Forecasting the spread of COVID-19 based on policy, vaccination, and Omicron data.

The COVID-19 pandemic caused by the novel SARS-COV-2 virus poses a great risk to the world. During the COVID-19 pandemic, observing and forecasting several important indicators of the epidemic (like new confirmed cases, new cases in intensive care unit, and new deaths for each day) helped prepare the appropriate response (e.g., creating additional intensive care unit beds, and implementing strict interventions). Various predictive models and predictor variables have been used to forecast these indicators. However, the impact of prediction models and predictor variables on forecasting performance has not been systematically well analyzed. Here, we compared the forecasting performance using a linear mixed model in terms of prediction models (mathematical, statistical, and AI/machine learning models) and predictor variables (vaccination rate, stringency index, and Omicron variant rate) for seven selected countries with the highest vaccination rates. We decided on our best models based on the Bayesian Information Criterion (BIC) and analyzed the significance of each predictor. Simple models were preferred. The selection of the best prediction models and the use of Omicron variant rate were considered essential in improving prediction accuracies. For the test data period before Omicron variant emergence, the selection of the best models was the most significant factor in improving prediction accuracy. For the test period after Omicron emergence, Omicron variant rate use was considered essential in deciding forecasting accuracy. For prediction models, ARIMA, lightGBM, and TSGLM generally performed well in both test periods. Linear mixed models with country as a random effect has proven that the choice of prediction models and the use of Omicron data was significant in determining forecasting accuracies for the highly vaccinated countries. Relatively simple models, fit with either prediction model or Omicron data, produced best results in enhancing forecasting accuracies with test data.

Association between exposure to antibiotics during pregnancy or early infancy and risk of autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children: population based cohort study.

OBJECTIVE: To evaluate the association between antibiotic use during pregnancy or early infancy and the risk of neurodevelopmental disorders in children. DESIGN: Nationwide population based cohort study and sibling analysis. SETTING: Korea's National Health Insurance Service mother-child linked database, 2008-21. PARTICIPANTS: All children live born between 2009 and 2020, followed up until 2021 to compare those with and without antibiotic exposure during pregnancy or early infancy (first six months of life). MAIN OUTCOMES MEASURES: Autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children. After 1:1 propensity score matching based on many potential confounders, hazard ratios with 95% confidence interval were estimated using Cox proportional hazard models. A sibling analysis additionally accounted for unmeasured familial factors. RESULTS: After propensity score matching, 1 961 744 children were identified for the pregnancy analysis and 1 609 774 children were identified for the early infancy analysis. Although antibiotic exposure during pregnancy was associated with increased risks of all four neurodevelopmental disorders in the overall cohort, these estimates were attenuated towards the null in the sibling analyses (hazard ratio for autism spectrum disorder 1.06, 95% confidence interval 1.01 to 1.12; intellectual disorder 1.00, 0.93 to 1.07; language disorder 1.05, 1.02 to 1.09; and epilepsy 1.03, 0.98 to 1.08). Likewise, no association was observed between antibiotic exposure during early infancy and autism spectrum disorder (hazard ratio 1.00, 0.96 to 1.03), intellectual disorder (1.07, 0.98 to 1.15), and language disorder (1.04, 1.00 to 1.08) in the sibling analyses; however, a small increased risk of epilepsy was observed (1.13, 1.09 to 1.18). The results generally remained consistent across several subgroup and sensitivity analyses, except for slightly elevated risks observed among children who used antibiotics during very early life and those who used antibiotics for more than 15 days. CONCLUSIONS: In this large cohort study, antibiotic exposure during pregnancy or early infancy was not associated with an increased risk of autism spectrum disorder, intellectual disorder, or language disorder in children. However, elevated risks were observed in several subgroups such as children using antibiotics during very early life and those with long term antibiotic use, which warrants attention and further investigation. Moreover, antibiotic use during infancy was modestly associated with epilepsy, even after control for indications and familial factors. When prescribing antibiotics to pregnant women and infants, clinicians should carefully balance the benefits of use against potential risks.

Effect of Poria cocos Terpenes: Verifying Modes of Action Using Molecular Docking, Drug-Induced Transcriptomes, and Diffusion Network Analyses.

We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds.

Post-traumatic Transient Neurological Dysfunction: A Proposal for Pathophysiology.

Unexplained neurological deterioration is occasionally observed in patients with traumatic brain injuries (TBIs). We aimed to describe the clinical features of post-traumatic transient neurological dysfunction and provide new insight into its pathophysiology. We retrospectively collected data from patients with focal neurological deterioration of unknown origin during hospitalization for acute TBI for 48 consecutive months. Brain imaging, including computed tomography, diffusion-weighted imaging and perfusion-weighted imaging, and electroencephalography were conducted during the episodes. Fourteen (2.0%) patients experienced unexplained focal neurological deterioration among 713 patients who were admitted for traumatic intracranial hemorrhage during the study period. Aphasia was the predominant symptom in all patients, and hemiparesis or hemianopia was accompanied in three patients. These symptoms developed within 14 days after trauma. Structural imaging did not show any significant interval change, and electroencephalography showed persistent arrhythmic slowing in the corresponding hemisphere in most patients. Perfusion imaging revealed increased cerebral blood flow in the symptomatic hemisphere. Surgical intervention and anti-seizure medications were ineffective in abolishing the symptoms. The symptoms disappeared spontaneously after 4 h to 1 month. Transient neurological dysfunction (TND) can occur during the acute phase of TBI. Although TND may last longer than a typical transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we postulate that this is a manifestation of spreading depolarization occurring in the injured brain, which is analogous to migraine aura.

Neural Biomarkers for Identifying Atopic Dermatitis and Assessing Acupuncture Treatment Response Using Resting-State fMRI.

Purpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not. Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models. Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level. Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.

An ultrasensitive label-free RNase H assay based on in vitro transcription of fluorogenic light-up aptamer.

Herein, we proposed a label-free method to identify RNase H activity by utilizing in vitro transcription of fluorogenic light-up aptamers. In this work, we employed the specially designed two pivotal components of the hairpin substrate probe (HP) containing an RNA/DNA chimeric stem region and the template probe (TP) as a transcription template, and the RNase H activity was made to lead to the formation of a complete ds T7 promoter. T7 RNA polymerase could then promote in vitro transcription to generate numerous light-up RNA aptamers that result in significant fluorescence enhancements upon binding to the cognate fluorogenic dye. By leveraging this deliberate design principle, we identified RNase H activity ultrasensitively as low as 0.000156 U mL-1 with excellent specificity against non-target enzymes. We further demonstrated that the strategy can also reliably identify RNase H activity in heterogeneous biological samples such as cell lysates, ensuring its robust practical applicability. This work would provide invaluable insight for the development of innovative biosensing systems utilizing in vitro transcription of light-up aptamers, and it could be broadened to construct other assays by appropriately redesigning the HPs.

Cellular abundance-based prognostic model associated with deregulated gene expression of leukemic stem cells in acute myeloid leukemia.

Background: Previous studies have reported that genes highly expressed in leukemic stem cells (LSC) may dictate the survival probability of patients and expression-based cellular deconvolution may be informative in forecasting prognosis. However, whether the prognosis of acute myeloid leukemia (AML) can be predicted using gene expression and deconvoluted cellular abundances is debatable. Methods: Nine different cell-type abundances of a training set composed of the AML samples of 422 patients, were used to build a model for predicting prognosis by least absolute shrinkage and selection operator Cox regression. This model was validated in two different validation sets, TCGA-LAML and Beat AML (n = 179 and 451, respectively). Results: We introduce a new prognosis predicting model for AML called the LSC activity (LSCA) score, which incorporates the abundance of 5 cell types, granulocyte-monocyte progenitors, common myeloid progenitors, CD45RA + cells, megakaryocyte-erythrocyte progenitors, and multipotent progenitors. Overall survival probabilities between the high and low LSCA score groups were significantly different in TCGA-LAML and Beat AML cohorts (log-rank p-value = 3.3×10-4 and 4.3×10-3, respectively). Also, multivariate Cox regression analysis on these two validation sets shows that LSCA score is independent prognostic factor when considering age, sex, and cytogenetic risk (hazard ratio, HR = 2.17; 95% CI 1.40-3.34; p < 0.001 and HR = 1.20; 95% CI 1.02-1.43; p < 0.03, respectively). The performance of the LSCA score was comparable to other prognostic models, LSC17, APS, and CTC scores, as indicated by the area under the curve. Gene set variation analysis with six LSC-related functional gene sets indicated that high and low LSCA scores are associated with upregulated and downregulated genes in LSCs. Conclusion: We have developed a new prognosis prediction scoring system for AML patients, the LSCA score, which uses deconvoluted cell-type abundance only.

Multifunctional self-priming hairpin probe-based isothermal nucleic acid amplification and its applications for COVID-19 diagnosis.

We herein present a multifunctional self-priming hairpin probe-based isothermal amplification, termed MSH, enabling one-pot detection of target nucleic acids. The sophisticatedly designed multifunctional self-priming hairpin (MSH) probe recognizes the target and rearranges to prime itself, triggering the amplification reaction powered by the continuously repeated extension, nicking, and target recycling. As a consequence, a large number of double-stranded DNA (dsDNA) amplicons are produced that could be monitored in real-time using a dsDNA-intercalating dye. Based on this unique design approach, the nucleocapsid (N) and the open reading frame 1 ab (ORF1ab) genes of SARS-CoV-2 were successfully detected down to 1.664 fM and 0.770 fM, respectively. The practical applicability of our method was validated by accurately diagnosing 60 clinical samples with 93.33% sensitivity and 96.67% specificity. This isothermal one-pot MSH technique holds great promise as a point-of-care testing protocol for the reliable detection of a wide spectrum of pathogens, particularly in resource-limited settings.

A CRISPR/Cas12 trans-cleavage reporter enabling label-free colorimetric detection of SARS-CoV-2 and its variants.

We present a label-free colorimetric CRISPR/Cas-based method enabling affordable molecular diagnostics for SARS-CoV-2. This technique utilizes 3,3'-diethylthiadicarbocyanine iodide (DISC2(5)) which exhibits a distinct color transition from purple to blue when it forms dimers by inserting into the duplex of the thymidine adenine (TA) repeat sequence. Loop-mediated isothermal amplification (LAMP) or recombinase polymerase amplification (RPA) was used to amplify target samples, which were subsequently subjected to the CRISPR/Cas12a system. The target amplicons would activate Cas12a to degrade nearby TA repeat sequences, preserving DISC2(5) in its free form to display purple as opposed to blue in the absence of the target. Based on this design approach, SARS-CoV-2 RNA was colorimetrically detected very sensitively down to 2 copies/µL, and delta and omicron variants of SARS-CoV-2 were also successfully identified. The practical diagnostic utility of this method was further validated by reliably identifying 179 clinical samples including 20 variant samples with 100% clinical sensitivity and specificity. This technique has the potential to become a promising CRISPR-based colorimetric platform for molecular diagnostics of a wide range of target pathogens.

Lower-Body Fractures and the Risk of Dementia: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: The association between physical activity and dementia has been shown in various observational studies. We aimed to determine the risk of dementia in the elderly with lower-body fractures. METHODS: We reconstructed a population-based matched cohort from the National Health Insurance Service-Senior Cohort data set that covers 511,953 recipients of medical insurance in South Korea. RESULTS: Overall 53,776 subjects with lower-body fractures were identified during 2006-2012, and triplicate control groups were matched randomly by sex, age, and years from the index date for each subject with a fracture. There were 3,573 subjects (6.6%) with and 7,987 subjects (4.9%) without lower-body fractures who developed dementia from 2008 up to 2015. Lower-body fractures were independently associated with a subsequent dementia diagnosis with a higher adjusted hazard ratio (aHR) (1.55, 95% confidence interval [CI]=1.49-1.62) compared with upper-body fractures (aHR=1.19, 95% CI=1.14-1.23). CONCLUSIONS: These results support the protective role of physical activity against dementia and highlight the importance of promoting fracture prevention in the elderly.

Leaky mutations in the zeaxanthin epoxidase in Capsicum annuum result in bright-red fruit containing a high amount of zeaxanthin.

Fruit color is one of the most important traits in peppers due to its esthetic value and nutritional benefits and is determined by carotenoid composition, resulting from diverse mutations of carotenoid biosynthetic genes. The EMS204 line, derived from an EMS mutant population, presents bright-red color, compared with the wild type Yuwolcho cultivar. HPLC analysis indicates that EMS204 fruit contains more zeaxanthin and less capsanthin and capsorubin than Yuwolcho. MutMap was used to reveal the color variation of EMS204 using an F3 population derived from a cross of EMS204 and Yuwolcho, and the locus was mapped to a 2.5-Mbp region on chromosome 2. Among the genes in the region, a missense mutation was found in ZEP (zeaxanthin epoxidase) that results in an amino acid sequence alteration (V291 → I). A color complementation experiment with Escherichia coli and ZEP in vitro assay using thylakoid membranes revealed decreased enzymatic activity of EMS204 ZEP. Analysis of endogenous plant hormones revealed a significant reduction in abscisic acid content in EMS204. Germination assays and salinity stress experiments corroborated the lower ABA levels in the seeds. Virus-induced gene silencing showed that ZEP silencing also results in bright-red fruit containing less capsanthin but more zeaxanthin than control. A germplasm survey of red color accessions revealed no similar carotenoid profiles to EMS204. However, a breeding line containing a ZEP mutation showed a very similar carotenoid profile to EMS204. Our results provide a novel breeding strategy to develop red pepper cultivars containing high zeaxanthin contents using ZEP mutations.

Development of virus-induced genome editing methods in Solanaceous crops.

Genome editing (GE) using CRISPR/Cas systems has revolutionized plant mutagenesis. However, conventional transgene-mediated GE methods have limitations due to the time-consuming generation of stable transgenic lines expressing the Cas9/single guide RNA (sgRNA) module through tissue cultures. Virus-induced genome editing (VIGE) systems have been successfully employed in model plants, such as Arabidopsis thaliana and Nicotiana spp. In this study, we developed two VIGE methods for Solanaceous plants. First, we used the tobacco rattle virus (TRV) vector to deliver sgRNAs into a transgenic tomato (Solanum lycopersicum) line of cultivar Micro-Tom expressing Cas9. Second, we devised a transgene-free GE method based on a potato virus X (PVX) vector to deliver Cas9 and sgRNAs. We designed and cloned sgRNAs targeting Phytoene desaturase in the VIGE vectors and determined optimal conditions for VIGE. We evaluated VIGE efficiency through deep sequencing of the target gene after viral vector inoculation, detecting 40.3% and 36.5% mutation rates for TRV- and PVX-mediated GE, respectively. To improve editing efficiency, we applied a 37°C heat treatment, which increased the editing efficiency by 33% to 46% and 56% to 76% for TRV- and PVX-mediated VIGE, respectively. To obtain edited plants, we subjected inoculated cotyledons to tissue culture, yielding successful editing events. We also demonstrated that PVX-mediated GE can be applied to other Solanaceous crops, such as potato (Solanum tuberosum) and eggplant (Solanum melongena). These simple and highly efficient VIGE methods have great potential for generating genome-edited plants in Solanaceous crops.

Atherogenic indices and risk of chronic kidney disease in metabolic derangements: Gangnam Severance Medical Cohort.

Background: The effects of atherogenic indices on kidney function remain unclear. This study evaluated the association between atherogenic indices and risk of chronic kidney disease (CKD) in adults with metabolic derangements. Methods: A total of 4,176 participants from the Gangnam Severance Medical Cohort (2006-2021), which consisted of participants who had at least one disease related to metabolic derangements including diabetes mellitus, fatty liver, and hypertension were enrolled and atherogenic indices (lipid ratios including atherogenic index of plasma [AIP]) were assessed. The study endpoint was a composite kidney outcome (estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 in at least two measurements in participants with baseline eGFR of ≥60 mL/min/1.73 m2; ≥30% decrease in eGFR from baseline in participants with baseline eGFR of <60 mL/min/1.73 m2; or the initiation of dialysis or kidney transplantation). Results: During a median follow-up of 6.0 years (interquartile range, 2.5-11.0 years), 1,266 composite kidney outcomes (30.3%) occurred. The highest quartile of AIP showed a higher risk of composite kidney outcome than the lowest quartile (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.12-1.54). This association was consistent when the AIP was treated as a continuous variable (HR per 1.0 increase, 1.51; 95% CI, 1.21-1.88). However, other atherogenic indices did not show significant associations with composite kidney outcome. Adding AIP to the traditional risk model to predict composite kidney outcomes significantly improved the C-index, net reclassification index, and integrated discrimination improvement. The association between high AIP and an increased risk of composite kidney outcome was consistent regardless of subgroup. Conclusion: High AIP was associated with an increased risk of CKD in adults with metabolic derangements.

Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

Retrieval of aerosol optical properties from GOCI-II observations: Continuation of long-term geostationary aerosol monitoring over East Asia.

Since the Geostationary Ocean Color Imager (GOCI) was successfully launched in 2010, the GOCI Yonsei aerosol retrieval (YAER) algorithm has been continuously updated to retrieve hourly aerosol optical properties. GOCI-II has 4 more channels including UV, finer spatial resolution (250 m), and daily full disk coverage as compared to GOCI, and was launched in February 2020, onboard the GEO-KOMPSAT-2B (GK-2B) satellite. In this study, we extended the YAER algorithm to GOCI-II data based on its improved performance in many aspects and present the first results of aerosol optical properties retrieved from GOCI-II data. Utilizing the overlapping period between the GOCI-II and GOCI in geostationary Earth orbit, we present GOCI-II aerosol retrievals for high aerosol-loading cases over East Asia and show that these have a consistent spatial distribution with those from GOCI. Furthermore, GOCI-II provides AOD at an even higher spatial resolution, revealing finer changes in aerosol concentrations. Validation results for one year data show that the GOCI-II AOD has a correlation coefficient of 0.83 and a ratio within the expected error (EE) of 59.4 % when compared with the aerosol robotic network (AERONET) data. We compared statistical metrics for the GOCI and GOCI-II AODs to assess the consistency between the two datasets. In addition, it was found that there is a strong correlation between the two datasets from the comparison of gridded GOCI and GOCI-II AOD products. It is expected that data from GOCI-II will continue long-term aerosol records with high accuracy that can be used to address air-quality issues over East Asia.

Sensory and emotional responses to deep pressure stimulation at myofascial trigger points: a pilot study.

Objective: Although manual pressure, such as that used during a massage, is often associated with pain, it can simultaneously be perceived as pleasant when applied to certain body areas. We hypothesized that stimulation of myofascial trigger points (TPs) leads to simultaneous pain and pleasure. TPs are hyperirritable points located in the taut band of the skeletal muscle. Method: In this study, we measured the muscle tone, muscle stiffness, and pressure pain threshold of TPs and control points in the left brachioradialis muscle of 48 healthy participants. We also applied deep compression to the two points and collected subjective data on pain, pleasantness, unpleasantness, and relief. Result: Greater muscle stiffness was observed in the TPs versus control points (t = 6.55, p < 0.001), and the pain threshold was significantly lower in the TPs (t = -6.21, p < 0.001). Unpleasantness ratings after deep compression were significantly lower in the TPs compared with control points (t = -2.68, p < 0.05). Participants experienced greater relief at the TPs compared with control points (t = 2.01, p < 0.05), although the perceived pain did not differ between the two types of points. Conclusion: We compared the properties of TPs and control points, and found that deep compression at TPs was associated with higher muscle tone and stiffness, lower unpleasantness ratings, and higher relief ratings compared with the control points. These findings suggest that, at least for some TPs, pain and pleasantness are simultaneously elicited by deep pressure stimulation.

Epileptic seizures associated with progressive multifocal leukoencephalopathy in HIV-infected patients in Korea.

We investigated the incidence and risk factors of seizures related to progressive multifocal leukoencephalopathy (PML) in Korean patients infected with HIV. Of the 34 patients, 14 (41.2%) developed epileptic seizures during a median follow-up of 82 months. The median time from PML diagnosis to seizure onset was 44 months, ranging from 0 to 133 months. Patients with PML who developed seizures more commonly had cognitive impairment and multiple or diffuse lesions on brain MRI. These findings highlight the increased seizure risk among HIV-infected patients with PML at any stage of the disease, particularly in cases with extensive involvement.

Gender and Age Bias in the Evaluation of Suicide Attempt Behavior in an Emergency Department.

We aimed to investigate whether demographic characteristics such as age and gender of attempted suicide patients are associated with bias in the post-Emergency Department (ED) discharge program manager's evaluation of genuineness of the patients' suicide attempts. In the ED-Based Post-Suicide Attempt Case Management (ED-PSACM) program, the manager interviews patients with suicide attempts and makes subjective judgement on the patient's genuineness of the suicide attempt. After patients' discharge, the manager provides follow-up post-discharge care management services. Compared to ≥ 65 years old male patients as a reference group, 18-39 years old female patients showed significantly lower judgment for a genuine suicide attempt (OR = 0.34; 95% CI 0.12-0.81). Other groups did not show significant differences from the reference group. Our study result suggests the possibility of the effects of bias on young females on the judgment of the suicide attempt genuineness. Medical staff and interventions managers in the ED should be concerned to avoid knowledge-mediated bias, especially by gender and age.

Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea.

OBJECTIVES: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC. PATIENTS AND METHODS: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently. RESULTS: aNSCLC patients with cfDNA test results (n = 405) were categorized into three groups: treatment naïve (n = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (n = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (n = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (n = 221) with common EGFR mutations or ALK/ROS1 fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment. CONCLUSIONS: In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC.

An Ethanol Extract of Coptidis rhizoma Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation.

In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation.