Search

RNA secondary structures can carry out essential cellular functions alone or interact with one another to form the hierarchical tertiary structures. Experimental structure identification approa ches can show the in vitro structures of RNA molecules. However, they usually have limits in the resolution and are costly. In silico structure prediction tools are thus primarily relied on for pre-experiment analysis. Various structure prediction models have been developed over the decades. Since these tools are usually used before knowing the actual RNA structures, evaluating and ranking the pile of secondary structure predictions of a given sequence is essential in computational analysis. In this research, we implemented a web service called SSRTool (RNA Secondary Structure prediction Ranking Tool) to assist in the ranking and evaluation of the generated predicted structures of a given sequence. Based on the computed species-specific interpretability significance in four common RNA structure–function aspects, SSRTool provides three functions along with visualization interfaces: (1) Rank user-generated predictions. (2) Provide an automated streamline of structure prediction and ranking for a given sequence. (3) Infer the functional aspects of a given structure. We demonstrated the applicability of SSRTool via real case studies and reported the similar trends between computed species-specific rankings and the corresponding prediction F1 values. The SSRTool web service is available online at https://cobisHSS0.im.nuk.edu.tw/SSRTool/, http://cosbi3.ee.ncku.edu.tw/SSRTool/, or the redirecting site https://github.com/cobisLab/SSRTool/.

Yu et al. provide evidence that Ustilago maydis employs two structurally distinct telomere-binding proteins to perform complementary functions in telomere maintenance in this organism. While UmTay1 regulates primarily telomere replication and recombination, UmTrf2 is responsible for telomere protection.

The ZnO:Al thin films were prepared by RF magnetron sputtering on Si substrateusing Pt as interdigitated electrodes. The structure was characterized by XRD and SEManalyses, and the ethanol vapor gas sensing as well as electrical properties have beeninvestigated and discussed. The gas sensing results show that the sensitivity for detecting400 ppm ethanol vapor was ~20 at an operating temperature of 250°C. The high sensitivity,fast recovery, and reliability suggest that ZnO:Al thin film prepared by RF magnetronsputtering can be used for ethanol vapor gas sensing.

The heterodimeric Ku complex has been shown to participate in DNA repair and telomere regulation in a variety of organisms. Here we report a detailed characterization of the function of Ku70 in the diploid fungal pathogen Candida albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type colony and cellular morphology, and are not sensitive to MMS or UV light. Interestingly, we observed complex effects of KU70 gene dosage on telomere lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres, and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of combination mutants suggests that the telomere elongation in the ku70 null mutant is due mostly to unregulated telomerase action. In addition, elevated levels of extrachromosomal telomeric circles were detected in the null mutant, consistent with activation of aberrant telomeric recombination. Altogether, our observations point to multiple mechanisms of the Ku complex in telomerase regulation and telomere protection in C. albicans, and reveal interesting similarities and differences in the mechanisms of the Ku complex in disparate systems.

Ethnopharmacological Relevance: Cheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects., Aim of the Study: The purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study., Materials and Methods: A single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors., Results: CWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca 2+ /calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction., Conclusions: CWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this study to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We performed a nationwide analysis to evaluate the impact of the early coronavirus disease 2019 (COVID-19) pandemic on emergency department (ED) visits by adult cancer patients having COVID-like symptoms., Methods: We analyzed the National Emergency Department Information System (NEDIS) data on ED visits by adult cancer patients who presented with chief complaints of fever or respiratory symptoms (FRS) indicative of COVID-19, from 2016 to 2020. An interrupted time series analysis with a quasi-Poisson regression model was performed, adjusting for seasonality and time, to evaluate whether underlying trends for monthly ED visits and the in-hospital mortality rate (%) per month changed with the pandemic among these patients. We also estimated the adjusted odds ratio (aOR) of in-hospital deaths among cancer patients using multivariable logistic regression analysis., Results: ED visits by cancer patients with FRS decreased during the COVID-19 pandemic (relative risk [RR] with 95% confidence interval [CI]: slope change, 0.99 [0.98-1.00] and step change, 0.84 [0.76-0.92]). However, the in-hospital mortality rate (%) for these patients was increased (slope change, 1.14 [1.04-1.25] and step change, 0.99 [0.98-1.01]). Factors such as urgent triage status, ambulance use, and treatment in hospitals with fewer than 300 staffed beds significantly contributed to increased aOR of in-hospital deaths during the COVID-19 pandemic compared to the pre-pandemic period., Conclusion: Further studies are needed to highlight the importance of ED service preparation in planning and managing resources for cancer patients during future pandemics., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in significant disruptions to critical care systems globally. However, research on the impact of the COVID-19 pandemic on intensive care unit (ICU) admissions via the emergency department (ED) is limited. Therefore, this study evaluated the changes in the number of ED-to-ICU admissions and clinical outcomes in the periods before and during the pandemic., Methods: We identified all adult patients admitted to the ICU through level 1 or 2 EDs in Korea between February 2018 and January 2021. February 2020 was considered the onset point of the COVID-19 pandemic. The monthly changes in the number of ED-to-ICU admissions and the in-hospital mortality rates before and during the COVID-19 pandemic were evaluated using interrupted time-series analysis., Results: Among the 555,793 adult ED-to-ICU admissions, the number of ED-to-ICU admissions during the pandemic decreased compared to that before the pandemic (step change, 0.916; 95% confidence interval [CI] 0.869-0.966], although the trend did not attain statistical significance (slope change, 0.997; 95% CI 0.991-1.003). The proportion of patients who arrived by emergency medical services, those transferred from other hospitals, and those with injuries declined significantly among the number of ED-to-ICU admissions during the pandemic. The proportion of in-hospital deaths significantly increased during the pandemic (step change, 1.054; 95% CI 1.003-1.108); however, the trend did not attain statistical significance (slope change, 1.001; 95% CI 0.996-1.007). Mortality rates in patients with an ED length of stay of ≥ 6 h until admission to the ICU rose abruptly following the onset of the pandemic (step change, 1.169; 95% CI 1.021-1.339)., Conclusions: The COVID-19 pandemic significantly affected ED-to-ICU admission and in-hospital mortality rates in Korea. This study's findings have important implications for healthcare providers and policymakers planning the management of future outbreaks of infectious diseases. Strategies are needed to address the challenges posed by pandemics and improve the outcomes in critically ill patients., (© 2024. The Author(s).)

Objectives: Geographic disparities in access to secondary pediatric care remain a significant issue in countries with universal health coverage, including Korea. This study investigated the link between geographic access to secondary pediatric care and mortality rates in children and adolescents (0-19 years) in Korea., Methods: We analyzed district-level data to assess the percentage of those aged 0-19 years residing outside of a 60-minute travel radius from the nearest secondary pediatric care provider (accessibility vulnerability index, AVI)., Results: The AVI ranged from 0% to 100% across the districts for the study period. The confidence interval (CI) was -0.30 (95% CI, -0.41 to -0.19) in 2017 and -0.41 (95% CI, -0.52 to -0.30) in 2021, indicating that the proportion of those who could not access care within 60 minutes was disproportionately higher in districts with lower socioeconomic status. We found 8% rise in mortality rates among individuals aged 0-19 years for every 10% increase in AVI (95% CI, 1.06 to 1.10)., Conclusions: The study highlights disparities in pediatric care access and their impact on child survival, emphasizing the need for improved access to achieve true universal health coverage.

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients' statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis., (© 2023. The Author(s).)

Quantitative phase imaging, integrated with artificial intelligence, allows for the rapid and label-free investigation of the physiology and pathology of biological systems. This review presents the principles of various two-dimensional and three-dimensional label-free phase imaging techniques that exploit refractive index as an intrinsic optical imaging contrast. In particular, we discuss artificial intelligence-based analysis methodologies for biomedical studies including image enhancement, segmentation of cellular or subcellular structures, classification of types of biological samples and image translation to furnish subcellular and histochemical information from label-free phase images. We also discuss the advantages and challenges of artificial intelligence-enabled quantitative phase imaging analyses, summarize recent notable applications in the life sciences, and cover the potential of this field for basic and industrial research in the life sciences., (© 2023. Springer Nature America, Inc.)

Background: With the epidemiological transition, sociodemographic changes and differential lifetime experiences of women, women's health research improves knowledge of diverse health issues and the impact of policies. To explore the initiatives of women's health research in Korea, the present study examined the trends and topics of research on women's health funded by the government., Methods: We searched all research projects on women's health funded by the government between 2012 and 2020 in Korea using the National Science & Technology Information Service database. We reviewed all the titles and abstract of the projects and examined the research trends by year. Content analysis was performed using both deductive and inductive approaches. Text network analysis and visualization by topic were conducted for keywords with a minimum of 10 occurrences in the title and abstract., Results: Total number and funding amount of research projects on women's health in 2020 increased by 2.4 and 2.2 times over 2012 levels, respectively. The Ministry of Health and Welfare and the Ministry of Food and Drug Safety funded 20.9% of all projects. The majority of the topics (59.8%) addressed breast and gynecological cancers. Those on sexual and reproductive health accounted for 16.7%, with steep growth in the number (6.1 times) and funding (11.1 times) over 2012 levels. The topic analysis presented a more complex keyword network in 2020 than in 2012; however, the keywords frequently used in 2020 were similar to those of 2012., Conclusion: Women's health research projects have been growing in number and funding, with limited diversity in topics. Diversifying the topics and focusing on issues beyond the breast and pregnancy would be needed to reflect the complete life course of women. Institutionalization of diverse communication channels with various interest groups for women's health would be needed to better understand women's health needs from a public health perspective., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background and Objectives : Multiple factors are associated with postoperative functional outcomes, such as acute kidney injury (AKI), following partial nephrectomy (PN). The pre-, peri-, and postoperative factors are heavily intertwined and change dynamically, making it difficult to predict postoperative renal function. Therefore, we aimed to build an artificial intelligence (AI) model that utilizes perioperative factors to predict residual renal function and incidence of AKI following PN. Methods and Materials : This retrospective study included 785 patients (training set 706, test set 79) from six tertiary referral centers who underwent open or robotic PN. Forty-four perioperative features were used as inputs to train the AI prediction model. XG-Boost and genetic algorithms were used for the final model selection and to determine feature importance. The primary outcome measure was immediate postoperative serum creatinine (Cr) level. The secondary outcome was the incidence of AKI (estimated glomerular filtration rate (eGFR) < 60 mL/h). The average difference between the true and predicted serum Cr levels was considered the mean absolute error (MAE) and was used as a model evaluation parameter. Results : An AI model for predicting immediate postoperative serum Cr levels was selected from 2000 candidates by providing the lowest MAE (0.03 mg/dL). The model-predicted immediate postoperative serum Cr levels correlated closely with the measured values (R 2 = 0.9669). The sensitivity and specificity of the model for predicting AKI were 85.5% and 99.7% in the training set, and 100.0% and 100.0% in the test set, respectively. The limitations of this study included its retrospective design. Conclusions : Our AI model successfully predicted accurate serum Cr levels and the likelihood of AKI. The accuracy of our model suggests that personalized guidelines to optimize multidisciplinary plans involving pre- and postoperative care need to be developed.

Hematology analysis, a common clinical test for screening various diseases, has conventionally required a chemical staining process that is time-consuming and labor-intensive. To reduce the costs of chemical staining, label-free imaging can be utilized in hematology analysis. In this work, we exploit optical diffraction tomography and the fully convolutional one-stage object detector or FCOS, a deep learning architecture for object detection, to develop a label-free hematology analysis framework. Detected cells are classified into four groups: red blood cell, abnormal red blood cell, platelet, and white blood cell. In the results, the trained object detection model showed superior detection performance for blood cells in refractive index tomograms (0.977 mAP) and also showed high accuracy in the four-class classification of blood cells (0.9708 weighted F1 score, 0.9712 total accuracy). For further verification, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were compared with values obtained from reference hematology equipment, with our results showing reasonable correlation in both MCV (0.905) and MCH (0.889). This study provides a successful demonstration of the proposed framework in detecting and classifying blood cells using optical diffraction tomography for label-free hematology analysis., Competing Interests: Dongmin Ryu, Daewoong Ahn, Hayoung Kang, Sangguen Oh, Hyun-seok Min, and Sumin Lee have financial interests in Tomocube Inc., a company that commercializes optical diffraction tomography and quantitative phase imaging instruments. The other authors declare no competing financial interests., (© 2023 The Author(s).)

Despite the enormous interest in inorganic/polymer composite solid-state electrolytes (CSEs) for solid-state batteries (SSBs), the underlying ion transport phenomena in CSEs have not yet been elucidated. Here, we address this issue by formulating a mechanistic understanding of bi-percolating ion channels formation and ion conduction across inorganic-polymer electrolyte interfaces in CSEs. A model CSE is composed of argyrodite-type Li 6 PS 5 Cl (LPSCl) and gel polymer electrolyte (GPE, including Li + -glyme complex as an ion-conducting medium). The percolation threshold of the LPSCl phase in the CSE strongly depends on the elasticity of the GPE phase. Additionally, manipulating the solvation/desolvation behavior of the Li + -glyme complex in the GPE facilitates ion conduction across the LPSCl-GPE interface. The resulting scalable CSE (area = 8 × 6 (cm × cm), thickness ~ 40 μm) can be assembled with a high-mass-loading LiNi 0.7 Co 0.15 Mn 0.15 O 2 cathode (areal-mass-loading = 39 mg cm -2 ) and a graphite anode (negative (N)/positive (P) capacity ratio = 1.1) in order to fabricate an SSB full cell with bi-cell configuration. Under this constrained cell condition, the SSB full cell exhibits high volumetric energy density (480 Wh L cell -1 ) and stable cyclability at 25 °C, far exceeding the values reported by previous CSE-based SSBs., (© 2023. The Author(s).)

We developed a machine learning algorithm (MLA) that can classify human thyroid cell clusters by exploiting both Papanicolaou staining and intrinsic refractive index (RI) as correlative imaging contrasts and evaluated the effects of this combination on diagnostic performance. Thyroid fine-needle aspiration biopsy (FNAB) specimens were analyzed using correlative optical diffraction tomography, which can simultaneously measure both, the color brightfield of Papanicolaou staining and three-dimensional RI distribution. The MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. We included 1535 thyroid cell clusters (benign: malignancy = 1128:407) from 124 patients. Accuracies of MLA classifiers using color images, RI images, and both were 98.0%, 98.0%, and 100%, respectively. As information for classification, the nucleus size was mainly used in the color image; however, detailed morphological information of the nucleus was also used in the RI image. We demonstrate that the present MLA and correlative FNAB imaging approach has the potential for diagnosing thyroid cancer, and complementary information from color and RI images can improve the performance of the MLA., (© 2023. The Author(s).)

Background: Lidocaine has been widely used as a short-acting local anesthetic agent to reduce the pain caused by needle insertion. Dissolving microneedles (DMNs), which are minimally invasive, can effectively deliver drugs by overcoming the oral mucosal barrier and relieving patient discomfort., Methods: Lidocaine solution prepared by mixing lidocaine-HCl and hyaluronic acid was used to fabricate oral lidocaine HCl-encapsulated DMNs (oral Li-DMNs) via centrifugal lithography. The dissolution, penetration ability, and local transmucosal drug delivery of oral Li-DMNs into the oral mucosa were evaluated in porcine jaws. Pharmacokinetic analysis and safety assessment were performed using rabbits., Results: The insertion depth of the oral Li-DMNs satisfies the safety standard. The oral Li-DMNs were completely dissolved after 3 min of application. The local transmucosal drug delivery, pharmacokinetic, and safety evaluations showed that the oral Li-DMNs can obtain a local anesthesia effect at a relatively lower dose, and there was no oral mucosal irritation in rabbits., Conclusions: A novel and safe oral Li-DMNs have potential applications in large animals and clinical trials and would possibly enter the anesthesia market.

Purpose: Total kidney volume (TKV) measurement is crucial for selecting treatment candidates in autosomal dominant polycystic kidney disease (ADPKD). We developed and investigated the performance of fully-automated 3D-volumetry model and applied it to software as a service (SaaS) for clinical support on tolvaptan prescription in ADPKD patients., Materials and Methods: Computed tomography scans of ADPKD patients taken between January 2000 and June 2022 were acquired from seven institutions. The quality of the images was manually reviewed in advance. The acquired dataset was split into training, validation, and test datasets at a ratio of 8.5:1:0.5. Convolutional, neural network-based automatic segmentation model was trained to obtain 3D segment mask for TKV measurement. The algorithm consisted of three steps: data preprocessing, ADPKD area extraction, and post-processing. After performance validation with the Dice score, 3D-volumetry model was applied to SaaS which is based on Mayo imaging classification for ADPKD., Results: A total of 753 cases with 95,117 slices were included. The differences between the ground-truth ADPKD kidney mask and the predicted ADPKD kidney mask were negligible, with intersection over union >0.95. The post-process filter successfully removed false alarms. The test-set performance was homogeneously equal and the Dice score of the model was 0.971; after post-processing, it improved to 0.979. The SaaS calculated TKV from uploaded Digital Imaging and Communications in Medicine images and classified patients according to height-adjusted TKV for age., Conclusions: Our artificial intelligence-3D volumetry model exhibited effective, feasible, and non-inferior performance compared with that of human experts and successfully predicted the rapid ADPKD progressor., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, is promising for safely treating type 2 diabetes mellitus (T2DM), compared to insulin, by significantly reducing the risk of glucose-dependent hypoglycemia. Concerns related to injection prevent T2DM patients from taking liraglutide regularly, even though once-a-day subcutaneous (SC) injections. Dissolving microneedles (DMNs) are promising substitutes for SC injection and for improving patient convenience. However, there are two fundamental limitations: the low drug delivery due to incomplete insertion and loss of drug activity during DMN fabrication. Here, it is shown that an egg microneedle (EMN) designed with three functional layered structures can maintain the maximum activity of the loaded compound during DMN fabrication and deliver it completely into the skin, with the base layer allowing the complete delivery of liraglutide, and the shell layer maintaining the drug activity by mimicking the role of albumin in eggs. In a diabetic mouse model, liraglutide administration via EMN exhibited similar effect when compared to that of injection. Therefore, EMN-mediated liraglutide administration is a good potential option for replacing liraglutide injections in T2DM treatment., (© 2023 Wiley-VCH GmbH.)

Purpose: This study aimed to develop a motivational interviewing pulmonary rehabilitation program based on self-determination theory to maintain pulmonary rehabilitation-related health behaviors in patients with chronic obstructive pulmonary disease. The program was developed by reviewing the literature on pulmonary rehabilitation guidelines, drawing on the self-determinism theory to establish its contents, recruiting experts to test its validity, and conducting a preliminary survey., Methods: A quasi-experimental design was used to confirm the effect of the program. The participants were outpatients diagnosed with chronic obstructive pulmonary disease at three general hospitals in Busan. There were 33 subjects: 15 in the experimental group and 18 in the control group. The experimental group performed a motivational interviewing pulmonary rehabilitation program which comprised 11 sessions delivered over 10 weeks. The outcomes were measured using basic psychological needs, dyspnea, 6-minute walking distance, and functional status. Intervention effects were analyzed using repeated-measures ANOVA., Results: The analysis revealed significant differences between the experimental and control groups in competence among the subdomains of basic psychological needs, dyspnea during exercise, and functional status., Conclusion: The developed program affects physical conditions and can be applied as an effective clinical nursing intervention to continuously improve the pulmonary rehabilitation behavior of patients with chronic obstructive pulmonary disease., Competing Interests: The authors declared no conflict of interest., (© 2023 Korean Society of Nursing Science.)

Dissolving microneedles (DMNs), despite their minimally invasive drug administration, face challenges in skin insertion and drug-loading capacity, which lead to less effective drug delivery. The micro-pillar tunnel stamp (MPTS) was designed to enhance the transdermal delivery efficacy of externally provided topical formulations via the creation of microchannels. The tunnel and canal of the MPTS enable the simultaneous application of DMNs and topical drugs. The application of micro-pillar-polycaprolactone (MP-PCL), which is a DMN made of a slowly dissolving polymer, exhibited a drug permeation rate 1.3-fold and 2.6-fold higher than that of micro-pillar-hyaluronic acid (MP-HA), a DMN made of a rapidly dissolving polymer, and the topical group, respectively. The base diameter of MP-PCL was set to 700 μm for maximized delivery efficacy, achieving 2.8-fold higher L-ascorbic acid accumulation than that of the topical group. In vivo analysis showed that, compared to topical administration, MPTS-delivered lidocaine had 5-fold greater permeation and the MPTS-delivered group showed 1.25-fold higher skin residual amount, confirming enhanced delivery. Thus, the optimized MPTS system can be presented as an attractive alternative to overcome the limitations of the existing MN systems such as incomplete insertion and limited drug-loading capacity, enhancing the delivery of topical formulations in the transdermal market. STATEMENT OF SIGNIFICANCE: We developed a micro-pillar tunnel stamp (MPTS) to enhance the delivery of externally provided topical formulations. The functional tunnel and canal of the MPTS enabled the simultaneous application of a dissolving microneedle (DMN) array insertion and administration of external topical drugs. Upon insertion, the DMNs created skin microchannels that allowed the externally administered drug to diffuse. DMNs were fabricated using polycaprolactone (PCL), a slowly dissolving polymer, to maintain their structure inside the skin and prolong the opening duration of the microchannels. This system achieved significantly improved delivery of topically administered external drugs via integration with slowly dissolving DMNs, while offering the possibility of its development as a universal delivery system for various topical pharmaceuticals., Competing Interests: Declaration of Competing Interest Hyungil Jung is an inventor of patents that have been or may be licensed to JUVIC Inc. and is a founder and shareholder JUVIC Inc., developing microneedle-based products. Huisuk Yang and Chansol Jeon are employees of JUVIC Inc. These potential conflicts of interests have been disclosed and are being managed by Yonsei University. The other authors declare that there is no conflict of interest., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: In most societies, women and men systematically differ in consumption of cosmetics and household products, which are interlinked with gendered norms and occupational segregation. We investigated the differences in personal care product (PCP) use and exposure to endocrine disrupting chemicals (EDCs) based on occupation and gender., Methods: We utilized data from the first to third Korean National Environmental Health Survey analyzing 9218 participants aged 20-59 years engaged in their current occupation for ≥3 months. Frequent PCP use (≥once/week) and exposure to EDCs were analyzed by gender and occupation. We used least-square geometric means (LSGMs) of urinary concentrations of the five EDCs adjusted for covariates., Results: Manual occupation was most common in men and no paid occupation was most frequent in women. In general, clerical, service, and sales workers showed the highest prevalence of frequent use of hair and body products. Women used body and makeup products more frequently than men. For all five EDCs, similarly, women showed higher urinary levels in all occupation groups. When stratified by gender, the differences in urinary concentration of EDCs across occupation groups were not observed in men. Among women, clerical, service, and sales workers showed higher bisphenol A (BPA) and mono-n-butyl phthalate (MnBP) levels than manual workers., Conclusions: Differentials in exposure to EDCs by occupation groups were not evident for men. Given the higher urinary concentration of EDCs in women compared to men, interventions to reduce the exposure to EDCs would need to focus on women, especially in clerical, service, and sales occupations., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The implementation of an effective suicide prevention program requires the identification and monitoring of subpopulations with elevated risks for suicide in consideration of demographic characteristics, to facilitate the development of tailored countermeasures for tackling the risk factors of suicide. We examined the annual trends in emergency department (ED) visits for suicide attempts (SAs) or self-harm and investigated the sex- and age-specific characteristics of individuals who visited the ED for SA and self-harm., Methods: Data on ED visits for SAs or self-harm in Korea from 2016 to 2020 were extracted from the National Emergency Department Information System and assessed. We evaluated the age-standardized incidence rate of ED visits for SAs or self-harm, and hospital mortality among individuals who visited the ED for SAs or self-harm. In addition, the characteristics of the individuals were compared according to sex and age., Results: We identified 145,963 ED visits for SAs or self-harm (0.42% of the total ED visits) during the study period. The rate of ED visits increased in the youngest age group (19-29 years old), and was more prominent among women (increased by an annual average of 22.5%), despite the coronavirus disease pandemic. The middle-aged group (45-64 years old) had a higher rate of mortality than other age groups, and the highest proportion of individuals on Medical Aid., Conclusion: It is necessary to plan age- and gender-specific suicide prevention programs that focus on improving the limited public mental health resources for the vulnerable populations., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Since 2014, Korea has been operating the National Emergency Medical Situation Room (NEMSR) to provide regional emergency departments (EDs) with coordination services for the interhospital transfer of critically ill patients. The present study aimed to describe the NEMSR's experience and interhospital transfer pattern from EDs nationwide, and investigate the factors related to delayed transfers or transfers that could not be arranged by the NEMSR., Methods: This study was a retrospective cross-sectional analysis of the NEMSR's coordination registry from 2017 to 2019. The demographic and hospital characteristics related to emergency transfers were analyzed with hierarchical logistic models., Results: The NEMSR received a total of 14,003 requests for the arrangement of the interhospital transfers of critically ill patients from 2017 to 2019. Of 10,222 requests included in the analysis, 8297 (81.17%) successful transfers were coordinated by the NEMSR. Transfers were requested mainly due to a shortage of medical staff (59.79%) and ICU beds (30.80%). Delayed transfers were significantly associated with insufficient hospital resources. The larger the bed capacity of the sending hospital, the more difficult it was to coordinate the transfer (odds ratio [OR] for transfer not arranged = 2.04; 95% confidence interval [CI]: 1.48-2.82, ≥ 1000 beds vs. < 300 beds) and the longer the transfer was delayed (OR for delays of more than 44 minutes = 2.08; 95% CI: 1.57-2.76, ≥ 1000 beds vs. < 300 beds)., Conclusions: The operation of the NEMSR has clinical importance in that it could efficiently coordinate interhospital transfers through a protocolized process and resource information system. The coordination role is significant as information technology in emergency care develops while regional gaps in the distribution of medical resources widen., (© 2023. The Author(s).)

Dissolving microneedles (DMNs) are used for minimally invasive transdermal drug delivery. Dissolution of drugs is achieved in the body after skin penetration by DMNs. Unlike injections, the insertion depth of the DMN is an important issue because the amount of dissolved DMN in the skin determines the amount of drug delivered. Therefore, the inaccurate drug delivery due to the incomplete insertion is one of the limitations of the DMN. Thus, many insertion and penetration tests have been essentially conducted in DMN studies, yet only incomplete insertion is known and the exact standard for how much it is not inserted is still unknown. Moreover, there are various shapes have been introduced in the microneedle field, there have been only few studies that have compared and evaluated the insertion depth of the shapes. Here, we present an intensive approach for DMN insertion based on DMN shape among various insertion deciding factors. We numerically analyzed the volumetric distribution of three types of DMN shapes: conical-shaped DMN, funnel-shaped DMN, and candlelit-shaped DMN, and introduced a new insertion evaluation criterion while covering previous insertion evaluations. Using optical coherence tomography, the images of DMNs embedded in the skin were analyzed in rea l-time, and the amount of drug delivered was analyzed at sectioned depth with a cryotome. The in vitro data confirmed that the insertion depth differed based on shape, and the resulting drug delivery depended on the volume assigned to the insertion depth. Insulin-loaded DMNs were applied to C57BL/6 mice, and the results of pharmacokinetic and pharmacodynamic analyses supported the results of the in vitro analysis. Our approach, which considers the correlation between DMN shape and insertion depth, will contribute to establishing criteria for various DMN design and maximizing drug delivery., Competing Interests: Declaration of competing interest Hyungil Jung has submitted patents that have been or may be licensed to Juvic Inc. and is a founder/shareholder at Juvic Inc., developing microneedle-based products. These potential conflicts of interest have been disclosed and are being managed by Yonsei University. Other authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Aging of the kidney is associated with complex molecular, histological, and functional changes. Although the aging process itself does not induce renal damage, underlying disease such as diabetes mellitus can aggravate kidney injury during aging. Although oxidative stress is considered an important mediator in age-related renal fibrosis, it is unclear how oxidative stress increases during normal and diabetic aging., Methods: In this study, we investigated molecular changes in the kidney in normal and diabetic aging mice. C57BL/6 mice were studied at 2, 12, and 24 months of age, and leptin receptor-deficient db/db mice were studied at 8, 12, 16, 20, 24, and 38 weeks of age. We measured renal functional parameters, fibrotic and inflammatory markers, and oxidative stress markers at all the above time points., Results: Both nondiabetic and diabetic mice exhibited progressive microalbuminuria during their lifespan. Interestingly, both diabetic aging and normal aging mice showed progressive increases in oxidative stress markers such as plasma and urinary 8-isoprostane, as well as renal lipid hydroperoxide content. In renal tissues, proinflammatory and profibrotic molecules were significantly upregulated in an age-dependent manner. Expression of three NADPH oxidase (Nox) isoforms, namely, Nox1, Nox2, and Nox4, was significantly increased during aging. Compared with normal aging mice, diabetic db/db mice demonstrated more dramatic changes during aging process., Conclusions: Our findings suggest that NADPH oxidases play an important role in the aging kidney under both normal and diabetic conditions. Targeting of these oxidases might be a new promising therapy to treat issues associated with aging kidneys., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

In this study, we investigated the effects of carbonated water concentration on swallowing function using surface electromyography (sEMG). Healthy subjects (n = 52, 26.77 ± 3.21 years old) were asked to perform two swallows each of noncarbonated water, low-concentration carbonated water, medium-concentration carbonated water, and high-concentration carbonated water. Onset time, the mean sEMG activity amplitude, and duration of muscle activity in each swallow were measured and analyzed for orbicularis oris, masseter, submental muscle complex and infrahyoid muscles. Onset time significantly decreased and mean sEMG activity amplitude significantly increased with carbonation concentration. Therefore, stimulation with carbonation can be effective for modulating a faster and stronger swallow in the oral and pharyngeal phases of swallowing, and its effect on amplitude was greater in the oral phase than in the pharyngeal phase.Clinical Trials Registration This study is registered with Clinical Research Information Service (KCT0005925)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Prolonged emergency department length of stay (EDLOS) in critically ill patients leads to increased mortality. This nationwide study investigated patient and hospital characteristics associated with prolonged EDLOS and in-hospital mortality in adult patients admitted from the emergency department (ED) to the intensive care unit (ICU)., Methods: We conducted a retrospective cohort study using data from the National Emergency Department Information System. Prolonged EDLOS was defined as an EDLOS of ≥ 6 h. We constructed multivariate logistic regression models of patient and hospital variables as predictors of prolonged EDLOS and in-hospital mortality., Results: Between 2016 and 2019, 657,622 adult patients were admitted to the ICU from the ED, representing 2.4% of all ED presentations. The median EDLOS of the overall study population was 3.3 h (interquartile range, 1.9-6.1 h) and 25.3% of patients had a prolonged EDLOS. Patient characteristics associated with prolonged EDLOS included night-time ED presentation and Charlson comorbidity index (CCI) score of 1 or higher. Hospital characteristics associated with prolonged EDLOS included a greater number of staffed beds and a higher ED level. Prolonged EDLOS was associated with in-hospital mortality after adjustment for selected confounders (adjusted odds ratio: 1.18, 95% confidence interval: 1.16-1.20). Patient characteristics associated with in-hospital mortality included age ≥ 65 years, transferred-in, artificially ventilated in the ED, assignment of initial triage to more urgency, and CCI score of 1 or higher. Hospital characteristics associated with in-hospital mortality included a lesser number of staffed beds and a lower ED level., Conclusions: In this nationwide study, 25.3% of adult patients admitted to the ICU from the ED had a prolonged EDLOS, which in turn was significantly associated with an increased in-hospital mortality risk. Hospital characteristics, including the number of staffed beds and the ED level, were associated with prolonged EDLOS and in-hospital mortality., (© 2022. The Author(s).)

Background: Infected bone nonunion is the toughest problem in fracture-related infection, leading to high disability and recurrence. The aim of this study was to evaluate the effectiveness of the Masquelet technique with radical debridement and alternative fixation in the management of infected bone nonunion., Patients and Methods: A retrospective study of prospectively collected data in two trauma centers was performed from 2016 to 2020. Patients diagnosed as infected bone nonunion were included in this study. The initial implant was removed and all patients received a two-stage Masquelet procedure with radical debridement and alternative fixation. The disappearance of inflammatory manifestations and regression of infection indicators (such as interleukin-6 (IL-6), C-reactive protein, white blood cell count) to the normal range were regarded as radical debridement. The alternative fixation depended on local soft tissue conditions. Results were evaluated according to clinical and radiographic assessment and patient satisfaction., Results: A total of 23 patients were included in our study. Six of them received internal fixation, while the other 17 received external fixation. Of the 23 cases, 21 were successfully reconstructed without infection recurrence, except 2 reinfected cases. Mean full weight bearing time was 6.6 months follow-up post last surgery. Out of the 23, 20 cases had satisfactory functional outcomes without additional bone or soft tissue comorbidities. Discrepancies in leg length and joint stiffness were observed in three cases and marked as unsatisfied results., Conclusions: Infected bone nonunion can be successfully managed using the Masquelet technique under radical debridement combined with an alternative fixation method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Liu, Min, Chai, Yu and Wen.)

Background: Dissolving microneedle (DMN) is a transdermal drug delivery system that creates pore in the skin and directly deliver drug through the pore channel. DMN is considered as one of the promising system alternatives to injection because it is minimally invasive and free from needle-related issues. However, traditional DMN patch system has limitations of incomplete insertion and need of complex external devices. Here, we designed film-trigger applicator (FTA) system that successfully delivered DMN inside the skin layers using fracture energy of carboxymethyl cellulose (CMC) film via micropillars. We highlighted advantages of FTA system in DMN delivery compared with DMN patch, including that the film itself can act as DMN applicator., Methods: FTA system consists of DMNs fabricated on the CMC film, DMN array holder having holes aligned to DMN array, and micropillars prepared using general purpose polystyrene. We analyzed punching force on the film by micropillars until the film puncture point at different CMC film concentrations and micropillar diameters. We also compared drug delivery efficiency using rhodamine B fluorescence diffusion and skin penetration using optical coherence tomography (OCT) of FTA with those of conventional DMN patch. In vivo experiments were conducted to evaluate DMN delivery efficiency using C57BL/6 mice and insulin as a model drug., Results: FTA system showed enhanced delivery efficiency compared with that of the existing DMN patch system. We concluded CMC film as a successful DMN applicator as it showed enhanced DMN penetration in OCT and rhodamine B diffusion studies. Further, we applied FTA on shaved mouse dorsal skin and observed successful skin penetration. The FTA group showed higher level of plasma insulin in vivo than that of the DMN patch group., Conclusions: FTA system consisting of simple polymer film and micropillars showed enhanced DMN delivery than that of the existing DMN patch system. Because FTA works with simple finger force without sticky patch and external devices, FTA is a novel and promising platform to overcome the limitations of conventional microneedle patch delivery system; we suggest FTA as a next generation applicator for microneedle application in the future., (© 2022. The Author(s).)

Background: The rapid spread of COVID-19 has caused an emergency situation worldwide. Investigating the association between environmental characteristics and COVID-19 incidence can be of the occurrence and transmission. The objective of this study was to evaluate the association between greenness exposure and COVID-19 cases at the district levels in South Korea. We also explored this association by considering several environmental indicators., Methods: District-level data from across South Korea were used to model the cumulative count of COVID-19 cases per 100,000 persons between January 20, 2020, and February 25, 2021. Greenness exposure data were derived from the Environmental Geographic Information Service of the Korean Ministry of Environment. A negative binomial mixed model evaluated the association between greenness exposure and COVID-19 incidence rate at the district level. Furthermore, we assessed this association between demographic, socioeconomic, environmental statuses, and COVID-19 incidence., Results: Data from 239 of 250 districts (95.6%) were included in the analyses, resulting in 127.89 COVID-19 cases per 100,000 persons between January 20, 2020 and February 25, 2021. Several demographic and socioeconomic variables, districts with a higher rate of natural greenness exposure, were significantly associated with lower COVID-19 incidence rates (incidence rate ratio (IRR), 0.70; 95% confidence interval (CI), 0.54-0.90; P-value = 0.008) after adjusting covariates, but no evidence for the association between built greenness and COVID-19 incidence rates was found., Conclusion: In this ecological study of South Korea, we found that higher rates of exposure to natural greenness were associated with lower rates of COVID-19 cases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare for this study., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The current study aimed to identify the overall characteristics of cancer-related emergency department (ED) visits by adult in Korea, including analyses of factors associated with ED stay time and outcomes nationwide., Materials and Methods: We collected data on cancer-related ED visits from the National Emergency Department Information System (NEDIS) database between 2017 and 2019., Results: ED visits by cancer patients comprised 5.5% (667,935 visits) of total ED visits from 2017 to 2019, which was slightly higher than in other counties. Patients with cancer who visited the ED were over 50 years old, the majority being males, and patients with cancer visited EDs in certified tertiary hospitals more frequently than patients without cancer. In multivariate analyses, the adjusted odds ratio for a length of stay more than 8 hours in the ED of certified tertiary hospitals was 126.34 (95% confidence interval, 1.422 to 1.460) when compared to hospitals. Nevertheless, the longer the patients stayed in the ED, the more likely they were to be admitted., Conclusion: The longer ED stay and higher proportion of cancer patient hospitalizations suggest that cancer patients visit ED to be admitted as well as to receive acute care. The frequency of ED visits and admission may be adjusted to some extent depending on outpatient education, such as self-management of symptoms and situations. Improving cancer care in local communities should be met though provisions such as linking treatment between hospitals or supplying appropriate medical personnel, even for the efficient use of ED resources in hospitals.

The healthcare industry is in dire need of rapid microbial identification techniques for treating microbial infections. Microbial infections are a major healthcare issue worldwide, as these widespread diseases often develop into deadly symptoms. While studies have shown that an early appropriate antibiotic treatment significantly reduces the mortality of an infection, this effective treatment is difficult to practice. The main obstacle to early appropriate antibiotic treatments is the long turnaround time of the routine microbial identification, which includes time-consuming sample growth. Here, we propose a microscopy-based framework that identifies the pathogen from single to few cells. Our framework obtains and exploits the morphology of the limited sample by incorporating three-dimensional quantitative phase imaging and an artificial neural network. We demonstrate the identification of 19 bacterial species that cause bloodstream infections, achieving an accuracy of 82.5% from an individual bacterial cell or cluster. This performance, comparable to that of the gold standard mass spectroscopy under a sufficient amount of sample, underpins the effectiveness of our framework in clinical applications. Furthermore, our accuracy increases with multiple measurements, reaching 99.9% with seven different measurements of cells or clusters. We believe that our framework can serve as a beneficial advisory tool for clinicians during the initial treatment of infections., (© 2022. The Author(s).)

Background: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19., Methods: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020., Results: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years., Conclusions: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The geographical disparity in the access to essential obstetric services is a public health issue in many countries. We explored the association between timely access to obstetric services and the individual risk of adverse birth outcomes., Design: Repeated cross-sectional design., Setting: South Korean national birth data linked with a medical service provision database., Participants: 1 842 718 singleton livebirths from 2014 to 2018., Primary Outcome Measures: Preterm birth (PTB), post-term birth, low birth weight (LBW) and macrosomia., Results: In the study population, 9.3% of mothers lived in districts where the Time Relevance Index (TRI) was as low as the first quartile (40.6%). Overall PTB and post-term birth rates were 5.0% and 0.1%, respectively. Among term livebirths, LBW and macrosomia occurred in 1.0% and 3.3%, respectively. When the TRI is lower, representing less access to obstetric care, the risk of macrosomia was higher (adjusted OR=1.15, 95% CI 1.11 to 1.20 for Q1 compared with Q4). Similarly, PTB is more likely to occur when TRI is lower (1.05, 95% CI 1.00 to 1.10 for Q1; 1.03, 95% CI 1.01 to 1.05 for Q2). There were some inverse associations between TRI and post-term birth (0.80, 95% CI 0.71 to 0.91, for Q2; 0.84, 95% CI 0.76 to 0.93, for Q3)., Conclusions: We observed less accessibility to obstetric service is associated with higher risks of macrosomia and PTB. This finding supports the role of obstetric service accessibility in the individual risk of adverse birth outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Distraction osteogenesis (DO) is a powerful method to reconstruct segmented bone defects in the extremities. However, the main shortcoming of DO is the time-consuming consolidation period. To shorten the consolidation process, two biocompatible inorganic ions, strontium and silicone, were applied to design a biocompatible material to enhance bone mineralization ability during DO. In the present study, we integrated strontium into a one-pot synthesis of mesoporous silica nanoparticles to obtain strontium-doped mesoporous silica nanoparticles characterized by a homogeneous spherical morphology and uniform ion-releasing dynamics. This dual-ion releasing osteogenic and angiogenic drug delivery system was investigated to accelerate mineralization in DO. Osteogenesis was promoted by activation of the Wnt/β-catenin pathway, while bone resorption was inhibited by reduction of the osteoclastogenic factor RANKL/OPG. In addition, angiogenesis may have been enhanced indirectly by secretion of vascular endothelial growth factor (VEGF) from bone marrow stem cells. Therefore, strontium-doped mesoporous silica nanoparticles could be a potential biomaterial candidate for accelerating consolidation during DO., (Copyright © 2021. Published by Elsevier Inc.)

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2022. The Korean Association of Immunologists.)

Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus-induced osteomyelitis and its underlying mechanisms. S. aureus-induced osteomyelitis mouse model was established in Merlin fl/fl Lyz2 cre/+ and Merlin fl/fl Lyz2 +/+ mice. Bone marrow-derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1 fl/fl mice were further crossed with Lyz2-Cre mice to establish myeloid cell conditional knockout mice (DCAF1 fl/fl Lyz2 cre/+ ). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus-infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1-Cul4-associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus-induced osteomyelitis through the regulation of DCAF1., (© 2021 Wiley Periodicals LLC.)

Simultaneous imaging of various facets of intact biological systems across multiple spatiotemporal scales is a long-standing goal in biology and medicine, for which progress is hindered by limits of conventional imaging modalities. Here we propose using the refractive index (RI), an intrinsic quantity governing light-matter interaction, as a means for such measurement. We show that major endogenous subcellular structures, which are conventionally accessed via exogenous fluorescence labelling, are encoded in three-dimensional (3D) RI tomograms. We decode this information in a data-driven manner, with a deep learning-based model that infers multiple 3D fluorescence tomograms from RI measurements of the corresponding subcellular targets, thereby achieving multiplexed microtomography. This approach, called RI2FL for refractive index to fluorescence, inherits the advantages of both high-specificity fluorescence imaging and label-free RI imaging. Importantly, full 3D modelling of absolute and unbiased RI improves generalization, such that the approach is applicable to a broad range of new samples without retraining to facilitate immediate applicability. The performance, reliability and scalability of this technology are extensively characterized, and its various applications within single-cell profiling at unprecedented scales (which can generate new experimentally testable hypotheses) are demonstrated., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The appropriate use of personal protective equipment (PPE) can significantly reduce the risk of infection associated with caring for patients. This study aimed to investigate the knowledge, awareness, and behaviors related to the PPE usage among frontline nurses in a nationally designated coronavirus disease 2019 (COVID-19) hospital during the COVID-19 pandemic., Materials and Methods: The study was performed in two phases: (1) a questionnaire survey to assess the knowledge, awareness, and behaviors related to PPE use, and (2) in-depth personal interviews to elaborate the survey findings. The questionnaires were distributed to all 121 registered nurses in three isolation wards and an intensive care unit which dedicated for patients with COVID-19 and 102 nurses completed survey (84.3% response rate). In-depth interviews were conducted with a total of 7 nurses., Results: Among the survey participant, 100% stated that they knew how to protect themselves while providing nursing care and 93.1% stated that they knew the recommended PPE by task. Most survey participant mainly wore gloves, face shield, N95 or equivalent respirator, and a long-sleeved gown, but one-third of the participants sometimes used coveralls instead of long-sleeved gown. In-depth interviews, the importance of timely updated and specific guidelines for selecting the appropriate type of PPE was highlighted. The adequate supply of PPE, convenience at work, and the role of responsible leadership mainly determined behaviors related to the PPE., Conclusion: As new information on COVID-19 continues to emerge, the up-to-date and specific PPE guideline with evidence should be prepared. The spread of accurate information, the role of accountable leadership, and the active communication under positive organizational culture are important for the proper use of PPE., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Increased inflammatory response is one of the major characteristics of osteonecrosis of the femoral head (ONFH). We aimed to investigate the function of bone morphogenetic protein 2 (BMP-2)/interleukin (IL)-34 axis in the inflammatory responses of ONFH. The systemic and local expression of BMPs in ONFH patients was detected by qRT-PCR and ELISA. In vitro osteoclast differentiation and ONFH mouse models, induced by 20 mg/kg methylprednisolone through i.m. injection, were established using WT and BMP-2-/- mice to explore the regulatory role of BMP-2 in pro-inflammatory responses and bone defects of ONFH. IL-34 expression and function were examined in vitro and in vivo through qRT-PCR, tartrate-resistant acid phosphatase (TRAP) staining, and gene knockout. The systemic and local expression of BMPs was elevated in ONFH patients. BMP-2 reduced the production of pro-inflammatory cytokines and inhibited the differentiation of osteoclasts. Mechanistically, BMP-2 inhibited osteoclasts formation through suppressing IL-34 expression and then promoted bone repair and alleviated ONFH. In conclusion, our study reveals that BMP-2 inhibits inflammatory responses and osteoclast formation through downregulating IL-34.

Objective and Impact Statement . We propose a rapid and accurate blood cell identification method exploiting deep learning and label-free refractive index (RI) tomography. Our computational approach that fully utilizes tomographic information of bone marrow (BM) white blood cell (WBC) enables us to not only classify the blood cells with deep learning but also quantitatively study their morphological and biochemical properties for hematology research. Introduction . Conventional methods for examining blood cells, such as blood smear analysis by medical professionals and fluorescence-activated cell sorting, require significant time, costs, and domain knowledge that could affect test results. While label-free imaging techniques that use a specimen's intrinsic contrast (e.g., multiphoton and Raman microscopy) have been used to characterize blood cells, their imaging procedures and instrumentations are relatively time-consuming and complex. Methods . The RI tomograms of the BM WBCs are acquired via Mach-Zehnder interferometer-based tomographic microscope and classified by a 3D convolutional neural network. We test our deep learning classifier for the four types of bone marrow WBC collected from healthy donors ( n = 10 ): monocyte, myelocyte, B lymphocyte, and T lymphocyte. The quantitative parameters of WBC are directly obtained from the tomograms. Results . Our results show >99% accuracy for the binary classification of myeloids and lymphoids and >96% accuracy for the four-type classification of B and T lymphocytes, monocyte, and myelocytes. The feature learning capability of our approach is visualized via an unsupervised dimension reduction technique. Conclusion . We envision that the proposed cell classification framework can be easily integrated into existing blood cell investigation workflows, providing cost-effective and rapid diagnosis for hematologic malignancy., Competing Interests: H.M. and Y.P. have financial interests in Tomocube Inc., a company that commercializes ODT and is one of the sponsors of the work., (Copyright © 2021 DongHun Ryu et al.)

Dissolving microneedles (DMNs) have been used as an alternative drug delivery system to deliver therapeutics across the skin barrier in a painless manner. In this study, we propose a novel heat-melting method for the fabrication of hydrophobic poly(lactic-co-glycolic acid) (PLGA) DMNs, without the use of potentially harmful organic solvents. The drug-loaded PLGA mixture, which consisted of a middle layer of the DMN, was optimized and successfully implanted into ex vivo porcine skin. Implanted HMP-DMNs separated from the patch within 10 min, enhancing user compliance, and the encapsulated molecules were released for nearly 4 weeks thereafter. In conclusion, the geometry of HMP-DMNs was successfully optimized for safe and effective transdermal sustained drug delivery without the use of organic solvents. This study provides a strategy for the innovative utilization of PLGA as a material for transdermal drug delivery systems.

Introduction: Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings., Material and Methods: Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry., Results: TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001)., Conclusion: Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: The aim of this study was to develop pre-procedural intravascular ultrasound (IVUS)-based models for predicting the occurrence of stent underexpansion., Background: Although post-stenting IVUS has been used to optimize percutaneous coronary intervention, there are no pre-procedural guidelines to estimate the degree of stent expansion and provide preemptive management before stent deployment., Methods: A total of 618 coronary lesions in 618 patients undergoing percutaneous coronary intervention were randomized into training and test sets in a 5:1 ratio. Following the coregistration of pre- and post-stenting IVUS images, the pre-procedural images and clinical information (stent diameter, length, and inflation pressure; balloon diameter; and maximal balloon pressure) were used to develop a regression model using a convolutional neural network to predict post-stenting stent area. To separate the frames with from those without the occurrence of underexpansion (stent area <5.5 mm 2 ), binary classification models (XGBoost) were developed., Results: Overall, the frequency of stent underexpansion was 15% (5,209 of 34,736 frames). At the frame level, stent areas predicted by the pre-procedural IVUS-based regression model significantly correlated with those measured on post-stenting IVUS (r = 0.802). To predict stent underexpansion, maximal accuracy of 94% (area under the curve = 0.94) was achieved when the convolutional neural network- and mask image-derived features were used for the classification model. At the lesion level, there were significant correlations between predicted and measured minimal stent area (r = 0.832) and between predicted and measured total stent volume (r = 0.958)., Conclusions: Deep-learning algorithms accurately predicted incomplete stent expansion. A data-driven approach may assist clinicians in making treatment decisions to avoid stent underexpansion as a preventable cause of stent failure., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea (HI17C1080) and the Ministry of Science and ICT (NRF-2017R1A2B4005886). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Optical diffraction tomography measures the three-dimensional refractive index map of a specimen and visualizes biochemical phenomena at the nanoscale in a non-destructive manner. One major drawback of optical diffraction tomography is poor axial resolution due to limited access to the three-dimensional optical transfer function. This missing cone problem has been addressed through regularization algorithms that use a priori information, such as non-negativity and sample smoothness. However, the iterative nature of these algorithms and their parameter dependency make real-time visualization impossible. In this article, we propose and experimentally demonstrate a deep neural network, which we term DeepRegularizer, that rapidly improves the resolution of a three-dimensional refractive index map. Trained with pairs of datasets (a raw refractive index tomogram and a resolution-enhanced refractive index tomogram via the iterative total variation algorithm), the three-dimensional U-net-based convolutional neural network learns a transformation between the two tomogram domains. The feasibility and generalizability of our network are demonstrated using bacterial cells and a human leukaemic cell line, and by validating the model across different samples. DeepRegularizer offers more than an order of magnitude faster regularization performance compared to the conventional iterative method. We envision that the proposed data-driven approach can bypass the high time complexity of various image reconstructions in other imaging modalities.