Search

Abstract Electrical cardioversion (ECV) a widely utilized intervention for persistent atrial fibrillation (AF) aimed at restoring sinus rhythm. However, ECV can be ineffective, raising questions about subsequent treatment options. This study aimed to compare the outcomes of non-ablation therapy versus ablation therapy following unsuccessful ECV. A total of 125 consecutive patients with persistent AF who underwent unsuccessful ECV between November 2017 and August 2023 was included in this retrospective analysis. Of these, 51.2% received only medical therapy (non-ablation therapy group, n = 64), while 48.8% underwent AF ablation (ablation therapy group, n = 61). Various ablation methods were employed, including catheter and thoracoscopic ablation. Ablation therapy was associated with significantly better AF-free survival compared to non-ablation therapy [hazard ratio (HR), 0.37; 95% confidence interval (CI) 0.22–0.61; p 5 year (HR 1.51; 95% CI 0.930–2.437; p = 0.10), BMI ≤ 25 kg/m2 (HR 1.61; 95% CI 1.004–2.581; p = 0.05) and diabetes (HR 2.38; 95% CI 0.902–6.266; p = 0.08) were considerable as predictor of AF recurrence. Ablation therapy following unsuccessful ECV was associated with maintaining sinus rhythm, regardless of the specific ablation method utilized.

Objectives: We evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. Design: This study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26–December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. Results: In total, 5516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. Conclusion: The short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

Background We hypothesized that analysis of serial ECGs could predict new‐onset atrial fibrillation (AF) more accurately than analysis of a single ECG by detecting the subtle cardiac remodeling that occurs immediately before AF occurrence. Our aim in this study was to compare the performance of 2 types of machine learning (ML) algorithms. Methods and Results Standard 12‐lead ECGs of patients selected by cardiologists between January 2010 and May 2021 were used for ML model development. Two ML models (single ECG and serial ECG) were developed using a light gradient boosting machine‐learning algorithm. Model performance was evaluated based on the area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, and F1 score. We trained the ML models on 415 964 ECGs from 176 090 patients. When testing the 2 ML models using external validation data sets, the performance of the serial‐ML model was significantly better than that of the single‐ML model for predicting new‐onset AF (single‐ versus serial‐ML model: sensitivity 0.744 versus 0.810; specificity 0.742 versus 0.822; accuracy 0.743 versus 0.816; F1 score 0.743 versus 0.815; area under the receiver operating characteristic curve 0.812 versus 0.880; P

Abstract Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

Background The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1-and Th2-like molecules in nodal PTCL is unclear. Methods Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL–not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. Results TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). Conclusions The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Abstract Body mass index (BMI), as an important risk factor related to metabolic disease. However, in some studies higher BMI was emphasized as a beneficial factor in the clinical course of patients after acute myocardial infarction (AMI) in a concept known as the “BMI paradox.” The purpose of this study was to investigate how clinical outcomes of patients treated for AMI differed according to BMI levels. A total of 10,566 patients in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) from May 2010 to June 2015 were divided into three BMI groups (group 1: BMI

BackgroundData on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.ObjectivesWe prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.MethodsThe multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.ResultsOf 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the “marginal zone,” defined as age 75–80 years, weight 60–65 kg, and creatinine levels 1.2–1.5 mg/dL.ConclusionsIn real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Achieving historically anticipated improvement in the performance of integrated circuits is challenging, due to the increasing cost and complexity of the required technologies with each new generation. To overcome this limitation, the exploration and development of novel interconnect materials and processes are highly desirable in the microelectronics field. Molybdenum (Mo) is attracting attention as an advanced interconnect material due to its small resistivity size effect and high cohesive energy; however, effective processing methods for such materials have not been widely investigated. Here, we investigate the electrochemical behavior of ions in the confined nanopores that affect the electrical properties and microstructures of nanoscale Mo and Mo–Co alloys prepared via template-assisted electrodeposition. Additives in an electrolyte allow the deposition of extremely pure metal materials, due to their interaction with metal ions and nanopores. In this study, boric acid and tetrabutylammonium bisulfate (TBA) were added to an acetate bath to inhibit the hydrogen evolution reaction. TBA accelerated the reduction of Mo at the surface by inducing surface conduction on the nanopores. Metallic Mo nanowires with a 130 nm diameter synthesized through high-aspect-ratio nanopore engineering exhibited a resistivity of (63.0 ± 17.9) μΩ·cm. We also evaluated the resistivities of Mo–Co alloy nanowires at various compositions toward replacing irreducible conventional barrier/liner layers. An intermetallic compound formed at a Mo composition of 28.6 at%, the resistivity of the Mo–Co nanowire was (58.0 ± 10.6) μΩ·cm, indicating its superior electrical and adhesive properties in comparison with those of conventional barriers such as TaN and TiN. Furthermore, density functional theory and non-equilibrium Green’s function calculations confirmed that the vertical resistance of the via structure constructed from Mo-based materials was 21% lower than that of a conventional Cu/Ta/TaN structure.

Abstract Background Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.

Background: There is limited research into the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic for non-COVID-19 pneumonia in older adults, as well as their quality of care or outcomes. This study aims to assess the process and outcome quality of care for hospitalized older adult patients with pneumonia before and after the pandemic. Methods: A retrospective cohort of older adult patients (age ≥ 65) hospitalized for non–COVID pneumonia were recruited from five Korean hospitals (January 20, 2019, to January 19, 2021). The quality of care before and after the COVID-19 pandemic was evaluated. Results: A total of 7356 hospitalization episodes of older adult pneumonia were identified, and 978 cases (552 pre-pandemic and 426 during the pandemic) were analyzed. The pneumonia severity score was higher during the pandemic, and the waiting time from the emergency room to admission was also longer. Furthermore, the pneumonia mortality rate during the pandemic was higher than that in the pre-pandemic period (in-hospital mortality: 10.1% vs. 18.1%; 90-day mortality: 11.6% vs. 22.3%). A significantly higher mortality risk was observed during the pandemic than in the period prior (adjusted odds ratio: 1.74, 95% confidence interval: 1.14–2.63). Conclusions: While the quality of care for hospitalized pneumonia has been maintained during the pandemic, there has been an increase in mortality rates. Further investigations are needed to understand the underlying causes of this increase.

In August 2021, water-soaking symptoms of bacterial spot disease were observed on castor bean in a field in Gangseo District, Busan. Bacteria isolated from the lesion when cultured on tryptic soy agar appeared to be nonmucoid and pale green. To confirm whether the isolates were the causative agent of the spot disease, they were inoculated onto healthy castor bean plants. The same symptoms were observed on the inoculated tissue, and the bacteria were reisolated from the lesion. Furthermore, the isolates were consistent with the biochemical and physiological features of Pseudomonas capsici. Sequencing analysis using 16S rRNA and housekeeping genes (gyrB, rpoD) showed that the isolates shared a high sequence similarity with P. capsici. These results confirmed that the strains belonged to P. capsici. To our knowledge, this is the first report of bacterial spot disease caused by P. capsici on castor bean in Korea.

Abstract Polygenic risk scores (PRSs) have been studied for predicting human diseases, and various methods for PRS calculation have been developed. Most PRS studies to date have focused on European ancestry, and the performance of PRS has not been sufficiently assessed in East Asia. Herein, we evaluated the predictive performance of PRSs for East Asian populations under various conditions. Simulation studies using data from the Korean cohort, Health Examinees (HEXA), demonstrated that SBayesRC and PRS-CS outperformed other PRS methods (lassosum, LDpred-funct, and PRSice) in high fixed heritability (0.3 and 0.7). In addition, we generated PRSs using real-world data from HEXA for ten diseases: asthma, breast cancer, cataract, coronary artery disease, gastric cancer, glaucoma, hyperthyroidism, hypothyroidism, osteoporosis, and type 2 diabetes (T2D). We utilized the five previous PRS methods and genome-wide association study (GWAS) data from two biobank-scale datasets [European (UK Biobank) and East Asian (BioBank Japan) ancestry]. Additionally, we employed PRS-CSx, a PRS method that combines GWAS data from both ancestries, to generate a total of 110 PRS for ten diseases. Similar to the simulation results, SBayesRC showed better predictive performance for disease risk than the other methods. Furthermore, the East Asian GWAS data outperformed those from European ancestry for breast cancer, cataract, gastric cancer, and T2D, but neither of the two GWAS ancestries showed a significant advantage on PRS performance for the remaining six diseases. Based on simulation data and real data studies, it is expected that SBayesRC will offer superior performance for East Asian populations, and PRS generated using GWAS from non-East Asian may also yield good results.

Background/Aims Atrial fibrillation (AF) is a common arrhythmia and is associated with cardiovascular morbidity and mortality. It is important to identify and control the modifiable risk factors of AF. We aimed to examine the association of exercise capacity with the risk of incident AF within 3 years in healthy subjects. Methods We evaluated asymptomatic adults who had undergone more than two consecutive health checkups. We included subjects who exhibited normal sinus rhythm on the first health examination and who developed AF on the second or subsequent health examinations. Subjects who underwent cardiopulmonary exercise testing within 3 years before the diagnosis of AF were examined. Results The study population in the analyses included 428 cases (mean age 58.4 ± 7.6 yr, male 95.6%). There were significant differences in maximal systolic blood pressure (SBP; case 169.4 ± 24.2 vs. control 173.9 ± 22.3 mmHg), peak VO2 (29.5 ± 5.4 vs. 30.4 ± 4.8 mL/kg per minute), and maximal metabolic equivalents (METs; 8.5 ± 1.6 vs. 8.7 ± 1.4) between the two groups. In the multivariable logistic models, adjusted odds ratios were 0.99 for maximal SBP (95% confidence interval [CI] 0.98–0.99), 0.97 for peak VO2 (95% CI 0.95–0.99), and 0.91 for maximal METs (95% CI 0.83–0.98). Conclusions We demonstrated that poorer exercise capacity was associated with the development of AF in a healthy population. A prospective, systematic trial is necessary to confirm that appropriate exercise training will be beneficial in preventing the development of AF in such patients.

Abstract Background In patients with non-paroxysmal AF (atrial fibrillation), various ablation strategies have been attempted to target non-pulmonary vein (PV) foci or to achieve substrate modification beyond pulmonary vein isolation. The efficacy of empirical ablation of the SVC, one of the most common non-PV foci, is unclear. The aim of this study was to investigate the efficacy and safety of additional superior vena cava (SVC) isolation in patients with non-paroxysmal AF undergoing thoracoscopic surgical ablation. Methods/results A total of 191 patients with persistent or long-standing persistent AF was enrolled. All patients underwent total thoracoscopic surgical ablation for AF, and half of them also received empirical SVC isolation. We compared the atrial tachyarrhythmia (ATa)-free survival rate and procedure-related complications in the two groups of patients. The 3-year ATa-free survival rate was 53% in the SVC isolation group and 52% in the no-SVC isolation group (p = 0.644). There were no differences between the two groups with respect to AF type or LA size. Procedure-related complications occurred in 12 patients (6%). Pacemakers were implanted only in three patients from the SVC isolation group. The only factor influencing recurrence of ATa was LA diameter. Conclusions Empirical SVC isolation during thoracoscopic ablation for persistent AF did not improve patient outcomes.

Glioblastoma (GBM) is the most aggressive and common malignant and CNS tumor, accounting for 47.7% of total cases. Glioblastoma has an incidence rate of 3.21 cases per 100,000 people. The regulation of autophagy, a conserved cellular process involved in the degradation and recycling of cellular components, has been found to play an important role in GBM pathogenesis and response to therapy. Autophagy plays a dual role in promoting tumor survival and apoptosis, and here we discuss the complex interplay between autophagy and GBM. We summarize the mechanisms underlying autophagy dysregulation in GBM, including PI3K/AKT/mTOR signaling, which is most active in brain tumors, and EGFR and mutant EGFRvIII. We also review potential therapeutic strategies that target autophagy for the treatment of GBM, such as autophagy inhibitors used in combination with the standard of care, TMZ. We discuss our current understanding of how autophagy is involved in TMZ resistance and its role in glioblastoma development and survival.

Abstract This study evaluated changes in the peripheral blood immune cell population in patients with advanced thyroid cancer receiving lenvatinib treatment to confirm the immune-modulatory effect of lenvatinib. After obtaining informed consent from patients, we prospectively collected 20 ml of whole blood at 2–3 months intervals 2–4 times from each patient; peripheral blood mononuclear cells (PBMCs) were separated, and the Maxpar Direct Immune Profiling Assay was performed. A total of 10 patients were enrolled, and 31 blood samples were obtained. The median age of patients was 65 years, and all patients showed durable responses to the lenvatinib treatment. When we compared the PBMC profiles between the pre-treatment, on-treatment, and off-treatment samples, the peripheral natural killer (NK) cell proportion differed significantly. The proportion of NK cells among total live cells significantly increased from 9.3 ± 4.5 (%) in the pre-treatment samples to 20.8 ± 7.9 (%) in the on-treatment samples (P = 0.009) and decreased to 13.3 ± 3.1 (%) in the off-treatment samples (P = 0.07). There was a significant increase in the peripheral NK cell population with lenvatinib treatment in advanced thyroid cancer patients. This finding confirms the immune-modulatory effect of lenvatinib.

With the growing demand for high‐speed electronic devices with low energy consumption, spin–orbit torque (SOT) has become a significant focus. SOT can switch the magnetization direction in a material system with broken inversion symmetry, such as a normal metal (NM)/ferromagnet (FM) heterojunction. The SOT consists of two mutually orthogonal vector components along with the injected current direction: the transverse damping‐like torque (DLT) and the longitudinal field‐like torque (FLT). Numerous studies have mainly centered on the DLT for the SOT switching mechanism. However, DLT and FLT are essential to enhance SOT efficiency because FLT boosts the magnetization precession motion. Herein, heterojunctions consisting of NM 1 (Ta, W, or Pt)/NM 2 (Nb)/FM (CoFeB) are devised to manipulate the FLT‐to‐DLT ratio (η) through the change in Nb thickness. Furthermore, experimental confirmation exists for reducing threshold current as η increases. The SOT devices with substantial η generate random numbers. The National Institute of Standards and Technology Special Publication 800‐90B test verifies randomness and confirms that the SOT devices are beneficial sources for true random number generators (TRNGs). These findings indicate the crucial role of FLT in the SOT switching process and underscore its significance in developing SOT‐based TRNG devices.

Organic pollutants in wastewater pose serious threats to human health and the environment. Nevertheless, potent strategies are being devised to tackle this critical issue. Specifically, advanced oxidation processes driven by solar energy and photocatalysts show promise for the degradation of organic pollutants. In particular, porous nanomaterials are effective as photocatalysts because of their high surface area, light‐harvesting properties, and ability to generate reactive oxygen species. To further expedite the development of feasible and sustainable organic‐pollutant‐degrading schemes, this article reports a strategy rooted in selective core etching for fabricating a core‐satellite‐type porous Fe3O4–Au nanocomposite. The Fe3O4 core behaves as a semiconductor to generate electron–hole pairs, whereas the Au satellite units serve as hot‐electron donors under visible‐light irradiation. The nanocomposite exhibits exceptional photocatalytic activity, degrading methylene blue molecules by 97% in just 1 h under visible light, and maintains its photocatalytic performance even after five rounds of recycling. Moreover, the nanocomposite achieves 90% tetracycline decomposition within 2 h. In addition to exhibiting noteworthy photocatalytic activity, the nanocomposite is magnetically separable, facilitating its recovery and reuse and exhibiting remarkable stability and cost‐effectiveness. These attributes underscore the practical viability of the core‐satellite‐type Fe3O4–Au nanocomposite in wastewater treatment.

Abstract Intelligent applications, with tactile sensors at their core, represent significant advancement in the field of artificial intelligence. However, achieving perception abilities in tactile sensors that match or exceed human skin remains a formidable challenge. Consequently, the design and implementation of hierarchical structural materials are considered the optimal solution to this challenge. In contrast to conventional methods, such as complicated lithography and three‐dimensional printing, the cost‐effective and scalable nature of advanced solution‐synthesis methods makes them ideal for preparing diverse tactile sensors with hierarchical structural materials. However, the process and applicability of advanced solution synthesis methods have yet to form a seamless system. Accordingly, the development and intellectualization of tactile sensors based on advanced solution synthesis methods are still in their early stages, and require a comprehensive and systematic review to usher in progress. This study delves into the advantages and disadvantages of various advanced solution synthesis methods, providing detailed insights. Furthermore, the positive effects of hierarchical structural materials constructed using these methods in tactile sensors and their intelligent applications are also discussed in depth. Finally, the challenges and future opportunities faced by this emerging field are summarized.

Abstract Developing electronic skins (e‐skins) that are comparable to or even beyond human tactile perception holds significant importance in advancing the process of intellectualization. In this context, a machine‐learning‐motivated micropyramid array bimodal (MAB) e‐skin based on capacitive sensing is reported, which enables spatial mapping applications based on bimodal sensing (proximity and pressure) implemented via fringing and iontronic effects, such as contactless measurement of 3D objects and contact recognition of Braille letters. Benefiting from the iontronic effect and single‐micropyramid structure, the MAB e‐skin in pressure mode yields impressive features: a maximum sensitivity of 655.3 kPa−1 (below 0.5 kPa), a linear sensitivity of 327.9 kPa−1 (0.5–15 kPa), and an ultralow limit of detection of 0.2 Pa. With the assistance of multilayer perceptron and convolutional neural network, the MAB e‐skin can accurately perceive 6 materials and 10 surface shapes based on the training and learning using the collected datasets from proximity and pressure modes, thus allowing it to achieve the precise perception of different objects within one proximity‐pressure cycle. The development of this MAB e‐skin opens a new avenue for robotic skin and the expansion of advanced applications.

Current evidence suggests that severe acute respiratory syndrome coronavirus 2 infection is associated with an increased incidence of adverse severe maternal and perinatal outcomes. However, vertical transmission is rare. The management of pregnant women with coronavirus disease 2019 (COVID-19) is similar to that of non-pregnant women, and effective treatments, including antiviral therapy, dexamethasone, and prophylactic anticoagulation should not be withheld during pregnancy. During the early COVID-19 pandemic period, the management of pregnant women was often delayed until the polymerase chain reaction (PCR) results came out or due to close contact, even among those without symptoms. Out of concern for the spread of infection, cesarean sections were performed instead of vaginal birth, since infection could have led to an increase in maternal and neonatal morbidities. Additionally, if the maternal PCR test was positive, the neonate was quarantined, and despite infectivity decreasing 10 days after symptom onset. It is necessary to ease the strict measures of infection control in the field of obstetrics. The presence or absence of maternal COVID-19 symptoms should be identified to stratify the risk, and vaginal delivery can be attempted in asymptomatic women with low infectivity. With more women being vaccinated safety data about vaccination is rapidly accumulating and no concerns have been detected. Globally, COVID-19 vaccines are recommended even during pregnancy. In order to prepare for future pandemics, it is necessary to apply lessons learned from this pandemic. Policymakers and healthcare leaders must determine efficient and effective strategies for preserving safe maternal care, even during an ongoing global emergency.

Abstract Photodynamic therapy (PDT) is a promising anticancer treatment because it is patient-friendly and non-invasive. Methyl pyropheophorbide-a (MPPa), one of the chlorin class photosensitizers, is a drug with poor aqueous solubility. The purpose of this study was to synthesize MPPa and develop MPPa-loaded solid lipid nanoparticles (SLNs) with improved solubility and PDT efficacy. The synthesized MPPa was confirmed 1H nuclear magnetic resonance (1H-NMR) spectroscopy and UV–Vis spectroscopy. MPPa was encapsulated in SLN via a hot homogenization with sonication. Particle characterization was performed using particle size and zeta potential measurements. The pharmacological effect of MPPa was evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay and anti-cancer effect against HeLa and A549 cell lines. The particle size and zeta potential ranged from 231.37 to 424.07 nm and − 17.37 to − 24.20 mV, respectively. MPPa showed sustained release from MPPa-loaded SLNs. All formulations improved the photostability of MPPa. The DPBF assay showed that SLNs enhanced the 1O2 generation from MPPa. In the photocytotoxicity analysis, MPPa-loaded SLNs demonstrated cytotoxicity upon photoirradiation but not in the dark. The PDT efficacy of MPPa improved following its entrapment in SLNs. This observation suggests that MPPa-loaded SLNs are suitable for the enhanced permeability and retention effect. Together, these results demonstrate that the developed MPPa-loaded SLNs are promising candidates for cancer treatment using PDT.

Abstract This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia ( 1) in a 5-point scoring system (0–4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949–0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Objective: This study evaluated the efficacy of antithyroid drugs (ATDs) and risk factors associated with the recurrence of Graves’ hyperthyroidism using a comprehensive retrospective cohort. Methods: We included 1829 patients newly diagnosed with Graves’ hyperthyroidism, with sufficient follow-up data. Clinical outcomes of the patients and risk factors associated with recurrence-free survival, including the changes in thyrotropin receptor antibody, were evaluated. Results: The median age of the patients was 44.5 years, and 69% were female. Among the patients, 1235 had a chance to withdraw ATD after a median of 23 (interquartile range (IQR) 17.0–35.5) months of treatment. The first remission rate was 55.6% during a median of 72.7 months of follow-up. After the first recurrence, 95% of patients underwent the second course of ATD treatment for a median of 21 .1 (IQR 14.8–31.7) months, and the remission rate was 54.1%. During a median of 67 months of follow-up, 7.7% of patients underwent surgery, and 10.5% underwent radioac tive iodine therapy. Approximately 30% were still on ATD therapy for recurrent disease or prolonged lowdose maintenance. Younger age (

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Totally thoracoscopic ablation (TTA) is a surgical treatment showing a high success rate as a hybrid procedure with radiofrequency catheter ablation to control AF. This study compared the early complications of warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) in patients who underwent TTA. Methods: This single-center retrospective cohort study enrolled patients who underwent planned TTA for AF from February 2012 to October 2020. All patients received postoperative anticoagulation, either with warfarin or a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban). Propensity score matching was performed for both groups. Early complications were assessed at 12 weeks after TTA and were divided into efficacy and safety outcomes. Both efficacy and safety outcomes were compared in the propensity score-matched groups. Results: Early complications involving efficacy outcomes, such as stroke and transient ischemic attack, were seen in 5 patients in the warfarin group and none in the NOAC group. Although the 2 groups differed in the incidence of efficacy outcomes, it was not statistically significant. In safety outcomes, 11 patients in the warfarin group and 24 patients in the NOAC group had complications, but likewise, the between-group difference was not statistically significant. Conclusion: Among patients who underwent TTA, those who received NOACs had a lower incidence of thromboembolic complications than those who received warfarin; however, both groups showed a similar bleeding complication rate. Using a NOAC after TTA does not reduce efficacy and safety when compared to warfarin.

Abstract Background The association between bundle branch block (BBB) and recurrence of atrial fibrillation (AF) after catheter ablation is unclear. The aim of this study was to determine whether AF combined with BBB is associated with AF recurrence after catheter ablation. Methods A total of 477 consecutive AF patients who underwent catheter ablation were included. The AF patients were divided into three groups according to BBB: AF without BBB (n = 427), AF with right bundle branch block (AF with RBBB) (n = 16), and AF with intraventricular conduction delay (AF with IVCD) (n = 34). Results Of the 477 AF patients (mean age 57 years, 81% men, median CHA2DS2‐VASc score of 1), 16 (3.4%) patients had RBBB, and 34 (7.1%) patients had IVCD. During a mean follow‐up of 15.2 ± 6.7 months, 119 patients (24.9%) had recurrence of AF. Of these, 111 (26%) patients were in the AF without BBB group, with 2 (12.5%) and 6 (17.6%) patients in the RBBB and IVCD groups, respectively. The Kaplan–Meier estimate of the rate of recurrent AF was not significantly different among the three groups (p = .39). Multivariable analysis showed that persistent AF (HR 1.7, 95% CI 1.15–2.50, p = .007), chronic kidney disease (HR 2.94, 95% CI 1.20–7.17, p = .01), and left atrial diameter (HR 1.04, 95% CI 1.009–1.082, p = .01) were significantly associated with AF recurrence. Conclusion AF with BBB was not significantly associated with the recurrence of AF after catheter ablation in middle‐aged patients with low‐risk cardiovascular profile.

Summary: Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18–64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68–14.32) also satisfied the non-inferiority criterion (95% CI lower limit > −5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Background: Treatments for inflammatory bowel diseases (IBD) have evolved in the era of biologics. However, the real-world data on their usage patterns and sequencing are still limited. Objectives: We aimed to investigate treatment persistence and dose intensification of first- and second-line biologics in patients with IBD. Design: In this retrospective, cohort study using nationwide claims data, 13,087 patients with IBD initiating biologic therapy between 2010 and 2020 were identified. Methods: Treatment persistence and dose intensification during the first 2 years and switching patterns of biologics were analysed while identifying predictors of non-persistence. Results: As a first-line treatment of Crohn’s disease (CD), ustekinumab had a lower risk for non-persistence compared to infliximab [adjusted hazard ratio (aHR), 0.69, p = 0.048]. Second-line ustekinumab and vedolizumab showed the highest and lowest persistence (79.2% and 54.9%), respectively. As a first-line treatment of ulcerative colitis (UC), golimumab had a higher risk for non-persistence compared to infliximab (aHR, 1.68, p

The need for high-throughput analysis of multiple analytes for inborn errors of metabolism in newborn screening (NBS) has led to the introduction of tandem mass spectrometry (MS/MS) into the NBS laboratory. In a flow-injection analysis (FIA), the predominant MS/MS method utilized for NBS, samples are introduced directly into the mass spectrometer without chromatographic separation. When a high-throughput FIA-based MS/MS method is implemented on newer generations of mass spectrometers with increased sensitivity, the risk of carryover and contamination increases. In the present study, we report the carryover of ornithine identified during the implementation of the NeoBase™ 2 (PerkinElmer) non-derivatized kits on the Xevo-TQD platform (Waters Corporation) and describe the source of the carryover, which was traced to the stainless-steel frit-type inline filter. Furthermore, a possible compound-dependent interaction with the stainless-steel frit is suggested based on the structure of ornithine and its effect on separation techniques. Investigation and mitigation of carryover can be a time and resource consuming process, and to this end, our report on identification of a stainless-steel frit as the source of delayed elution and carryover of ornithine should be recognized as a rare, albeit possible source of carryover in FIA-MS/MS methods adopted for NST.

Abstract Migration of methane-rich fluids at submarine cold seeps drives intense microbial activity and precipitation of authigenic carbonates. In this study, we analyzed microbially derived authigenic carbonate samples recently recovered from active gas hydrate mounds on the southwestern slope of the Chukchi Borderlands (CB), western Arctic Ocean. Our main aim was to characterize the distribution patterns of trace elements in carbonate-hosted lipid fractions to assess metalloenzyme requirements of microbes involved in anaerobic oxidation of methane (AOM). We measured stable isotopes, trace elements, lipid biomarkers, and genomic DNA, and results indicate the dominance of AOM-related lipid biomarkers in studied carbonate samples, as well as a predominant occurrence of the anaerobic methanotrophic archaea (ANME)-1. We also report evidence for significant preferential enrichments of various trace elements (Li, Ni, Co, Cu, Zn, and Mo) in the total lipid fractions of CB carbonates, relative to elemental compositions determined for corresponding carbonate fractions, which differ from those previously reported for other seep sites. We hypothesize that trace element enrichments in carbonate-hosted lipid fractions could vary depending on the type of AOM microbial assemblage. Additional work is required to further investigate the mechanisms of lipid-bound trace elements in cold seep carbonates as potential metalloenzymes in AOM.

Abstract Background An exponential rise in clinical demand for cardiac implantable electronic device (CIED) therapy is observed all over the world due to the rapidly expanding lifespan. Accordingly, appropriate lead management including lead extraction is becoming increasingly essential components for the comprehensive care of patients with various CIEDs. Main body With a high success rate and a low complication rate, transvenous lead extraction (TLE) has now been established as first-line therapy for lead extraction. However, TLE is often challenging when there are heavily calcified fibrous adhesions between leads and cardiovascular structures. Recently, rotational mechanical dilator (RMD) sheaths were introduced to resolve this issue and facilitate TLE procedure. There are two types of commercially available RMD sheaths, Evolution® systems and TightRail™. Thorough knowledge of the proper use of the RMD devices is essential to increase success rate and to reduce complications of TLE. In the present review, mechanical features, various techniques, and clinical data of RMD sheaths will be described. Conclusion According to recent advancement of device technology, the clinical outcomes of TLE using the RMD sheaths are continuously improving. However, as the RMD sheath is a potentially aggressive tool, special care should be taken when used in patients with longer lead ages. Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, family name). Author 2 Given name: Ju Youn, Family name: Kim; Author 4 Given name: Young Keun, Family name: On; Author 5 Given name: June Soo, Family name: Kim. Also, kindly confirm the details in the metadata are correct.All of the author names are correct.

Abstract Background Atrial fibrillation (AF) is a well-known, long-term complication of atrial septal defect (ASD) in adults, even after device closure. Left atrial (LA) strain rate applied to the analysis of chamber function has been demonstrated to be an important predictor of LA reverse remodeling. This study aimed to determine the changes in chamber function after device closure of ASD. Methods This prospective study enrolled adults with secundum ASD undergoing transcatheter device closure from December 2016 to August 2017. We analyzed the clinical characteristics and LA strain rate before and six months after ASD closure. Results A total of 11 patients were enrolled. The mean age was 42.6 ± 9.9 years, and six (54.5%) were females. There was no significant change of conventional echocardiographic parameters after ASD closure. The mean global LA reservoir strain rate before ASD closure was 1.17 ± 0.34 and 0.85 ± 0.30 after ASD closure (p = 0.030). The median global LA conduit strain rate was 0.68 (0.42–1.16) and 0.41 (0.16–0.79) before and after ASD closure (p = 0.213), respectively. The mean global LA contractile strain rate at the six-month follow-up showed significant improvement compared with pre-procedural strain rate (0.33 ± 0.65 vs. − 0.43 ± 0.38, p = 0.006). Conclusions LA functional changes occurred during the six-month follow-up, while LA and right atrial (RA) geometric changes were not significant. LA reverse remodeling was proved by restoration of LA late diastolic contractile function.

Abstract Integrated circuits (ICs) are challenged to deliver historically anticipated performance improvements while increasing the cost and complexity of the technology with each generation. Front‐end‐of‐line (FEOL) processes have provided various solutions to this predicament, whereas the back‐end‐of‐line (BEOL) processes have taken a step back. With continuous IC scaling, the speed of the entire chip has reached a point where its performance is determined by the performance of the interconnect that bridges billions of transistors and other devices. Consequently, the demand for advanced interconnect metallization rises again, and various aspects must be considered. This review explores the quest for new materials for successfully routing nanoscale interconnects. The challenges in the interconnect structures as physical dimensions shrink are first explored. Then, various problem‐solving options are considered based on the properties of materials. New materials are also introduced for barriers, such as 2D materials, self‐assembled molecular layers, high‐entropy alloys, and conductors, such as Co and Ru, intermetallic compounds, and MAX phases. The comprehensive discussion of each material includes state‐of‐the‐art studies ranging from the characteristics of materials by theoretical calculation to process applications to the current interconnect structures. This review intends to provide a materials‐based implementation strategy to bridge the gap between academia and industry.

Abstract Recently, polymer materials have been at the forefront of other materials in building high‐performance flexible electronic skin (e‐skin) devices due to conspicuous advantages including excellent mechanical flexibility, good compatibility, and high plasticity. However, most research works just paid considerable attention and effort to the design, construction, and possible application of e‐skins that reproduce the tactile perception of the human skin sensory system. Compared with tactile sensing devices, e‐skins that aim to imitate the non‐contact sensing features in the sensory system of human skin tend to avoid undesired issues such as bacteria spreading and mechanical wear. To further promote the development of e‐skins to the human skin sensory system where tactile perception and non‐contact sensing complement each other, significant progress and advances have been achieved in the field of polymer materials enabled e‐skins for both tactile perception and non‐contact sensing applications. In this review, the latest progress in polymer material‐based e‐skins with regard to tactile, non‐contact sensing capabilities and their practical applications are introduced. The fabrication strategies of polymer materials and their role in building high‐performance e‐skins for tactile and non‐contact sensing are highlighted. Furthermore, we also review the research works that integrated the polymer‐based tactile and non‐contact e‐skins into robots and prostheses, smart gloves, and VR/AR devices and addressed some representative problems to demonstrate their suitability in practical applications in human–machine interactions. Finally, the current challenges in the construction of high‐performance tactile and non‐contact e‐skins are highlighted and promising properties in this direction, by taking advantage of the polymer materials, are outlined.

Abstract Physically unclonable functions (PUFs) are used for various applications such as anticounterfeiting, authentication, and secret key generation. They are generally evaluated through electrical measurements, requiring much time and effort due to the many electrical connections required. This study proposes an optical verification of spin‐orbit torque (SOT) devices for PUF design. SOT devices have gained much attention because they resist degradation and thermal changes and can generate secret keys with high reproducibility. A simple optical method based on the magneto‐optical Kerr effect is introduced to verify the authenticity of the proposed SOT PUF device. Furthermore, this study assesses the feasibility of using a W/CoFeB/MgO/Ta structure as a PUF. The 24‐bit device shows a reliability of 97.8 ± 1.03%, making it a promising candidate for use as a spintronics‐based PUFs.

This study investigates the effects of laser deposition and laser rescanning (LR) on the microstructure and mechanical properties of high-manganese steel (HMnS) deposited by laser-directed energy deposition (L-DED) comprising 24 wt.% Mn. Four types of laser deposition and LR strategies were investigated: unidirectional L-DED scanning without laser rescanning, L-DED scanning with 90° alterations in the laser scanning path on each layer without laser rescanning, unidirectional L-DED with laser rescanning in the same direction, and L-DED with laser rescanning with 90° alterations in the laser scanning path. The L-DED-processed HMnS had only a few small pores and exhibited a microstructure without any serious defects such as cracks. Additionally, a strong fibrous texture along the /building direction of the fully austenite phase was found. The mechanical properties (microhardness and tensile strength) of HMnS were improved by the LR with a grain refinement effect and fine solidification cell size due to the significantly faster solidification rate in LR than that in L-DED.

This study investigates the wear resistance of an Fe–12Mn–5Cr–1Ni-0.4C (high-manganese steel) produced by direct energy deposition (DED) and spheroidal graphite cast iron. The high-manganese steel was deposited on the spheroidal graphite cast iron substrate. Near the deposit/substrate interface, the graphite phases of the cast iron are completely solutionized owing to the low carbon content of the high-manganese steel. In addition, the steel was deposited with a dense microstructure without interfacial cracks owing to the strong austenite stabilization effect. The wear behavior for various wear loads and sliding speeds was studied using ball-on-disk tribology tests with counterpart balls (KS STB2 bearing steel). The results show that the wear rates of the deposited high-manganese steel and the spheroidal graphite cast iron depended more on the wear load than on the sliding speed. At a low wear load of 20 N or less, the spheroidal graphite cast iron showed a higher wear rate than the deposited high-manganese steel owing to the self-lubricating effect of graphite. When the wear load condition was 50 N, the high-manganese steel had a higher wear resistance than the cast iron owing to the work-hardening effect. Therefore, it is expected that high-manganese steels, produced by DED, with high wear resistance under a high wear load will be effective for repairing spheroidal graphite cast iron products.

ABSTRACT: Objectives: Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea. Methods: The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated. Results: The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699). Conclusion: This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

Arsenic (As)-contaminated soil inevitably exists in nature and has become a global challenge for a sustainable future. Current processes for As capture using natural and structurally engineered nanomaterials are neither scientifically nor economically viable. Here, we established a feasible strategy to enhance As-capture efficiency and ecosystem health by structurally reorganizing iron oxyhydroxide, a natural As stabilizer. We propose crystallization to reorganize FeOOH-acetate nanoplatelets (r-FAN), which is universal for either scalable chemical synthesis or reproduction from natural iron oxyhydroxide phases. The r-FAN with wide interlayer spacing immobilizes As species through a synergistic mechanism of electrostatic intercalation and surface chemisorption. The r-FAN rehabilitates the ecological fitness of As-contaminated artificial and mine soils, as manifested by the integrated bioassay results of collembolan and plants. Our findings will serve as a cornerstone for crystallization-based material engineering for sustainable environmental applications and for understanding the interactions between soil, nanoparticles, and contaminants.

Seismic airgun sound was measured with an autonomous passive acoustic recorder as a function of distance from 18.6 to 164.2 km in shallow water (

There is a growing recognition of the importance of health security to economic development globally. ‘Health security’ as a phenomenon continues to receive the attention of academics and policymakers in the course of ensuring a state of complete physical, mental and social well-being for all. Nigeria’s health policy equally gives a premium to this. The aim of this study, hinging on archival and qualitative research design, is to explore health security in Nigeria vis-à-vis the constraining social and environmental vulnerabilities. The discourse took into account unfolding social challenges and various environmental problems coupled with the high level of poverty. This article indicates that social and environmental uncertainties interact with many parts of the health care system in a variety of ways. This hurts health security in Nigeria as a result of poor infrastructure development, insufficient government financing, the lack of an integrated system for disease prevention and monitoring, frequent policy reversals, security issues, and unimpressive health indicators. Because of this and considering the state of the Nigerian health care that is worsening on a global standard, it is obvious that health security is yet to have a strong footing. For health security to have a meaningful impact on people's wellbeing, appropriate health services should be made accessible to those who need them.

Abstract Background The recent explosion of cancer genomics provides extensive information about mutations and gene expression changes in cancer. However, most of the identified gene mutations are not clinically utilized. It remains uncertain whether the presence of a certain genetic alteration will affect treatment response. Conventional statistics have limitations for causal inferences and are hard to gain sufficient power in genomic datasets. Here, we developed and evaluated a C-search algorithm for searching the causal genes that maximize the effect of the treatment. Methods The algorithm was developed based on the potential outcome framework and Bayesian posterior update. The precision of the algorithm was validated using a simulation dataset. The algorithm was implemented to a cBioPortal dataset. The genes discovered by the algorithm were externally validated within CancerSCAN screening data from Samsung Medical Center. Results Simulation data analysis showed that the C-search algorithm was able to identify nine causal genes out of ten. The C-search algorithm shows the discovery rate rapidly increasing until the 1500 data instances. Meanwhile, the log-rank test shows a slower increase in performance. The C-search algorithm was able to suggest nine causal genes from the cBioPortal Metabric dataset. Treating the patients with the causal genes is associated with better survival outcome in both the cBioPortal dataset and the CancerSCAN dataset which is used for external validation. Conclusions Our C-search algorithm demonstrated better performance to identify causal effects of the genes than multiple log-rank test analysis especially within a limited number of data. The result suggests that the C-search can discover the causal genes from various genetic datasets, where the number of samples is limited compared to the number of variables.

Abstract Background Cancer stem-like cells (CSCs) play a pivotal role in lung tumor formation and progression. Nerve injury-induced protein 1 (Ninjurin1, Ninj1) has been implicated in lung cancer; however, the pathological role of Ninj1 in the context of lung tumorigenesis remains largely unknown. Methods The role of Ninj1 in the survival of non-small cell lung cancer (NSCLC) CSCs within microenvironments exhibiting hazardous conditions was assessed by utilizing patient tissues and transgenic mouse models where Ninj1 repression and oncogenic Kras G12D/+ or carcinogen-induced genetic changes were induced in putative pulmonary stem cells (SCs). Additionally, NSCLC cell lines and primary cultures of patient-derived tumors, particularly Ninj1high and Ninj1low subpopulations and those with gain- or loss-of-Ninj1 expression, and also publicly available data were all used to assess the role of Ninj1 in lung tumorigenesis. Results Ninj1 expression is elevated in various human NSCLC cell lines and tumors, and elevated expression of this protein can serve as a biomarker for poor prognosis in patients with NSCLC. Elevated Ninj1 expression in pulmonary SCs with oncogenic changes promotes lung tumor growth in mice. Ninj1high subpopulations within NSCLC cell lines, patient-derived tumors, and NSCLC cells with gain-of-Ninj1 expression exhibited CSC-associated phenotypes and significantly enhanced survival capacities in vitro and in vivo in the presence of various cell death inducers. Mechanistically, Ninj1 forms an assembly with lipoprotein receptor-related protein 6 (LRP6) through its extracellular N-terminal domain and recruits Frizzled2 (FZD2) and various downstream signaling mediators, ultimately resulting in transcriptional upregulation of target genes of the LRP6/β-catenin signaling pathway. Conclusions Ninj1 may act as a driver of lung tumor formation and progression by protecting NSCLC CSCs from hostile microenvironments through ligand-independent activation of LRP6/β-catenin signaling.

Abstract Atrial fibrillation (AF) is the most common and increasing cardiac arrhythmia. AF increases thromboembolic events and hospitalizations and deteriorates quality of life. The mechanism of AF is not completely understood. James Cox proposed a concept of Maze procedure in 1987 which was based on a surgical ablation lesion for electrical conduction pathway. Although surgical ablation offers a higher success rate, it should be performed with minimally invasive techniques because of its high invasiveness. Haissaguerre et al. identified potential sources of AF in the pulmonary veins as triggers and developed the percutaneous catheter ablation as the treatment strategy for paroxysmal AF refractory to pharmaceutical therapy. The atrial remodeling occurs electrically and structurally in persistent or longstanding persistent AF, and the catheter ablation and surgical ablation have variable success rates. Persistent or longstanding persistent AF presents a major challenge. Despite continuous improvements, catheter-based procedures have shown relatively far from satisfactory outcomes and may need to be repeated to achieve sinus rhythm. A hybrid approach consisting of the sequential combination of a surgical minimally invasive epicardial ablation and a transvenous catheter endocardial ablation would be an alternative option that supplements the limitations of endo- and epicardial strategies. Close cooperation between cardiac surgeons and electrophysiologists for optimal selection of patients and management for arrhythmia recurrence seems suggestible for persistent or longstanding persistent AF.

Oriented attachment is a non-classical growth mechanism of nanomaterials that can lead to tunable properties and functionalities. Here the authors show that the crystallographic alignment between magnetite mesocrystal building-blocks can be tuned by the surface ligands, influencing the resulting magnetic properties.

Abstract It is unclear which factors are associated with progressive sinus node dysfunction after cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) ablation. We sought to evaluate the incidence and predictors for permanent pacemaker (PPM) implantation after CTI-dependent AFL ablation. Between January 2011 and June 2021, 353 patients underwent CTI-dependent AFL ablation were studied. During a median follow-up of 31.6 months, 30 patients (8.5%) received PPM implantation, 24 for sick sinus syndrome and 6 for atrioventricular block. In multivariable model, prior atrial fibrillation (AF) (HR 3.570; 95% CI 1.034–12.325; P = 0.044), lowest previous sinus heart rate (HR 0.942; 95% CI 0.898–0.988; P = 0.015), and left atrial volume index (LAVI) (HR 1.067; 95% CI 1.024–1.112; P = 0.002) were independently associated with PPM implantation after CTI-dependent AFL ablation. The best cut-off points for predicting PPM implantation were 60.1 ml/m2 for LAVI and 46 beats per minute for lowest previous sinus heart rate. Among the patients discharged without PPM implantation after ablation, sinus pause over three seconds at AFL termination during ablation was an independent predictor of PPM implantation (HR 17.841; 95% CI 4.626–68.807; P