Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, Corynebacterium matruchotii, via Bioactivity-HiTES.

In the field of natural product research, the rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation, and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, the human oral bacterium, with 3120 clinical drugs as potential elicitors. As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with an IC50 value of 185.7 µM. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 µM, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 µM through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes.

Functional trait dataset of benthic macroinvertebrates in South Korean streams.

Functional traits are the result of evolution and adaptation, providing important ecological insights into how organisms interact with their environment. Benthic macroinvertebrates, in particular, have garnered attention as biomonitoring indicators for freshwater ecosystems. This study presents a functional trait dataset for benthic macroinvertebrates, comprising 447 taxa (393 at genus level, 53 at family level and one at class level) from five phyla (Annelida, Arthropoda, Mollusca, Nematomorpha, and Platyhelmenthes), categorized into nine traits related to life history, morphology, and habit. To account for variation in available trait information, we assigned confidence levels to each taxon and functional trait based on the level of evidence using fuzzy coding. Our dataset provides an important resource for understanding the ecology of benthic macroinvertebrates in South Korea, serving as a valuable baseline dataset for studying their biodiversity, conservation, and biomonitoring in freshwater ecosystems.

Risk factors for severe postpartum hemorrhage requiring blood transfusion after cesarean delivery for twin pregnancy: a nationwide cohort study.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. Twin pregnancy and cesarean delivery are well-known risk factors for PPH. However, few studies have investigated PPH risk factors in mothers who have undergone cesarean delivery for twin pregnancies. Therefore, this study investigated the risk factors associated with severe PPH after cesarean delivery for twin pregnancies. METHODS: We searched and reviewed the Korean Health Insurance Review and Assessment Service's claims data from July 2008 to June 2021 using the code corresponding to cesarean delivery for twin pregnancy. Severe PPH was defined as hemorrhage requiring red blood cell (RBC) transfusion during the peripartum period. The risk factors associated with severe PPH were identified among the procedure and diagnosis code variables and analyzed using univariate and multivariate logistic regressions. RESULTS: We analyzed 31,074 cesarean deliveries for twin pregnancies, and 4,892 patients who underwent cesarean deliveries for twin pregnancies and received RBC transfusions for severe PPH were included. According to the multivariate analysis, placental disorders (odds ratio, 4.50; 95% confidence interval, 4.09- 4.95; P < 0.001), general anesthesia (2.33, 2.18-2.49; P < 0.001), preeclampsia (2.20, 1.99-2.43; P < 0.001), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (2.12, 1.22-3.68; P = 0.008), induction failure (1.37, 1.07-1.76; P = 0.014), and hypertension (1.31, 1.18-1.44; P < 0.001) predicted severe PPH. CONCLUSIONS: Placental disorders, hypertensive disorders such as preeclampsia and HELLP syndrome, and induction failure increased the risk of severe PPH after cesarean delivery for twin pregnancy.

Anti-Inflammatory, Neurotrophic, and Cytotoxic Oxylipins Isolated from Chaenomeles sinensis Twigs.

Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A-D (1-4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including 1H NMR-based empirical rules and homonuclear-decoupled 1H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 µM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC50 = 27.4 µM).

Interpretable machine learning approach to analyze the effects of landscape and meteorological factors on mosquito occurrences in Seoul, South Korea.

Mosquitoes are the underlying cause of various public health and economic problems. In this study, patterns of mosquito occurrence were analyzed based on landscape and meteorological factors in the metropolitan city of Seoul. We evaluated the influence of environmental factors on mosquito occurrence through the interpretation of prediction models with a machine learning algorithm. Through hierarchical cluster analysis, the study areas were classified into waterside and non-waterside areas, according to the landscape patterns. The mosquito occurrence was higher in the waterside area, and mosquito abundance was negatively affected by rainfall at the waterside. The mosquito occurrence was predicted in each cluster area based on the landscape and cumulative meteorological variables using a random forest algorithm. Both models exhibited good performance (both accuracy and AUROC > 0.8) in predicting the level of mosquito occurrence. The embedded relationship between the mosquito occurrence and the environmental factors in the models was explained using the Shapley additive explanation method. According to the variable importance and the partial dependence plots for each model, the waterside area was more influenced by the meteorological and land cover variables than the non-waterside area. Therefore, mosquito control strategies should consider the effects of landscape and meteorological conditions, including the temperature, rainfall, and the landscape heterogeneity. The present findings can contribute to the development of mosquito forecasting systems in metropolitan cities for the promotion of public health.

The value of the glenohumeral joint cross-sectional area as a morphological parameter of glenohumeral osteoarthritis.

Glenohumeral joint (GHJ) space narrowing has been demonstrated to be an important morphologic parameter of glenohumeral osteoarthritis (GHO). However, the morphology of GHJ space is irregular because of degeneration of subchondral bone and articular cartilage. Thus, we devised GHJ cartilage cross-sectional area (GHJCCSA) as a new diagnostic morphological parameter to assess the irregular morphologic change of GHJ. GHJ samples were acquired from 33 patients with GHO and from 33 normal controls without evidence of GHO based on shoulder magnetic resonance imaging. T2-weighted coronal MRIs were collected at the GHJ level for all individuals. GHJCCSA and GHJ cartilage thickness (GHJCT) at the GHJ were measured on MRIs using a graphic measuring system. The GHJCCSA was measured as the whole cartilage cross-sectional area of the GHJ. The average GHJCCSA was 115.28 ±â€…17.36 mm2 in normal individuals and 61.77 ±â€…13.74 mm2 in the GHO group. The mean GHJCT was 2.06 ±â€…0.35 mm in normal individuals and 1.50 ±â€…0.28 mm in the GHO group. GHO patients had significantly lower GHJCCSA (P < .001) and GHJCT (P < .001) than normal individuals. Receiver operator characteristics curve analysis revealed that the optimal cutoff score of the GHJCCSA was 82.21 mm2, with a sensitivity of 97.0%, a specificity of 97.0%, and an area under the curve of 0.99 (95% CI: 0.97-1.00). Although GHJCCSA and GHJCT were both significantly associated with GHO, the GHJCCSA was a more sensitive measurement parameter.

Structure Revision of Balsamisides A-D and Establishment of an Empirical Rule for Distinguishing Four Classes of Biflavonoids.

Balsamisides A-D (1-4) are anti-inflammatory and neurotrophic biflavonoidal glycosides originally proposed to possess an epoxide functionality at the C-2/C-3 position. However, there are inconsistencies in their 13C NMR chemical shift values with those of previously reported analogs, indicating that reanalysis of NMR data for structures of 1-4 is necessary. Computational methods aided by the DP4+ probability technique and ECD calculations enabled structural reassignment of 1-4 to have a 2,3-dihydro-3-hydroxyfuran (3-DHF) instead of an epoxide. Additionally, two new biflavonoidal glycosides, balsamisides E and F (14 and 18), possessing a 2,3-dihydro-2-hydroxyfuran (2-DHF) and a 1,4-dioxane ring, respectively, were characterized by conventional NMR and MS data analysis as well as DP4+ and ECD methods. Systematic 13C NMR analysis was performed on the four aforementioned classes of biflavonoids with a 2- or 3-DHF, epoxide, or 1,4-dioxane. As a result, diagnostic 13C NMR chemical shift values of C-2/C-3 for rapid determination of these four biflavonoid classes were formulated, and based on this first empirical rule for (bi)flavonoids eight previously reported ones were structurally revised.

Revisiting diaphragmatic hernia of Joseon period Korean mummy by three-dimensional liver and heart segmentation and model reconstruction.

A three-dimensional (3D) segmentation and model reconstruction is a specialized tool to reveal spatial interrelationship between multiple internal organs by generating images without overlapping structures. This technique can also be applicable to mummy studies, but related reports have so far been very rare. In this study, we applied 3D segmentation and model reconstruction to computed tomography images of a Korean mummy with congenital diaphragmatic hernia. As originally revealed by the autopsy in 2013, the current 3D reconstruction reveals that the mummy's heart is shifted to the left due to the liver pushing up to thoracic cavity thorough diaphragmatic hernial defect. We can generate 3D images by calling up the data exclusively from mummy's target organs, thus minimizing the confusion of diagnosis that could be caused by overlapping organs.

Prospective comparative analysis of noninvasive body temperature monitoring using zero heat flux technology (SpotOn sensor) compared with esophageal temperature monitoring during pediatric surgery.

Maintaining body temperature in pediatric patients is critical, but it is often difficult to use currently accepted core temperature measurement methods. Several studies have validated the use of the SpotOn sensor for measuring core temperature in adults, but studies on pediatric patients are still lacking. The aim of this study was to investigate the accuracy of the SpotOn sensor compared with that of esophageal temperature measurement in pediatric patients intraoperatively. Children aged 1-8 years with American Society of Anesthesiology Physical Condition Classification I or II scheduled to undergo elective ear surgery for at least 30 min under general anesthesia were enrolled. Body core temperature was measured every 15 min after induction till the end of anesthesia with an esophageal probe, axillary probe, and SpotOn sensor. We included 49 patients, providing a total 466 paired measurements. Analysis of Pearson rank correlation between SpotOn and esophageal pairs showed a correlation coefficient (r) of 0.93 (95% confidence interval [CI] 0.92-0.94). Analysis of Pearson rank correlation between esophageal and axillary pairs gave a correlation coefficient (r) of 0.89 (95% CI 0.87-0.91). Between the SpotOn and esophageal groups, Bland-Altman analysis revealed a bias (SD, 95% limits of agreement) of -0.07 (0.17 [-0.41-0.28]). Between the esophageal and axillary groups, Bland-Altman analysis showed a bias (SD, 95% limits of agreement) of 0.45 (0.22 [0-0.89]). In pediatric patients during surgery, the SpotOn sensor showed high correlation and agreement with the esophageal probe, which is a representative core temperature measurement method.

Taxonomic and Functional Diversity of Benthic Macroinvertebrate Assemblages in Reservoirs of South Korea.

Numerous community indices have been developed to quantify the various aspects of communities. However, indices including functional aspects have been less focused on. Here, we examined how community composition varies in response to the environment and discovered the relationship between taxonomic diversity and functional diversity while considering the environment. Macroinvertebrate communities were collected from 20 reservoirs in South Korea. To characterize functional diversity, functional traits in four categories were considered: generation per year, adult lifespan, adult size, and functional feeding groups. Based on their community composition, we classified the reservoirs using hierarchical cluster analysis. Physicochemical and land use variables varied considerably between clusters. Non-metric multidimensional scaling indicated differences between reservoirs and clusters in terms of structure, functional diversity, and environmental variables. A self-organizing map was used to categorize functional traits, and network association analysis was used to unravel relationships between functional traits. Our results support the characteristics of species' survival strategies such as r- and K-selection. Functional richness exhibited a relationship with taxonomic diversity. Our findings suggest that different types of diversity could play complementary roles in identifying biodiversity. Our findings should prove useful in developing new criteria for assessing freshwater ecosystem health, as well as in evaluating and predicting future alteration of benthic macroinvertebrate communities facing anthropogenic disturbances.

Clinical application of 3D virtual and printed models for cerebrovascular diseases.

OBJECTIVE: Three-dimensional (3D) printing techniques are rapidly advancing in the medical industry and in clinical practice. We aimed to evaluate the usefulness of 3D virtual and printed models of 6 representative cerebrovascular diseases using the software we developed. METHODS: Six cases consisted of 4 intracranial aneurysms (IAs) including complex ones with intrasaccular thrombosis, large size and a skull base location; 1 cavernous malformation in the pons; and 1 arteriovenous malformation in the parietal lobe. The 3D modeling process was performed retrospectively in 3 cases and prospectively in 1 IA. Segmentation of raw data and rendering and modification for 3D virtual models were processed mostly automatically. RESULTS: Most intracranial structures were satisfactorily made, including the skull, brain, vessels, thrombus, tentorium and major cranial nerves. Based on 3D modeling, surgical plan was changed in 1 prospective IA case. However, it was still difficult to discriminate small vessels and cranial nerves, to feel a realistic tactile sense and to directly perform presurgical simulations, such as dissection, removal, clipping and microanastomosis. CONCLUSIONS: The 3D modeling was thought to be very helpful in experiencing the operative views from various directions in advance, in selecting an appropriate surgical approach, and in educating physicians and patients. With advancements in radiological resolution, processing techniques and material properties, 3D modeling is expected to simulate real brain tissues more closely.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66-3.61 in the 1H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (Kp) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 h to the last time point (AUCt) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Distribution Patterns of Odonate Assemblages in Relation to Environmental Variables in Streams of South Korea.

Odonata species are sensitive to environmental changes, particularly those caused by humans, and provide valuable ecosystem services as intermediate predators in food webs. We aimed: (i) to investigate the distribution patterns of Odonata in streams on a nationwide scale across South Korea; (ii) to evaluate the relationships between the distribution patterns of odonates and their environmental conditions; and (iii) to identify indicator species and the most significant environmental factors affecting their distributions. Samples were collected from 965 sampling sites in streams across South Korea. We also measured 34 environmental variables grouped into six categories: geography, meteorology, land use, substrate composition, hydrology, and physicochemistry. A total of 83 taxa belonging to 10 families of Odonata were recorded in the dataset. Among them, eight species displayed high abundances and incidences. Self-organizing map (SOM) classified sampling sites into seven clusters (A⁻G) which could be divided into two distinct groups (A⁻C and D⁻G) according to the similarities of their odonate assemblages. Clusters A⁻C were characterized by members of the suborder Anisoptera, whereas clusters D⁻G were characterized by the suborder Zygoptera. Non-metric multidimensional scaling (NMDS) identified forest (%), altitude, and cobble (%) in substrata as the most influential environmental factors determining odonate assemblage compositions. Our results emphasize the importance of habitat heterogeneity by demonstrating its effect on odonate assemblages.