Reconfigurable Hanging Drop Microarray Platform for On-Demand Preparation and Analysis of Spheroid Array.

In response to the increasing demand for spheroid-based cancer research, the importance of developing integrated platforms that can simultaneously facilitate high-throughput spheroid production and multiplexed analysis is emphasized. In addition, the understanding of how the size and cellular composition of tumors directly influence their internal structures and functionalities underlines the critical need to produce spheroids of diverse sizes and compositions on a large scale. To address this rising demand, this work presents a configurable and linkable in vitro three-dimensional (3D) cell culture kit (CLiCK) for spheroids, termed CLiCK-Spheroid. This platform consists of three primary components: a hanging drop microarray (HDMA), a concave pillar microarray (CPMA), and gradient blocks. The HDMA alone produces a homogeneous spheroid array, while its combination with the gradient block enables one-step generation of a size-gradient spheroid array. Using the size-gradient spheroid arrays, the occurrence of necrotic cores based on spheroid size is demonstrated. Additionally, spheroids in a single batch can be conveniently compartmentalized and regrouped using a CPMA, enhancing the versatility of spheroid arrays and enabling multiplexed drug treatments. By combining the different assembly methods, this work has achieved high-throughput production of cell composition-gradient spheroid arrays, with noticeable variations in morphology and vascularization based on cell compositions.

Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

Magnetically Actuated Trigger Transient Soft Actuators Comprising On-Demand Photo-Initiated and Thermo-Degradable Polypropylene Carbonate-Photo-Acid Generator.

Lifetime-reconfigurable soft robots have emerged as a new class of robots, emphasizing the unmet needs of futuristic sustainability and security. Trigger-transient materials that can both actuate and degrade on-demand are crucial for achieving life-reconfigurable soft robots. Here, we propose the use of transient and magnetically actuating materials that can decompose under ultraviolet light and heat, achieved by adding photo-acid generator (PAG) and magnetic particles (Sr-ferrite) to poly(propylene carbonate) (PPC). Chemical and thermal analyses reveal that the mechanism of PPC-PAG decomposition occurs through PPC backbone cleavage by the photo-induced acid. The self-assembled monolayer (SAM) encapsulation of Sr-ferrite preventing the interaction with the PAG allowed the transience of magnetic soft actuators. We demonstrate remotely controllable and degradable magnetic soft kirigami actuators using blocks with various magnetized directions. This study proposes novel approaches for fabricating lifetime-configurable magnetic soft actuators applicable to diverse environments and applications, such as enclosed/sealed spaces and security/military devices.

Three Virtual Reality Environments for the Assessment of Executive Functioning Using Performance Scores and Kinematics: An Embodied and Ecological Approach to Cognition.

Virtual reality (VR) is an attractive technology for cognitive assessment, as it provides a more embodied experience compared with typical test situations, such as those using paper and pencil. In addition, VR can immerse individuals in complex situations similar to real-life ones, thereby improving the ecological validity (i.e., face validity) of the assessment. VR also offers improved scoring of tests as it facilitates the tracking of kinematic information and the temporal tracking of activities. This study assesses the correlation between scores on executive function assessments using standard neuropsychological tasks in paper-and-pencil format, on a tablet, and in three immersive VR environments, each designed to involve specific aspects of executive function. This study also aims to assess the correlation between these performance scores and a set of kinematic measures (speed, duration, and distance traveled by the hand) collected in VR. The outcomes, including performance scores and kinematic measures, correlate both with traditional assessment methods (such as paper and pencil, and computerized 2D tests) and with each other, suggesting their potential usefulness in clinical and research contexts. The discussion focuses on the advantages of embodied, situated, and spatialized tests for cognitive assessment and the benefits of kinematic tracking in VR tests for the quality of this assessment.

Socioeconomic Deprivation and the Risk of Sight-Threatening Diabetic Retinopathy: A Population-Based Cohort Study in the U.K.

OBJECTIVE: To evaluate the associations between socioeconomic deprivation and sight-threatening diabetic retinopathy (STDR) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Data from 175,628 individuals with diabetes in the Health Improvement Network were used to assess the risk of STDR across Townsend Deprivation Index quantiles using Cox proportional hazard regression. RESULTS: Among individuals with T1D, the risk of STDR was three times higher (adjusted hazard ratio [aHR] 2.67, 95% CI 1.05-7.78) in the most deprived quintile compared with the least deprived quintile. In T2D, the most deprived quintile had a 28% higher risk (aHR 1.28; 95% CI 1.15-1.43) than the least deprived quintile. CONCLUSIONS: Increasing socioeconomic deprivation is associated with a higher risk of developing STDR in people with diabetes. This underscores persistent health disparities linked to poverty, even within a country offering free universal health care. Further research is needed to address health equity concerns in socioeconomically deprived regions.

Long-term prognosis after decoronation of avulsed teeth with replacement resorption: a report of three cases.

The complications of replacement resorption following tooth injury in growing children include infrapositioning of the tooth, tilting of the adjacent teeth, and alveolar ridge deformity. Decoronation is a conservative treatment method that facilitates bone preservation. The current case report focuses on the long-term preservation of alveolar ridge dimension following decoronation in three patients. Decoronation was performed prior to occurrence of the pubertal growth spurt, and the patients' ridge width and vertical apposition were monitored for at least 4 years. Timely intervention and regular monitoring are essential for maximization of the benefits of decoronation, a simple procedure that preserves esthetics and minimizes the need for further treatments. The importance of space management for prosthetic treatment has also been highlighted. The findings of this study show that infrapositioned teeth in growing children can be treated successfully using decoronation.

Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy.

Cancer immunotherapy, which harnesses the power of the immune system, has shown immense promise in the fight against malignancies. Messenger RNA (mRNA) stands as a versatile instrument in this context, with its capacity to encode tumor-associated antigens (TAAs), immune cell receptors, cytokines, and antibodies. Nevertheless, the inherent structural instability of mRNA requires the development of effective delivery systems. Lipid nanoparticles (LNPs) have emerged as significant candidates for mRNA delivery in cancer immunotherapy, providing both protection to the mRNA and enhanced intracellular delivery efficiency. In this review, we offer a comprehensive summary of the recent advancements in LNP-based mRNA delivery systems, with a focus on strategies for optimizing the design and delivery of mRNA-encoded therapeutics in cancer treatment. Furthermore, we delve into the challenges encountered in this field and contemplate future perspectives, aiming to improve the safety and efficacy of LNP-based mRNA cancer immunotherapies.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Background/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. Methods: This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. Results: In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. Conclusions: This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Multifunctional porous microspheres encapsulating oncolytic bacterial spores and their potential for cancer immunotherapy.

Clostridium novyi-NT (C. novyi-NT) is an anaerobic bacterium that can be used for targeted cancer therapy because it germinates selectively in the hypoxic regions of tumor tissues. However, systemic administration of C. novyi-NT spores cannot effectively treat tumors because of the limited intratumoral delivery of active spores. In this study, we demonstrated that multifunctional porous microspheres (MPMs) containing C. novyi-NT spores have the potential for image-guided local tumor therapy. The MPMs can be repositioned under an external magnetic field, enabling precise tumor targeting and retention. Polylactic acid-based MPMs were prepared using the oil-in-water emulsion technique and then coated with a cationic polyethyleneimine polymer prior to loading with negatively charged C. novyi-NT spores. The C. novyi-NT spores delivered by MPMs were released and germinated in a simulated tumor microenvironment, effectively secreting proteins cytotoxic to tumor cells. In addition, the germinated C. novyi-NT induced immunogenic death of the tumor cells and M1 polarization of macrophages. These results indicate that MPMs encapsulated with C. novyi-NT spores have great potential for image-guided cancer immunotherapy.

Chromatographic Method for Monitoring of Pesticide Residues and Risk Assessment for Herbal Decoctions Used in Traditional Korean Medicine Clinics.

The presence of pesticide residues in herbs and the herbal products derived from them raises serious health concerns. This study was conducted to investigate the residual pesticide concentrations and assess potential human health risks from herbal medicines used in traditional Korean medicine clinics. A total of 40 samples of herbal decoctions were collected from 10 external herbal dispensaries. The pesticide residues were analyzed by the multiresidue method for 320 different pesticides using liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS). As a result of the monitoring, carbendazim was detected at 0.01 and 0.03 µg/g in eight samples and no pesticide was detected in the other herbal decoctions. Carbendazim was set for each individual item as less than 0.05 µg/g in Paeoniae radix, less than 0.05 µg/g in Cassiae semen, less than 2.0 µg/g in Lycii fructus, and less than 10 µg/g in Schisandrae fructus (dried). Therefore, the results of this study suggested that the detected pesticide residues in herbal decoctions could not be considered as posing a serious health risk.

Nanoparticle-Based Chimeric Antigen Receptor Therapy for Cancer Immunotherapy.

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) has emerged as an innovative immunotherapy for hematological cancer treatment. However, the limited effect on solid tumors, complex processes, and excessive manufacturing costs remain as limitations of CAR-T therapy. Nanotechnology provides an alternative to the conventional CAR-T therapy. Owing to their unique physicochemical properties, nanoparticles can not only serve as a delivery platform for drugs but also target specific cells. Nanoparticle-based CAR therapy can be applied not only to T cells but also to CAR-natural killer and CAR-macrophage, compensating for some of their limitations. This review focuses on the introduction of nanoparticle-based advanced CAR immune cell therapy and future perspectives on immune cell reprogramming.

Bee Venom Acupuncture for Neck Pain: A Review of the Korean Literature.

Bee venom is a natural toxin that is effective in treating various types of pain. The purpose of this paper was to review all the features of clinical studies conducted on bee venom acupuncture (BVA) for the treatment of neck pain in Korean publications. Six Korean databases and 16 Korean journals were searched in August 2022 for clinical studies on BVA for neck pain. We identified 24 trials that met our inclusion criteria, of which 316 patients with neck pain were treated with BVA. The most common diagnosis in the patients with neck pain was herniated intervertebral discs (HIVDs) of the cervical spine (C-spine) (29.2%), and the concentration and dosage per session were 0.05-0.5 mg/mL and 0.1-1.5 mL, respectively. The visual analog scale was most often measured for neck pain severity (62.5%), and all clinical research reported improvements in 16 outcome measures. This study shows that BVA could be recommended for the treatment of neck pain, especially HIVD of the C-spine; however, the adverse effects of BVA must be examined in future studies.

On-chip microfluidic dual detection of amino acid metabolism disorders using cell-free protein synthesis.

Various metabolic diseases are associated with the accumulation of specific amino acids due to abnormal metabolic pathways, and thus can be diagnosed by measuring the level of amino acids in body fluids. However, present methods for amino acid analysis are not readily accessible because they require a complex experimental setup, expensive equipment, and a long processing time. Here, we present a dual sensing microfluidic device that enables fast, portable, and quantitative analysis of target amino acids, harnessing the biological mechanism of protein synthesis. In this device, the working principle of a finger-actuated pumping unit is applied, and the microchannels are designed to perform cell-free synthesis of a reporter protein in response to the target amino acids in the assay samples. Multiple steps required for the translational assay are controlled by the simple operation of two pushbuttons on the device. It is demonstrated that the developed microfluidic device provides precise quantification of two amino acids (methionine and phenylalanine) within 30 min at room temperature. We expect that the application of the presented device can be readily extended to the point-of-care testing of other metabolic compounds.

Liposome-mediated small RNA delivery to convert the macrophage polarity: A novel therapeutic approach to treat inflammatory uterine disease.

Macrophages are present in all tissues for maintaining tissue homeostasis, and macrophage polarization plays a vital role in alleviating inflammation. Therefore, specific delivery of polarization modulators to macrophages in situ is critical for treating inflammatory diseases. We demonstrate that a size-controlled miRNA-encapsulated macrophage-targeting liposomes (miR/MT-Lip) specifically targets macrophages to promote M1-to-M2 polarization conversion, alleviating inflammation without cytotoxicity. miR/MT-Lip, approximately 1.2 µm, showed excellent internalization through phagocytosis and/or macropinocytosis in macrophages. miR-10a/MT-Lip, but not scramble miR-Fluorescein amidite (FAM)/MT-Lip as control, effectively converted the polarization of lipopolysaccharide (LPS)-induced M1 macrophages to M2 in vitro. When miR-10a/MT-Lip was intravenously delivered to mice insulted with LPS for inflammation, the proportion of M2 macrophages was significantly increased without disturbing the population of other immune cells. Furthermore, scramble miR-FAM/MT-Lip was mainly detected in macrophages, but not other immune cells. When our miR/MT-Lip was administered to mice with Asherman's syndrome that suffer from infertility because of sterile uterine inflammation, macrophage-specific targeting of miR-10a/MT-Lip facilitated M1-to-M2 conversion for angiogenesis in the impaired uterus, resulting in restoration of healthy uterine conditions. The results indicate that our MT-Lip encapsulating small RNAs has excellent potential to treat various inflammatory disorders by fine-tuning macrophage polarization in vivo without any side effects.

Association between Sleep Duration and Symptoms of Depression Aged between 18 and 49: The Korea National Health and Nutrition Examination Survey (KNHANES â ¦) from 2016 to 2018.

This study aimed to determine the association between symptoms of depression and sleep duration in a representative sample of the Korean population. Using national cross-sectional data from the seventh Korea National Health and Nutrition Examination Surveys (KNHANES-VII), 5461 adults aged 18−49 years were analyzed using logistic regression models. The proportions of participants with total daily sleep durations (24 h) of <6 h, 6−8 h, and ≥9 h were 26.2%, 60.6%, and 13.3%, respectively. The proportions of individuals with symptoms of depression in the <6 h, 6−8 h, and ≥9 h sleep duration groups were 37.4%, 46.3%, and 16.3%, respectively. The odds ratios (ORs) were significantly higher in the <6 h and ≥9 h sleep groups than in the 6−8 h sleep group. There was a significant association between short (<6 h/day) and long (≥9 h/day) sleep duration and symptoms of depression among the general Korean population. In particular, our findings suggest that short sleep (<6 h/day) is more associated with symptoms of depression than long sleep (≥9 h/day).

Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study.

In this study, we investigated whether the levels of sulfur dioxide (SO2), benzopyrene, and mycotoxins in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for SO2, benzopyrene, and mycotoxins using 10 samples. SO2 and benzopyrene were not detected in any of the herbal decoctions. With regard to mycotoxins, aflatoxin B1 was not detected, but B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). None of these values exceeded the restrictions in prior studies. Thus, we confirm that the amounts of SO2, benzopyrene, and mycotoxins in herbal decoctions are at safe levels and provides the basis of establishing safety management criteria for herbal decoctions.

The Acceptance Behavior of Smart Home Health Care Services in South Korea: An Integrated Model of UTAUT and TTF.

With the COVID-19 pandemic, the importance of home health care to manage and monitor one's health status in a home environment became more crucial than ever. This change raised the need for smart home health care services (SHHSs) and their extension to everyday life. However, the factors influencing the acceptance behavior of SHHSs have been inadequately investigated and failed to address why users have the intention to use and adopt the services. This study aimed to analyze the influential factors and measure the behavioral acceptance of SHHSs in South Korea. This study adopted the integrated model of the unified theory of acceptance and use of technology (UTAUT) and task-technology fit (TTF) to understand the behavioral acceptance of SHHSs from users' perceptions and task-technology fit. Multiple-item scales were established based on validated previous measurement scales and adjusted in accordance with SHHS context. Data from 487 valid samples were analyzed statistically, applying partial least square structural equation modeling. The results indicated that the integrated acceptance model explained 55.2% of the variance in behavioral intention, 44.9% of adoption, and 62.5% of the continuous intention to use SHHSs, supporting 11 of the 13 proposed hypotheses. Behavioral intention was positively influenced by users' perceptions on performance expectancy, effort expectancy, social influence, and functional conditions. Task-technology fit significantly influenced performance expectancy and behavioral intention, validating the linkage between the two models. Meanwhile, task characteristics were insignificant to determine task-technology fit, which might stem from complex home health care needs due to the COVID-19 pandemic, but were not sufficiently resolved by current service technologies. The findings implied that the acceptance of SHHSs needs to be evaluated according to both the user perceptions of technologies and the matching fit of task and technology. Theoretically, this study supports the applicability of the integrated model of UTAUT and TTF to the domain of SHHS, and newly proposed the measurement items of TTF reflecting the domain specificity of SHHS, providing empirical evidence during the pandemic era in South Korea. Practically, the results could suggest to the planners and strategists of home health care services how to promote SHHS in one's health management.

Image-guided in situ cancer vaccination with combination of multi-functional nano-adjuvant and an irreversible electroporation technique.

Cancer immunotherapy is a next-generation treatment strategy; however, its side effects limit its clinical translation. Here, a novel combination of a multi-functional nano-adjuvant (M-NA) prepared with an iron oxide/gold core and a cationic polymer shell via multilayer synthesis with CpG oligodeoxynucleotide (CpG-ODN) electrostatically complexed on its surface, and irreversible electroporation (IRE) technique was developed for effective image-guided in situ cancer vaccination. The M-NA can be retained long-term in the dense tumoral extracellular matrix after intratumoral injection and internalized by antigen-presenting cells (APCs). The IRE can induce immunogenic cell death. Indeed, in a mouse tumor model, the M-NA showed longer tumor retention time than free CpG-ODN. Compared with other treatments, the combined treatment significantly inhibited tumor growth with 100% survival rate for ∼60 days. The therapy induced the activation of cytotoxic lymphocytes and the maturation of APCs in vivo. This treatment could be effective in image-guided local cancer immunotherapy.

Clinical Studies of Bee Venom Acupuncture for Lower Back Pain in the Korean Literature.

This study aimed to identify all of the characteristics of bee venom acupuncture (BVA) for the treatment of lower back pain (LBP) that are described in the Korean literature, and to provide English-speaking researchers with bibliometrics. Six Korean electronic databases and sixteen Korean journals on BVA treatment for back pain were searched up to February 2022. This report included and analyzed 64 clinical studies on BVA interventions for back pain and 1297 patients with LBP. The most common disease in patients with back pain was lumbar herniated intervertebral discs (HIVD) of the lumbar spine (L-spine). All studies used bee venom (BV) diluted with distilled water. The concentration of BVA for HIVD of L-spine patients with LBP ranged from 0.01 to 5.0 mg/mL; the dosage per treatment was 0.02-2.0 mL, and for a total session was 0.3-40.0 mL. The most used outcome measure was the visual analogue scale for back pain (n = 45, 70.3%), and most of the papers reported that each outcome measure had a positive effect. Korean clinical studies were typically omitted from the review research, resulting in potential language bias. This study provides clinical cases in Korea for future development and standardization of BVA treatment for back pain.

Monitoring of Heavy Metals and Pesticide Residues of Herbal Decoctions in Traditional Korean Medicine Clinics in Korea.

In this study, we investigated whether the levels of heavy metal and pesticide residues in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for heavy metal content such as lead, arsenic, and cadmium using inductively coupled plasma optical emission spectrometry. For mercury, an automatic mercury analyzer based on the gold amalgamation process was used. For pesticide residues, gas chromatography with electron capture detection and gas chromatography with mass selective detection were used for the analyses. Based on the testing, heavy metals were identified in most of the decoctions (Cd: 0.000-0.003 ppm, Pb: 0.003-0.023 ppm, As: 0.000-0.016 ppm, Hg: 0.000-0.002 ppm). Pesticide residues (e.g., total DDT, total BHC, aldrin, endrin, dieldrin) were not detected at all. All of these were no more than the limit values in preceding studies. Therefore, this study confirms that the contents of heavy metals and pesticides in herbal decoctions are within safe levels based on a previous study and provides evidence for establishing safety management standards for herbal decoctions in Korea.