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Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αβγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

Abstract Artificial intelligence (AI) is being increasingly applied in healthcare to improve patient care and clinical outcomes. We previously developed an AI model using ICD-10 (International Classification of Diseases, Tenth Revision) codes with other clinical variables to predict in-hospital mortality among trauma patients from a nationwide database. This study aimed to externally validate the performance of the AI model. Validation was conducted using a multicenter retrospective cohort study design, analyzing patient data from January 2020 to December 2021. The study included trauma patients based on specific ICD-10 codes, with other clinical variables. The performance of the AI model was evaluated against conventional metrics, including the ISS, and the ICISS (ICD-based ISS), using sensitivity, specificity, accuracy, balanced accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUROC) analyses. Data from 4,439 patients were analyzed. The AI model demonstrated high overall performance, achieving an AUROC of 0.9448 and a balanced accuracy of 85.08%, thereby outperforming traditional scoring systems such as ISS, or ICISS. Furthermore, the model accurately predicted mortality across datasets from each hospital (AUROCs of 0.9234 and 0.9653, respectively) despite significant differences in hospital characteristics. In the subset of patients with ISS

Abstract Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter’s (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses. This study revealed that one-point mutated IL-32θ (A94V) plays an important role in attenuating skin inflammation. IL-32θ (A94V) inhibited PM-induced COX-2, a pro-inflammatory cytokine GM-CSF and CYP1A1 in PM-exposed human keratinocytes HaCaT cells. IL-32θ (A94V) modulating effects were mediated via down-regulating ERK/p38/NF-κB/ AP-1 and AhR/ARNT signaling pathways. Our study indicates that PM triggers skin inflammation by upregulating COX-2, GM-CSF and CYP1A1 expression. IL-32θ (A94V) suppresses the expressions of COX-2, GM-CSF, and CYP1A1 by blocking the nuclear translocation of NF-κB and AP-1, as well as inhibiting the activation of the AhR/ARNT signaling pathway. Our findings offer valuable insights into developing therapeutic strategies and potential drugs to mitigate PM-induced skin inflammation by inhibiting the ERK/p38/NF-κB/AP-1 and AhR/ARNT signaling pathways.

Chytridiomycota is the most species-rich phylum of basal lineage fungi with a worldwide distribution. Its species constitute essential components of freshwater ecosystems. However, the diversity of this group in Korea remains understudied. A survey of Chytridiales and Rhizophydiales fungi was conducted in soil and freshwater environments in Korea, and seven strains were isolated. Based on morphological and molecular data, a previously unidentified, novel Rhizophydium species was discovered, designated Rhizophydium multiplex sp. nov. In addition, Chytriomyces hyalinus and Globomyces pollinis-pini were isolated for the first time in Korea. Detailed descriptions and illustrations of the three species are provided. This study highlights the potential diversity of chytrid fungi in Korea.

In the advanced landscape of materials science, particularly in the development of ceramic materials, artificial intelligence (AI) emerged as a transformative tool for accelerating innovation. This study proposed a comprehensive analysis of the Transformer-based Inverse Learning model to optimize component and process recommendations. K-Nearest Neighbors (KNN) imputation was first applied, improving data accuracy and completeness to address data gaps. Subsequently, Variational Autoencoders (VAE) were used for data augmentation, enriching the dataset’s diversity. The Transformer model, leveraging this enhanced data, demonstrated strong predictive performance, achieving an R2 score of 0.966 for component analysis and an outstanding R2 score of 0.982 for process analysis in Barium Titanate (BaTiO3) material data. These results show the effectiveness of combining imputation, augmentation, and advanced AI modeling in capturing complex material properties. The study highlights the potential of AI-driven methodologies to significantly improve prediction accuracy in material discovery, offering valuable insights for developing future ceramic materials.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Accurate Object distance estimation with recognition is essential for various computer vision (CV) applications, including autonomous vehicles and many military operations. While significant advancements have been achieved in supervised and self-supervised techniques for short-range and real-time recognition, existing methods often focus on monocular depth estimation. They are constrained by the limitations of supervised deep learning (DL) models. Taking advantage of temporal information from sequential frames through attention mechanisms to address these challenges offers a promising avenue for enhancing recognition quality. For a real-time military object recognition system, this study integrates RGB images along Depth maps from the KITTI Dataset for short-range measurements. Due to the limitation of the KITTI dataset, a synthetic dataset is generated for long-range object recognition. YOLOv8 is trained for real-time object detection, utilizing the KITTI and a synthetic dataset for long-range analysis. Our method achieves an RMSE of 1.24 meters and an RMSE(log) of 0.18 for depth estimation, outperforming existing approaches. Furthermore, the system accurately detects objects at distances of up to 250 meters, with an average inference time of 15 ms per frame for short-range detection and 18 ms per frame for long-range detection. Comparative evaluations against state-of-the-art methods demonstrate our approach’s superior accuracy and efficiency.

Background: Jeoryeong-tang (JRT) was first recorded in Shanghanlun. It is composed of Polyporus Sclerotium, Poria, Asini Corii Colla, Alisma Rhizome, and Talcum at the same weight ratio. These medicinal materials are known for diuretic and hemostatic effects and have been traditionally used to treat kidney and bladder diseases. However, their potential therapeutic effects on colon diseases, particularly inflammatory bowel disease (IBD), have not been extensively studied. Therefore, this study aimed to investigate the therapeutic efficacy of JRT in IBD and explore its underlying anti-inflammatory mechanisms using a murine model of colitis induced by dextran sulfate sodium (DSS). Methods: Mice were treated with 3.0 % or 2.5 % DSS for 6 days to induce colitis and JRT extract was then administered at a low level of 40 mg/kg (JRT-L), a medium level of 120 mg/kg (JRT-M), or a high level of 400 mg/kg (JRT-H) once a day. During the administration period, clinical disease activity index (DAI) reflecting survival rate, diarrhea, bloody stool, and weight loss rate was evaluated. The degree of colonic tissue damage was scored and evaluated through hematoxylin and eosin staining. Cyclooxygenase-2 (COX-2), p-STAT3 and p-ERK expression were examined with immunohistochemistry. Tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and -1β levels were analyzed using a cytokine enzyme-linked immunosorbent assay. Results: Among mice treated with 3.0 % DSS, JRT-M significantly improved the survival rate compared to other treatments as a result of observation for a total of 14 days. While, in the 2.5 % DSS-treated model, the average body weights of mice in both of JRT-M and JRT-H groups were significantly higher than that in the DSS group. In addition, the JRT-M group showed significantly lower DAI score than that in the DSS group. As a result of evaluating the extent of colon tissue damage, JRT-M and JRT-H groups both showed significantly lower inflammatory index and thinner muscular externa thickness than the DSS group. The expression of COX-2, p-STAT3 and p-ERK in colon tissue were significantly suppressed in JRT-M and JRT-H groups compared to that in the DSS group. Moreover, serum TNF-α was significantly suppressed in the JRT-H group compared to that in the DSS group. Conclusions: Jeoryeong-tang has a promising therapeutic potential for treating IBD through its anti-inflammatory properties. Findings of this study suggest that JRT could be a valuable candidate for further clinical investigations in the treatment of IBD.

Background and Objectives The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments. Methods In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments. Results We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied). Conclusion Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.

Abstract Background In aquaculture, the secretions of cultured organisms contribute to the development of aquatic antibiotic resistance. However, the antibiotic-induced changes in fish feces remain poorly understood. This study aimed to assess the short-term dynamics of fecal microbiome and antibiotic resistance in juvenile rainbow trout (Oncorhynchus mykiss) upon antibiotic treatment and withdrawal period. Methods Fish were orally administered diets supplemented with oxytetracycline (OTC) or sulfadiazine/trimethoprim (SDZ/TMP) for 10 consecutive days, followed by a 25-day withdrawal period. Fecal samples were collected before antibiotic treatment (day 0), and at 1, 3, 7, and 10 days post antibiotic administration (dpa), as well as 1, 3, 7, 14, and 25 days post antibiotic cessation (dpc). The fecal microbiome community was profiled using both culture-dependent and -independent methods. The relative abundance of antibiotic resistance genes (ARGs) and the class 1 integron-integrase gene (intI1) in the feces were quantified using real-time PCR. Results Antibiotic treatment disrupted the fecal microbial communities, and this alteration persisted even after antibiotic cessation. Moreover, OTC treatment increased the relative abundance of tet genes, while sul and dfr genes increased in the SDZ/TMP-treated group. Notably, Flavobacterium, Pseudomonas, and Streptococcus exhibited a significant correlation with the abundance of ARGs, suggesting their potential role as carriers for ARGs. Conclusion This study demonstrates the antibiotic-induced changes in the fecal microbiome and the increase of ARGs in rainbow trout feces. These findings provide novel insights into the dynamics of microbiome recovery post-antibiotic cessation and suggest that fish feces provide a non-invasive approach to predict changes in the fish gut microbiome and resistome.

Abstract Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness.

Abstract The unique saddle articulation of the trapeziometacarpal joint allows for a wide range of motion necessary for routine function of the thumb. Inherently unstable characteristics of the joint can lead painful instability. In this study, we modified a surgical dorsal ligament reconstruction technique for restoring trapeziometacarpal joint stability. We evaluated and compared the biomechanical efficacy of our reconstruction technique with that of dorsoradial capsulodesis by creating a cadaveric model of rotational instability. Twenty-four specimens were subjected to dorsoradial capsulodesis (n = 12) or dorsoradial ligament reconstruction using the abductor pollicis longus (APL) (n = 12). The modified dorsoradial ligament reconstruction entailed detaching one distally based slip of the APL. The harvested tendon’s proximal end was passed through a bone tunnel created at the dorsoradial ridge of the trapezium. A suture anchor was inserted at the dorsal base of the metacarpal bone. The tendon stump was sutured to the metacarpal bone using fiber wire in figure-of-eight configuration. The load to failure of the trapeziometacarpal joint under compression was higher in the reconstruction group (p = 0.003). The improvement in the rotational arc (observed in all specimens) was significantly greater in the reconstruction group than the capsulodesis group (p = 0.003). Our technique reconstructs only the necessary ligament, requires a smaller incision and relatively simpler surgical procedure, and enables precise determination of the insertion and exit sites of the tendon, making it a promising treatment for trapeziometacarpal joint instability.

Background: This study aimed to evaluate the effects of kombucha on the surface of composite resins and to examine the degradation-inhibiting effect of adding calcium to kombucha. Methods: Six experimental groups were established, with three types of liquid kombucha: one with 3% added calcium, carbonated water as a positive control, and mineral water as a negative control. The pH and titratable acidity values of the experimental groups were measured. The samples were filled with condensed composite resin and placed in the experimental drinks for 5, 15, 30, and 60 minutes. The Vickers microhardness of the surface was measured before and after immersion, and the changes were compared. Results: The pH values of the experimental group were I’m alive (2.87±0.02), Hollys (2.95±0.01), Ediya (2.99±0.01), I’m alive +3% Ca (4.09±0.01), carbonated water (4.66±0.01), and mineral water (7.67±0.02). I’m alive (–12.35) showed the largest reduction in surface hardness, followed by Hollys (–9.78), carbonated water (–7.97), I’m alive +3% Ca (–7.82), Ediya (–7.60), and mineral water (–1.56). In the Vickers microhardness measurements, all experimental groups, except for the mineral water group, showed significant differences (p＜0.05). The scanning electron microscope results showed that the experimental group and positive control had rough surfaces and micropores. Conclusion: The surface hardness was significantly reduced in all experimental groups except for water. In particular, in the case of kombucha with low pH, the reduction rate increased, weakening the physical properties of the material. In addition, the reduction rate of surface hardness was lower in kombucha with added calcium, and it is believed that drinking kombucha containing calcium can minimize the erosion of dental materials.

Background: Angelica gigas Nakai Root (AGN) is a medicinal plant with various therapeutic effects. The purpose of this study was to determine the effect of a 70% ethanol extract of AGN (EAGN) on biofilm formation and metabolic activities of Streptococcus mutans according to exposure to xylitol and sucrose, and to confirm the possibility of using EAGN as an effective medicinal plant-derived anti-cariogenic substance. Methods: Bacterial growth and disk diffusion test were performed to confirm the antibacterial effects of EAGN against S. mutans in a brain-heart infusion (BHI) medium containing 1% xylitol and 1% sucrose, measurement of. Biofilm formation was confirmed using a biofilm formation assay and glycosyltransferase (GTF) activity. Metabolic activity was evaluated using a calcium assay, acid production assay and buffering capacity measurements. Results: EAGN showed antibacterial activity against S. mutans in a BHI medium containing 1% xylitol and sucrose. At 3.75 and 5.0 mg/ml EAGN in S. mutans-inoculated medium containing 1% sucrose, the antibacterial effect was greater than those of BHI only and 1% xylitol BHI media. In S. mutans-inoculated medium containing 1% sucrose, cariogenic biofilm formation, GTF activity, released Ca2+ levels, and acidogenicity were significantly increased, but the buffering capacity was significantly decreased. According to EAGN treatment, cariogenic biofilm formation, GTF activity, measured released Ca2+ levels, and acidogenicity were significantly decreased and buffering capacity was significantly increased. An EAGN over 3.75 mg/ml significantly reduced biofilm formation and Ca2+. Regardless of the concentration of EAGN, acidogenicity was reduced, and the buffering capacity was increased. Conclusion: EAGN is a safe natural anti-cariogenic substance that inhibits biofilm formation by directly inhibiting GTF activity and adjusts the microenvironment for tooth remineralization by reducing Ca2+ and acidogenicity and increasing the buffering capacity according to exposure to sucrose in S. mutans.

Background: This study aimed to investigate the erosive potential of powdered vitamin C on the bovine enamel tooth surface. Methods: The experiment included five groups: Lemona, Vitagran, Korea Eundan, Coca-Cola (positive controls), and artificial saliva (negative controls). The pH and titratable acidity were measured. Bovine enamel specimens were immersed in the experimental solutions for 15 minutes each day for 7 days. The surface microhardness was measured using the Vickers hardness number before immersion and on the 1st, 3rd, 5th, and 7th days. The surfaces of the bovine enamel specimens were observed by scanning electron microscopy (SEM). Results: The pH of the experimental groups was as follows: Lemona (2.04±0.04) had the lowest pH, followed by Vitagran (2.56±0.01), the positive control group Coca-Cola (2.60±0.03), Korea Eundan (3.14±0.02), and the negative control group artificial saliva (7.06±0.05). Surface microhardness decreased significantly during the immersion period (p＜0.001). The largest surface microhardness reduction value was shown in Lemona (–201.22±20.60), followed by Vitagran (–190.02±14.73), Korea Eundan (–189.27±27.14), Coca-Cola (–99.28±17.21), artificial saliva (–10.99±9.94). According to the SEM findings, the experimental and positive control groups exhibited rough surfaces with micropores, whereas the negative control group exhibited smooth surfaces before specimen immersion. Conclusion: Consuming powdered vitamin C at a low pH may degrade the enamel surface. To reduce the erosive effect, it is recommended to rinse the mouth with water and brush the teeth after an hour.

Background Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors. Methods Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, long-term clinical outcomes, and prognostic factors for recurrence and mortality were analyzed. Results The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group. Conclusion Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Objectives: To determine growth inhibitory and anti-cancer effects of Cannabigerol (CBG) in human colorectal cancer cells.Methods: Anti-proliferative effect of CBG was examined using MTT assay and two colorectal cancer cells (SW480 and LoVo cells). Cell death ratio was analyzed using Annexin V/ PI staining experiment. Cell cycle distribution was analyzed using flow cytometry. We also performed western blot analysis on apoptotic marker proteins.Results: CBG showed growth inhibitory effect in colorectal cancer cells using MTT assay. IC50 concentration of CBG was 34.89 μM in SW480 cells and 23.51 μM in LoVo cells. Annexin V/PI staining showed that CBG treatment increased apoptotic cells from 4.8% to 31.7% in SW480 cells and from 7.7% to 33.9% in LoVo cells. Flow cytometry confirmed that CBG increased sub G1 population via G1 arrest in both SW480 and LoVo cells. Western blot analysis showed that CBG increased expression levels of cell death-related proteins such as cleaved PARP-1, cleaved caspase 9, p53, and caspase 3.Conclusion: CBG treatment shows antiproliferative activity and causes apoptosis of colorectal cancer cells, suggesting that CBG is applicable as a promising anticancer drug.

Vaccinium oldhamii Miquel 1866 is a deciduous shrub native to Northeast Asia, including Korea, China, and Japan. Its polyphenol-rich edible berries may aid in managing chronic diseases. Despite its importance, the mitogenome of this species remains understudied. This study assembled the complete mitogenome, consisting of 626,941 bp with 45.34% GC content, using NOVOPlasty and Illumina sequencing. The genome includes 38 protein-coding genes, 24 tRNA genes, and three rRNA genes. Phylogenetic analysis revealed a close relationship with V. macrocarpon. This mitogenome provides a valuable resource for phylogenomic studies and insights into evolutionary relationships within the Vaccinium genus and the Ericales order. Vaccinium oldhamii Miquel 1866 is a deciduous shrub in the Ericales and the Ericaceae and is native to Northeast Asia including Korea, China, and Japan. Particular emphasis has been placed on the edible berries of Vaccinium species and their use as dietary supplements. Specifically, the edible berries of V. oldhamii contain high levels of polyphenols, which may aid in preventing and managing chronic diseases. However, the mitogenome sequence of this species, a valuable resource for studying evolutionary relationships and genetic diversity within the Vaccinium genus, has not been thoroughly investigated. In this study, the complete mitochondrial genome sequence of V. oldhamii was assembled into 626,941 bp circular nucleotides with a GC content of 45.34% using NOVOPlasty and Illumina sequencing data. The comprehensive annotation for mitogenome of V. oldhamii revealed that the mitogenome comprises 38 known protein-coding genes, 24 tRNA genes, and three rRNA genes. Phylogenetic analysis using ML method showed that this species is closely related to the V. macrocarpon. This newly sequenced mitochondrial genome offers a valuable resource for phylogenomic analysis and will enhance our understanding of evolutionary relationships within the Ericales order and/or the Vaccinium genus.

Abstract Adjunctive rosuvastatin for rifampicin-susceptible pulmonary tuberculosis (rs-PTB) shows no effect on microbiological or radiological outcomes in a phase IIb randomised, controlled trial (NCT04504851). We explore the impact of adjunctive rosuvastatin on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging in a sub-study of 24 participants. Changes in standardised uptake value (SUVmax, SUVmean), Total Metabolic Volume, (TMV), Total Lesion Glycolysis (TLG), cavity diameter and volume, between week 0 and week 8 post-randomisation, are evaluated. Here we show no evidence of difference in the reduction in TLG [median 65.8% for the rosuvastatin group (Q1, Q3 38.6, 94.5) vs 64.3% for standard tuberculosis treatment group (Q1, Q3 −20.0, 81.7), P = 0.32], reduction in cavity volume on CT [median 3.2 cm3 (IQR 11.1, 0.5) for rosuvastatin, 2.2 cm3 (IQR 4.6, 0.7) for control (p = 0.72)], or any other PET-CT parameter measured. We show that the first 8-weeks of standard tuberculosis treatment results in a reduction in the volumetric indices (TLG and TMV), but had little change in SUVmax or SUVmean. Change in TLG and TMV holds promise as biomarkers of tuberculosis treatment response: future PET-CT studies should evaluate their role in predicting relapse-free cure, and the overall role of 18F-FDG-PET-CT as a tool for early-phase tuberculosis clinical trials.

Abstract Efficient light generation from triplet states of organic molecules has been a hot yet demanding topic in academia and the display industry. Herein, we propose a strategy for developing triplet emitter by creating heterostructures of organic chromophores and transition metal dichalcogenides (TMDs). These heterostructures emit microsecond phosphorescence at room temperature, while their organic chromophores intrinsically exhibit millisecond phosphorescence under vibration dissipation-free conditions. This enhancement in phosphorescence is indicative of significantly enhanced spin-orbit coupling efficiency through coupling with TMDs. Through detailed studies on these hybrids from various perspectives, we elucidate key features of each component essential for generating microsecond triplet emission, including 2H-TMDs with heavy transition metals and aromatic carbonyl with an ortho-hydroxy group. Our intriguing findings open avenues for exploring the universal applicability of fast and stable hybrid triplet emitters.

Developing new strawberry varieties with high level of disease resistance and superior fruit quality is critical for strawberry production. Despite the complexity of the octoploid strawberry genome, recent advances in genomics and DNA sequencing technologies have allowed us to identify causal sequence variants associated with specific phenotypes. These have enabled the development of new and improved DNA markers for integration in marker-assisted breeding (MAB) efforts. The use of MAB has significantly improved the efficiency of stacking loci responsible for disease resistance and fruit quality characteristics. The “Strawberry DNA Testing Handbook” is currently accessible in the Genome Database for Rosaceae and has been an essential resource for the national and international strawberry research community. Based on the information provided in the handbook, the UF strawberry breeding program implemented seedling selection from 2021 to 2023, retaining 25.3%, 19.2%, and 37.9% of seedlings for further evaluation in each respective year. In this report, we provide updates on DNA markers associated with disease resistance and fruit quality traits. Additionally, we demonstrate the practical implementation of these markers in high-throughput marker-assisted selection and their potential to enhance strawberry breeding.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells present in adult tissues that are recognized as promising candidates for cell therapy due to their ease of access, straightforward isolation, and capacity for bio-preservation with minimal loss of potency. However, the clinical application of MSCs faces significant challenges, such as donor site morbidity, underscoring the need for alternative sources. Recent studies have suggested that inferior turbinate tissues, which are commonly removed during turbinate surgery, may be a viable donor site for MSCs. Turbinate surgery is a safe and effective procedure frequently performed to alleviate nasal obstruction, a prevalent chronic condition treated by otolaryngologists. This implies that harvesting MSCs from turbinate tissue for tissue engineering and regenerative medicine could serve as a simple, minimally invasive method with faster healing and minimal risk of morbidity or scarring at the donor site. This review highlights previous research indicating that MSCs derived from human turbinate tissues maintain their stability and demonstrate multi-differentiation potential. Therefore, the turbinate could be an alternative to traditional MSC sources for producing functionally competent cells for future clinical applications.

Abstract The application of deep learning techniques for the analysis of neuroimaging has been increasing recently. The 3D Convolutional Neural Network (CNN) technology, which is commonly adopted to encode volumetric information, requires a large number of datasets. However, due to the nature of the medical domain, there are limitations in the number of data available. This is because the cost of acquiring imaging is expensive and the use of personnel to annotate diagnostic labels is resource-intensive. For these reasons, several prior studies have opted to use comparatively lighter 2D CNNs instead of the complex 3D CNN technology. They analyze using projected 2D datasets created from representative slices extracted from 3D volumetric imaging. However, this approach, by selecting only projected 2D slices from the entire volume, reflects only partial volumetric information. This poses a risk of developing lesion diagnosis systems without a deep understanding of the interrelations among volumetric data. We propose a novel 3D-to-2D knowledge distillation framework that utilizes not only the projected 2D dataset but also the original 3D volumetric imaging dataset. This framework is designed to employ volumetric prior knowledge in training 2D CNNs. Our proposed method includes three modules: (i) a 3D teacher network that encodes volumetric prior knowledge from the 3D dataset, (ii) a 2D student network that encodes partial volumetric information from the 2D dataset, and aims to develop an understanding of the original volumetric imaging, and (iii) a distillation loss introduced to reduce the gap in the graph representation expressing the relationship between data in the feature embedding spaces of (i) and (ii), thereby enhancing the final performance. The effectiveness of our proposed method is demonstrated by improving the classification performance orthogonally across various 2D projection methods on two datasets from the 123I-DaTscan SPECT and 18 F-AV133 PET from Parkinson’s Progression Markers Initiative (PPMI). Notably, when our approach is applied to the FuseMe approach, it achieves an F1 score of 98.30%, which is higher than that of the 3D teacher network (97.66%).

In the rapidly evolving healthcare environment, radiologists strive to establish their rightful place. Thus, there is a need for enhanced outpatient and clinical education within the Department of Radiology and exploration of its methodologies. Accordingly, the Korean Society of Radiology established a task force to investigate the clinical and outpatient practice status of radiologists overseas, current state of related education, involvement of other specialties in radiologic practices and education in Korea, and clinical and outpatient practice status among Korean radiologists. Furthermore, a survey on clinical competency enhancement was conducted among the members of the Korean Society of Radiology. These findings suggest the need for visibility and clinical competency enhancement in radiologists and methodologies for strengthening clinical competencies.

Abstract We evaluate the effects of rebuilding a mackerel fishery in Korea using a bioeconomic computable general equilibrium (CGE) model. The effects include three different measures of the benefits of the stock rebuilding—the fishing sector’s rent, its value-added, and the aggregate regional welfare. In the baseline simulation, we run 20 scenarios over 30 years, depending on the magnitude of the annual percentage reduction in the harvest required to recover the stock to the target level (Bmsy). We find that the percentage reductions that yield the largest increase in the three measures of the benefits are 70% (yielding the largest rent increase), 35% (yielding the largest value-added increase), and 20% (yielding the largest aggregate welfare gain), respectively, to rebuild the stock to the target level. Results shed some light on which measure the policymakers should use when implementing a stock rebuilding policy.

Abstract Microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits high tumor-infiltrating lymphocyte (TIL) density. Despite the recognized significance of the immune microenvironment in MSI-H GC, our understanding of TIL remains limited. This study aimed to investigate the clinicopathologic and prognostic implications of T cell subsets in MSI-H GC. Single immunohistochemistry (IHC) for CD8, TCF1, and CD103, and double IHC for CD8/TCF1 and CD8/CD103 were performed in 382 surgically resected MSI-H GC samples. Densities of single or double positive immune cells were quantified and correlated with clinicopathologic features and overall survival (OS). TCF1 + cell densities showed weak correlations with CD8 + and CD103 + cell densities, while CD8+/TCF1 + cell density moderately correlated with CD8+/CD103 + cell density (R2 = 0.539, p 0.05). Notably, elevated CD8+/TCF1 + cell density and a high CD8+/TCF1 + to CD8 + ratio correlated with less aggressive clinicopathologic features and improved OS (p = 0.017 and 0.001, respectively). Multivariable Cox-regression identified CD8+/TCF1 + to CD8 + ratio as an independent prognostic factor (p = 0.028). We demonstrated the prognostic significance of CD8+/TCF1 + to CD8 + ratio using double IHC in a large cohort of MSI-H GC.

Abstract HEPN–MNT, a type VII TA module, comprises the HEPN toxin and the MNT antitoxin, which acts as a nucleotidyltransferase that transfers the NMP moiety to the corresponding HEPN toxin, thereby interfering with its toxicity. Here, we report crystal structures of the Legionella pneumophila HEPN–MNT module, including HEPN, AMPylated HEPN, MNT, and the HEPN–MNT complex. Our structural analysis and biochemical assays, suggest that HEPN is a metal-dependent RNase and identify its active site residues. We also elucidate the oligomeric state of HEPN in solution. Interestingly, L. pneumophila MNT, which lacks a long C-terminal α4 helix, controls the toxicity of HEPN toxin via a distinct binding mode with HEPN. Finally, we propose a comprehensive regulatory mechanism of the L. pneumophila HEPN–MNT module based on structural and functional studies. These results provide insight into the type VII HEPN–MNT TA system.

Abstract Sensations of the internal state of the body play crucial roles in regulating the physiological processes and maintaining homeostasis of an organism. However, our understanding of how internal signals are sensed, processed, and integrated to generate appropriate biological responses remains limited. Here, we show that the C. elegans PIEZO channel, encoded by pezo-1, regulates food movement in the intestine by detecting food accumulation in the anterior part of the intestinal lumen, thereby triggering rhythmical movement of the pharynx, referred to as the pharyngeal plunge. pezo-1 deletion mutants exhibit defects in the pharyngeal plunge, which is rescued by PEZO-1 or mouse PIEZO1 expression, but not by PIEZO2, in a single isolated non-neuronal tissue of the digestive tract, the pharyngeal-intestinal valve. Genetic ablation or optogenetic activation of this valve inhibits or induces the pharyngeal plunge, respectively. Moreover, pressure built in the anterior lumen of the intestine results in a pezo-1-dependent pharyngeal plunge, which is driven by head muscle contraction. These findings illustrate how interoceptive processes in a digestive organ regulate swallowing through the PIEZO channel, providing insights into how interoception coordinates ingestive processes in higher animals, including humans.

MltG, a membrane-bound lytic transglycosylase, has roles in terminating glycan polymerization in peptidoglycan and incorporating glycan chains into the cell wall, making it significant in bacterial cell-wall biosynthesis and remodeling. This study provides the first reported MltG structure from Mycobacterium abscessus (maMltG), a superbug that has high antibiotic resistance. Our structural and biochemical analyses revealed that MltG has a flexible peptidoglycan-binding domain and exists as a monomer in solution. Further, the putative active site of maMltG was disclosed using structural analysis and sequence comparison. Overall, this study contributes to our understanding of the transglycosylation reaction of the MltG family, aiding the design of next-generation antibiotics targeting M. abscessus.

Background/Aims: Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them. Methods: We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness. Results: Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4. Conclusions: Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Background/Aims: Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones. Methods: This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated. Results: Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890). Conclusions: UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

To evaluate the long-term effects of submucosal Medpor implants in patients with empty nose syndrome (ENS), using the Sinonasal Outcome Test (SNOT) score as a measure of clinical improvement. A comprehensive search of six databases was conducted up to October 2024. The analysis included studies that examined the impact of submucosal Medpor implants on refractory ENS symptoms, as assessed by various symptom-specific questionnaires. Post-intervention SNOT scores were evaluated during follow-up periods of over 12 months, showing a statistically significant improvement in ENS symptoms (standardized mean difference [95% confidence interval]= 1.4676 [1.2067; 1.7285]; I2=37.2%). This meta-analysis indicates that submucosal Medpor implantation in patients with ENS is associated with significant long-term improvements in nasal symptoms.

Abstract Despite the association between spinal cord injury (SCI) and various neurological diseases, the risk of Parkinson’s disease (PD) in SCI is not elucidated yet. Especially, the role of SCI severity and injury level in the risk of PD development is not investigated. Based on the nation-wide cohort data the Korean National Health Insurance Service between 2010 and 2018, we investigated the incidence of PD in 7,182 patients with SCI compared with 24,844 age- and sex-matched controls. Adjusted hazard ratio and 95% confidence interval (CI) were calculated using Cox proportional hazards regression. We compared the risk of PD based on the degree of disability (without disability, mild, severe) and SCI level (cervical, thoracic, and lumbar). During the mean follow-up duration of 4.31 years, patients with SCI had a higher risk of PD compared with matched controls. The PD risk was greater among patients with SCI with disability than in those without disability, especially those with mild disability. Additionally, cervical-level injury was associated with the highest risk in patients with SCI without disability, while thoracic-level injury was associated with the highest risk in those with disability. Our study found patients with SCI have increased risk of PD, particularly those with disability and thoracic-level injuries.

Abstract Dyskalemia is a common electrolyte abnormality. Since dyskalemia can cause fatal arrhythmias and cardiac arrest in severe cases, it is crucial to monitor serum potassium (K+) levels on time. We developed deep learning models to detect hyperkalemia (K+ ≥ 5.5 mEq/L) and hypokalemia (K+

Abstract Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Abstract Background Orthopedic surgeons use manual measurements, acetate templating, and dedicated software to determine the appropriate implant size for total knee arthroplasty (TKA). This study aimed to use deep learning (DL) to assist in deciding the femoral and tibial implant sizes without manual manipulation and to evaluate the clinical validity of the DL decision by comparing it with conventional manual procedures. Methods Two types of DL were used to detect the femoral and tibial regions using the You Only Look Once algorithm model and to determine the implant size from the detected regions using convolutional neural network. An experienced surgeon predicted the implant size for 234 patient cases using manual procedures, and the DL model also predicted the implant sizes for the same cases. Results The exact accuracies of the surgeon’s template were 61.54% and 68.38% for predicting femoral and tibial implant sizes, respectively. Meanwhile, the proposed DL model reported exact accuracies of 89.32% and 90.60% for femoral and tibial implant sizes, respectively. The accuracy ± 1 levels of the surgeon and proposed DL model were 97.44% and 97.86%, respectively, for the femoral implant size and 98.72% for both the surgeon and proposed DL model for the tibial implant size. Conclusion The observed differences and higher agreement levels achieved by the proposed DL model demonstrate its potential as a valuable tool in preoperative decision-making for TKA. By providing accurate predictions of implant size, the proposed DL model has the potential to optimize implant selection, leading to improved surgical outcomes.

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

Abstract Background Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane generally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming 'beige’ adipocytes. Results In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking functional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased glycolysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of co-cultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Abstract Background Critical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI. Methods Ex vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model. Results VPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141+VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141+VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo. Conclusion Dual-cell therapy using BM-derived CD141+ VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers.

Abstract Background Adaptation of evidence-based interventions (EBIs) often occurs when implemented in new local contexts and settings. It is unclear, however, during which phase of implementation adaptations are most frequently made and how these changes may impact the fidelity, effectiveness, and sustainability of the EBI. Pediatric Early Warning Systems (PEWS) are EBIs for early identification of deterioration in hospitalized children with cancer. This study evaluates adaptations of PEWS made among resource-variable pediatric oncology hospitals in Latin America implementing and sustaining PEWS. Methods We conducted a cross-sectional survey among pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), a collaborative to implement PEWS. Adaptations to PEWS were assessed via 3 multiple choice and 1 free text question administered as part of a larger study of PEWS sustainability. Descriptive statistics quantitatively described what, when, and why adaptations were made. Qualitative analysis of free text responses applied the Framework for Reporting Adaptations and Modifications Expanded (FRAME) to describe respondent perspectives on PEWS adaptations. Results We analyzed 2,094 responses from 58 pediatric oncology centers across 19 countries in Latin America. Participants were predominantly female (82.5%), consisting of nurses (57.4%) and physicians (38.2%) who were PEWS implementation leaders (22.1%) or clinical staff (69.1%). Respondents described multiple PEWS adaptations across all implementation phases, with most occurring during the planning and piloting of EBIs. Adaptations included changes to PEWS content (algorithm, scoring tool, terminology, and use frequency) and context (personnel delivering or population). Respondents felt adaptations streamlined monitoring, enhanced effectiveness, improved workflow, increased comprehension, and addressed local resource limitations. Qualitative analysis indicated that most adaptations were categorized as fidelity consistent and planned; fidelity inconsistent adaptations were unplanned responses to unanticipated challenges. Conclusion Adaptations made to PEWS across implementation phases demonstrate how EBIs are adapted to fit dynamic, real-world clinical settings. This research advances implementation science by highlighting EBI adaptation as a potential strategy to promote widespread implementation and sustainability in hospitals of all resource levels.

Abstract Direct cardiac reprogramming represents a novel therapeutic strategy to convert non-cardiac cells such as fibroblasts into cardiomyocytes (CMs). This process involves essential transcription factors, such as Mef2c, Gata4, Tbx5 (MGT), MESP1, and MYOCD (MGTMM). However, the small molecules responsible for inducing immature induced CMs (iCMs) and the signaling mechanisms driving their maturation remain elusive. Our study explored the effects of various small molecules on iCM induction and discovered that the combination of FGF4 and ascorbic acid (FA) enhances CM markers, exhibits organized sarcomere and T-tubule structures, and improves cardiac function. Transcriptome analysis emphasized the importance of ECM-integrin-focal adhesions and the upregulation of the JAK2–STAT3 and TGFB signaling pathways in FA-treated iCMs. Notably, JAK2–STAT3 knockdown affected TGFB signaling and the ECM and downregulated mature CM markers in FA-treated iCMs. Our findings underscore the critical role of the JAK2–STAT3 signaling pathway in activating TGFB signaling and ECM synthesis in directly reprogrammed CMs. Schematic showing FA enhances direct cardiac reprogramming and JAK–STAT3 signaling pathways underlying cardiomyocyte maturation.

Abstract The Internet of Things (IoT) generates substantial data through sensors for diverse applications, such as healthcare services. This article addresses the challenge of efficiently utilizing resources in resource-scarce IoT-enabled sensors to enhance data collection, transmission, and storage. Redundant data transmission from sensors covering overlapping areas incurs additional communication and storage costs. Existing schemes, namely Asymmetric Extremum (AE) and Rapid Asymmetric Maximum (RAM), employ fixed and variable-sized windows during chunking. However, these schemes face issues while selecting the index value to decide the variable window size, which may remain zero or very low, resulting in poor deduplication. This article resolves this issue in the proposed Controlled Cut-point Identification Algorithm (CCIA), designed to restrict the variable-sized window to a certain threshold. The index value for deciding the threshold will always be larger than the half size of the fixed window. It helps to find more duplicates, but the upper limit offset is also applied to avoid the unnecessarily large-sized window, which may cause extensive computation costs. The extensive simulations are performed by deploying Windows Communication Foundation services in the Azure cloud. The results demonstrate the superiority of CCIA in various metrics, including chunk number, average chunk size, minimum and maximum chunk number, variable chunking size, and probability of failure for cut point identification. In comparison to its competitors, RAM and AE, CCIA exhibits better performance across key parameters. Specifically, CCIA outperforms in total number of chunks (6.81%, 14.17%), average number of chunks (4.39%, 18.45%), and minimum chunk size (153%, 190%). These results highlight the effectiveness of CCIA in optimizing data transmission and storage within IoT systems, showcasing its potential for improved resource utilization and reduced operational costs.

Abstract Background Medical students perceive the transition to clerkship education as stressful and challenging and view themselves as novices during their rotation in clerkship education. The developmental perspective is thus important because the transition to clerkship supports rather than hinders growth. Accordingly, this study examines medical students’ transition to clerkship and their developmental features. Methods In-depth interviews were conducted with 18 medical students or graduates who had completed clerkships as medical students. Based on Straussian grounded theory, the collected data were analyzed in terms of the differences between pre- and post-clerkship education. Results Our data analysis revealed five stages of the transition process: “anticipation and anxiety,” “reality check,” “seeking solutions,” “practical application,” and “transition and stability.” The core category, that is, “growing up from being students to being student doctors,” was driven by patients who perceived the participants as student doctors. Meanwhile, the participants recognized that having a solution that is agreed upon by colleagues was more important than knowing the correct answer. The participants undergoing the transition to clerkship showed developmental features divided into three categories: personal, social, and professional. Specifically, they attempted to balance clerkship and life through personal development, learned to navigate around the hospital and reduced tension through social development, and developed clinical competencies focused on efficiency through professional development. Conclusions This study explores the process of students’ transition to clerkship education and the developmental features that emerge during this period. The students were motivated by patients who perceived them as student doctors. Through the transition, they maintained a work-life balance and adapted to hospitals but developed an overly doctor-centered attitude by cultivating clinical competencies with a focus on efficiency. To develop them into medical professionals, it is essential to assist their transition and cultivate a patient-centered attitude.

Abstract This review paper explores the history, cultural significance, and functional characteristics of soybean paste (doenjang) in Korean cuisine. In particular, it covers its origins, cultural importance, production methods, functionalities, and associated risks. This review delves into the nutritional and functional aspects of fermented soybean products, focusing on compounds in soybean paste linked to health benefits, such as anticancer, anti-obesity, anti-diabetic, and antithrombotic properties. The key bioactive compounds identified in soybean paste include total phenols, total flavonoids, γ-Aminobutyric acid, vitamin B group, and vitamin E. These compounds are primarily produced through microbial fermentation, which enhances their biological activity. Additionally, the review addresses potential risks such as biogenic amines, aflatoxins, Bacillus cereus contamination, and high sodium levels, and suggests methods for mitigating these risks. By synthesizing current research, this paper aims to provide a comprehensive understanding of the physiological compounds in soybean paste and their health benefits. It also highlights the need for strategies to reduce associated risks.

Abstract This study aims to (1) compare the kinetics of pulmonary oxygen uptake (VO2p), skeletal muscle deoxygenation ([HHb]), and microvascular O2 delivery (QO2mv) between heart failure (HF) patients with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), and (2) explore the correlation between body composition, kinetic parameters, and exercise performance. Twenty-one patients (10 HFpEF and 11 HFrEF) underwent cardiopulmonary exercise testing to assess VO2 kinetics, with near-infrared spectroscopy (NIRS) employed to measure [HHb]. Microvascular O2 delivery (QO2mv) was calculated using the Fick principle. Dual-energy X-ray absorptiometry (DEXA) was performed to evaluate body composition. HFrEF patients exhibited significantly slower VO2 kinetics (time constant [t]: 63 ± 10.8 s vs. 45.4 ± 7.9 s; P

Abstract Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal genes, thereby diminishing histone H3K27 acetylation, restricting chromatin accessibility, and downregulating lysosomal gene expression. Under starvation, USF2 competes with transcription factor EB (TFEB), a master transcriptional activator of lysosomal and autophagy genes, to bind to target gene promoters in a phosphorylation-dependent manner. The GSK3β-mediated phosphorylation of the USF2 S155 site governs USF2 DNA-binding activity, which is involved in lysosomal gene repression. These findings have potential applications in the treatment of protein aggregation-associated diseases, including α1-antitrypsin deficiency. Notably, USF2 repression is a promising therapeutic strategy for lysosomal and autophagy-related diseases.