A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma.

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.

Swift and precise detection of unlabeled pathogens using a nanogap electrode impedimetric sensor facilitated by electrokinetics.

For the protection of human health and environment, there is a growing demand for high-performance, user-friendly biosensors for the prompt detection of pathogenic bacteria in samples containing various substances. We present a nanogap electrode-based purely electrical impedimetric sensor that utilizes the dielectrophoresis (DEP) mechanism. Our nanogap sensor can directly and sensitively detect pathogens present at concentrations as low as 1-10 cells/assay in buffers and drinking milk without the need for separation, purification, or specific ligand binding. This is achieved by minimizing the electrical double-layer effect and electrode polarization in nanogap impedance sensors, reducing signal loss. In addition, even at low DEP voltages, nanogap sensors can quickly establish strong DEP forces between the nanogap electrodes to control the spatial concentration of pathogens around the electrodes. This activates and stabilizes inter-electrode signal transmission along the nanogap-aligned pathogens, increasing sensitivity and reducing errors during repeated measurements. The DEP-enabled nanogap impedance sensor developed in this study is valuable for a variety of pathogen detection and monitoring systems including point-of-care testing (POCT) as it can detect pathogens in diverse samples containing multiple substances quickly and with high sensitivity, is compatible with complex solutions such as food and beverages, and provides highly reproducible results without the need for separate binding and separation processes.

Fluid inertia controls mineral precipitation and clogging in pore to network-scale flows.

Mineral precipitation caused by fluid mixing presents complex control and predictability challenges in a variety of natural and engineering processes, including carbon mineralization, geothermal energy, and microfluidics. Precipitation dynamics, particularly under the influence of fluid flow, remain poorly understood. Combining microfluidic experiments and three-dimensional reactive transport simulations, we demonstrate that fluid inertia controls mineral precipitation and clogging at flow intersections, even in laminar flows. We observe distinct precipitation regimes as a function of Reynolds number (Re). At low Reynolds numbers (Re < 10), precipitates form a thin, dense layer along the mixing interface, which shuts precipitation off, while at high Reynolds numbers (Re > 50), strong three-dimensional flows significantly enhance precipitation over the entire intersection, resulting in rapid clogging. When injection rates from two inlets are uneven, flow symmetry-breaking leads to unexpected flow bifurcation phenomena, which result in enhanced concurrent precipitation in both downstream channels. Finally, we extend our findings to rough channel networks and demonstrate that the identified inertial effects on precipitation at the intersection scale are also present and even more dramatic at the network scale. This study sheds light on the fundamental mechanisms underlying mixing-induced mineral precipitation and provides a framework for designing and optimizing processes involving mineral precipitation.

2023 Korean Society of Echocardiography position paper for diagnosis and management of valvular heart disease, part I: aortic valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the clinical management of valvular heart diseases with reference to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee tried to reflect the recently published results on the topic of valvular heart diseases and Korean data by a systematic literature search based on validity and relevance. In part I of this article, we will review and discuss the current position of aortic valve disease in Korea.

2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

Chiral Kirigami for Bend-Tolerant Reconfigurable Hologram with Continuously Variable Chirality Measures.

Despite the commonality of static holograms, the holography with multiple information layers and reconfigurable grey-scale images at communication frequencies remain a confluence of scientific challenges. One well-known difficulty is the simultaneous modulation of phase and amplitude of electromagnetic wavefronts with a high modulation depth. A less appreciated challenge is scrambling of the information and images with hologram bending. Here, this work shows that chirality-guided pixelation of plasmonic kirigami sheets enables tunable multiplexed holography at terahertz (THz) frequencies. The convex and concave structures with slanted Au strips exhibit gradual variations in geometries facilitating modulation of light ellipticity reaching 40 deg. Real-time switching of 3D images of the letter "M" and the Mona Lisa demonstrates the possibility of complex grey-scale information content and importance of continuously variable mirror asymmetry. Microscale chirality measures of each pixel experiences little change with bending while retaining controllable reconfigurability upon stretching, which translates to remarkable resilience of chiral holograms to bending. Simplicity of their design with local chirality measures opens the door to information technologies with fault-tolerant THz encryption, wearable holographic devices, and new communication technologies.

Double entrapment neuropathy of the ulnar nerve at the elbow and the wrist : double crush syndrome?

BACKGROUND: Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. METHODS: The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. RESULTS: In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. CONCLUSION: Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.

Characteristics of Korean medical care utilization in patients with traffic injury: Analysis of 3 hospital electronic health record databases.

This retrospective study aimed to identify the characteristics of Korean medical care utilization in patients with traffic injury (TI) and to explore the clinical effectiveness of Korean medical interventions for TI through a multicenter chart review. This multicenter, retrospective registry study gathered electronic health records from 3 hospitals between January 1, 2018 and December 31, 2021. Data included treatment dates, demographic information, the Korean Standard Classification of Diseases codes, collision data, Korean medicine treatment modalities, and treatment outcomes. In total, 384 patients (182 inpatients and 202 outpatients) were included in the analysis. Patients were categorized into acute (207 patients, 53.9%), subacute (77 patients, 20.1%), and chronic (100 patients, 26.0%) phases based on the period until the visit. The most frequent Korean Standard Classification of Diseases code was "sprain and strain of cervical spine (S13.4)." All patients, except one, received Korean physiotherapy, followed by acupuncture and cupping. Comparative intragroup analysis revealed significant pain reduction in patients treated with the combination of Chuna manual therapy, herbal medicine, and pharmacopuncture and those treated with pharmacopuncture and herbal medicine only. This study highlights the characteristics of patients with TI visiting medical institutions providing Korean medicine and describes the effectiveness of Korean medicine interventions. Further comprehensive analysis with more data is necessary for future research.

Examining spatiotemporal crowdsensing and caching for population-dynamic OTT content delivery.

This study proposes a novel spatiotemporal crowdsensing and caching (SCAC) framework to address the surging demands of urban wireless network traffic. In the context of rampant urbanization and ubiquitous digitization in cities, effective data traffic management is crucial for maintaining a dynamic urban ecosystem. Leveraging user mobility patterns and content preferences, this study formulates an offloading policy to alleviate congestion across urban areas. Our approach uses an AI-based method at the cell level, providing a practical and scalable solution that can be readily adapted to bustling metropolitan areas. The implementation of our model demonstrated its effectiveness in reflecting real-world urban dynamics, resulting in significant reductions in peak-hour traffic and robust performance across diverse urban settings. The deployment strategy initiates from densely populated transportation hubs, gradually expanding to broader urban areas. This systematic expansion adheres to a policy framework that emphasizes data privacy and sustainable urban development, ensuring alignment with societal needs and regulatory frameworks. By addressing technological efficacy and societal impact, this study enhances the understanding of urban wireless traffic management. It offers mobile network operators, policymakers, and urban planners a comprehensive strategy to harness the potential of spatiotemporal technology, thereby ensuring that cities remain dynamic, efficient, and well-prepared for the future of digital connectivity.

Usefulness of multiple bioabsorbable Mg screws/K­wires for comminuted radial head fractures.

PURPOSE: We hypothesized that multiple absorbable screws/K-wires would be effective for native head preservation in comminuted radial head fracture fixation (com-RHFs). METHODS: Seventeen patients who met the inclusion criteria between 2018 and 2020 were included. Radiologic findings indicating proper union and clinical outcomes such as the range of elbow motion, visual analog scale score, and Mayo Elbow Performance Score were assessed prospectively after surgery and at least three years of follow-up. RESULTS: The mean follow-up period was 4.6 years. Eleven, one, three, and two patients presented with isolated com-RHFs, type 2 (accompanied injury of medial collateral ligament), type 4 ("terrible triad") fractures, and type 5 posterior olecranon fracture-dislocations, respectively. Union was achieved after a mean of nine weeks postoperatively. The head and shaft angles did not differ significantly from the contralateral normal values (p = 0.778 and 0.872, coronal and sagittal, respectively). At the final follow-up, the mean flexion-extension/pronation-supination arcs were 126.47 ± 4.92°/135.59 ± 10.13°, and thus were significantly different from those on the contralateral side (p < 0.001, both), however the arcs were functional ranges for ordinary daily life. Also, functional status was satisfactory in all individuals. The arthritis grade and extent of heterotrophic ossification were satisfactory in all cases, and there were no serious complications requiring revision surgery. CONCLUSIONS: Absorbable screw/K-wire fixation for com-RHFs is an option before radial head arthroplasty associated with a low complication rate and no need for revision.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Phyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and reactive oxygen species generation in Caenorhabditis elegans.

We confirmed that the hexane layer of Hydrangea macrophylla leaf extract (HLH) is rich in phyllodulcin (PD), an alternative sweetener, through high performance liquid chromatography (HPLC) analysis. To investigate in vivo activity of HLH and its PD, acute toxicity and growth rate of Caenorhabditis elegans were tested and there are no clinical abnormalities at 125-500 µg/mL of HLH. HLH decreased the total lipid and triglyceride contents dose-dependently in glucose-induced obese worms. Also, HLH increased survival rates under oxidative and thermal stress and decreased body reactive oxygen species (ROS) contents significantly. Such antioxidant properties of HLH were attributed to the enhanced activity of the antioxidant enzyme catalase. To determine whether the effect of HLH was due to PD, worms were treated with PD (concentration contained in HLH), and inhibitory effects on total lipids and ROS were observed. Our results suggest that HLH and its PD as a natural alternative sweetener can be used as materials to improve metabolic diseases.

Locking plate fixation in comminuted coronoid fractures with partial loss of the articular cartilage - Of basal-1 type according to the O'Driscoll classification.

BACKGROUND: We have attempted to restore the arc of motion by considering trochlear-coronoid articulation as a complete circle during fixation of the coronoid, even for comminuted coronoid fractures with partial loss of articular cartilage (CCFPLAC), using various kinds of locking plates. Herein, we report the radiological and clinical outcomes after fixation of the basal-1 type of CCFPLAC (O'Driscoll classification) using our method. METHODS: Thirty-one patients diagnosed with CCFPLAC were admitted between January 2012 and December 2020. Sixteen of these patients met the inclusion/exclusion criteria and were enrolled in this study. Surgically, the lost area (defect of articular cartilage) was never compressed or minimized, but the original height and shape of the coronoid were preserved as is. Provisionally, a few K-wires were used to maintain the original shape and position of the CCFPLAC, and various kinds of locking plates/screws were used to fix the fragment anatomically and firmly. If needed, the plate was bent to ensure stable compression of the coronoid according to its size. In a few cases, locking plates were adjusted by cutting extra screw holes. RESULTS: Among the 16 patients, the mean age was 46.2 years, and the male:female ratio was 10:6. The mean follow-up period was 3.63 years. 8, 6, and 2 patients were designated as group 1 (isolated CCFPLAC), 2 [CCFPLAC in type 4 (terrible triad) injury), and 3 (CCFPLAC in type 5 posterior olecranon fracture-dislocations), respectively. Complete union was achieved after a mean of 8.94 weeks. The mean flexion-extension and pronation-supination arcs were 127.19 ± 4.46° and 135.31.59 ± 8.06°, respectively, which were significantly different from those on the contralateral (normal) side (p < 0.001); however, the arcs were within the functional ranges for ordinary daily living. Additionally, the functional status was satisfactory in all patients. However, Mayo Elbow Performance Score and the degree of arthritis were statistically poor in group 2. CONCLUSIONS: CCFPLAC of the basal-1 type (O'Driscoll classification) can be treated satisfactorily if already designed and widely distributed locking plates are properly manipulated to maintain the original geometry of the coronoid according to the individual joint characteristics. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

Automated BigSMILES conversion workflow and dataset for homopolymeric macromolecules.

The simplified molecular-input line-entry system (SMILES) has been utilized in a variety of artificial intelligence analyses owing to its capability of representing chemical structures using line notation. However, its ease of representation is limited, which has led to the proposal of BigSMILES as an alternative method suitable for the representation of macromolecules. Nevertheless, research on BigSMILES remains limited due to its preprocessing requirements. Thus, this study proposes a conversion workflow of BigSMILES, focusing on its automated generation from SMILES representations of homopolymers. BigSMILES representations for 4,927,181 records are provided, thereby enabling its immediate use for various research and development applications. Our study presents detailed descriptions on a validation process to ensure the accuracy, interchangeability, and robustness of the conversion. Additionally, a systematic overview of utilized codes and functions that emphasizes their relevance in the context of BigSMILES generation are produced. This advancement is anticipated to significantly aid researchers and facilitate further studies in BigSMILES representation, including potential applications in deep learning and further extension to complex structures such as copolymers.

Knockout of formyl peptide receptor 1 reduces osteogenesis and bone healing.

AIMS: Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo. MATERIALS AND METHODS: Primary BMSCs were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A closed, transverse fracture at the femoral midshaft was created to compare bone healing between KO and WT mice. Biomechanical and structural properties of femur were compared between healthy WT and KO mice. KEY FINDINGS: FPR1 expression increased significantly during osteogenesis of both primary and cloned BMSCs. Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably improved compared to FPR1 KO mice analyzed by X-ray and micro-CT. SIGNIFICANCE: These findings indicated that FPR1 played a vital role in osteogenic differentiation and regenerative capacity of fractured bone, probably through the activation of FoxO1 related signaling pathways.

Genome-based taxonomic identification and safety assessment of an Enterococcus strain isolated from a homemade dairy product.

The aim of this study was to explore the taxonomic identification and evaluate the safety of a bacterium, Enterococcus lactis IDCC 2105, isolated from homemade cheese in Korea, using whole genome sequence (WGS) analysis. It sought to identify the species level of this Enterococcus spp., assess its antibiotic resistance, and evaluate its virulence potential. WGS analysis confirmed the bacterial strain IDCC 2105 as E. lactis and identified genes responsible for resistance to erythromycin and clindamycin, specifically msrC, and eatAv, which are chromosomally located, indicating a minimal risk for horizontal gene transfer. The absence of plasmids in E. lactis IDCC 2105 further diminishes the likelihood of resistance gene dissemination. Additionally, our investigation into seven virulence factors, including hemolysis, platelet aggregation, biofilm formation, hyaluronidase, gelatinase, ammonia production, and ß-glucuronidase activity, revealed no detectable virulence traits. Although bioinformatic analysis suggested the presence of collagen adhesion genes acm and scm, these were not corroborated by phenotypic virulence assays. Based on these findings, E. lactis IDCC 2105 presents as a safe strain for potential applications, contributing valuable information on its taxonomy, antibiotic resistance profile, and lack of virulence factors, supporting its use in food products.

Evaluating the operational efficiency of NBA teams on franchise value: An assessment of data envelopment analysis.

The main purpose of this research is to empirically analyze the determinants of organizational performance using National Basketball Association (NBA) team data. Based on the resource-based theory of the firm, prior studies posit that operational efficiency encompasses the ability of professional sports teams to translate their resources into creating organizational performance. The contention is that NBA teams enhance organizational performance in the market when possessing valuable, rare, inimitable, and non-substitutable resources and capabilities. In this sense, the operational efficiencies of NBA teams align with the concept of core competence, enabling teams to achieve competitive advantages through superior performance. The exploration of the level of operating efficiency in NBA teams and its role in organizational performance is beyond essential. This study conceptualizes operating efficiency as the degree of competence exhibited by professional sports teams, drawing on comprehensive game-related statistics and financial performance data derived from human assets and team budgets. To bridge theory and empirical investigation, data spanning six seasons (2015-2016 to 2020-2021) for all 30 NBA teams were collected. The results reveal that 29 out of 180 decision-making units exhibit outstanding organizational efficiency, significantly contributing to franchise value.

pH-Responsive Cellulose/Silk/Fe3O4 Hydrogel Microbeads Designed for Biomedical Applications.

In this study, cellulose/Fe3O4 hydrogel microbeads were prepared through the sol-gel transition of a solvent-in-oil emulsion using various cellulose-dissolving solvents and soybean oil without surfactants. Particularly, 40% tetrabutylammonium hydroxide (TBAH) and 40% tetrabutylphosphonium hydroxide (TBPH) dissolved cellulose at room temperature and effectively dispersed Fe3O4, forming cellulose/Fe3O4 microbeads with an average diameter of ~15 µm. Additionally, these solvents co-dissolved cellulose and silk, allowing for the manufacture of cellulose/silk/Fe3O4 hydrogel microbeads with altered surface characteristics. Owing to the negatively charged surface characteristics, the adsorption capacity of the cellulose/silk/Fe3O4 microbeads for the cationic dye crystal violet was >10 times higher than that of the cellulose/Fe3O4 microbeads. When prepared with TBAH, the initial adsorption rate of bovine serum albumin (BSA) on the cellulose/silk/Fe3O4 microbeads was 18.1 times higher than that on the cellulose/Fe3O4 microbeads. When preparing TBPH, the equilibrium adsorption capacity of the cellulose/silk/Fe3O4 microbeads for BSA (1.6 g/g) was 8.5 times higher than that of the cellulose/Fe3O4 microbeads. The pH-dependent BSA release from the cellulose/silk/Fe3O4 microbeads prepared with TBPH revealed 6.1-fold slower initial desorption rates and 5.2-fold lower desorption amounts at pH 2.2 than those at pH 7.4. Cytotoxicity tests on the cellulose and cellulose/silk composites regenerated with TBAH and TBPH yielded nontoxic results. Therefore, cellulose/silk/Fe3O4 microbeads are considered suitable pH-responsive supports for orally administered protein pharmaceuticals.

Novel percutaneous technique for creation of porcine model of tricuspid regurgitation via two routes.

OBJECTIVE: To develop an experimental porcine model of tricuspid regurgitation using two induction routes: the inferior vena cava and superior vena cava. METHODS: Tricuspid regurgitation was generated using the loop wire cutting method. The tricuspid regurgitation jet direction was controlled by accessing the valve through the inferior (n = 7) or superior (n = 6) vena cava. The occurrence, direction, and progression of tricuspid regurgitation were assessed postoperatively, and echocardiography was performed at 4 to 6 weeks. Right heart dilatation was assessed using computed tomography after 6 weeks. RESULTS: Moderate to severe or torrential tricuspid regurgitation occurred immediately after the procedure in 12 of 13 animals. The jet was directed toward the septum in five of seven animals in the inferior vena cava group and toward the posterolateral side in four of six animals in the superior vena cava group. The dimensions of the right heart (right atrium, ventricle, and tricuspid valve annulus) were significantly enlarged at the 4- to 6-week follow-up echocardiographic examination and confirmed to be enlarged by computed tomography, independent of the route used. CONCLUSION: The loop wire cutting method successfully induced a disease model of tricuspid regurgitation while controlling the regurgitation jet direction via two procedural routes.