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Dysregulated host response against infection triggers sepsis that leads to multiple organ dysfunction due to uncontrolled inflammatory responses. Despite marked progress in understanding of sepsis, numerous clinical trials for treatment of sepsis have proven daunting and a new therapeutic approach is highly needed. CE9A215 (inotodiol), a fungal secondary metabolite, has been researched for its pharmacological activities and has shown potent anti-allergic effects. In this study, we evaluated the anti-inflammatory activities of CE9A215 upon lipopolysaccharide (LPS) stimulation in vivo and in vitro for the first time. CE9A215 decreased the production of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-1β in a concentration-dependent manner in LPS-stimulated RAW264.7 cells. Intriguingly, in human mast cell line LUVA, CE9A215 significantly lowered IL-4 and IL-10, and this effect could be beneficial for the clearance of bacterial infection. In addition, administration of CE9A215 improved the survival rate of LPS-stimulated mice and inhibited the pro-inflammatory cytokines, IL-6, TNF-α, and IL-1β in blood. Moreover, CE9A215 enhanced the expression levels of plasma phospholipid transfer protein (PLTP), apolipoprotein E (ApoE), and ATP-binding cassette transporter (ABCA1) in LPS-stimulated RAW246.7 cells. Liver PLTP level increased significantly in the CE9A215-administered group compared with the control group, which implies that CE9A215 promotes LPS clearance and neutralization by reverse transport of LPS by increasing the expressions of PLTP, ApoE, and ABCA1. Our results highlight CE9A215's potential as a novel therapeutic option for the treatment of sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information, while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: (1) MRI-to-CT and (2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (≥0.87/0.90) and gamma pass rates for photon (≥98.1%/99.0%) and proton (≥97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy. It showcased the growing capacity of deep learning to produce high-quality sCT, reducing reliance on conventional CT for treatment planning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Maspero reports financial support was provided by EWUU alliance. Manya Afonso, Maureen van Eijnatten reports financial support was provided by EWUU alliance. Runqi Wang, Tao Song, Zhihao Zhang, Long Wang reports a relationship with Subtle Medical that includes: employment. Alexandra Alain-Beaudoin, Silvain Bériault reports a relationship with Elekta Ltd that includes: employment. Alexandra Alain-Beaudoin, Silvain Beriault has patent pending to Elekta Ltd. Pengxin Yu reports a relationship with Infervision Medical Technology Co., Ltd that includes: employment. Gengwan Li, Xueru Zhang reports a relationship with Canon Medical Systems Corporation that includes: employment. Lujia Zhong, Zhiwei Deng reports financial support was provided by University of Southern California. Valentin Boussot reports financial support was provided by French National Research Agency. Valentin Boussot reports financial support was provided by Rennes Métropole. Cédric Hémon reports financial support was provided by Elekta AB. Cédric Hémon reports financial support was provided by CominLabs. Valentin Boussot reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with Centre Eugène Marquis that includes: employment. Lu Bai, Shaobin Wang reports a relationship with MedMind Technology Co. Ltd that includes: employment. Lu Bai and Shaobing Wang had adopted some training ideas from Du Yi who is a staff in Institute of Medical Technology, Peking University Health Science Center, Beijing, China Derk Mus, Bram Kooiman reports a relationship with MRI Guidance BV that includes: employment. Chelsea Sargeant reports a relationship with Elekta AB that includes: funding grants and travel reimbursement. Edward Henderson reports a relationship with Manchester Cancer Research Centre that includes: funding grants and travel reimbursement. Zijie Chen, Enpei Wang reports a relationship with Shenying Medical Technology (Shenzhen) Co., Ltd that includes: employment. 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which leads to demyelination, axonal loss, and neurodegeneration. Increased oxidative stress and neurodegeneration have been implicated in all stages of MS, making neuroprotective therapeutics a promising strategy for its treatment. We previously have reported vinyl sulfones with antioxidative and anti-inflammatory properties that activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that induces the expression of cytoprotective genes against oxidative stress. In this study, we synthesized vinyl sulfoximine derivatives by modifying the core structure and determined therapeutic potential as Nrf2 activators. Among them, 10v effectively activated Nrf2 (EC 50 = 83.5 nM) and exhibited favorable drug-like properties. 10v successfully induced expression of Nrf2-dependent antioxidant enzymes and suppressed lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells. We also confirmed that 10v effectively reversed disease progression and attenuated demyelination in an experimental autoimmune encephalitis (EAE) mouse model of MS.

Early diagnostics of breast cancer is crucial to reduce the risk of cancer metastasis and late relapse. Exosome, which contains distinct information of its origin, can be the target object as a liquid biopsy. However, its low sensitivity and inadequate diagnostic tools interfere with the point-of-care testing (POCT) of the exosome. Recently, Surface-enhanced Raman Scattering (SERS) spectroscopy, which amplifies the Raman scattering, has been proved as a promising tool for exosome detection. However, the fabrication process of SERS probe or substrate is still inefficient and far from large-scale production. This study proposes rapid and label-free detection of breast cancer-derived exosomes by statistical analysis of SERS spectra using silver-nanoparticle-based SERS substrate fabricated by selective laser ablation and melting (SLAM). Employing silver nanowires and optimizing laser process parameters enable rapid and low-energy fabrication of SERS substrate. The functionalities including sensitivity, reproducibility, stability, and renewability are evaluated using rhodamine 6G as a probe molecule. Then, the feasibility of POCT is examined by the statistical analysis of SERS spectra of exosomes from malignant breast cancer cells and non-tumorigenic breast epithelial cells. The presented framework is anticipated to be utilized in other biomedical applications, facilitating cost-effective and large-scale production performance., (© 2024 Wiley‐VCH GmbH.)

Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA., Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group., Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants., Conclusion: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

In 2009, Lyubashevsky proposed a lattice-based signature scheme using the Schnorr-like identification and the Fiat-Shamir heuristic and proved its security under the collision resistance of a generalized compact knapsack function. However, their security analysis requires the witness indistinguishability property, leading to significant inefficiency and an increase of sizes of public key and signature. To overcome the efficiency issue associated with the WI property, we introduce a new lattice-based assumption, called the target-modified one-wayness problem of the GCK function and show its reduction to well-known lattice-based problems. Additionally, we present a simple and efficient GCK-based signature scheme, GCKSign, whose security is based on the Module GCK-TMO problem in the random oracle model. GCKSign is a natural extension of Lyubashevsky's scheme in a module setting, but achieves considerable efficiency gains due to eliminating the witness indistinguishability property. As a result, GCKSign achieves approximately 3.4 times shorter signature size and 2.4 times shorter public key size at the same security level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Woo 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.)

Erastin, a ferroptosis-inducing system x c - inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system x c - ., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cartilage, a critical tissue for joint function, often degenerates due to osteoarthritis (OA), rheumatoid arthritis (RA), and trauma. Recent research underscores necroptosis, a regulated form of necrosis, as a key player in cartilage degradation. Unlike apoptosis, necroptosis triggers robust inflammatory responses, exacerbating tissue damage. Key mediators such as receptor-interacting serine/threonine-protein kinase-1 (RIPK1), receptor-interacting serine/threonine-protein kinase-3(RIPK3), and mixed lineage kinase domain-like (MLKL) are pivotal in this process. Studies reveal necroptosis contributes significantly to OA and RA pathophysiology, where elevated RIPK3 and associated proteins drive cartilage degradation. Targeting necroptotic pathways shows promise; inhibitors like Necrostatin-1 (Nec-1), GSK'872, and Necrosulfonamide (NSA) reduce necroptotic cell death, offering potential therapeutic avenues. Additionally, autophagy's role in mitigating necroptosis-induced damage highlights the need for comprehensive strategies addressing multiple pathways. Despite these insights, further research is essential to fully understand necroptosis' mechanisms and develop effective treatments. This review synthesizes current knowledge on necroptosis in cartilage degeneration, aiming to inform novel therapeutic approaches for OA, RA, and trauma.

Duck hepatitis A virus type 1 (DHAV-1) is the main pathogen causing viral hepatitis in ducks, marked by high contagion and acute mortality. Live attenuated DHAV-1 vaccines are widely used to control the disease. This study aims to develop a mismatch amplification mutation assay (MAMA)-PCR for the rapid detection and differentiation of Korean DHAV-1 wild-type strains from vaccine strains. A MAMA primer was designed to target a single nucleotide polymorphism (SNPs) at position 2276 within the VP1 gene, allowing differentiation in a single PCR reaction. The MAMA-PCR accurately identified both strains, with detection limits of 10 0.5 ELD 50 /mL and 10 2.3 ELD 50 /mL, respectively. The MAMA-PCR demonstrated specificity, showing no cross-reactivity with 12 other viral and bacterial pathogens. The MAMA-PCR was applied to 89 farms, yielding results consistent with nested-PCR and sequence determination, identifying four positive farms for DHAV-1 vaccine strains. In conclusion, this study is the first to employ the MAMA-PCR method to distinguish between DHAV-1 wild-type and vaccine strains. The developed method is rapid, simple, specific, and sensitive, thereby serving as an effective tool for clinical diagnostics in identifying and differentiating between Korean DHAV-1 wild-type and vaccine strains.

Background/Objectives : Geriatric hip fracture patients have an increased risk of malnutrition. Proper nutritional supply in the perioperative period is very important for their recovery. Oral nutritional supplements (ONSs) are recommended in geriatric hip fracture patients to improve dietary intake and prevent complications. This study aimed to evaluate the efficacy of postoperative ONSs after total hip arthroplasty in geriatric hip fracture patients. Methods : A retrospective study of elderly patients who underwent total hip arthroplasty for hip fracture was conducted. Data from patients who received ONSs postoperatively until hospital discharge (ONS group, n = 69) were compared with patients who did not receive ONSs (control group, n = 168). Laboratory test results, including serum protein and albumin levels, length of hospital stay, and the incidence of postoperative medical complications of the two groups, were analyzed. Results : Preoperative serum protein and albumin levels were significantly higher in the control group ( p = 0.002 and p = 0.010, respectively). However, the degree of decline for both protein and albumin levels was significantly less in the ONS group ( p < 0.001 for both). Serum albumin levels were significantly higher in the ONS group at postoperative two-week follow-up ( p = 0.006). The length of hospital stay was shorter in the ONS group ( p < 0.001). The incidence of postoperative delirium was significantly higher in the control group ( p = 0.007). Conclusions : In geriatric hip fracture patients, postoperative ONSs can improve postoperative nutritional status, shorten the length of hospital stay, and reduce the incidence of postoperative delirium.

The objectives of this study were to produce biochars using sulfur-rich acidified lignin discharged from a biorefinery process and to evaluate their physicochemical properties and Pb adsorption capacity. As the pyrolysis temperature increased, the lignin acidified by the desulfurization process was converted to neutralized biochar (LBC), which exhibited high carbon content and stability. The carbon content of biochar manufactured at a pyrolysis temperature of 600 °C or higher was over 90 % and showed no significant difference, and their surface structures were found to be different, as revealed through XRD and FTIR analyses. The adsorption capacity of Pb by LBC increased with increasing pyrolysis temperature, and their adsorption capacity was well described by the pseudo-second-order model and the Langmuir isotherm adsorption model. In particular, the internal diffusion effect on the adsorption capacity of Pb was greater for LBC900 than for LBC600. In complex heavy metal solutions, LBC selectively exhibited high affinity for Pb, while the adsorption capacity of other metals was significantly reduced. The adsorption mechanism of Pb by LBC was verified through various analytical methods, and these results demonstrated that the adsorption of Pb by LBC was influenced by functional groups existing on the surface and inside of LBC and by some cation exchange., 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.)

Single-cell data analysis can infer dynamic changes in cell populations, for example across time, space or in response to perturbation, thus deriving pseudotime trajectories. Current approaches comparing trajectories often use dynamic programming but are limited by assumptions such as the existence of a definitive match. Here we describe Genes2Genes, a Bayesian information-theoretic dynamic programming framework for aligning single-cell trajectories. It is able to capture sequential matches and mismatches of individual genes between a reference and query trajectory, highlighting distinct clusters of alignment patterns. Across both real world and simulated datasets, it accurately inferred alignments and demonstrated its utility in disease cell-state trajectory analysis. In a proof-of-concept application, Genes2Genes revealed that T cells differentiated in vitro match an immature in vivo state while lacking expression of genes associated with TNF signaling. This demonstrates that precise trajectory alignment can pinpoint divergence from the in vivo system, thus guiding the optimization of in vitro culture conditions., (© 2024. The Author(s).)

Introduction: The Mindfulness-Based Stress Reduction (MBSR) Program for breast cancer survivors (BCS) is designed to enhance cognitive training through formal and informal meditational practices. This randomized clinical trial (RCT) aimed to evaluate if BCS assigned to either the MBSR(BC), Breast Cancer Education Support (BCES), or Usual Care (UC) regimens experienced greater improvements at 6, 12, and 26 weeks on objective and subjective cognitive performance. Methods: BCS ( n = 212) randomized to a three-group RCT: MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31) were assessed on cognitive performance and symptoms at baseline, 6, 12, and 26 weeks. Linear mixed models were fit to evaluate the effects of the MBSR(BC) program, hypothesizing ordered effect improvements: (MBSR[BC] highest, BCES intermediate, UC lowest) along with baseline characteristics evaluated as moderators. Results: Of the BCS (mean age of 57), 73% were White, and non-Hispanic, and 77% received both chemotherapy (CT) and radiation. Cognitive performance improved in all groups. Although there were no statistically significant between-group differences in cognitive outcomes, significant symptom reductions occurred for the MBSR(BC) group ( p = 0.003). Within-group effect size analysis at 26 weeks showed substantial improvements in all three groups (effect sizes >0.50) in subjective impairments and quality of life (effect size >0.50) and objective measures of cognitive performance. MBSR(BC) showed the largest within-group effect size in the reduction of fatigue (effect size = 0.81). Effect sizes occurred in the hypothesized direction for 10 of the 18 outcomes. Discussion: Although the MBSR(BC) program did not show significant differences in cognitive performance compared with BCES and UC, all groups improved and reductions in fatigue were beneficial for MBSR(BC). Results suggest that cognitive performance may improve after CT over time considering one's natural history. Furthermore, BCS enrolled in RCTs may be more motivated to improve their health status (NCT02786797).

Background: Endovascular therapy (EVT) has become the preferred treatment modality for femoropopliteal disease. However, there is limited evidence regarding its procedural and clinical outcomes according to the affected area., Aims: The aim of this study is to investigate clinical outcomes and device effectiveness according to treatment extent in the superficial femoral artery (SFA), popliteal artery (PA), or both., Methods: In this study, we analysed EVT for SFA (2,404 limbs), PA (155 limbs), SFA/PA (383 limbs) using the population in the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry. The primary endpoint was target lesion revascularisation (TLR) at 2 years., Results: The SFA/PA group exhibited a higher prevalence of anatomical complexity, characterised by long lesions, moderate to severe calcification, and total occlusion. The procedures were successful in 97.2% of SFA, 92.9% of PA, and 95.6% of SFA/PA EVTs. The 2-year TLR rates were 21.1%, 18.6%, and 32.7% in the SFA, PA, and SFA/PA groups, respectively. SFA/PA EVT was associated with a significantly increased risk for TLR compared to the SFA group (adjusted hazard ratio [HR] 1.48 [1.09-2.00]; p=0.008) and a trend towards an increased risk compared to the PA group (adjusted HR 1.80 [1.00-3.27]; p=0.052). After overlap weighting, the use of a drug-coated balloon (DCB) was shown to be beneficial, with the lowest TLR rate after SFA and SFA/PA EVT., Conclusions: In this large real-world registry, SFA/PA EVT was associated with an increased risk for TLR at 2 years compared to the SFA or PA EVT groups, with favourable outcomes when using a DCB or drug-eluting stent in the SFA/PA EVT group.

Introduction: Thiazides are utilized in general hypertension management, however, their role in chronic kidney disease (CKD) hypertension management remains unclear. Although data support thiazide efficacy in advanced CKD, the adverse effect profile (including estimated glomerular filtration rate [eGFR] decline and electrolyte abnormalities) may lead to thiazide discontinuation. The authors assessed the thiazide discontinuation rate in Kaiser Permanente Southern California members with moderate-to-severe CKD and hypertension., Methods: This study was a multicenter retrospective analysis evaluating Kaiser Permanente Southern California members with hypertension and CKD 3B or 4 who filled a thiazide prescription in 2021, with follow-up through 2022. The outcomes were thiazide discontinuation rate, reason for thiazide discontinuation, time to thiazide discontinuation, and discontinuing practitioner specialty. Mean changes in blood pressure and eGFR from baseline were also evaluated., Results: Of the 401 patients followed for 1 year after thiazide initiation, 65 patients discontinued a thiazide (discontinuation rate: 16.2%, mean time to discontinuation: 7.5 months). Of the 201 patients followed for 2 years after thiazide initiation, 57 patients discontinued a thiazide (discontinuation rate: 28.4%, mean time to discontinuation: 15.5 months). The most commonly documented thiazide discontinuation reason was increased serum creatinine (30% of total reasons at 1 year and 39% of total reasons at 2 years)., Conclusion: Most patients with hypertension and CKD 3B or 4 continued on a thiazide with favorable blood pressure lowering effects and modest eGFR decline. Thiazides may be considered viable antihypertensive options with close renal function monitoring for patients with moderate-to-severe CKD., Competing Interests: Conflicts of Interest None declared

Monzogranite is known for its high surface area and cation exchange capacity, which play a crucial role in ameliorating the challenges by enhancing nutrient adsorption and facilitating nutrient availability during the weaning period. Weaned crossbred piglets (Duroc × Yorkshire × Landrace), initially weighing 5.36 ± 0.26 kg, were allocated into four treatments with 6 replicates each (10 pigs per replicate). The treatments encompassed CON (basal diet), Z0.1 (0.1% monzogranite supplementation in basal diet), Z0.2 (0.2% monzogranite supplementation), and Z0.3 (0.3% monzogranite supplementation). In phase 1, a linear increase in total average daily gain (ADG) was observed across treatment groups, with a concomitant linear increase in ADG and gain-to-feed ratio (G/F). The overall results showed a linear increase in ADG and G/F. A linear decrease in aspartate aminotransferase and lactate dehydrogenase levels was observed across treatment groups. Conversely, no significant differences were noted in the levels of albumin, alkaline phosphatase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, blood urea nitrogen, triglycerides, and gamma-glutamyl transferase among the treatment groups. Faecal scoring indicated a linear reduction in scores at Day 7 among the treatment groups. However, no significant differences were observed at Days 14 and 28. The assessment of immunoglobulins demonstrated a significant increase in both immunoglobulin G and immunoglobulin A levels in the Z0.1 treatment group compared to the CON. In both phase 1 and phase 2, a linear decrease in cortisol levels was evident. In conclusion, a linear increase in total ADG and G/F during phase 1, sustained across both phases, suggests monzogranite potential to enhance growth performance. Moreover, stress mitigation was shown through a consistent linear decrease in cortisol levels across phases. These findings underscore monzogranite multifaceted impact, emphasizing its potential as a dietary supplement to enhance growth, liver health, and stress resilience in weanling pigs., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background/objectives: Nasal morphology is a significant aspect of facial anatomy and is often used for forensic identification and aesthetic surgery. This study aims to compare nasal dimensions based on sex, facial index (FI), and nasal index (NI) using cone-beam computed tomography (CBCT) and 3D modeling., Methods: To observe differences in nasal dimensions by sex and analyze the relationships between facial shapes (FI) and nasal forms (NI), a total of 100 participants (50 males, 50 females) in their 20s were selected from Dankook University Dental Hospital. CBCT scans were performed, and 3D models were created using Mimics software (version 22.0). The measurement items included the alaria distance between (AL), the distance between N (nasion) and SN (subnasale), the distance between N (nasion) and PRN (pronasale), and the distance between SN (subnasale) and PRN (pronasale). A T -test was used for the sex-based analysis of the nasal dimensions, and the facial index- and nasal index-based nasal dimensions were analyzed using a one-way ANOVA with Scherffe's post hoc test. Additionally, all the statistical analyses were performed using SPSS software (version 23.0)., Results: The results indicated that males generally have larger nasal dimensions than females. Additionally, the mesoprosopic facial type (round face) showed the largest nasal dimensions in the FI classification, while the platyrrhine nasal type (broad and short nose) exhibited the largest dimensions in the NI classification., Conclusions: This study demonstrates that the nasal size varies significantly with sex, facial shape, and nasal form. The findings can contribute to forensic identification and provide valuable data for clinical practices in facial reconstruction and nasal surgery.

Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The current approach for predicting the likelihood of response to ICB is a single proportional biomarker (PD-L1) expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with ICB response than PD-L1. However, their exact composition, size, and spatial biology in HNSCC remain understudied. A detailed understanding of TLS is required for future use as a clinically applicable predictive biomarker., Methods: Pre-ICB tumor tissue sections were obtained from 9 responders (complete response, partial response, or stable disease) and 11 non-responders (progressive disease) classified via RECISTv1.1. A custom multi-immunofluorescence (mIF) staining assay was designed, optimized, and applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblasts (alpha-Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). Spatial metrics were compared among groups. Serial tissue sections were scored for TLS in both H&E and mIF slides. A machine learning model was employed to measure the effect of these metrics on achieving a response to ICB (SD, PR, or CR)., Results: A higher density of B lymphocytes (CD20+) was found in responders compared to non-responders to ICB (p=0.022). A positive correlation was observed between mIF and pathologist identification of TLS (R2= 0.66, p-value= <0.0001). TLS trended toward being more prevalent in responders to ICB (p=0.0906). The presence of TLS within 100 um of the tumor was associated with improved overall (p=0.04) and progression-free survival (p=0.03). A multivariate machine learning model identified TLS density as a leading predictor of response to ICB with 80% accuracy., Conclusion: Immune cell densities and TLS spatial location within the tumor microenvironment play a critical role in the immune response to HNSCC and may potentially outperform CPS as a predictor of ICB response.

Background: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race., Methods: We evaluated associations between aggressive prostate cancer and four ND metrics-Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004-2021)., Results: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00-1.30; RI, OR = 1.27, CI, 1.07-1.51; redlining, OR = 1.77; CI, 1.23-2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13-1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men., Conclusions: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race., Impact: Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities., (©2024 American Association for Cancer Research.)

Using three-dimensional (3D) printing technology to fabricate Bi 2 Te 3 -based thermoelectric (TE) generators opens a potential way to create shape-conformable devices capable of recovering waste heat from thermal energy sources with diverse surface morphologies. However, pores formed in 3D-printed Bi 2 Te 3 -based materials by the removal of the organic ink binder result in unsatisfactory performance compared to the bulk materials, which has limited the widespread application of the ink-based 3D printing process. Furthermore, managing the volatile Se element in the n-type materials poses significant technological challenges compared to the p-type counterparts, resulting in a scarcity of research on 3D printing of n-type Bi 2 Te 3 . Here, we synthesized edge-oxidized graphene (EOG)-incorporated Se-free n-type Bi 1.7 Sb 0.3 Te 3 (BST) using a direct ink writing (DIW) process with a binder-free novel ink. The incorporated EOG provides connectivity between small BST grains separated by pores and induces a bimodal-like grain structure during the DIW and sintering process. The optimal EOG content of 0.1 wt % in 3D-printed n-type BST simultaneously achieved both carrier transport control and active phonon scattering, due to its unique microstructure. A maximum ZT of 0.71 was obtained in the 0.1 wt % EOG/BST materials at 448 K, comparable to commercial bulk n-type Bi 2 Te 3 -based materials. Further, a single-element device composed of the EOG-BST material exhibited a 2-fold improvement in performance compared to pure-BST. These results open a technological route for the application of 3D printing technology for ink-based TE materials.

Background and Objectives : This study investigated whether there is an association between elderly frailty and asthma. Material Methods : We examined 9745 elderly participants who did not have asthma and 275 elderly patients who had asthma diagnosed by a doctor from the 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons Survey. Study Selections: The Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale was used to determine their level of frailty. The relationship between frailty and geriatric asthma was examined using multiple logistic regression analysis, which was adjusted for a number of confounding variables (socioeconomic, health behavior, psychological characteristics, and functional status). Results : Frailty as defined by the K-FRAIL scale was significantly higher in the asthma group (7.6%) than the non-asthma group (4.9%). The frailty phenotype component showed that resistance, ambulation, and illness severity were more severe in the asthma group than the non-asthma group. After adjusting, asthma was significantly associated with an increased risk of frailty (OR 1.45; 95% confidence interval [CI] 1.01-2.09) compared to the non-asthma group. Conclusions : Frailty might be associated with elderly asthma in patients from the Korean population. Frailty may not only be associated with asthma, but also with other diseases. So, more evidence is needed to establish this association.

Maintaining a healthy intestinal environment, optimal epithelial barrier integrity, and balanced gut microbiota composition are essential for the growth performance of weaning pigs. We identified Lactiplantibacillus argentoratensis AGMB00912 (LA) in healthy porcine feces as having antimicrobial activity against pathogens and enhanced short-chain fatty acid (SCFA) production. Herein, we assess the protective role of LA using a weaning mouse model with enterotoxigenic Escherichia coli (ETEC) infection. LA treatment improves feed intake and weight gain and alleviates colon shortening. Furthermore, LA inhibits intestinal damage, increases the small intestine villus height compared with the ETEC group, and enhances SCFA production. Using the Kyoto Encyclopedia of Genes and Genomes and other bioinformatic tools, including InterProScan and COGNIZER, we validated the presence of SCFA-producing pathways of LA and Lactiplantibacillus after whole genome sequencing. LA mitigates ETEC-induced shifts in the gut microbiota, decreasing the proportion of Escherichia and Enterococcus and increasing SCFA-producing bacteria, including Kineothrix , Lachnoclostridium , Roseuburia , Lacrimispora , Jutongia , and Blautia . Metabolic functional prediction analysis revealed enhanced functions linked to carbohydrate, amino acid, and vitamin biosynthesis, along with decreased functions associated with infectious bacterial diseases compared to the ETEC group. LA mitigates the adverse effects of ETEC infection in weaning mice, enhances growth performance and intestinal integrity, rebalances gut microbiota, and promotes beneficial metabolic functions. These findings validate the functionality of LA in a small animal model, supporting its potential application in improving the health and growth performance of weaning pigs., 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 © 2024 Yoon, Yang, Yeom, Kim, Park, Song, Eun, Park, Lee, Kim, Lee and Kim.)

Nanopatterned halide perovskites have emerged to improve the performance of optoelectronic devices by controlling the crystallographic and optical properties via morphological modification. However, the correlation between the photophysical property and morphology transformation in nanopatterned perovskite films remains elusive, which hinders the rational design of nanopatterned halide perovskites for optoelectronic devices. In this study, we employed nanoimprinting lithography on a perovskite film to exert a precise control over grain growth and manipulate electronic structures at the level of individual grains. Surface-selective fluorescence lifetime imaging microscopy (FLIM) analyzes the spatiotemporally disentangled geometrical variations in carrier recombination rate and band structure modulation according to different pattern morphologies. Consequently, the stereoscopic mechanism of confined grain growth was unveiled, highlighting the quantitative grain size-based parameters that are crucial for nanoscale material engineering. Notably, the pattern-induced reduction of effective charge mass enabled exclusive control over the subdiffusive carrier transport dynamics on perovskite surfaces, ultimately realizing the surface-selective perovskite photodetectors. The implications of this study are expected to provide valuable guidelines, inspiring innovative design protocols for advancing the next-generation optoelectronic technologies.

Sialylation during N-glycosylation plays an important role in the half-life of therapeutic glycoproteins in vivo and has sparked interest in the production of therapeutic proteins using recombinant Chinese hamster ovary (rCHO) cells. To improve the sialylation of therapeutic proteins, we examined the effect of sialyllactose supplementation on sialylation of Fc-fusion glycoproteins produced in rCHO cells. Two enzymatically-synthesized sialyllactoses, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), were administered separately to two rCHO cell lines producing the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44, respectively. Two sialyllactoses successfully increased sialylation of Fc-fusion glycoprotein in both cell lines, as evidenced by isoform distribution, sialylated N-glycan formation, and sialic acid content. Increased sialylation by adding sialyllactose was likely the result of increased amount of intracellular CMP-sialic acid (CMP-SA), the direct nucleotide sugar for sialylation. Furthermore, the degree of sialylation enhanced by sialyllactoses was slightly effective or nearly similar compared with the addition of N-acetylmannosamine (ManNAc), a representative nucleotide sugar precursor, to increase sialylation of glycoproteins. The effectiveness of sialyllactose was also confirmed using three commercially available CHO cell culture media. Taken together, these results suggest that enzymatically-synthesized sialyllactose represents a promising candidate for culture media supplementation to increase sialylation of glycoproteins in rCHO cell culture., 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.)

The burgeoning field of bioinformatics has seen a surge in computational tools tailored for omics data analysis driven by the heterogeneous and high-dimensional nature of omics data. In biomedical and plant science research multi-omics data has become pivotal for predictive analytics in the era of big data necessitating sophisticated computational methodologies. This review explores a diverse array of computational approaches which play crucial role in processing, normalizing, integrating, and analyzing omics data. Notable methods such similarity-based methods, network-based approaches, correlation-based methods, Bayesian methods, fusion-based methods and multivariate techniques among others are discussed in detail, each offering unique functionalities to address the complexities of multi-omics data. Furthermore, this review underscores the significance of computational tools in advancing our understanding of data and their transformative impact on research., Competing Interests: Declaration of competing interest All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

Sageretia thea, a notable species within the mock buckthorn genus, is recognized for its intriguing biogeographical distribution and diverse medicinal properties. Despite this significance, genomic studies on S. thea are still in the nascent stages. We present the first chromosome-level genome assembly of S. thea that was generated using a combination of Oxford Nanopore long-read and Illumina short-read sequencing technologies complemented by Pore-C chromatin conformation capture. The genome assembly had a size of 197.8 Mb with 12 chromosomal scaffolds and a scaffold N50 length of 15.9 Mb. A total of 25,434 protein-coding genes were identified and functionally annotated, and the gene model indicated 96.5% complete eukaryotic BUSCOs. Additionally, orthologous gene profiling and synteny analysis were performed to elucidate the evolutionary relationships within the Rhamnaceae family and Rosales. This high-quality chromosomal genome is the first genomic view of S. thea, which will serve as the basis for future studies on its biological and medicinal properties, and evolutionary history., (© 2024. The Author(s).)

The matrisome, a group of proteins constituting or interacting with the extracellular matrix (ECM), has garnered attention as a potent regulator of cancer progression. An increasing number of studies have focused on cancer matrisome utilizing diverse -omics approaches. Here, we present diverse patterns of matrisomal populations within cancer tissues, exploring recent -omics studies spanning different '-omics' levels (epigenomics, genomics, transcriptomics, and proteomics), as well as newly developed sequencing techniques such as single-cell RNA sequencing and spatial transcriptomics. Some matrisome genes showed uniform patterns of upregulated or downregulated expression across various cancers, while others displayed different expression patterns according to the cancer types. This matrisomal dysregulation in cancer was further examined according to their originating cell type and spatial location in the tumor tissue. Experimental studies were also collected to demonstrate the identified roles of matrisome genes during cancer progression. Interestingly, many studies on cancer matrisome have suggested matrisome genes as effective biomarkers in cancer research. Although the specific mechanisms and clinical applications of cancer matrisome have not yet been fully elucidated, recent techniques and analyses on cancer matrisomics have emphasized their biological importance in cancer progression and their clinical implications in deciding the efficacy of cancer treatment., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF., Methods and Results: This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H 2 FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP-peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H 2 FPEF score subgroup (all P <0.05). LAP-peak increased with pacing (19.5 to 22.5 mm Hg) but decreased with isoproterenol (20.4 to 18.4 mm Hg). Under pacing, patients with PAF exhibited a significantly lower LAP-peak (90 bpm) than those with persistent AF (17.7±8.2 versus 21.1±9.3 mm Hg, P <0.001). However, there was no difference in LAP-peak (120 bpm) between the 2 groups (22.1±8.1 versus 22.9±8.4 mm Hg, P =0.056) because the LAP-peak significantly increased with heart rate in the group with PAF., Conclusions: Patients with PAF exhibited lower baseline LAP with greater increases during rapid pacing compared with individuals with persistent AF, indicating a need to revise the H 2 FPEF score for distinguishing PAF from persistent AF and emphasizing the importance of rate and rhythm control in PAF for symptom control., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02138695.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Abnormal glial activation promotes neurodegeneration in Alzheimer's disease (AD), the most common cause of dementia. Stimulation of the cGAS-STING pathway induces microglial dysfunction and sterile inflammation, which exacerbates AD. We showed that inhibiting STING activation can control microglia and ameliorate a wide spectrum of AD symptoms. The cGAS-STING pathway is required for the detection of ectopic DNA and the subsequent immune response. Amyloid-β (Aβ) and tau induce mitochondrial stress, which causes DNA to be released into the cytoplasm of microglia. cGAS and STING are highly expressed in Aβ plaque-associated microglia, and neuronal STING is upregulated in the brains of AD model animals. The presence of the APOE ε4 allele, an AD risk factor, also upregulated both proteins. STING activation was necessary for microglial NLRP3 activation, proinflammatory responses, and type-I-interferon responses. Pharmacological STING inhibition reduced a wide range of AD pathogenic features in App NL-G-F /hTau double-knock-in mice. An unanticipated transcriptome shift in microglia reduced gliosis and cerebral inflammation. Significant reductions in the Aβ load, tau phosphorylation, and microglial synapse engulfment prevented memory loss. To summarize, our study describes the pathogenic mechanism of STING activation as well as its potential as a therapeutic target in AD., (© 2024. The Author(s).)

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance antioxidant and anti-inflammatory activity. Among PG derivatives, 6 a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6 a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1β, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6 a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6 a, is a potential treatment for neurodegenerative diseases., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Background: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea., Methods: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023., Results: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ 2  = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ 2  = 9.056, p = .029)., Conclusion: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Addressing the critical health concerns posed by domoic acid (DA), a neurotoxic compound produced by toxic marine algae and bioaccumulated in shellfish, necessitates the development of a rapid, precise, and robust detection system. Traditional DA detection methods have stability and sensitivity issues, which hinder effective toxin detection. To overcome these limitations, we developed a novel direct competitive enzyme-linked immunosorbent assay (dc-ELISA) platform that utilizes peptide-immobilized magnetic beads (MGBs/peptide). The affinity peptides identified through phage display and chemically synthesized with biotin labels present an innovative alternative to conventional antibodies for ELISA applications. Streptavidin-modified MGBs were used as the bioreceptor carriers to facilitate magnetic separation and simplify sample preparation, making the MGB/peptide-based dc-ELISA platform an ideal tool for comprehensive monitoring efforts. The developed platform exhibits a detection range of 0.5-10 ng mL -1 and a low limit of detection of 0.29 ng mL -1 , offering enhanced sensitivity and cost-effectiveness. Moreover, our developed dc-ELISA demonstrated a high recovery rate when validated with DA-spiked CRM-mussel samples. This method overcomes the limitations of traditional detection techniques and offers a scalable and efficient approach to marine toxin surveillance with improved marine environmental monitoring and public health management., 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 Ltd. All rights reserved.)

Introduction: The geriatric nutritional risk index (GNRI) can easily identify malnutrition-associated morbidity and mortality. We investigated the association between preoperative GNRI and 30-d mortality in geriatric burn patients who underwent surgery., Methods: The study involved geriatric burn patients (aged ≥ 65 y) who underwent burn surgery between 2012 and 2022. The GNRI was computed using the following formula: 1.489 × serum albumin concentration (mg/L) + 41.7 × patient body weight/ideal body weight. Patients were dichotomized into the high GNRI (≥ 82) and low GNRI (< 82) groups. GNRI was evaluated as an independent predictor of 30-d postoperative mortality. The study also evaluated the association between GNRI and sepsis, the need for continuous renal replacement therapy (CRRT), major adverse cardiac events (MACE), and pneumonia., Results: Out of 270 patients, 128 (47.4%) had low GNRI (< 82). Multivariate Cox regression analysis revealed that low GNRI was significantly associated with 30-d postoperative mortality (hazard ratio: 1.874, 95% confidence interval [CI]: 1.146-3.066, P = 0.001). Kaplan-Meier analysis revealed that the 30-day mortality rate differed significantly between the low and high GNRI groups (log-rank test, P < 0.001). The 30-d postoperative mortality (hazard ratio: 2.677, 95% CI: 1.536-4.667, P < 0.001) and the incidence of sepsis (odds ratio [OR]: 2.137, 95% CI: 1.307-3.494, P = 0.004), need for CRRT (OR: 1.919, 95% CI: 1.101-3.344, P = 0.025), MACE (OR: 1.680, 95% CI: 1.018-2.773, P = 0.043), and pneumonia (OR: 1.678, 95% CI: 1.019-2.764, P = 0.044), were significantly higher in the low GNRI group than in the high GNRI group., Conclusions: Preoperative low GNRI was associated with increased 30-d postoperative mortality, sepsis, need for CRRT, MACE, and pneumonia in geriatric burn patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microglia play a crucial role in synaptic elimination by engulfing dystrophic neurons via triggering receptors expressed on myeloid cells 2 (TREM2). They are also involved in the clearance of beta-amyloid (Aβ) plaques in Alzheimer's disease (AD); nonetheless, the driving force behind TREM2-mediated phagocytosis of beta-amyloid (Aβ) plaques remains unknown. Here, using advanced 2D/3D/4D co-culture systems with loss-of-function mutations in TREM2 (a frameshift mutation engineered in exon 2) brain organoids/microglia/assembloids, it is identified that the clearance of Aβ via TREM2 is accelerated by externalized phosphatidylserine (ePtdSer) generated from dystrophic neurons surrounding the Aβ plaques. Moreover, it is investigated whether microglia from both sporadic (CRISPR-Cas9-based APOE4 lines) and familial (APP NL-G-F /MAPT double knock-in mice) AD models show reduced levels of TREM2 and lack of phagocytic activity toward ePtdSer-positive Aβ plaques. Herein new insight is provided into TREM2-dependent microglial phagocytosis of Aβ plaques in the context of the presence of ePtdSer during AD progression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: The objective of this study was to identify the difference on pain intensity and disability between particulate and nonparticulate steroid injections in patients with lumbar radicular pain. Subgroup analysis by study design, type of particulate steroid, and follow-up duration were performed., Data Sources: We performed the literature search in the PubMed, Embase, and Cochrane Library up March, 2023., Study Selection: Studies, including randomized controlled trials (RCTs) and nonrandomized studies, that compared particulate steroid injection and nonparticulate steroid injection in patients with lumbar radicular pain were independently reviewed by 2 reviewers for eligibility for inclusion., Data Extraction: Outcomes of interest were pain intensity and disability. Two reviewers independently assessed the quality of included studies using the revised Cochrane Risk of Bias (RoB2.0) tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions Tool (ROBINS-I) for nonrandomized studies. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD)., Data Synthesis: A total of 10 studies were included in this meta-analysis. The results showed no significant difference in visual analog scale, disability score and the numbers of patients with 50% pain reduction between particulate and nonparticulate steroid injection groups (P>.05). Particulate steroid injections showed significant better effect in pain scale in RCTs (MD=0.62; 95% CI 0.08-1.16, P=.02). In subgroup analysis with steroid types, methylprednisolone showed better effect compared with dexamethasone, while dexamethasone showed better effect compared with betamethasone., Conclusions: This meta-analysis suggested no significant differences between the particulate and nonparticulate steroid groups in pain or disability score. Therefore, considering the safety profile of nonparticulate steroids, nonparticulate steroid injection may be helpful in patients with lumbar radicular pain., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF., Methods: This hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF., Results: After adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51-3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70-4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19-3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56-9.05), was associated with IPF after adjusting for age, sex, and smoking., Conclusions: Smoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans . The refined PPTEE-glycan demonstrated robust immune stimulation in vitro , activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo , promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans -derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

Background and Aims: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls., Methods and Results: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20)., Conclusion: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry., Methods: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR)., Results: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years., Conclusions: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Background: A new Liobagrus fish was reported from the Korean Peninsula, but research on this taxon is lacking. Moreover, existing research on the mitogenome of the genus Liobagrus in Korea is very limited, and no studies have been conducted on structural characteristics of transfer RNA (tRNA) or gene order comparisons between taxa; instead, research has been restricted to basic phylogeny., Objective: The complete mitochondrial genome of Liobagrus geumgangensis was analyzed for the first time. We then aimed to reconstruct the phylogenetic relationships of the genus Liobagrus and estimate the divergence time of speciation events., Methods: We used a dissected fin clip from an adult of Liobagrus geumgangensis. Genomic DNA was extracted and analyzed with whole genome sequencing (WGS) and assembled by the NOVOPlasty method. The mitogenome sequence was annotated, and a genome map, tRNA structure, and phylogenetic tree were constructed using maximum likelihood analysis. In addition, divergence time was estimated., Results: The mitochondrial genome was 16,522 bp in length and comprised 37 genes. The overall base composition was 30.5% A, 25.5% T, 28.4% C, and 15.7% G. Most tRNAs exhibited the typical clover leaf shape, except trnS1. Phylogenetic analysis revealed that Liobagrus geumgangensis clustered within a clade with four other Liobagrus species exclusive to the southern region of the Korean Peninsula. Its divergence was estimated to have occurred during the late Miocene., Conclusion: Characteristics of Liobagrus geumgangensis mitogenome were consistent with those of other torrent catfish species. Time scale estimation revealed distinct groupings, with some distributed across mainland Asia and others in the southern region of the Korean Peninsula. Notably, the Korean Peninsula group was identified as its own lineage, comprising entirely endemic species., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Aim of the Study: This study aimed to develop an artificial intelligence (AI) model capable of predicting shockable rhythms from electrocardiograms (ECGs) with compression artifacts using real-world data from emergency department (ED) settings. Additionally, we aimed to explore the black box nature of AI models, providing explainability., Methods: This study is retrospective, observational study using a prospectively collected database. Adult patients who presented to the ED with cardiac arrest or experienced cardiac arrest in the ED between September 2021 and February 2024 were included. ECGs with a compression artifact of 5 s before every rhythm check were used for analysis. The AI model was designed based on convolutional neural networks. The ECG data were assigned into training, validation, and testing sets on a per-patient basis to ensure that ECGs from the same patient did not appear in multiple sets. Gradient-weighted class activation mapping was employed to demonstrate AI explainability., Results: A total of 1,889 ECGs with compression artifacts from 172 patients were used. The area under the receiver operating characteristic curve (AUROC) for shockable rhythm prediction was 0.8672 (95% confidence interval [CI]: 0.8161-0.9122). The AUROCs for manual and mechanical compression were 0.8771 (95% CI: 0.8054-0.9408) and 0.8466 (95% CI: 0.7630-0.9138), respectively., Conclusion: This study was the first to accurately predict shockable rhythms during compression using an AI model trained with actual patient ECGs recorded during resuscitation. Furthermore, we demonstrated the explainability of the AI. This model can minimize interruption of cardiopulmonary resuscitation and potentially lead to improved outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Sukyo Lee reports financial support was provided by the Korean Association of Cardiopulmonary Resuscitation (KACPR). 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 © 2024 Elsevier B.V. All rights reserved.)

Dosimetry modeling and point of departure (POD) estimation using in vitro data are essential for mechanism-based hazard identification and risk assessment. This study aimed to develop a putative adverse outcome pathway (AOP) for humidifier disinfectant (HD) substances used in South Korea through a systematic review and benchmark dose (BMD) modeling. We collected in vitro toxicological studies on HD substances, including polyhexamethylene guanidine hydrochloride (PHMG-HCl), PHMG phosphate (PHMG-p), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), CMIT, and MIT from scientific databases. A total of 193 sets of dose-response data were extracted from 34 articles reporting in vitro experimental results of HD toxicity. The risk of bias (RoB) in each study was assessed following the office of health assessment and translation (OHAT) guideline. The BMD of each HD substance at different toxicity endpoints was estimated using the US Environmental Protection Agency (EPA) BMD software (BMDS). Interspecies- or interorgan differences or most critical effects in the toxicity of the HD substances were analyzed using a 95% lower confidence limit of the BMD (BMDL). We found a critical molecular event and cells susceptible to each HD substance and constructed an AOP of PHMG-p- or CMIT/MIT-induced damage. Notably, PHMG-p induced ATP depletion at the lowest in vitro concentration, endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), inflammation, leading to fibrosis. CMIT/MIT enhanced mitochondrial reactive oxygen species (ROS) production, oxidative stress, mitochondrial dysfunction, resulting in cell death. Our approach will increase the current understanding of the effects of HD substances on human health and contribute to evidence-based risk assessment of these compounds., 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 Ltd. All rights reserved.)

Manipulating the grain boundary and chiral structure of enantiomorphic inorganic thermoelectric materials facilitates a new degree of freedom for enhancing thermoelectric energy conversion. Chiral twist mechanisms evolve by the screw dislocation phenomenon in the nanostructures; however, contributions of such chiral transport have been neglected for bulk crystals. Tellurium (Te) has a chiral trigonal crystal structure, high band degeneracy, and lattice anharmonicity for high thermoelectric performance. Here, Sb-doped Te crystals are grown to minimize the severe grain boundary effects on carrier transport and investigate the interface of chiral Te matrix and embedded achiral Sb 2 Te 3 precipitates, which induce unusual lattice twists. The low grain boundary scattering and conformational grain restructuring provide electrical-favorable semicoherent interfaces. This maintains high electrical conductivity leading to a twofold increase in power factor compared to polycrystal samples. The embedded Sb 2 Te 3 precipitates concurrently enable moderate phonon scattering leading to a remarkable decrease in lattice thermal conductivity and a high dimensionless figure of merit (zT) of 1.1 at 623 K. The crystal growth and chiral atomic reorientation unravel the emerging benefits of interface engineering as a crucial contributor to effectively enhancing carrier transport and minimizing phonon propagation in thermoelectric materials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background and Aims: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS., Methods: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year., Results: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome., Conclusions: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT., Study Registration: PROSPERO (ID: CRD42023476470)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: This study introduces RealCAC-Net, an artificial intelligence (AI) system, to quantify carotid artery compressibility (CAC) and determine the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation., Methods: A prospective study based on data from a South Korean emergency department from 2022 to 2023 investigated carotid artery compressibility in adult patients with cardiac arrest using a novel AI model, RealCAC-Net. The data comprised 11,958 training images from 161 cases and 15,080 test images from 134 cases. RealCAC-Net processes images in three steps: TransUNet-based segmentation, the carotid artery compressibility measurement algorithm for improved segmentation and CAC calculation, and CAC-based classification from 0 (indicating a circular shape) to 1 (indicating high compression). The accuracy of the ROSC classification model was tested using metrics such as the dice similarity coefficient, intersection-over-union, precision, recall, and F1 score., Results: RealCAC-Net, which applied the carotid artery compressibility measurement algorithm, performed better than the baseline model in cross-validation, with an average dice similarity coefficient of 0.90, an intersection-over-union of 0.84, and a classification accuracy of 0.96. The test set achieved a classification accuracy of 0.96 and an F1 score of 0.97, demonstrating its efficacy in accurately identifying ROSC in cardiac arrest situations., Conclusions: RealCAC-Net enabled precise CAC quantification for ROSC determination during cardiopulmonary resuscitation. Future research should integrate this AI-enhanced ultrasound approach to revolutionize emergency care., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)