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During the pandemic surge, including SARS-CoV-2 and influenza, pooling samples emerged as an efficient strategy to identify infected individuals in large groups. While pooling enhances RT-PCR throughput, reducing costs and resources, it dilutes positive samples with negative ones, lowering sensitivity and increasing false negatives. This study proposes a new method to address the trade-off between pool sizes and RT-PCR accuracy. This method integrates large-scale pooling with sample enrichment using a nano-hybrid membrane, preventing the pooling-induced decrease in viral concentration and maintaining cycle threshold (Ct) values close to individual positive samples. The nano-hybrid membrane, named SIMPLE (streamlined, simple, and inexpensive method for preconcentration, lysis, and nucleic acid extraction), comprises layered red blood cell membranes, polyethersulfone, and silica membranes. Using SIMPLE, a Ct value reduction to ≈2.6 is demonstrated in pooled COVID-19 samples with a pool size of 6 and found Ct values from larger pool sizes (8, 16, 32, 64, and 128) comparable to individual positive samples., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with limited treatment options, often associated with Merkel cell polyomavirus (MCPyV) and marked by hypoxic tumor microenvironments that promote resistance to therapies. Belzutifan, an FDA-approved hypoxia-inducible factor-2α (HIF-2α) inhibitor, has shown promise in inhibiting tumor growth; however, its clinical efficacy is hindered by its low solubility, rapid clearance, and limited bioavailability. In this study, we present a strategy using porous silicon (pSi) microparticles and nanoparticles as carriers for the sustained delivery of benzoate to MCC cells. The pSi carriers were engineered to securely encapsulate and gradually release belzutifan, overcoming the limitations of free drug administration. Microparticles provided sustained extracellular release, while nanoparticles enabled efficient intracellular delivery, enhancing HIF-2α inhibition. Moreover, the use of biodegradable silicon particles enables long-term consistent release of belzutifan over 10 days in vitro with a single dose administration in the tumor microenvironment, while free belzutifan is rapidly deactivated within 1 day postadministration. In vitro studies demonstrated significant immunogenic cell death (ICD) in MCC cells, marked by the cytosolic localization of HMGB1 and elevated expression of pro-inflammatory cytokines as well as strong upregulation of TLR9. Particularly, the increased TLR9 expression in both MCC cell lines with pSi carrier treatment reinforces immune activation through toll-like receptor signaling, enhancing both innate and adaptive immune responses within the tumor microenvironment. These findings indicate that pSi carriers not only enhance belzutifan's stability and release profile but also amplify antitumor immune responses within the tumor microenvironment. Our results suggest that belzutifan-loaded pSi carriers offer a potent and targeted therapeutic strategy for MCC, potentially addressing key challenges in cancer immunotherapy by combining HIF-2α inhibition with robust immune activation. This platform highlights the universal utility of pSi-based delivery systems to advance MCC treatment with implications for broader cancer therapies.

Background: Graft selection is an important part of preoperative planning for anterior cruciate ligament reconstruction (ACLR). In addition, ACLR with the remnant preservation technique has recently gained attention due to potential benefit in bone-tendon healing, graft revascularization, and proprioceptive nerve remodeling. However, the ideal graft choice remains controversial, and there is limited research comparing autograft and allograft in ACLR with remnant preservation., Purpose: To compare knee muscle strength, neuromuscular control, and patient-reported outcomes between hamstring (HS) tendon autografts and tibialis anterior (TA) allografts in patients undergoing ACLR with remnant preservation through posterior transseptal portal for >1 year., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 70 patients who underwent ACLR with remnant preservation between 2018 and 2021 using HS tendon autograft (n = 35) or TA allograft (n = 35) were analyzed at 3 different time points (preoperative, 6 months, and 12 months). Quadriceps and HS muscle strengths were measured with an isokinetic device. Proprioception was evaluated with reproduction of passive positioning for joint position sense and overall stability index (OSI) for dynamic postural stability. Patient-reported outcomes included the Lysholm score and the International Knee Documentation Committee score., Results: There were no significant differences in demographic information including age, body mass index, concomitant meniscal injuries, and sports activities ( P > .05) between HS tendon autograft and TA allograft groups. Quadriceps and HS strength in both groups, HS strength in deep knee flexion in both groups, and OSI in the HS tendon autograft group significantly improved at 12 months ( P < .05). Repeated-measures analysis of variance revealed significant interactions between time and grafts for OSI ( F [2, 136] = 5.08; P = .007). The subsequent independent t test demonstrated that the OSI was significantly higher in the TA allograft group (2.7 ± 1.0) than that of the HS tendon autograft group (2.1 ± 0.8) at 12 months ( P = .009), indicating better dynamic postural stability in the HS tendon autograft group., Conclusion: No significant differences were found in knee muscle strength or patient-reported outcomes between HS tendon autograft and TA allograft after ACLR with remnant preservation for up to 1 year except for dynamic postural stability favoring HS tendon autograft., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: 1475013503, RS-2023-00210209). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from Anam Hospital, Korea University (2018AN0261 / K2018-0444-003)., (© The Author(s) 2025.)

Dynamic communication between hepatocytes and the environment is critical in hepatocellular carcinoma (HCC) development. Clinical immunotherapy against HCC is currently unsatisfactory and needs more systemic considerations, including the identification of new biomarkers and immune checkpoints. Transmembrane 4 L six family member 5 (TM4SF5) is known to promote HCC, but it remains unclear how cancerous hepatocytes avoid immune surveillance and whether avoidance can be blocked. We investigated how TM4SF5-mediated hepatic tumorigenesis avoids surveillance by natural killer (NK) cells, which are prevalent in the liver, and whether the avoidance can be blocked by anti-TM4SF5 agents. We used comprehensive structure activity relationship analysis to identify TM4SF5-specific isoxazole (TSI)-based small molecules that inhibit TM4SF5-mediated effects. TM4SF5 expressed by hepatocytes reduced NK cell cytotoxicity by downregulating stimulatory ligands/receptors, including signaling lymphocytic activation molecule family member 7 (SLAMF7). TM4SF5 bound SLAMF7 depending on N-glycosylation and caused intracellular trafficking of SLAMF7 from the plasma membrane to lysosomes for degradation. TSI treatments in cell lines and animal models of HCC blocked this binding, intracellular trafficking, and downregulation, resulting in higher levels of stimulatory NK cell ligands. In mouse xenograft models, TSI treatment abrogated HCC development by increasing the abundance and dispersion of Slamf7-positive cells in liver tissues, recapitulating the phenotype of Tm4sf5-knockout mice and indicating TSI-mediated restoration of NK cell surveillance. These findings suggest that TSIs can inhibit TM4SF5-mediated liver carcinogenesis by increasing NK cell surveillance., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Microstructure optimization and high-performance material development are crucial for improving the electrochemical performance of all-solid-state batteries (ASSBs). Researchers frequently record numerous micro-scale or nano-scale electron micrographs for unbiased post-mortem analysis, performance evaluation, and improvement of ASSBs. However, these micrographs are often underutilized and typically analyzed qualitatively without ensuring an accurate representation of the experimental objectives. This study explores machine learning (ML)-based quantitative analysis techniques using electron microscopy images, combined with a stereology-driven linear-intercept concept method and semantic segmentation, to extract quantitative microstructural parameters for optimizing ASSB performance. The applicability of ML-assisted image analytics is demonstrated by employing composite cathodes in ASSBs to achieve unbiased automation and deep semantic segmentation during microstructural characterization. Furthermore, the ramifications of this ML-assisted method are discussed, along with its advantages and disadvantages in battery research., (© 2025 Wiley‐VCH GmbH.)

Macrophages encounter a myriad of biochemical and mechanical stimuli across various tissues and pathological contexts. Notably, matrix rigidity has emerged as a pivotal regulator of macrophage activation through mechanotransduction. However, the precise mechanisms underlying the interplay between mechanical and biochemical cues within the nuclear milieu remain elusive. Here We elucidate how the increased matrix rigidity drives macrophages to amplify alternatively-activated (M2 phenotype) signaling cooperatively with biochemical cues (e.g., IL4/13) through altered nuclear mechanics. We demonstrate that reconstructed podosome-like F-actins and contractility induce nucleus deformation, opening nuclear pores, which facilitates nuclear translocation of the key transcription factor STAT6. Furthermore, the altered nuclear mechanics increases chromatin accessibility induced by H3K9 methylation, particularly of M2-associated gene promoters. These cooperative events of the mechano-chemical signaling at the cytoskeletal-to-nuclear domains facilitate M2 transcriptional activation and cellular functions. We further evidence the rigidity-primed M2 macrophages are immunosuppressive and accumulated within stiffened tumors in patients. This study proposes a mechanism by which matrix mechanics crosstalks with biochemical signals to potentiate macrophage activation through nuclear mechanosensing and chromatin modifications, offering insights into macrophage mechanobiology and its therapeutic modulations., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background and Objectives: We propose the use of GPT-4 to facilitate initial history-taking in neurology and other medical specialties. A large language model (LLM) could be utilized as a digital twin which could enhance queryable electronic medical record (EMR) systems and provide healthcare conversational agents (HCAs) to replace waiting-room questionnaires., Methods: In this observational pilot study, we presented verbatim history of present illness (HPI) narratives from published case reports of headache, stroke, and neurodegenerative diseases. Three standard GPT-4 models were designated Models P : patient digital twin; N : neurologist to query Model P; and S : supervisor to synthesize the N-P dialogue into a derived HPI and formulate the differential diagnosis. Given the random variability of GPT-4 output, each case was presented five separate times to check consistency and reliability., Results: The study achieved an overall HPI content retrieval accuracy of 81%, with accuracies of 84% for headache, 82% for stroke, and 77% for neurodegenerative diseases. Retrieval accuracies for individual HPI components were as follows: 93% for chief complaints, 47% for associated symptoms and review of systems, 76% for relevant symptom details, and 94% for histories of past medical, surgical, allergies, social, and family factors. The ranking of case diagnoses in the differential diagnosis list averaged in the 89th percentile., Discussion: Our tripartite LLM model demonstrated accuracy in extracting essential information from published case reports. Further validation with EMR HPIs, and then with direct patient care will be needed to move toward adaptation of enhanced diagnostic digital twins that incorporate real-time data from health-monitoring devices and self-monitoring assessments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Lee, Choi, Angulo, McDougal and Lytton.)

We aimed to determine whether emergency department (ED) overcrowding affects the occurrence of in-hospital cardiac arrest (IHCA) requiring resuscitation in the ED. This retrospective study was conducted in the ED of a single hospital. We applied the propensity score-matching method to adjust for differences in clinical characteristics in patients who visited the ED during overcrowded conditions. The indicators of overcrowding were: the total number of patients, number of patients undergoing treatment, and number of boarded patients awaiting hospital admission at the time of a patient's arrival. We defined the existence of ED overcrowding based on the 75%, 80%, and 90% thresholds of each indicator. We included 153,353 patients, and 160 cases of IHCA occurred, showing an incidence rate of 0.10%. The IHCA incidence rate increased during overcrowding, as indicated by the total number of patients and the number of boarded patients rising to 0.15% and 0.17%, respectively, at the 90% threshold (p = 0.0407 and 0.0203, respectively). The IHCA incidence rate did not increase during overcrowding based on the number of patients undergoing treatment. In the comparison conducted after propensity score matching, the incidence of IHCA was significantly higher in the overcrowding group than in the non-overcrowding group, indicated by 80% boarded patients (0.15% vs. 0.08%, p = 0.0222). The logistic regression results indicated that both the full-study and propensity score-matched cohorts showed a tendency for increased IHCA during overcrowding, as indicated by the total number of patients and number of boarded patients. The number of patients undergoing treatment did not affect the occurrence of IHCA. Although this needs to be confirmed in larger studies, we found in this study that ED overcrowding, particularly blocked access, tends to increase the incidence of IHCA requiring resuscitation in the ED. This suggests that to protect patient safety in ED overcrowding, it is essential for the entire hospital to make concerted efforts to maintain the flow of patients in the ED., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Jun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/aims: Besifovir (BSV) showed comparable antiviral activity superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment., Methods: In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks., Results: The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% CI -0.01 to 0.04; P=1.000), with a predefined margin of -0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (-1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group., Conclusions: In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF. ClinicalTrials.gov Identifier: NCT04202536.

Cancer immunotherapy has revolutionized cancer treatment due to its precise, target-specific approach compared with conventional therapies. However, treating solid tumors remains challenging as these tumors are inherently immunosuppressive, and their tumor microenvironment (TME) often limits therapeutic efficacy. Interestingly, certain bacterial species offer a promising alternative by exhibiting an innate ability to target and proliferate within tumor environments. Bacterial structural and functional components can activate innate and adaptive immune responses, creating tumor-suppressive conditions that reduce tumor mass. Additionally, bacteria can deliver effector molecules directly into tumor cells, inducing apoptotic and necrotic cell death. Despite their potential, the use of bacteria in cancer immunotherapy poses risks due to possible toxicities and unpredictable in vivo behavior. Advances in genetic engineering have addressed these concerns by enabling the development of attenuated bacterial strains with enhanced anticancer properties for safer medical applications. This review highlights the role of bacteria in TME modulation, recent strategies to bioengineer bacterial pathogens as therapeutic tools, and the synergistic effects of combining bacteria with other immunotherapies. It also discusses the challenges and prospects of translating this innovative approach into clinical practice, offering a comprehensive overview of bacteria-based cancer immunotherapy's potential to reshape the future of cancer treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Most NMR samples are cylindrical, which is ideal for obtaining high-resolution NMR spectra, especially in superconducting magnets with a vertical bore. However, expanding NMR applicability to samples that are not necessarily cylindrical requires a new approach. In this study, we introduce a method for obtaining solution NMR signals from flat samples, such as flat containers or layered structures like a fuel cell. A flat rectangular NMR coil was developed for RF application and sensitive signal detection, while biplanar shim coils were designed using Bfieldtools and manufactured on multilayered printed circuit boards to improve NMR resolution. Water and ethanol molecules in flat rectangular and flat circular containers, as well as in a direct ethanol fuel cell, were observed with narrow NMR linewidths. We believe that our spectrometer design will enable NMR analysis of samples that need to be contained in flat structures and support in-situ analysis of various devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Artificial vascular grafts, as blood vessel substitutes, are a prime challenge in tissue engineering and biomaterial research. An ideal artificial graft must have physiological and mechanical properties similar to those of a natural blood vessel, and hemocompatibility on its surface. We designed and fabricated artificial grafts by applying 3D printing and templated technology, which is endowed with morphologically patient-specific vascular reconstruction. To optimize mechanical properties, the graft wall was engineered with a controllable hybrid porous structure through a multilayer combination of porous and nonporous coatings, thereby achieving biomimetic mechanical flexibility with reduced stiffness. Further, we successfully synthesized dopamine-conjugated heparin (Hep-DA) utilizing carbodiimide chemistry, and coated it on a 3D porous graft to improve both surface adhesion and anticoagulant ability. The Hep-DA-coated 3D graft did not show significant cytotoxic effects with a long-term sustained heparin release. We performed a preclinical study in swine using the developed graft along with commercially available graft ePTFE and Dacron as a reference. They were implanted in the swine aorta for 28 days and the implanted grafts were harvested for further analysis. Histopathology study results showed the feasibility of the developed artificial vascular grafts that have less calcification, fibrosis, and collagen deposition than commercially available grafts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tae Hee Kim reports financial support was provided by Institute of Information and Communication Technology Planning and Evaluation (IITP). Suk-Hee Park reports financial support was provided by Korea Health Industry Development Institute (KHIDI). Won-Min Jo reports financial support was provided by Korea University Ansan Hospital grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of fibrous actuators with diverse actuation modes is expected to accelerate progress in active textiles, robotics, wearable electronics, and haptics. Despite the advances in responsive polymer-based actuating fibers, the available actuation modes are limited by the exclusive reliance of current technologies on thermotropic contraction along the fiber axis. To address this gap, the present study describes a reversible and spontaneous thermotropic elongation (~30%) in liquid crystal elastomer fibers produced via ultraviolet-assisted melt spinning. This elongation arises from the orthogonal alignment of smectogenic mesogens relative to the fiber axis, which contrasts the parallel alignment typically observed in nematic liquid crystal elastomer fibers and is achieved through mesophase control during extrusion. The fibers exhibiting thermotropic elongation enable active textiles increase pore size in response to temperature increase. The integration of contracting and elongating fibers within a single textile enables spatially distinct actuation, paving the way for innovations in smart clothing and fiber/textile actuators.

Background: Intravascular ultrasound (IVUS) guidance has been shown to yield favorable outcomes for endovascular treatment of femoropopliteal artery (FPA) disease with drug-coated balloon (DCB) angioplasty. However, the specific benefits of IVUS for treatment of complex FPA lesions remain uncertain., Objectives: In this study, the authors compared the clinical impact of IVUS-guided vs angiography-guided DCB angioplasty in patients with complex or noncomplex FPA lesions., Methods: This study was a prespecified, primary subgroup analysis of the randomized IVUS-DCB trial. Patients with FPA undergoing DCB angioplasty were randomized to receive the procedure under IVUS or angiography guidance. The primary endpoint was 12-month primary patency; secondary endpoints included clinically driven target lesion revascularization (CD-TLR), sustained clinical improvement, and hemodynamic improvement., Results: Among the 237 patients enrolled, 158 had complex FPA (Trans-Atlantic Inter-Society Consensus II [TASC II] type C/D), and 79 had noncomplex FPA (TASC II type A/B). In complex FPA, IVUS guidance was associated with significantly higher rates of primary patency (82.1% vs 60.3%; HR for loss of primary patency: 0.34; 95% CI: 0.16-0.70; P = 0.002), freedom from CD-TLR (90.0% vs 76.9%; HR: 0.31; 95% CI: 0.13-0.75; P = 0.01), and sustained clinical and hemodynamic improvement relative to angiography guidance. There was no significant difference in primary patency (87.5% vs 88.2%; HR: 1.84; 95% CI: 0.39-8.60; P = 0.44) or occurrence secondary endpoints between the IVUS-guidance and angiography-guidance groups for patients with noncomplex FPA., Conclusions: In endovascular treatment of FPA using DCB, IVUS guidance was significantly associated with improved 12-month clinical outcomes, particularly in patients with complex FPA lesions.(Intravascular Ultrasound-Guided Drug-Coated Balloon Angioplasty for Femoropopliteal Artery Disease [IVUS-DCB] trial; NCT03517904)., Competing Interests: Funding Support and Author Disclosures This study was funded by Medtronic Inc. and Korea United Pharmaceutical, and supported by the Cardiovascular Research Center, Seoul, Korea. Dr Ko has received research grants from Medtronic, Korea United Pharm, Cook Medical, Boston Scientific, Otsuka Korea, Dong-A ST, Samjin Pharm, and Cordis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A facultative anaerobic, Gram-stain-negative, non-motile, rod-shaped bacterial strain AGMB14963 T was isolated from the feces of a dairy cow. A 16S rRNA gene sequence-based phylogenetic analysis revealed that strain AGMB14963 T belongs to the genus Gallibacterium, with Gallibacterium salpingitidis F150 T being the closest species (95.8% 16S rRNA gene sequence similarity). Whole-genome sequence analysis revealed that strain AGMB14963 T had a 37.0% G + C genomic DNA content and a genome size of 2.58 Mb. In addition, the strain contained 53 tRNA and 2 rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strains AGMB14963 T and G. salpingitidis F150 T were 82.3 and 24.9%, respectively. Further, strain AGMB14963 T was positive for oxidase and catalase, but negative for urease. Optimal growth of strain AGMB14963 T occurred at 37 ℃, pH 8, and in 0.5% NaCl-containing medium. The predominant cellular fatty acids (> 10%) in strain AGMB14963 T were C 14:0 , C 16:0 , and summed feature 3. Strain AGMB14963 T produced lactic acid and isobutyric acid as the major end products of glucose fermentation. Polar lipids consisted of one phospholipid and one phosphoaminolipid. According to the genomic, physiologic, and chemotaxonomic characteristics, strain AGMB14963 T represents a novel species of the genus Gallibacterium, for which the name Gallibacterium faecale sp. nov. is proposed. The type strain is AGMB14963 T (= KCTC 25487  T  = NBRC 116419  T )., Competing Interests: Declarations. Conflicts of interest: The authors declare that there are no conflicts of interest., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We announce the complete genome of Escherichia coli strain PEC1003 belonging to ST7366, isolated from sewage water in Pakistan. This strain harbored a plasmid carrying various antibiotic resistance genes, including extended-spectrum β-lactamase (ESBL), bla CTX-M-15 , emphasizing the management and surveillance of ESBL-producing E. coli in the environment of developing countries., Competing Interests: The authors declare no conflict of interest.

Background and Objectives: Distal tibia fractures are high-energy injuries characterized by a mismatch between standard plate designs and the patient's specific anatomical bone structure, which can lead to severe soft tissue damage. Recent advancements have focused on the development of customized metal plates using three-dimensional (3D) printing technology. However, 3D-printed metal plates using titanium alloys have not incorporated a locking system due to the brittleness of these alloys. Therefore, this study aimed to determine whether a locking mechanism can be effectively implemented using 3D-printed pure titanium and further evaluate the clinical outcomes of such implants in patients with distal tibia fractures. Materials and Methods : Between March 2021 and June 2022, nine patients who underwent open reduction and internal fixation for distal tibia fractures using 3D-printed pure titanium plates were enrolled. Pure titanium powder (Ti Gr.2, Type A, 3D Systems, USA) was spread to a thickness of 30 μm and partially sintered using a 500 W laser to produce the 3D-printed metal plates. The locking screws were fabricated using a milling process. Open reduction and internal fixation were performed on the nine patients using 10 customized plates. The clinical efficacy was analyzed using the union rate, and complications, such as infection and skin irritation, were evaluated to ensure a comprehensive outcome assessment. Results: Surgical treatment was successfully performed on nine patients, with nine of ten plates remaining stable and undamaged. However, one patient with neurofibromatosis experienced a fractured metal plate, which necessitated revision surgery using a metal rod. No screw loosening or surgical wound complications occurred. Conclusions: This study showed that 3D-printed pure titanium plates with integrated locking screw systems provide a viable and effective solution for managing distal tibia fractures. Three-dimensional printing and pure titanium show promise for orthopedic advancements.

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo. Here, we describe the development of mature, expandable AT2 organoids derived from human fetal lungs which are phenotypically stable, can differentiate into AT1-like cells, and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health., Competing Interests: Disclosure and competing interests statement. SAT is a remunerated member of the scientific advisory boards of Qiagen, Foresite Labs, and Element Biosciences, a co-founder and equity holder of TransitionBio, and a part-time employee of GlaxoSmithKline since January 2024. JCM has been an employee of Genentech, Inc. since September 2022. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme N -acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life, and respiratory function in patients with MPS IVA; however, owing to the rarity of MPS IVA, data on Korean patient characteristics are limited. This retrospective study reports clinical, radiographic, biochemical, and molecular findings, and analyzes long-term clinical outcomes, from the largest cohort of Korean patients with MPS IVA in a single center. The analysis included 17 patients from 14 families (58.8 % females; median [range] age at diagnosis 5.2 [1.8-33.7] years). The majority of patients (64.7 %) were classified as having a severe phenotype, 23 % had an intermediate phenotype, and 11.8 % had an attenuated phenotype. Skeletal manifestations and radiologic abnormalities at initial diagnosis included gait abnormality (35.3 %), short stature (23.5 %), chest deformity (23.5 %), scoliosis (17.6 %), kyphosis (11.8 %), dysmorphic face (6 %), hip pain (6 %), and leg deformity (6 %). Twelve different GALNS mutations were identified. Patients received ERT for a median (range) 7.4 years (3.0-12.1). Twelve patients reached final adult height, and all patients with the severe/intermediate phenotype had short stature (<3rd percentile). Hemiepiphysiodesis was the most common surgical intervention among patients with the severe/intermediate phenotype. Drug-related adverse events (urticaria, rash, and anaphylaxis) were reported in four patients but were managed with antihistamines or desensitization. At follow-up, patients experienced improvements in functional independence measure score, ejection fraction, and the 6-min walk test compared with the pre-treatment baseline. This study provides real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among patients with MPS IVA treated with ERT, with no new safety concerns identified., Competing Interests: The authors have no relevant financial relationships or conflicts of interest to disclose., (© 2025 The Authors.)

Background/aims: The incidence of steatotic liver disease (SLD) is increasing across all age groups as the incidence of obesity increases worldwide. The existing noninvasive prediction models for SLD require laboratory tests or imaging and perform poorly in the early diagnosis of infrequently screened populations such as young adults and individuals with healthcare disparities. We developed a machine learning-based point-of-care prediction model for SLD that is readily available to the broader population with the aim of facilitating early detection and timely intervention and ultimately reducing the burden of SLD., Methods: We retrospectively analyzed the clinical data of 28,506 adults who had routine health check-ups in South Korea from January to December 2022. A total of 229,162 individuals were included in the external validation study. Data were analyzed and predictions were made using a logistic regression model with machine learning algorithms., Results: A total of 20,094 individuals were categorized into SLD and non-SLD groups on the basis of the presence of fatty liver disease. We developed three prediction models: SLD model 1, which included age and body mass index (BMI); SLD model 2, which included BMI and body fat per muscle mass; and SLD model 3, which included BMI and visceral fat per muscle mass. In the derivation cohort, the area under the receiver operating characteristic curve (AUROC) was 0.817 for model 1, 0.821 for model 2, and 0.820 for model 3. In the internal validation cohort, 86.9% of individuals were correctly classified by the SLD models. The external validation study revealed an AUROC above 0.84 for all the models., Conclusions: As our three novel SLD prediction models are cost-effective, noninvasive, and accessible, they could serve as validated clinical tools for mass screening of SLD.

With recent advancements in gene editing technology using the CRISPR/Cas system, there is a demand for more effective gene editors. A key factor facilitating efficient gene editing is effective CRISPR delivery into cells, which is known to be associated with the size of the CRISPR system. Accordingly, compact CRISPR-Cas systems derived from various strains are discovered, among which Un1Cas12f1 is 2.6 times smaller than SpCas9, providing advantages for gene therapy research. Despite extensive engineering efforts to improve Un1Cas12f1, the editing efficiency of Un1Cas12f1 is still shown to be low depending on the target site. To overcome this limitation, we develop enhanced Cas12f1 (eCas12f1), which exhibits gene editing activity similar to SpCas9 and AsCpf1, even in gene targets where previously improved Un1Cas12f1 variants showed low gene editing efficiency. Furthermore, we demonstrate that eCas12f1 efficiently induces apoptosis in cancer cells and is compatible with base editing and regulation of gene expression, verifying its high utility and applicability in gene therapy research., Competing Interests: Competing interests: S.-J.P. and K.K. have submitted a patent application to the Korea patent office pertaining to the enhanced Cas12f1 variants and their uses described in this work (application number 10-2024-0058649). The remaining authors declare no competing interests., (© 2025. The Author(s).)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has the potential to improve neurological outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA), offering an alternative to conventional cardiopulmonary resuscitation (CCPR). However, its effectiveness in OHCA remains controversial despite advancements in resuscitation techniques. Methods: This retrospective single-center study compared neurological outcomes and 30-day survival between ECPR and CCPR patients from January 2014 to January 2022. Patients aged 18-75 with witnessed OHCA, minimal no flow and low flow times, and cardiac arrests occurring at home or in public places were included. All patients were transported directly to our institution, a tertiary medical center serving the southeastern region of Seoul, where extracorporeal membrane oxygenation implantation was consistently performed in the emergency department. Neurological outcomes were assessed using Cerebral Performance Category scores, with good outcomes defined as scores of 1-2. Statistical analyses included logistic regression models and Kaplan-Meier survival curves, adjusted for confounders using inverse probability of treatment weighting. Results: ECPR was associated with significantly better neurological outcomes than CCPR ( p < 0.001). Factors predicting poor outcomes included older age and longer low flow times, while male sex and shockable rhythms were protective. No significant difference was found in 30-day survival between the ECPR and CCPR groups, although a trend toward better survival was noted with ECPR. Conclusions: ECPR may improve neurological outcomes in patients with refractory OHCA compared to CCPR, although it does not significantly affect 30-day survival. Further studies are necessary to validate these findings and explore the long-term impacts of ECPR.

Diamine-functionalized metal-organic frameworks (MOFs) based on Mg 2 (dobpdc) (dobpdc 4- =4,4'-dioxidobihyenyl-3,3'-dicarboxylate) are considered promising CO 2 adsorbents owing to their characteristic stepwise adsorption behavior. However, the high temperatures required for CO 2 desorption from diamine-Mg 2 (dobpdc)-based adsorbents induce gradual diamine loss. Additionally, the existence of an exotic CO 2 adsorption mode remains experimentally unanswered. Herein, we present CO 2 adsorbents obtained by functionalizing Mn 2 (dobpdc) with a series of diaminopropane derivatives. The low regeneration energies of these adsorbents allow for CO 2 desorption at temperatures lower than those reported for Mg-based analogs. Our first-principles density functional theory calculations indicated that the bond strength between the diamine and Mn ions in Mn 2 (dobpdc) is greater than that between the diamine and Mg ions in Mg 2 (dobpdc). This stronger bonding prevents diamine loss even at high temperatures and enables efficient regeneration. Additionally, the computational and experimental results showed that MOFs functionalized with primary-tertiary diamine exhibit unique one-channel flipped adsorption structures that have not been previously observed. Our findings provide valuable insights into the role of metal ions in diamine loss for the future development of efficient amine-based CO 2 adsorbents., (© 2024 Wiley-VCH GmbH.)

Recently, the demand for respiratory disease-related products has surged due to the influence of coronavirus disease 2019, prompting warnings about illegal dietary supplements containing unauthorized substances. Additionally, adulterated dietary supplements are continuously detected in open markets, posing significant public health safety problem. In this study, we developed and validated an analytical method for 11 respiratory drug substances using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and proposed optimal conditions for LC-quadrupole time-of-flight MS (LC-QTOF-MS) to determine the fragmentation patterns of each substance. This method underwent thorough validation considering specificity, linearity, limits of detection and quantification, accuracy, precision, matrix effect, stability, etc. All results met international guidelines. These validated methods were applied to 52 dietary supplements advertised for treating respiratory diseases and enhancing respiratory function, among which one sample was found to contain 313.7 mg/g of theobromine. This determination was made by comparing the product ion ratios with the standards and subsequent quantification. To re-confirm the detected substances, their fragmentation patterns were compared with those of the standards using LC-QTOF-MS. In conclusion, the mass-based information, coupled with the LC-ESI-MS/MS method development, can be successfully applied to rapidly identify 11 respiratory drug substances in illegal dietary supplements used for respiratory disease treatment. The developed simultaneous detection method contributes to public health and safety improvements., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite numerous studies aimed at solving the detrimental dissolution issue of organic electrode materials (OEMs), a fundamental understanding of their dissolution mechanism has not yet been established. Herein, we systematically investigate how changes in electrolyte composition affect the ion-solvent interactions propagating to OEM dissolution by changing the cation. The cyclability of OEM is significantly different by alkali cations, where the OEM with K is stable even after 300 cycles and that with Li is drastically decayed within 100 cycles. This different behavior is owing to the dissolution of OEM into electrolytes, and the dissolution of OEMs was found to be highly dependent on the cation-solvent interaction. Strong cation-solvent interactions induce cointercalation into the layered structure of the electrode and cause electrode deformation. This behavior allows OEMs to easily detach from their original location, consequently leading to dissolution and severe capacity decay. The cation-solvent interaction-dependent phenomenon is similar to that of OEMs with high-concentration electrolytes, in which fewer cation-solvent pairs exist. The result provides insight into proper electrolyte selection and is expected to set a constructive milestone in the utilization of organic electrodes.

Ultrasmall-scale semiconductor devices (≤5 nm) are advancing technologies, such as artificial intelligence and the Internet of Things. However, the further scaling of these devices poses critical challenges, such as interface properties and oxide quality, particularly at the high- k /semiconductor interface in metal-oxide-semiconductor (MOS) devices. Existing interlayer (IL) methods, typically exceeding 1 nm thickness, are unsuitable for ultrasmall-scale devices. Here, we propose a one-atom-thick amorphous carbon monolayer (ACM) as the IL to address these issues for MOS devices. ACM is disordered, randomly arranged, and short of long-range periodicity with sp 2 hybridized carbon network, offering impermeability, van der Waals (vdW) bonding, insulating behavior, and effective seeding layer. With these advantages, we have utilized ACM vdW IL (vIL) in Al 2 O 3 /H-Ge MOS capacitors. The interface trap density was suppressed by ∼2 orders of magnitude to 7.21 × 10 10 cm -2 eV -1 , with no frequency-dependent flat band shift. The slow trap density is decreased to 2 orders of magnitude, and the C - V hysteresis width is minimized by >75%, indicating enhanced oxide quality. These results are supported by high-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy analysis, confirming the creation of an atomically well-defined interface in the Al 2 O 3 /H-Ge heterojunction with ACM vIL, even under high-temperature annealing conditions. Density functional theory calculations further clarify that ACM vIL preserves the hydrogen-passivated Ge surface without altering its electronic band structure. These results demonstrate that ACM vIL effectively improves the interface properties and enhances the oxide quality, enabling further advancements in ultrasmall-scale MOS devices.

Vibrios are naturally present in marine ecosystems and are commonly allied with live seafood. Vibrio species frequently cause foodborne infections, with Vibrio parahaemolyticus recently becoming a significant contributor to foodborne illness outbreaks. In response, aniline and 68 of its aniline derivatives were studied due to their antibacterial effects targeting V. parahaemolyticus and Vibrio harveyi . Among these, 4-amino-3-chloro-5-nitrobenzotrifluoride (ACNBF) and 2-iodo-4-trifluoromethylaniline (ITFMA) demonstrated both antibacterial and antibiofilm properties. The minimum inhibitory concentrations (MIC) for ACNBF and ITFMA were 100 µg/mL and 50 µg/mL, respectively, against planktonic cells. The active compounds effectively suppressed biofilm formation in a manner dependent on the dosage. Additionally, these trifluoro-anilines significantly reduced virulence factors such as motility, protease activity, hemolysis, and indole production. Both trifluoro-anilines caused noticeable destruction to the membrane of bacterial cells and, at 100 µg/mL, exhibited bactericidal activity against V. parahaemolyticus within 30 min. Toxicity assays using the Caenorhabditis elegans and seed germination models showed that the compounds displayed mild toxicity. As a result, ACNBF and ITFMA inhibited the growth of both planktonic cells and biofilm formation. Furthermore, these active compounds effectively prevented the formation of biofilm on the surfaces of shrimp and squid models, highlighting their potential use in controlling seafood contamination., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Patients with systemic lupus erythematosus (SLE) are susceptible to infectious diseases owing to various immunosuppressive treatments and disease characteristics. Meningococcal infections progress rapidly with a high incidence of severe complications and mortality; therefore, meningococcal vaccination is needed. However, there is limited evidence regarding the immunity and immunogenicity of patients with SLE., Purpose: This study aimed to analyze the serum bactericidal activity against meningococci in patients with SLE in two domestic institutions in Korea., Methods: Serum samples were collected from patients diagnosed with SLE (age < 19 years) at Seoul National University Children's Hospital and Ewha Womans University Mokdong Hospital in 2016-2018. Serum bactericidal activity against the four meningococcal serogroups was analyzed using a serum bactericidal assay with rabbit serum. The patients' demographic information, diagnostic history, and disease activity status were obtained from electronic medical records., Results: The mean age of the 41 included patients was 20.3±5.4 (range, 10-35) years. All but one patient received steroids. The sera of most of the patients (34/41 [82.9%]) lacked bactericidal activity against serogroup A. Some patients showed bactericidal activity against serogroups C, W-135, and Y (63.4%, 56.1%, and 61.0%, respectively). There were no significant differences in the geometric mean indices based on complement consumption state or anti-double-stranded DNA antibody positivity., Conclusion: Although the sera of some patients exhibited serum bactericidal activity against meningococci, most remained seronegative. It is important that patients with SLE at risk of meningococcal infection receive appropriate vaccinations. Our findings serve as baseline serological data for meningococcal vaccination policies for patients with SLE.

The current study investigates the use of mixed-mode chromatography as a combination of anion-exchange (AEX) and hydrophobic interaction chromatography (HIC) for the analysis and purification of single-stranded antisense oligonucleotides with stereo-controlled phosphorothioate inter- nucleotide linkages. Initially a Scherzo-SS-C18 trimodal stationary phase with reversed-phase/AEX/ cation-exchange (CEX) functionalities is systematically evaluated to reveal the presence of U-shaped retention composed of two retention modes namely AEX and HIC, where the latter was also observed on related trimodal Scherzo SM and SW analogues. For the first time, retention and separation of deprotected oligonucleotides was described on a single mixed-mode column using a combination of AEX and HIC. This methodology was later applied to an alternative reversed-phase/AEX support, Newcrom BH, displaying similar retention trends under dual salt / organic modifier gradients. The merit of the method was assessed on the basis of separations between a phosphodiester (PO) impurity and phosphorothioate (PS) target for an assortment of selected 2'-O-methoxyethyl 18- to 20-mer single-stranded antisense oligonucleotides. Various parameters were evaluated mostly under HIC conditions including organic modifier percentage, type of salt, temperature, pH and type of buffer in the mobile phase. Retention of the oligonucleotides was significantly affected by the acetonitrile composition and the type of salt ((NH 4 ) 2 SO 4 , NaBr, NaCl) where the latter NaCl also afforded resolution between the PS target and closely eluting PO impurities. Small changes in pH between 6.5 and 7 using MES and TRIS respectively demonstrated notable differences in retention and resolution. The optimized methods were compared against a range of traditional supports and applied to various mixed-mode analogues, possessing embedded amino acid, complex forming weak cation-exchange and terminal strong cation-exchange functionalities. The mixed-mode supports displayed HIC retention and better resolution between PS target and PO impurity was evident with a more focused 5 % acetonitrile gradient over its 10 % counterpart. Overall, throughout the study AEX and HIC demonstrated comparable resolution trends. Finally, the optimized HIC method was applied to a selected 18-mer antisense oligonucleotide at semi-preparative scale using the Newcrom BH column, affording purities of 60-80 % and recoveries of 52-76 %. Although HIC does not provide better separations between PS and PO than AEX, it opens possibilities to operate under non-denaturing conditions and allows purification of samples containing high salt content, as a standalone method or post AEX without a prior desalting step, which can result in 20-30 % sample loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Connective tissue disease (CTD) comprising a various range of autoimmune disorders is often accompanied by lung involvement, which can lead to life-threatening complications. The main types of CTDs that can present as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD poses a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis by clinical, serological, and radiographic assessments is crucial to differentiate CTD-ILD from idiopathic forms and to adopt appropriate therapeutic strategies. Therefore, we have reviewed the numerous clinical manifestations and diagnostic approaches for each type of CTD-ILD, considering the diversity and complexity of CTD-ILD. The significance of a multidisciplinary approach in optimizing the management of CTD-ILD has been underscored by recent therapeutic advancements, which include the use of immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways implicated in the pathogenesis. Therapeutic strategies should be tailored to each condition, considering the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Furthermore, we aimed to provide clinical guidance including therapeutic recommendations for the effective management of CTD-ILD, based on PICO analysis.

Background: Regular physical activity (PA) is important for reducing the risk of chronic diseases and improving overall health. Activity Quotient (AQ) is a novel metric that translates heart rate during PA into a weekly score, providing an objective measure of an individual's PA. We prospectively examined the association of AQ with cancer and cardiovascular (CVD) mortality outcomes, the two major causes of death, in a Taiwanese population., Methods: A cohort of 515,608 healthy adults (52 % women) enrolled in a standard medical screening program was followed for mortality outcomes. The weekly AQ score of each participant was estimated based on self-reported PA intensity and weekly duration, and placed into six categories (0, ≤50, 51-99,100-149, 150-199, or ≥ 200 AQ per week). We used multivariable Cox proportional hazard models adjusted for potential confounders to estimate the hazard ratios (HR) and 95 % confidence intervals (CI)., Results: Higher weekly AQ scores were associated with lower risks of CVD, cancer, and all-cause mortalities. Compared with inactive individuals, HRs (CI) for the association of AQ scores of ≤50, 50-99, 100-149, 150-199, and ≥ 200 were 0.93 (0.89-0.97), 0.91 (0.85-0.96), 0.84 (0.77-0.91), 0.84 (0.74-0.96), and 0.81 (0.73-0.90) with cancer mortality; and 0.88 (0.83-0.93), 0.86 (0.80-0.93), 0.81 (0.73-0.90), 0.71 (0.60-0.85), and 0.73 (0.64-0.84) with CVD mortality, respectively. Subgroup analyses showed that meeting 50 AQ a week was associated with lower risk of disease specific mortality risk across age groups and among individuals with known risk factors. Higher weekly AQ scores were also associated with longer life expectancy, with the highest gains observed among those achieving 150-199 weekly AQ., Conclusion: Our findings show that AQ may be an objective tool for assessing and tracking PA and predicting mortality risks. Encouraging individuals to achieve ≥50 AQ a week could have substantial public health benefits, including lower mortality from major chronic diseases as well as prolonged health- and life expectancy., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Inc.)

Kiwifruit ( Actinidia deliciosa )-derived actinidin, a cysteine protease, is renowned for its meat-tenderizing and milk-clotting activities. Despite its potential in various biotechnological applications, an efficient expression platform for actinidin production has not yet been developed. Instead, actinidin has traditionally been purified directly from the fruits of various plants. This study aimed to produce kiwifruit-derived actinidin in the leaves of Nicotiana benthamiana . The expressed actinidin was directed to the lumen of the endoplasmic reticulum (ER) using the binding immunoglobulin protein (BiP) signal sequence and an ER retention signal. To facilitate cost-effective purification, the family 3 cellulose-binding module (CBM3) was employed as an affinity tag, along with microcrystalline cellulose beads that bind efficiently to CBM3. A significant portion of the expressed actinidin was recovered in the soluble fraction without proteolytic degradation. The purified actinidin exhibited β-casein-degrading activity, with optimal efficiency observed at 55°C and pH 7.0. These results establish a promising plant-based platform for the efficient production and functional application of kiwifruit-derived actinidin in diverse biotechnological processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Kang, Lee and Lee.)

Antarctic organisms are known for producing unique secondary metabolites, and this study specifically focuses on the less-explored metabolites of the moss Warnstorfia fontinaliopsis. To evaluate their potential bioactivity, we extracted secondary metabolites using four different solvents and identified significant lipase inhibitory activity in the methanol extract. Non-targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on this extract predicted the presence of 12 compounds, including several not previously reported in mosses. To gain insights into their enzyme inhibitory activity, the binding affinities of these candidate compounds to lipase were evaluated through in silico molecular docking. Further validation by molecular dynamics (MD) simulations revealed that hyocholic acid and pheophorbide A form stable complexes with human pancreatic lipase (HPL). Based on these results, targeted fractionation experiments were performed, yielding eight fractions. Among these, Fractions 4 and 6, which are assumed to contain those compounds, exhibited higher lipase inhibitory activity compared to the crude extract. Additionally, pharmacokinetic properties of those compounds were analyzed using SwissADME and Molinspiration calculations, suggesting their potential as drug candidates. This study establishes a promising methodology for identifying rare bioactive compounds of low abundance in underexplored natural resources by combining LC-MS/MS analysis with molecular docking. These findings also provide new insights into the chemical ecology of Antarctic mosses and their potential applications in pharmaceutical development., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Informed consent was obtained from 6 participants included in the study. Consent for Publish: The authors give the consent for publication. Conflict of Interest: The authors declare no competing interests. Disclaimer: The content is solely the responsibility of the authors., (© 2025. The Author(s).)

Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known for its anti-inflammatory properties. In this study, we investigated the effects of CBG in a cellular model of 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). In the cellular model, we confirmed the cytotoxicity of CBG and downregulated the expression of inflammatory markers CCL26 , IL1B , IL6 , and TNF ( p < 0.001). In the mouse model, clinical, histological, and immunological changes were analyzed. The results showed that CBG improved dermatitis severity score, epidermal thickness, and mast cell count and reduced inflammatory cytokines ( Tslp , Il1b , Il4 , Il6 , Il13 , Il17 , Il18 , Il22 , and Il33 ) by qRT-PCR ( p < 0.001). Western blot results showed modulated changes in JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, and p-STAT6 ( p < 0.05). Subsequently, p-IκBα, NF-κB, and p-NF-κB signaling factors were also reduced ( p < 0.05), with corresponding changes in skin barrier factors. The results of this study indicate that CBG effectively alleviates AD-like symptoms and suggest the potential of CBG as a therapeutic agent.

Membrane capacitive deionization (MCDI) is an electrochemical ion separation process that combines ion-exchange membranes (IEMs) with porous carbon electrodes to enhance desalination efficiency and address the limitations of conventional capacitive deionization (CDI). In this study, a cation-exchange membrane (CEM) embedded with a metal-organic framework (MOF) was developed to effectively separate monovalent and multivalent cations in influent solutions via MCDI. To fabricate CEMs with high monovalent ion selectivity, ZIF-8 was incorporated into sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (SPPO) at various weight ratios. The resulting membranes were systematically characterized using diverse electrochemical methods. The ZIF-8-embedded CEMs demonstrated a sieving effect based on differences in ion size and hydration energy, achieving excellent permselectivity for monovalent ions. MCDI tests using the prepared CEMs showed a Na + ion removal rate exceeding 99% in Na + /Mg 2+ and Na + /Ca 2+ mixed feed solutions, outperforming a commercial membrane (CSE, Astom Corp., Tokyo, Japan), which achieved a removal rate of 94.1%. These findings are expected to provide valuable insights for advancing not only MCDI but also other electro-membrane processes capable of selectively separating specific ions.

This study aimed to investigate the effects of β-glucan derived from Euglena gracilis (EGB), an edible microalga, on particulate matter (PM 2.5 )-induced airway inflammation in A549 cells and BALB/c mice. EGB effectively suppressed the mRNA and protein levels of inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-8) and mediators (iNOS, COX-2), while inhibiting the NF-κB and MAPK signaling pathways triggered by PM 2.5 exposure and reducing nuclear NF-κB levels. Additionally, EGB decreased PM 2.5 -induced ROS production and increased the protein levels of NRF2 and HO-1, along with genes encoding antioxidant enzymes (catalase, GPx, SOD1), associated with elevated nuclear NRF2 levels. EGB reduced immune cell infiltration and inflammatory cytokine levels in BALF and serum, both of which increased by PM 2.5 exposure. EGB also significantly increased alveolar numbers while decreasing the gene expression of MMP1/9/13. Furthermore, EGB suppressed PM 2.5 -induced bronchial thickening and collagen-1 deposition by downregulating TGF-β1 expression, and alleviated goblet cell hyperplasia and mucin production in lung tissues. These results suggest that EGB effectively reduces PM 2.5 -induced airway inflammation by suppressing NF-κB and MAPK signaling pathways, lowering pro-inflammatory cytokines, and activating the NRF2-HO-1 signaling pathway to enhance antioxidant enzyme expression. This study highlights the potential of EGB as an edible functional agent for controlling PM-related airway inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

The development of quantum dot light-emitting diodes (QLEDs) represents a promising advancement in next-generation display technology. However, there are challenges, especially in achieving efficient hole injection, maintaining charge balance, and replacing low-stability organic materials such as PEDOT:PSS. To address these issues, in this study, self-assembled monolayers (SAMs) were employed to modify the surface properties of NiO, a hole injection material, within the structure of ITO/HIL/TFB/QDs/ZnMgO/Al QLEDs. Specifically, using Br-2PACz-based SAMs resulted in surface defect passivation, improved hole injection, reduced exciton quenching, and enhanced electrical characteristics. Notably, QLEDs based on (NiO+Br-2PACz) demonstrated a turn-on voltage of 2.4 V, a maximum external quantum efficiency (EQE) of 8.30%, a maximum luminance of 88,831 cd/m 2 , and a maximum current efficiency of 32.78 cd/A. Compared to NiO-based QLEDs, these results represent a reduction in turn-on voltage by approximately 1.5 V, a 1.99-fold increase in EQE, and a 3.63-fold increase in luminance, indicating significantly enhanced performance with notable improvements in turn-on voltage, EQE, and luminance. They also showed higher EQE and luminance than PEDOT:PSS-based QLEDs; this could be attributed to the downshifting of energy levels by Br-2PACz, which reduced the hole injection barrier, increased the conductivity, and improved charge balance. In particular, the reduction in exciton quenching and the increase in electrical conductivity contributed significantly to the overall performance enhancement of the (NiO+Br-2PACz)-based QLEDs. This paper proposes a simple method for inorganic hole injection layer functionalize and application.

Background: While evidence from preclinical and observational cohort studies have suggested potential disparities in tumour behaviour associated with the choice of intra-operative anaesthetics, clinical evidence of tumour recurrence and metastasis remains inconclusive. We aimed to compare the impact of intra-operative anaesthesia on oncologic outcomes following hepatectomy for hepatocellular carcinoma., Methods: Adult patients scheduled for elective hepatectomy for hepatocellular carcinoma were assigned randomly (1:1) to either propofol-based total intravenous anaesthesia or sevoflurane-based inhalational anaesthesia. For recurrence-free survival, overall survival, intrahepatic recurrence-free survival and extrahepatic recurrence-free survival, the survival curves of the two groups were estimated using the Kaplan-Meier method and compared with the log-rank test. The primary outcome was one-year recurrence-free survival., Results: Among the 536 patients enrolled, primary analysis comprised 228 and 226 patients in the total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia groups, respectively. The probability of recurrence-free survival at one year was 79.1% (47 events) and 77.7% (50 events) in the total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia groups, respectively (adjusted hazard ratio 1.04, 95%CI 0.72-1.52). The probability of intrahepatic and extrahepatic recurrence-free survival, as well as overall survival at one year, was not significantly different between total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia: 81.3% (42 events) vs. 81.7% (41 events); 91.5% (19 events) vs. 88.8% (25 events); 99.1% (2 events) vs. 100.0% (no event), respectively. Subgroup analyses revealed that in patients undergoing open hepatectomy, total intravenous anaesthesia was associated with a significantly lower hazard of tumour recurrence or death (hazard ratio 0.49, 95%CI 0.25-0.95, p = 0.034), while in patients undergoing laparoscopic surgery, no significant difference was observed (hazard ratio 1.14, 95%CI 0.73-1.80, p = 0.558)., Discussion: Intra-operative anaesthesia technique did not affect postoperative recurrence and overall survival in patients with hepatocellular carcinoma undergoing hepatectomy., (© 2025 Association of Anaesthetists.)

Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression., Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule., Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days. Blood samples for PK analysis were collected pre-dose and up to 24 hours post-dose. The primary PK parameters (AUC last and AUC τ ) were evaluated. PD endpoints included integrated gastric acidity, percentage of time with intragastric pH > 4 over 24-hour and nighttime intervals, and percent change in serum gastrin levels after multiple dosing., Results: A total of 22 participants completed the study. YYD601 displayed more prolonged plasma concentration-time profiles than the conventional formulation, although the extent of the systemic exposure (AUC values) showed no statistically significant difference between the two formulations. With regard to the 24-hour gastric acid inhibition, YYD601 was comparable to the conventional formulation. The YYD601 showed a greater tendency for acid inhibition at night, as indicated by the percentage change of time with nocturnal acid breakthrough and other PD parameters. Both treatments were well tolerated, with no serious adverse events reported., Conclusion: Through extended systemic exposure of esomeprazole, YYD601 produces gastric acid suppression that is comparable to that of the conventional esomeprazole formulation, with a greater tendency to suppress acid at night. YYD601 20 mg was safe and well tolerated following single and multiple oral administrations, supporting its use as an effective alternative to conventional esomeprazole therapy., Clinical Trial Registry: http://clinicaltrials.gov, NCT03985319 (Date of registration: May 29, 2019; Study period: between July 2019 and March 2020)., Competing Interests: The authors report no conflicts of interest regarding the content of this article., (© 2025 Lee et al.)

Background and Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan., Materials and Methods: We quantified iNPH, Parkinson disease, Alzheimer disease, and healthy controls on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for the Evans index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction., Results: A total of 452 patients (200 men; mean age, 73.2 [SD, 6.5] years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained area under the curve (AUC) values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intraclass correlation values of 0.824 for the callosal angle and 0.924 for the Evans index were measured. By means of the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936., Conclusions: We demonstrated a machine learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRIs with minimal human intervention, making possible large-scale iNPH screening., (© 2025 by American Journal of Neuroradiology.)

Background: We investigated whether plasma β-hydroxybutyrate levels, a genetic risk score for Alzheimer's disease, and their interaction are associated with incident Alzheimer's disease., Methods: Using data from the UK Biobank-a population-based cohort study of adults aged 40-69 years, we assessed associations between baseline plasma β-hydroxybutyrate level, genetic risk score for Alzheimer's disease, and incident Alzheimer's disease. Incident Alzheimer's disease data were collected through linked data from hospital admissions and death registries., Results: In total, 261,933 adults were included, 1978 of whom developed incident Alzheimer's disease. Plasma β-hydroxybutyrate concentrations were not independently associated with Alzheimer's disease incidence after adjusting for covariates, whereas a higher genetic predisposition was linked to increased Alzheimer's disease incidence. Interactions were observed between plasma β-hydroxybutyrate concentrations and genetic risk for Alzheimer's disease on Alzheimer's disease incidence (P < 0.001)., Conclusions: Further studies are warranted to elucidate the impact of plasma β-hydroxybutyrate status on Alzheimer's disease incidence., Competing Interests: Conflict of interest John C. Newman is co-founder and stockholder in BHB Therapeutics Ltd and Selah Therapeutics Ltd, which develop consumer products and therapeutics related to ketone bodies., (Copyright © 2025. Published by Elsevier Ltd.)

Key Message: The single recessive Chilli veinal mottle virus resistance locus, cvr4, was fine-mapped in pepper through bulked segregant RNA sequencing combined with gene silencing analysis. Chilli veinal mottle virus (ChiVMV) is a widespread pathogen affecting the production of peppers (Capsicum annuum L.) in Asia and Africa. Few loci conferring resistance to ChiVMV have been identified, severely limiting the development of resistant cultivars. To identify ChiVMV resistance genes, we constructed an F 2:3 segregating population derived from a cross between the ChiVMV-resistant cultivar 'CV9' and the susceptible cultivar 'Jeju'. The inheritance study of F 2:3 populations showed a 1:3 ratio of resistant to susceptible individuals, demonstrating the existence of a single recessive ChiVMV resistance gene in CV9; we named this gene cvr4. To map the cvr4 locus, we employed bulked segregant analysis by RNA sequencing (BSR-seq) of pools from resistant and susceptible F 2:3 individuals. We mapped cvr4 to the telomeric region of pepper chromosome 11. To narrow down the cvr4 locus, we developed additional molecular markers in the cvr4 target region, leading to a 2-Mb region of chromosome 11 showing complete co-segregation with the ChiVMV resistance phenotype. Using the polymorphisms identified during BSR-seq, we defined a list of 15 candidate genes for cvr4, which we tested through virus-induced gene silencing analysis for ChiVMV resistance. Of these, the silencing of several genes (DEM.v1.00021323, DEM.v1.00021336, and DEM.v1.00021337) restricted virus spread. Although DEM.v1.00021323 transcript levels were similar between the resistant and susceptible bulks, its alternative spliced isoforms differed in abundance, suggesting that the splicing variants of DEM.v1.00021323 might affect viral infection. These findings may facilitate the breeding of ChiVMV-resistant cultivars in pepper., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

Endovascular treatment of femoropopliteal artery (FPA) disease with drug-coated balloons (DCBs) may face complications such as arterial recoil, dissection, and residual stenosis. Angiography has limited accuracy for evaluating blood flow through revascularized target lesions. Thus, there is a need for postprocedure hemodynamic assessment in treated limbs. This study aims to explore how postprocedure ankle-brachial index (ABI) influences outcomes following DCB treatment for FPA disease. This study included patients in a multicenter registry (K-VIS ELLA) treated with DCB for FPA disease between January 2006 and August 2021. Optimal postprocedure ABI cutoff for predicting clinically driven target lesion revascularization (TLR) was determined using receiver operating characteristic curve analysis. Independent predictors of TLR were identified using multivariable Cox regression analysis. A total of 654 limbs (514 patients) treated with DCB for FPA were evaluated by ABI at 1-day (median, interquartile range, 1 to 2 days) postprocedure and followed up for a median of 370 days. The optimal immediate postprocedure ABI cutoff value for predicting TLR was 0.72 (area under the curve, 0.68). Significantly improved TLR-free and major adverse limb event-free survival rates were observed with a postprocedure ABI ≥ 0.72 (hazard ratio [HR] = 0.24, 95% confidence intervals [CI] = 0.16 to 0.37, p < 0.001; HR = 0.25, 95% CI = 0.16 to 0.38, p < 0.001, respectively). Independent predictors of TLR were postprocedure ABI < 0.72 (HR 3.76; 95% CI, 2.33 to 6.07; p < 0.001) and presence of anemia (HR 2.01; 95% CI, 1.03 to 3.92; p = 0.041). An immediate postprocedure ABI is a significant predictor of TLR risk following DCB treatment for FPA disease, underscoring the value of hemodynamic assessment in optimizing angioplasty outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Young-Guk Ko reports financial support was provided by Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea. Young-Guk Ko reports financial support was provided by Cardiovascular Research Center (Seoul, Korea). Young-Guk Ko reports a relationship with Medtronic that includes: funding grants. Young-Guk Ko reports a relationship with Korea United Pharm that includes: funding grants. Young-Guk Ko reports a relationship with Cook Medical that includes: funding grants. Young-Guk Ko reports a relationship with Boston Scientific that includes: funding grants. Young-Guk Ko reports a relationship with Otsuka Korea that includes: funding grants. Young-Guk Ko reports a relationship with Dong-A ST that includes: funding grants. Young-Guk Ko reports a relationship with Samjin Pharm that includes: funding grants. Young-Guk Ko reports a relationship with Cordis that includes: funding grants. Donghoon Choi reports a relationship with Medtronic that includes: funding grants. Donghoon Choi reports a relationship with Korea United Pharm that includes: funding grants. Donghoon Choi reports a relationship with Cook Medical that includes: funding grants. Donghoon Choi reports a relationship with Boston Scientific that includes: funding grants. Donghoon Choi reports a relationship with Otsuka Korea that includes: funding grants. Donghoon Choi reports a relationship with Dong-A ST that includes: funding grants. Donghoon Choi reports a relationship with Samjin Pharm that includes: funding grants. Donghoon Choi reports a relationship with Cordis that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Objective: This study analysed the characteristics of new drugs listed under the pharmaco-economic evaluation exemption (PEE) system from 2015 to 2022 in South Korea and examined the factors influencing the pricing decisions under this system., Methods: A mixed-methods statistical approach was used to comprehensively evaluate the factors influencing drug pricing under PEE system. Descriptive statistics provide an overview of the dataset, while inferential statistics, including t-tests and Pearson's correlation analyses, are used to explore variable associations. Multiple and hierarchical regression models identify and quantify the key determinants of drug prices, controlling for multicollinearity among the variables., Results: From 2015 to 2022, 30 new drugs were listed under the PEE system. The average annual number of new drugs was four, but this figure significantly increased to eight in 2022. The "KOR/A7 lowest" variable exhibited a strong negative correlation with the budget impact variable (coefficient: 0.838, P < 0.001), indicating that drugs with higher budget impact tend to have lower prices compared to the A7 countrie's lowest price., Conclusion: Since the introduction of the PEE system in South Korea, patient access to new drugs has significantly improved. However, the rising expenditure on pharmaceuticals has made budget impact a significant consideration in pricing decisions, highlighting the need for ongoing monitoring of drug expenditure by payers. As the system evolves, enhanced oversight and policy adjustments will be crucial for balancing cost containment with equitable patient access. Developing tiered RSA models based on drug classification or therapeutic impact could be a viable approach to achieving this balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Yu and Lee.)

Cold stress during the seedling stage significantly threatens rice ( Oryza sativa L.) production, specifically in temperate climates. This study aimed to identify quantitative trait loci (QTLs) associated with cold tolerance at the seedling stage. QTL analysis was conducted on a doubled haploid (DH) population derived from a cross between the cold-sensitive indica cultivar 93-11 and the cold-tolerant japonica cultivar Milyang352. Phenotypic analysis was conducted over 2 years (2022-2023) under cold water treatment (13°C) at the Chuncheon Substation, South Korea. Cold tolerance scores were used to classify the DH populations and parental lines. In 2022, three QTLs were identified on chromosomes 3, 10, and 11; in 2023, a single QTL was identified on chromosome 10. The QTL qCTS10 22/23 on chromosome 10 was consistently observed across both years, explaining up to 16.06% and 40.55% of the phenotypic variance, respectively. Fine-mapping of qCTS10 22/23 narrowed the candidate region to a 300-kb interval containing 44 polymorphic single-nucleotide polymorphisms. Among the candidate genes, Os10g0409400 was significantly expressed in the cold-tolerant japonica parent Milyang352 under cold stress, indicating its role in conferring cold tolerance. These findings offer valuable insights into the genetic mechanisms of cold tolerance and highlight qCTS10 22/23 as a potential target for marker-assisted selection in rice breeding programs to enhance cold tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Jo, Jang, Lee, Lee, Cho, Kang, Kwon, Lee, Park, Kwon and Lee.)

Carbon nanotubes (CNTs) have garnered significant interest in the field of nanotechnology owing to their unique structure and exceptional properties. These materials find applications across a diverse array of fields, including electronics, environmental science, energy, and biotechnology. CNTs serve as potent reinforcing agents in polymer composites; even minimal additions can significantly improve the mechanical, electrical, and thermal properties of polymers. With the growing demand for polymer composites across various industries, there is an anticipation for CNT/polymer composites to evolve in increasingly diverse directions. This paper reviews recent advancements in the manufacturing techniques of various CNT/polymer composites and discusses the enhancements in their mechanical, electrical, and thermal properties. Furthermore, it explores the potential applications of these composites.

To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated. The resolution of subretinal fluid(SRF), intraretinal fluid(IRF), and serous pigment epithelial detachment(PED) was also assessed. In addition, factors associated with complete resolution of SRF and IRF were investigated. A total of 69 patients were included in this study. BCVA significantly improved from a mean logarithm of minimal angle of resolution of 0.64 ± 0.41 at baseline to 0.47 ± 0.39 at 3 months (P < 0.001). CRT significantly decreased from 424.1 ± 155.5 μm at baseline to 266.3 ± 71.7 μm at 3 months (P < 0.001). At baseline, SRF was observed in 55 eyes (79.7%), IRF in 39 eyes(56.5%), and serous PED in 57 eyes(82.6%). By 3 months, the number of eyes showing these findings had decreased to 11 eyes(15.9%) for SRF, 6 eyes(8.7%) for IRF, and 10 eyes(14.5%) for serous PED. The presence of type 2 (88.2%) and type 3 (94.7%) macular neovascularization(MNV) was associated with a high incidence of complete resolution of SRF and IRF after treatment. Three loading injections of faricimab resulted in significant functional and anatomical improvements in treatment-naïve neovascular AMD, with a high rate of resolution of SRF, IRF, and serous PED. The anatomical effects were especially pronounced in cases of type 2 and type 3 MNV., Competing Interests: Declarations. Competing interests: Jae Hui Kim received lecture fees from Bayer, Novartis, Roche, Samsung Bioepis, and Chong Kun Dang Pharmaceutical Corp. Han Joo Cho received lecture fees from Bayer, Novartis, Roche. The remaining authors (H.Y.H., S.M.P., J.H.L., C.G.K., J.W.K.) declare no conflicts of interest., (© 2025. The Author(s).)

Background: The Field Epidemiology Training Program Frontline, initiated by the Korea Disease Control and Prevention Agency in 2019, aims to enhance the competencies of infectious disease practitioners across 17 regions in South Korea. With the September 2024 amendment to the Infectious Disease Prevention Act mandating infectious disease prevention and crisis response training for government employees who are associated with infectious diseases responses, there is an urgent need to assess and optimize the effectiveness and cost-efficiency of such competency-based education programs amidst constraints of budget and manpower., Methods: This study examined the educational needs and priorities of public health competencies among infectious disease practitioners. The competency framework for Infectious Disease Response Practitioners (IDRP) in South Korea was used to evaluate the validity, importance, and performance level of competencies for infectious disease response personnel. For the training needs analysis, differences in performance by group were analyzed, and an importance performance analysis (IPA) was conducted using the Borich Needs Assessment based on the IPA matrix to derive training priorities., Results: The analysis revealed a significant gap between perceived importance and self-reported performance levels in most competencies, especially epidemiologic methods. Competencies related to safety and ethics, fieldwork, and crisis management have high importance and performance ratings, indicating a need for ongoing training. Of the 27 competencies, the IPA identified specific training needs and priorities, suggesting eight competencies for focused intervention to strengthen the capacity of IDRPs., Conclusion: The IDRP competency framework in South Korea plays a pivotal role in establishing a standardized, competency-based approach to training IDRP. The identified gaps and training priorities highlight the need for continued curriculum development and the integration of real-world, field-based scenarios into training programs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2025 The Korean Academy of Medical Sciences.)

High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.S using a sequential target trial emulation framework. The primary end point was kidney recovery at hospital discharge, defined as survival to discharge with serum creatinine <1.5-fold baseline and without dialysis-dependence. Key secondary end points were time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death. Using multivariable logistic and Cox regression models, we compared outcomes in patients who received glucarpidase within 4 days following MTX initiation with those in patients who did not. Among 708 patients with MTX-AKI, 209 (29.5%) received glucarpidase. Overall, 183 (25.8%) had a primary end point event. Glucarpidase receipt was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% CI, 1.69-4.31) compared to no glucarpidase receipt. Patients treated with glucarpidase also had faster time-to-kidney recovery (adjusted hazard ratio [aHR], 1.88, 95% CI, 1.18-3.33) and lower risks of grade ≥2 neutropenia (adjusted odds ratio [aOR], 0.50, 95% CI, 0.28-0.91) and grade ≥2 transaminitis (aOR, 0.50, 95% CI, 0.28-0.91) on day 7. There was no difference in time-to-death (aHR, 0.76; 95 CI, 0.49-1.18). These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI., (Copyright © 2025 American Society of Hematology.)