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Background: Rheumatoid arthritis (RA) and prolonged high-dose glucocorticoid (GC) treatment are established risk factors for osteoporosis., Objectives: In this study, we aimed to evaluate the therapeutic efficacy of denosumab according to the GC dose considered to increase the risk of glucocorticoid-induced osteoporosis (GIOP) in patients with RA., Design: A retrospective analysis of collected data on RA patients with osteoporosis starting denosumab., Methods: We included 418 patients with RA who were started on denosumab therapy and categorized them into those with and without GC intake ⩾2.5 mg/day for >3 months. The T -score and areal bone mineral density (aBMD) at the lumbar spine, total hip, and femur neck, as well as serum bone turnover markers, were measured at baseline and 12 months. We performed between-group and within-group comparisons of the BMD values at baseline and at 12 months., Results: Denosumab significantly increased the T -scores and aBMD at the lumbar spine, total hip, and femur neck after 12 months, regardless of GC intake. However, apart from the T -score at the lumbar spine, the other parameters did not show significant between-group differences. Similarly, in patients with anti-cyclic citrullinated peptide (CCP) antibody positivity or those treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), although there were significant increases in the T -score and areal BMD at all sites in both groups, there were no significant between-group differences., Conclusion: Our findings suggest that the GC dose considered to increase the risk of GIOP did not significantly attenuate the therapeutic efficacy of denosumab in RA patients, including those positive for anti-CCP antibodies and users of biologic or targeted synthetic DMARDs., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2025.)

Toxic and carcinogenic compounds, such as synthetic dyes and polyphenols, were widely employed and released as pollutants in a variety of industries, including textiles, food, and cosmetics. Biological oxidation process that used oxidizing enzymes to breakdown pollutant compounds were environmentally favorable. However, due to the cell toxicity of metal ions supplements used for the biosynthesis of oxidizing enzymes like laccase, their efficient application for biological degradation is limited. In this study, we aimed to boost laccase activity by introducing high copper resistance into whole-cell biocatalysts through irradiation-based accelerated evolution. Bacillus velezensis MBLB 0692, a laccase producing bacterium, was employed as model strain that exhibited severe sensitivity under 10 mM copper. The selected Cu-resistant mutants not only overcame growth inhibition, but also increased laccase activity by 2.6-fold. The qRT-PCR analysis confirmed that mutants showed significant change in gene expressions related to laccase generation and copper-related functions. Furthermore, dye decolorization assays showed that mutants degrade synthetic dyes more efficiently under high copper conditions. The varying decolorization efficiencies across dyes were attributed to differences in dye structure and the potential influence of copper on enzyme activity. Collectively, these findings emphasize the interaction between copper concentration and laccase activity, and present implications for environmental bioremediation., 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 Inc.)

Objective: Osteoporosis is a common comorbidity in patients with SLE, and bone loss in patients with SLE has a multifactorial aetiology. This study aimed to evaluate the therapeutic efficacy of denosumab in patients with SLE with osteoporosis and to analyse the factors influencing therapeutic efficacy., Methods: A total of 166 patients with SLE with osteoporosis who initiated denosumab between January 2016 and December 2023 were included. Changes in the T-score and areal bone mineral density (BMD) at the lumbar spine, total hip and femur neck from denosumab initiation to 12 months were measured. Correlation analysis was performed between the degree of BMD improvement and covariates including SLE-specific factors such as SLE duration, SLE Disease Activity Index 2000 (SLEDAI-2K) score, glucocorticoid dose and hydroxychloroquine use. Multiple linear regression analysis was conducted to identify predictors of the therapeutic efficacy of denosumab., Results: Denosumab significantly increased BMD and decreased bone turnover markers at 12 months compared with baseline. The degree of BMD improvement revealed a significant negative correlation with SLEDAI-2K score, hydroxychloroquine use, prior osteoporosis treatment and baseline BMD values. In contrast, body mass index and c-telopeptide of collagen type 1 levels were positively correlated with the degree of BMD improvement. Higher baseline BMD values, SLEDAI-2K scores and hydroxychloroquine use were significant predictors of attenuated BMD improvement., Conclusions: Our study suggests that denosumab is an effective treatment option for osteoporosis in patients with SLE. The therapeutic efficacy of denosumab can be predicted by baseline BMD values, SLEDAI-2K scores and hydroxychloroquine use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: While the significance of care navigation in facilitating access to health care within the lesbian, gay, bisexual, transgender, queer, and other (LGBTQ+) communities has been acknowledged, there is limited research examining how care navigation influences an individual's ability to understand and access the care they need in real-world settings. By analyzing private sector data, we can bridge the gap between theoretical research findings and practical applications, ultimately informing both business strategies and public policy with evidence grounded in real-world efficacy., Objective: The objective of this study was to evaluate the impact of specialized virtual care navigation services on LGBTQ+ individuals' ability to comprehend and access necessary care within a national cohort of commercially insured members., Methods: This case study is based on the experience of commercially insured members, aged 18 or older, who used the LGBTQ+ Health Care Navigation (LGBTQ+ Navigation) service by Included Health between January 26 and July 31, 2023. Care coordinators assisted members by connecting them with vetted identity-affirming in-network providers, helping them navigate and understand their LGBTQ+ health benefits, and providing education and advocacy for clinical and nonclinical needs. We examined the impact of navigation on 5 member-reported outcomes. In addition to reporting the proportion who agreed or strongly agreed, we calculated an impact score that averaged assigned numerical values to all 5 question responses (1=strongly disagree to 5=strongly agree) for each respondent. We used ANOVA with Tukey post hoc tests and t tests to explore the relationships between the impact score and member characteristics, including optional self-reported demographics., Results: Out of 4703 LGBTQ+ Navigation cases, 7.53% (n=354) had member-reported outcomes. A large majority of LGBTQ+ members agreed or strongly agreed that care navigation resulted in less stress (315/354, 89%), less care avoidance (305/354, 86.2%), higher confidence in finding an identity-affirming provider (327/354, 92.4%), improved ability to comprehend health care information (312/354, 88.1%), and improved ability to engage with providers (308/354, 87%). The average impact score was 4.44 (SD 0.69), with statistically significant differences by gender identity (P=.003), race (P=.01), ethnicity (P=.008), and pronouns (P=.02). The scores were highest for members with multiple gender identities (mean 4.56, SD 0.37), and members who did not provide their race, ethnicity, or their pronouns (mean 4.55, SD 0.64). Impact scores were lowest for transgender members (mean 4.11, SD 0.95)., Conclusions: The LGBTQ+ Navigation service, by enhancing members' comprehension and use of necessary care, demonstrates potential public health utility and value. Continuous evaluation of navigation services can serve as a supplementary tool for employers seeking to promote health equity and improve belonging among employees. This is particularly important as discrimination and stigma against LGBTQ+ communities persist in the United States. Therefore, scalable and system-level changes that use navigation services are essential to reach a larger proportion of the LGBTQ+ population., (© Seul Ki Choi, Jaclyn Marshall, Patrina Sexton Topper, Andrew Pregnall, José Bauermeister. Originally published in JMIR Formative Research (https://formative.jmir.org).)

Background: This study aims to investigate how A1 segment asymmetry-also known as A1 dominancy-influences the development of the anterior communicating artery aneurysm (AcomA) as it affects hemodynamic conditions within the circle of Willis (COW). Using time-of-flight magnetic resonance angiography (TOF-MRA), the research introduces a novel approach to assessing shear stress in A1 segments to uncover the hemodynamic factors contributing to AcomA formation., Method: An observational study was conducted over 6 years at a tertiary university hospital's outpatient clinic. Recruited patients who underwent TOF-MRA imaging were divided into AcomA and non-AcomA groups. MRA images were analyzed using semi-automatic software (VINT, Mediimg, Inc.) to calculate the signal intensity gradient (SIG), which reflects wall shear stress. The comparison metrics included general demographics, anatomical characteristics, and hemodynamic attributes of the COW, mainly focusing on A1 segment asymmetry., Results: Among the 700 subjects, 106 were categorized into the AcomA group, while 594 were placed in the non-AcomA group. The AcomA group showed a more significant difference in the bilateral A1 diameter (49.0% vs. 20.8%, p  < 0.001) and a greater prevalence of unilateral A1 aplasia (32.1% vs. 6.7%, p  < 0.001) compared to the non-AcomA group. Increased bilateral A1 asymmetry in the AcomA group corresponded with notable variations in A1 SIG, indicating increased wall shear stress. The occurrence of AcomA is associated with both anatomical factors of the circle of Willis, represented by the bilateral A1 diameter ratio, and hemodynamic factors, represented by the bilateral A1 SIG ratio, suggesting that both factors are almost equally significant., Conclusion: Our findings suggest that A1 segment asymmetry influences hemodynamic changes within the COW, contributing to AcomA formation. Hemodynamic factors provide an intuitive understanding of how anatomical characteristics within the COW can lead to aneurysm development., 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, Jeong and Hong.)

Benign prostatic hyperplasia (BPH) is a distressing health problem that can cause serious complications in aging men. Androgens are implicated in the causation of BPH. Portulaca oleracea (PO) is a natural product with diverse pharmacological effects. The objective of this study was to investigate the effect of PO in a rat model of testosterone propionate (TP)-induced BPH and explore the underlying mechanisms. Thirty-five Sprague-Dawley (SD) rats were divided into the following equal groups (n = 7): normal control (NC) group, TP (3 mg/kg) group, finasteride (10 mg/kg) group, 25 and 50 mg/kg PO groups. At the end of the experiment, the body weights (BWs) of the rats were measured before they were euthanized to the establishment obtain serum and prostate weight (PW). TP-induced levels of androgen-related proteins in the prostate were also investigated. In the TP group, prostate size, BW, serum DHT level, prostate epithelial cell thickness and androgen-related protein level were higher than those in the NC group (p < 0.001). PO reversed TP-induced BPH in a dose-dependent manner (p < 0.01) and its effect was similar to that of finasteride. A similar effect of PO on the androgen-related protein level was also observed. We successfully established a TP-induced BPH rat model. This is the first study to demonstrate that inhibition of androgen-related proteins using PO can alleviate BPH., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

There is evidence that BRCA1, particularly cytoplasmic BRCA1, plays a significant role in initiating apoptosis through various mechanisms. Maintaining the stability of BRCA1 in cancer cells may be a promising therapeutic strategy for breast cancer, especially in cases of triple-negative breast cancer (TNBC) lacking appropriate therapeutic targets. Previously, it was reported that cathepsin S (CTSS) interacts with the BRCT domain of BRCA1, leading to ubiquitin-mediated degradation. We further investigated the critical role of BRCA1 phosphorylation at Ser1387, which is mediated by ionizing radiation (IR)-induced activation of ATM. This phosphorylation event was identified as a key factor in CTSS-mediated ubiquitin degradation of BRCA1. The functional inhibition of CTSS, using small molecules or a knockdown system, sensitized TNBC cells when exposed to IR by restoring the stability of cytoplasmic BRCA1. The increase in cytoplasmic BRCA1 led to the degradation of anti-apoptotic BCL2, which was responsible for the radiosensitization effect observed with CTSS inhibition. These results suggest that inhibiting CTSS may be an effective strategy for radiosensitization in TNBC cells through BCL2 degradation that is mediated by inhibition of CTSS-induced BRCA1 degradation., 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. TNBC cell lines were exposed to irradiation (10 Gy) after pre-treatment with CTSS inhibitors; RO5461111 (RO) and Z-FL-COCHO (Z-FL). TNBC cell lines with wild-type BRCA1 (WT); MDA-MB-231 (231) & HCC70 and mutant BRCA1 (MT); MDA-MB-436 (436) & HCC1937 (1937). (A) Western blot analysis and the quantification of cleaved-PARP1 induction; (B) Cell death was evaluated with PI staining. Results are the means and SD (*p < 0.05, ANOVA)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aims: Interstitial lung disease (ILD) is a potentially serious but underdiagnosed manifestation of primary Sjögren's syndrome (pSS). This observational study investigated the prevalence and clinical course of ILD in pSS, together with prognostic factors., Methods: A multicenter, retrospective longitudinal study was performed using findings from baseline and follow-up pulmonary function tests and chest computed tomography. Predisposing factors for the development of ILD and acute exacerbation (AE) were identified using a logistic regression model. The risk factors for a significant decline of pulmonary function were determined by the Cox proportional hazard model., Results: A total of 1,306 patients with pSS were included in this study (female, 98%; mean age, 54 years). Among them, 79 patients with pSS were comorbid with ILD. ILD was more frequently found in male, older patients. Nonspecific interstitial pneumonia was the most prevalent imaging pattern in pSS-ILD (51%), followed by usual interstitial pneumonia (22%). At diagnosis with pSS-ILD, 54% of patients had restrictive pulmonary function, and 41% of patients initiated pharmacological treatment. During the median 4-year follow-up period, AE, a significant decline in pulmonary function, and death occurred in 19%, 29%, and 9% of patients with pSS-ILD, respectively. The neutrophil-to-lymphocyte ratio (NLR) increased 3 months prior to AE, and it was associated with AE. Older age at pSS-ILD diagnosis was a prognostic factor for a significant decline in pulmonary function., Conclusion: ILD accounted for 6% of the comorbidity of pSS. AE was associated with a significant decline in pulmonary function, and the NLR may predict AE.

Background/aim: To elucidate the relationship between metabolic syndrome (Mets) and somatic composition [fat mass, fat-free (FF) mass, and fat to fat-free (F-FF) ratio] among health checkup recipients (7,776 males and 10,121 females)., Patients and Methods: We classified study subjects into four types considering Japanese criteria for Mets; Type A is for males with waist circumference (WC) <85 cm and females with WC <90 cm, Type B is for males with WC ≥85 cm and females with WC ≥90 cm, but without any metabolic abnormalities, Type C is for males with WC ≥85 cm and females with WC ≥90 cm and one metabolic disorder (pre-Mets), and Type D is Mets. We compared baseline characteristics among types of A, B, C, and D., Results: F index, FF index, and F-FF ratio showed an increasing trend with increasing risk factors for Mets in both sexes., Conclusion: This study demonstrates a clear correlation between somatic composition and the severity of metabolic syndrome (Mets). As Mets risk factors increase, fat mass, fat-free mass, and the fat-to-fat-free ratio also rise, indicating that body composition shifts with disease progression. These findings emphasize the need for early intervention, such as exercise and diet, to manage somatic composition imbalances and reduce complications like insulin resistance., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endometrial cancer, a common gynecological malignancy, poses significant clinical challenges, particularly in advanced or recurrent cases. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, plays crucial roles in inflammation and immunity by activating nuclear factor (NF)-κB and interferon regulatory factor 3. However, its specific roles in endometrial cancer remain unknown. In this study, we aimed to investigate the anti-cancer effects and underlying mechanisms of amlexanox, a TBK1 inhibitor, against endometrial cancer. The main genetic mutations in TBK1 were found to be mRNA downregulation and missense mutations. Kaplan-Meier plotter analysis revealed that low TBK1 expression was associated with a good prognosis in patients with uterine corpus endometrial carcinoma (UCEC). In vitro experiments demonstrated that TBK1 knockdown or amlexanox significantly inhibited the proliferation, cell cycle progression, and migration of endometrial cancer cells. Furthermore, the inhibitory effects of targeting TBK1 on cancer cell proliferation and migration were mediated by the protein kinase B (AKT)/NF-κB signaling pathway. Xenograft experiments revealed that both amlexanox treatment and TBK1 knockdown effectively suppressed the tumor growth. Overall, this study highlights the potent anti-cancer effects of amlexanox against endometrial cancer by modulating AKT/NF-κB signaling, thus providing a new avenue for the development of novel TBK1-targeting therapeutic strategies for UCEC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Impaired skeletal muscle glycogen synthesis contributes to insulin resistance (IR). Aerobic exercise reported to ameliorate IR by augmenting insulin signaling, however the detailed mechanism behind this improvement remains unclear. This study investigated whether aerobic exercise enhances glycogen anabolism and insulin sensitivity via EGR-1/PTP1B signaling pathway in skeletal muscle of rats., Methods: Sprague-Dawley rats fed a high-fat diet (HFD), and performed treadmill exercise training for 6-week. Oral glucose tolerance test was conducted to confirm the IR. Periodic Acid-Schiff (PAS) staining and anthrone colorimetry were used to assess the skeletal muscle glycogen. RT-qPCR, western blot, and immunofluorescence were used to detect the EGR-1/PTP1B pathway and associated signaling molecules., Results: We found that exercise training significantly decreased blood glucose, insulin, and homeostasis model assessment for IR (HOMA-IR) against HFD-induced elevation. Decreased muscle glycogen content due to HFD was significantly restored after exercise training. Exercise training promoted mRNA expressions of Irs1, Akt, and Glut4, while inhibited Gsk-3β expression against HFD. Next, the decreased IRS1 (phosphorylated/total), AKT (phosphorylated/total), and GLUT4, and increased GSK-3β proteins with HFD were significantly reversed by exercise. Furthermore, HFD-induced overexpression of EGR-1 and PTP1B evidenced by mRNA, protein, and immunofluorescence intensity, were substantially inhibited by exercise, which may contribute to promote insulin sensitivity and glycogen anabolism., Conclusions: Aerobic exercise training promotes insulin sensitivity and skeletal muscle glycogen synthesis in HFD-fed rats. The beneficial effects of exercise might be mediated by EGR-1/PTP1B signaling pathway in skeletal muscle, however further studies are necessary to confirm this mechanism., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This paper presents a novel approach to fabricate substrate integrated waveguides (SIWs) on glass substrates with tin (Sn) through glass vias (TGVs) tailored for millimeter-wave applications. The fabrication process employs a custom-designed vacuum suctioning system to rapidly fill precise TGV holes in the glass substrate, which are formed by wafer-level glass reflow micromachining techniques with molten tin in a minute. This method offers a very fast and cost-effective alternative for complete via filling without voids compared to the conventional metallization techniques such as electroplating or sputtering. An SIW with a 3-dB cutoff frequency of 17.2 GHz was fabricated using the proposed process. The fabricated SIW shows an average insertion loss of 1.65 ± 0.54 dB across the 20-35 GHz range. These results highlight the potential of glass substrates with tin TGVs for fabricating millimeter-wave devices.

Background and objectives : The development of a five-in-one vaccine microneedle patch (five-in-one MN patch) aims to address challenges in administering vaccines against Diphtheria (DT), Tetanus (TT), Pertussis (wP), Hepatitis B (HBsAg), and Haemophilus influenzae type b (Hib). Combining multiple vaccines into a single patch offers a novel solution to improve vaccine accessibility, stability, and delivery efficiency, particularly in resource-limited settings. Methods : The five-in-one MN patch consists of four distinct microneedle arrays: DT and TT vaccines are coated together on one array, while wP, HepB, and Hib vaccines are coated separately on individual arrays. The patch was tested for long-term stability (12 months at 25 °C) and evaluated for immunogenicity in mice and minipigs. Antibody titers were measured using ELISA to compare immune responses between microneedle-based delivery and traditional intramuscular (IM) injection. Results : The five-in-one MN patch demonstrated stable antigenicity for up to 12 months at room temperature. In animal studies, the patch induced antibody titers comparable to traditional IM injections for all vaccines. Notably, immunogenic responses to Pertussis and Haemophilus influenzae type b vaccines via microneedles were reported for the first time. The patch facilitated the simultaneous yet independent delivery of vaccines, preserving their immunogenicity without interference. Conclusions : The five-in-one MN patch represents a significant advancement in vaccine delivery by enabling stable, minimally invasive, and efficient immunization. Its innovative design addresses the critical limitations of combination vaccines and has the potential to enhance vaccine accessibility in low- and middle-income countries. Future studies will focus on optimizing patch application techniques and evaluating broader clinical applicability.

Endosymbionts are important for insect species as they provide essential substances to the host. Due to the technical advance of NGS technology and de novo assemblers, many endosymbionts bacterial genomes are available now. Here, we analysed fourteen endosymbiont bacterial genomes of Aphis genius, one of notorious pest species. Fourteen genomes displayed the length between 628,098 bp to 634,931 bp; GC ratio was from 24.2 % to 25.6 % with no structural variation found. The nucleotide diversity distribution across the 14 endosymbiont genomes revealed three distinct regions, each separated by varying levels of nucleotide diversity. Intraspecific variations identified from endosymbiont bacterial genomes of the same host species revealed numbers of SNPs ranging from 31 (0.0049%) to 1,652 (0.26%) and those of INDELs ranging from 7 (21 bp; 0.0033%) to 104 (285 bp; 0.0045%). 250 unique SSRs, 28 different common SSR groups, and one different SSR group in two genomes were identified and used as a potential molecular marker to distinguish intraspecific population. Phylogenetic analysis further showed congruence between the endosymbiont bacterial genomes and the host species phylogeny, except Aphis nasturtii , Aphis helianth , and Aphis auranti , which require additional endosymbiont genomes for clarification. This comparative analysis result could serve as a cornerstone for understanding the relationship between host and endosymbiont species from a genomic perspective.

Background and Objectives : Rib fractures are common in patients with trauma, and patients with multiple rib fractures often require surgical stabilization. Because rib fractures may occur at different sites along the ribs, the technical approach to surgical stabilization varies. Here, we present a case of posterior rib fractures with multiple paraspinal fragmented rib segments that were successfully treated with costovertebral plate fixation. Case Presentation : A truck driver was injured after falling from the top of a truck. Computed tomography scans of the chest showed multiple flail segments along the paraspinal and posterolateral regions with a clinically evident flail chest. Owing to the proximity of the flail segments to the thoracic spine, rib plating was performed across the ribs and the transverse processes of the thoracic spine with the assistance of a neurosurgeon. The patient was extubated on postoperative day 1 and discharged successfully after the other traumatic injuries were treated. Discussion : Far posterior rib fractures close to the spine may be challenging, particularly if plates for rib fractures cannot be placed on the ribs alone. For such challenges, costotransverse plating is a feasible surgical option. However, the anatomical orientation of the rib and the transverse process of the thoracic spine are different, which complicates surgical planning and maneuvers. Therefore, a thorough understanding of the costotransverse anatomy is critical for successful surgical stabilization of fractured ribs. Conclusions : This is a good example of a challenging case of rib fractures requiring paraspinal plate stabilization.

The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO 2 laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody. Using unsupervised clustering based on four biomarker concentrations, we predicted thrombotic events in 49 of 53 patients. The four-biomarker combination yielded an area under the receiver operating characteristic curve (AUC) of 0.95, demonstrating high sensitivity and specificity for acute thrombosis prediction compared to the AUC values for individual biomarkers: CRP (0.773), calprotectin (0.711), sP-selectin (0.683), and D-dimer (0.739). Thus, a nanoengineered multichannel platform with unsupervised clustering provides accurate and efficient methods for predicting thrombosis, guiding personalized medicine.

Postoperative imaging of musculoskeletal tumors poses a significant diagnostic challenge for radiologists. The complexity arises from the need to differentiate between expected postoperative changes, potential complications, and local recurrence. The choice of imaging modality depends on the type of primary tumor. Standard radiological modalities such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are widely utilized. Radiography and CT are especially valuable for assessing primary bone tumors, as they provide detailed views of bone structures and alignment, as well as revealing postoperative complications. MRIs are particularly effective for evaluating soft tissue tumors and identifying local recurrences due to its superior soft tissue contrast. The advanced imaging techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, have significantly improved diagnostic accuracy in detecting tumor recurrence. An in-depth understanding of surgery-specific imaging findings, as well as the ability to detect recurrent disease, is crucial for early diagnosis of complications and improved patient outcomes. Familiarity with normal postoperative changes helps radiologists distinguish them from abnormal findings indicative of complications or tumor recurrence. This review article aims to outline the surgical options for musculoskeletal tumors, detail the various imaging techniques used in postoperative surveillance, and discuss the potential complications. By understanding the role of different imaging modalities and their applications associated with various surgical procedures, clinicians and radiologists can provide accurate and timely diagnoses.

Seafood quality preservation remains a critical focus in the food industry, particularly as the freeze-thaw process significantly impacts the freshness and safety of aquatic products. This study investigated quality changes in frozen mackerel subjected to two thawing methods, room temperature (RT) and running water (WT), and assessed the potential of hyperspectral imaging (HSI) for classifying these methods. After thawing, mackerel samples were stored at 5 °C for 21 days, with physicochemical, textural, and spectroscopic analyses tracking quality changes and supporting the development of a spectroscopic classification model. Compared with the WT method, the RT method delayed changes in key quality indicators, including pH, total volatile basic nitrogen (TVB-N), and total viable count (TVC), by 1-2 days, suggesting it may better preserve initial quality. Texture profile analysis showed similar trends, supporting the benefit of RT in maintaining quality. A major focus was on using HSI to assess quality and classify thawing methods. HSI achieved high classification accuracy (R c 2 = 0.9547) in distinguishing thawing methods up to three days post-thaw, with 1100, 1200, and 1400 nm wavelengths identified as key spectral markers. The HIS's ability to detect differences between thawing methods, even when conventional analyses showed minimal variation, highlights its potential as a powerful tool for quality assessment and process control in the seafood industry, enabling detection of subtle quality changes that traditional methods may miss.

This study examined the chemoselectivity and diastereoselectivity of silyl nitronate alkenyn-nitroethers in Intramolecular Silyl Nitronate Cycloadditions (ISNCs) to produce isoxazole derivatives with interesting medicinal properties. These reactions resulted in the formation of either dihydrofuro[3,4-c]isoxazolines/isoxazolidines and/or alkynyl moieties attached to 2,5-dihydrofuryl carbonyls. This study also discerned the diastereoselectivities of the resulting cyclic adducts and compared them to previous findings. The reactions were also investigated with Spartan molecular modeling computations to aid in the understanding of any displayed chemo- and/or stereoselectivity. These [3+2]-cycloaddition reactions demonstrated excellent to complete chemospecificity. The cycloadditions also demonstrated remarkable diastereospecificity in that each diastereomer of the nitroethers resulted in the formation of only one of four possible diastereomeric outcomes. The stereochemistry of the major diastereomers did not agree with previously published findings.

The current state-of-the-art climate models when combined together suggest that the anthropogenic weakening of the Atlantic Meridional Overturning Circulation (AMOC) has already begun since the mid-1980s. However, continuous direct observational records during the past two decades have shown remarkable resilience of the AMOC. To shed light on this apparent contradiction, here we attempt to attribute the interdecadal variation of the historical AMOC to the anthropogenic and natural signals, by analyzing multiple climate and surface-forced ocean model simulations together with direct observational data. Our analysis suggests that an extensive weakening of the AMOC occurred in the 2000s, as evident from the surface-forced ocean model simulations, and was primarily driven by anthropogenic forcing and possibly augmented by natural variability. However, since the early 2010s, the natural component of the AMOC has greatly strengthened due to the development of a strong positive North Atlantic Oscillation. The enhanced natural AMOC signal in turn acted to oppose the anthropogenic weakening signal, leading to a near stalling of the AMOC weakening. Further analysis suggests that the tug-of-war between the natural and anthropogenic signals will likely continue in the next several years., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background/objectives: To assess the incidence of and risk factors for black triangles between the central incisors after orthodontic treatment; Methods: Ninety-seven post-treatment patients (29 men and 68 women; mean age, 22.7 years) were retrospectively divided into two groups based on the presence or absence of black triangles, using intraoral photographs. Based on the Jemt Index, the black triangle occurrence group was further classified into mild, moderate, and severe groups. Parameters from periapical radio graphs, lateral cephalograms, and study models were compared between the occurrence and the non-occurrence groups by using independent t -tests. Logistic regression analysis was performed to identify the risk factors for black triangles; Results: The incidence of black triangles between the central incisors was 51% and 64% in the maxilla and in the mandible, respectively. The factors significantly associated with the occurrence of black triangles were age, treatment duration, the lingual inclination of the maxillary incisors in the maxilla, and age in the mandible ( p < 0.05); Conclusions: This study showed the diverse risk factors associated with black triangles between central incisors after orthodontic treatment and revealed that the formation of black triangles is relatively common. Considering these risk factors during orthodontic diagnosis and treatment planning can help minimize the occurrence of black triangles.

Hydrogen is an alternative fuel for transportation vehicles because it is clean, sustainable, and highly flammable. However, the production of hydrogen from lignocellulosic biomass by microorganisms presents challenges. This microbial process involves multiple complex steps, including thermal, chemical, and mechanical treatment of biomass to remove hemicellulose and lignin, as well as enzymatic hydrolysis to solubilize the plant cell walls. These steps not only incur costs but also result in the production of toxic hydrolysates, which inhibit microbial growth. A hyper-thermophilic bacterium of Caldicellulosiruptor bescii can produce hydrogen by decomposing and fermenting plant biomass without the need for conventional pretreatment. It is considered as a consolidated bioprocessing (CBP) microorganism. This review summarizes the basic scientific knowledge and hydrogen-producing capacity of C. bescii. Its genetic system and metabolic engineering strategies to improve hydrogen production are also discussed. KEY POINTS: • Hydrogen is an alternative and eco-friendly fuel. • Caldicellulosiruptor bescii produces hydrogen with a high yield in nature. • Metabolic engineering can make C. bescii to improve hydrogen production., (© 2024. The Author(s).)

Background/objectives: Perceived diet quality (PDQ) has been suggested as an easy-to-use dietary assessment tool. However, its practicality and efficiency are still questionable. This study aimed to gauge the utility of PDQ as an alternative dietary assessment tool among Korean adults by examining PDQ and its associated factors., Subjects/methods: An online survey was conducted on 514 Korean adults aged 19 to 64 years in October 2022. PDQ was assessed using a 5-point Likert scale, and participants were categorized into healthy, fair, or unhealthy PDQ groups. The participants were asked about the perceived importance of nutrients and food groups for health and the extent to which they considered these factors in their usual diets using a 5-point Likert scale. A multivariate linear regression model was used to identify the factors associated with PDQ., Results: About 26.7% of participants rated their diets as healthy, while 63.2% rated them as fair and 10.1% rated them as unhealthy. Participants with a healthy PDQ rated perceived importance and consideration of nutrients and food groups higher than the fair or unhealthy PDQ groups. A healthier PDQ was associated with the male gender, an older age, being normal or underweight, having better subjective health, lower use of alcohol, being physically active, having a high interest in healthy diets, and a higher perception of the importance of nutrients and food groups for health., Conclusion: The PDQ could serve as a simple and rapid screening tool for identifying individuals at risk of poor diets., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

The rapid evolution of microelectronics and display technologies has driven the demand for advanced manufacturing techniques capable of precise, high-speed microchip transfer. As devices shrink in size and increase in complexity, scalable and contactless methods for microscale placement are essential. Laser-induced forward transfer (LIFT) has emerged as a transformative solution, offering the precision and adaptability required for next-generation applications such as micro-light-emitting diodes (μ-LEDs). This study optimizes the LIFT process for the precise transfer of silicon microchips designed to mimic μ-LEDs. Critical parameters, including laser energy density, laser pulse width, and dynamic release layer (DRL) thickness are systematically adjusted to ensure controlled blister formation, a key factor for successful material transfer. The DRL, a polyimide-based photoreactive layer, undergoes photothermal decomposition under 355 nm laser irradiation, creating localized pressure that propels microchips onto the receiver substrate in a contactless manner. Using advanced techniques such as three-dimensional profilometry, X-ray photoelectron spectroscopy, and ultrafast imaging, this study evaluates the rupture dynamics of the DRL and the velocity of microchips during transfer. Optimization of the DRL thickness to 1 µm and a transfer velocity of 20 m s⁻ 1 achieves a transfer yield of up to 97%, showcasing LIFT's potential in μ-LED manufacturing and semiconductor production.

Background/objectives: Since the initial approach towards the clinical presentation of soft-tissue masses is challenging for frontline physicians, some countries use clinical practice guidelines. Proper imaging work-up is crucial to differentiate between soft-tissue tumors. Recently, ultrasonography and magnetic resonance imaging (MRI) have been widely used. But there is some controversy about whether pre-referral evaluations are being conducted properly. Thus, this study aims to assess whether the ultrasonography investigation of soft-tissue masses prior to referral to the musculoskeletal tumor center is being performed adequately in terms of indications, diagnostic accuracy, and referral interval, and to evaluate whether the pre-referral MRI for soft-tissue masses is being conducted reasonably concerning indications, imaging protocol, reporting, diagnostic accuracy, and cost-effectiveness., Methods: The study protocol was registered. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We performed a database search of the MEDLINE, Embase, and Cochrane Library. Then, two authors reviewed the studies, and the third author resolved any disagreement between them. A total of nine studies were included. The Risk Of Bias In Non-Randomized Studies-of Interventions was applied. Relevant data were extracted by two authors., Results: This review showed that the way that the imaging investigations are performed in non-specialized centers before referral was generally considered inappropriate., Conclusions: Frontline physicians should regard the alarm symptom as an indication for advanced imaging evaluation. Education and certification may be required for ultrasonography. MRI should be performed and interpreted in a specialized center or by a specialist with relevant expertise. Guidance may help reduce inappropriate imaging.

Strain engineering provides an attractive approach to enhance device performance by modulating the intrinsic electrical properties of materials. This is especially applicable to 2D materials, which exhibit high sensitivity to mechanical stress. However, conventional methods, such as using polymer substrates, to apply strain have limitations in that the strain is temporary and global. Here, we introduce a novel approach to induce permanent localized strain by fabricating a stressor on SiO 2 /Si substrates using fiber laser irradiation, thereby enabling precise control of the surface topography. MoS 2 is transferred onto this stressor, which results in the application of ~0.8% tensile strain. To assess the impact of the internal strain on the operation of ReRAM devices, the flat-MoS 2 -based and the strained-MoS 2 -based devices are compared. Both devices demonstrate forming-free, bipolar, and non-volatile switching characteristics. The strained devices exhibit a 30% reduction in the operating voltage, which can be attributed to bandgap narrowing and enhanced carrier mobility. Furthermore, the strained devices exhibit nearly a two-fold improvement in endurance, presumably because of the enhanced stability from lattice release effect. These results emphasize the potential of strain engineering for advancing the performance and durability of next-generation memory devices.

Future changes to the year-to-year swings between active and inactive North Atlantic tropical cyclone (TC) seasons have received little attention, yet may have great societal implications in areas prone to hurricane landfalls. This work investigates past and future changes in North Atlantic TC activity, focusing on interannual variability and evaluating the contributions from anthropogenic forcing. We show that interannual variability of Atlantic TC activity has already increased, evidenced by an increase in the occurrence of both extremely active and inactive TC seasons. TC-resolving general circulation models project a 36% increase in the variance of North Atlantic TC activity, measured by accumulated cyclone energy, by the middle of the 21st century. These changes are the result of increased variability in vertical wind shear and atmospheric stability, in response to enhanced Pacific-to-Atlantic interbasin sea surface temperature variations. Robust anthropogenic-forced intensification in the variability of Atlantic TC activity will continue in the future, with important implications for emergency planning and societal preparedness.

Background: Choline alfoscerate, a cholinergic precursor with limited evidence of efficacy in dementia management, has been used for various cognitive impairments in Korea. Partly due to its insurance coverage, this agent appears to incur significant expense for the insurance system. Thus, we aimed to describe choline alfoscerate prescription patterns and analyze their long-term effects in an older adult cohort with dementia., Methods: This observational study used the National Health Insurance Service Senior Cohort Dataset. Choline alfoscerate -naïve patients who were diagnosed with dementia between 2003 and 2014 with at least 12 months of follow-up were selected. Time-dependent Cox regression was employed to estimate the association between drug exposure and the risk of treatment failure events., Results: There were 11,463 eligible participants, of whom approximately 73% were female, and 19% had been exposed to choline alfoscerate. According to the main regression survival analysis, the association between longitudinal choline alfoscerate use and the risk of progression events related to treatment failure was unclear. However, a significant decrease of nearly 20% in the risk of all-cause mortality was associated with choline alfoscerate exposure, and a slight reduction in progression regarding treatment failure was observed with CA use only during the early stages of diagnosis. Age, sex, insurance premiums, several comorbidities and concurrent medications were significantly associated with the probability of the events according to the multivariate models., Conclusions: Further analyses are needed to confirm the early-stage and long-term effectiveness of choline alfoscerate in specific populations, which will help in considering its reimbursement., Competing Interests: Declarations Ethics approval and consent to participate This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval was granted by the Research Ethics Committee of Chungnam National University (Date March 11, 2021/ No. 202102-SB-020-01). Consent to participate: Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The semiconductor industry increasingly relies on high aspect ratio etching facilitated by Amorphous Carbon Layer (ACL) masks for advanced 3D-NAND and DRAM technologies. However, carbon contamination in ACL deposition chambers necessitates effective fluorine-based plasma cleaning. This study employs a high-temperature inductively coupled plasma (ICP) system and Time-of-Flight Mass Spectrometry (ToF-MS) to analyze gas species variations under different process conditions. We applied Principal Component Analysis (PCA) and Non-negative Matrix Factorization (NMF) to identify key gas species, and used the First-Order Plus Dead Time (FOPDT) model to quantify dynamic changes in gas signals. Our analysis revealed the formation of COF3 at high gas temperatures and plasma power levels, indicating the presence of additional reaction pathways under these conditions. This study provides a comprehensive understanding of high-temperature plasma interactions and suggests new strategies for optimizing ACL processes in semiconductor manufacturing.

Photopolymerization-based three-dimensional (3D) printing techniques such as stereolithography (SLA) attract considerable attention owing to their superior resolution, low cost, and relatively high printing speed. However, the lack of studies on improving the mechanical properties of 3D materials highlights the importance of delving deeper into additive manufacturing research. These materials possess considerable potential in the medical field, particularly for applications such as anatomical models, medical devices, and implants. In this study, we investigated the enhancement of mechanical strength in 3D-printed photopolymers through the incorporation of potassium titanate powder (K 2 Ti 8 O 17 ), with a particular focus on potential applications in medical devices. The mechanical strength of the photopolymer containing potassium titanate was analyzed by measuring its flexural strength, hardness, and tensile strength. Additionally, poly(ethylene glycol) (PEG) was used as a stabilizer to optimize the dispersion of potassium titanate in the photopolymer. The flexural strengths of the printed specimens were in the range of 15-39 MPa (Megapascals), while the measured surface hardness and tensile strength were in the range of 41-80 HDD (Hardness shore D) and 2.3-15 MPa, respectively. Furthermore, the output resolution was investigated by testing it with a line-patterned structure. The 3D-printing photopolymer without PEG stabilizers produced line patterns with a thickness of 0.3 mm, whereas the 3D-printed resin containing a PEG stabilizer produced line patterns with a thickness of 0.2 mm. These findings demonstrate that the composite materials not only exhibit improved mechanical performance but also allow for high-resolution printing. Furthermore, this composite material was successfully utilized to print implants for pre-surgical inspection. This process ensures the precision and quality of medical device production, emphasizing the material's practical value in advanced medical applications.

Objectives: Uncomplicated cystitis is a leading form of bacterial UTI; the most common causative bacterium worldwide is Escherichia coli . This internet-based, prospective, multicenter, and national observational study aimed to report the antimicrobial resistance of E. coli in patients with uncomplicated cystitis through the use of the Korean Antimicrobial Resistance Monitoring System (KARMS) in 2023. Results: Data for a total of 654 patients were retrieved from the KARMS database. The mean (standard deviation) patient age was 55.9 (18.3) years. The numbers of postmenopausal women and patients with recurrent cystitis were 381 (59.4%) and 78 (11.9%), respectively. Regarding antimicrobial susceptibility, 96.8% were susceptible to fosfomycin, 98.9% to nitrofurantoin, 50.9% to ciprofloxacin, and 82.4% to cefotaxime. Extended-spectrum beta-lactamase positivity was 14.4% (89/616), and was significantly higher in tertiary hospitals (24.6%, p < 0.001) and recurrent cystitis (27.6%, p < 0.001). Fluoroquinolone resistance was significantly higher in tertiary hospitals (57.8%, p < 0.001), postmenopausal women (54.2%, p < 0.001), and recurrent cystitis (70.3%, p < 0.001). In addition, postmenopausal status (95% confidence interval [CI]: 1.44-3.17, odds ratio [OR] 2.13, p < 0.001), recurrent cystitis (95% CI: 1.40-4.66, OR 2.56, p = 0.002) and tertiary hospitals (95% CI: 1.00-2.93, OR 1.71, p = 0.049) were associated with significantly increased fluoroquinolone resistance. Methods: Any female patient diagnosed with clinical uncomplicated cystitis and microbiologically proven E. coli infection in 2023 was eligible for this study. Patient data were obtained from the web-based KARMS database. The antimicrobial susceptibility of E. coli was analyzed according to clinical factors, including hospital region, hospital type, menopause status, and recurrence status. Conclusions: The antimicrobial resistance of E. coli in patients with uncomplicated cystitis in the Republic of Korea has reached a serious level, especially in fluoroquinolone resistance. Therefore, major efforts should be made to reduce antimicrobial resistance.

This study investigates the design of additive manufacturing for controlled crack propagation using process parameters and lattice structures. We examine two lattice types-octet-truss (OT) and diamond (DM)-fabricated via powder bed fusion with Ti-6Al-4V. Lattice structures are designed with varying densities (10%, 30%, and 50%) and process using two different laser energies. Using additive-manufactured specimens, Charpy impact tests are conducted to evaluate the fracture behavior and impact energy levels of the specimens. Results show that the type of the lattice structures, the density of the lattice structures, and laser energy significantly influence crack propagation patterns and impact energy. OT exhibits straighter crack paths, while DM demonstrates more random fracture patterns. Higher-density lattices and increased laser energy generally improve the impact energy. DM consistently outperformed OT in the impact energy for angle specimens, while OT showed superior performance in stair specimens. Finally, a case study demonstrates the potential for combining OT and DM structures to guide crack propagation along predetermined paths, offering a novel approach to protect critical components during product failure.

Background and Aims: We aimed to clarify the relationship between alanine aminotransferase (ALT) level and body composition in Japanese medical health checkups, especially in cases with ALT ≤ 30 IU/L (7569 men and 9497 women)., Methods: We categorized our study cohort into four groups: type A (ALT value ≤ 10 IU/L), type B (11 ≤ ALT value ≤ 20 IU/L), type C (21 ≤ ALT value ≤ 30 IU/L) and type D (ALT value > 30 IU/L (ALT over 30)). We retrospectively compared body composition-related parameters (body mass index (BMI), waist circumference (WC), fat (F) index, fatty liver index (FLI), fat-free (FF) index and F-FF ratio) among the four types., Results: Type A/B/C/D in men and women was found in 262/3279/2107/1921 and 1549/5736/1495/717 ( p < 0.0001). BMI, WC, F-index, FLI, FF index and F-FF ratio were all significantly stratified among the four types, regardless of whether they were male or female and over or under 50 years old., Conclusions: With a decrease in ALT level in medical health checkups, fat mass decreases, and F-FF ratio decreases, but a decrease in skeletal muscle mass cannot be overlooked.

25-hydroxycholesterol (25HC) is an oxysterol derived from cholesterol and plays a role in various cellular processes, such as lipid metabolism, inflammatory responses, and cell survival. Extravillous trophoblasts (EVTs) are a major cell type found in the placenta, which are highly energetic cells with proliferative and invasive properties. EVT dysfunction can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction. This study investigated the effects and underlying mechanisms of action of 25HC on EVT proliferation. Swan 71 cells, an EVT cell line, were treated with different concentrations of 25HC. Next, cell proliferation was assessed. The mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potentials (MMPs), lipid peroxidation (LPO), and glutathione (GSH) levels were measured. Apoptosis, ferroptosis, and autophagy were evaluated by western blotting and flow cytometry. The results revealed that 25HC significantly inhibited proliferation and decreased the metabolic activity of EVTs. Moreover, 25HC caused oxidative stress by altering mtROS, LPO, MMPs, and GSH levels. Additionally, 25HC induces apoptosis, ferroptosis, and autophagy through the modulation of relevant protein levels. Interestingly, pretreatment with Z-VAD-FMK, an apoptosis inhibitor, and ferrostatin-1, a ferroptosis inhibitor, partially restored the effects of 25HC on cell proliferation, oxidative stress, and cell death. In summary, our findings suggest that 25HC treatment inhibits EVT proliferation and triggers apoptosis, ferroptosis, and autophagy, which are attributable to oxidative stress., 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. Published by Elsevier B.V.)

Background: Discrimination against lesbian, gay, bisexual, transgender, queer or questioning, and other sexual and gender diverse (LGBTQ+) individuals in healthcare settings remains a priority issue. Nurse leaders, who oversee the largest healthcare workforce, are critical in implementing inclusive practices to address LGBTQ+ discrimination, yet implementing LGBTQ+ inclusive practices and effective strategies is inconsistent. This qualitative descriptive study explored nurse leaders' perceptions of LGBTQ+ inclusive practices across the United States to inform recommended strategies within health systems., Methods: Twenty-one nurse leaders (e.g., chief nurse executives) from diverse healthcare settings (e.g., children's hospitals and public health centers) in 12 states across the United States participated in semi-structured interviews from October to December 2023. Interview transcripts were analyzed using content analysis to (1) describe nurse leaders' definitions of LGBTQ+ inclusive practices and (2) identify effective strategies for their implementation., Results: Nurse leaders defined LGBTQ+ inclusive practices to include delivering culturally responsive and competent care, fostering safe and affirming environments, integrating inclusivity into daily interactions and organizational culture, and supporting the needs of both LGBTQ+ staff and patients. Key implementation strategies included fostering a flexible organizational culture through open communication; a diverse workforce; and inclusive mission statements, policies, and strategic plans. Supportive infrastructure involved effective LGBTQ+ training and adapting electronic health record systems to include information on sexual orientation and gender identity. Active and interdisciplinary engagement from staff and leadership, as well as systematic data collection on patient and staff experiences, were essential for driving inclusivity. The advocacy highlighted included legislative support, discourse within the nursing profession, and the incorporation of LGBTQ+ inclusion into healthcare regulations and accreditation standards. Additionally, multisectoral partnerships with LGBTQ+ health experts and external organizations, along with multilevel evaluations, were recommended to develop tailored interventions and promote LGBTQ+ inclusive practices., Conclusion: Implementing LGBTQ+ inclusive practices in healthcare is a multifaceted effort influenced by strategies at various levels. Promoting a supportive organizational culture, establishing comprehensive support structures, encouraging active engagement, and fostering community partnerships can address the needs of LGBTQ+ individuals more effectively. Future implementation efforts should tailor strategies to accommodate variability across healthcare settings and regions, ensuring that practices are both adaptable and sustainable., 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., (© 2024 The Author(s).)

Background: Certain cancers present challenges for treatment because they are resistant to immune checkpoint blockade (ICB), attributed to low tumor mutational burden and the absence of T cell-inflamed features. Among these, glioblastoma (GBM) is notoriously resistant to ICB. To overcome this resistance, the identification of T cells with heightened stemness marked by T-cell factor 1 (TCF1) expression has gained attention. Several studies have explored ways to preserve stem-like T cells and prevent terminal exhaustion. In this study, we investigate a target that triggers stem-like properties in CD8 T cells to enhance the response to ICB in a murine GBM model., Methods: Using Fcgr2b -/- mice and a murine GL261 GBM model, we confirmed the efficacy of anti-programmed cell death protein-1 (PD-1) immunotherapy, observing improved survival. Analysis of immune cells using fluorescence-activated cell sorting and single-cell RNA sequencing delineated distinct subsets of tumor-infiltrating CD8 T cells in Fcgr2b -/- mice. The crucial role of the stem-like feature in the response to anti-PD-1 treatment for reinvigorating CD8 T cells was analyzed. Adoptive transfer of OT-I cells into OVA-expressing GL261 models and CD8 T cell depletion in Fcgr2b -/- mice confirmed the significance of Fcgr2b -/- CD8 T cells in enhancing the antitumor response. Last, S1P 1 inhibitor treatment confirmed that the main source of tumor antigen-specific Fcgr2b -/- CD8 T cells is the tumor-draining lymph nodes (TdLNs)., Results: In a murine GBM model, anti-PD-1 monotherapy and single-Fc fragment of IgG receptor IIb (FcγRIIB) deletion exhibit limited efficacy. However, their combination substantially improves survival by enhancing cytotoxicity and proliferative capacity in tumor-infiltrating Fcgr2b -/- CD8 T cells. The improved response to anti-PD-1 treatment is associated with the tumor-specific memory T cells (Ttsms) exhibiting high stemness characteristics within the tumor microenvironment (TME). Ttsms in the TdLN thrives in a protective environment, maintaining stem-like characteristics and serving as a secure source for tumor infiltration. This underscores the significance of FcγRIIB ablation in triggering Ttsms and enhancing ICB therapy against GBM., Conclusions: Deletion of FcγRIIB on CD8 T cells leads to the generation of a Ttsms, which is localized in TdLN and protected from the immunosuppressive TME. Incorporating these highly stemness-equipped Ttsms enhances the response to anti-PD-1 therapy in immune-suppressed brain tumors., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Selective perturbation of protein interactions with chemical compounds enables dissection and control of developmental processes. Differentiation of stomata, cellular valves vital for plant growth and survival, is specified by the basic-helix-loop-helix (bHLH) heterodimers. Harnessing a new amination reaction, we here report a synthesis, derivatization, target identification, and mode of action of an atypical doubly-sulfonylated imidazolone, Stomidazolone, which triggers stomatal stem cell arrest. Our forward chemical genetics followed by biophysical analyses elucidates that Stomidazolone directly binds to the C-terminal ACT-Like (ACTL) domain of MUTE, a master regulator of stomatal differentiation, and perturbs its heterodimerization with a partner bHLH, SCREAM in vitro and in plant cells. On the other hand, Stomidazolone analogs that are biologically inactive do not bind to MUTE or disrupt the SCREAM-MUTE heterodimers. Guided by structural docking modeling, we rationally design MUTE with reduced Stomidazolone binding. These engineered MUTE proteins are fully functional and confer Stomidazolone resistance in vivo. Our study identifies doubly-sulfonylated imidazolone as a direct inhibitor of the stomatal master regulator, further expanding the chemical space for perturbing bHLH-ACTL proteins to manipulate plant development., (© 2024. The Author(s).)

Objective: This study aims to evaluate and compare the Cervex-Brush ® and Orcellex ® Brush as sampling devices for vaginal vault smear cytology in cervical cancer patients treated primarily with radiotherapy., Method: A randomized crossover trial was conducted at a gynecological oncology center in Hong Kong to compare the Cervex-Brush ® and Orcellex ® Brush in terms of their vault smear adequacy rate in cervical cancer patients who underwent radiotherapy., Results: One hundred sixty cervical cancer patients treated with primary radiotherapy and undergoing follow-up surveillance by vaginal vault cytology were recruited. The smear adequacy rate was 90.6% for Cervex-Brush ® and 91.9% for Orcellex ® Brush. The rates of low cellularity for both brushes were similar (76.8% for Cervex-Brush ® vs. 76.1% for Orcellex ® Brush). The detection rates of abnormal smears were also not significantly different (2.8% for Cervex-Brush ® vs. 4.2% for Orcellex ® Brush). The 2 brushes were also not significantly different in terms of pain score and degree of bleeding. It was further observed that the second smear collection was more painful and patients who were on hormonal replacement therapy demonstrated less bleeding., Conclusion: There was no difference between the Orcellex ® brush and the Cervex-Brush ® in terms of smear adequacy rate, rate of high cellularity and the detection of abnormal smears. There was also no significant difference between the 2 brushes in terms of pain and the degree of bleeding. Therefore, the Orcellex ® Brush can be considered a suitable alternative sampling device for vault smear collection in patients who have undergone radiotherapy for cervical cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT04461574., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

This study aimed to examine the factors influencing Chinese tourists' shopping behavior during shopping tourism in Korea using a theoretical framework based on the modified theory of planned behavior (TPB). A quantitative research method was used; the questionnaire for this study was posted on Wenjuanxing for data collection and 269 valid questionnaires were analyzed in September 2024 using partial least-squares structural equation modeling (PLS-SEM). The results of analyzing the 269 questionnaires showed that attitude, conformity, perceived behavioral control, and perceived quality of goods influenced shopping intention. However, face consciousness did not affect shopping intentions. Additionally, Chinese tourists' shopping intentions influenced their shopping behavior during shopping tourism in Korea. The results of this study reveal the potential mechanisms of the influence of shopping intentions with conformity (a factor of Chinese-subjective norms) and the perceived quality of goods (a new factor) in shopping behavior, and they provide theoretical guidance and appropriate marketing strategies for companies in the Korean tourism field.

Background: The dissemination of Klebsiella spp. producing multiple carbapenemases has been increasingly recognized. Between July 2019 and August 2021, ten patients were found to carry Klebsiella spp. co-harboring bla KPC-4 and bla VIM-1 across multiple wards at a Korean hospital, and one isolate was recovered from a hand-washing sink, more than a year after the outbreak. This study aimed to investigate the outbreak and conduct a genomic study of these isolates., Methods: Whole-genome sequencing, including long-read sequencing, was performed to analyze plasmid structures and mobile genetic elements (MGEs). Bioinformatics analyses were performed to trace clonal transmission chains and horizontal gene transfer., Results: The findings suggested that the inter-ward spread of Klebsiella spp. seemed to be facilitated by healthcare worker contact or patient movement. Of the nine isolates collected (eight clinical and one environmental), seven (including the environmental isolate) were identified as K. pneumoniae (ST3680) and two were K. variicola (single-locus variant of ST5252). These isolates showed high genetic relatedness within their species and harbored the IncHI5B plasmid carrying both bla KPC-4 and bla VIM-1 (pKPCVIM.1). On this plasmid, bla VIM-1 was located in the Class 1 integron associated with IS1326::IS1353 (In2), and Tn4401b carrying bla KPC-4 was inserted into IS1326::IS1353, creating a novel MGE construct (In2&#95;bla VIM-1 -Tn4401b&#95;bla KPC-4 )., Conclusion: The hospital-wide spread of bla KPC-4 and bla VIM-1 was facilitated by clonal spread and horizontal plasmid transfer. The persistence of this strain in the hospital sink suggests a potential reservoir of the strain. Understanding the transmission mechanisms of persistent pathogens is important for improving infection control strategies in hospitals., (© 2024. The Author(s).)

In the present investigation, we have devised a hyperspectral imaging (HSI) apparatus to assess the chemical characteristics and freshness of the yellow croaker ( Larimichthys polyactis ) throughout its storage period. This system operates within the shortwave infrared spectrum, specifically ranging from 900 to 1700 nm. A variety of spectral pre-processing techniques, including standard normal variate (SNV), multiple scatter correction, and Savitzky-Golay (SG) derivatives, were employed to augment the predictive accuracy of total volatile basic nitrogen (TVB-N)-which serves as a critical freshness parameter. Among the assessed methodologies, SG-1 pre-processing demonstrated superior predictive accuracy (R p 2 = 0.8166). Furthermore, this investigation visualized freshness indicators as concentration images to elucidate the spatial distribution of TVB-N across the samples. These results indicate that HSI, in conjunction with chemometric analysis, constitutes an efficacious instrument for the surveillance of quality and safety in yellow croakers during its storage phase. Moreover, this methodology guarantees the freshness and safety of seafood products within the aquatic food sector.

Breast cancer remains a significant public health issue, often resulting in severe side effects such as neutropenia, highlighting the need for reliable predictors of clinical outcomes. This study aimed to evaluate the predictive value of body composition measures for mortality, recurrence, and chemotherapy-induced neutropenia in patients with breast cancer following surgery and chemotherapy. We retrospectively analyzed 85 breast cancer patients who underwent surgery and chemotherapy between 2006 and 2016. Body composition was assessed using computed tomography (CT) or positron emission tomography (PET) at diagnosis and three years and five years post-diagnosis. Metrics included skeletal muscle area (SMA), skeletal muscle index (SMI), subcutaneous adipose tissue area (SAT), and visceral adipose tissue area (VAT). Longitudinal analysis revealed a decrease in muscle mass (P < 0.001 for both SMA and SMI) and nonsignificant changes in fat mass (P = 0.449 for SAT and P = 0.798 for VAT). A lower SMI at diagnosis was significantly associated with increased mortality (P = 0.019) and a higher incidence of grade 4 neutropenia (P = 0.008). There was no significant association between SMI at diagnosis and recurrence (P = 0.691). No associations were found between body composition measurements during the follow-up period and the clinical outcomes. Lower skeletal muscle mass at diagnosis is strongly associated with higher mortality and chemotherapy-induced complications in patients with breast cancer, highlighting the potential of readily available imaging techniques as valuable predictors of clinical outcomes., (© 2024. The Author(s).)

Regular exercise as part of one's lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

Breast cancer metastasis is associated with a poor prognosis and a high rate of mortality. Cathepsin L (CTSL) is a lysosomal cysteine protease that promotes tumor metastasis by degrading the extracellular matrix. Gene set enrichment analysis revealed that CTSL expression was higher in tumorous than in non-tumorous tissues of breast cancer patients and that high-level CTSL expression correlated positively with the epithelial-mesenchymal transition. Therefore, we hypothesized that inhibiting CTSL activity in tumor cells would prevent metastasis. In this study, we characterized the inhibitory activity of SnuCalCpI15, the I29 domain of a CTSL-like cysteine protease from Calotropis procera R. Br., and revealed that the propeptide stereoselectively inhibited CTSL in a reversible slow-binding manner, with an inhibitory constant (K i ) value of 1.38 ± 0.71 nM, indicating its potency as an exogenous inhibitor in anti-cancer therapy. SnuCalCpI15 was localized intracellularly in MDA-MB-231 breast cancer cells and suppressed tumor cell migration and invasion. These results demonstrate the potential of SnuCalCpI15 as a novel agent to prevent breast cancer metastasis., (© 2024. The Author(s).)

Objective: This study aimed to elucidate the clinical and laboratory differences between chronic sclerosing sialadenitis (CSS) and primary Sjögren's syndrome (pSS), highlighting CSS as a distinct pathological entity within the spectrum of salivary gland pathology., Methods: This retrospective, single-center study was conducted at Seoul St. Mary's Hospital between January 2000 and December 2022. Patients diagnosed with CSS via salivary gland biopsy were included, and those with IgG4-related disease (IgG4-RD) or other confounding factors were excluded. Clinical and laboratory CSS profiles were compared with those of a control group of patients with typical pSS from the Korean Initiative of Primary Sjögren's Syndrome (KISS) prospective cohort study. Twenty-one with CSS and 501 patients with pSS from Seoul St. Mary's Hospital were retrospectively analyzed., Results: Patients with CSS were older at diagnosis, had a lower prevalence of ocular symptoms, and exhibited distinct immunological markers compared to those with pSS. Logistic regression analysis revealed that anti-Ro antibody positivity, elevated erythrocyte sedimentation rate levels, low serum complement 3 levels, and accompanying dry eye symptoms were factors distinguishing pSS from CSS., Conclusion: Even after excluding IgG4-RD, CSS was significantly different from pSS in terms of clinical and laboratory findings. Recognition of these differences is crucial for the accurate diagnosis and management of CSS, underscoring its status as a distinct pathological entity among salivary gland pathologies., Competing Interests: CONFLICT OF INTEREST J.H.J. has been an editorial board member since May 2018; however, has no role in the decision to publish this article., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Abscission is the shedding of plant organs in response to developmental and environmental cues. Abscission involves cell separation between two neighboring cell types, residuum cells (RECs) and secession cells (SECs) in the floral abscission zone (AZ) in Arabidopsis thaliana. However, the regulatory mechanisms behind the spatial determination that governs cell separation are largely unknown. The class I KNOTTED-like homeobox (KNOX) transcription factor BREVIPEDICELLUS (BP) negatively regulates AZ cell size and number in Arabidopsis. To identify new players participating in abscission, we performed a genetic screen by activation tagging a weak complementation line of bp-3. We identified the mutant ebp1 (enhancer of BP1) displaying delayed floral organ abscission. The ebp1 mutant showed a concaved surface in SECs and abnormally stacked cells on the top of RECs, in contrast to the precisely separated surface in the wild-type. Molecular and histological analyses revealed that the transcriptional programming during cell differentiation in the AZ is compromised in ebp1. The SECs of ebp1 have acquired REC-like properties, including cuticle formation and superoxide production. We show that SEPARATION AFFECTING RNA-BINDING PROTEIN1 (SARP1) is upregulated in ebp1 and plays a role in the establishment of the cell separation layer during floral organ abscission in Arabidopsis., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)