A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

Innovative strategies for protein content determination in dried laver (Porphyra spp.): Evaluation of preprocessing methods and machine learning algorithms through short-wave infrared imaging.

In this study, we explored the application of Short-Wave Infrared (SWIR) hyperspectral imaging combined with Competitive Adaptive Reweighted Sampling (CARS) and advanced regression models for the non-destructive assessment of protein content in dried laver. Utilizing a spectral range of 900-1700 nm, we aimed to refine the quality control process by selecting informative wavelengths through CARS and applying various preprocessing techniques (standard normal variate [SNV], Savitzky-Golay filtering [SG], Orthogonal Signal Correction [OSC], and StandardScaler [SS]) to enhance the model's accuracy. The SNV-OSC-StandardScaler- Support vector regression (SVR) model trained on CARS-selected wavelengths significantly outperformed the other configurations, achieving a prediction determination coefficient (Rp2) of 0.9673, root mean square error of prediction of 0.4043, and residual predictive deviation of 5.533. These results highlight SWIR hyperspectral imaging's potential as a rapid and precise tool for assessing dried laver quality, aiding food industry quality control and dried laver market growth.

The Effect of Rubber-Metal Interactions on the Mechanical, Magneto-Mechanical, and Electrical Properties of Iron, Aluminum, and Hybrid Filler-Based Styrene-Butadiene Rubber Composites.

Multifunctional stretchable rubber composites are gaining attention due to their unique electrical, mechanical, and magnetic properties. However, their high production costs pose economic challenges. This study explores the use of cost-effective metal powders-iron, aluminum, and their 1:1 (vol/vol) hybrid filler-in styrene-butadiene rubber composites, varying from 10 to 20 vol%. The effects of these metal particles on the mechanical, electrical, morphological, and swelling properties were investigated. Metal particles generally act as non-reinforcing fillers but can significantly enhance the mechanical modulus, electrical, and magnetic properties based on the filler structure and the filler-rubber interactions. Iron-based composites exhibit significant electrical conductivity and excellent magnetic properties. Aluminum enhances the modulus, while the combination yields average mechanical properties with added magnetic characteristics. Iron demonstrates higher reactivity with sulfur-based crosslinking ingredients, adversely affecting the rubber matrix's crosslinks, as shown by swelling tests. This reactivity is attributed to iron's transition metal characteristics. At 20 vol%, iron-filled composites display the highest magnetic anisotropic effect on toughness (~25%) under a magnetic field by permanent magnets and excellent electrical conductivity (1.5 × 10-2 S/m). While iron significantly boosts the electrical and magnetic properties, higher filler amounts degrade the mechanical properties. These composites are currently suitable for electrical and smart mechanical applications, but incorporating reinforcing fillers could enhance their robustness for broader applications.

Impacts of Just Culture on Perioperative Nurses' Attitudes and Behaviors with regard to Patient Safety Incident Reporting: Cross-sectional Nationwide Survey.

PURPOSE: Just culture refers to a culture that encourages members of an organization to exchange important safety information and compensates them when they perform such information exchanges. The establishment of a just culture in hospital organizations might be an important means of enhancing patient safety incident reporting. This study aimed to investigate the impact of just culture on the attitudes and behaviors toward patient safety incident reporting in perioperative nurses. METHODS: A nationwide cross-sectional survey was performed using structured questionnaires. The participants were 208 perioperative nurses in tertiary general hospitals in South Korea. Data were collected by self-reported on-line questionnaires, from August to September 2020. Data were analyzed with descriptive statistics, independent t-test, chi-square test, Fisher's exact test, one-way ANOVA, Scheffé test, Pearson's correlation analysis, Spearman rank correlation analysis, hierarchical multiple regression, and hierarchical logistic regression using the SPSS WIN 23.0 program. RESULTS: Hierarchical multiple regression analysis revealed that just culture explained an additional 34.5%p of the attitudes on patient safety incident reporting. Hierarchical logistic regression analysis showed that just culture was a significant predictor of behaviors regarding patient safety incident reporting (odds ratio = 2.25, p = 0.017). The final regression model accounted for 16.0% of the behaviors regarding patient safety incident reporting. CONCLUSIONS: This study empirically shows that just culture impacted the attitudes and behaviors regarding patient safety incident reporting in perioperative nurses. This study provides an evidence about the importance of the just culture in every day nursing practice setting. Personnel and organizational efforts for improving or implementing just culture are required to ensure greater patient safety by enhancing the patient safety incident reporting of perioperative nurses in hospitals.

Dysbiosis of the gut microbiota is associated with in-hospital mortality in patients with antibiotic-associated diarrhoea: a metagenomic analysis.

BACKGROUND: The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear. METHODS: Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses. RESULTS: Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20-4.99). CONCLUSION: This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.

Predictive performance of urinalysis for urine culture results according to causative microorganisms: an integrated analysis with artificial intelligence.

Urinary tract infections (UTIs) are pervasive and prevalent in both community and hospital settings. Recent trends in the changes of the causative microorganisms in these infections could affect the effectiveness of urinalysis (UA). We aimed to evaluate the predictive performance of UA for urinary culture test results according to the causative microorganisms. In addition, UA results were integrated with artificial intelligence (AI) methods to improve the predictive power. A total of 360,376 suspected UTI patients were enrolled from two university hospitals and one commercial laboratory. To ensure broad model applicability, only a limited range of clinical data available from commercial laboratories was used in the analyses. Overall, 53,408 (14.8%) patients were identified as having a positive urine culture. Among the UA tests, the combination of leukocyte esterase and nitrite tests showed the highest area under the curve (AUROC, 0.766; 95% CI, 0.764-0.768) for predicting urine culture positivity but performed poorly for Gram-positive bacteriuria (0.642; 0.637-0.647). The application of an AI model improved the predictive power of the model for urine culture results to an AUROC of 0.872 (0.870-0.875), and the model showed superior performance metrics not only for Gram-negative bacteriuria (0.901; 0.899-0.902) but also for Gram-positive bacteriuria (0.745; 0.740-0.749) and funguria (0.872; 0.865-0.879). As the prevalence of non-Escherichia coli-caused UTIs increases, the performance of UA in predicting UTIs could be compromised. The addition of AI technologies has shown potential for improving the predictive performance of UA for urine culture results.IMPORTANCEUA had good performance in predicting urine culture results caused by Gram-negative bacteria, especially for Escherichia coli and Pseudomonas aeruginosa bacteriuria, but had limitations in predicting urine culture results caused by Gram-positive bacteria, including Streptococcus agalactiae and Enterococcus faecalis. We developed and externally validated an AI model incorporating minimal demographic information of patients (age and sex) and laboratory data for UA, complete blood count, and serum creatinine concentrations. The AI model exhibited improved performance in predicting urine culture results across all the causative microorganisms, including Gram-positive bacteria, Gram-negative bacteria, and fungi.

Hospital nurse managers' perspectives of the Magnet Recognition Program using an importance-performance analysis: A quantitative cross-sectional study.

AIM: To explore the perspectives of nursing managers in Korean hospitals on the Magnet Recognition Program using importance-performance analysis. DESIGN: A descriptive quantitative cross-sectional design with a survey methodology was used to evaluate nursing managers' perceptions of the Magnet Recognition Program criteria. METHODS: After the Magnet Recognition Program's content validity was confirmed, an online survey was administered to 150 nursing managers from 10 hospitals. The results were analysed using importance-performance analysis. RESULTS: The average importance of the questionnaire for the developed Magnet Recognition Program criteria was 3.19 ± 135 and the performance was 2.90 ± 222. Items corresponding to the areas 'Concentrate here', 'Keep up the good work', 'Possible overkill' and 'Low priority' were identified using two importance-performance analysis frames. The items corresponding to 'Concentrate here' included evidence-based nursing practice, the nursing professional practice model, nurses' participation in improving turnover rate and cases of innovation in nursing. CONCLUSION: This study highlights areas for improvement within the Magnet Recognition Program as perceived by Korean nursing managers, emphasizing evidence-based practice, professional models and nurses' involvement in turnover reduction and fostering innovation. PUBLIC CONTRIBUTION: To achieve Magnet recognition, hospitals must understand nursing managers' perspectives on the Magnet Recognition Program criteria. This study provides insights into enhancing the work environment for nurses in South Korean hospitals and lays the groundwork for developing effective Magnet certification programs. Introducing the Magnet program into South Korean hospitals may improve the overall nursing work environment and mitigate the serious problem of nursing staff turnover. REPORTING METHOD: The findings were reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.

Evaluation of the Accuracy of Estimated Endpoint Titer of NOVA View in Indirect Immunofluorescent Antinuclear Antibody Testing.

For antinuclear antibody (ANA) screening, the gold standard method is an indirect immunofluorescence assay (IIFA) using HEp-2 cells, and a serial dilution test is needed to determine the endpoint titer. We aimed to evaluate the accuracy of the estimated endpoint titer (eEPT) by the NOVA View system, by comparing it with the EPT by the serial dilution method (dEPT). The endpoint titers of a total of 1518 ANA positive cases with five major patterns including speckled, homogeneous, centromere, nucleolar, and nuclear dots patterns were determined using both the estimation function and the serial dilution method by the NOVA View system. A significant correlation between the light intensity unit (LIU) values and dEPTs was identified in all five patterns with high ρ values, ranging from 0.666 to 0.832. However, the overall exact match rate between dEPT and eEPT was 22.1% (336/1518), with the ±one-titer match rate being highest in the centromere pattern (62.8%, 81/129), and lowest in the homogeneous pattern (37.6%, 200/532). This suggests that while LIU values correlate well with dEPT, there are discrepancies in numerical agreement. Most cases that did not show an exact match, showed one-to-three-titer overestimations by eEPT. Therefore, adjusting eEPT downward significantly improved the concordance rates with dEPTs. Further investigation for an appropriate cutoff of LIU values for determining eEPT should be performed for clinical application and contribution to the standardization of the ANA titer.

Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer.

PURPOSE: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. METHODS: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. RESULTS: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. CONCLUSIONS: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning.

Standardization of an antimicrobial resistance surveillance network through data management.

Introduction: The rapid spread of COVID-19 worldwide within 2 months demonstrated the vulnerability of the world's population to infectious diseases. In 2015, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) was launched to combat antimicrobial resistance (AMR). However, there has been no comprehensive assessment of the decade-long global battle against AMR based on GLASS data. Methods: South Korea established Kor-GLASS (Korean-GLASS) to proactively monitor data quality and enable international collaborations. A unique feature of Kor-GLASS is the quality control center (QCC), which uses network hubs and ensures standardized, high-quality data through interlaboratory proficiency testing (IPT) and external quality assessment (EQA). In addition, the QCC multifaceted endeavors for integrated data quality management. Results: Since 2020, high-quality AMR data have indicated fluctuating antibiotic resistance rates in South Korea. This trend does not align with the decrease in antibiotic usage seen in humans but coincides with non-human antibiotic sales, indicating a need for greater monitoring of non-human antibiotic resistance. Comprehensive and robust management taking account of the intricate interplay among humans, animals, and the environment is essential. Kor-GLASS has been expanded into a "One Health" multiagency collaborative initiative. Discussion: Although a standardized solution is not suitable for all countries, it must align with the local context and international standards. A centralized top-down management structure such as that of the QCC is essential to ensure continuous data quality coordination. Sustained efforts and surveillance systems are crucial for monitoring and managing AMR and safeguarding human health.

Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial.

PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

Fitness costs of Tn1546-type transposons harboring the vanA operon by plasmid type and structural diversity in Enterococcus faecium.

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.

Efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with autologous bone for the treatment of long bone nonunion: A report of a prospective case series.

INTRODUCTION: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. MATERIALS AND METHODS: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. RESULTS: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. CONCLUSION: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

Stable and reusable calcium-responsive biopolymer for affinity precipitation of therapeutic antibodies.

Affinity precipitation is an attractive method for protein purification due to its many advantages, including the rapid capture of target proteins, simple processing, high specificity, and ease of scale-up. We previously reported a robust antibody purification method using Ca2+-dependent precipitation of ZZ-hCSQ2, a fusion protein of human calsequestrin 2, and the antibody-binding protein ZZ. However, the stability of this fusion protein was not sufficiently high for industrial use because the antibody recovery yield decreased to 60% after being reused 10 times. To identify a more stable calsequestrin (CSQ), we calculated Rosetta energy values for the folding stabilities of various CSQ homologs and selected human CSQ1 (hCSQ1) with lowest energy value (-992.6) as the new CSQ platform. We also identified that the linker sequence between ZZ and CSQ was vulnerable to proteases and alkaline pH by N-terminal protein sequencing. Therefore, we changed the linker to four asparagine (4N) sequences, which were shorter and less flexible than the previous glycine-rich linker. The new version of ZZ-CSQ, ZZ-4N-hCSQ1, was stable in a protease-containing conditioned medium obtained from the cultured Chinese hamster ovary cell or high pH condition (0.1M sodium hydroxide) for more than 5 days and could be reused at least 25 times for antibody purification without loss of recovery yield. The antibodies purified by ZZ-4N-hCSQ1 precipitation also showed greater purity (~33.6-fold lower host cell DNA and ~6.4-fold lower host cell protein) than those purified by protein A chromatography. These data suggest that ZZ-4N-hCSQ1 precipitation is more efficient and can achieve cost-effectiveness of up to 12.5-fold cheaper than previous antibody purification methods and can lower the production costs of therapeutic antibodies.

Comparative 1H NMR-Based Metabolomics of Traditional Landrace and Disease-Resistant Chili Peppers (Capsicum annuum L.).

Chili peppers (Capsicum annuum L.) are economically valuable crops belonging to the Solanaceae family and are popular worldwide because of their unique spiciness and flavor. In this study, differences in the metabolomes of landrace (Subicho) and disease-resistant pepper cultivars (Bulkala and Kaltanbaksa) widely grown in Korea are investigated using a 1H NMR-based metabolomics approach. Specific metabolites were abundant in the pericarp (GABA, fructose, and glutamine) and placenta (glucose, asparagine, arginine, and capsaicin), highlighting the distinct physiological and functional roles of these components. Both the pericarp and placenta of disease-resistant pepper cultivars contained higher levels of sucrose and hexoses and lower levels of alanine, proline, and threonine than the traditional landrace cultivar. These metabolic differences are linked to enhanced stress tolerance and the activation of defense pathways, imbuing these cultivars with improved resistance characteristics. The present study provides fundamental insights into the metabolic basis of disease resistance in chili peppers, emphasizing the importance of multi-resistant varieties to ensure sustainable agriculture and food security. These resistant varieties ensure a stable supply of high-quality peppers, contributing to safer and more sustainable food production systems.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

BACKGROUND & AIMS: Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. RESULTS: The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

SUnSeT: spectral unmixing of hyperspectral images for phenotyping soybean seed traits.

KEY MESSAGE: Hyperspectral features enable accurate classification of soybean seeds using linear discriminant analysis and GWAS for novel seed trait genes. Evaluating crop seed traits such as size, shape, and color is crucial for assessing seed quality and improving agricultural productivity. The introduction of the SUnSet toolbox, which employs hyperspectral sensor-derived image analysis, addresses this necessity. In a validation test involving 420 seed accessions from the Korean Soybean Core Collections, the pixel purity index algorithm identified seed- specific hyperspectral endmembers to facilitate segmentation. Various metrics extracted from ventral and lateral side images facilitated the categorization of seeds into three size groups and four shape groups. Additionally, quantitative RGB triplets representing seven seed coat colors, averaged reflectance spectra, and pigment indices were acquired. Machine learning models, trained on a dataset comprising 420 accession seeds and 199 predictors encompassing seed size, shape, and reflectance spectra, achieved accuracy rates of 95.8% for linear discriminant analysis model. Furthermore, a genome-wide association study utilizing hyperspectral features uncovered associations between seed traits and genes governing seed pigmentation and shapes. This comprehensive approach underscores the effectiveness of SUnSet in advancing precision agriculture through meticulous seed trait analysis.

Shifting trends in bloodstream infection-causing microorganisms and their clinical impact in patients with haematologic malignancies in South Korea: A propensity score-matched study.

BACKGROUND: This study aimed to identify recent trends in the epidemiology of bloodstream infection (BSI)-causing microorganisms among patients with haematologic malignancies (HMs) between 2011 and 2021, and to determine their impact on patient outcomes. METHODS: This retrospective study included 6792 patients with HMs, of whom 1308 (19.3%) developed BSI within 1 y of diagnosis. The incidence of BSI-causing microorganisms was determined, and a propensity score-matched study was performed to identify risk factors for 28-d all-cause mortality in patients with HM. RESULTS: A total of 6792 patients with HMs were enrolled. The cumulative incidence of BSI and neutropenia was significantly higher in the acute myeloid leukaemia and acute lymphoblastic leukaemia groups compared to other groups, and neutropenia and type of HMs were risk factors for the development of BSI. The annual incidence of coagulase-negative staphylococci (CoNS)-BSI decreased significantly (P < 0.001), whereas Klebsiella pneumoniae-BSI increased (P = 0.01). Carbapenem nonsusceptibility rates in K. pneumoniae isolates increased from 0.0% to 76.5% (P < 0.001). BSI caused by K. pneumoniae (adjusted odds ratio 2.17; 95% confidence interval 1.12-4.21) was associated with higher 28-d all-cause mortality compared to that caused by CoNS (adjusted odds ratio 0.86; 95% confidence interval 0.48-1.55). CONCLUSION: The pathogenic spectrum of BSI-causing bacteria in patients with HMs gradually shifted from Gram-positive to Gram-negative, especially from CoNS to K. pneumoniae. Considering that K. pneumoniae-BSI had a significantly higher 28-d mortality rate than CoNS-BSI, this evolving trend could adversely impact the clinical outcomes of patients with HMs.

Factors Associated With Health-promoting Behaviors Among Nurses in South Korea: Systematic Review and Meta-analysis Based on Pender's Health Promotion Model.

PURPOSE: Although the importance of health promotion for nurses is increasing, there is a lack of meta-analyses targeting nurses in the world. This study aimed to identify the effect sizes between the health-promoting behaviors and related variables of nurses working in Korea. METHODS: Systematic review and meta-analysis were conducted according to the PRISMA and MOOSE guidelines. The literature included in this meta-analysis was published between 1994 and 2022 in core databases such as KMbase, KISS, KoreaMed, ScienceON, DBpia, NAL, RISS, CINAHL, CENTRAL, WoS, PubMed, and hand searched. In this study, the PICO-SD framework was applied with Participants being nurses actively working in various healthcare settings across Korea, and for a more comprehensive search, intervention and comparisons were not set. The outcomes measured were nurses' health-promoting behaviors, assessed using structured tools. The study design included observational studies. The Comprehensive Meta-Analysis and the R software program were used for meta-analysis. RESULTS: In total, 50 articles were selected for the systematic review and meta-analysis. The total effect size of the 50 articles was moderate (correlation effect size [ESr] = 0.30). The individual variables presented in the 50 articles were classified into nine sub-categories according to Pender's Health Promotion Model (HPM). Among them, situational influences demonstrated the largest effect size (ESr = 0.44, number of studies [k] = 2), followed by perceived self-efficacy (ESr = 0.39, k = 10) and activity-related affect (ESr = 0.32, k = 12). CONCLUSIONS: To achieve the optimal health status of nurses through health promotion intervention programs, these effective variables - situational influences, perceived self-efficacy, and activity-related affect - should be considered when developing the intervention program for nurses. REGISTRATION: CRD42022299907.

Whole-genome sequences reveal zygotic composition in chimeric twins.

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.