclusions : This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (NRF-2018M3A9H3021707), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI21C0239)

Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

Significance Contributions of rare variants to common and complex traits such as type 2 diabetes (T2D) are difficult to measure. This paper describes our results from deep whole-genome analysis of large Mexican-American pedigrees to understand the role of rare-sequence variations in T2D and related traits through enriched allele counts in pedigrees. Our study design was well-powered to detect association of rare variants if rare variants with large effects collectively accounted for large portions of risk variability, but our results did not identify such variants in this sample. We further quantified the contributions of common and rare variants in gene expression profiles and concluded that rare expression quantitative trait loci explain a substantive, but minor, portion of expression heritability.</jats:p