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Dongseong Shin,1 Sook Joung Lee,2 Yu-Mi Ha,3 Young-Sim Choi,3 Jae-Won Kim,3 Se-Rin Park,3 Min Kyu Park3 1Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 2Department of Rehabilitation Medicine, 3Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea Objective: Prostaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.Materials and methods: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation.Results: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.Conclusion: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme. Keywords: ibuprofen, different formulation, COX2-inhibitory effects

As control of the Rashba spin splitting size is highly desirable for spintronic devices, intensive studies have been performed to vary the splitting size by, for example, applying an electric field or designing novel heterostructures. However, direct observation of Rashba spin splitting size change via spectroscopic measurements has not been done so far. Here, we report results of angle-resolved photoemission studies on ferroelectric α-GeTe(111). We observe that the Rashba splitting size of α-GeTe(111) surface states is reduced upon dosing with potassium (K) which has a very low electron affinity. Based on density functional theory calculations, we find that the electric potential energy at the topmost atomic layer and the surface potential energy barrier is reduced upon K dosing. This change in the surface potential induces both delocalization of the surface states and reduction of the splitting size. We expect to increase the splitting size by dosing other elements or molecules with high electron affinity.

Each plane of layered ReS2 and ReSe2 materials has 1D chain structure, from which intriguing properties such as 1D character of the exciton states and linearly polarized photoluminescence originate. However, systematic studies on the 1D character of charge carriers have not been done yet. Here, we report on systematic and comparative studies on the energy-momentum dispersion relationships of layered transition metal dichalcogenides ReS2 and ReSe2 by angle resolved photoemission. We found that the valence band maximum or the minimum energy for holes is located at the high symmetric Z-point for both materials. However, the out-of-plane ([Formula: see text]) dispersion for ReSe2 (20 meV) is found to be much smaller than that of ReS2 (150 meV). We observe that the effective mass of the hole carriers along the direction perpendicular to the chain is about 4 times larger than that along the chain direction for both ReS2 and ReSe2. Remarkably, the experimentally measured hole effective mass is about twice heavier than that from first principles calculation for ReS2 although the in-plane anisotropy values from the experiment and calculations are comparable. These observation indicate that bulk ReS2 and ReSe2 are unique semiconducting transition metal dichalcogenides having strong one-dimensional characters.

Direct band-gap semiconductors play the central role in optoelectronics. In this regard, monolayer (ML) MX2 (M = Mo, W; X = S, Se) has drawn increasing attention due to its novel optoelectronic properties stemming from the direct band-gap and valley degeneracy. Unfortunately, the more practically usable bulk and multilayer MX2 have indirect-gaps. It is thus highly desired to turn bulk and multilayer MX2 into direct band-gap semiconductors by controlling external parameters. Here, we report angle-resolved photoemission spectroscopy (ARPES) results from Rb dosed MoSe2 that suggest possibility for electric field induced indirect to direct band-gap transition in bulk MoSe2. The Rb concentration dependent data show detailed evolution of the band-gap, approaching a direct band-gap state. As ionized Rb layer on the surface provides a strong electric field perpendicular to the surface within a few surface layers of MoSe2, our data suggest that direct band-gap in MoSe2 can be achieved if a strong electric field is applied, which is a step towards optoelectronic application of bulk materials.

OBJECTIVE: To determine the diagnostic value of voice analysis to screen for patients with high risk of clinically significant aspiration. DESIGN: A total of 93 patients referred for a videofluoroscopic swallowing study were included in the study. Voice analyses were performed before and after videofluoroscopic swallowing study, and five acoustic variables were measured, including average fundamental frequency, relative average perturbation, shimmer percentage, noise-to-harmonic ratio, and voice turbulence index. The patients were divided into two groups based on the results of the videofluoroscopic swallowing study: a high-risk group with patients who had the ingested materials on or below the vocal cords and a low-risk group with patients who did not have the ingested materials on or below the vocal cords. The changes of each acoustic variable before and after the videofluoroscopic swallowing study were compared between the two groups. RESULTS: Relative average perturbation, shimmer percentage, noise-to-harmonic ratio, and voice turbulence index were significantly increased after videofluoroscopic swallowing study in the high-risk group as compared with the low-risk group (P < 0.05). The change of average fundamental frequency, however, was not significantly different between the two groups (P > 0.05). According to the receiver operating characteristics curve, the sensitivity of these acoustic variables in detecting aspiration or penetration ranged from 68.9% to 91.1% and specificity ranged from 68.8% to 97.9%. Relative average perturbation was the most accurate variable, with a sensitivity of 91.1% and a specificity of 97.9% in predicting aspiration or penetration. The combination of relative average perturbation and noise-to-harmonic ratio increased the sensitivity to 100% but reduced the specificity to 77.1%. CONCLUSION: Voice analysis is a safe, noninvasive, and reliable screening tool for patients with dysphagia and can detect patients at high risk of clinically significant aspiration, thereby augmenting clinical bedside examination. [ABSTRACT FROM AUTHOR]

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

Background and Purpose: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action., Experimental Approach: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting., Key Results: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1β, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model., Conclusion and Implications: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Skin wounds heal faster during stem cell differentiation. Cold plasma reportedly enhances cell proliferation and differentiation and enhances the efficacy of stem cell therapy. However, the exact mechanism of action involved remains unknown. Therefore, this study aimed to evaluate the effect of a combination therapy involving the transplantation of mouse mesenchymal stem cells (mMSCs) into mice with wounds followed by their activation using no-ozone cold plasma (NCP). Balb/c mMSCs were transplanted into BALB/c mice and treated with NCP for 5 min. The animals were divided into four groups based on treatments received: no treatment (Wound), mMSCs only (mMSC), NCP only (NCP), and both mMSC and NCP (mMSC + NCP). NCP treatment was administered six times over two weeks, and tissue samples were prepared by sacrificing the mice in the 1st and 2nd weeks. The wound healing efficacy was assessed using morphological, histological, and molecular approaches including wound healing length measurements, hematoxylin and eosin staining, Masson trichrome staining, immunofluorescence staining, immunohistochemistry, and real-time polymerase chain reaction. The wound healing effect was better in the mMSC + NCP group than that in the groups treated with either. Tracking the injected mMSCs in mice also revealed that the mMSC + NCP group had a greater survival rate. Furthermore, upon wound healing, the mMSC + NCP group exhibited elevated levels of growth factors, like platelet-derived growth factor, transforming growth factor-beta, and vascular endothelial growth factor. These results suggest that NCP stimulated transplanted mMSCs, resulting in faster wound healing. Therefore, further studies are warranted in preclinical and clinical studies to confirm this effect., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gyoo Cheon Kim reports a relationship with Pusan National University that includes: funding grants. Gyoo Cheon Kim has patent #2016M3A9C6918283 pending to Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives : Enhanced osteoblast differentiation may be leveraged to prevent and treat bone-related diseases such as osteoporosis. No-ozone cold plasma (NCP) treatment is a promising and safe strategy to enhance osteoblast differentiation. Therefore, this study aimed to determine the effectiveness of direct and indirect NCP treatment methods on osteoblast differentiation. Mouse osteoblastic cells (MC3T3-E1) were treated with NCP using different methods, i.e., no NCP treatment (NT group; control), direct NCP treatment (DT group), direct NCP treatment followed by media replacement (MC group), and indirect treatment with NCP-treated media only (PAM group). Materials and Methods : The MC3T3-E1 cells were subsequently assessed for cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and ALP and osteocalcin mRNA expression using real-time polymerase chain reaction. Results : Cell proliferation significantly increased in the NCP-treated groups (DT and PAM; MC and PAM) compared to the NT group after 24 h ( p < 0.038) and 48 h ( p < 0.000). ALP activity was increased in the DT and PAM groups at 1 week ( p < 0.115) and in the DT, MC, and PAM groups at 2 weeks ( p < 0.000) compared to the NT group. Calcium deposition was higher in the NCP-treated groups than in NT group at 2 and 3 weeks ( p < 0.000). ALP mRNA expression peaked in the MC group at 2 weeks compared to the NP group ( p < 0.014). Osteocalcin mRNA expression increased in the MC group at 2 weeks ( p < 0.000) and was the highest in the PAM group at 3 weeks ( p < 0.000). Thus, the effects of direct (DT and MC) and indirect (PAM) treatment varied, with MC direct treatment showing the most significant impact on osteoblast activity. Conclusions : The MC group exhibited enhanced osteoblast differentiation, indicating that direct NCP treatment followed by media replacement is the most effective method for promoting bone formation.

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Flow cytometry plays a pivotal role in biotechnology by providing quantitative measurements for a wide range of applications. Nonetheless, achieving precise particle quantification, particularly without relying on counting beads, remains a challenge. In this study, we introduce a novel exhaustive counting method featuring a sample loop-based injection system that delivers a defined sample volume to a detection system to enhance quantification in flow cytometry. We systematically assess the performance characteristics of this system with micron-sized polystyrene beads, addressing issues related to sample introduction, adsorption, and volume measurement. Results underscore the excellent analytical performance of the proposed method, characterized by high linearity and repeatability. We compare our approach to counting bead-based measurements, and while an approximate bias value was observed, the measured values were found to be similar between the methods, demonstrating its comparability and reliability. This method holds great promise for improving the accuracy and precision of particle quantification in flow cytometry, with implications for various fields including healthcare and environmental monitoring., (© 2024. The Author(s).)

Use of a template triggers an epitaxial interaction with the depositing material during synthesis. Recent studies have demonstrated that two-dimensional tellurium (tellurene) can be directionally oriented when grown on transition metal dichalcogenide (TMD) templates. Specifically, employing a T-phase TMD, such as WTe 2 , restricts the growth direction even further due to its anisotropic nature, which allows for the synthesis of well-oriented tellurene films. Despite this, producing large-area epitaxial films still remains a significant challenge. Here, we report the continuous synthesis of a 1T'-MoTe 2 template via chemical vapor deposition and tellurene via vapor transport. The interaction between helical Te and the 1T'-MoTe 2 template facilitates the Te chains to collapse into ribbon shapes, enhancing lateral growth at a rate approximately 6 times higher than in the vertical direction, as confirmed by scanning electron microscopy and atomic force microscopy. Interestingly, despite the predominance of the lateral growth, cross-sectional transmission electron microscopy analysis of the tellurene ribbons revealed a consistent 60-degree incline at the edges. This suggests that the edges of the tellurene ribbons, where they contact the template surface, are favorable sites for additional Te absorption, which then stacks along the incline angle to expand. Furthermore, controlling the synthesis temperature, duration, and preheating time has facilitated the successful synthesis of tellurene films. The resultant tellurene exhibited hole mobility as high as ∼400 cm 2 /V s. After removing the underlying metallic template with plasma treatment, the film showed a current on/off ratio of ∼10 3 . This ratio was confirmed by two-terminal field-effect transistor measurements and supported by near-field terahertz (THz) spectroscopy mapping.

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy., Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort., Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively., Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued., Competing Interests: We have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery., Patients and Methods: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model., Results: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%., Conclusions: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment., (© 2024. Society of Surgical Oncology.)

The reciprocal crosstalk between testicular Sertoli and Leydig cells plays a vital role in supporting germ cell development and maintaining testicular characteristics and spermatogenesis. Conventional 2D and the recent 3D assay systems fail to accurately replicate the dynamic interactions between these essential endocrine cells. Furthermore, most in vitro testicular tissue models lack the ability to capture the complex multicellular nature of the testis. To address these limitations, we developed a 3D multicellular testis-on-a-chip platform that effectively demonstrates the reciprocal crosstalk between Sertoli cells and the adjacent Leydig cells while incorporating various human testicular tissue constituent cells and various natural polymers infused with blood coagulation factors. Additionally, we identified SERPINB2 as a biomarker of male reproductive toxicity that is activated in both Sertoli and Leydig cells upon exposure to various toxicants. Leveraging this finding, we designed a fluorescent reporter-conjugated toxic biomarker detection system that enables both an intuitive and quantitative assessment of material toxicity by measuring the converted fluorescence intensity. By integrating this fluorescent reporter system into the Sertoli and Leydig cells within our 3D multicellular chip platform, we successfully developed a testis-on-chip model that can be utilized to evaluate the male reproductive toxicity of potential drug candidates. This innovative approach holds promise for advancing toxicity screening and reproductive research., (© 2024. The Author(s).)

Adapted immune cells are known to develop memory functions that increase resistance to subsequent infections after initial pathogen exposure, however, it is unclear whether non-immune cells, like tissue-resident stem cells, have similar memory functions. Here, it is found that tissue-resident stem cells crucial for tissue regeneration show diminished adverse effects on diverse stem cell functions against successive exposure to foreign antigen (β-glucan) to maintain tissue homeostasis and stability both in vitro and in vivo. These data suggest that endometrial stem cells may possess a robust memory function, in contrast, fully differentiated cells like fibroblasts and vesicular cells do not show these memory mechanisms upon consecutive antigen exposure. Moreover, the pivotal role of Angiopoietin-like 4 (ANGPTL4) in regulating the memory functions of endometrial stem cells is identified through specific shRNA knockdown in vitro and knockout mice in vivo experiments. ANGPTL4 is associated with the alteration of diverse stem cell functions and epigenetic modifications, notably through histone H3 methylation changes and two pathways (i.e., PI3K/Akt and FAK/ERK1/2 signaling) upon consecutive antigen exposure. These findings imply the existence of inherent self-defense mechanisms through which local stem cells can adapt and protect themselves from recurrent antigenic challenges, ultimately mitigating adverse consequences., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Metrology is the science of measurement and its applications, whereas biometrology is the science of biological measurement and its applications. Biometrology aims to achieve accuracy and consistency of biological measurements by focusing on the development of metrological traceability, biological reference measurement procedures, and reference materials. Irreproducibility of biological and multi-omics research results from different laboratories, platforms, and analysis methods is hampering the translation of research into clinical uses and can often be attributed to the lack of biologists' attention to the general principles of metrology. In this paper, the progresses of biometrology including metrology on nucleic acid, protein, and cell measurements and its impacts on the improvement of reliability and comparability in biological research are reviewed. Challenges in obtaining more reliable biological and multi-omics measurements due to the lack of primary reference measurement procedures and new standards for biological reference materials faced by biometrology are discussed. In the future, in addition to establishing reliable reference measurement procedures, developing reference materials from single or multiple parameters to multi-omics scale should be emphasized. Thinking in way of biometrology is warranted for facilitating the translation of high-throughput omics research into clinical practices., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95‑2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95‑2 cells were transduced with lentiviral particles targeting ADIPOR1 . Reverse transcription‑quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid‑secretory phase compared with that in the proliferative phase and in receptive RL95‑2 cells compared with that in non‑receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E‑cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP‑activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5‑aminoimidazole‑4‑carboxamide ribonucleotide affected E‑cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E‑cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.

Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC., Trial Registration: The trial was registered at ClinicalTrials.gov under the identifier NCT03785496., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms., Experimental Design: Primary specimens, cell lines, patient-derived xenograft models, commercially available, and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation., Results: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), and gamma/delta T-cell lymphoma (G/D TCL). The majority of the CD8+/CD57+ or CD3-/CD56+ leukemic cells derived from patients with T- and NK-large granular lymphocytic leukemia (T-LGLL and NK-LGLL), respectively, expressed surface KLRG1. The humanized afucosylated anti-KLRG1 monoclonal antibody (mAb208) optimized for mouse in vivo use depleted KLRG1+ TCL cells by mechanisms of ADCC, ADCP, and CDC rather than apoptosis. mAb208 induced ADCC and ADCP of T-LGLL patient-derived CD8+/CD57+ cells ex vivo. mAb208 effected ADCC of subsets of healthy donor-derived KLRG1+ NK, CD4+, CD8+ Tem, and TemRA cells while sparing KLRG1- naïve and CD8+ Tcm cells. Treatment of cell line and TCL patient-derived xenografts with mAb208 or anti-CD47 mAb alone and in combination with the PI3K-δ/γ inhibitor duvelisib extended survival. The depletion of macrophages in vivo antagonized mAb208 efficacy., Conclusions: Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms. See related commentary by Varma and Diefenbach, p. 2300., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib., Methods: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1., Results: The median age was 60 years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively., Conclusion: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs., (© 2024. Asian Pacific Association for the Study of the Liver.)

Competing Interests: Conflict of interest statement. None declared.

Service-oriented organizational citizenship behavior refers to service workers' helping, cooperating, sharing, and donating actions that benefit others at a cost to themselves. Based on ethical climate theory, this research investigates whether corporations adopting environmental, social, and governance (ESG) management enhance service-oriented organizational citizenship behavior (SO OCB) among service employees. A total of 230 surveys were collected from call center workers in the insurance industry, and STATA 14.0 was used to analyze the 204 responses with useable data. The results show that employees' recognized ESG activities enable SO OCB through organizational commitment. Additionally, ESG activity recognition has a positive relationship with self-efficacy and empowerment, which helps service employees regulate external expectations. Thus, this finding is significant for call center workers experiencing emotional labor. Furthermore, the results suggest that firms can contribute to employees' SO OCB by practicing ESG activities. Firms should inform employees of their ESG management efforts as employees' recognition of an ethical climate can enhance their willingness to perform service-oriented behavior. Finally, ESG activity recognition can increase employees' organizational commitment, an important predictor of employee satisfaction and negative turnover rates., 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 Authors.)

Background: Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions., Materials and Methods: Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36 o C), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups., Results: Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30 min after the operation was started., Conclusions: Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform., Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment., Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers., Trial Registration: NCT05525858., (© 2024. The Author(s).)

This study investigated the correlation between piglet performance and sow body weight change (BWC) during two gestational periods: 35-70, 70-105, and 35-105 days. A cohort of 70 sows was evaluated for BWC, backfat thickness change (BFC), caliper score change (CALC), feed intake, and weaning-to-estrus interval (WEI). The collected data were then analyzed according to the two specified periods. Our findings highlighted that piglet birth weight, weaning weight, and average daily weight gain (ADG) correlated with sow body characteristics, including BFC and CALC. The strongest correlation was observed with BWC. Piglet mortality was intimately associated with BFC. Piglet birth weight, weaning weight, and ADG showed a positive correlation with sow BWC, particularly during the 35-70 day period. Furthermore, sows displaying a higher BWC during the 70-105 day period, and also exhibiting a higher BW gain from 35-70 days, registered greater piglet weight gains and higher weaning weights. These trends became more apparent as the sow's BWC increased during the 70-105 day period. Piglet mortality increased when the sow exhibited a lower BWC during both the 35-70 and 70-105 day periods. No significant observations were found concerning the number of stillborn piglets, live-born piglets, or weaned piglets, and no interaction effects were detected between these periods. In conclusion, our findings underscore the significance of sow BWC during the early stages of gestation (d 35-70) for enhancing piglet performance from birth to weaning., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Key Message: OsICS1 but not OsICS1-L mediates the rice response to Xoo inoculation, with its overexpression increasing resistance against this pathogen. OsICS1 but not OsICS-L is directly upregulated by OsWRKY6. Rice (Oryza sativa) is a staple crop for about half of the global population and is particularly important in the diets of people living in Asia, Latin America, and Africa. This crop is continually threatened by bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), which drastically reduces yields; therefore, it is needed to elucidate the plant's resistance mechanisms against Xoo. Isochorismate synthase (ICS1) generates salicylic acid (SA) and increases resistance against bacterial disease. The OsICS1 is differently annotated in rice genome databases and has not yet been functionally characterized in the context of Xoo infection. Here, we report that the expression of the OsICS1 is directly regulated by OsWRKY6 and increases plant resistance against Xoo. Inoculation with Xoo increased the expression of OsICS1 but not that of the long variant of OsICS1 (OsICS1-L). OsWRKY6 directly activated the OsICS1 promoter but not the OsICS1-L promoter. OsICS1 overexpression in rice increased resistance against Xoo through the induction of SA-dependent bacterial defense genes. These data show that OsICS1 promotes resistance against Xoo infection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three Fe(III)-based coordination complexes [Fe(dqmp) 2 ](NO 3 )·H 2 O (1), [Fe(dqmp) 2 ](BF 4 )·2CH 3 COCH 3 (2), and [Fe(dqmp) 2 ](ClO 4 ) (3) were synthesized from Fe(NO 3 ) 3 ·9H 2 O/Fe(ClO 4 ) 3 ·xH 2 O, NaBF 4 , and 2,4-dichloro-6-((quinoline-8-ylimino)methyl)phenol (Hdqmp) in methanol/acetone and characterized. The structures of complexes 1-3 were determined via single-crystal X-ray crystallography at 100 K and room temperature, and their magnetic properties in the solid and solution forms were investigated. All complexes showed meridional structures with two tridentate dqmp - ligands coordinated with Fe(III) cations. In the solid state, complex 1 showed an abrupt and complete spin crossover at 225 K, whereas complexes 2 and 3 exhibited an incomplete spin crossover at 135 and 150 K, respectively. In a dimethylformamide solution, the complexes showed counterion-dependent spin transitions. In contrast to the solid state, in solution, complex 1 did not exhibit complete spin crossover. However, complexes 2 and 3 showed more complete spin transitions in solutions than in the solid state. The relaxation times, T 1 and T 2 , for 1 and 2 were determined and both increased with temperature from 220 to 380 K. The T 1 of 1 was larger than that of 2 at 380 K, and the T 1 values were larger than the T 2 values.

This study retrospectively assessed radiographic outcomes and risk factors associated with non-union in femoral shaft fragmentary segmental fractures (AO/OTA 32C3) treated with reamed antegrade intra-medullary nailing. Radiological outcomes, including union and alignment, were evaluated. The risk factors for non-union were investigated, including demographics and treatment-related characteristics, such as the number of interlocking screws, segmentation length, main third fragment length, distance of the main third fragment, width ratio and exposed nail length in one cortex from immediate post-operative radiographs. Multivariate logistic regression was used for statistical analysis. Among 2295 femoral shaft fracture patients from three level-1 trauma centers, 51 met the inclusion criteria. The radiological union was achieved in 37 patients (73%) with a mean union time of 10.7 ± 4.8 months. The acceptable axial alignment was observed in 30 patients (59%). Multiple logistic regression analysis identified only exposed nail length as a significant risk factor for non-union (odds ratio: 1.599, p = 0.003) and the cut-off value was 19.1 mm (sensitivity, 0.786; specificity, 0.811). The study revealed high rates of non-union (27%) and malalignment (41%). Therefore, patients who underwent intramedullary nailing with an exposed nail length greater than 19.1 mm or about twice the nail diameter should be cautioned of the potential non-union., (© 2024. The Author(s).)

Key Message: Bulked segregant RNA seq of pools of pepper accessions that are susceptible or resistant to Broad bean wilt virus 2 identifies a gene that might confer resistance to this devastating pathogen. The single-stranded positive-sense RNA virus Broad bean wilt virus 2 (BBWV2) causes substantial damage to pepper (Capsicum annuum) cultivation. Here, we describe mapping the BBWV2 resistance locus bwvr using a F 7:8 recombinant inbred line (RIL) population constructed by crossing the BBWV2-resistant pepper accession 'SNU-C' with the susceptible pepper accession 'ECW30R.' All F 1 plants infected with the BBWV2 strain PAP1 were susceptible to the virus, and the RIL population showed a 1:1 ratio of resistance to susceptibility, indicating that this trait is controlled by a single recessive gene. To map bwvr, we performed bulked segregant RNA-seq (BSR-seq). We sequenced pools of resistant and susceptible lines from the RILs and aligned the reads to the high-quality 'Dempsey' reference genome to identify variants between the pools. This analysis identified 519,887 variants and selected the region from 245.9-250.8 Mb of the Dempsey reference genome as the quantitative trait locus region for bwvr. To finely map bwvr, we used newly designed high-resolution melting (HRM) and Kompetitive allele specific PCR (KASP) markers based on variants obtained from the BSR-seq reads and the PepperSNP16K array. Comparative analysis identified 11 SNU-C-specific SNPs within the bwvr locus. Using markers derived from these variants, we mapped the candidate bwvr locus to the region from 246.833-246.949 kb. SNU-C-specific variants clustered near DEM.v1.00035533 within the bwvr locus. DEM.v1.00035533 encodes the nitrate transporter NPF1.2 and contains a SNP within its 5' untranslated region. The bwvr locus, which contains four genes including DEM.v1.00035533, could represent a valuable resource for global pepper breeding programs., (© 2024. The Author(s).)

Study Design: Retrospective observational study., Objective: To determine the proximity between screw and endplate of the upper instrumented vertebra (UIV) using a cortical bone trajectory (CBT) screw as a predictive factor for radiographic adjacent segment degeneration (ASD) in patients surgically treated with transforaminal lumbar interbody fusion (TLIF) with CBT screws (CBT-TLIF) with lumbar spinal stenosis., Summary of Background Data: The risk factors for radiographic ASD after CBT-TLIF remain unknown., Methods: Among patients surgically treated with CBT-TLIF at a single institute, 239 consecutive patients (80 males and 159 females) were enrolled. ASD was defined by the presence of one or more of the following three radiologic criteria on the adjacent segment: >3 mm anteroposterior translation, >10° segmental kyphosis, or >50% loss of disc height comparing immediate postoperative and 1-year follow-up radiographs. Clinical and radiological features associated with the development of ASD were retrospectively measured. Univariate and multivariate analyses were performed to identify risk factors associated with radiographic ASD., Results: Radiographic ASD was observed in 71 (29.7%) cases at 1-year postoperative follow-up. The preoperative Pfirrmann grade of the adjacent segment (>grade 2), multi-level fusion (>2 levels), and proximity between the tip of CBT screws and endplate on the UIV were significantly associated with radiographic ASD (OR = 3.98, 95% CI [1.06-15.05], P=0.042 versus OR = 3.03, 95% CI [1.00-9.14], P=0.049 versus OR = 0.53, 95% CI [0.40-0.72], P<0.001). The cut-off value of the distance between the tip of the screw and endplate on UIV for radiographic ASD was approximately 2.5 mm (right-sided CBT screw; cut-off value 2.48 mm/ left-sided CBT screw; cut-off value 2.465 mm)., Conclusion: Radiographic adjacent segment degeneration progression can occur when the cortical trajectory bone screw is close to the endplate of the upper instrumented vertebrae in patients with lumbar spinal stenosis undergoing fusion surgery., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest in relation to the present study including financial, consultant, institutional, or other relationships., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To develop and validate an artificial intelligence (AI)-based diagnostic system for analysing facial skin images using expert judgements and explore its feasibility for skin ageing research, specifically by evaluating facial skin changes in Korean women of various ages., Methods: Our AI-based facial skin diagnosis system (Dr. AMORE®) uses facial images of Korean women to analyse wrinkles, pigmentation, skin pores, and other skin red spots. The system is trained using clinical expert evaluations and deep learning. We assessed the system's precision and sensitivity by analysing the correlation between the diagnoses by the AI system and those of the experts. We used 120 images of Korean women aged 10-60 years to evaluate the changes in various facial skin characteristics with ageing., Results: The precision and sensitivity of the developed system were excellent (>0.9%), and the diagnosis scores using the detected area and intensity of each item were correlated significantly higher with the visual evaluation results of the clinical experts (>0.8, p < 0.001). We also analysed facial images of Korean women aged 10-60 years to quantify changes in the scores of wrinkles, pigmentation, and skin pores with age. We identified the age group with the most significant changes as 20s to 30s. Analysis of the detailed skin characteristics of each item showed that wrinkles and pigmentation changed significantly in the 20s-30s, and skin pores increased significantly in the 10s-20s. There was no significant correlation with age or change according to the age group for skin red spots., Conclusion: Developed AI-based facial skin diagnosis system can automatically diagnose skin conditions based on clinical expert judgement using only photographic images and analyse various items in detail, quantitatively, and visually. This AI system can provide new and useful approaches in research areas that require a lot of resources and different characterizations, such as the study of facial skin ageing., (© 2023 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)