Artificial intelligence for ultrasound microflow imaging in breast cancer diagnosis.

PURPOSE: To develop and evaluate artificial intelligence (AI) algorithms for ultrasound (US) microflow imaging (MFI) in breast cancer diagnosis. MATERIALS AND METHODS: We retrospectively collected a dataset consisting of 516 breast lesions (364 benign and 152 malignant) in 471 women who underwent B-mode US and MFI. The internal dataset was split into training (n = 410) and test datasets (n = 106) for developing AI algorithms from deep convolutional neural networks from MFI. AI algorithms were trained to provide malignancy risk (0-100%). The developed AI algorithms were further validated with an independent external dataset of 264 lesions (229 benign and 35 malignant). The diagnostic performance of B-mode US, AI algorithms, or their combinations was evaluated by calculating the area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC of the developed three AI algorithms (0.955-0.966) was higher than that of B-mode US (0.842, P < 0.0001). The AUROC of the AI algorithms on the external validation dataset (0.892-0.920) was similar to that of the test dataset. Among the AI algorithms, no significant difference was found in all performance metrics combined with or without B-mode US. Combined B-mode US and AI algorithms had a higher AUROC (0.963-0.972) than that of B-mode US (P < 0.0001). Combining B-mode US and AI algorithms significantly decreased the false-positive rate of BI-RADS category 4A lesions from 87% to 13% (P < 0.0001). CONCLUSION: AI-based MFI diagnosed breast cancers with better performance than B-mode US, eliminating 74% of false-positive diagnoses in BI-RADS category 4A lesions.

Safety of concomitant administration of 23-valent polysaccharide pneumococcal vaccine and influenza vaccine among the elderly.

BACKGROUND: The current recommendation for the elderly is to receive both a single dose 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and an annual inactivated influenza vaccine. There is a lack of post-marketing safety studies on concomitant vaccination using real-world data. We aimed to evaluate the safety of administering PPSV-23 and influenza vaccine concomitantly versus sequentially. METHODS: We performed a retrospective cohort study using a linked database that combines vaccination registry from the Korea Disease Control and Prevention Agency and claims data from the National Health Insurance Service. The study population included all those aged over 65 who received PPSV-23 at least once from Jan 1, 2016, to Dec 31, 2020. This study evaluated the 16 prespecified events of interest. Concomitant vaccination was defined as receiving both PPSV-23 and influenza vaccine on the same day. For sequential vaccination, we defined it as receiving influenza vaccination during the period from 30 to 365 days prior to the date of PPSV-23 injection. We performed 1:4 propensity score matching and estimated adjusted incidence rate ratio (aIRR) with a 95 % confidence interval (CI) using conditional Poisson regression. RESULTS: Of the 2,885,144 elderly patients who received PPSV-23 vaccination at least once from Jan 1, 2016, to Dec 31, 2020, a total 87,899 were included in the concomitant vaccination group and 1,200,091 were included in the sequential vaccination group. After adjusting for confounders, the concomitant group exhibited a significantly lower risk of allergic reactions (aIRR: 0.71, 95 % CI: 0.58-0.87), neuritis (aIRR: 0.72, 95 % CI: 0.57-0.91), and pneumonia (aIRR: 0.85, 95 % CI: 0.80-0.90), while demonstrating significantly higher risks of paralysis (aIRR: 1.63, 95 % CI: 1.05-2.52) compared to the sequential group. CONCLUSIONS: Concomitant administration of PPSV-23 and influenza vaccine in the elderly was not associated with a higher risk of most prespecified adverse events (AEs) compared to sequential vaccination. This study supports the safety of concomitant administration of PPSV-23 and influenza vaccine.

The effects of flipped learning and gamification on nursing students' patient safety education: A mixed method study.

Background: The importance of enhancing education to promote nursing students' patient safety competency is increasing. Hence, implementing diverse educational programs and assessing their outcomes is essential. Objectives: To examine the effects of flipped learning and gamification on nursing students' patient safety education. Design: A mixed-method design employing a quasi-experimental design with a pre-post control group design and qualitative thematic analysis. Methods: The study was conducted at a South Korean university in W City from September to December 2022. It included 55 s-year nursing students. The experimental group (n = 28) participated in a 30-h patient safety education course using flipped learning and gamification, whereas the control group (n = 27) received only written patient safety education materials. Learning motivation, collective efficacy, patient safety competency, and game evaluations were measured. Data were analyzed using the χ2 test, Fisher's exact test, t-test, repeated-measures multivariate analysis of covariance, repeated measure analysis of covariance, and generalized estimating equations. Self-reflection journals on game participation experiences were analyzed using qualitative thematic analysis. Results: Learning motivation scores did not differ significantly between groups for time, or interactions between groups and time, but collective efficacy and patient safety competency scores showed significant differences in the interactions between groups and time. The experimental group showed a high satisfaction score in game evaluation. Qualitative analyses were used to extract four themes-three positives: "fun and immersion differentiated from existing classes," "improved the learning outcomes and learning motivation," and "realized the value of collaboration and communication," and one negative: "feeling down due to unfamiliarity." Conclusions: This program creates positive learning experiences and enhances nursing students' collective efficacy and patient-safety competencies. It is expected to be utilized in various future nursing courses.

Improved Neural Inductivity of Size-Controlled 3D Human Embryonic Stem Cells Using Magnetic Nanoparticles.

Background: To improve the efficiency of neural development from human embryonic stem cells, human embryoid body (hEB) generation is vital through 3-dimensional formation. However, conventional approaches still have limitations: long-term cultivation and laborious steps for lineage determination. Methods: In this study, we controlled the size of hEBs for ectodermal lineage specification using cell-penetrating magnetic nanoparticles (MNPs), which resulted in reduced time required for initial neural induction. The magnetized cells were applied to concentrated magnetic force for magnet-derived multicellular organization. The uniformly sized hEBs were differentiated in neural induction medium (NIM) and suspended condition. This neurally induced MNP-hEBs were compared with other groups. Results: As a result, the uniformly sized MNP-hEBs in NIM showed significantly improved neural inductivity through morphological analysis and expression of neural markers. Signaling pathways of the accelerated neural induction were detected via expression of representative proteins; Wnt signaling, dopaminergic neuronal pathway, intercellular communications, and mechanotransduction. Consequently, we could shorten the time necessary for early neurogenesis, thereby enhancing the neural induction efficiency. Conclusion: Overall, this study suggests not only the importance of size regulation of hEBs at initial differentiation stage but also the efficacy of MNP-based neural induction method and stimulations for enhanced neural tissue regeneration.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies.

BACKGROUND: The effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. METHODS: To assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination ("control window") and the period in which immunity is achieved ("exposure windows"). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. RESULTS: Of 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64-1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22-0.34). CONCLUSION: COVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.

A long-term storable gel-laden chip composite built in a multi-well plate enablingin situcell encapsulation for high-throughput liver model.

Hydrogels are widely used as scaffold materials for constructingin vitrothree-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enablesin situcell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform,in situcell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications.

A well plate-based GelMA photo-crosslinking system with tunable hydrogel mechanical properties to regulate the PTH-mediated osteogenic fate.

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5-30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.

Pathogenic GATA2 genetic variants utilize an obligate enhancer mechanism to distort a multilineage differentiation program.

Mutations in genes encoding transcription factors inactivate or generate ectopic activities to instigate pathogenesis. By disrupting hematopoietic stem/progenitor cells, GATA2 germline variants create a bone marrow failure and leukemia predisposition, GATA2 deficiency syndrome, yet mechanisms underlying the complex phenotypic constellation are unresolved. We used a GATA2-deficient progenitor rescue system to analyze how genetic variation influences GATA2 functions. Pathogenic variants impaired, without abrogating, GATA2-dependent transcriptional regulation. Variants promoted eosinophil and repressed monocytic differentiation without regulating mast cell and erythroid differentiation. While GATA2 and T354M required the DNA-binding C-terminal zinc finger, T354M disproportionately required the N-terminal finger and N terminus. GATA2 and T354M activated a CCAAT/Enhancer Binding Protein-ε (C/EBPε) enhancer, creating a feedforward loop operating with the T-cell Acute Lymphocyte Leukemia-1 (TAL1) transcription factor. Elevating C/EBPε partially normalized hematopoietic defects of GATA2-deficient progenitors. Thus, pathogenic germline variation discriminatively spares or compromises transcription factor attributes, and retaining an obligate enhancer mechanism distorts a multilineage differentiation program.

Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their ß-glucuronidase inhibitory activity.

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.

Effect of rice milling, washing, and cooking on reducing pesticide residues.

The effects of milling, washing, and cooking on etofenprox, flubendiamide, and tebufenozide levels in brown and polished rice were investigated by HPLC using a UV detector. The reduction rates of etofenprox, flubendiamide, and tebufenozide after milling were 68.74-93.16%, 64.49-90.25%, and 69.74-92.58%, respectively, 11.64-41.44%, 31.36-65.37%, and 31.61-73.79%, respectively, after washing brown rice, and 30.85-82.08%, 52.13-83.05%, and 43.04-83.89%, respectively, after washing polished rice. The residue levels of the three pesticides in brown rice decreased after electric and pressure cooking by 56.49 and 54.41%, 75.80 and 73.42%, and 70.01 and 71.27%, respectively, and the corresponding levels in polished rice decreased after electric and pressure cooking by 85.58 and 85.82%, 86.70 and 87.06%, and 89.89 and 89.68%, respectively. In conclusion, various processing methods decrease the residual levels of etofenprox, flubendiamide, and tebufenozide in rice.

Sucrosephenylpropanoid esters and isoflavonoids isolated from Belamcanda chinensis roots and their potential anti-osteoclastogenic activity.

Repeated chromatography of the CH2Cl2 and EtOAc soluble fractions from the methanol extract of Belamcanda chinensis root yielded six new sucrosephenylpropanoid esters (1-6) and twenty-one known compounds (7-27). The structures of 1-6 were elucidated using diverse nuclear magnetic resonance (NMR) techniques and high-resolution mass spectrometry (HRMS) data analysis, together with chemical methods. All the twenty-seven isolated compounds were evaluated for their anti-osteoclastogenic activities. Preliminary screening results revealed that compounds 1 and 19 exhibited strong effects against RANKL-induced osteoclast formation in RAW264.7 cells. In addition, the treatment of mouse bone marrow macrophages (BMMs) with compounds 1 and 19 significantly decreased RANKL-induced TRAP-positive multinucleated osteoclast formation in a concentration-dependent manner without affecting cell viability. Further bioassay investigation showed that compounds 1 and 19 inhibited the expression of some osteoclast-specific marker genes and the transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in response to RANKL. To the best of our knowledge, this is the first investigation of anti-osteoclastogenic activity for compounds isolated from B. chinensis.

Influence of choroidal microvasculature dropout on progressive retinal nerve fibre layer thinning in primary open-angle glaucoma: comparison of parapapillary ß-zones and γ-zones.

BACKGROUND/AIMS: To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary ß-zones and γ-zones. METHODS: 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (ß-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable. RESULTS: Of the 294 eyes, 186 and 108 were classified as having ß-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with ß-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with ß-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone. CONCLUSIONS: The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with ß-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures.

Neutralization Testing-based Immunogenicity Analysis of Recent Prevalent Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Sublineages.

Although WHO declared the end of the public health emergency for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), XBB lineages continue to evolve and emerge globally. In particular, XBB.1.5 and XBB.1.16 are raising concerns because of their high immune evasion, leading to apprehensions regarding vaccine efficacy reduction and potential reinfection. We aimed to investigate the COVID-19 outbreak in Korea and predict the likelihood of reinfection by testing neutralizing activity against live viruses from the S clade and 19 Omicron sublineages. We found a significant risk of infection with the currently prevalent XBB lineage for individuals who were either vaccinated early or infected during the initial Omicron outbreak. Vaccinated individuals were better equipped than unvaccinated individuals to produce neutralizing antibodies for other SARS-CoV-2 variants upon infection. Therefore, unvaccinated individuals do not easily develop neutralizing activity against other variants and face the highest risk of reinfection by the XBB lineage. Our study provides important information to facilitate the development of strategies for monitoring populations that would be the most susceptible to new COVID-19 outbreaks.

Three distinct ORF1a recombinants of the SARS-CoV-2 Delta variant of concern.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergency of various lineages through mutations and recombination. In the Delta lineage, we identified recombination events in the ORF1a gene, which divided the Delta sublineages into three different genotypes (Delta R1-R3). The regional distributions of Delta R1 and Delta R2 were not correlated, indicating that recombination occurred early in the Delta outbreak. The impact of the ORF1a gene on SARS-CoV-2 transmission remains unclear; however, our findings suggest that recombination may have contributed to the evolution and global spread of the Delta lineage.

An Exploration of Nurses' Experience Following a Face-to-Face or Web-Based Intervention on Patient Deterioration.

A web-based clinical simulation program, known as FIRST2ACT (Feedback Incorporating Review and Simulation Techniques to Act on Clinical Trends), was designed to increase the efficacy of clinicians' actions in the recognition and immediate response to a patient's deterioration. This study, which was nested in a larger mixed method project, used ten focus groups (n = 65) of graduate, enrolled, registered nurses, associate nurse unit managers, and general managers/educators/coordinators from four different institutions to investigate whether nurses felt their practice was influenced by participating in either a face-to-face or web-based simulation educational programme about patient deterioration. The results indicate that individuals who were less "tech-savvy" appreciated the flexibility of web-based learning, which increased their confidence. Face-to-face students appreciated self-reflection through performance evaluation. While face-to-face simulations were unable to completely duplicate symptoms, they showed nurses' adaptability. Both interventions enhanced clinical practice by improving documentation and replies while also boosting confidence and competence. Web learners initially experienced tech-related anxiety, which gradually subsided, demonstrating healthcare professionals' resilience to new learning approaches. Overall, the study highlighted the advantages and challenges of web-based and face-to-face education in clinical practice, emphasising the importance of adaptability and reflective learning for healthcare professionals. Further exploration of specific topics is required to improve practice, encourage knowledge sharing among colleagues, and improve early detection of patient deterioration.

Genomic epidemiology of SARS-CoV-2 variants in South Korea between January 2020 and February 2023.

The Korea Disease Control and Prevention Agency (KDCA) has been conducting national genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). To monitor and characterize circulating SARS-CoV-2 variants in South Korea, 102,873 oropharyngeal/nasopharyngeal swab samples collected from patients with confirmed COVID-19 were sequenced, assigned lineages, and phylogenetically analyzed. Each wave followed a pattern of variants emerging first abroad and then spreading domestically. In 2020, B.41 lineage led the first wave, and B.1.497 dominated the second and third waves. In 2021, the fourth wave was driven by Delta (AY.69 and AY.122.5). In 2022, the fifth to seventh waves were dominated by Omicron sub-lineages BA.1/BA.1.1 and BA.2/BA.2.3, BA.5/BA.5.2, and BN.1, sequentially. The KDCA detected and monitored increasing variants in advance prior to large-scale epidemics, but the repeated emergence of new variants could threaten public health again. Therefore, it is important to continue to monitor and characterize emerging and circulating variants through national genomic surveillance.

Increased viral load in patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in the Republic of Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owing to the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2. Its Delta and Omicron variants are more transmissible and pathogenic than other variants. Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. METHODS: The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared using epidemiological data collected at the time of diagnosis. RESULTS: The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. CONCLUSION: Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load.

Complete genome sequence of pectin-degrading Flavobacteriaceae bacterium GSB9.

Pectic oligosaccharides, which are considered to be potential prebiotics, may be generated by pectin-degrading enzymes. Here, we report the complete genome sequence of the pectin-degrading marine bacterium, Flavobacteriaceae bacterium GSB9, which was isolated from seawater of South Korea. The complete genome sequence revealed that the chromosome was 3,630,376 bp in size, had a G + C content of 36.6 mol%, and was predicted to encode 3100 protein-coding sequences (CDSs), 40 tRNAs, and six 16S-23S-5S rRNAs. Genome sequence analysis revealed that this strain possesses multiple genes predicted to encode pectin-degrading enzymes. Our analysis may facilitate the future application of this strain against pectin in various industries.

Insights into the inhibitory activities of neolignans and diarylnonanoid derivatives from nutmeg (Myristica fragrans Houtt.) seeds on soluble epoxide hydrolase using in vitro and in silico approaches.

Two new neolignans, myrifralignans F-G (14 and 18), four new diarylnonanoid derivatives, myrifragranones A-D (21-24), and 18 known compounds were isolated and structurally elucidated from nutmeg (Myristica fragrans Houtt.) seeds. The absolute configurations of these secondary metabolites were determined using the electronic circular dichroism technique. The inhibitory potential of these isolated compounds on soluble epoxide hydrolase (sEH) was investigated for the first time. Among them, malabaricones B and C (19 and 20) and four new compounds 21-24 displayed inhibitory activities against sEH, with IC50 values ranging from 14.24 to 46.35 µM. Additionally, the binding mechanism, key binding interactions, stability, and dynamic behaviour of the active compounds with the sEH enzyme were analysed using in silico molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.

Phylodynamic analysis revealed that human mobility and vaccination were correlated to the local spread of SARS-CoV-2 in Republic of Korea.

Following the global emergence of the SARS-CoV-2 Alpha variant of concern (VOC) in 2020, the Delta variant triggered another wave in 2021. The AY.69 lineage, a Delta VOC, was particularly prevalent in Republic of Korea (South Korea) from May 2021 to January 2022, despite the synchronized implementation of vaccination programmes and non-pharmaceutical interventions (NPIs) such as social distancing. In this study, we used phylogeographic analysis combined with a generalized linear model (GLM) to examine the impact of human movement and vaccination on viral transmission. Our findings indicated that transmission primarily originated in South Korea's metropolitan areas, and a positive correlation was observed between total human mobility (tracked by GPS on mobile phones and estimated through credit card consumption) and viral spread. The phylodynamic analysis further revealed that non-vaccinated individuals were the primary transmitters of the virus during the study period, even though vaccination programmes had commenced three months prior to the AY.69 outbreak. Our study emphasizes the need to focus on controlling SARS-CoV-2 transmission in metropolitan regions and among unvaccinated populations. Furthermore, the positive correlation between mobility data and viral dissemination could contribute to the development of more accurate predictive models for local spread of pandemics.