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Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Although many people with CF (pwCF) are treated using CFTR modulators, some are non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, in which the CFTR cDNA has been replaced, may enable a durable therapy for all pwCF. Previously, CRISPR-Cas9 with two AAVs was used to sequentially insert two-halves of the CFTR cDNA and an enrichment cassette into the CFTR locus. However, the editing efficiency was <10% and required enrichment to restore CFTR function. Further improvement in gene insertion may enhance cell therapy production. To improve CFTR cDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558, which inhibit non-homologous end-joining (NHEJ) and micro-homology mediated end-joining (MMEJ). Adding AZD7648 alone improved gene insertion by 2- to 3-fold. Adding both ART558 and AZD7648 improved gene insertion but induced toxicity. ABCs edited in the presence of AZD7648 produced differentiated airway epithelial sheets with restored CFTR function after enrichment. Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

A N-Co-N core is embedded within [Co(CNC) 2 ] 2+ (1) supported by two bis(4-methyl-2-(3-methyl-imidazolium)phenyl)amine (CNC) ligands. This species reveals a stable S = 1/2 state and its spin density is significantly delocalized within the N-Co-N core via parallel π-bonding interaction. Interestingly, it displays unusual stability towards O 2 and water, proving that the core is well protected. Upon reduction, compound 1 was converted to its reduced diamagnetic species [Co(CNC) 2 ] + (2) having two amide donors and a low-spin Co(III) ion, which can be oxidized by air to regenerate 1.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Although many people with CF (pwCF) are treated using CFTR modulators, some are non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, in which the CFTR cDNA has been replaced, may enable a durable therapy for all pwCF. Previously, CRISPR-Cas9 with two AAVs was used to sequentially insert two halves of the CFTR cDNA and an enrichment cassette into the CFTR locus. However, the editing efficiency was <10% and required enrichment to restore CFTR function. Further improvement in gene insertion may enhance cell therapy production. To improve CFTR cDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558 which inhibit non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ). Adding AZD7648 alone improved gene insertion by 2-3-fold. Adding both ART558 and AZD7648 improved gene insertion but induced toxicity. ABCs edited in the presence of AZD7648 produced differentiated airway epithelial sheets with restored CFTR function after enrichment. Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations., Competing Interests: Declaration of Interests None of the authors have any conflict to declare.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter , against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Targeting actionable fusions has emerged as a promising approach to cancer treatment. Next-generation sequencing (NGS)-based techniques have unveiled the landscape of actionable fusions in cancer. However, these approaches remain insufficient to provide optimal treatment options for patients with cancer. This article provides a comprehensive overview of the actionability and clinical development of targeted agents aimed at driver fusions. It also highlights the challenges associated with fusion testing, including the evaluation of patients with cancer who could potentially benefit from testing and devising an effective strategy. The implementation of DNA NGS for all tumor types, combined with RNA sequencing, has the potential to maximize detection while considering cost effectiveness. Herein, we also present a fusion testing strategy aimed at improving outcomes in patients with cancer.

We developed a method to produce a soluble form of a single-chain fragment variable (scFv) targeting human epithelial growth factor receptor 2 (HER2) in Escherichia coli. By optimizing the orientations of the variable heavy (VH) and variable light (VL) domains and the His-tag, we identified the HL-His type antibody with the highest HER2-binding activity. Purification of HL-His yielded 40.7 mg from a 1 L culture, achieving >99% purity. The limit of detection was determined to be 2.9 ng, demonstrating high production yield, purity, and sensitivity. Moreover, we successfully labeled HER2 + cell lines with fluorescent dye-conjugated scFv, resulting in a significantly higher observed signal-to-background ratio, compared to that of HER2 - cell lines. This highlights the potential of these fluorescent scFvs as valuable probes for HER2 + breast cancer diagnostics. Notably, the process for the complete scFv production was streamlined and required only 4-5 days. Additionally, the product maintained its activity after freeze storage, allowing for large-scale production and a wide range of practical applications., (© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.)

Purpose: This study aimed to develop the Health Belief Model scale for premature birth prevention (HBM-PBP) and evaluated its psychometric properties in women of childbearing age., Methods: This study employed a cross-sectional design and included 724 women of childbearing age with intentions of future childbirth or in their first trimester of pregnancy. An item pool was formulated from the literature and in-depth interviews based on the health belief model. Content validation was conducted by experts and through cognitive interviews with women of childbearing age. Construct and concurrent validity and reliability were evaluated using factor analysis, Pearson's correlation analysis, and Cronbach's alpha., Results: The HBM-PBP consisted of 96 items, including perceived susceptibility (21 items, 5 subscales), severity (26 items, 5 subscales), benefits (27 items, 5 subscales), and barriers (22 items, 5 subscales). Convergent and discriminant validity were supported. The Cronbach's alpha coefficient of the domains ranged from 0.87 to 0.94., Conclusion: The HBM-PBP is a valid and reliable measurement scale with good psychometric properties. It can be used to measure health beliefs in women, either as a whole or in individual domains. Health professionals can leverage the HBM-PBP to discern women's health beliefs on premature birth, facilitating tailored interventions and educational efforts., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kim et al.)

The bearing capacity of fiber-reinforced plastic (FRP) helical screw piles is determined by the lesser of the breaking load at the bolted joint and the resistance provided by the screw tip area. In this study, compression and tensile tests were performed with the number of bolts and edge distance as variables. It showed similar strength when compared to the failure stress derived from material testing. In addition, considering load resistance performance, the optimal screw cross section was obtained through parametric analysis. Considering the structural behavior of the screw, a prediction equation was presented to design the screw cross-section as a tapered cross-section using a theoretical method. As a result of comparing the screw cross-section with the finite element analysis results, it was confirmed that the design stress and analysis stress showed an error of 1.1 MPa and were within the allowable stress of 80 MPa.

Background: Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in December 2019, it has spread rapidly, and many coronavirus disease (COVID-19) cases have occurred in Gwangju, South Korea. Viral mutations following the COVID-19 epidemic have increased interest in the characteristics of epidemics in this region, and pathogen genetic analysis is required for infection control and prevention., Methods: In this study, SARS-CoV-2 whole-genome analysis was performed on samples from patients with COVID-19 in Gwangju from 2020 to 2022 to identify the trends in COVID-19 prevalence and to analyze the phylogenetic relationships of dominant variants. B.41 and B.1.497 prevailed in 2020, the early stage of the COVID-19 outbreak; then, B.1.619.1 mainly occurred until June 2021. B.1.617.2, classified as sublineages AY.69 and AY.122, occurred continuously from July to December 2021. Since strict measures to strengthen national quarantine management had been implemented in South Korea until this time, the analysis of mutations was also able to infer the epidemiological relationship between infection transmission routes. Since the first identification of the Omicron variant in late December 2021, the spread of infection has been very rapid, and weekly whole-genome analysis of specimens has enabled us to monitor new Omicron sublineages occurring in Gwangju., Conclusions: Our study suggests that conducting regional surveillance in addition to nation-level genomic surveillance will enable more rapid and detailed variant surveillance, which will be helpful in the overall prevention and management of infectious diseases., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures., (© 2024. The Author(s).)

The social restriction measures implemented due to the COVID-19 pandemic have impacted the pattern of occurrences of respiratory viruses. According to surveillance results in the Gwangju region of South Korea, respiratory syncytial virus (RSV) did not occur during the 2020/2021 season. However, there was a delayed resurgence in the 2021/2022 season, peaking until January 2022. To analyze this, a total of 474 RSV positive samples were investigated before and after the COVID-19 pandemic. Among them, 73 samples were selected for whole-genome sequencing. The incidence rate of RSV in the 2021/2022 season after COVID-19 was found to be approximately three-fold higher compared to before the pandemic, with a significant increase observed in the age group from under 2 years old to under 5 years old. Phylogenetic analysis revealed that, for RSV-A, whereas four lineages were observed before COVID-19, only the A.D.3.1 lineage was observed during the 2021/2022 season post-pandemic. Additionally, during the 2022/2023 season, the A.D.1, A.D.3, and A.D.3.1 lineages co-circulated. For RSV-B, while the B.D.4.1.1 lineage existed before COVID-19, both the B.D.4.1.1 and B.D.E.1 lineages circulated after the pandemic. Although atypical RSV occurrences were not due to new lineages, there was an increase in the frequency of mutations in the F protein of RSV after COVID-19. These findings highlight the need to continue monitoring changes in RSV occurrence patterns in the aftermath of the COVID-19 pandemic to develop and manage strategies in response.

The reaction of Li[(TAML)Co III ]·3H 2 O (TAML = tetraamido macrocyclic tetraanionic ligand) with iodosylbenzene at 253 K in acetone in the presence of redox-innocent metal ions (Sc(OTf) 3 and Y(OTf) 3 ) or triflic acid affords a blue species 1 , which is converted reversibly to a green species 2 upon cooling to 193 K. The electronic structures of 1 and 2 have been determined by combining advanced spectroscopic techniques (X-band electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), X-ray absorption spectroscopy/extended X-ray absorption fine structure (XAS/EXAFS), and magnetic circular dichroism (MCD)) with ab initio theoretical studies. Complex 1 is best represented as an S = 1/2 [(Sol)(TAML •+ )Co III ---OH(LA)] - species (LA = Lewis/Brønsted acid and Sol = solvent), where an S = 1 Co(III) center is antiferromagnetically coupled to S = 1/2 TAML •+ , which represents a one-electron oxidized TAML ligand. In contrast, complex 2 , also with an S = 1/2 ground state, is found to be multiconfigurational with contributions of both the resonance forms [(H-TAML)Co IV ═O(LA)] - and [(H-TAML •+ )Co III ═O(LA)] - ; H-TAML and H-TAML •+ represent the protonated forms of TAML and TAML •+ ligands, respectively. Thus, the interconversion of 1 and 2 is associated with a LA-associated tautomerization event, whereby H + shifts from the terminal -OH group to TAML •+ with the concomitant formation of a terminal cobalt-oxo species possessing both singlet ( S Co = 0) Co(III) and doublet ( S Co = 1/2) Co(IV) characters. The reactivities of 1 and 2 at different temperatures have been investigated in oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions to compare the activation enthalpies and entropies of 1 and 2 .

Background: Premature birth poses significant health challenges globally, impacting infants, families, and society. Despite recognition of its contributing factors, efforts to reduce its incidence have seen limited success. A notable gap exists in the awareness among women of childbearing age (WCA) regarding both the risks of premature birth and the preventative measures they can take. Research suggests that enhancing health beliefs and self-management efficacy in WCA could foster preventive health behaviors. Interactive webtoons offer an innovative, cost-effective avenue for delivering engaging, accessible health education aimed at preventing premature birth., Objective: This protocol describes a randomized controlled trial to assess the effectiveness and feasibility of a novel, self-guided, web-based intervention-Pregnancy Story I Didn't Know in Interactive Webtoon Series (PSIDK-iWebtoons)-designed to enhance self-management efficacy and promote behaviors preventing premature birth in WCA., Methods: Using an explanatory sequential mixed methods design, this study first conducts a quantitative analysis followed by a qualitative inquiry to evaluate outcomes and feasibility. Participants are randomly assigned to 2 groups: one accessing the PSIDK-iWebtoons and the other receiving Pregnancy Story I Didn't Know in Text-Based Information (PSIDK-Texts) over 3 weeks. We measure primary efficacy through the self-management self-efficacy scale for premature birth prevention (PBP), alongside secondary outcomes including perceptions of susceptibility, severity, benefits, and barriers based on the health belief model for PBP and PBP intention. Additional participant-reported outcomes are assessed at baseline, the postintervention time point, and the 4-week follow-up. The feasibility of the intervention is assessed after the end of the 3-week intervention period. Outcome analysis uses repeated measures ANOVA for quantitative data, while qualitative data are explored through content analysis of interviews with 30 participants., Results: The study received funding in June 2021 and institutional review board approval in October 2023. Both the PSIDK-iWebtoons and PSIDK-Texts interventions have been developed and pilot-tested from July to November 2023, with the main phase of quantitative data collection running from November 2023 to March 2024. Qualitative data collection commenced in February 2024 and will conclude in May 2024. Ongoing analyses include process evaluation and data interpretation., Conclusions: This trial will lay foundational insights into the nexus of interactive web-based interventions and the improvement of knowledge and practices related to PBP among WCA. By demonstrating the efficacy and feasibility of a web-based, interactive educational tool, this study will contribute essential evidence to the discourse on accessible and scientifically robust digital platforms. Positive findings will underscore the importance of such interventions in fostering preventive health behaviors, thereby supporting community-wide efforts to mitigate the risk of premature births through informed self-management practices., Trial Registration: Korea Disease Control and Prevention Agency (KDCA) KCT0008931; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=25857., International Registered Report Identifier (irrid): DERR1-10.2196/58326., (©Sun-Hee Kim, Jennie C De Gagne. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.05.2024.)

Programmed cell death-ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single-chain fragment of variable domain (scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof-of-concept data for the effect of scFv using PDL1-expressing cells was lacking. In this study, we conducted two kinds of cell-based immunoassays, western blotting and enzyme-linked immunosorbent assay, using anti-PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell-based immunoassays to detect PDL1., (© 2024 American Institute of Chemical Engineers.)

Background: Premature birth rates have slightly increased globally, making its prevention critical for both short-term and long-term health outcomes. Various interventions have been developed in response to the multifaceted risk factors for premature birth, including internet-based programs. These programs offer accessibility and enhanced engagement; however, their overall efficacy in preventing premature births requires thorough evaluation., Objective: This systematic review aims to identify the study designs and assess the effectiveness of internet-based interventions in preventing premature birth among pregnant women., Methods: A comprehensive search of the MEDLINE, Embase, CINAHL, and Cochrane Library databases was conducted to identify randomized trials and quasi-experimental studies evaluating internet-based interventions for premature birth prevention in pregnant women. The search was inclusive, with no restrictions based on language or geographical location, allowing for a comprehensive global perspective. The time frame for the inclusion of studies extended until February 2023. The risk of bias (RoB) in each study was independently assessed by 3 authors forming pairs, using the revised Cochrane RoB tool (RoB 2) for randomized trials, as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Owing to heterogeneity in populations, measurements, and interventions, a meta-analysis was not conducted., Results: This review included 26 articles, comprising 12 intention-to-treat and 14 per-protocol studies. The overall RoB was high in most intention-to-treat studies and of some concern in most per-protocol studies. The target populations varied, including nonspecific pregnant women, those with gestational diabetes mellitus (GDM) or those at risk of GDM, individuals with anxiety or depression, and those experiencing preterm labor. Psychosocial, physiological, and wellness health outcomes were evaluated. Internet-based interventions effectively reduced stress/distress in nonspecific pregnant women but not in those experiencing preterm labor. Their effectiveness in reducing anxiety and depression varied, with inconsistent results among different groups. In women with GDM or those at risk of GDM, interventions successfully controlled fasting plasma glucose and 2-hour postprandial plasma glucose levels but did not consistently manage glycated hemoglobin levels. These interventions did not reduce the incidence of premature births across the various populations studied. The effectiveness of these internet-based interventions in addressing substance or alcohol abuse and insomnia also varied., Conclusions: Internet-based interventions show promise in improving psychosocial health and managing blood sugar to prevent premature birth, highlighting variability in effectiveness across different risk factors. Further research, including clinical trials, is vital for developing, evaluating, and disseminating effective, safe internet-based interventions. Establishing standardized measurement tools and rigorous evaluation processes is crucial for enhancing these interventions' effectiveness and reliability in clinical practice, significantly contributing to preventing premature births and improving maternal health outcomes., Trial Registration: PROSPERO CRD42021278847; https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021278847., (©Sun-Hee Kim, Jin-Hwa Park, Sun-Young Jung, Jennie C De Gagne. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 02.04.2024.)

Concrete sleepers in operation are commonly damaged by various internal and external factors, such as poor materials, manufacturing defects, poor construction, environmental factors, and repeated loads and driving characteristics of trains; these factors affect the vibration response, mode shape, and natural frequency of damaged concrete sleepers. However, current standards in South Korea require only a subjective visual inspection of concrete sleepers to determine the damage degree and necessity of repair or replacement. In this study, an impact hammer test was performed on concrete sleepers installed on the operating lines of urban railroads to assess the field applicability of the modal test method, with the results indicating that the natural frequency due to concrete sleeper damage was lower than that of the undamaged state. Furthermore, the discrepancy between the simulated and measured natural frequencies of the undamaged concrete sleeper was approximately 1.87%, validating the numerical analysis result. The natural frequency of the damaged concrete sleepers was lower than that of the undamaged concrete sleeper, and cracks in both the concrete sleeper core and the rail seat had the lowest natural frequency among all the damage categories. Therefore, the damage degrees of concrete sleepers can be quantitatively estimated using measured natural-frequency values.

A novel class of nonpeptide melanocortin type 2 receptor (MC2R) antagonists was discovered through modification of known nonpeptide MC4R ligands. Structure-activity relationship (SAR) studies led to the discovery of 17h (CRN04894), a highly potent and subtype-selective first-in-class MC2R antagonist, which demonstrated remarkable efficacy in a rat model of adrenocorticotrophic hormone (ACTH)-stimulated corticosterone secretion. Oral administration of 17h suppressed ACTH-stimulated corticosterone secretion in a dose-dependent manner at doses ≥3 mg/kg. With its satisfactory pharmaceutical properties, 17h was advanced to Phase 1 human clinical trials in healthy volunteers with the goal of moving into patient trials to evaluate CRN04894 for the treatment of ACTH-dependent diseases, including congenital adrenal hyperplasia (CAH) and Cushing's disease (CD)., Competing Interests: The authors declare the following competing financial interest(s): All authors are employees of Crinetics Pharmaceuticals, Inc., except S.H. and G.R. who were previous employees and A.K.K. and Y.Z. who were also previous employees and are currently consultants for Crinetics., (© 2024 American Chemical Society.)

This study, conducted on a group older than 60-years-of-age, sought to verify if healing garden activities control stress in older people. The experimental group performed garden activities once a week for 12 weeks, for 2 h each day, and the control group continued their daily lives. Each group's cumulative stress at the beginning and end, along with total power (TP), the standard deviation of the normal-to-normal interval (SDNN), and the root mean square differences of successive R-R intervals (RMSSD), were measured using u-Bio MACPA, a stress index meter. The analysis showed that the experimental group had a statistically significant decrease in cumulative stress, compared to the control group; and also that TP significantly increased, compared to the control group. The SDNN and RMSSD of the experimental group increased, and decreased in the control group, but the changes were not statistically significant. The fact that cumulative stress decreased and stress evaluation indicators increased shows that daily stress can be controlled through healing garden activities. However, due to the small number of participants in the experiment, its ability to be generalized to all elderly people is subject to a number of limitations. Nevertheless, I think it is meaningful that the finding that garden activities are significant in mediating stress in the elderly was verified using a scientific measurement instrument. Future studies should explore the healing effectiveness of gardens in other age groups.

Purpose: Nurses have been reported to be at an increased risk for miscarriage and preterm labor. However, there is limited knowledge regarding nurses' preconception health behaviors. Therefore, this study aimed to identify factors influencing these behaviors., Methods: One hundred sixty nurses, who were planning their first pregnancy within the upcoming year, participated in an online survey from August 11 to October 31, 2021. Data on preconception health behavior, perceived health status, pregnancy anxiety, nursing practice environment, and social support were analyzed using the t-test, Pearson correlation coefficients, and multiple regression analysis., Results: Age (р=.024), educational level (р=.010), marital status (р=.003), work experience (р=.003), satisfaction with the work department (р<.001), smoking status (р=. 039), and previous health problems related to pregnancy outcomes (р=.004) were significantly associated with nurses' preconception health behaviors. Furthermore, perceived health status (р<.001), pregnancy anxiety (р=.011), nursing practice environment (р=.003), and social support (р<.001) showed significant correlations with preconception health behaviors. Social support (β=. 28, р=.001), satisfaction with the work department (β=.23, р=.032), marital status (β=.22, р=.002), and perceived health status (β=.23, р=.002) were confirmed as factors associated with preconception health behaviors. These factors explained 40.9% of the variance in preconception health behaviors (F=6.64, р<.001)., Conclusion: Clinical nurses' preconception health behaviors were influenced by social support, perceived health status, satisfaction with the work department, and marital status. Interventions to improve clinical nurses' preconception health behaviors should target social support and perceived health status. A preconception health behavior education program considering clinical nurses' marital status and satisfaction with the workplace can also be implemented.

The reinforcing fibers in filament winding fiber-reinforced polymer (FFRP) are not arranged in the axial direction; thus, the members are vulnerable to bending and shear stresses. To address the limitations, this study evaluated FRP-concrete composite piles with reinforcing fiber arranged in circumferential directions. In particular, modular pultruded FRP (PFRP) members were fabricated with reinforcing fibers arranged in the axial and circumferential directions. The exterior of the fabricated PFRP members was reinforced with FFRP, and the flexural performance of these members was investigated through flexural strength tests. The results obtained from the flexural tests and flexural-stiffness prediction formula differed by approximately 0.72-1.36 times. A comparison between the results of the flexural test and flexural-strength prediction equation showed an error of approximately 1 to 10%.

Background: This study aimed to develop and evaluate the validity and reliability of a self-management self-efficacy for premature birth prevention (SMSE-PBP) in women of childbearing age (WCA)., Methods: Instrument development and validation were undertaken in three phases: conceptualization, item generation and evaluation of content validity, and evaluation of construct and concurrent validity and reliability. Data were analyzed using exploratory and second-order confirmatory factor analyses, and concurrent validity was examined using Pearson's correlation coefficients. The reliability was analyzed using omega hierarchical and Cronbach's ⍺., Results: Content validity was assessed by experts and cognitive interviews of WCA. The SMSE-PBP consists of a second-order 3-dimension and 10-factor scale with 60 items; therefore, the construct and concurrent validity of the SMSE-PBP were supported. The omega values were 0.93 for pre-pregnancy SMSE-PBP, 0.92 for pregnancy SMSE-PBP, and 0.94 for hospital SMSE-PBP. Cronbach's ⍺ was 0.88 for pre-pregnancy SMSE-PBP, 0.96 for pregnancy SMSE-PBP, and 0.96 for hospital SMSE-PBP., Conclusions: The SMSE-PBP scale is valid and reliable for WCA; it is helpful for WCA and health professionals to assess women's SMSE-PBP and pre-pregnancy, pregnancy, or hospital SMSE-PBP. The next steps should include assessing the relationship with pregnancy health behaviors., (© 2024. The Author(s).)

The water oxidation reaction, the most important reaction for hydrogen production and other sustainable chemistry, is efficiently catalyzed by the Mn 4 CaO 5 cluster in biological photosystem II. However, synthetic Mn-based heterogeneous electrocatalysts exhibit inferior catalytic activity at neutral pH under mild conditions. Symmetry-broken Mn atoms and their cooperative mechanism through efficient oxidative charge accumulation in biological clusters are important lessons but synthesis strategies for heterogeneous electrocatalysts have not been successfully developed. Here, we report a crystallographically distorted Mn-oxide nanocatalyst, in which Ir atoms break the space group symmetry from I 4 1 / amd to P1. Tetrahedral Mn(II) in spinel is partially replaced by Ir, surprisingly resulting in an unprecedented crystal structure. We analyzed the distorted crystal structure of manganese oxide using TEM and investigated how the charge accumulation of Mn atoms is facilitated by the presence of a small amount of Ir.

Myelodysplastic neoplasm (MDS) is a heterogeneous group of myeloid neoplasms affected by germline and somatic genetic alterations. The incidence of MDS increases with age but rarely occurs at a young age. We investigated the germline and somatic genetic alterations of Korean patients with young-onset MDS (<40 years). Among the thirty-one patients, five (16.1%) had causative germline variants predisposing them to myeloid neoplasms (three with GATA2 variants and one each with PGM3 and ETV variants). We found that PGM3 deficiency, a subtype of severe immunodeficiency, predisposes patients to MDS. Somatic mutations were identified in 14 patients (45.2%), with lower rates in patients aged < 20 years (11.1%). Nine (29%) patients had U2AF1 S34F/Y mutations, and patients with U2AF1 mutations showed significantly worse progression-free survival ( p < 0.001) and overall survival ( p = 0.006) than those without U2AF1 mutations. A UBA1 M41T mutation that causes VEXAS syndrome was identified in a male patient. In conclusion, a germline predisposition to myeloid neoplasms occurred in ~16% of young-onset MDS patients and was largely associated with primary immunodeficiencies, including GATA2 deficiency. Furthermore, the high frequency of somatic U2AF1 mutations in patients with young-onset MDS suggests the presence of a distinct MDS subtype.

In this study, a flexural test and residual stress evaluation using the aspect ratio (65 and 80) and steel fiber content (20, 30, and 40 kg/m 3 ) as variables were conducted according to the EN 14651 standard to investigate the flexural toughness of concrete reinforced with high-performance arched steel fibers. The result of the flexural test show that the residual stress was 114.5% higher in the test specimen with high curvature and high content of arched steel fibers than that in the other conditions. In addition, the energy absorption capacity of arched steel fiber-reinforced concrete increased by 138.88% compared to concrete.

The non-pharmaceutical interventions implemented to prevent the spread of COVID-19 have affected the epidemiology of other respiratory viruses. In South Korea, Human metapneumovirus (HMPV) typically occurs from winter to the following spring; however, it was not detected for two years during the COVID-19 pandemic and re-emerged in the fall of 2022, which is a non-epidemic season. To examine the molecular genetic characteristics of HMPV before and after the COVID-19 pandemic, we analyzed 427 HMPV-positive samples collected in the Gwangju area from 2018 to 2022. Among these, 24 samples were subjected to whole-genome sequencing. Compared to the period before the COVID-19 pandemic, the incidence rate of HMPV in 2022 increased by 2.5-fold. Especially in the age group of 6-10 years, the incidence rate increased by more than 4.5-fold. In the phylogenetic analysis results, before the COVID-19 pandemic, the A2.2.2 lineage was predominant, while in 2022, the A2.2.1 and B2 lineage were observed. The non-pharmaceutical interventions implemented after COVID-19, such as social distancing, have reduced opportunities for exposure to HMPV, subsequently leading to decreased acquisition of immunity. As a result, HMPV occurred during non-epidemic seasons, influencing the age distribution of its occurrences.

Purpose: This study aimed to develop and test a reward scale for hospital nurses., Methods: The initial items were identified through a literature review and focus group interviews with ten hospital nurses. The content validity of the items was evaluated by ten experts. Fifty-one items were derived from the pilot survey. Four hundred eighty-eight nurses participated in the study: 248 for exploratory factor analysis (EFA) and 240 confirmatory factor analysis (CFA). Data were analyzed using item analysis, EFA, CFA, convergent validity, known-group validity, and internal consistency using IBM SPSS Statistics 29.0 and IBM SPSS AMOS 29.0., Results: The final scale consisted of 31 items and eight factors (decent wage, opportunity to grow and develop, support for special situations, various benefits, flexibility of work, job-related achievement, reflecting career and performance, and recognition), which explained 67.3% of the total variance. The eight-subscale model was validated by CFA. Convergent validity was evaluated by analyzing correlation with intention to leave (r = -.63, p < .001) and job satisfaction (r = .54, p < .001). The known-group validity was evaluated by comparing the reward scales according to age, clinical career, income level and hospital type. The scale was found to be reliable with a Cronbach's α of .89., Conclusion: Both the validity and reliability of the reward scale for hospital nurses are verified, which can enhance the understanding of the range of rewards and may assist nurse managers in establishing an effective reward system., Competing Interests: Kim, Eun-Young has been the editorial board member of JKAN since 2022 but has no role in the review process. Except for that, no potential conflict of interest relevant to this article was reported., (© 2023 Korean Society of Nursing Science.)

Concrete sleepers used in railway engineering are subject to damage, such as cracks and breakage. Damaged concrete sleepers undergo changes to their material and structural properties, including response, mode shape, and natural frequency. Therefore, we have proposed modal testing in this study to quantitatively evaluate the structural integrity of concrete sleepers. The results of modal testing were compared with those of numerical analysis and visual inspection. In addition, an impact hammer test was conducted to evaluate the structural performance of damaged concrete sleepers. The results show that natural-frequency analysis using the modal-testing technique can usefully complement visual inspection for structural performance evaluation in the field.

Aim: This study was aimed at investigating the level of patient activation, and its association with self-care behaviours in older people with heart failure., Design: Cross-sectional secondary data analysis was conducted., Methods: We included a total of 182 Korean patients with heart failure who were aged ≥65 years for a cardiovascular outpatient clinic visit. Baseline characteristics, the Patient Activation Measure (PAM), health literacy, disease knowledge and self-care behaviours were collected via a self-administered questionnaire., Results: The proportion of patient activation at Levels 1 and 2 was 22.5% and 14.3%, respectively. Highly activated patients had a high level of health literacy, disease knowledge and self-care behaviours. After adjusting for confounding factors, we observed that patient activation was the only statiscally significant predictor of self-care behaviours among older people with heart failure. Healthcare professionals should help patients take active roles in their self-care through a comprehensive needs assessment including health literacy and disease knowledge., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited similar tumorigenicity to that of COX-2-deficient cells, despite a lower ability to suppress PGE2 synthesis by mPGES-1 depletion, indicating the presence of factors other than PGE2 that are likely to regulate tumor immunity. RNA-sequencing analysis revealed that mPGES-1 depletion reduced the expressions of collagen-related genes, which have been found to be associated with immunosuppressive signatures. In our mouse model, collagen was reduced in mPGES-1-deficient tumors, and phenotypic analysis of tumor-infiltrating lymphocytes indicated that mPGES-1-deficient tumors had fewer TIM3 + exhausted CD8 + T cells compared with COX-2-deficient tumors. CAY10678, an mPGES-1 inhibitor, was equivalent to celecoxib, a selective COX-2 inhibitor, in reinforcing anti-PD-1 treatment. Our study indicates that mPGES-1 inhibitors represent a promising adjuvant for immunotherapies in melanoma by reducing collagen deposition and T-cell exhaustion., Significance: Collagen is a predominant component of the extracellular matrix that may influence the tumor immune microenvironment for cancer progression. We present here that mPGES-1 has specific roles in regulating tumor immunity, associated with several collagen-related genes and propose that pharmacologic inhibition of mPGES-1 may hold therapeutic promise for improving immune checkpoint-based therapies., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Genomically-informed therapy requires consideration of the functional impact of genomic alterations on protein expression and/or function. However, a substantial number of variants are of unknown significance (VUS). The MD Anderson Precision Oncology Decision Support (PODS) team developed an actionability classification scheme that categorizes VUS as either "Unknown" or "Potentially" actionable based on their location within functional domains and/or proximity to known oncogenic variants. We then compared PODS VUS actionability classification with results from a functional genomics platform consisting of mutant generation and cell viability assays. 106 (24%) of 438 VUS in 20 actionable genes were classified as oncogenic in functional assays. Variants categorized by PODS as Potentially actionable (N = 204) were more likely to be oncogenic than those categorized as Unknown (N = 230) (37% vs 13%, p = 4.08e-09). Our results demonstrate that rule-based actionability classification of VUS can identify patients more likely to have actionable variants for consideration with genomically-matched therapy., (© 2023. The Author(s).)

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (p K a 7.0) of Gly-Gly-His-NH 2 (GGHa, a canonical ATCUN peptide) with thiazole (p K a 2.7) and oxazole (p K a 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest p K a among known analogues. Despite similar square-planar Cu(II)-N 4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.

This experimental study investigates the fundamental mechanical characteristics of the carbon fiber-reinforced polymer (CFRP) bars, including the tensile strength, compressive strength, shear strength, and modulus of elasticity of the CFRP bar. The properties need to be accurately determined to understand the behavior of the concrete structures reinforced with CFRP rebars. The CFRP rebar was coated with sand to enhance the adhesive strength of the concrete. Three diameters of CFRP rebar (D10, D12, and D16) were considered in accordance with ASTM provisions. A coefficient, i.e., the ratio of shear strength to tensile strength, was employed to predict the tensile strength of the CFRP rebar specimens. The test results confirm that the tensile strength of CFRP rebar is dependent on its diameter due to the shear lag effect. A coefficient in the range of 0.17 to 0.2 can be used to predict the tensile strength of CFRP rebar using shear strength.

Respiratory viruses, such as influenza, decrease airway cilia function and expression, which leads to reduced mucociliary clearance and inhibited overall immune defense. Ubiquitination is a posttranslational modification using E3 ligases, which plays a role in the assembly and disassembly of cilia. We examined the role of membrane-associated RING-CH (MARCH) family of E3 ligases during influenza infection and determined that MARCH10, specifically expressed in ciliated epithelial cells, is significantly decreased during influenza infection in mice, human lung epithelial cells, and human lung tissue. Cellular depletion of MARCH10 in differentiated human bronchial epithelial cells (HBECs) using CRISPR/Cas9 showed a decrease in ciliary beat frequency. Furthermore, MARCH10 cellular knockdown in combination with influenza infection selectively decreased immunoreactive levels of the ciliary component, dynein axonemal intermediate chain 1. Cellular overexpression of MARCH10 significantly decreased influenza hemagglutinin protein levels in the differentiated HBECs and knockdown of MARCH10 increased IL-1β cytokine expression, whereas overexpression had the reciprocal effect. These findings suggest that MARCH10 may have a protective role in airway pulmonary host defense and innate immunity during influenza infection.

Reductive amination has been widely used for manufacturing carbon-nitrogen-containing building blocks. Despite its versatility, the need for a chemical reductant or harmful hydrogen gas has limited its further utilization in modern chemical applications. Here, we report electrochemical reductive amination (ERA) to pursue sustainable synthetic routes. Faradaic efficiencies of about 83% are achieved using Cu metal electrodes. In-depth electrokinetic studies reveal the rate-determining step and overall reaction nature of ERA. Through the experiments using deuterated solvent and additional proton sources, we scrutinize the origin of protons during the ERA. Furthermore, CW-EPR analysis captures the radical intermediate species, formed during the catalytic cycle, advancing mechanistic understanding of ERA process.

Background: The intensive care unit at Asklepios Klinik Langen started a therapeutic drug monitoring (TDM) project in cooperation with the Aukamm pharmacy in Wiesbaden to measure antibiotic concentrations in the serum of intensive care patients for providing plasma level guided anti-infective therapy., Methods: The serum levels of the β‑lactam antibiotics meropenem, piperacillin, ceftriaxone and ceftazidime as well as the glycylcycline antibiotic tigecycline measured between January 1 and December 31, 2020, were evaluated retrospectively. Quantification by high performance liquid chromatography was carried out by the Aukamm pharmacy., Results: During the observation period 288 serum level measurements were carried out in 131 patients with normal as well as impaired kidney or liver function, an increased volume of distribution as well as in patients with extracorporeal organ replacement therapies. The results of the most frequently measured antibiotic piperacillin/tazobactam showed a range of 1.95-308.50 µg/ml (median 76.54 µg/ml). The median serum level for meropenem was 26.46 µg/ml (0.75-157.36 µg/ml), for ceftriaxone 33.53 µg/ml (8.38-236.26 µg/ml) and for ceftazidime 158.56 µg/ml (24.09-204.61 µg/ml). The median trough level for tigecycline was 0.42 µg/ml (0.25-3.7 µg/ml) and therefore lower compared to administration via continuous infusion (median 0.88 µg/ml, 0.26-3.81 µg/ml)., Conclusions: Therapeutic drug monitoring was successfully implemented in the intensive care unit of the Asklepios Klinik Langen. The serum level measurements showed considerable clinically relevant fluctuations in the antibiotic concentrations. Even an only rough approximation of effective antibiotic serum levels is not possible without TDM., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were codetected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Determination of the release from isolation for coronavirus disease 2019 (COVID-19) in immunocompromised patients who need additional hospitalization for treatment of non-COVID-19 related disease is important to prevent nosocomial transmission. However, there is insufficient evidence for an extended isolation period., Materials and Methods: In September 2021, when the Delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in the nephrology ward of a tertiary hospital in Gwangju, Korea. We conducted epidemiological investigations and whole-genome sequencing (WGS) of this virus., Results: A man who underwent kidney transplantation was admitted to our hospital for the treatment of acute kidney injury. He was diagnosed with asymptomatic COVID-19 infection during a pre-admission screening test on September 1, 2021 and underwent isolation. After 10 days of isolation in the COVID-19-designated ward, he was transferred to the general nephrology ward. He underwent steroid pulse therapy (September 17 to September 23, >60 mg/day prednisolone) due to acute T-cell rejection. On September 28, 2021, the first patient with COVID-19 was identified in the nephrology ward, and a rapid-response team was activated to identify additional patients with COVID-19 and prevent the spread of COVID-19. Epidemiological investigations revealed that 12 patients, two caregivers, and three healthcare workers from the nephrology ward were diagnosed with COVID-19. The WGS of specimens from 14 nosocomial outbreak samples and released an index patient exhibited the same Delta variant originating from the B.1.617.2 lineage. This hospital-acquired COVID-19 outbreak in the nephrology ward resulted in two (11.7%) deaths in patients who underwent kidney transplantation., Conclusion: We demonstrated that an immunocompromised patient can cause a nosocomial outbreak due to the prolonged shedding of infectious viruses. Prolonged isolation in patients under active immunosuppressive therapy may be necessary to prevent transmission, especially in the hospital setting., Competing Interests: SIJ is associate editor of Infect Chemother; however, she did not involve in the peer reviewer selection, evaluation, and decision process of this article. Otherwise, no potential conflicts of interest relevant to this article was reported., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Traditionally, whooping cough or pertussis caused by the obligate human pathogen Bordetella pertussis (Bp) is described as an acute disease with severe symptoms. However, many individuals who contract pertussis are either asymptomatic or show very mild symptoms and yet can serve as carriers and sources of bacterial transmission. Biofilms are an important survival mechanism for bacteria in human infections and disease. However, bacterial determinants that drive biofilm formation in humans are ill-defined. In the current study, we show that Bp infection of well-differentiated primary human bronchial epithelial cells leads to formation of bacterial aggregates, clusters, and highly structured biofilms which are colocalized with cilia. These findings mimic observations from pathological analyses of tissues from pertussis patients. Distinct arrangements (mono-, bi-, and tri-partite) of the polysaccharide Bps, extracellular DNA, and bacterial cells were visualized, suggesting complex heterogeneity in bacteria-matrix interactions. Analyses of mutant biofilms revealed positive roles in matrix production, cell cluster formation, and biofilm maturity for three critical Bp virulence factors: Bps, filamentous hemagglutinin, and adenylate cyclase toxin. Adherence assays identified Bps as a new Bp adhesin for primary human airway cells. Taken together, our results demonstrate the multi-factorial nature of the biofilm extracellular matrix and biofilm development process under conditions mimicking the human respiratory tract and highlight the importance of model systems resembling the natural host environment to investigate pathogenesis and potential therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fullen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human enteroviruses (EVs) are associated with a broad spectrum of diseases. To understand EV epidemiology, we present longitudinal data reflecting changing EV prevalence patterns in South Korea. We collected 7160 specimens from patients with suspected EV infections in ten hospitals in Gwangju, Korea during 2011-2020. RNA extraction and real-time reverse transcription polymerase chain reaction using EV-specific probes and primers were performed. EV genotyping and phylogenetic analysis were performed; EVs were detected in 3076 samples (43.0%), and the annual EV detection rate varied. EV infection rates did not differ with sex, and children aged ≤ 4 years were the most prone to EV infection; this trend did not change over time. Overall, 35 different EV types belonging to four distinctive species and rhinoviruses were identified. Although serotype distribution changed annually, the most frequently observed EVs were EV-A71 (13.1% of the cases), CVA6 (8.3%), CVB5 (7.6%), CVA16 (7.6%), CVA10 (7.5%), E18 (7.5%), E30 (7.0%), and E11 (5.0%) during 2011-2020. The predominant EV genotypes by clinical manifestation were CVB5 for aseptic meningitis; EV-A71 for hand, foot, and mouth disease cases; and CVA10 for herpangina. These results will aid the development of vaccines against EV infection and allow comprehensive disease control., (© 2023. The Author(s).)

Background: Epstein-Barr virus (EBV) quantitation and current imaging modalities are used for diagnosis and disease monitoring in Extranodal NK/T cell lymphoma (ENKTL) but have limitations. Thus, we explored the utility of circulating tumor DNA (ctDNA) as a diagnostic biomarker., Methods: Through in-depth sequencing of 118 blood samples collected longitudinally at different time points from 45 patients, we examined the mutational profile of each sample, estimated its impact on the clinical outcome, and assessed its role as a biomarker in comparison with EBV DNA quantitation., Results: The ctDNA concentration was correlated with treatment response, stage, and EBV DNA quantitation. The detection rate of ctDNA mutation was 54.5%, with BCOR (21%) being the most commonly mutated gene in newly diagnosed patients; TP53 mutation (33%) was the most prevalent in patients that experienced a relapse. Additionally, patients in complete remission exhibited a rapid clearance of ENKTL-related somatic mutations, while relapsed patients frequently presented with persisting or emerging mutations. We detected ctDNA mutations in EBV-negative patients (50%) and mutation clearance in EBV-positive patients in remission, suggesting ctDNA genotyping as an efficient complementary monitoring method for ENKTL. Additionally, mutated DDX3X (PFS HR, 8.26) in initial samples predicted poor outcome., Conclusion: Our results suggest that ctDNA analysis can be used to genotype at diagnosis and estimate the tumor burden in patients with ENKTL. Furthermore, ctDNA dynamics indicate the potential use of testing it to monitor therapeutic responses and develop new biomarkers for precision ENKTL therapy., Competing Interests: ZC, SH, HJ, JC, and S-TL are employees of Dxome co., Ltd. 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 Kim, Kim, Choi, Hwang, Jeong, Choi, Yoon, Kim, Kim, Kim, Shin, Lee and Kim.)

This study entailed performance tests to confirm the bond performance of the proposed new repair material and the pressurization effect of the developed mechanical pressurizing equipment. The physical property changes of the new repair material were reviewed by varying the mixing ratio of high aluminate cement (HAC)-mixed mortar. Strength tests were performed according to the mixing ratios of polymer and silica fume to improve the bond performance. To improve water retention, the mixing ratios of the cellulose and nylon fibers were adjusted, and the change in water retention was measured. The proposed repair material mixing ratio yielded the best performance when pressure was applied to the repair surface. Comparing the existing repair materials and the new repair material prepared by adjusting the ratios of HAC-mixed mortar, cellulose fiber, redispersible powder resin, and other factors confirmed that the new repair material has a high bond strength.

Covalently linked dimers (CLDs) and their structural isomers have attracted much attention as potential materials for improving power conversion efficiencies through singlet fission (SF). Here, we designed and synthesized two covalently ortho-linked pyrene (Py) dimers, anti- and syn-1,2-di(pyrenyl)benzene (Anti-DPyB and Syn-DPyB, respectively), and investigated the effect of molecular configuration on SF dynamics using steady-state and time-resolved spectroscopies. Both Anti-DPyB and Syn-DPyB, which have different Py-stacking configurations, form excimers, which then relax to the correlated triplet pair ((T 1 T 1 )) state, indicating the occurrence of SF. Unlike previous studies where the excimer formation inhibited an SF process, the (T 1 T 1 )'s of Anti-DPyB and Syn-DPyB are formed through the excimer state. The dissociation of (T 1 T 1 )'s to 2T 1 in Anti-DPyB is more favorable than in Syn-DPyB. Our results showcase that the molecular configuration of a CLD plays an important role in SF dynamics., (© 2023. The Author(s).)

The discovery of a novel 4-(4-aminopiperidinyl)-3,6-diarylquinoline series of potent SST2 agonists is described. This class of molecules exhibit excellent selectivity over SST1, SST3, SST4, and SST5 receptors. The compound 3-[4-(4-aminopiperidin-1-yl)-3-(3,5-difluorophenyl)quinolin-6-yl]-2-hydroxybenzonitrile ( 22 , paltusotine, formerly known as CRN00808) showed no direct inhibition of major cytochrome P450 enzymes or the hERG ion channel and had sufficient exposure in rats and excellent exposure in dogs upon oral dosing. In pharmacodynamic studies, compound 22 dose-dependently suppressed growth hormone (GH) secretion induced by an exogenous growth-hormone-releasing hormone (GHRH) challenge in both male and female rats following a single oral dose and suppressed IGF-1 levels with repeated oral administration in both rats and dogs. To the best of our knowledge, compound 22 is the first non-peptide SST2 agonist to advance to human clinical trials and is currently in Phase 3 trials in acromegaly patients and a Phase 2 trial in neuroendocrine tumor patients suffering from carcinoid syndrome., Competing Interests: The authors declare the following competing financial interest(s): All of the authors are employees of Crinetics Pharmaceuticals, Inc., except for S.H., who was a previous employee; A.M., A.K.K., and Y.Z. were previous employees and are currently consultants for Crinetics., (© 2022 American Chemical Society.)

Purpose: This study aimed to develop an emotive role-play program for nursing students focusingon high-risk pregnancy and analyze its effects on communication skills, clinical performance, andemotional intelligence., Methods: A quasi-experimental nonequivalent comparison group design was adopted with 83nursing students (experimental group, 45; comparison group, 38) who participated voluntarily in anextracurricular program. The preliminary survey was conducted on November 3 and November 4,2020, and the follow-up survey was conducted on November 12, 2020, for the comparison groupand on November 27, 2020, for the experimental group. A program that included five role-play scenarios related to induced labor, preeclampsia, premature rupture of membranes, preterm labor, andinfertility was developed by a group of experts and presented to the experimental group over 11 totalhours across 3 days. Each student participated in a role-play scenario as a patient, family member, ornurse and observed three other scenarios. The comparison group received a workbook after the follow-up evaluation. The independent t-test was performed to analyze changes in communicationskills, clinical performance, and emotional intelligence., Results: Communication skills (t=1.84, p=.035) and clinical performance (t=2.75, p=.004) significantly increased in the experimental group compared to the comparison group. A significant difference was not observed between the experimental and comparison groups for emotional intelligence(t=1.36, p=.088)., Conclusion: The emotive role-play program concerning high-risk pregnancy was effective in improving nursing students' communication skills and clinical performance and can be used in nursingeducation related to high-risk pregnancy and childbirth.

Background: The measurement invariance and latent mean differences in emotional labor across different hospital and monthly salary levels among registered nurses have never been confirmed for the Emotional Labour Scale. These issues may influence the application and efficacy of this scale in practice., Purpose: This study was developed to evaluate the factor structure of the nurses' Emotional Labour Scale and to examine the measurement invariance and latent mean differences for this scale across different hospital and monthly salary levels., Methods: Data were collected from 461 registered nurses working in four general hospitals and 12 long-term care hospitals. Confirmatory factor analysis and a multigroup confirmatory factor analysis were performed to determine the internal structure and measurement invariance of the Emotional Labour Scale., Results: The results of the confirmatory factor analysis indicate that the factor structure model proposed by the original scale fits well with our data as well as configural invariance, factor loading invariance, intercept invariance, and uniqueness invariance. Moreover, factor variance/covariance invariance across two hospital levels as well as configural invariance, factor loading invariance, and intercept invariance across two monthly salary levels were supported. The mean score for emotional control effort in the profession of general hospital nurses was lower than that for long-term care hospital nurses. No statistically significant latent mean differences were found across monthly salary levels., Conclusions/implications for Practice: The findings show the Emotional Labour Scale to be a valid and reliable tool for assessing registered nurses and also comparing the mean score for emotional labor across hospital and monthly salary levels to be feasible. The scale may contribute to the development of human resource strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

The fermentation of traditional vinegar is a spontaneous and complex process that involves interactions among various microorganisms. Here, we used a microbiome approach to determine the effects of networks, such as fermentation temperature, location, physicochemical and sensory characteristics, and bacterial profile, within traditional grain vinegar samples collected from various regions of Korea. Acetic acid and lactic acid were identified as the major metabolites of grain vinegar, and sourness and umami were determined as taste fingerprints that could distinguish between vinegar samples. Acetobacter ghanensis and Lactobacillus acetotolerans were the predominant bacterial species, and the functional composition of the microbiota revealed that the nucleotide biosynthesis pathway was the most enriched. These results reveal that vinegar samples fermented outdoors are more similar to each other than vinegar samples fermented at 30 °C, when comparing the distance matrix for comprehending bacterial networks among samples. This study may help obtain high-quality vinegar through optimized fermentation conditions by suggesting differences in sensory characteristics according to the fermentation environment.

Background/aim: Most deaths from colon cancer are due to metastasis. Recently, PGE2 was found to influence colon cancer invasion and metastasis. 15-PGDH, an enzyme that metabolizes PGE2, is known as a tumor suppressor in colonic carcinogenesis. This study investigated the effect of 15-PGDH on colon cancer metastasis., Materials and Methods: 15-PGDH expression by immunohistochemical staining, clinicopathologic features, and 5-year cancer-specific survival were investigated in colon cancer patients. Liver metastasis was examined by assaying 15-PGDH activity in an animal model. Changes in PGE2, proliferation, migration, and invasion of the colorectal cancer cell line HCT116, were examined using a 15-PGDH inhibitor (SW033291) or enhancer (CDDO-ME). The expression of genes involved in the epithelial-to-mesenchymal transition (EMT) was also studied., Results: The absence of 15-PGDH expression significantly correlated with advanced-stage, lymph node metastasis, and decreased cancer-specific survival in colon cancer patients. Inhibition of 15-PGDH increased colon cancer liver metastasis in the animal model. The 15-PGDH inhibitor, SW033291, increased PGE2 and decreased 15-PGDH expression on HCT116. However, treatment with CDDO-ME, a substance that enhances 15-PGDH, showed the opposite results. Inhibition of 15-PGDH increased cell proliferation, migration, and invasion, but activation of 15-PGDH showed the opposite effect. Inhibition of 15-PGDH also affected the EMT markers, N-cadherin, Snail, and Twist2., Conclusion: 15-PGDH inhibition increased colon cancer metastasis by inducing changes in EMT-related genes via an increase in PGE2 expression and could be a promising biomarker for anticancer treatment., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Somatic CALR mutations occur in approximately 70% of patients with JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the CALR mutant type and burden on the phenotype of CALR -mutated myeloproliferative neoplasms (MPN). Of the 510 patients with suspected or diagnosed MPN, all 49 patients detected with CALR mutations were diagnosed with ET (n = 32) or PMF (n = 17). The CALR mutant burden was significantly higher in PMF than in ET (45% vs. 34%), and type 1-like and type 2-like mutations were detected in 49% and 51% patients, respectively. Patients with MPN and type 2-like mutation showed a significantly higher median platelet count than those with type 1-like mutation. Particularly, patients with ET and type 2-like mutation had no thrombotic events, despite higher platelet counts. The effect of CALR mutant burden differed depending on the mutant type. A higher mutant burden tended to be associated with a cytopenic phenotype (i.e., lower hemoglobin levels and platelet counts) in patients with the type 1-like mutation and a proliferative hematological phenotype (i.e., higher platelet and neutrophil counts) in patients with the type 2-like mutation. This study suggests that the disease phenotype of MPN may be altered through CALR mutant burden and mutant type.