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Abstract To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated. The resolution of subretinal fluid(SRF), intraretinal fluid(IRF), and serous pigment epithelial detachment(PED) was also assessed. In addition, factors associated with complete resolution of SRF and IRF were investigated. A total of 69 patients were included in this study. BCVA significantly improved from a mean logarithm of minimal angle of resolution of 0.64 ± 0.41 at baseline to 0.47 ± 0.39 at 3 months (P

Abstract Background Breast cancer (BC) survivorship presents significant health disparities, particularly affecting Black women, who experience a 40% higher BC death rate compared to White women. These disparities are exacerbated by comorbidities, which contribute to poorer overall health outcomes. Additionally, Black BC survivors often face psychosocial challenges, including increased stress and lower well-being, which can lead to adverse physical health effects. This pilot study aims to assess the feasibility and efficacy of a culturally sensitive gratitude journaling intervention designed to enhance spiritual well-being, exercise self-efficacy, and reduce inflammation among Black BC survivors. Methods This pilot study employed a two-group, parallel random-assignment experimental design to compare a gratitude journaling intervention with a general memory journaling control group. Twenty-six Black women aged 40 to 70 years with a history of BC were randomly assigned to either the gratitude journaling intervention group (n = 13) or the control group (n = 13). The gratitude intervention group engaged in gratitude journaling twice weekly for eight weeks, while the control group documented daily memories. Outcomes measured included Gratitude Questionnaire-6, FACIT-Spiritual Well-Being 12 Item Scale, Perceived Stress Scale, Giscombe Superwoman Schema Questionnaire, and the Stage of Motivational Readiness for Physical Activity questionnaire and inflammatory biomarkers. Statistical analyses included the Wilcoxon rank sum test and Fisher’s exact test. Results Twenty-six participants were enrolled, with 73% completing baseline and post-intervention assessments. The intervention group showed a significant improvement in spiritual well-being (p = 0.014) with a large effect size (ES = 0.57). Marginal improvements in exercise self-efficacy were also observed (ES = 0.39). Although there were no significant differences in dispositional gratitude and perceived stress between groups, the intervention group exhibited trends toward increased gratitude and reduced stress. Inflammatory biomarker analysis indicated non-significant changes, though IL-6 levels increased in the intervention group. Conclusion This study demonstrates the feasibility and acceptability of a gratitude journaling intervention among Black BC survivors. The intervention significantly enhanced spiritual well-being and showed promise in improving exercise self-efficacy, suggesting its potential for promoting holistic wellness in this population. These findings provide a foundation for future larger-scale randomized controlled trials to further evaluate the efficacy of gratitude-based interventions for Black BC survivors. Trial registration This study was registered prospectively at ClinicalTrials.gov (NCT05473026) on 07-13-2022.

Objectives We investigated the impact of an advanced “Nutrition Education Program” on patients with Diabetes mellitus, type 2 from public health centers enrolled in a primary health care-based chronic disease management project. This 12-week dietary management program was developed by the Korea Health Promotion and Development Institute. We assessed if this program improved glycemic control and other health indicators through dietary and nutritional improvements. Methods Seventeen patients with Diabetes mellitus type 2 were enrolled in the “Nutrition Education Program.” These patients were referred to public health centers for lifestyle management based on physician assessments at local clinics that were participating in a pilot project on primary health care-based chronic disease management. The participants attended the program comprising face-to-face basic, in-depth, and practical training sessions at the health center during the third, fifth, and seventh weeks, respectively. Anthropometric measurements, body composition analysis, blood biochemical characteristics, nutritional knowledge, and self-efficacy evaluation were performed before and after the program. Data were analyzed using SPSS ver. 28.0. Results The mean age of the participants was 62 years, and most participants were female (14, 82.4%). No significant changes in patients’ anthropometric measurements or body composition were observed after the training. However, significant reductions were observed in the blood biochemical characteristics, including glycated hemoglobin, total cholesterol, and low-density lipoprotein levels. Additionally, patients’ nutritional knowledge and self-efficacy scores increased significantly. Conclusions The “Nutrition Education Program” helped in improving glycemic control and other health indicators in patients with Diabetes mellitus type 2. Further research is required to objectively confirm the long-term and sustained effects of the program in a controlled study. Trial Registration Clinical Research Information Service Identifier: KCT0010010.

Abstract Detecting individuals with low bone mineral density (BMD) before clinical fractures occur may help improve the outcomes of osteoporosis and osteopenia. Although computed tomography (CT) is useful for opportunistic BMD measurement, the modality most suitable for opportunistic screening remains unclear. In this retrospective study, we compared the diagnostic performance of low-dose chest CT (LDCT) and contrast-enhanced abdominopelvic CT (APCT) for measuring BMD at L1 level using dual-energy X-ray absorptiometry (DEXA) as a reference in individuals who underwent LDCT, APCT, and DEXA assessments on the same day. We included 512 individuals (median age: 60 years; interquartile range, 55−65 years; 307 men). Both LDCT (r = 0.706; P

Background This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children’s hospital in South Korea. Methods A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results A total of 6,691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1,457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225/1457] vs. 6.2% [322/5234]; P < 0.001, odds ratio: 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions To achieve successful sedation with chloral hydrate, the patient’s sedation history, risk factors, and the type and duration of the procedure should be considered.

Abstract Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients.

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Abstract Non-suicidal self-injury (NSSI) among adolescents continues to be a significant public health concern worldwide. A recent systematic review and meta-analysis found that the global prevalence of NSSI in adolescents aged 12–18 years was 17.2%, with higher rates reported among females (19.7%) than males (14.8%). This behavior has been linked to several negative outcomes, such as depression, anxiety, substance abuse, and suicidal ideation. The present study aimed to classify adolescents based on intrapersonal and interpersonal factors associated with NSSI proposed in Nock’s (2009) integrated model of NSSI, to identify distinct clusters targeting specific risk factors. This encompassed negative cognition, emotional vulnerability, poor coping skill, peer-victimization, family adaptability, and perceived stress. A total of 881 adolescents aged 11–16 years in South Korea completed self-reported questionnaires on automatic thoughts, depression, emotional regulation, peer victimization, family adaptability and perceived stress. Latent profile analysis (LPA) revealed three distinct classes: “the severe group”, “the moderate group”, “the mild group”. Class 3 (“severe group”: N = 127) exhibited greater severity related to NSSI, including negative cognition, emotional vulnerability, poor coping skills, peer victimization, and perceived stress, with weaker levels of factors that can prevent NSSI compared to class 1 (“mild group”: N = 416) and class 2 (“moderated group”: N = 338). The present study emphasizes the importance of considering both intrapersonal (e.g., negative automatic thoughts & emotional dysregulation) and interpersonal factors (i.e., peer victimization) when understanding NSSI - among adolescents. These findings can be utilized to develop interventions aimed at reducing the prevalence and severity of NSSI among adolescents.

Topical corticosteroids manage inflammatory skin conditions via their action on the immune system. An effect of application of corticosteroids to the skin is skin blanching caused by peripheral vasoconstriction. This has been used to characterize, in some cases relative potency and also as a way to compare skin penetration. Chromameters have been used to assess skin blanching—the outcome of vasoconstriction caused by topical corticosteroids—but do not directly measure vasoconstriction. Here, we demonstrate quantitative volumetric photoacoustic microscopy (PAM) as a tool for directly assessing the vasoconstriction followed by topical corticosteroid application, noninvasively visualizing skin vasculature without any exogeneous contrast agent. We photoacoustically differentiated the vasoconstrictive ability of four topical corticosteroids in small animals through multiparametric analyses, offering detailed 3D insights into vasoconstrictive mechanisms across different skin depths. Our findings highlight the potential of PAM as a noninvasive tool for measurement of comparative vasoconstriction with potential for clinical, pharmaceutical, and bioequivalence applications.

Abstract Although facial flushing after drinking alcohol (alcohol flushing response) is common in Asian populations, the epidemiological features in a large sample have been investigated in only a few studies. This study assessed the epidemiologic characteristics and associated factors for alcohol flushing in a Korean population. This study was based on data collected during the 2019 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5572 Korean adults was included in the general population group, and the alcohol flushing group consisted of 2257 participants. Smoking and physical activity were evaluated as possible associated factors for alcohol flushing. The overall prevalence of alcohol flushing was estimated at 40.56% of the general population (43.74% in males and 37.4% in females), and the prevalence was highest at 60–69 years of age and lowest in individuals older than 80 years. Occasional, frequent, and persistent alcohol flushing was reported by 11.9%, 3.7% and 15.0% of current flushers, among whom persistent flushers consumed the least amount of alcohol. Subjects who currently smoke had a higher propensity of alcohol flushing (adjusted OR 1.525, 95% CI 1.2–1.938), and subjects with smoking history of 20–29 pack-years (PYs) showed the highest association (adjusted OR 1.725, 95% CI 1.266–2.349) with alcohol flushing after adjustment for confounders. In contrast, significant association was not found between physical activity and alcohol flushing. The results demonstrated that current smoking status is shown to be significantly associated with alcohol flushing, and that current smokers with a history of smoking ≥ 20 PYs had a higher likelihood of alcohol flushing than non-smokers or ex-smokers.

Abstract Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.

Abstract Background External apical root resorption (EARR) is a common undesirable outcome of orthodontic treatment, this study aimed to identify genetic polymorphisms associated with the susceptibility to extreme orthodontic-induced EARR in a Korean population using extreme phenotype analysis sampling. Methods Genomic DNA was isolated from the saliva of 77 patients who underwent orthodontic treatment involving two maxillary premolar extractions. The patients were divided into two groups based on EARR values measured on periapical radiographs: The significant resorption group (SG, EARR ≥ 4 mm) and the normal group (NG, EARR

Abstract Atomically dispersed single‐atom catalysts (SACs) on carbon supports show great promise for H2O2 electrosynthesis, but conventional wet chemistry methods using particulate carbon blacks in powder form have limited their potential as two‐electron (2e−) oxygen reduction reaction (ORR) catalysts. Here, we demonstrate high‐performance Co SACs supported on a free‐standing aligned carbon nanofiber (CNF) using electrospinning and arc plasma deposition (APD). Based on the surface oxidation treatment of aligned CNF and precise control of the deposition amount in a dry‐based APD process, we successfully form densely populated Co SACs on aligned CNF. Through experimental analyses and density functional theory calculations, we reveal that Co SAC has a Co–N2–O2 moiety with one epoxy group, leading to excellent 2e− ORR activity. Furthermore, the aligned CNF significantly improves mass transfer in flow cells compared to randomly oriented CNF, showing an overpotential reduction of 30 mV and a 1.3‐fold improvement (84.5%) in Faradaic efficiency, and finally achieves an outstanding production rate of 15.75 mol gcat−1 h−1 at 300 mA cm−2. The high‐performance Co SAC supported on well‐aligned CNF is also applied in an electro‐Fenton process, demonstrating rapid removal of methylene blue and bisphenol F due to its exceptional 2e− ORR activity.

BackgroundAdherence to oral anticoagulant therapy is essential to prevent ischemic stroke in patients with atrial fibrillation (AF). ObjectiveThis study aimed to evaluate whether smartphone app–based interventions improve medication adherence in patients with AF. MethodsThis open-label, multicenter randomized controlled trial (ADHERE-App [Self-Awareness of Drug Adherence to Edoxaban Using an Automatic App Feedback System] study) enrolled patients with AF treated with edoxaban for stroke prevention. They were randomly assigned to app-conditioned feedback (intervention; n=248) and conventional treatment (control; n=250) groups. The intervention group received daily alerts via a smartphone app to take edoxaban and measure blood pressure and heart rate at specific times. The control group received only standard, guideline-recommended care. The primary end point was edoxaban adherence, measured by pill count at 3 or 6 months. Medication adherence and the proportion of adequate medication adherence, which was defined as ≥95% of continuous medication adherence, were evaluated. ResultsMedication adherence at 3 or 6 months was not significantly different between the intervention and control groups (median 98%, IQR 95%-100% vs median 98%, IQR 91%-100% at 3 months, P=.06; median 98%, IQR 94.5%-100% vs median 97.5%, IQR 92.8%-100% at 6 months, P=.15). However, the proportion of adequate medication adherence (≥95%) was significantly higher in the intervention group at both time points (76.8% vs 64.7% at 3 months, P=.01; 73.9% vs 61% at 6 months, P=.007). Among patients aged >65 years, the intervention group showed a higher medication adherence value and a higher proportion of adequate medication adherence (≥95%) at 6 months. ConclusionsThere was no difference in edoxaban adherence between the groups. However, the proportion of adequate medication adherence was higher in the intervention group, and the benefit of the smartphone app–based intervention on medication adherence was more pronounced among older patients than among younger patients. Given the low adherence to oral anticoagulants, especially among older adults, using a smartphone app may potentially improve medication adherence. Trial RegistrationInternational Clinical Trials Registry Platform KCT0004754; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=28496&search_page=L International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2021-048777

Abstract is missing (Short communication)

Abstract Background Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for the tachycardia–bradycardia syndrome (TBS) has not been evaluated adequately. We tried to compare the efficacy and safety outcomes of CA and PM implantation as an initial treatment option for TBS in paroxysmal atrial fibrillation (AF) patients. Methods Sixty-eight patients with paroxysmal AF and TBS (mean 63.7 years, 63.2% male) were randomized, and received CA (n = 35) or PM (n = 33) as initial treatments. The primary outcomes were unexpected emergency room visits or hospitalizations attributed to cardiovascular causes. Results In the intention-to-treatment analysis, the rates of primary outcomes were not significantly different between the two groups at the 2-year follow-up (19.8% vs. 25.9%; hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.25–2.20, P = 0.584), irrespective of whether the results were adjusted for age (HR 1.12, 95% CI 0.34–3.64, P = 0.852). The 2-year rate of recurrent AF was significantly lower in the CA group compared to the PM group (33.9% vs. 56.8%, P = 0.038). Four patients (11.4%) in the CA group finally received PMs after CA owing to recurrent syncope episodes. The rate of major or minor procedure related complications was not significantly different between the two groups. Conclusion CA had a similar efficacy and safety profile with that of PM and a higher sinus rhythm maintenance rate. CA could be considered as a preferable initial treatment option over PM implantation in patients with paroxysmal AF and TBS. Trial registration KCT0000155.

Abstract The bioartificial liver (BAL) system can potentially rescue acute liver failure (ALF) patients by providing partial liver function until a suitable donor liver can be found or the native liver has self-regenerated. In this study, we established a suitable cryopreservation process for the development of an off-the-shelf BAL system. The viability of hepatocyte spheroids cryopreserved in liquid nitrogen was comparable to that of fresh primary hepatocyte spheroids. When hepatocyte spheroids were subjected to cryopreservation in a deep freezer, no statistically significant differences were observed in ammonia removal rate or urea secretion rate based on the cryopreservation period. However, the functional activity of the liver post-cryopreservation in a deep freezer was significantly lower than that observed following liquid nitrogen cryopreservation. Moreover, cryopreserving spheroid hydrogel beads in a deep freezer resulted in a significant decrease (approximately 30%) in both ammonia removal and urea secretion rates compared to the group cryopreserved in liquid nitrogen. The viabilities of spheroid hydrogel beads filled into the bioreactor of a BAL system were similar across all four groups. However, upon operating the BAL system for 24 h, the liver function activity was significantly higher in the group comprising hydrogel beads generated after thawing hepatocyte spheroids cryopreserved in liquid nitrogen. Consequently, the manufacturing of beads after the cryopreservation of hepatocyte spheroids is deemed the most suitable method, considering efficiency, economic feasibility, and liver function activity, for producing a BAL system.

Abstract In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0–1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1–11-year-old group. Conversely, the 12–19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

Abstract In blue phosphorescent dopants, the tetradentate platinum(II) complex is a promising material showing high efficiency and stability in devices. However, metal-metal-to-ligand charge transfer (MMLCT) formation leads to low photo-luminescence quantum yields (PLQYs), wide spectra, and intermolecular interaction. To suppress MMLCT, PtON-tb-TTB and PtON-tb-DTB are designed using theoretical simulation by modifying t-butyl in PtON-TBBI. Both materials effectively suppress MMLCT and exhibit high PLQYs of 99% and 78% in 5 wt% doped film, respectively. The PtON-tb-TTB and PtON-tb-DTB devices have maximum external quantum efficiencies of 26.3% and 20.9%, respectively. Additionally, the PtON-tb-DTB device has an extended lifetime of 169.3 h with an initial luminescence of 1200 nit, which is 8.5 times greater than the PtON-TBBI device. Extended lifetime because of suppressed MMLCT and smaller displacement between the lowest triplet and triplet metal-centered states compared to other dopants. The study provides an effective approach to designing platinum(II) complexes for long device lifetimes.

Kombucha, a fermented tea beverage, is produced through the symbiotic interaction of several microbial strains, including acetic acid bacteria, lactic acid bacteria, and yeast, collectively known as symbiotic culture of bacteria and yeast (SCOBY). As its health benefits and distinctive flavor gain wider recognition, consumer demand and research on kombucha fermentation have increased. This study focused on developing starter cultures to produce functional kombucha through precision fermentation technology using selected microbial strains newly isolated from food sources. The isolated bacterial and yeast strains were evaluated and selected based on their fermentation characteristics. Notably, a lactic acid bacterial strain was chosen for its ability to overproduce the γ-amino butyric acid (GABA), a functional food component known to enhance cognitive function and reduce mental stress. To produce the GABA-fortified kombucha, selected single strains of Acetobacter pasteurianus, Lactiplantibacillus plantarum, and Saccharomyces cerevisiae were mixed and used as starter cultures. By optimizing the inoculation ratios and initial sugar concentration, a functional kombucha enriched with acetic acid, lactic acid, and GABA was successfully produced. The resulting kombucha demonstrated 2.2 mg/L of GABA production and 1.15 times higher antioxidant activity after the fermentation, highlighting its enhanced health-promoting properties.

Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known for its anti-inflammatory properties. In this study, we investigated the effects of CBG in a cellular model of 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). In the cellular model, we confirmed the cytotoxicity of CBG and downregulated the expression of inflammatory markers CCL26, IL1B, IL6, and TNF (p < 0.001). In the mouse model, clinical, histological, and immunological changes were analyzed. The results showed that CBG improved dermatitis severity score, epidermal thickness, and mast cell count and reduced inflammatory cytokines (Tslp, Il1b, Il4, Il6, Il13, Il17, Il18, Il22, and Il33) by qRT-PCR (p < 0.001). Western blot results showed modulated changes in JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, and p-STAT6 (p < 0.05). Subsequently, p-IκBα, NF-κB, and p-NF-κB signaling factors were also reduced (p < 0.05), with corresponding changes in skin barrier factors. The results of this study indicate that CBG effectively alleviates AD-like symptoms and suggest the potential of CBG as a therapeutic agent.

Due to climate change, heat-tolerant species have become increasingly important; however, the selection system for herbaceous plants has yet to be well established. This study aimed to establish a selection system for heat-tolerant plant species and to identify such species. Heat stress at 50 °C for 120 min was applied to 27 plant species using a heat treatment and recovery model. Among them, four herbaceous species—Hemerocallis fulva, Heliopsis longipes, Hosta plantagines, and Scilla scilloides—were selected by measuring their electrolyte leakage index (ELI). Additionally, species with high ELI values (Centaurea cyanus) and low ELI values (S. scilloide) were selected to determine the optimal temperature and time for the heat treatment using linear regression analysis. The selected heat-tolerant herbaceous plants survived under optimal heat stress conditions (120 min at 50 °C). The degree of cell death in the selected plant species was measured using Evans blue staining. The results showed that the cell death indexes of heat-tolerant species were less than 22% after heat treatment, compared to over 57% in heat-sensitive species. Furthermore, the recovery ability at room temperature after heat treatment was assessed using the DAB staining method. The selected heat-tolerant plant species recovered quickly (within 90 min), whereas the heat-sensitive species required over 480 min for recovery. The analytical method developed in this study can more accurately determine the response of various plants to heat stress and has high reproducibility. Therefore, it is considered an excellent method for establishing a heat-tolerant plant selection system.

BackgroundThe extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable.MethodsIn this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions.ResultsImaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25–20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/− thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61–0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge.ConclusionAC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy.

BackgroundAlthough several biomarkers exist for patients with heart failure (HF), their use in routine clinical practice is often constrained by high costs and limited availability. ObjectiveWe examined the utility of an artificial intelligence (AI) algorithm that analyzes printed electrocardiograms (ECGs) for outcome prediction in patients with acute HF. MethodsWe retrospectively analyzed prospectively collected data of patients with acute HF at two tertiary centers in Korea. Baseline ECGs were analyzed using a deep-learning system called Quantitative ECG (QCG), which was trained to detect several urgent clinical conditions, including shock, cardiac arrest, and reduced left ventricular ejection fraction (LVEF). ResultsAmong the 1254 patients enrolled, in-hospital cardiac death occurred in 53 (4.2%) patients, and the QCG score for critical events (QCG-Critical) was significantly higher in these patients than in survivors (mean 0.57, SD 0.23 vs mean 0.29, SD 0.20; P0.5) had higher mortality rates than those with low QCG-Critical scores (

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen’s efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE’s that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Abstract The major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3′-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time. BOLT-seq was successfully used to cluster small molecule drugs based on their mechanisms of action and intended targets. BOLT-seq competes effectively with alternative library construction and transcriptome profiling methods.

Abstract Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532–0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160–0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Background/Aims We aimed to clarify the clinical characteristics of psoriatic arthritis (PsA) in Korean patients focusing on PsA with axial involvement. Methods A retrospective medical chart review was performed to identify PsA patients at a single tertiary center. Cases of AS patients with psoriasis were recruited from a prospective AS registry of the same center. Demographics, laboratory findings, and radiologic characteristics were assessed. Results A total of 69 PsA patients were identified. In PsA patients, spondylitis (46.4%) was the most common form. Compared to AS patients with psoriasis, PsA patients with radiographic axial involvement were older (50.9 vs. 32.4 years; p < 0.001) and showed greater peripheral disease activity (peripheral arthritis 78.1 vs. 12.5%, p < 0.001; enthesitis 50.0 vs. 6.3%, p = 0.003). AS patients with psoriasis presented a higher rate of HLA-B*27 positivity (81.3 vs. 17.2%; p < 0.001) and a more frequent history of inflammatory back pain (100.0 vs. 75.0%; p = 0.039) than PsA patients with radiographic axial involvement. Significant proportions of PsA patients with radiographic axial involvement had cervical spine involvement (10/18, 55.6%) and spondylitis without sacroiliitis (10/23, 43.5%). Conclusions We demonstrate that axial involvement is common in Korean PsA patients, and its characteristics can be distinct from those of AS.

Abstract Background Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. Methods We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. Results Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. Conclusions We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. Trial registration NCT05338931; Date: 2022–04-01.

Abstract Background We investigated the prognostic significance of body mass index in small‐cell lung cancer and explored whether skeletal muscle status affects the body mass index–survival relationship. Methods This retrospective study evaluated data from patients who underwent platinum‐etoposide chemotherapy for small‐cell lung cancer between March 2010 and December 2021. Skeletal muscle status was assessed using non‐contrast computed tomography images of baseline positron‐emission tomography‐computed tomography, with the skeletal muscle index defined as the cross‐sectional area of skeletal muscle divided by height squared, and the average attenuation values of skeletal muscle. Cox proportional hazards regression analysis was used to determine the correlations of body mass index, skeletal muscle metrics, and overall survival. Results We analysed the data of 1146 Asian patients (1006 men and 140 women, with a median age of 67 years [interquartile range: 61–72 years]), including 507 and 639 patients with limited and extensive disease, respectively. Being underweight, defined as a body mass index

Abstract Background The obesity paradox in patients with advanced non‐small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival. Methods This retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non‐small cell lung cancer between October 2015 and October 2021. We used abdominal cross‐sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2/m2) by dividing the cross‐sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional‐hazards regression was performed to determine the correlation between BMI according to the Asia‐Pacific classification, body composition metrics and overall survival. Results We analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1‐year mortality rate of 0.58 (95% confidence interval, 0.55–0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52–0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53–0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41–0.70). No association was observed between sex and the impact of BMI on overall survival (P‐value for interaction >0.05). Conclusions In Asian patients with advanced non‐small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1–3% of the global population; however, the mechanisms remain unclear. This study investigated CBD’s effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2–STAT3 signaling pathway, leading to the downregulation of Il1b, Il6, Il12b, Il17a, Il22, and Tnf expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2–STAT3 pathway.

Abstract Gynecologic cancer, including ovarian cancer and endometrial cancer, is characterized by morphological and molecular heterogeneity. Germline and somatic testing are available for patients to screen for pathogenic variants in genes such as BRCA1/2. Tissue expression levels of immunogenomic markers such as PD-L1 are also being used in clinical research. The basic therapeutic approach to gynecologic cancer combines surgery with chemotherapy. Immunotherapy, while not yet a mainstream treatment for gynecologic cancers, is advancing, with Dostarlimab recently receiving approval as a treatment for endometrial cancer. The goal remains to harness stimulated immune cells in the bloodstream to eradicate multiple metastases, a feat currently deemed challenging in a typical clinical setting. For the discovery of novel immunotherapy-based tumor targets, tumor-infiltrating lymphocytes (TILs) give a key insight on tumor-related immune activities by providing T cell receptor (TCR) sequences. Understanding the TCR repertoires of TILs in metastatic tissues and the circulation is important from an immunotherapy standpoint, as a subset of T cells in the blood have the potential to help kill tumor cells. To explore the relationship between distant tissue biopsy regions and blood circulation, we investigated the TCR beta chain (TCRβ) in bulk tumor and matched blood samples from 39 patients with gynecologic cancer. We found that the TCR clones of TILs at different tumor sites were globally shared within patients and had high overlap with the TCR clones in peripheral blood.

Background To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk

Background Optimizing endotracheal tube (ETT) shape is important for successful videolaryngoscope-aided intubation. This prospective randomized controlled study aimed to compare the tube-handling time between a C-curved and hockey stick-shaped stylet in infants and neonates using the C-MAC® videolaryngoscope Miller blade. Methods A total of 110 infants (age < 1 year) were randomly assigned to either the hockey stick-curved stylet group (group H, n = 53) or the C-curved stylet group (group C, n = 57). The primary outcome was tube handling time after glottis visualization and the secondary outcomes were the total intubation time, incidence of successful intubation, initial tube tip location at the laryngeal inlet, and numerical rating scale for ease of intubation. Results Tube insertion time and total intubation duration (both in seconds) were significantly shorter in group C than in group H (13.3 ± 8.9 vs. 25.1 ± 27.0, P = 0.002; 19.9 ± 9.4 vs. 32.8 ± 27.1, P = 0.001, respectively). Group C displayed a higher rate of intubation success within 30 s than group H (87.7% vs. 69.8%, P = 0.029). The initial tube tip was located at the center in 34 children in group C (59.6%) and 12 children in group H (26.1%, P < 0.001). Laryngoscope operators rated intubation as easier when provided with a C-curved stylet. Conclusions In neonates and infants, modification of the ETT shape into a C-curve may reduce tube handling time compared to the conventional hockey stick-shaped tube during intubation using a C-MAC® video laryngoscope Miller blade.

Abstract Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3′-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.

BackgroundElderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population.MethodsA total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes.ResultsAmong the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis.ConclusionIVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG’s potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies.

Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes, and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.

Background Many studies have examined the risk factors for postoperative acute kidney injury (AKI), but few have focused on intraoperative peripheral perfusion index (PPI) that has recently been shown to be associated with postoperative morbidity and mortality. Therefore, this study aimed to evaluate the relationship between intraoperative PPI and postoperative AKI under the hypothesis that lower intraoperative PPI is associated with AKI occurrence. Methods We retrospectively searched electronic medical records to identify patients who underwent surgery at the general surgery department from May 2021 to November 2021. Patient baseline characteristics, pre- and post-operative laboratory test results, comorbidities, intraoperative vital signs, and discharge profiles were obtained from the Institutional Clinical Data Warehouse and VitalDB. Intraoperative PPI was the primary exposure variable, and the primary outcome was postoperative AKI. Results Overall, 2,554 patients were identified and 1,586 patients were included in our analysis. According to Kidney Disease Improving Global Outcomes (KDIGO) criteria, postoperative AKI occurred in 123 (7.8%) patients. We found that risks of postoperative AKI increased (odds ratio: 2.00, 95% CI [1.16, 3.44], P = 0.012) when PPI was less than 0.5 for more than 10% of surgery time. Other risk factors for AKI occurrence were male sex, older age, higher American Society of Anesthesiologists physical status, obesity, underlying renal disease, prolonged operation time, transfusion, and emergent operation. Conclusions Low intraoperative PPI was independently associated with postoperative AKI.

Background Although fiberoptic-guided endotracheal intubation using a supraglottic airway device (SAD) is a good alternative for the management of difficult airways, its learning curve for residents has not been evaluated in pediatric patients. We aimed to train residents using a pediatric manikin and obtain learning curves to evaluate the efficiency of the training. Methods We conducted a single-armed prospective study with anesthesiology residents. Plain endotracheal tube (ETT) intubation guided by a fiberoptic bronchoscope through Ambu® AuraGainTM was demonstrated in a pediatric manikin to the participants before training. The procedure was divided into four steps: SAD insertion, vocal cord identification, carina identification, and ETT insertion into the trachea. The results and elapsed procedure times of each trial were recorded. The learning curves for the participants were constructed and analyzed using the cumulative sum method. Results All the 30 participants acquired proficiency at the end of practice between eight and 25 trials. The overall success rate for the procedure was 92.8%, and above 80% for all participants. Mean ± standard deviation procedure time was 71.3 ± 50.7 s. The 4th step accounted for 86.2% and 48.0% of the total failures and procedure time, respectively. The procedure time rapidly decreased in the 2nd trial; a modest decline was observed thereafter. Conclusions Trainees can obtain proficiency for fiberoptic-guided intubation through SAD within 25 times when using pediatric manikin. Effect of the training on performance in actual clinical situation should be studied.

Abstract Background Genome editing has been considered as powerful tool in agricultural fields. However, genome editing progress in cattle has not been fast as in other mammal species, for some disadvantages including long gestational periods, single pregnancy, and high raising cost. Furthermore, technically demanding methods such as microinjection and somatic cell nuclear transfer (SCNT) are needed for gene editing in cattle. In this point of view, electroporation in embryos has been risen as an alternative. Results First, editing efficiency of our electroporation methods were tested for embryos. Presence of mutation on embryo was confirmed by T7E1 assay. With first combination, mutation rates for MSTN and PRNP were 57.6% ± 13.7% and 54.6% ± 13.5%, respectively. In case of MSTN/BLG, mutation rates were 83.9% ± 23.6% for MSTN, 84.5% ± 18.0% for BLG. Afterwards, the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing. Thirteen recipients were transferred for MSTN/PRNP, 4 calves were delivered, and one calf underwent an induction for double KO. Ten surrogates were given double-KO embryos for MSTN/BLG, and four of the six calves that were born had mutations in both genes. Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied. Finally, MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

Abstract Obesity is a modifiable risk factor in cancer development, especially for gastrointestinal cancer. While the etiology of colorectal cancer is well characterized by the adenoma-carcinoma sequence, it remains unclear how obesity influences colorectal cancer development. Dietary components of a high fat diet along with obesity have been shown to modulate the cancer risk by perturbing the homeostasis of intestinal stem cells, yet how adiposity impacts the development of genomic instability has not been studied. Mutational signatures are a powerful way to understand how a complex biological response impacts genomic stability. We utilized a mouse model of diet-induced obesity to study the mutational landscape of intestinal crypt cells after a 48-week exposure to an experimental high fat diet in vivo. By clonally enriching single crypt derived cells in organoid culture and obtaining whole genome sequences, we analyzed and compared the mutational landscape of intestinal epithelial cells from normal diet and high fat diet mice. Single nucleotide substitution signatures and indel signatures present in our cohort are found equally active in both diet groups and reflect biological processes of normal aging, cellular replication, and oxidative stress induced during organoid culturing. Thus, we demonstrate that in the absence of activating mutations or chemical exposure, high fat diet alone is not sufficient to increase genomic instability.

Abstract Background Detecting high‐risk arrhythmia is important in diagnosing patients with palpitations. We compared the diagnostic accuracies of 7‐day patch‐type electrocardiographic (ECG) monitoring and 24‐h Holter monitoring for detecting significant arrhythmias in patients with palpitations. Methods This was a single‐center prospective trial with 58 participants who presented with palpitations, chest pain or syncope. Outcomes were defined as the detection of any one of six arrhythmias, including supraventricular tachycardia (SVT), atrial fibrillation or atrial flutter lasting more than 30 s, pauses of more than 3 s, high‐degree atrioventricular block, ventricular tachycardia (VT) >3 beats, or polymorphic VT/ventricular fibrillation. The McNemar test for paired proportions was used to compare arrhythmia detection rates. Results The overall arrhythmia detection rate was higher with 7‐day ECG patch monitoring than with 24‐h Holter monitoring (34.5% vs. 19.0%, p = .008). Compared with the use of 24‐h Holter monitors, the use of 7‐day ECG patch monitors was associated with higher detection of SVT (29.3% vs. 13.8%, p = .042). No serious adverse skin reactions were reported among the ECG patch‐monitored participants. Conclusions The results suggest that a 7‐day patch‐type continuous ECG monitor is more effective for the detection of supraventricular tachycardia than is a 24‐h Holter monitor. However, the clinical significance of device detected arrhythmia should be consolidated.

Abstract Background Many stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints. Methods The disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3–5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed. Results Among 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3–5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p