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Off-target pesticide drift in paddy fields following unmanned aerial vehicle (UAV) spraying was evaluated using cellulose deposition samplers (CDSs). An analytical method for quantifying ferimzone Z and E isomers deposited on CDSs was developed using LC-MS/MS. The suitability of the CDS method was confirmed by comparing deposition patterns on CDSs with residue levels in rice plant samples. To assess pesticide deposition in paddy fields, CDSs were strategically placed at varying distances from target areas, followed by UAV spraying. The fungicide agrochemicals were applied with and without adjuvants, and wind direction affected the drift trajectory for all treatment groups. Adjuvants, particularly soy lecithin as the major component, significantly enhanced pesticide deposition within the spray pathway while reducing drift rates relatively by 47.9-68.0 %. Higher wind speeds were found to exacerbate drift, but adjuvant-treated sprays showed less variability in deposition patterns under these conditions. Pesticide residues in harvested brown rice were found to be below the maximum residue limits (MRLs), ensuring safety for consumption. These findings highlight the importance of selecting appropriate adjuvants in UAV-based pesticide applications to optimize deposition efficiency and minimize environmental contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment., Methods: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment., Results: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3., Discussion: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year., Methods: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed., Findings: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups., Interpretation: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions., Funding: Abbott Vascular and Cardiovascular Research Center., Translation: For the Korean translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests S-JH reports speaker fees from AstraZeneca, Amgen, ChongKunDang, Hanmi, and Viatris; and participation on the data safety monitoring board of the IVUS-DCB trial. S-JL reports research grants and speaker fees from Boston Scientific, Medtronic, ChongKunDang, and Sam Jin Pharmaceutical. JHH reports consulting and speaker fees from Abbott Vascular. J-WL reports consulting fees from Genoss; speaker fees from Yuhan, Boryoung, Sam Jin Pharmaceutical, ChongKunDang, Korea United Pharm, HK inno.N, Novartis, Boehringer Ingelheim, AstraZeneca, Medtronic, Abbott Vascular, Amgen, Sanofi, Boston Scientific, Daiichi-Sankyo, Daewoong Pharmaceutical, Biosensors, Dong-A ST, and JW Pharmaceutical; and participation on the data safety monitoring board of the Rescue-SHOCK trial. J-SK reports grants from Sam Jin Pharmaceutical, Yuhan, Daiichi-Sankyo, Biosensors, and Qualitech Korea and proctoring fees from Abbott Vascular. Y-GK reports research grants from Medtronic, Korea United Pharm, Cook Medical, Boston Scientific, Otsuka Korea, Dong-A ST, Sam Jin Pharmaceutical, Cordis, HK inno.N, and GC Biopharma. M-KH reports research grants, paid to their institution, from Sam Jin Pharmaceutical and ChongKunDang and honoraria for lectures from Medtronic and Edwards Lifesciences. YJ reports research grants, paid to their institution, from Abbott Vascular. B-KK reports research grants and speaker or consulting fees from Abbott Vascular, Yuhan, Sam Jin Pharmaceutical, ChongKunDang, Medtronic, Boston Scientific, Biotronik, Genoss, CGBIO, MicroPort, Daewoong Pharmaceutical, Amgen, Bayer Korea, DIO Medical, Hanmi, AstraZeneca, and Novartis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease., Methods: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline., Results: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract., Conclusions: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease., (Copyright © 2024. Published by Elsevier Inc.)

In animal cells, vacuoles are absent, but can be induced by diseases and drugs. While phosphoinositides are critical for membrane trafficking, their role in the formation of these vacuoles remains unclear. The immunosuppressive KRP203/Mocravimod, which antagonizes sphingosine-1-phosphate receptors, has been identified as having novel multimodal activity against phosphoinositide kinases. However, the impact of this novel KRP203 activity is unknown. Here, we show that KRP203 disrupts the spatial organization of phosphoinositides and induces extensive vacuolization in tumor cells and immortalized fibroblasts. The KRP203-induced vacuoles are primarily from endosomes, and augmented by inhibition of PIKFYVE and VPS34. Conversely, overexpression of PTEN decreased KRP203-induced vacuole formation. Furthermore, V-ATPase inhibition completely blunted KRP203-induced vacuolization, pointing to a critical requirement of the endosomal maturation process. Importantly, nearly a half of KRP203-induced vacuoles are significantly decorated with PI4P, a phosphoinositide typically enriched at the plasma membrane and Golgi. These results suggest a model that noncanonical spatial reorganization of phosphoinositides by KRP203 alters the endosomal maturation process, leading to vacuolization. Taken together, this study reveals a previously unrecognized bioactivity of KRP203 as a vacuole-inducing agent and its unique mechanism of phosphoinositide modulation, providing a new insight of phosphoinositide regulation into vacuolization-associated diseases and their molecular pathologies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 μM. Exposure to 50 μM BBP, approximating the IC 50 of 53.9 μM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 μM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity., 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 Inc.)

Background and Aims: Cardiovascular disease (CVD) remain one of the leading causes of mortality in breast cancer survivors. This study aimed to investigate the association between body composition and subsequent CVD in breast cancer survivors., Methods and Results: A retrospective cohort study of more than 70 thousand 5-year breast cancer survivors aged 40 years or older was conducted using data from the National Health Insurance Service of South Korea. Based on the percentage of predicted lean body mass (pLBMP), appendicular skeletal muscle mass (pASMP), and body fat mass (pBFMP), which were calculated using prediction equations with anthropometric data and health habits, groups were equally divided into quartiles. The risk of CVD was evaluated using multivariate Cox proportional hazards regression. Compared to those with the lowest pLBMP and pASMP, those with the highest pLBMP and pASMP had a 38% and 42% lower risk of CVD, respectively. In contrast, those with the highest pBFMP had a 57% higher risk of CVD compared to those with the lowest pBFMP. Each 1 % increase in pLBMP and pASMP was associated with a decreased risk of CVD [pLBMP, adjusted hazard ratio (aHR): 0.96, 95% CI 0.94-0.98, p < 0.05; pASMP, aHR: 0.91, 95% CI 0.87-0.95, p < 0.05] while each 1 % increase in pBFMP was associated with the increased risk of CVD (aHR: 1.05, 95% CI 1.03-1.07, p < 0.01)., Conclusion: In this cohort study, a high pLBMP, a high pASMP, and a low pBFMP were associated with a lower risk of CVD., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The left atrial appendage (LAA) is the predominant site of thrombus formation in atrial fibrillation (AF), which is associated with ischemic stroke. This study comparatively evaluated the complete LAA closure rates between LAA clipping and stapled resections., Methods: The study included 333 patients who underwent thoracoscopic operation with both preoperative and postoperative computed tomographic scans. Propensity score matching (4:1 ratio) was applied, matching 90 LAA clipping patients with 206 stapled resection patients. The primary end point was complete LAA closure, defined as a residual LAA depth of <1 cm on computed tomographic images obtained 1 year postoperatively., Results: No 30-day death was observed. Complete LAA closure was achieved in 85.9% (286 of 333) of patients. After propensity score matching, the clipping group demonstrated a significantly higher complete LAA closure rate than the stapled resection group (95.6% vs 83.0%, P = .003). The residual LAA stump depth was also shorter in the clipping group compared with the stapled resection group (2.9 vs 5.3 mm, P = .001). Two patients with a residual LAA stump exhibited an association with ischemic stroke during follow-up., Conclusions: The clipping group demonstrated a higher rate of complete LAA closure compared with the stapled resection group. Close monitoring of patients with residual LAA stumps is essential. Further research with larger cohorts is needed to elucidate impact of the residual LAA stump on thromboembolic events., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI)., Objectives: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation., Methods: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization., Results: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69)., Conclusions: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872)., Competing Interests: Funding Support and Author Disclosures This trial is investigator initiated with grant support from Abbott Vascular and Boston Scientific. The sponsors were not involved with the protocol development or study process, including site selection, management, data collection, or analysis of the results. Dr Chan Joon Kim has received research grants from Basic Science Research Program, National Research Foundation of Korea, Ministry of Education, Hanmi Pharmaceutical, Chong Keun Dang Pharm, Handoc Kalos Medical, Donga-ST, and Boryung Corporation. Dr Joo Myung Lee has received institutional research grants from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Zoll Medical, and Donga-ST. Dr Hyeon-Cheol Gwon has received institutional research grants from Abbott Vascular, Boston Scientific, and Medtronic Inc. Dr Joo-Yong Hahn has received institutional research grants from the National Evidence-based Healthcare Collaborating Agency, Ministry of Health and Welfare (Korea), Abbott Vascular, Biosensors, Boston Scientific, Daiichi-Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Foot-and-mouth disease (FMD) is an economically important disease, and the FMD virus (FMDV) can spread rapidly in susceptible animals. FMD is usually controlled through vaccination. However, commercial FMD vaccines are only effective 4-7 days after vaccination. Furthermore, FMDV comprises seven serotypes and various topotypes, and these aspects should be considered when selecting a vaccine. Antiviral agents could provide rapid and broad protection against FMDV. Therefore, this study aimed to develop a fusion protein of consensus porcine interferon-α and Fc portion of porcine antibody IgG (poIFN-α-Fc) using a baculovirus expression system to develop a novel antiviral agent against FMDV. We measured the antiviral effects of the poIFN-α-Fc protein against FMDV and the enhanced duration in vitro and in vivo. The broad-spectrum antiviral effects were tested against seven FMDV serotypes, porcine reproductive and respiratory syndrome virus (PRRSV), and bovine enterovirus (BEV). Furthermore, the early protective effects and neutralizing antibody levels were tested by co-injecting poIFN-α-Fc and an FMD-inactivated vaccine into mice or pigs. Sustained antiviral effects in pig sera and mice were observed, and pigs injected with a combination of the poIFN-α-Fc and an inactivated FMD vaccine were protected against FMDV in a dose-dependent manner at 2- and 4-days post-vaccination. In addition, combined with the inactivated FMD vaccine, poIFN-α-Fc increased the neutralizing antibody levels in mice. Therefore, poIFN-α-Fc is a potential broad-spectrum antiviral and adjuvant candidate that can be used with inactivated FMD vaccines to protect pigs against FMDV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults., Study Design: This was a retrospective observational study., Methods: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence., Results: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831)., Conclusions: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although benefits of intravascular imaging (IVI) in percutaneous coronary intervention (PCI) have been observed in previous studies, it is not known whether changes in contemporary practice, especially with application of standardized optimization protocols, have improved clinical outcomes., Objectives: The authors sought to investigate whether clinical outcomes of IVI-guided PCI are different before and after the application of standardized optimization protocols in using IVI., Methods: 2,972 patients from an institutional registry (2008-2015, before application of standardized optimization protocols, the past group) and 1,639 patients from a recently published trial (2018-2021 after application of standardized optimization protocols, the present group) were divided into 2 groups according to use of IVI. The primary outcome was 3-year target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization., Results: Significant reduction of TVF was observed in the IVI-guided PCI group compared with the angiography-guided PCI group (10.0% vs 6.7%; HR: 0.77; 95% CI: 0.61-0.97; P = 0.027), mainly driven by reduced cardiac death or myocardial infarction in both past and present IVI-guided PCI groups. When comparing past IVI and present IVI groups, TVF was significantly lower in the present IVI group (8.5% vs 5.1%; HR: 0.63; 95% CI: 0.42-0.94; P = 0.025), with the difference being driven by reduced target vessel revascularization in the present IVI group. Consistent results were observed in inverse-probability-weighting adjusted analysis., Conclusions: IVI-guided PCI improved clinical outcomes more than angiography-guided PCI. In addition, application of standardized optimization protocols when using IVI further improved clinical outcomes after PCI. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE-COMPLEX-PCI]; NCT03381872; and the institutional cardiovascular catheterization database of Samsung Medical Center: Long-Term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815)., Competing Interests: Funding Support and Author Disclosures The RENOVATE-COMPLEX-PCI trial is investigator-initiated with grant support from Abbott Vascular and Boston Scientific. Other than providing financial support, the sponsors were not involved with protocol development or the study process, including site selection, study management, data collection, and analysis of the results. Prof Gwon has received institutional research grants from Boston Scientific, Genoss, and Medtronic Inc. Prof Hahn has received institutional research grants from National Evidence-based Healthcare Collaborating Agency, Ministry of Health & Welfare, Korea, Abbott Vascular, Biosensors, Boston Scientific, Daiichi Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. Dr J.M. Lee has received institutional research grants from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Zoll Medical, and Donga-ST. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins., Methods: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed., Results: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426)., Conclusion: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings., Competing Interests: Declaration of competing interest none., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Although pericardiectomy is an effective treatment for constrictive pericarditis (CP), clinical outcomes are not always successful. Pericardial calcification is a unique finding in CP, although the amount and localization of calcification can vary. We investigated how the pattern and amount of pericardial calcification affect mid-term postoperative outcomes after pericardiectomy to treat CP., Methods: All patients of total pericardiectomy in our hospital from 2010 to 2020 were enrolled. Preoperative Computed tomography (CT) scans of 98 consecutive patients were available and analyzed. Medical records were reviewed retrospectively. Cardiovascular events were defined as cardiovascular death or hospitalization associated with a heart failure symptom, and all-cause events were defined as any event that required admission. CT scans were analyzed, and the volume and localization pattern of peri-calcification were determined. Pericardium calcium scores are presented using Agatston scores., Results: Of the 98 patients, 25 (25.5%) were hospitalized with heart failure symptoms after pericardiectomy. The median follow-up duration for all patients was 172 weeks. The group with a cardiovascular event had a lower calcium score than patients without an event. Multivariate Cox proportional analysis showed that high ln(calcium score+1) before pericardiectomy was a dependent predictor of cardiovascular event (hazard ratio, 0.90; p = 0.04) after pericardiectomy. When we set the cut-off value (ln(calcium score+1) = 7.22), there was a significant difference in cardiovascular events in the multivariate Cox proportional analysis (p = 0.04)., Conclusion: A low burden of pericardial calcification was associated with a high rate of mid-term clinical events after pericardiectomy to treat CP., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Vitamin D is an important immune modulator and is associated with susceptibility to infection. However, past studies have reported inconsistent results regarding the association between vitamin D deficiency and mortality in patients with sepsis, and early-stage data regarding septic shock are limited. This study aimed to determine the relationship between vitamin D deficiency on admission to the emergency department (ED) and mortality in patients with septic shock., Methods: We analyzed prospectively collected data on adult patients with septic shock who were treated with protocol-driven resuscitation bundle therapy in the ED between September 2019 and February 2021. Septic shock was defined by the sepsis-3 definition and vitamin D deficiency was defined as a 25-hydroxyvitamin D <20 ng/ml. The primary outcome was 30-day mortality., Results: A total of 302 patients were included, 236 (78.1%) patients had vitamin D deficiency; it was significantly higher in non-survivors than in survivors (89.3% vs. 73.9%, P = 0.004). Mortality was higher in vitamin D deficient patients than in non-deficient patients (31.8% vs. 13.6%, P = 0.004). In multivariate analysis, vitamin D deficiency (odds ratio [OR], 2.43; 95 % confidence interval [CI], 1.03-5.74), hyperlactatemia (OR, 3.65; 95 % CI, 1.95-6.83), Sequential Organ Failure Assessment scores (OR, 1.22; 95% CI, 1.09-1.36), and albumin levels (OR, 0.39; 95% CI, 0.21-0.73) were significantly associated with 30-day mortality., Conclusions: Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Left-sided frontal alpha asymmetry on electroencephalograms, which indicates decreased relative left-hemispheric activity, has been associated with depression, anxiety, and stress responsivity. We aimed to evaluate the association between perioperative measures of frontal alpha asymmetry and quality of recovery (QoR) after surgery., Methods: We enrolled 110 female patients undergoing thyroidectomy and recorded perioperative electroencephalograms. The power of the prefrontal alpha band (8-13 Hz) was measured in the Fp1 and Fp2 leads. Left-sided frontal alpha asymmetry was defined as a higher alpha band power in Fp1 than in Fp2 and vice versa. QoR was assessed using the QoR-15 score on the day before surgery and postoperative days 1 and 2. The primary study endpoint was a difference in postoperative global QoR-15 score between preoperative left-sided and right-sided alpha asymmetry groups. The predictability of frontal alpha asymmetry for poor QoR-15 score was also evaluated., Results: The global QoR-15 score showed a significant group-by-time interaction, and post-hoc analysis revealed significantly lower scores on postoperative days 1 (P=0.006) and 2 (P<0.001) in the left-sided frontal alpha asymmetry group. In the multivariate logistic regression analysis, preoperative left-sided frontal alpha asymmetry was associated with a 3.3-fold increased risk of the lowest tertile for the postoperative day 1 QoR-15 score (95% CI: 1.31-8.24; P=0.011)., Conclusions: Preoperative left-sided frontal alpha asymmetry was independently associated with a lower postoperative QoR-15 score in female patients undergoing thyroidectomy, highlighting the potential role of preoperative frontal electroencephalography in predicting patient-centred outcomes after surgery., Clinical Trial Registration: KCT0006586 (http://cris.nih.go.kr/)., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: To present the long-term clinical outcomes of laparoscopic gastric greater curvature plication (LGGCP) in terms of weight loss and revision surgery rate., Material and Methods: This single-center study involved a retrospective analysis of patients that underwent revision surgery after LGGCP due to weight regain. Demographic and anthropometric data, comorbidities, operation time, hospital stays, mortalities, and immediate and long-term postoperative complications were analyzed. Postoperative Body Mass Index (BMI), %total weight loss (TWL), and complications were collected during follow-up., Results: Of the 75 patients that underwent LGGCP at our hospital from March 2013 to February 2016, 13 (13/75, 17.3%) underwent revision surgery. All patients except one opted for sleeve gastrectomy. The mean interval between LGGCP and revision surgery was 71.0 ± 12.0 months (range, 54.8-93.6), and mean body weight, BMI, and TWL at revision were 89.2 ± 11.3 kg, 33.9 ± 4.2 kg/m 2 , and 4.7 ± 9.3%, respectively. The main reason for revision was weight regain. Additional problems were chronic intermittent GERD (4/13, 30.8%), dyspepsia (4/13,30.8%), and chronic relapsing melena (1/13, 7.7%). Two patients experienced immediate postoperative complications (Clavien-Dindo II and III). At one year after revision surgery, the mean body weight, BMI, and additional %TWL from revision surgery were 63.0 ± 5.3 kg, 24.0 ± 2.9 kg/m 2 , and 28.7 ± 8.0%, respectively. One of four patients (1/4, 25%) that complained of GERD before revision surgery, was still on PPI medication at 1 year after revision surgery., Conclusion: Although LGGCP showed initial acceptable weight loss outcomes, long term (>5 years) follow-up showed that LGGCP is associated with a high rate of revision surgery (17.3%) due to weight regain., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to evaluate associations between abdominal fat distribution (AFD) parameters and incisional hernia (IH) in patients who underwent transumbilical single-port laparoscopic surgery (SPLS) for gynecological disease., Methods: Medical records of 2116 patients who underwent SPLS for gynecological disease at Daejeon St. Mary's Hospital between March 2014 and February 2021 were reviewed. Among 21 (1.0%) patients who developed IH requiring surgical treatment after SPLS, 18 had preoperative abdominopelvic computed tomography (CT) images. As a control group, we randomly selected 72 patients who did not develop IH and who had undergone preoperative abdominopelvic CT scan, matched to test patients by type of surgery. Total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), visceral-to-subcutaneous fat ratio (VSR), and waist circumference (WC) were measured at the level of the third lumbar vertebral body on the preoperative abdominopelvic CT images, using National Institutes of Health (NIH) ImageJ version 1.53 k., Results: Receiver operating curve analysis showed that VFA has the highest predictive value for IH among AFD parameters (AUC = 0.749, 95% CI 0.630-0.869, p < 0.001). Univariate analysis showed that age, BMI, hypertension, dyslipidemia, TFA, VFA, VSR and WC were significant factors for IH. In multivariate analysis, only high VFA was identified as an independent risk factor for IH (HR 6.18, 95% CI 1.13-33.87, p = 0.04), whereas BMI, TFA, SFA, VSR, and WC failed to show statistical significance., Conclusion: We could find high VFA as an independent risk factor of IH in patients who underwent SPLS for gynecologic disease., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Objective: Biomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS., Methods: We reviewed the medical records of 76 GBS patients with C3 and C4 measurements during hospitalization between 2010 and 2021. Clinical outcomes were correlated with baseline serum C3, C4, and seven additional predictors: four existing biomarkers (GM1, albumin, immunoglobulin G, neutrophil-lymphocyte ratio) and three clinical factors from the modified Erasmus GBS outcome score model. Five complement activation products (C3a, C4a, C5a, soluble C5b-9, factor Bb) were measured in 35 patients and were compared with C3 and C4 levels. Longitudinal changes in C3 and C4 levels were compared with the disease course in 12 patients., Results: Higher C3, but not C4, was associated with poorer outcomes: lower Medical Research Council sum scores (MRCSS), higher GBS disability score (GBSDS), longer hospitalization, and more frequent treatment-related fluctuations. Age, MRCSS at admission, and baseline serum C3 were significant independent indicators of 1- and 3-month GBSDS. We found that C3 was positively correlated with C3a (r = 0.32) and C5a (r = 0.37), which indicates an activated complement cascade with high C3. Longitudinal change of C3 coincided with clinical severity of the disease course., Interpretation: This study highlights the use of serum C3 as a novel mechanistic biomarker in GBS. Larger prospective studies are needed to validate our findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background: Data regarding long-term cardiac and cerebrovascular adverse events in patients with hypertrophic cardiomyopathy (HCM) and apical aneurysm (AAn) are scarce and specific treatment strategies that include the use of anticoagulants have not yet been established. We aimed to evaluate the prevalence and long-term prognostic implication based on characteristics of AAn in patients with HCM., Methods: A total of 458 consecutive patients diagnosed with HCM underwent cardiovascular magnetic resonance imaging and echocardiography from August 1, 2008 to December 31, 2015. AAn was classified into Grade 1 and Grade 2 based on size and morphology. The patients were followed up for a median duration of 6.3 years (range, 4.2-8.7 years) for major adverse cardiac and cerebral events (MACCEs); a composite of cardiac death, HCM-related hospitalization, cerebrovascular accident (CVA), heart transplantation, myocardial infarction, and implantable cardiac defibrillator/cardiac resynchronization therapy., Results: AAn was detected in 9.2%. MACCEs developed more frequently in patients with AAn than in those without AAn (30.1% vs. 20.7%, P = 0.015), with the rate of CVA as the main difference (9.7% vs. 5.3%, P = 0.011). Grade 2 AAn group showed significantly higher MACCE than Grade 1 AAn group (41.8% vs. 21.9%, P < 0.001). In multivariate analysis, the presence of AAn was independently associated with increased risk of MACCEs (adjusted hazard ratio: 1.95; 95% confidence interval, CI: 1.16-3.28; P = 0.012)., Conclusions: AAn is independently associated with increased risk of HCM-related adverse events, especially cerebral infarction, with significant relationship between aneurysm size and adverse events., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to the submitted work., (Copyright © 2022. Published by Elsevier B.V.)

Radioactive elements released into the environment by accidental discharge constitute serious health hazards to humans and other organisms. In this study, three gasified biochars prepared from feedstock mixtures of wood, chicken manure, and food waste, and a KOH-activated biochar (40% food waste + 60% wood biochar (WFWK)) were used to remove cesium (Cs + ) and strontium (Sr 2+ ) ions from water. The physicochemical properties of the biochars before and after adsorbing Cs + and Sr 2+ were determined using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, extended X-Ray absorption fine structure (EXAFS) spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). The WFWK exhibited the highest adsorption capacity for Cs + (62.7 mg/g) and Sr 2+ (43.0 mg/g) among the biochars tested herein. The removal of radioactive 137 Cs and 90 Sr exceeded 80% and 47%, respectively, in the presence of competing ions like Na + and Ca 2+ . The functional groups present in biochar, including -OH, -NH 2 , and -COOH, facilitated the adsorption of Cs + and Sr 2+ . The Cs K-edge EXAFS spectra revealed that a single coordination shell was assigned to the Cs-O bonding at 3.11 Å, corresponding to an outer-sphere complex formed between Cs and the biochar. The designer biochar WFWK may be used as an effective adsorbent to treat radioactive 137 Cs- and 90 Sr-contaminated water generated during the operation of nuclear power plants and/or unintentional release, owing to the enrichment effect of the functional groups in biochar via alkaline activation., 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 © 2022. Published by Elsevier Inc.)

Objectives: We investigated the association between metabolic syndrome (MetS) and mortality among coronavirus disease 2019 (COVID-19) patients in Korea., Methods: We analyzed 3876 individuals aged ≥ 20 years who were confirmed with COVID-19 from January 1 to June 4, 2020 based on the Korea National Health Insurance Service (NHIS)-COVID-19 database and had undergone health examination by NHIS between 2015 and 2017. Multivariable Cox proportional hazard regression analyses were performed., Results: Of total participants, the prevalence of MetS was 21.0% (n = 815). During 58.6 days of mean follow-up, 3.1 % (n = 120) of the participants died. Compared to individuals without MetS, COVID-19 patients with MetS had a significantly increased mortality risk after adjusting for confounders in total participants (hazard ratio [HR]: 1.68, 95 % confidence interval [CI]: 1.14-2.47) and women (HR: 2.41, 95 % CI: 1.17-4.96). A low high-density lipoprotein cholesterol level in total participants (HR: 1.63, 95 % CI: 1.12-2.37) and hyperglycemia in women (HR: 1.97, 95 % CI: 1.01-3.84) was associated with higher mortality risk. The mortality risk increased as the number of MetS components increased among total participants and women (P for trend = 0.009 and 0.016, respectively). In addition, MetS groups had higher mortality risk in aged ≥ 60 years (HR: 1.60, 95 % CI: 1.07-2.39), and never-smokers (2.08, 1.21-3.59)., Conclusions: The presence of MetS and greater number of its components were associated with increased mortality risks particularly in female patients with COVID-19. Managing MetS may contribute to better outcomes of COVID-19., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Foot-and-mouth disease (FMD) is an acute contagious disease of cloven-hoofed animals such as cows, pigs, sheep, and deer. The current emergency FMD vaccines, to induce early protection, have limited use, as their protective effect in pigs does not begin until 7 days after vaccination. Therefore, the use of antiviral agents would be required for reducing the spread of foot-and-mouth disease virus (FMDV) during outbreaks. Vesatolimod (GS-9620), a toll-like receptor 7 agonist, is an antiviral agent against various human disease-causing viruses. However, its antiviral effect against FMDV has not been reported yet. The aim of this study was to investigate the antiviral effects of GS-9620 against FMDV both in vitro and in vivo. The inhibitory effect of GS-9620 on FMDV in swine cells involved the induction of porcine interferon (IFN)-α and upregulation of interferon-simulated genes. Protective effect in mice injected with GS-9620 against FMDV was maintained for 5 days after injection, and cytokines such as IFN-γ, interleukin (IL)-12, IL-6, and IFN-γ inducible protein-10 could be detected following the treatment with GS-9620. Furthermore, the combination of GS-9620 with an FMD-inactivated vaccine was found to be highly effective for early protection in mice. Overall, we suggest GS-9620 as a novel and effective antiviral agent for controlling FMDV infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although several vaccines and antiviral drugs against SARS-CoV-2 are currently available, control and prevention of COVID-19 through these interventions is limited due to inaccessibility and economic issues in some regions and countries. Moreover, incomplete viral clearance by ineffective therapeutics may lead to rapid genetic evolution, resulting in the emergence of new SARS-CoV-2 variants that may escape the host immune system as well as currently available COVID-19 vaccines. Here, we report that phytochemicals extracted from Chlorella spp. and Psidium guajava possess broad-spectrum antiviral activity against a range of SARS-CoV-2 variants. Through chromatography-based screening, we identified four bioactive compounds and subsequently demonstrated their potential antiviral activities in vivo. Interestingly, in hACE2 mice, treatment with these compounds significantly attenuates SARS-CoV-2-induced proinflammatory responses, demonstrating their potential anti-inflammatory activity. Collectively, our study suggests that phytochemicals from edible plants may be readily available therapeutics and prophylactics against multiple SARS-CoV-2 strains and variants., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Research Question: What are the awareness, intentions and attitudes of female medical staff towards planned oocyte cryopreservation?, Design: A cross-sectional survey was conducted during June 2019 among 171 female medical staff at a single tertiary hospital. The self-administered questionnaire consisted of 39 questions., Results: A total of 151 responses (88%) were received from 13 doctors and 138 nurses. The mean age of the respondents was 26.4 years. Fewer than half of the women (47.7%) answered correctly on the age at which female fertility markedly declines. The study demonstrated that 28.5% of respondents considered themselves as 'potential freezers' while 30.5% would not consider the procedure. Potential freezers (58.1% versus 21.7%, P < 0.001) and older age participants (44.2% versus 28.4, P = 0.014) were more interested in consulting about fertility preservation during an obstetrician/gynaecologist (OB/GYN) visit. If respondents were to consider oocyte cryopreservation, they thought that lack of information would be a major obstacle to accepting the procedure (57.6%). Of the respondents, 85.3% believed that oocyte cryopreservation is a woman's right. A strong majority of respondents (96.0%) agreed or were neutral on the statement that all women have the right to receive education on fertility preservation during OB/GYN visits, but none had ever received medical education about fertility preservation, reflecting lack of access to fertility preservation care., Conclusions: This study indicated that there was widespread awareness about planned oocyte cryopreservation among female medical staff. The majority of participants considered planned oocyte cryopreservation as a woman's right. There appears to be a critical need for proper education about fertility preservation., (Copyright © 2022 Reproductive Healthcare Ltd. All rights reserved.)

Scaffolds functionalized with biomolecules have been developed for bone regeneration but inducing the regeneration of complex structured bone with neovessels remains a challenge. For this study, we developed three-dimensional printed scaffolds with bioactive surfaces coated with minerals and platelet-derived growth factor. The minerals were homogeneously deposited on the surface of the scaffold using 0.01 M NaHCO 3 with epigallocatechin gallate in simulated body fluid solution (M2). The M2 scaffold demonstrated enhanced mineral coating amount per scaffold with a greater compressive modulus than the others which used different concentration of NaHCO 3 . Then, we immobilized PDGF on the mineralized scaffold (M2/P), which enhanced the osteogenic differentiation of human adipose derived stem cells in vitro and promoted the secretion of pro-angiogenic factors. Cells cultured in M2/P showed remarkable ratio of osteocalcin- and osteopontin-positive nuclei, and M2/P-derived medium induced endothelial cells to form tubule structures. Finally, the implanted M2/P scaffolds onto mouse calvarial defects had regenerated bone in 80.8 ± 9.8% of the defect area with the arterioles were formed, after 8 weeks. In summary, our scaffold, which composed of minerals and pro-angiogenic growth factor, could be used therapeutically to improve the regeneration of bone with a highly vascularized structure. STATEMENT OF SIGNIFICANCE: Surface engineered scaffolds have been developed for bone regeneration but inducing the volumetric regeneration of bone with neovessels remains a challenge. In here, we developed 3D printed scaffolds with bioactive surfaces coated with bio-minerals and platelet-derived growth factors. We proved that the 0.01 M NaHCO 3 with polyphenol in simulated body fluid solution enhanced the deposition of bio-minerals and even distribution on the surface of scaffold. The in vitro studies demonstrated that the attached cells on the bioactive surface showed the enhanced osteogenic differentiation and secretion of pro-angiogenic factors. Finally, the scaffold with bioactive surface not only improved the regenerated volume of bone tissues but also increased neovessel formation after in vivo implantation onto mouse calvarial defect., 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 © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Both human and mouse allergic contact dermatitis (ACD) frequently demonstrates a combined type 1 and type 2 immune response. However, the relative importance of type 2 immunity in this setting has been incompletely understood yet., Objective: To explore an effector function of type 2 immunity in ACD with mixed type 1/type 2 immune response., Methods: Gene expression characteristics of contact hypersensitivity (CHS) model was examined by quantitative polymerase chain reaction. Cytokine profile of T cells was analyzed by flow cytometry. The involvement of type 2 immunity was assessed by antibody-mediated cytokine neutralization and cell depletion. The role of specific subset of cutaneous dendritic cells was evaluated using diphtheria toxin-induced cell-depleting mouse strains., Results: Oxazolone-induced CHS revealed a combination of type 1/type 2 gene expression. The severity of oxazolone-induced CHS was ameliorated by neutralization of IL-4 but not of IFN-γ, indicating that type 2 immunity plays a dominant effector function in this mixed type 1/type 2 model. Mechanistically, type 2 effector immunity was mounted by CD301b+Langeirn- dermal dendritic cells in part through thymic stromal lymphopoietin-interleukin 7 receptor alpha signaling-dependent manner., Conclusion: Our findings suggest the clinical rationale for targeting type 2 immunity as a relevant therapeutic strategy for the mixed immune phenotype of ACD., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Prevalence rates of opioid use disorder (OUD) have increased dramatically, accompanied by a surge of overdose deaths. While opioid dependence has been extensively studied in preclinical models, an understanding of the biological alterations that occur in the brains of people who chronically use opioids and who are diagnosed with OUD remains limited. To address this limitation, RNA sequencing was conducted on the dorsolateral prefrontal cortex and nucleus accumbens, regions heavily implicated in OUD, from postmortem brains in subjects with OUD., Methods: We performed RNA sequencing on the dorsolateral prefrontal cortex and nucleus accumbens from unaffected comparison subjects (n = 20) and subjects diagnosed with OUD (n = 20). Our transcriptomic analyses identified differentially expressed transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric orderlap. Weighted gene coexpression analyses identified OUD-specific modules and gene networks. Integrative analyses between differentially expressed transcripts and genome-wide association study datasets using linkage disequilibrium scores assessed the genetic liability of psychiatric-related phenotypes in OUD., Results: Rank-rank hypergeometric overlap analyses revealed extensive overlap in transcripts between the dorsolateral prefrontal cortex and nucleus accumbens in OUD, related to synaptic remodeling and neuroinflammation. Identified transcripts were enriched for factors that control proinflammatory cytokine, chondroitin sulfate, and extracellular matrix signaling. Cell-type deconvolution implicated a role for microglia as a potential driver for opioid-induced neuroplasticity. Linkage disequilibrium score analysis suggested genetic liabilities for risky behavior, attention-deficit/hyperactivity disorder, and depression in subjects with OUD., Conclusions: Overall, our findings suggest connections between the brain's immune system and opioid dependence in the human brain., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background/objective: Open thyroidectomy has been the standard approach for patients undergoing thyroidectomy. However, this approach leads to prominent scars, hypesthesia, paresthesia, and uncomfortable sensations. We aimed to describe our modified technique of minimally invasive open thyroidectomy (MIT) and to compare the results with those of conventional thyroidectomy., Methods: This study included 880 patients who underwent surgery between January 2016 and December 2016. Modified MIT was performed in 249 patients (28.3%), and conventional thyroidectomy was performed in the remaining 631 patients., Results: Lobectomy was performed in the majority of cases (MIT 204 [81.9%] vs. conventional 429 [67.9%]). There were no significant differences in complications between the two approaches (6 [2.4%] vs. 8 [1.3%]). Patients who underwent surgery using the minimally invasive approach had a shorter operative time (77.99 ± 34.5 vs. 91.23 ± 36.58 min) and were discharged earlier (2.4 ± 0.8 vs. 3.2 ± 0.8) than those who underwent conventional thyroidectomy., Conclusion: Modified MIT is a safe alternative to standard open thyroidectomy and allows the performance of bilateral total thyroidectomy with proper central compartment neck dissection., Level of Evidence: 2b., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

The 3T3-L1 murine pre-adipocyte line is an established cell culture model for screening Metabolism Disrupting Chemicals (MDCs). Despite a need to accurately identify MDCs for further evaluation, relatively little research has been performed to comprehensively evaluate reproducibility across laboratories, assess factors that might contribute to varying degrees of differentiation between laboratories (media additives, plastics, cell source, etc.), or to standardize protocols. As such, the goals of this study were to assess interlaboratory variability of efficacy and potency outcomes for triglyceride accumulation and pre-adipocyte proliferation using the mouse 3T3-L1 pre-adipocyte cell assay to test chemicals. Ten laboratories from five different countries participated. Each laboratory evaluated one reference chemical (rosiglitazone) and three blinded test chemicals (tributyltin chloride, pyraclostrobin, and bisphenol A) using: 1) their Laboratory-specific 3T3-L1 Cells (LC) and their Laboratory-specific differentiation Protocol (LP), 2) Shared 3T3-L1 Cells (SC) with LP, 3) LC with a Shared differentiation Protocol (SP), and 4) SC with SP. Blinded test chemical responses were analyzed by the coordinating laboratory. The magnitude and range of bioactivities reported varied considerably across laboratories and test conditions, though the presence or absence of activity for each tested chemical was more consistent. Triglyceride accumulation activity determinations for rosiglitazone ranged from 90 to 100% across test conditions, but 30-70 % for pre-adipocyte proliferation; this was 40-80 % for triglyceride accumulation induced by pyraclostrobin, 80-100 % for tributyltin, and 80-100 % for bisphenol A. Consistency was much lower for pre-adipocyte proliferation, with 30-70 % active determinations for pyraclostrobin, 30-50 % for tributyltin, and 20-40 % for bisphenol A. Greater consistency was observed for the SC/SP assessment. As such, working to develop a standardized adipogenic differentiation protocol represents the best strategy for improving consistency of adipogenic responses using the 3T3-L1 model to reproducibly identify MDCs and increase confidence in reported outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI)., Background: The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR., Methods: The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n = 31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n = 309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up., Results: In the diagnostic cohort, angio-IMR correlated well with IMR (R = 0.778; P < 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR ≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95% CI: 1.670-5.067; P < 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95% CI: 1.157-4.079; P = 0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index = 0.726 vs 0.666 [P < 0.001], net reclassification index = 0.704 [P < 0.001])., Conclusions: Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377)., Competing Interests: Funding Support and Author Disclosures This work was supported by Rainmed (which provided the software and console for angio-FFR and angio-IMR). The company had no role in study design or conduct, data analysis, or manuscript preparation. Dr J.M. Lee has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Hahn has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The development of a lignin peroxidase (LiP) that is thermostable even under acidic pH conditions is a main issue for efficient enzymatic lignin degradation due to reduced repolymerization of free phenolic products at acidic pH (< 3). Native LiP under mild conditions (half-life (t 1/2 ) of 8.2 days at pH 6) exhibits a marked decline in thermostability under acidic conditions (t 1/2 of only 14 min at pH 2.5). Thus, improving the thermostability of LiP in acidic environments is required for effective lignin depolymerization in practical applications. Here, we show the improved thermostability of a synthetic LiPH8 variant (S49C/A67C/H239E, PDB: 6ISS) capable of strengthening the helix-loop interactions under acidic conditions. This variant retained excellent thermostability at pH 2.5 with a 10-fold increase in t 1/2 (2.52 h at 25 °C) compared with that of the native enzyme. X-ray crystallography analysis showed that the recombinant LiPH8 variant is the only unique lignin peroxidase containing five disulfide bridges, and the helix-loop interactions of the synthetic disulfide bridge and ionic salt bridge in its structure are responsible for stabilizing the Ca 2+ -binding region and heme environment, resulting in an increase in overall structural resistance against acidic conditions. Our work will allow the design of biocatalysts for ligninolytic enzyme engineering and for efficient biocatalytic degradation of plant biomass in lignocellulose biorefineries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anti-cancer strategies using nanocarrier systems have been explored in a variety of cancers; these systems can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect leading to enhanced anti-tumor activity while reducing systemic toxicity by specific tumor-targeting. The prognosis of hepatocellular carcinoma (HCC) is extremely poor when the condition is diagnosed at the unresectable stage as treatment options are limited. In order to improve the treatment of cancer and the overall anti-cancer effect, polymerized phenylboronic acid conjugated doxorubicin (pPBA-Dox) nanocomplexes were generated, and conjugated doxorubicin, which is conventionally used in HCC. The nanocomplexes exhibited enhanced anti-tumor activity via tumor-specific targeting in the subcutaneous and orthotopic HCC syngeneic mice tumor model, implying that the nanocomplexes facilitate the targeted Dox delivery to liver cancer in which the sialic acid is over-expressed. Therefore, this study provides insight into the novel targeted therapy using the nanocomplexes for the treatment of HCC., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Neuromuscular disease is well known to be at increased risk of complications following hip replacement surgeries. This study is prospectively conducted to investigate clinical performance and survivorship of total hip arthroplasty (THA) using dual mobility articulation in femoral neck fractures of elderly with neuromuscular disease., Materials and Methods: We prospectively enrolled 162 patients (162 hips) with displaced femoral neck fracture who gave informed consent for dual mobility articulation THA. Of the 162 patients, 35 patients had neuromuscular disease including cerebral palsy, poliomyelitis, hemiplegia, and Parkinson disease (NM group). The other 127 patients had no history of neuromuscular disease (non-NM group). The mean age was 76.5 years (range, 60 - 95) and female ratio was 71.0% (115/162). Clinical outcomes including Harris hip score (HHS), University of California Los Angles activity (UCLA) score were compared between the two groups. Computed tomography and serial radiographs were obtained after surgery. Postoperative complications and reoperation including revision were recorded., Results: Pain-VAS and all clinical scores of the NM group were comparable to those of the non-NM group. The incidence of dislocation in the NM group did not differ from that in Non-NM group (2/35, 5.7% versus 5/127, 3.9%, p = 0.645). Reoperation was performed in 3 hips (3/35, 8.6%) of the NM group and in 4 hips (4/127, 3.1%) of the non-NM group (p = 0.173). Kaplan-Meier survivorship with an end point of revision for any reason was 97.1% (95% confidence interval [CI], 0.92 to 1.03) in the NM group and 98.4% (95% CI, 0.96 to 1.01) in the non-NM group at 7.3 years after surgery., Conclusions: In elderly with neuromuscular disease, THA with dual mobility articulation is a reasonable option as a treatment for femoral neck fractures., 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 © 2021. Published by Elsevier Ltd.)

Objective: To evaluate whether the degree of cervical length change was associated with successful cervical dilatation during labor induction., Materials and Methods: We conducted a secondary analysis of a prospective observational study of term singleton pregnant women who underwent labor inductions. Cases of Cesarean section due to fetal distress or maternal request during the first stage of labor were excluded. The enrolled women were categorized into two groups according to achievement of full cervical dilatation. The cervical length near induction and cervical length shortening over the last four weeks of pregnancy were compared between the two groups. A receiver operating characteristics (ROC) analysis was performed to evaluate the screening performance for failed cervical dilatation during labor induction., Results: A total of 165 women were enrolled for the final analysis; of these, 145 (87.9%) women reached the second stage of labor and 20 (12.1%) women failed to achieve full cervical dilatation. Women who failed to achieve full cervical dilatation had a significantly longer cervical length near induction and less cervical length change over previous four weeks compared with women who achieved full cervical dilatation (P = 0.018 and 0.005, respectively). Multivariate analysis showed that cervical length >29 mm (odds ratios [OR], 4.15; 95% confidence interval [CI], 1.290-13.374, P = 0.017) and cervical length shortening ≦ 6 mm (OR, 5.87; 95% CI, 1.552-22.271, P = 0.009) were significantly associated with failed cervical dilatation after adjusting for birthweight and previous history of vaginal delivery. Cervical length shortening alone provided a better prediction of failed cervical dilatation than the combination of cervical length and shortening (sensitivity, 76.9%; specificity, 63.8%)., Conclusion: The probability of failed cervical dilatation during labor induction was significantly increased in cases when the cervical length was greater than 29 mm near induction or when the cervical length shortening was less than 6 mm over the last four weeks., Competing Interests: Declaration of competing interest The researcher claims no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

A freestanding lipid bilayer or black lipid membrane is a powerful tool for studying ion channels and for biophysical studies of other membrane proteins under controlled chemical and physical conditions. Even though the lipid bilayer has been considered an excellent sensing platform to detect diverse single molecules from nucleotides to cells, it is not yet widely used, mainly due to its low stability and the expertise needed for membrane formation. To ameliorate the issues of conventional membrane formation techniques, we report a novel layered film that consists of a nonporous layer sandwiched between two porous layers to facilitate bilayer formation. Moreover, the absorption of excess solvent present in the membrane precursor solution can be achieved by the film, enabling control over the membrane formation process. Through this layered design, we could obtain an ideal film that has a reduced and controlled membrane formation time (<30 min) and a sufficient bilayer lifetime (3 h) for ion channel studies and biosensing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The effects of commercial vegetable oils and duck skin on quality characteristics of a reduced-fat duck meat emulsion were examined. The cooking loss, emulsion stability, and hardness were lower for emulsions preemulsified with vegetable oils and duck skin (P < 0.05) than for the control. Storage modulus (G') and loss modulus (G″) of reduced-fat duck meat emulsions treated with corn, grape seed, soy, and olive oils were similar to the values of control; the highest G' and G″ values were reported for the reduced-fat duck meat emulsion treated with coconut oil. Myofibril protein solubility was the highest for the reduced-fat duck meat emulsion treated with coconut oil and duck skin (P < 0.05). Replacing of pork back fat with different vegetable oils for emulsification may impart superior quality to reduced-fat duck meat emulsion. We recommend preemulsion with vegetable oils and duck skin to enhance the quality characteristics of reduced-fat duck meat emulsion., (Copyright © 2020. Published by Elsevier Inc.)

This study aimed to evaluate the relationship between postoperative condylar displacement (PCD) after sagittal split ramus osteotomy (SSRO) and the glenoid fossa depth. A total of 29 patients who underwent computed tomography (CT) before surgery (T0), immediately after (T1), and 6 months after (T2) surgery were studied. The fossa depth was measured, and the amount of displaced condylar center and axis were evaluated on CT at T0, T1, and T2 using three-dimensional analysis software. PCD and the fossa depth relationship was investigated by Pearson's correlation analysis. The fossa depth varied from 3.9 mm to 12.0 mm, and the mean value was 8.15 ± 1.60 mm. The condylar center was displaced by 1.12 ± 0.66 mm at T1 compared with it at T0. The amount of displaced condylar center negatively correlated with the fossa depth (r = -0.424, p = 0.001). The displacement of the condylar center between T0 and T2 was 0.85 ± 0.51 mm. The amount of condylar center displacement between T0 and T1 showed a positive correlation with it between T0 and T2 (r = 0.481, p < 0.001). In conclusion, more attention is needed in patients with small fossa depth during condylar repositioning after SSRO and postoperative management to minimize complications., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: We aimed to determine whether there are any differences in all-cause and cause-specific mortality with cardiovascular disease (CVD) risk between health screening attenders and non-attenders among young adults., Study Design: We performed a retrospective cohort study using claim data from the Korean National Health Insurance Service database., Methods: Individuals aged 20-39 years who had received health screening at least once between 2002 and 2005 were classified as attenders, and the others were classified as non-attenders. After propensity score matching according to attendance of health screening, 2,060,409 attenders and 2,060,409 non-attenders were included. We estimated adjusted hazard ratios (HRs) and 95% confidence interval (CI) for all-cause mortality, cause-specific mortality, and hospitalization of CVD from 2006 to 2015., Results: Survival from all-cause mortality was greater among attenders than among non-attenders (log rank P < 0.001). Similarly, death from CVD (log rank P = 0.007) and CVD events (log rank P < 0.001) were less likely among attenders. The risk for all-cause mortality in attenders was significantly lower than that in non-attenders (HR = 0.83, 95% CI = 0.81 to 0.84). The risk for CVD mortality (HR = 0.80, 95% CI = 0.73 to 0.87) and hospitalization of CVD (HR = 0.92, 95% CI = 0.91 to 0.94) were lower in attenders. In stratified analyses, the risk for all-cause and cause-specific mortalities was lower among attenders regardless of insurance type., Conclusions: Among young adults, the risk for all-cause mortality, CVD mortality, and hospitalization of CVD were lower for those who underwent health screenings. Future studies that evaluate the cost-effectiveness of health screening with additional consideration of psychosocial aspects are needed., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS)., Background: Myocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS., Methods: Patients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation., Results: Patients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e' <7 cm/s) and increased LV filling pressure (E/e' ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e' and higher E/septal e' ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function., Conclusions: Diffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis., Competing Interests: Author Disclosures This work was supported by a National Research Foundation grant funded by the government of Korea (Ministry of Science and ICT; 2019R1A2C2084099) and a fund from ChongKunDang Pharmaceutical (0620121110). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Thyroxine (T4) contains four iodine atoms and is a major thyroid hormone synthesized in the thyroid gland. Abnormal levels of T4 in the body cause various endocrine diseases. The present study describes the fabrication of an electrochemical biosensor composed of a multi-functional DNA structure/rhodium nanoplates heterolayer for precise detection of T4 concentration. A DNA 3-way junction (3WJ) structure was designed as a multi-functional bioprobe to perform several functions (including target detection, electrochemical signal reporting, and immobilization) simultaneously. Binding between T4 and the T4 DNA aptamer was confirmed through enzyme-linked aptamer assays (ELAAs) and filtration experiments. The multi-functional DNA was immobilized on porous rhodium nanoplates (pRhNPs)-heterolayer modified Au micro-gap electrode. The pRhNPs provided an increment in the surface area and amplification of the electrochemical signal. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to detect T4. Under optimal conditions, the limit of detection of T4 was found to be 10.33 pM. Furthermore, up to 11.41 pM of T4 could be detected in clinical samples. This study demonstrates the possibility of label-free detection of the T4 with multi-functional DNA/pRhNPs heterolayer that can be applied to small molecule detection platform in the near future., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus., Methods: To demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection., Results: SARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16-2.09 ± 0.85 log 10 copies/mL, saliva 1.07 ± 0.34-1.65 ± 0.46 log 10 copies/mL, stool 1.17 ± 0.32 log 10 copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12-1.34 ± 0.30 log 10 copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool., Discussion: Viable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11-15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver of normal fed zebrafish larvae. High glucose (HG, 25 mM)-induced lipid accumulation was suppressed by l-glutamine-d-fructose 6-phosphate amidotransferase inhibitors. ER stress inhibitors did not suppress HG or GlcN-mediated lipid accumulation. HG and GlcN stimulated protein expression, DNA binding and O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP). Furthermore, both HG and GlcN increased nuclear sterol regulatory element-binding protein-1 (SREBP-1) levels in HepG2 cells. In contrast to its stimulatory effect under NG, GlcN suppressed lipid accumulation in HepG2 cells under HG conditions. Similarly, GlcN suppressed lipid accumulation in livers of overfed zebrafish. In addition, GlcN activity on DNA binding and O-GlcNAcylation of ChREBP was stimulatory under NG and inhibitory under HG conditions. Moreover, GlcN enhanced ChREBP, SREBP-1c, ACC, FAS, L-PK and SCD-1 mRNA expression under NG but inhibited HG-induced upregulation in HepG2 cells. The O-GlcNAc transferase inhibitor, alloxan, reduced lipid accumulation by HG or GlcN while the O-GlcNAcase inhibitor, PUGNAc, enhanced lipid accumulation in HepG2 cells and liver of zebrafish larvae. GlcN-induced lipid accumulation was inhibited by the AMPK activator, AICAR. Phosphorylation of AMPK (p-AMPK) was suppressed by GlcN under NG while increased by GlcN under HG. PUGNAc downregulated p-AMPK while alloxan restored GlcN- or HG-induced p-AMPK inhibition. Our results collectively suggest that GlcN regulates lipogenesis by sensing the glucose or energy states of normal and excess fuel through AMPK modulation., 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 © 2020 Elsevier B.V. All rights reserved.)

Foot-and-mouth disease (FMD) is an economically devastating animal disease. There are seven serotypes, A, O, C, Asia 1, Southern African Territories 1, 2, and 3 (SAT1, SAT2, and SAT3), among which serotype O shows the greatest distribution worldwide. Specifically, the O/ME-SA/Ind-2001 lineage, which was reported in India in 2001, has since emerged worldwide, with the O/ME-SA/Ind-2001d and O/ME-SA/Ind-2001e sublineages recently emerging in North Africa, Middle East Asia, Southeast Asia, and East Asia. The antigenic relationship (r1) value for the O1 Manisa and O/Mya-98 lineage inactivated vaccine against various O/ME-SA/Ind-2001 lineages of FMDV isolates, were matching (r1 > 0.3) or non-matching (r1 < 0.3), indicating that the vaccine based on the O/ME-SA/Ind-2001 lineage FMDV, is valuable. In this study, we developed a new vaccine strain, O/SKR/Boeun/2017 isolate, belonging to the O/ME-SA/Ind-2001e sublineage as an outbreak of this sublineage occurred in 2017 in the Boeun county of the Republic of Korea (O/SKR/Boeun/2017). This experimental vaccine exhibited high immunogenicity in pigs and cattle and was antigenically matched with representative FMDV lineages (ME-SA, O/ME-SA/PanAsia, O/SEA/Mya-98, and O/Cathay) in Asia, as demonstrated by two-dimensional virus neutralization tests (2D-VNT). In addition, a 100% survival rate in C56BL/6 mice vaccinated with 1/15 of a pig dose was observed following challenge with FMDV O/VIT/2013 (O/ME-SA/PanAsia) at 10 days post-vaccination. Further, we analyzed the major antigenic sites of the O/SKR/Boeun/2017 vaccine strain as well as other viruses, by 2D-VNT. These results suggest that the O/ME-SA/Ind-2001e sublineage is a promising vaccine strain candidate in Asia, and other countries, for protection against the emerging FMDV., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/purpose: There has not been an international multicentric study to examine the relationship between thyroid cancer clinical outcomes and geographic location for South Korea, Colombia, and Turkey, whereas thyroid cancer is amongst the highest three cancer types seen in South Korea and Turkey. The aim of the study was to assess regional differences of T1 papillary thyroid cancer outcomes in Korea, Turkey and Colombia., Methods: This is an observational non-randomized study. A total of 2720 patients who have been operated for T1 papillary thyroid cancer between 2011 and 2014 and are on routine follow-up have been recruited. The mean follow-up was 46.4 ± 10.7 months. Data were collected in a commonly used database and analyses were conducted., Results: Patients participated in South Korea (88.2%), Turkey (9.1%) and Colombia (2.6%). Eighty percent were female. Female dominance tended to be higher in Colombia (p = 0.01). Mean age at diagnosis was 45.2 years. There was no mortality. Recurrence tended to be higher in Colombia (p < 0.001). Moreover, statistical analysis revealed differences among patients regarding symptoms (p < 0.001), family history (p < 0.001), euthyroidism (p < 0.001), anti-Tg and/or anti-TPO positivity (p < 0.001), FNAB results (p < 0.001), type of resection (p < 0.001), prophylactic central node dissection (p < 0.001), tumor size (p < 0.001), multifocality (p < 0.001), bilaterality (p < 0.001), tumor subtype (p < 0.001) and radioactive iodine treatment (p < 0.01)., Conclusion: Thyroid cancer is becoming more commonly diagnosed worldwide. This international multicentric study has identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Background: The effect of antipsychotics adherence on the risk of cardiovascular disease (CVD) among schizophrenia patients has not been studied. While antipsychotic adherence is favorable for all-cause mortality, its association with CVD incidence is unclear due to the potential risk of CVD caused by antipsychotics., Methods: Using the Korean National Health Insurance Service Database, we constructed a case-cohort of 80,581 newly-diagnosed schizophrenia patients between 2004 and 2013 from a cohort of all Koreans 20-40 years old. Patients were divided into quartiles by adherence determined by their two-year medication possession ratio. Patients were followed from two years following the diagnosis of schizophrenia until Dec. 31st, 2017 for the primary outcome of incident CVD and secondary outcomes of stroke, myocardial infarction, and all-cause mortality. Cox proportional hazards analysis was performed adjusting for conventional risk factors., Outcomes: Newly diagnosed schizophrenia patients were followed for a median of 7.0 years resulting in 1396 incident CVD cases over 5.73 × 10 5 person-years. When adjusted for potential confounders, the best adherence quartile group had significantly lower risk of CVD (HR, 95%CI; 0.78, 0.66-0.92; p-trend, 0.003), stroke (HR, 95%CI; 0.79, 0.66-0.94; p-trend, 0.015), and all-cause mortality (HR, 95%CI; 0.86, 0.78-0.95; p-trend, 0.003) compared to the worst adherent quartile group. Subgroup analysis by antipsychotics generation, concurrent medication, and comorbidities did not significantly alter results., Interpretation: Among newly diagnosed schizophrenia patients, better adherence to antipsychotics lowered the risk CVD incidence despite previously suggested antipsychotic-associated CVD risk. Thus, efforts to improve antipsychotics adherence may improve CVD outcomes in schizophrenia patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biologically relevant synthetic hydroxyapatite (HA) has become a much-desired material for use within the medical field with an emphasis on orthopedic applications. However, there are very few sources of sub-micron scale HA powders that are economical. Many current procedures to generate synthetic HA, that is both biological and chemically analogous to naturally occurring HA, tend to involve complicated synthesis procedures that are difficult to simultaneously produce desired stoichiometric ratios and particle diameter. This paper reports the development of a one-step hydrothermal method with in situ ball milling of synthetic HA. That has the potential to be a biological substitute with similar calcium to phosphate stoichiometric ratio and particle diameter of HA found in many natural biologically occulting sources. Parameters affecting particle diameter investigated included varying ball milling media, in situ and ex situ ball milling, and simultaneous agitation. The stoichiometric ratios of the resulting powders indicated that 4-hour hydrothermal reaction time produced materials that are analogous to natural HA, confirmed from spectra acquired via Fourier Transform Infrared spectroscopy (FT-IR). X-ray diffraction and Scanning Electron Microscopy both indicate that the predominant size of primary crystallites is around ~25 nm. Particle size distributions of dried in situ ball-milled HA suggest that primary crystallites exist as aggregates, with aggregate diameters ranging between 1 and 100 μm., Competing Interests: Declaration of competing interest All authors involved with presented manuscript have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)