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The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis
No full textAnkylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS.Key messagesSerum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients.Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS.CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control.Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.N
An Artificial Neural Network (ANN) Prediction Model Approach to Predict Shock Metamaterial Shock Mitigation Behavior
No full textThis work was supported by Basic Science Research Program of the National Research Foundation (NRF) of Korea funded by the Ministry of Education (grant number: NRF-2022R1I1A1A01071752), Republic of Korea. The tests in this work were conducted with the assistance of the Institute of Construction and Environmental Engineering and Extreme Performance Testing Center and at Seoul National University.We propose the use of Artificial Neural Networks (ANNs) to predict the response of auxetic metamaterial structures under various shock impact velocities. To develop a predictive model for Y-direction acceleration, we designed a 3x[N]n x 1-layer ANN architecture, utilizing metamaterial dimensions, impact velocity, and impactor shape as input parameters, with acceleration as the output. Among tested configurations, Model 9 (3 x 100 x 100 x 100 x 1) demonstrated optimal predictive performance, with a high R² of 0.998
Increasing the stability of electrolyte-gated organic synaptic transistors for neuromorphic implants
No full textElectrolyte-gated organic synaptic transistors (EGOSTs) can have versatile synaptic plasticity in a single device, so they are promising as components of neuromorphic implants that are intended for use in neuroprosthetic electronic nerves that are energy-efficient and have simple system structure. With the advancement in transistor properties of EGOSTs, the commercialization of neuromorphic implants for practical long-term use requires consistent operation, so they must be stable in vivo. This requirement demands strategies that maintain electronic and ionic transport in the devices while implanted in the human body, and that are mechanically, environmentally, and operationally stable. Here, we cover the structure, working mechanisms, and electrical responses of EGOSTs. We then focus on strategies to ensure their stability to maintain these characteristics and prevent adverse effects on biological tissues. We also highlight state-of-the-art neuromorphic implants that incorporate these strategies. We conclude by presenting a perspective on improvements that are needed in EGOSTs to develop practical, neuromorphic implants that are long-term useable.N
Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial
No full textBackground: DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline. Patients and methods: Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR. Results: As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1. Conclusions: Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.Y
Incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in South Korea
No full textIntroduction: Children's rare lung diseases are a heterogeneous group of rare lung diseases with significant morbidity and mortality. There is very limited information on the incidence and prevalence of children's rare lung diseases in Asia. We investigated the nationwide incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in Korea. Methods: We studied patients who were diagnosed with rare lung diseases coded per International Statistical Classification of Diseases and Related Health Problems, 10th Edition and registered in the national rare diseases database of confirmed patients. Data was extracted from the Korean National Health Insurance Service Claims database over 2019−2021. Results: Average incidence rate was 12.9 new cases per million children per year, and average prevalence rate was 60.2 cases per million children during the study period of 2019−2021. We found that more than 65% of new cases were diagnosed before 2 years of age. ChILD, primary ciliary dyskinesia, and cystic fibrosis were usually diagnosed after 6 years of age. Congenital airway and lung anomalies were often diagnosed before 2 years of age. Busan and Gyeongsangnam-do residents tended to visit hospitals near their place of residence, while residents of other areas tended to visit hospitals in Seoul regardless of their area of residence. Conclusions: We examined the epidemiology of rare lung diseases in children in South Korea. Our estimation of the incidence and prevalence could be used for sustainable health care and equitable distribution of health care resources.N
Noise-Robust Online Measurement of the On-State Resistance of the Power Semiconductor Devices in PWM Converters
No full textThe increase in RDUT, the on-state resistance of power semiconductor devices, is used to estimate the remaining useful life (RUL) of the devices. Conventional online measurement of RDUT involves on-state voltage measurement of the on-state device, which is easily polluted by switching noise to limit the measurement accuracy. This paper proposes a new noise-robust method to measure the increment of RDUT by inductor current and input/output DC voltage of DC-DC converters. The proposed method features higher accuracy in predicting RUL than the conventional one because the inductor current is immune to switching noise. The aging of MOSFET is emulated in this paper by adding a series resistor Rext. Experiments showed that the resistance increment measured by the proposed method is up to 99.2% accurate to value of Rext.Y
Recent advances in synthesis and properties of silver nanoclusters
No full textAchieving atomic precision in nanostructured materials is essential for comprehending formation mechanisms and elucidating structure-property relationships. Within the realm of nanoscience and technology, atomically precise ligand-protected noble metal nanoclusters (NCs) have emerged as a rapidly expanding area of interest. These clusters manifest quantum confinement-induced optoelectronic, photophysical, and chemical properties, along with remarkable catalytic capabilities. Among coinage metals, silver distinguishes itself for the fabrication of stable nanoclusters, primarily due to its cost-effectiveness compared to gold. This minireview provides an overview of recent advancements since 2020 in synthetic methodologies and ligand selections toward attaining NCs boasting a minimum of two free valence electrons. Additionally, it explores strategies for fine-tuning optical properties. The discussion extends to surface reactivity, elucidating how exposure to ligands, heat, and light induces transformations in size and structure. Of paramount significance are the applications of silver NCs in catalytic reactions for energy and chemical conversion, supplemented by in-depth mechanistic insights. Furthermore, the review delineates challenges and outlines future directions in the NC field, with an eye toward the design of new functional materials and prospective applications in diverse technologies, including optoelectronics, energy conversion, and fine chemical synthesis. This minireview outlines recent progress in synthetic strategies, photophysical, surface reactivity, and catalytic properties of Ag(0)-containing ligand-protected atomically precise silver nanoclusters.N
The crowds of Shadows in the Shape of Man and women: John Keats and the Reading Public
No full textThis essay explores how the reading public shaped John Keats's self-consciousness as an author and influenced his writing practices, by examining his literary and publishing activities. While the traditional image of Romantic poets often highlights their individual creativity as the foundation of their artistic expression, this view oversimplifies their complex interaction with external realities. Instead of characterizing them as isolated bearers of original creativity, it is crucial to acknowledge that their private emotions and artistic expressions were deeply influenced by the socio-economic conditions of their time, particularly within the capitalist framework that intensified during the 18th century. The commercialized publishing market and its associated reading public notably influenced the direction of their literary works. For Keats, who had a vulnerable socio-economic base, the reading public had a profound impact on his writing practices. Thus, tracing his relationship with the reading public is essential for understanding the historicity behind what seems to be his original expressions of personal emotions. More specifically, this essay argues that the complex emotions and self-consciousness Keats exhibited during three publishing projects reflect the vivid consciousness of a Romantic poet who was compulsively contemplating how to reconcile his authorial ideals with the contemporary publishing markets demands, thus revealing the public significance and historicity embedded within the domain of individual creativity that Romantic poets were thought to have pioneered.N
Differences in severity of chemotherapy-induced nausea and vomiting between neoadjuvant and adjuvant chemotherapy in patients with breast cancer: analysis of data from two prospective observational studies
No full textPurpose We assessed the differences in chemotherapy-induced nausea and vomiting (CINV) severity in patients with breast cancer, receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Methods CINV severity in patients on anthracycline-based NAC (n = 203) and AC (n = 79) was assessed at baseline (C0) and after the first and fourth chemotherapy using a 10-point Likert scale. Group-by-time interaction term was used to evaluate the effect of the group on changes in CIN (cCIN) and CIV (cCIV) from C0 to the follow-up periods (C1, C4). If insignificant, group effects were analyzed without the interaction term. Subgroup analysis was performed based on age 50. In statistical analyses, sociodemographic and clinical variables that differed between groups were adjusted for. Results The effect of group by follow-up period was not significant in cCIN and cCIV. The AC group showed a significantly higher change in the severity of cCIN compared to the NAC group (estimated mean = 1.133, 95% CI = 0.104-2.161, p = 0.031), but there was no difference in cCIV. In those <= 50 years, significant differences in cCIN severity (estimated mean = 1.294, 95% CI = 0.103-2.484, p = 0.033) were observed, but not in cCIV. In those > 50 years, neither cCIN nor cCIV differed significantly between groups. Conclusions NAC in breast cancer patients showed less severe CIN than adjuvant chemotherapy AC, but not in those over 50. Clinicians should recognize that the severity of CIN may vary across different chemotherapy settings and adjust their management accordingly. Trial registration The clinical trial registration (www.ClinicalTrials.gov) numbers were NCT 01887925 (the registration date is from June 20, 2013, to November 27, 2015) and NCT02011815 (the registration date is from December 10, 2013, to September 22, 2019).N
Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study
No full textBackground: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. Methods: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. Findings: The 2,486 participants (age = 69.1 +/- 6.5 years, 57.6% women) were followed for 5.9 +/- 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score ( b = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score ( b = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. Interpretation: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults. (Am J Geriatr Psychiatry 2024; 32:957 - 967)N