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Although the efficacy of trastuzumab deruxtecan (T-DXd) against HER2-positive gastric cancers (GCs) has driven its clinical application, the precise mechanisms governing its immunomodulatory role remain unclear. In this study, we examined the immune-related mechanisms of action of T-DXd in GC cells. T-DXd exhibited potent antitumor effects in GC cells across diverse HER2 expression levels by inducing DNA damage and apoptosis. Activation of the DNA damage response by T-DXd led to increased PD-L1 expression. RNA-Seq analysis revealed that T-DXd modulated immune-related pathways, resulting in the upregulation of genes associated with inflammation and IFN signaling. Importantly, T-DXd activated the cGAS-STING pathway, inducing an IFN-I response in HER2-positive GC cells. Furthermore, T-DXd activated dendritic cells via the cancer cell-intrinsic cGAS-STING-IFN axis and enhanced PBMC-mediated tumor cell killing by activating CD8 + T cells. These findings provide valuable insights into the role of the cytosolic DNA sensing pathway in the action of T-DXd and offer a compelling rationale for combining T-DXd with immune checkpoint blockade therapies in GC treatment., (© 2024. The Author(s).)

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Volatile organic compounds (VOCs) are the air pollutants emitted from the petrochemical industry known to pose adverse health effects on workers. The database based on the third phase of The Environmental Health Study in the Korean National Industrial Complexes (EHSNIC) in Ulsan conducted from 2018 to 2021 was used. Subjects were divided into the exposed and control group according to the estimated pollution level and distances from the industrial complexes. Ambient benzene, ethylbenzene, and xylene were significantly higher in the exposed group compared to the controls, as well as their metabolites. Risk of chronic disease and atopic dermatitis was higher in the exposed group which was supported by higher serum inflammatory markers and high hazard index of the exposed region. These results can draw attention to people engaged with environmental plans and used as primary data when making policies to reduce pollutant levels around industrial complexes.

Objectives: Nasal valve surgery for internal nasal valve (INV) compromise has become increasingly popular. However, this rise in popularity has sparked debates regarding its indications and disputes over insurance coverage, primarily due to the lack of a gold-standard evaluation method. Therefore, we aimed to identify objective parameters for the INV compromise., Methods: We analyzed 186 INVs in 93 patients who underwent nasal valve surgery. The data comprised facial computed tomography (CT) images, acoustic rhinometry, the modified Cottle test, and symptom scores. Patients were categorized based on their symptoms and the., Results: of the modified Cottle test. We measured the INV angle, area, volume, lateral wall thickness, septal angle, and nasal bone area using CT., Results: The compromised INV group, characterized by nasal obstruction with a positive modified Cottle test, exhibited smaller INV areas in both coronal and axial views, reduced INV volume in the axial view, and a thinner lateral wall in the coronal view (all P<0.05). Acoustic rhinometry indicated a smaller minimal cross-sectional area and volume in the compromised INV group (both P<0.001). Regression analysis demonstrated significant associations between a compromised INV and reduced INV area on the axial view, as well as the minimal cross-sectional area measured by acoustic rhinometry., Conclusion: Relying solely on the INV angle in CT scans has limitations in assessing compromised INV. Alternatively, the INV area on axial CT scans and the minimal cross-sectional area measured by acoustic rhinometry may serve as objective parameters for evaluating INV compromise.

Motivated by the increasing cost, environmental concerns, and limited availability of Co, researchers are actively seeking alternative cathode materials for lithium-ion batteries. A promising strategy involves structure-modified materials, such as a NiMn core/shell system. This design leverages the high energy density of a Ni-rich core while employing an Mn-rich shell to enhance interfacial stability by suppressing unwanted reactions with the electrolyte. This approach offers improved cycling stability and reduced reliance on Co. However, the interdiffusion of Mn ions between the core and shell remains a significant challenge during synthesis. This work presents a facile approach to address the issue of Mn interdiffusion in core/shell cathode materials. The study demonstrates that partial oxidation of the precursor during the drying stage effectively enhances the Mn oxidation state. This strategy successfully suppresses Mn interdiffusion during subsequent calcination, leading to the preservation of the core/shell architecture in the final cathode material. This optimized structure mitigates interfacial reactions, enhances chemomechanical properties, and reduces crosstalk, a major contributor to rollover failure. This work presents a novel approach for synthesizing high-performance core/shell cathode materials for next-generation lithium-ion batteries., (© 2024 Wiley‐VCH GmbH.)

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Objectives: To evaluate the effect of proton pump inhibitor (PPI) after laryngeal microsurgery (LMS) in patients with benign vocal fold (VF) mucosal disease and in patients with overt reflux symptom according to subjective and objective voice assessment., Methods: The improvement of voice handicap index-10 (VHI-10) score, reflux symptom index (RSI) score, grade, roughness, breathiness, asthenia, and strain (GRBAS) score, Jitter, Shimmer, noise to harmonics ratio (NHR), maximum phonation time of acoustic voice analysis RESULTS: A total of 47 patients (PPI group [n = 24] and non-PPI group [n = 23]) completed the study. The scores for VHI-10, RSI, GRBAS, and acoustic parameters significantly improved in both groups after surgery. In the subgroup analysis of patients with overt reflux symptoms (RSI ≥ 13; non-PPI group [n = 12], PPI group [n = 15]), significant between-group differences were observed in terms of the improvement in NHR and the strain factor., Conclusion: Postoperative PPI administration in patients with VF benign mucosal disease with reflux symptoms might improve subjective and objective voice outcomes after LMS., Competing Interests: Conflict of interest No potential conflict of interest relevant to this article was reported., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Gold nanoclusters (Au NCs), composed of only a few atoms, exhibit molecule-like behavior due to their distinct electronic structures arising from quantum confinement effects. Unlike their plasmonic nanoparticle counterparts, these nonplasmonic Au NCs possess unique properties with significant potential for photosensitizer applications. While traditional and NC-based electrodes share architectural similarities, the photoelectrochemical (PEC) behavior of the latter diverges significantly. Sensitizing TiO 2 with Au NCs introduces additional surface trap states. In contrast to conventional photosensitizers, where surface states typically have a negligible impact on hole transfer, these trap states actively mediate the charge transfer process in Au NC-sensitized TiO 2 electrodes. In this study, we employed impedance spectroscopy to elucidate the role of surface trap states in photocurrent generation. Our investigation revealed that these states are critical in determining PEC performance, presenting a dichotomy: they facilitate charge transfer (enhancing PEC performance) while simultaneously promoting carrier recombination (limiting efficiency). We demonstrated that the judicious control of otherwise deleterious surface trap states can significantly boost photocurrent. Our findings highlight that the dual nature of surface trap states demands a comprehensive investigation to fully understand their intricate impact on PEC performance.

Background: The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans)., Methods: Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3., Results: Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group., Conclusions: Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Background: Studies have reported that the combination of two or more therapeutic compounds at certain ratios has more noticeable pharmaceutical properties than single compounds and requires reduced dosage of each agent. Red ginseng and velvet antler have been extensively used in boosting immunity and physical strength and preventing diseases. Thus, this study was conducted to elucidate the skin-protective potentials of red ginseng extract (RGE) and velvet antler extract (VAE) alone or in combination on ultraviolet (UVB)-irradiated human keratinocytes and SKH-1 hairless mice., Methods: HaCaT cells were preincubated with RGE/VAE alone or in combination for 2 h before UVB (30 mJ/cm 2 ) irradiation. SKH-1 mice were orally given RGE/VAE alone or in combination for 15 days before exposure to single dose of UVB (600 mJ/cm 2 ). Treated cells and treated skin tissues were collected and subjected to subsequent experiments., Results: RGE/VAE pretreatment alone or in combination significantly prevented UVB-induced cell death, apoptosis, reactive oxygen species production, and DNA damage in keratinocytes and SKH-1 mouse skins by downregulating mitogen-activated protein kinases/activator protein 1/nuclear factor kappa B and caspase signaling pathways. These extracts also strengthened the antioxidant defense systems and skin barriers in UVB-irradiated HaCaT cells and SKH-1 mouse skins. Furthermore, RGE/VAE co-administration appeared to be more effective in preventing UVB-caused skin injury than these extracts used alone., Conclusion: Overall, these findings suggest that the consumption of RGE/VAE, especially in combination, offers a protective ability against UVB-caused skin injury by preventing inflammation and apoptosis and enhancing antioxidant capacity., Competing Interests: The authors declare no conflict of interest., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Amaranth is a nutritionally valuable crop, as it contains phenolic acids and flavonoids, yielding diverse plant secondary metabolites (PSMs) like phytosterol, tocopherols, and carotenoids. This study explored the variations in the contents of seventeen polyphenolic compounds within the leaves of one hundred twenty Amaranthus accessions representing nine Amaranthus species. The investigation entailed the analysis of phenolic content across nine Amaranthus species, specifically A. hypochondriacus , A. cruentus , A. caudatus , A. tricolor , A. dubius , A. blitum , A. crispus , A. hybridus , and A. viridis , utilizing ultra performance liquid chromatography with photodiode array detection (UPLC-PDA). The results revealed significant differences in polyphenolic compounds among accessions in which rutin content was predominant in all Amaranthus species in both 2018 and 2019. Among the nine Amaranthus species, the rutin content ranged from 95.72 ± 199.17 μg g -1 ( A. dubius ) to 1485.09 ± 679.51 μg g -1 ( A. viridis ) in 2018 and from 821.59 ± 709.95 μg g -1 ( A. tricolor ) to 3166.52 ± 1317.38 μg g -1 ( A. hypochondriacus ) in 2019. Correlation analysis revealed, significant positive correlations between rutin and kaempferol-3-O-β-rutinoside (r = 0.93), benzoic acid and ferulic acid (r = 0.76), and benzoic acid and kaempferol-3-O-β-rutinoside (r = 0.76), whereas gallic acid showed consistently negative correlations with each of the 16 phenolic compounds. Wide variations were identified among accessions and between plants grown in the two years. The nine species and one hundred twenty Amaranthus accessions were clustered into six groups based on their seventeen phenolic compounds in each year. These findings contribute to expanding our understanding of the phytochemical traits of accessions within nine Amaranthus species, which serve as valuable resources for Amaranthus component breeding and functional material development.

Introduction: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD)., Aim: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD., Methods: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries., Results: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF., Conclusions: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA., (© 2024. Italian Society of Hypertension.)

This study investigated the anatomical details of the axillary and radial nerves in 50 upper limbs from 29 adult formalin-embalmed cadavers, and ten fresh upper limbs. The focus was on understanding the course, division, and ramifications of these nerves to improve treatment of shoulder dysfunction caused by axillary nerve damage. The axillary nerve divided anteriorly and posteriorly before passing the quadrangular space in all specimens, with specific distances to the first ramifications. It was found that the deltoid muscle's clavicular and acromial parts were always innervated by the anterior division of the axillary nerve, whereas the spinous part was variably innervated. The longest and thickest branches of the radial nerve to the triceps muscles were identified, with no statistically significant differences in fiber numbers among triceps branches. The study concludes that nerve transfer to the anterior division of the axillary nerve can restore the deltoid muscle in about 86% of shoulders, and the teres minor muscle can be restored by nerve transfer to the posterior division. The medial head branch and long head branch of radial nerve were identified as the best donor options., (© 2024. The Author(s).)

Objectives: Otitis media (OM) has a high prevalence worldwide and the treatment is crucial because hearing loss in children can lead to growth disorders such as language development disorders. The aim of this study is to analyse the changes in bacterial strains and the trends of antibiotic susceptibility in otitis media with effusion (OME), chronic otitis media (COM) and cholesteatomatous otitis media (Chole OM)., Design: This retrospective study involved 2926 patients diagnosed with OME, COM, or Chole OM between January 2000 and December 2020. The clinical data were collected and analysed through chart review from May 2021 to July 2021., Setting: Two tertiary medical centres., Participants: The 2926 OM patients., Main Outcomes and Measures: An otorrhea sample was collected on the first day of their hospital visit. Middle ear fluid samples for bacterial culture and antibiotics susceptibility test were collected from patients during middle ear surgery, including ventilation tube insertion. In each type of OM, the distribution of bacterial strains in the 2000s and the 2010s was compared. In addition, changes in the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) and trends in their antibiotic susceptibility over the last 10 years were analysed., Results: The most frequently detected bacterial strains in OME, COM and Chole OM over the study period were coagulase-negative Staphylococcus (CNS) (29.6%), MRSA (24.1%), and PA (20.1%). Compared to the 2000s, the proportion of non-typable Haemophilus influenzae in OME and MRSA in COM increased in the 2010s (27.4%-31.6% and 1.5%-29.5%, respectively). In total three types of OM, although there was no significant trend of change in detection rates of MRSA, PA, and multidrug resistant-P. aeruginosa (MDR-PA) during the last 10 years, resistance to the Quinolone class of MRSA and PA tended to increase (P < .05)., Conclusions: The composition of bacterial strains in each types of OM has changed over the past 20 years. Additionally, the antibiotic resistance of MRSA and PA has increased in the last decade. Therefore, when using empirical antibiotics in necessary situations, it is necessary to change to an appropriate antibiotic through a bacterial culture test and antimicrobial susceptibility test., (© 2023 John Wiley & Sons Ltd.)

Certain cancers, such as triple-negative breast cancer (TNBC), pose a challenging prognosis due to the absence of identifiable hormone-related receptors and effective targeted therapies. Consequently, novel therapeutics are required for these cancers, offering minimal side effects and reduced drug resistance. Unexpectedly, siRNA-7, initially employed as a control, exhibited significant efficacy in inhibiting cell viability in MDA-MB-231 cells. Through a genome-wide search of seed sequences, the targets of siRNA-7 were identified as cancer-related genes, namely PRKCE, RBPJ, ZNF737, and CDC7 in MDA-MB-231 cells. The mRNA repression analysis confirmed the simultaneous suppression by siRNA-7. Combinatorial administration of single-targeting siRNAs demonstrated a comparable reduction in viability to that achieved by siRNA-7. Importantly, siRNA-7 selectively inhibited cell viability in MDA-MB-231 cells, while normal HDF-n cells remained unaffected. Furthermore, in a xenograft mouse model, siRNA-7 exhibited a remarkable 76% reduction in tumor volume without any loss in body weight. These findings position siRNA-7 as a promising candidate for a novel, safe, specific, and potent TNBC cancer therapeutic. Moreover, the strategy of multiple suppressing small interfering RNA holds potential for the treatment of various diseases associated with gene overexpression., (© 2023 Wiley-VCH GmbH.)

Antioxidant and anti-inflammatory mechanisms counteract the pathogenesis of chronic diseases, such as diabetes, aging, and cancer. Therefore, enhancing antioxidant and anti-inflammatory functions may help manage these pathological conditions. This study aimed to assess the antioxidant and anti-inflammatory potentials of lipophilic fraction of Liriope platyphylla seeds (LLPS) using network pharmacology, molecular docking, and in vitro experiments. Here GC-MS analysis tentatively identified forty-three lipophilic compounds in LLPS. LLPS exhibited powerful antioxidant activity, according to the results from chemical-based antioxidant assays on DPPH, ABTS + , superoxide anion, hydrogen peroxide, nitric oxide, and hydroxyl radicals scavenging, lipid peroxidation, reducing antioxidant powers, and total antioxidant capacity. Additionally, LLPS enhanced cellular antioxidant capacity by inhibiting reactive oxygen species formation and elevating antioxidant enzyme levels, including catalase and heme oxygenase-1. Moreover, LLPS attenuated inflammatory response by reducing nitric oxide secretion and downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β in lipopolysaccharide-treated macrophages. Network pharmacology and molecular docking analyses showed that key compounds in LPPS, particularly phytosterols and fatty acid esters, exerted antioxidant and anti-inflammatory properties through regulating NFKB1, PTGS1, PTGS2, TLR4, PRKCA, PRKCD, KEAP1, NFE2L2, and NR1l2. Overall, these data suggest that LLPS may be a potential antioxidant and anti-inflammatory agent for developing functional foods.

Introduction: Based on the "2019 Living Time Survey" data conducted by the National Statistical Office, this study is aimed at comparing the time usage of single-parent families by classifying the occupation area based on the fourth edition of the occupational therapy practice framework (OTPF) and dividing time use according to weekdays and weekends and by gender., Methods: After extracting the subjects who were selected belonging to a single-parent family from the original data of the "2019 Living Time Survey," 404 subjects who were single parents were selected, and the data were analysed. The sample consisted of 134 males and 270 females. The time usage by occupation area during weekdays and weekends and according to the gender of the subjects was checked. By using SPSS 25.0 version for data analysis, the general characteristics and time usage of subjects were presented as frequency analysis and technical statistics, and an independent sample t -test was conducted to compare time usage on weekdays and weekends., Results: Subjects spent more time on "education" and "work" on weekdays, and on weekends, they spent more time on "activities of daily living," "rest and sleep," "leisure," and "social participation." After classifying the subjects by gender, men spent more time on "work" on weekdays, and on weekends, they spent more time on "activities of daily living," "rest and sleep," "leisure," and "social participation." Women spent more time on "education" and "work" on weekdays, and on weekends, they spent more time on "rest and sleep," "leisure," and "social participation.", Conclusion: By examining the time usage of single-parent families according to the day of the week, we hope that it will be used as basic data to suggest in which areas they have difficulty managing time, depending on the day of the week, and to establish solutions to insufficient time use due to gender differences., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Woo-Hyuk Jang and Jin-Hyuk Bang.)

Capacity fading as a function of lithiation/delithiation cycles is a major limitation of Li-ion batteries. Most Li storage materials are susceptible to this phenomenon due to the degradation of the crystal structure and particle integrity as a result of volume changes associated with lithiation/delithiation processes and/or irreversible redox reactions. However, some Li storage materials show an increase in capacity with an increase in cycles; this phenomenon has been termed "negative fading." Negative fading in Li host materials is usually associated with the additional charge storage at the particle/solid-electrolyte interface (SEI) layer, decomposition/formation of the SEI layer, or redox reactions of various Li species at the interface. In this work, we report the observation of negative fading in a newly discovered anode material, TiNbO 4 (TNO), and reveal amorphization as a new mechanism for negative fading in Li host materials. This assertion was confirmed via a close relationship between changes in the crystal structure and the Li storage mechanism in TNO. Given that other titanium niobium oxide analogues (e.g., TiNb 2 O 7 ) suffer from capacity loss due to amorphization, this unique electrochemical behavior of TNO may provide an interesting new direction to tune the titanium niobium oxides for high-performance, stable battery anodes.

Background: Single-parent families are burdened with dual roles as parents amidst economic poverty due to the lack of a spouse. Single parents also face the complications of time poverty., Aim: To examine the time use of single-parent families by dividing their time into occupational area and explore the differences in time deficiency and life satisfaction., Methods: In this study, the time usage in the '2019 time of life survey' data of the National Statistical Office is classified based on the fourth edition of the Occupational Therapy Practice Framework, and the time use and satisfaction of single-parent families classified according to sex. In the '2019 time of life survey' of the National Statistical Office, the subjects who selected single-parent families in the 'single parent-parent-grandchild households' item were first selected. The data of 404 parents from single-parent families were selected next. The time usage, time deficiency, and life satisfaction were analyzed by occupational area., Results: The subjects spent the most time resting and sleeping, followed by engaging in instrumental activities of daily living (IADLs), work, and health management. As a result of comparing the subjects by sex, it was found that the male subjects spent more time on work than the female subjects, and the female subjects spent more time on IADLs, education and social participation. As a result of comparing time deficiency and life satisfaction, the male subjects felt that they lacked time compared to the female subjects. There was no significant difference in life satisfaction. By examining whether single-parent families' time use by occupational area affected the time deficiency, it was found that male's working time make them feel they have less time, while female's leisure time makes them feel they have more time., Conclusion: This study made it possible to determine the characteristics of single-parent households' time use and sex differences. Furthermore, it is expected to be used as basic data for measures to solve not only time poverty, but also economic poverty in single-parent families., Competing Interests: Conflict-of-interest statement: All the authors declare having no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bimetallic spinel and perovskite metal oxide materials are advanced electrode materials for supercapacitor (SC) applications because of their low-cost, distinct crystal structures, eco-friendly nature, and high conductivity. However, they suffer from the disadvantages of poor ion-diffusion kinetics and pulverization issues during cyclability tests. Along with a deeper understanding of redox chemistry, the role of oxygen vacancies (OVs) in electrode materials to support the reaction kinetics for excellence in SCs must be clarified. In this review, we highlight for the first time the importance of OVs and summarize various design strategies for the preparation of advanced bimetallic spinel oxides and perovskites with improved electrochemical performances for SC applications. With new insights, we envision that the SC research community would endeavor to utilize the benefits of OVs effectively for the development of high-performance SCs.

Background: Disinfection of gloves might reduce the workload of healthcare workers, protect the environment, and bring economic benefits. Thus, the safety of hand hygiene of gloved hands is an important issue., Aim: We aimed to evaluate the risk of microbial transmission by comparing residual micro-organisms after multiple patient contacts, with or without gloves, in clinical practice., Methods: Researchers, two with gloved hands (single or double gloves) and one with bare hands, made rounds of patients, followed by alcohol-based hand rub. Hand imprints were obtained before and after the rounds and cultured. The number of colony-forming units (cfu) of gloved and bare hands was compared, and the colony distribution was evaluated semi-quantitatively by hand region., Findings and Conclusion: A total of 108 imprints were obtained after 10 rounds. The median cfu counts were significantly higher in the gloved hands (single and double) than in the bare hands (9.00 vs 3.50, P=0.028). The cfu counts of single- and double-gloved hands were higher after than before contact (P=0.044 and P=0.001, respectively). Carbapenem-resistant Acinetobacter baumannii was identified in a pair of double gloves after a round, which included patients with the same organism with identical antibiotic susceptibility results. The mean percentage of colony-growing compartments from gloved hands was significantly higher than that of bare hands in the finger and wrist regions (P=0.019 and P=0.049, respectively). Compared with bare hands, reuse of gloves increased residual microbial colonies and potential for transmission of multi-drug-resistant organisms, even after using alcohol-based hand rub., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19., Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively., Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19., Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Choe, Kang, Lee, Song, Bang, Kim, Kim, Kim, Kim, Kim, Lee, Shin, Park, Park and Oh.)

Korean red ginseng has been widely used as an herbal medicine. Red ginseng dietary fiber (RGDF) is a residue of the processed ginseng product but still contains bioactive constituents that can be applied as prebiotics. In this study, we evaluated changes on fermentation profiles and probiotic properties of strains that belong to family Lactobacillaceae with RGDF supplementation. Metabolomic analyses were performed to understand specific mechanisms on the metabolic alteration by RGDF and to discover novel bioactive compounds secreted by the RGDF-supplemented probiotic strain. RGDF supplementation promoted short-chain fatty acid (SCFA) production, carbon source utilization, and gut epithelial adhesion of Lactiplantibacillus plantarum and inhibited attachment of enteropathogens. Intracellular and extracellular metabolome analyses revealed that RGDF induced metabolic alteration, especially associated with central carbon metabolism, and produced RGDF-specific metabolites secreted by L. plantarum , respectively. Specifically, L. plantarum showed decreases in intracellular metabolites of oleic acid, nicotinic acid, uracil, and glyceric acid, while extracellular secretion of several metabolites including oleic acid, 2-hydroxybutanoic acid, hexanol, and butyl acetate increased. RGDF supplementation had distinct effects on L. plantarum metabolism compared with fructooligosaccharide supplementation. These findings present potential applications of RGDF as prebiotics and bioactive compounds produced by RGDF-supplemented L. plantarum as novel postbiotic metabolites for human disease prevention and treatment., Competing Interests: S-HY and S-KK were employed by Korea Ginseng Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeon, You, Nam, Truong, Bang, Bae, Rarison, Kim, Jeong, Jung and Shin.)

Thermo-compression bonding (TCB) properties of Cu/SnAg pillar bumps on electroless palladium immersion gold (EPIG) were evaluated in this study. A test chip with Cu/SnAg pillar bumps was bonded on the surface-finished Cu pads with the TCB method. The surface roughness of the EPIG was 82 nm, which was 1.6 times higher than that of the ENEPIG surface finish because the EPIG was so thin that it could not flatten rough bare Cu pads. From the cross-sectional SEM micrographs, the filler trapping of the TC-bonded EPIG was much higher than that of the ENEPIG sample. The high filler trapping of the EPIG sample was due to the high surface roughness of the EPIG surface finish. The contact resistance increased as the thermal cycle time increased. The increase of the contact resistance with 1500 cycles of the thermal cycle test was 26% higher for the EPIG sample than for the ENEPIG sample.

Background: Spontaneous dissection of the hepatic artery is a rare finding for which there is no specific treatment algorithm. Even though endovascular treatment and surgery have been used to treat other visceral artery dissections, these approaches can be challenging in the case of hepatic artery dissection because it is difficult to access the hepatic artery., Case Summary: 2 patients with spontaneous dissection of the hepatic artery were admitted due to epigastric pain. Although the liver function test results were normal, and there were no complications such as bleeding, shock, or ischemia in other organs, a subsequent computed tomography scan directly revealed the spontaneous dissection of the hepatic artery in both patients. The patients were treated with anticoagulants without surgery. Because it is difficult to perform surgery or endovascular treatment on the hepatic artery, we focused on preventing the progression of hepatic artery dissection and the formation of a new thrombus in the dissection., Conclusion: Considering the risk of surgical treatment for the hepatic artery and the condition of the patients, medical treatment with anticoagulants may be considered as an initial treatment and provide more benefits than surgical treatment.

Objectives: Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia occur within a few days after the onset of bacteraemia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteraemia., Methods: Clinical information on all patients with CRAB bacteraemia in 10 hospitals during a 1-year period was collected. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively., Results: In total, 212 CRAB bacteraemia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score was significantly higher in patients with EM than those with LM. Although urinary tract infection as the site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM., Conclusion: Our results suggest that a large proportion of CRAB bacteraemia with high severity progresses to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed., Methods: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model., Results: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss., Conclusions: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden., (© 2022. The Author(s).)

A kenaf-derived activated carbon (KAC) for a high-power density supercapacitor was developed in this study through phosphoric acid activation. The N 2 /77K isothermal adsorption-desorption curve was used to estimate the textural properties of KAC based on BET and BJH and the pore size distribution based on NLDFT. The electrochemical properties of KAC were analyzed by using the coin-type cell applying 1 M SPBBF 4 /PC electrolyte, and the specific surface area and total pore volume were 1490-1942 m 2 /g and 1.18-3.18 cm 3 /g, respectively. The pore characteristics of KAC varied according to the activation temperature, and most KAC showed a mesoporous structure. As the activation temperature increased, the mesopore volume increased up to 700 °C, then decreased. The mesoporous structure of KAC resulted in a substantial decrease in the Warburg impedance as the ion diffusion resistance decreased. Hence, the specific capacitance of KAC decreased from 82.9 F/g to 59.48 F/g as the charge-discharge rate increased from 1 mA/g to 10 mA/g, with the rate of reduction at approximately 30%. The rate of reduction of KAC's specific capacitance was 50% lower compared with commercial activated carbon; hence, KAC is a more suitable electrode-active material for high power density supercapacitors.

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

Despite its clinical efficacy in HER2-positive cancers, resistance to trastuzumab inevitably occurs. The DNA damage response (DDR) pathway is essential for maintaining genomic stability and cell survival. However, the role of the DDR pathway in HER2-positive tumors and trastuzumab resistance remains elusive. In this study, we verified that increased PARP1 expression in trastuzumab-resistant (TR) cells, owing to its augmented stability by escape from proteasomal degradation, confers tolerability to trastuzumab-induced DNA damage. Interruption of PARP1 in TR cells restrains its cellular growth, while simultaneously activating ATM to retain its genome stability. Dual inhibition of PARP and ATM induces synthetic lethality in TR cells by favoring the toxic NHEJ pathway instead of the HRR pathway. Our results highlight the potential of clinical development of DDR-targeting strategies for trastuzumab-resistant HER2-positive cancer patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Calcium carbonate is one of the most common minerals, and its polymorphic formation and transformation pathways from the amorphous to crystalline phases are well documented. However, the effects of locally created pH changes on the preferential formation of amorphous calcium carbonate (ACC) or its crystalline phase remain poorly understood. In this study, the influence of the initial solution pH on the precipitated polymorphs of calcium carbonate was investigated by the rapid mixing of each solution containing calcium or carbonate ions in the absence of additives. The results showed that the amount of recovered ACC particles was associated with the availability of fully deprotonated carbonate ions. A secondary crystalline phase was identified as the vaterite phase, but no polymorphic change to produce the more stable calcite was detected during 5 h of stirring. Interestingly, during the early stage of pouring, the vaterite morphology was dependent on the generated pH range, over which ACC particles were stabilized (pH > 10.3), followed by the hydration-condensation processes. When the pH was sufficiently low (pH < 10.3) for bicarbonate ions to participate in the carbonation reaction, croissant- or cauliflower-like aggregates with layered structures were obtained. In contrast, typical spherical vaterite particles were obtained at a high initial pH when the carbonate ions were dominant. Meanwhile, vaterite particles that were formed in the presence of an excess of carbonate ions were irregular and separate agglomerates. These results elucidate the formation of ACC and the morphologies of the vaterite products., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination., Methods: Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4 + or CD8 + T cells., Results: A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4 + T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group., Conclusion: Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions., Competing Interests: Declaration of Competing Interest All authors report no potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Choroidal neovascularization (CNV) is a defining characteristic feature of neovascular age-related macular degeneration (nAMD) that frequently results in irreversible vision loss. The current strategies for the treatment of nAMD are mainly based on neutralizing vascular endothelial growth factor (VEGF). However, anti-VEGF therapies are often associated with subretinal fibrosis that eventually leads to damages in macula. In this study, we tested whether an anti-fibrotic and anti-angiogenic protein CCN5 can potentially be an effective and safe therapeutic modality in a mouse model of CNV. Laser photocoagulation was utilized to induce CNV, which was followed by intravitreal injection of recombinant adeno-associated virus serotype 2 encoding CCN5 (rAAV2-CCN5). Our data demonstrated that rAAV2-CCN5, but not a control viral vector, rAAV2-VLP, prominently attenuated both CNV lesions and angiogenesis. Aflibercept, which was utilized as a positive control, exhibited similar effects on CNV lesions and angiogenesis in our experimental settings. Upon laser photocoagulation, retinal pigmented epithelium (RPE) cells underwent significant morphological changes including cellular enlargement and loss of hexagonality. rAAV2-CCN5 significantly normalized these morphological defects. Laser photocoagulation also led to fibrotic deformation in RPE cells through inducing epithelial-mesenchymal transition (EMT), which was completely blocked by rAAV2-CCN5. In a striking contrast, aflibercept as well as rAAV2-VLP failed to exhibit any effects on EMT. Collectively, this study suggest that CCN5 might provide a potential novel strategy for the treatment of nAMD with a capability to inhibit CNV and fibrosis simaultaneously., Competing Interests: K.M.W. and W.J.P share co-ownership of Olives Biotherapeutics. No potential conflicts of interest exist for other authors.

Gold nanoclusters (NCs) can be used as sensitizers to extend the absorption capabilities of TiO 2 as photoelectrodes. However, the adsorption of NCs also creates additional surface states on the TiO 2 surface, which gives rise to intricacies in the understanding of various interfacial phenomena occurring in NC-sensitized TiO 2 . One of the complexities that have recently been discovered is the size-dependent hole-transfer mechanism. In this work, we reveal another anomalous behavior in the hole-transfer process that the hole scavenging ability of the electrolyte also plays a role in determining the hole-transfer mechanism in the NC-TiO 2 system, which is unprecedented in other photoelectrode systems. In the presence of an efficient hole scavenger (Na 2 SO 3 ), the hole transfer in Au 18 -TiO 2 occurs directly through the highest occupied molecular orbital (HOMO) of Au 18 NCs. However, in the presence of a less efficient hole scavenger (ethylenediaminetetraacetic acid), hole transfer in Au 18 -TiO 2 does not occur through the HOMO and shifts to surface state-assisted hole transfer. Due to surface state charging, this surface state-assisted hole-transfer mechanism results in delayed photocurrent response in Au 18 -TiO 2 . Evidence for this exotic hole-transfer mechanism shift is provided by photoelectrochemical electrochemical impedance spectroscopy, and its implications are discussed.

Background: Immunotherapies have shown clinical activity in patients with advanced biliary tract cancer, for which outcomes remain poor despite standard of care treatment with gemcitabine and cisplatin. We aimed to evaluate gemcitabine and cisplatin plus durvalumab with or without tremelimumab as first-line treatment in patients with advanced biliary tract cancer., Methods: This open-label, single-centre, phase 2 study was conducted at Seoul National University Hospital. Eligible patients were treatment-naïve adults aged 18 years or older with histologically proven unresectable or recurrent biliary tract cancer, at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (version 1.1), an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 12 weeks or longer, and adequate healthy organ and bone marrow function. Initially, all patients received one 3-week cycle of gemcitabine (1000 mg/m 2 ) and cisplatin (25 mg/m 2 ) on day 1 and 8 followed by gemcitabine and cisplatin plus durvalumab (1120 mg) and tremelimumab (75 mg) on day 1 of each cycle, starting with the second cycle (chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group). Following protocol amendment, patients were recruited to receive gemcitabine and cisplatin plus durvalumab, starting on day 1 of the first cycle (chemotherapy plus durvalumab group) or gemcitabine and cisplatin plus durvalumab and tremelimumab also from day 1 of the first cycle (chemotherapy plus durvalumab and tremelimumab group) in parallel and allocated using a random block method. Assessors and patients were not masked to the treatment group. The primary endpoint was objective response rate, assessed in the efficacy population (ie, patients who were treated at least until the first tumour response assessment). This study is registered with ClinicalTrials.gov, NCT03046862 (active)., Findings: Between March 2, 2017, and Feb 13, 2020, 128 patients were enrolled (32 in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 49 in the chemotherapy plus durvalumab group, and 47 in the chemotherapy plus durvalumab and tremelimumab group). Four patients (two in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group and two in the chemotherapy plus durvalumab group) were excluded and 124 were evaluable for tumour response. The median duration of follow-up was 48·2 months (IQR 41·5-49·4) for the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 26·6 months (19·0-27·9) for the chemotherapy plus durvalumab group, and 24·2 months (20·7-31·7) for the chemotherapy plus durvalumab and tremelimumab group. 82 (66%) of 124 patients achieved an objective response (15 [50%] of 30 in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 34 [72%] of 47 in the chemotherapy plus durvalumab group, and 33 [70%] of 47 in the chemotherapy plus durvalumab and tremelimumab group). The most common grade 3 and 4 adverse events were decreased neutrophil count (67 [53%] of 126), anaemia (50 [40%]), and decreased platelet count (24 [19%]), with no unexpected safety events. No adverse events leading to discontinuation or death occurred., Interpretation: Gemcitabine and cisplatin plus immunotherapy showed promising efficacy and acceptable safety in patients with biliary tract cancer. Gemcitabine and cisplatin plus durvalumab are being evaluated in the phase 3, TOPAZ-1 study (NCT03875235) as first-line treatment in patients with advanced biliary tract cancer., Funding: AstraZeneca; National Research Foundation of Korea (Grant No. 2021R1A2C2007430)., Competing Interests: Declaration of interests D-YO received research grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, Merck Sharp & Dohme, and Handok and has been a consultant or adviser for AstraZeneca, Novartis, Genentech, Merck Serono, Bayer, Taiho, ASLAN Pharmaceuticals, Halozyme, Zymeworks, Bristol Myers Squibb, BeiGene, Basilea, and Turning Point. YL, VG, PM, WL, SW, QZ, and MCR are or were employees and shareholders of AstraZeneca. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed., (© 2022. The Author(s).)

The limited capacity of graphite anodes in high-performance batteries has led to considerable interest in alternative materials in recent years. Due to its high capacity, titanium niobium oxide (TiNb 2 O 7 , TNO) with a Wadsley-Roth crystallographic sheared structure holds great promise as a next-generation anode material, but a comprehensive understanding of TNO's electrochemical behavior is lacking. In particular, the mechanism responsible for the capacity fading of TNO remains poorly elucidated. Given its metastable nature (as an entropy-stabilized oxide) and the large volume change in TNO upon lithiation and delithiation, which has long been overlooked, the factors governing capacity fading warrant investigation. Our studies reveal that the structural weakness of TNO is fatal to the long-term cycling stability of TNO and that the capacity fading of TNO is driven by amorphization, which results in a significant increase in impedance. While nanostructuring can kinetically boost lithium intercalation, this benefit comes at the expense of capacity fading. Carbon doping in TNO can effectively suppress the critical impedance increase despite the amorphization, providing a possible remedy to the stability issue.

Background: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19)., Methods: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated., Results: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score., Conclusion: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Despite the enormous attention paid to cobalt oxide materials as efficient water splitting electrocatalysts, a deep understanding of their activity discrepancy is still elusive. In this work, we showed that stabilization of the internally generated oxygen evolution reaction (OER) active phase (oxyhydroxide) is crucial for ZnCo 2 O 4 electrocatalysts. A systematic evaluation of the bulk and nanostructured ZnCo 2 O 4 system concomitant with nanostructured Co 3 O 4 showed that leaching of Zn is the driving force behind the near-surface transformation to the oxyhydroxide phase. The relative contribution to this near-surface reconstruction was found to be surface-sensitive. The electrochemical observations combined with Raman and impedance spectroscopy revealed that the good catalytic activity could be attributed to the formation of the cobalt oxyhydroxide phase, which was created by the dissolution of Zn from the nanostructured surface. Moreover, this study sheds light on previous contradicting postulates regarding the discrepancy of the OER activity of ZnCo 2 O 4 . Our finding regarding the formation of the OER active phase in spinel Zn-Co oxide will motivate researchers to focus more on the near-surface reconstruction behavior of cobalt-based oxide electrocatalysts in the future.

Purpose: Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC., Materials and Methods: We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments., Results: In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug., Conclusion: This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND 50 ) titers in serum samples. ND 50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0-12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7-294.0]) and delta (24.3 [14.3-81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND 50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND 50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants ( P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Changes in worldwide crop trends and climate change has increased the introduction of alien crops. However, there are always potential side effect issues related to introduced crops, such as the introduced crop becoming a nuisance at the new country or bringing insect pests or microorganisms with the introduced crops. In this study, we developed a crop introduction risk assessment system using text mining method to prevent this problem. First, we designed the "Preliminary Environmental Impact Assessment Index for Alien Crops" based on ecological researches to assess the risks of introduced crops to the natural environment. The questionaries evaluate the target alien crop with previous cases reporting the target crops' adverse effects on the environment, the potential of target crops' direct or indirect damage on the environment. The index has sixteen questions with allocated scores that are divided into 4 categories. The detailed rationales of the questionaries and the assessment index are discussed in main text. Second, we assessed 67 crop species that were introduced or scheduled to be introduced to South Korea with this Preliminary Assessment Index. The literature and data were collected with JabRef, search engines, and from the documents of six international institutions. Finally, based on the preliminary assessment results of selected species, we developed the protocols and a manual for the preliminary environmental risk assessment of introduced species. Final evaluation scores for risk evaluation for introducing crops are suggested (over 70 total score for 'danger' and over 50 points for 'caution required', and under 50 points for 'low expected impact'). Presented crop introduction risk assessment system is effective to identify potential problem making crop species. The protocols and a manual that we provide in this study could be applied to other countries which have similar climate and environmental conditions, or after being adequately modified to their environmental factors such as climate, neighboring countries, major crops according to eating habits, and major vegetation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The cause of the allergic disease is known to be multifactorial, and there is growing evidence of environmental factors triggering the disease. Indeed, it is essential to find modifiable environmental factors related to allergic disease. Noise is an environmental pollutant causing various health problems, especially when exposed during the night-time. This study assessed the impact of night-time noise exposure in allergic disease. Subjects were selected from a panel data survey containing questions on allergic disease and related factors. Incidence of allergic disease, covariates, and addresses was derived from survey questionnaires. By applying the Land Use Regression modeling method, each subject's night-time noise estimates were elicited based on the night-time noise level collected from the noise monitoring site. Association between night-time noise difference rate and incidence of asthma were analyzed by Cox proportional hazard regression. Incidence of allergic disease increased when night-time noise difference was positive compared to the negative difference. Additionally, the incidence of allergic disease increased by per interquartile range of night-time noise difference rate. The result showed that exposure to night-time noise tends to increase the risk of allergic disease. With further studies, the result of our study may serve as supplementary data when determining noise limits.

TiO 2 offers several advantages over graphite as an anode material for Li-ion batteries (LIBs) but suffers from low electrical conductivity and Li-diffusion issues. Control over defect chemistry has proven to be an effective strategy to overcome these issues. However, defect engineering has primarily been focused on oxygen vacancies (V O ). The role of another intrinsic TiO 2 vacancy [i.e., titanium vacancies (V Ti )] with regard to the Li + storage behavior of TiO 2 has largely evaded attention. Hence, a comparison of V O - and V Ti -defective TiO 2 can provide valuable insight into how these two types of defects affect Li + storage behavior. To eliminate other factors that may also affect the Li + storage behavior of TiO 2 , we carefully devised synthesis protocols to prepare TiO 2 with either V O (n-TiO 2 ) or V Ti (p-TiO 2 ). Both TiO 2 materials were verified to have a very similar morphology, surface area, and crystal structure. Although V O provided additional sites that improved the capacity at low C-rates, the benefit obtained from over-lithiation turned out to be detrimental to cycling stability. Unlike V O , V Ti could not serve as an additional lithium reservoir but could significantly improve the rate performance of TiO 2 . More importantly, the presence of V Ti prevented over-lithiation, significantly improving the cycling stability of TiO 2 . We believe that these new insights could help guide the development of high-performance TiO 2 for LIB applications.