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Akin to the impact that digital microelectronics had on electronic devices for information technology, digital microfluidics (DMF) was anticipated to transform fluidic devices for lab-on-a-chip (LoC) applications. However, despite a wealth of research and publications, electrowetting-on-dielectric (EWOD) DMF has not achieved the anticipated wide adoption, and commercialization has been painfully slow. By identifying the technological and resource hurdles in developing DMF chip and control systems as the culprit, we envision democratizing DMF by building a standardized design and manufacturing platform. To achieve this vision, we introduce a proof-of-concept cloud platform that empowers any user to design, obtain, and operate DMF chips (https://edroplets.org). For chip design, we establish a web-based EWOD chip design platform with layout rules and automated wire routing. For chip manufacturing, we build a web-based EWOD chip manufacturing platform and fabricate four types of EWOD chips (i.e., glass, paper, PCB, and TFT) to demonstrate the foundry service workflow. For chip control, we introduce a compact EWOD control system along with web-based operating software. Although industrial fabrication services are beyond the scope of this work, we hope this perspective will inspire academic and commercial stakeholders to join the initiative toward a DMF ecosystem for the masses.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

BackgroundDespite the advances in the diagnosis and treatment of heart failure (HF), the current hospital-oriented framework for HF management does not appear to be sufficient to maintain the stability of HF patients in the long term. The importance of self-care management is increasingly being emphasized as a promising long-term treatment strategy for patients with chronic HF. ObjectiveThe objective of this study was to evaluate whether a new information communication technology (ICT)–based telehealth program with voice recognition technology could improve clinical or laboratory outcomes in HF patients. MethodsIn this prospective single-arm pilot study, we recruited 31 consecutive patients with chronic HF who were referred to our institute. An ICT-based telehealth program with voice recognition technology was developed and used by patients with HF for 12 weeks. Patients were educated on the use of this program via mobile phone, landline, or the Internet for the purpose of improving communication and data collection. Using these systems, we collected comprehensive data elements related to the risk of HF self-care management such as weight, diet, exercise, medication adherence, overall symptom change, and home blood pressure. The study endpoints were the changes observed in urine sodium concentration (uNa), Minnesota Living with Heart Failure (MLHFQ) scores, 6-min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as surrogate markers for appropriate HF management. ResultsAmong the 31 enrolled patients, 27 (87%) patients completed the study, and 10 (10/27, 37%) showed good adherence to ICT-based telehealth program with voice recognition technology, which was defined as the use of the program for 100 times or more during the study period. Nearly three-fourths of the patients had been hospitalized at least once because of HF before the enrollment (20/27, 74%); 14 patients had 1, 2 patients had 2, and 4 patients had 3 or more previous HF hospitalizations. In the total study population, there was no significant interval change in laboratory and functional outcome variables after 12 weeks of ICT-based telehealth program. In patients with good adherence to ICT-based telehealth program, there was a significant improvement in the mean uNa (103.1 to 78.1; P=.01) but not in those without (85.4 to 96.9; P=.49). Similarly, a marginal improvement in MLHFQ scores was only observed in patients with good adherence (27.5 to 21.4; P=.08) but not in their counterparts (19.0 to 19.7; P=.73). The mean 6-min walk distance and NT-proBNP were not significantly increased in patients regardless of their adherence. ConclusionsShort-term application of ICT-based telehealth program with voice recognition technology showed the potential to improve uNa values and MLHFQ scores in HF patients, suggesting that better control of sodium intake and greater quality of life can be achieved by this program.

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIMETM system, exhibited EpCAM/CK+/CD45- phenotype in BioViewCCBSTM. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group (p = 0.034). Patients with high platelets at C1 (PLThi, >252 × 103/µL) had worse median PFS than those with low platelets (PLTlo) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLThi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLThi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLThi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.

We explored Asian international students' successful learning experiences and adjustment through the lens of self-determination theory. To explore how international students perceive their classroom learning environments and learning experiences in more detail, a sequential explanatory mixed-methods approach was used. In the quantitative phase, empirical relationships between autonomy-supportive environments and affective (language anxiety), behavioral (discussion participation), and cognitive (adaptive beliefs about classroom assessments) learning components in the classroom were examined. In the qualitative phase, results from the quantitative study were further explored for additional explanations through follow-up interviews. Autonomy-supportive environments seemed to satisfy international students' basic psychological needs, which decreased language anxiety and increased classroom participation and adaptive perspectives about classroom assessments. The discussion focuses on the theoretical and classroom implications of the quantitative and qualitative findings. This study contributes to the literature by suggesting a solid theoretical foundation to support successful academic adjustment among Asian international students.