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Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process. Treg-specific deletion of Glut3 abrogates tumor immune tolerance, while steady-state immune homeostasis remains largely unaffected in mice. Furthermore, by employing mouse tumor models and human clinical data, we identified the NF-κB subunit c-Rel as one such factor that, through Glut3-dependent O-GlcNAcylation, functionally orchestrates gene expression in Tregs at tumor sites. Together, these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology, specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Recent advancements in digital phenotypic analysis have revolutionized the morphological analysis of crops, offering new insights into genetic trait expressions. This manuscript presents a novel 3D phenotyping pipeline utilizing the cutting-edge Neural Radiance Fields (NeRF) technology, aimed at overcoming the limitations of traditional 2D imaging methods. Our approach incorporates automated RGB image acquisition through unmanned greenhouse robots, coupled with NeRF technology for dense Point Cloud generation. This facilitates non-destructive, accurate measurements of crop parameters such as node length, leaf area, and fruit volume. Our results, derived from applying this methodology to tomato crops in greenhouse conditions, demonstrate a high correlation with traditional human growth surveys. The manuscript highlights the system's ability to achieve detailed morphological analysis from limited viewpoint of camera, proving its suitability and practicality for greenhouse environments. The results displayed an R-squared value of 0.973 and a Mean Absolute Percentage Error (MAPE) of 0.089 for inter-node length measurements, while segmented leaf point cloud and reconstructed meshes showed an R-squared value of 0.953 and a MAPE of 0.090 for leaf area measurements. Additionally, segmented tomato fruit analysis yielded an R-squared value of 0.96 and a MAPE of 0.135 for fruit volume measurements. These metrics underscore the precision and reliability of our 3D phenotyping pipeline, making it a highly promising tool for modern agriculture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TM declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2024 Choi, Park, Park and Lee.)

This concept analysis study identified attributes and defined psychiatric nursing competency among psychiatric nurses. The approach of Walker and Avant was used for concept analysis, and a literature review was completed including eight steps. The concept of psychiatric nursing competency was identified as five attributes: professional assessment, situation coping skills, communication, cooperation, and self-management. Antecedents of the concept were psychiatric nursing education and experience, and the consequences were patient outcomes, patient safety, and efficiency of care. Psychiatric nursing competency was defined as the comprehensive ability to care for psychiatric patients appropriately and effectively in the nursing situation. This study is meaningful in that it clarified psychiatric nursing competency among psychiatric nurses, and the attributes and empirical referents of this study will be the basis for development to a psychiatric nursing competency measurement tool., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Choi, Hwa Bok reports financial support was provided by THE KOREAN ACADEMY OF PSYCHIATRIC AND MENTAL HEALTH NURSING. 2 reviews in Archives of Psychiatric Nursing in December 2023 and June 2024 - Choi HB If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This case report describes a rare occurrence of pyogenic granuloma (PG) in the hard palate deviating from its typical gingival location that led to the formation of an alveolar cleft. The aggressive growth pattern of the lesion, with atypical progression from a pedunculated nodule to an alveolar cleft, raised concern. The diagnosis was based on magnetic resonance imaging and computed tomography findings, which revealed a tadpole-shaped lesion originating from the midline hard palate. The differential diagnosis included a minor salivary gland tumor. Surgical excision was performed under general anesthesia and resulted in a mucosal defect without nasolabial fistula formation or bone exposure. The palatal defect was packed with oxidized regenerated cellulose and closed with Vicryl Rapide sutures, both of which contributed to the patient's successful outcomes. Our comprehensive approach, extending across the stages of surgical planning, execution, and postoperative care, demonstrated the advantages of a multidisciplinary strategy for the accurate diagnosis and effective treatment of palatal PGs. This report makes a meaningful contribution to the existing literature on common oral lesions by emphasizing the importance of a broad differential diagnosis and a systematic approach to oral pathologies. It also raises clinical awareness of PGs with atypical presentations and the diagnostic challenge that they pose.

In this study, a novel exploration method for centralized training and decentralized execution (CTDE)-based multi-agent reinforcement learning (MARL) is introduced. The method uses the concept of strangeness, which is determined by evaluating (1) the level of the unfamiliarity of the observations an agent encounters and (2) the level of the unfamiliarity of the entire state the agents visit. An exploration bonus, which is derived from the concept of strangeness, is combined with the extrinsic reward obtained from the environment to form a mixed reward, which is then used for training CTDE-based MARL algorithms. Additionally, a separate action-value function is also proposed to prevent the high exploration bonus from overwhelming the sensitivity to extrinsic rewards during MARL training. This separate function is used to design the behavioral policy for generating transitions. The proposed method is not much affected by stochastic transitions commonly observed in MARL tasks and improves the stability of CTDE-based MARL algorithms when used with an exploration method. By providing didactic examples and demonstrating the substantial performance improvement of our proposed exploration method in CTDE-based MARL algorithms, we illustrate the advantages of our approach. These evaluations highlight how our method outperforms state-of-the-art MARL baselines on challenging tasks within the StarCraft II micromanagement benchmark, underscoring its effectiveness in improving MARL., 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 Ltd.. All rights reserved.)

Objective: The Geriatric Nutritional Risk Index is a simple nutritional screening method, and this study aimed to investigate the association between the initial Geriatric Nutritional Risk Index and all-cause mortality in incident patients in the first year after the initiation of hemodialysis., Materials and Methods: This study is a retrospective cohort study and used the Korean Renal Data System database. Patients who were eligible for Geriatric Nutritional Risk Index assessment and underwent hemodialysis from January 2016 to December 2019 were included. The primary outcome was all-cause mortality, and outcome evaluation was performed in December 2020. A Cox proportional hazard model was used to analyze the association between the Geriatric Nutritional Risk Index and mortality., Results: A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. The patients were divided into four groups by the quartile of the Geriatric Nutritional Risk Index with a mean value of 96.2 ± 8.2. During the study period, 545 (5.2%) deaths occurred. The surviving patients had higher Geriatric Nutritional Risk Index values than ones who died in the first year of hemodialysis initiation (96.6 ± 7.5 vs. 88.2 ± 9.3, p < 0.001). Quartile 1 (Geriatric Nutritional Risk Index < 91.8) showed a significantly increased risk of all-cause (Hazard Ratio: 2.56; 95% Confidence Interval: 2.13-3.09; p < 0.001) and cardiovascular mortality (Hazard Ratio: 22.29; 95% Confidence Interval: 1.71- 3.08; p < 0.001) at the first year in comparison with Quartile 4 (Geriatric Nutritional Risk Index ≥ 101.3). In areas under the receiver-operating characteristic curves of all-cause mortality, the Geriatric Nutritional Risk Index model improved predictive values, compared to the baseline model. The area with the Geriatric Nutritional Risk Index model was significantly higher than the one with a model including albumin or body mass index ( p < 0.001)., Conclusions: These findings suggest that a low Geriatric Nutritional Risk Index (<91.8) is associated with first-year all-cause and cardiovascular mortality in patients who start hemodialysis and may be a useful and reproducible tool for assessing prognoses in this population.

Salt, one of the most commonly consumed food additives worldwide, is produced in many countries. The chemical composition of edible salts is essential information for quality assessment and origin distinction. In this work, a simple laser-induced breakdown spectroscopy instrument was assembled with a diode-pumped solid-state laser and a miniature spectrometer. Its performances in analyzing Mg and Ca in six popular edible sea salts consumed in South Korea and classification of the products were investigated. Each salt was dissolved in water and a tiny amount of the solution was dropped and dried on the hydrophilicity-enhanced silicon wafer substrate, providing homogeneous distribution of salt crystals. Strong Mg II and Ca II emissions were chosen for both quantification and classification. Calibration curves could be constructed with limits-of-detection of 87 mg/kg for Mg and 45 mg/kg for Ca. Also, the Mg II and Ca II emission peak intensities were used in a k -nearest neighbors model providing 98.6% classification accuracy. In both quantification and classification, intensity normalization using a Na I emission line as a reference signal was effective. A concept of interclass distance was introduced, and the increase in the classification accuracy due to the intensity normalization was rationalized based on it. Our methodology will be useful for analyzing major mineral nutrients in various food materials in liquid phase or soluble in water, including salts.

Neuronal swelling during cytotoxic edema is triggered by Na + and Cl - entry and is Ca 2+ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Panx1 channel inhibitors reduce and delay neuronal death in swelling triggered by voltage-gated Na + entry with veratridine. Neuronal swelling causes downstream production of reactive oxygen species (ROS) that opens Panx1 channels. We confirm that ROS activates Panx1 currents with whole-cell electrophysiology and find scavenging ROS is neuroprotective. Panx1 opening and subsequent ATP release attract microglial processes to contact swelling neurons. Depleting microglia using the CSF1 receptor antagonist PLX3397 or blocking P2Y 12 receptors exacerbates neuronal death, suggesting that the Panx1-ATP-dependent microglia contacts are neuroprotective. We conclude that cytotoxic edema triggers oxidative stress in neurons that opens Panx1 to trigger death but also initiates neuroprotective feedback mediated by microglia contacts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The production and use of dibutyl phthalate (DBP) are increasing, and the resulting health and environmental problems are of concern. Therefore, the present study focused on the biodegradation of DBP in liquid fermentation using endophytic Penicillium species and evaluated the cytotoxic, ecotoxic, and phytotoxic effects of the fermented filtrate (by-product). Higher biomass yield was observed in fungal strains grown in DBP-containing media (DM) compared to DBP-free (control) media (CM). The highest esterase activity was observed at 240 h during fermentation with Penicillium radiatolobatum (PR) grown in DM (PR-DM). As per gas chromatography/mass spectrometry (GC/MS) results, the PR degraded 99.986 % of DBP after 288 h of fermentation. Furthermore, compared to DM treatment, the fermented filtrate of PR-DM demonstrated negligible toxicity in HEK-293 cells. Besides, the treatment of PR-DM in Artemia salina indicated >80 % viability and showed a trivial ecotoxic effect. However, compared to the control, the fermented filtrate of PR-DM treatment resulted in ~90 % of the roots and shoots growth of Zea mays seeds, indicating no phytotoxicity. Overall, the findings of this study suggested that PR can degrade DBP in liquid fermentation without generating toxic byproducts., 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 © 2023 Elsevier B.V. All rights reserved.)

Nitrate sources in surface water have been identified using dual-isotope compositions of nitrate with various tools to efficiently manage the water quality at the local scale. Correlation between Cl and NO 3 has also been used to identify NO 3 . In this study, we assess the reliability of the dual-isotope approach and Cl in terms of nitrate source apportionment. To this end, we collected stream water samples throughout South Korea to estimate nitrate sources in streams and determine whether the land-use pattern was closely related to nitrate sources. The δ 15 N-NO 3 ranging from -1.3 to 14.8‰ showed a spatial distribution that was lower in mountain ranges (<7‰) than plain areas (>8‰). The Cl concentration in this national-scale distribution was also assessed. The relationship between the proportion of Cl and δ 15 N-NO 3 classifies nitrate sources into areas characterized by three land-use patterns: (1) agricultural and business areas, (2) forests in highlands, and (3) lowland forests, of which (1) had proportions of Cl >50%, while (2) and (3) were <50%. The samples in (3) showed δ 15 N-NO 3 values > 6‰, similar to those of (1). Deuterium excess of samples was negatively correlated (R 2  = 0.53) with δ 15 N-NO 3 , accounting for the fact that δ 15 N-NO 3 reflected land-use patterns. Samples were dominantly affected by agriculture-derived sources and domestic sewage showed NO 3 /Cl of <0.4 and δ 15 N-NO 3 of >6‰. These results suggest that nitrate source apportionment should be comprehensively evaluated considering the dual-isotope approach, land-use patterns, and Cl proportions., 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 © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Trace element concentrations and isotope ratios of hair reflect the blood levels at the time of hair formation, but can be affected by external factors such as dyeing, bleaching, and bathing. To investigate the effect of dyeing, bleaching, and bathing on hair, hair was immersed in tap water, and changes in trace element concentrations and the Sr isotope ratio were observed over time. During soaking, alkaline earth metals (Ca, Mg, and Sr) from tap water were gradually absorbed into the hair over time. After about one day, the adsorption capacity of hair reached a maximum and the reverse reaction started to occur. In contrast, alkaline metals (Na and K) behaved in reverse. In dyed and bleached hair, Na was significantly desorbed from the hair and gradually migrated to the water over time. The adsorption and desorption of trace elements were minimal in untreated original hair, but much higher in dyed and bleached hair. Thus, dyeing and bleaching appear to damage the hair surface structure and greatly promote the exchange of trace elements. The rapid exchange of trace elements, including Sr, between hair and tap water observed in this study indicates that hair samples can be easily contaminated during bathing., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Codonopsis lanceolata (Campanulaceae) is a perennial plant commonly known as the bonnet bellflower. This species is widely used in traditional medicine and is considered to have multiple medicinal properties. In this study, we found that shoots and roots of C. lanceolata contained various types of free triterpenes (taraxerol, β-amyrin, α-amyrin, and friedelin) and triterpene acetates (taraxerol acetate, β-amyrin acetate, and α-amyrin acetate). The content of triterpenes and triterpene acetates by GC analysis was higher in the shoot than in the roots. To investigate the transcriptional activity of genes involved in triterpenes and triterpene acetate biosynthesis, we performed de novo transcriptome analysis of shoots and roots of C. lanceolata by sequencing using the Illumina platform. A total of 39,523 representative transcripts were obtained. After functional annotation of the transcripts, the differential expression of genes involved in triterpene biosynthetic pathways was investigated. Generally, the transcriptional activity of unigenes in the upstream region (MVA and MEP pathway) of triterpene biosynthetic pathways was higher in shoots than in roots. Various triterpene synthases (2,3-oxidosqualene cyclase, OSC) participate to produce triterpene skeletons by the cyclization of 2,3-oxidosqualene. A total of fifteen contigs were obtained in annotated OSCs in the representative transcripts. Functional characterization of four OSC sequences by heterologous expression in yeast revealed that ClOSC1 was determined as taraxerol synthase, and ClOSC2 was a mixed-amyrin synthase producing α-amyrin and β-amyrin. Five putative contigs of triterpene acetyltransferases showed high homology to the lettuce triterpene acetyltransferases. Conclusively, this study provides the basis of molecular information, particularly for the biosynthesis of triterpenes and triterpene acetates in C. lanceolata .

Successful application and accurate interpretation of strontium (Sr) isotope ratios ( 87 Sr/ 86 Sr) requires underlying information about the large-scale variabilities in their signatures from a variety of environmental samples, which can be correlated with the Sr isotopic signatures of underlying local geology. In this national-scale study, we analyzed 87 Sr/ 86 Sr in soil, plants, stream water, and Chinese mystery snail (Cipangopaludina chinensis) shells collected from South Korea to evaluate large-scale spatial variabilities, interpret relationships among isotopic signatures of various sample types, and generate spatial distribution isoscapes reflecting the heterogeneity of isotopic signatures across South Korea. Non-parametric comparisons among environmental samples showed non-significant differences in their isotopic ratios. The 87 Sr/ 86 Sr of plant and soil samples were strongly correlated (R 2 adj  = 0.93), suggesting that both reflect national-scale lithological properties. Similarly, the 87 Sr/ 86 Sr of shells showed strong correlations with the 87 Sr/ 86 Sr of both plant and soil samples (R 2 adj  = 0.90). The 87 Sr/ 86 Sr signatures of environmental samples in this study aligned with expected Sr isotopic values and generally reflected local geology. Spatial distribution maps of samples showed similar 87 Sr/ 86 Sr spatial patterns, with high radiogenic values from granitic and granitic gneiss rocks systems and low radiogenic values from volcanic and sedimentary rock systems. Stream water samples showed significant correlations with soil and plant isotopic ratios, but with a low coefficient of determination (R 2 adj  = 0.68). The deviations were much larger for samples with 87 Sr/ 86 Sr > 0.720. Further study is needed to improve the accuracy of baseline determination and interpretation of stream water isotopic variations., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Underwater detection is accomplished using an underwater ultrasonic sensor, sound navigation and ranging (SONAR). Stealth to avoid detection by SONAR plays a major role in modern underwater warfare. In this study, we propose a smart skin that avoids detection by SONAR via controlling the signal reflected from an unmanned underwater vehicle (UUV). The smart skin is a multilayer transducer composed of an acoustic window, a double-layer receiver, and a single-layer transmitter. It separates the incident signal from the reflected signal from outside through the time-delay separation method and cancels the reflected wave from the phase-shifted transmission sound. The characteristics of the receiving and transmitting sensors were analyzed using a finite element analysis. Three types of devices were compared in the design of the sensors. Polyvinylidene fluoride (PVDF), which had little effect on the transmitted sound, was selected as the receiving sensor. A stacked piezoelectric transducer with high sensitivity compared to a cymbal transducer was used as the transmitter. The active reflection control system was modeled and verified using 2D 360° reflection experiments. The stealth effect that could be achieved by applying a smart skin to a UUV was presented through an active reflection-control omnidirectional reflection model.

Background: Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients., Methods: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter., Results: The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae., Conclusion: Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.

The inter-relationship between microglia dynamics and oxidative stress (Ox-stress) in dystrophic neurites (DNs) at Alzheimer's Disease (AD) plaques may contribute to the pathological changes in neurons. We developed new in vivo imaging strategies to combine EGFP expression in microglia with neuronal expression of genetically encoded ratiometric redox sensors (rogRFP2 or roGFP1), and immunohistochemistry to investigate how microglia influence Ox-stress at amyloid plaques in 5xFAD AD mice. By simultaneously imaging microglia morphology and neuronal Ox-stress over time in vivo and in fixed brains we found that microglia preferentially enwrapped DNs exhibiting the greatest degree of Ox-stress. After microglia were partially depleted with the CSF1 receptor antagonist PLX3397, Ox-stress in DNs increased in a manner that was inversely correlated to the extent of coverage of the adjacent Aβ plaques by the remaining microglia. These data suggest that microglia do not create Ox-stress at Aβ plaques but instead create protective barriers around Aβ plaques possibly reducing the spread of Aβ. Intracranial injection of Aβ was sufficient to induce neuronal Ox-stress suggesting it to be the initial trigger of Ox-stress generation. Although Ox-stress is increased in DNs, neuronal survival is enhanced following microglia depletion indicating complex and multifactorial roles of microglia with both neurotoxic and neuroprotective components. Increased Ox-stress of DNs was correlated with higher LAMP1 and ubiquitin immunoreactivity supporting proposed mechanistic links between lysosomal accumulation in DNs and their intrinsic generation of Ox-stress. Our results suggest protective as well as neurotoxic roles for microglia at plaques and that the generation of Ox-stress of DNs could intrinsically be generated via lysosomal disruption rather than by microglia. In Brief: Simultaneous imaging of microglia and neuronal Ox-stress revealed a double-edged role for microglia in 5xFAD mice. Plaque associated microglia were attracted to and enwrapped Aβ plaques as well as the most highly oxidized DNs. After partial depletion of microglia, DNs were larger with greater levels of Ox-stress. Despite increased Ox-stress after microglia removal neuronal survival improved. Greater Ox-stress was correlated with increased levels of LAMP1 and ubiquitin thereby linking lysosome accumulation and Ox-stress in DNs., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated recycled aggregates of Jeju Island-where porous basalt exists as a natural aggregate-and is a study aimed at verifying the applicability of the basalt-based recycled aggregate in the field. To this end, the application properties of concrete were analyzed using the quality improvement of the recycled aggregate (PRA), the type of fine aggregate received in the region, and the cement content as variables. In an experiment using concrete in which 50% of the PRA was replaced with basalt (BA), the air content of the fresh concrete decreased due to the increasing solid content of the aggregate when PRA and fine aggregates (with an even particle size distribution) were used. Regarding the properties of the hardened concrete, when the PRA and fine aggregate (with a high fineness modulus) were used, the compressive strength was 33.6 MPa and the modulus of elasticity was 23.1 GPa, which are higher than those of the BA specimen. The resistance to carbonation increased due to the improved quality of the PRA specimen. Pores that are 0.3 mm in size or larger decreased when the PRA and fine aggregates of even particle sizes were used. This form of pore reduction was found to have a direct correlation with the improvement of mechanical properties.

To replace porous basalt, the mechanical properties of concrete with recycled resources and durability improvement were analyzed in this study. The analysis was based on the quality improvement of recycled aggregate, use of fly ash, and changes in curing conditions. Basalt aggregate (BA) with a 3% water absorption, raw recycled aggregate and basalt (RRA), and improved recycled aggregate and basalt (PRA) were the main experimental variables. As PRA was applied to concrete, the compressive strength was lower than that of the specimen comprising BA in the normal strength region, but the modulus of elasticity (22.9 GPa) was equivalent or higher. The initial drying shrinkage increased because of the use of basalt-based recycled aggregate (B-RA). The drying shrinkage of PRA was similar to that of BA with an average difference of <7% as the age increased. The specimens subjected to steam curing exhibited the lowest drying shrinkage. These results showed that pores in the old paste of recycled aggregate increased freeze−thaw resistance because of the increase in the spacing factor. Although the PRA did not satisfy the quality criteria, the efficient use of recycled aggregate achieved an equivalent or higher performance than that of concrete comprising BA and improved durability.

The study is aimed to evaluate the diagnostic and prognostic role of the immunohistochemical expression of the Caudal-type homeobox transcription factor 2 (CDX2) in colorectal cancers (CRCs) through a meta-analysis. By searching relevant databases, 38 articles were eligible to be included in this study. We extracted the information for CDX2 expression rates and the correlation between CDX2 expression and clinicopathological characteristics. The estimated rates of CDX2 expression were 0.882 [95% confidence interval (CI) 0.774−0.861] and 0.893 (95% CI 0.820−0.938) in primary and metastatic CRCs, respectively. Furthermore, based on their histologic subtype, CDX2 expression rates of adenocarcinoma and medullary carcinoma were 0.886 (95% CI 0.837−0.923) and 0.436 (95% CI 0.269−0.618), respectively. There was a significant difference in CDX2 expression rates between adenocarcinoma and medullary carcinoma in the meta-regression test (p < 0.001). In addition, CDX2 expression was significantly lower in CRCs with the BRAFV600E mutation than in CRCs without mutation. Patients with CDX2 expression had better overall and cancer-specific survival rates than those without CDX2 expression. Thus, CDX2 is a useful diagnostic and prognostic marker CRCs.

Background: Incisional hernia (IH) is a commonly encountered problem even in the era of minimally invasive surgery (MIS). Numerous studies on IH are available in English literature, but there are lack of data from the Eastern part of the world. This study aimed to evaluate the risk factors as well as incidence of IH by analyzing a large cohort collected from a single tertiary center in Korea., Methods: Among a total number of 4276 colorectal cancer patients who underwent a surgical resection from 2006 to 2019 in Korea University Anam Hospital, 2704 patients (2200 laparoscopic and 504 robotic) who met the inclusion criteria were analyzed. IH was confirmed by each patient's diagnosis code registered in the hospital databank based on physical examination and/or computed tomography findings. Clinical data including specimen extraction incision (transverse or vertical midline) were compared between IH group and no IH group. Risk factors of developing IH were assessed by utilizing univariable and multivariable analyses., Results: During the median follow-up of 41 months, 73 patients (2.7%) developed IH. Midline incision group (n = 1472) had a higher incidence of IH than that of transverse incision group (n = 1232) (3.5% vs. 1.7%, p = 0.003). The univariable analysis revealed that the risk factors of developing IH were old age, female gender, obesity, co-morbid cardiovascular disease, transverse incision for specimen extraction, and perioperative bleeding requiring transfusion. However, on multivariable analysis, specimen extraction site was not significant in developing IH and transfusion requirement was the strongest risk factor., Conclusions: IH development after MIS is uncommon in Korean patients. Multivariable analysis suggests that specimen extraction site can be flexibly chosen between midline and transverse incisions, with little concern about risk of developing IH. Careful efforts are required to minimize operative bleeding because blood transfusion is a strong risk factor for developing IH., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera , had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy.

Iron overload in the brain, defined as excess stores of iron, is known to be associated with neurological disorders. In neurodegeneration accompanied by brain iron accumulation, we reported a specific point mutation, c.974-1G>A in WD Repeat Domain 45 ( WDR45 ), showing iron accumulation in the brain, and autophagy defects in the fibroblasts. In this study, we investigated whether fibroblasts with mutated WDR45 accumulated iron, and other effects on cellular organelles. We first identified the main location of iron accumulation in the mutant fibroblasts and then investigated the effects of this accumulation on cellular organelles, including lipid droplets, mitochondria and lysosomes. Ultrastructure analysis using transmission electron microscopy (TEM) and confocal microscopy showed structural changes in the organelles. Increased numbers of lipid droplets, fragmented mitochondria and increased numbers of lysosomal vesicles with functional disorder due to WDR45 deficiency were observed. Based on correlative light and electron microscopy (CLEM) findings, most of the iron accumulation was noted in the lysosomal vesicles. These changes were associated with defects in autophagy and defective protein and organelle turnover. Gene expression profiling analysis also showed remarkable changes in lipid metabolism, mitochondrial function, and autophagy-related genes. These data suggested that functional and structural changes resulted in impaired lipid metabolism, mitochondrial disorder, and unbalanced autophagy fluxes, caused by iron overload.

This study demonstrated the use of KCl separated from chlorine bypass dust (CBD) as an activator for plain concrete. The separated KCl was mixed with either ground granulated blast-furnace slag (BFS) alone, or a mixture of BFS and cement. The mixed paste of separated KCl and BFS set within 24 h, and exhibited a compressive strength of 22.6 MPa after 28 d. The separated KCl, cement, and BFS mixture exhibited a more rapid setting and a higher initial activity. Further, the compressive strength at 28 d was 57.7 MPa, which was 26.2% higher than that of the mixture without the activator. Water curing of samples with added separated KCl led to the generation of hydrocalumite, or Friedel's salt. However, this hydrocalumite was decomposed while being cured under autoclave conditions at 180 °C. Overall, KCl was an effective activator for composite materials containing cement, and resulted in superior properties compared to mineral admixtures without an activator.

Recycled aggregate is essential to protect Jeju Island's natural environment, but waste concrete, including porous basalt, is a factor that lowers the quality of recycled aggregate. Therefore, an experiment was conducted to analyze the properties of concrete application of basalt-based recycled aggregate (B-RA) through quality improvement. The absorption of the B-RA ranged from 3-5%; restricting its absorption to less than 3% was challenging owing to its porosity and irregular shape. However, the increase in the solid volume percentage of the concrete when replacing 25 or 50% of fresh basalt aggregate with recycled basalt aggregate improved the mechanical performance of the concrete, especially at 25%, for which a compressive strength of 55.9 MPa and modulus of elasticity of 25.9 GPa exceeded those of concrete with fresh basalt aggregate. Moreover, increasing the replacement ratio of the fresh basalt with recycled aggregate reduced the slump and decreased the air content, consequently increasing the concrete drying shrinkage. However, the replacement of fresh basalt aggregate with recycled basalt aggregate unaltered the mechanical performance of the concrete. The results indicate that efficient use of recycled aggregates can yield superior performance to that of fresh basalt, irrespective of aggregate quality.

Introduction: Intersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR., Materials and Methods: Retrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis., Results: Median follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976-6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941-11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015-9.838); p < 0.001) was a prognostic factor on multivariate analysis., Conclusions: This study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS., 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 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Loss-of-function variant in the gene encoding the KCNQ4 potassium channel causes autosomal dominant nonsyndromic hearing loss (DFNA2), and no effective pharmacotherapeutics have been developed to reverse channel activity impairment. Phosphatidylinositol 4,5-bisphosphate (PIP 2 ), an obligatory phospholipid for maintaining KCNQ channel activity, confers differential pharmacological sensitivity of channels to KCNQ openers. Through whole-exome sequencing of DFNA2 families, we identified three novel KCNQ4 variants related to diverse auditory phenotypes in the proximal C-terminus (p.Arg331Gln), the C-terminus of the S6 segment (p.Gly319Asp), and the pore region (p.Ala271&#95;Asp272del). Potassium currents in HEK293T cells expressing each KCNQ4 variant were recorded by patch-clamp, and functional recovery by PIP 2 expression or KCNQ openers was examined. In the homomeric expression setting, the three novel KCNQ4 mutant proteins lost conductance and were unresponsive to KCNQ openers or PIP 2 expression. Loss of p.Arg331Gln conductance was slightly restored by a tandem concatemer channel (WT-p.R331Q), and increased PIP 2 expression further increased the concatemer current to the level of the WT channel. Strikingly, an impaired homomeric p.Gly319Asp channel exhibited hyperactivity when a concatemer (WT-p.G319D), with a negative shift in the voltage dependence of activation. Correspondingly, a KCNQ inhibitor and chelation of PIP 2 effectively downregulated the hyperactive WT-p.G319D concatemer channel. Conversely, the pore-region variant (p.Ala271&#95;Asp272del) was nonrescuable under any condition. Collectively, these novel KCNQ4 variants may constitute therapeutic targets that can be manipulated by the PIP 2 level and KCNQ-regulating drugs under the physiological context of heterozygous expression. Our research contributes to the establishment of a genotype/mechanism-based therapeutic portfolio for DFNA2., (© 2021. The Author(s).)

Immunometabolism refers to the rearrangement of metabolic pathways in response to immune stimulation, and the ability of these metabolic pathways themselves to control immune functions. Many aspects of immunometabolism have been revealed through studies of peripheral immune cells. However, immunometabolic reprogramming of microglia, the resident immune cell of the central nervous system, and the consequential outcome on neuronal activity have remained difficult to unravel. Microglia are highly sensitive to subtle changes in their environment, limiting the techniques available to study their metabolic and inflammatory profiles. Here, using fluorescence lifetime imaging of endogenous NAD(P)H, we measure the metabolic activity of individual microglia within acute hippocampal slices. We observed an LPS-induced increase in aerobic glycolysis, which was blocked by the addition of 5 mM 2-deoxyglucose (2DG). This LPS-induced glycolysis in microglia was necessary for the stabilization of hypoxia inducible factor-1α (HIF-1α) and production of the proinflammatory cytokine, interleukin-1β (IL-1β). Upon release, IL-1β acted via the neuronal interleukin-1 receptor to inhibit the formation of synaptic long-term potentiation (LTP) following high frequency stimulation. Remarkably, the addition of 2DG to blunt the microglial glycolytic increase also inhibited HIF-1α accumulation and IL-1β production, and therefore rescued LTP in LPS-stimulated slices. Overall, these data reveal the importance of metabolic reprogramming in regulating microglial immune functions, with appreciable outcomes on cytokine release and neuronal activity., (© 2020 Wiley Periodicals LLC.)

The aim of this study was to investigate the protective effects of dendropanoxide (DPx) isolated from Dendropanax morbifera against cis-diamminedichloroplatinum (II) (CDDP)-induced nephrotoxicity in NRK-52E cells and in Sprague-Dawley rats. DPx was administered to Sprague-Dawley rats by oral gavage (5 and 10 mg/kg) for 7 consecutive days, 24 h after intraperitoneal injection with CDDP (6 mg/kg). All rats were euthanized 24 h after the last DPx administration, and histopathological damage, acute kidney injury (AKI) biomarkers, inflammatory cytokines, and oxidative damages were evaluated. DPx (5 and 10 μg/mL) was found to protect against CDDP-induced cytotoxicity and apoptotic cell death in NRK-52E cells. CDDP-induced serum blood urea nitrogen (BUN), creatinine (sCr), and pro-inflammatory cytokines levels were significantly ameliorated by DPx in a dose-dependent manner. Furthermore, excretion of kidney injury molecules (KIM-1), selenium binding protein-1 (SBP-1), and neutrophil gelatinase-associated lipocalin (NGAL) in the urine was significantly reduced in response to DPx administration in CDDP-treated rats. Activities of antioxidant enzymes and lipid peroxidation levels were markedly altered in the kidney of CDDP-treated rats in response to DPx administration. Serum pro-inflammatory cytokine levels were dramatically suppressed by DPx in CDDP-treated rats. DPx also restored renal-cell apoptosis via regulation of AMPK/mTOR signaling in CDDP-treated rats. Our results clearly suggest that DPx ameliorates CDDP-induced nephrotoxicity in vitro and in vivo by inhibiting oxidative stress, inflammation, and apoptosis. Overall, our data demonstrates that DPx may serve as a therapeutic agent in patients with solid tumors to prevent CDDP-induced AKI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Resuming driving is a common concern among patients undergoing hip arthroscopy. The present study aimed to assess whether patients who had undergone right hip arthroscopy presented with poorer driving performance than patients with normal hips and to analyze the time required to regain preoperative driving performance., Methods: Forty-seven patients who had undergone right hip arthroscopy and consented to our test protocol were included in this study. Using an immersive driving simulator, the patients were tested for their brake reaction time (BRT), total brake time (TBT), and brake pedal depression (BPD) preoperatively and postoperatively. The first postoperative assessments were conducted when the patients could comfortably sit on the driving seat, and the follow-up assessments were conducted for 6 consecutive weeks at weekly intervals. The patients were divided into the following two groups based on the type of surgery that they underwent: the femoroacetabular impingement (FAI) surgery group and the simple hip arthroscopy (SA) group. Twenty healthy volunteers underwent driving assessments thrice at weekly intervals and constituted the control group. The braking parameters were compared between preoperative and postoperative measurements and among the FAI surgery, SA, and control groups., Results: The preoperative braking parameters of the patients who underwent arthroscopy did not differ significantly from those of the controls (p = 0.373, 0.763, and 0.447 for the BRT, TBT, and BPD, respectively). All braking parameters returned to normal in 2 weeks in the FAI surgery group and in 1 week in the SA group., Conclusions: Our study suggests that the driving performance of patients who underwent right hip arthroscopy is comparable to that of individuals with normal hips and that the braking parameters may normalize to the preoperative state at 1 week after SA and 2 weeks after FAI surgery.

Intralogistics is a technology that optimizes, integrates, automates, and manages the logistics flow of goods within a logistics transportation and sortation center. As the demand for parcel transportation increases, many sortation systems have been developed. In general, the goal of sortation systems is to route (or sort) parcels correctly and quickly. We design an n -grid sortation system that can be flexibly deployed and used at intralogistics warehouse and develop a collaborative multi-agent reinforcement learning (RL) algorithm to control the behavior of emitters or sorters in the system. We present two types of RL agents, emission agents and routing agents, and they are trained to achieve the given sortation goals together. For the verification of the proposed system and algorithm, we implement them in a full-fledged cyber-physical system simulator and describe the RL agents' learning performance. From the learning results, we present that the well-trained collaborative RL agents can optimize their performance effectively. In particular, the routing agents finally learn to route the parcels through their optimal paths, while the emission agents finally learn to balance the inflow and outflow of parcels.

Background: We investigated the association of waist circumference (WC) and abdominal obesity with the incident colorectal cancer risk in Korean adults., Methods: This nationwide population-based cohort study was based on health insurance claims data. We analyzed data from 9,959,605 participants acquired through health check-ups of the Korean National Health Insurance Service in 2009 who were followed up until the end of 2017. We performed multivariable Cox proportional hazards regression analysis., Results: During 8.3 years of follow up, 101,197 cases (1.0%) of colorectal cancer were recorded. After adjusting for potential confounders, there was a positive association between WC and colorectal cancer risk ( p for trend <0.001). Abdominal obesity was associated with an increased risk of colorectal (hazard ratio: 1.10, (95% confidence interval: 1.08-1.12)), colon (1.11, 1.09-1.13), and rectal cancer (1.08, 1.05-1.10). These associations were independent of body mass index and were more pronounced in men and elderly individuals., Conclusion: We revealed that higher WC is related to colorectal cancer risk, thus suggesting that abdominal obesity may be a risk factor for colorectal cancer in this East Asian population.

The demand for display technology is expected to increase with the continuous spread of portable electronics and with the expected emergence of flexible, wearable, and transparent display devices. A touch screen is a critical component in display technology that enables user interface operations, and the future generation of touch screens, the so-called 3D touch screens, is expected to be able to detect multiple levels of pressure. To enable 3D touch screens, transparent pressure sensors with high linearity over a working range that encompasses the pressure range of human touch (10-100 kPa) are required. In this work, a transparent and linear capacitive pressure sensor is reported with a transmittance over 85% and high linearity ( R 2 = 0.995) over 5-100 kPa of pressure. To render the sensor transparent, a microstructured "hard" elastomer layer was filled in with a refractive index matching a "soft" elastomer layer, through which light scattering was minimized. High linearity was attained from the sensor's unique architecture that increases the effective area of the capacitor with applied pressure. These attributes render our sensor highly suitable for future 3D touch screen applications.

Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain. Microglia are metabolically flexible and can rapidly adapt to consume glutamine as an alternative metabolic fuel in the absence of glucose. During insulin-induced hypoglycemia in vivo or in aglycemia in acute brain slices, glutaminolysis supports the maintenance of microglial process motility and damage-sensing functions. This metabolic shift sustains mitochondrial metabolism and requires mTOR-dependent signaling. This remarkable plasticity allows microglia to maintain their critical surveillance and phagocytic roles, even after brain neuroenergetic homeostasis is compromised.

The greenhouse effect is closely related to elevated atmospheric CO 2 concentrations and therefore, carbon capture and storage (CCS) has attracted attention worldwide as a method for preventing the release of CO 2 into the atmosphere, which highlights the importance of monitoring CO 2 released from subsurface deposits. In this study, CO 2 gas with a δ 13 C value of -30‰ was injected into soil through pipes installed at a depth of 2.5 m, and samples of CO 2 gas released from the soil surface and three soil depths were collected from September 2015 to March 2016 to estimate subsurface CO 2 movement. Before and after CO 2 injection, the δ 13 C values of CO 2 released from the soil surface ranged from -24.5 to -13.4‰ (average -20.2 ± 2.1‰, n = 25) and from -31.6 to -11.9‰ (average -23.2 ± 4.3‰, n = 49), respectively. The results indicated that the leakage of injected CO 2 was successfully detected at the surface. The δ 13 C values were visualized using an interpolation map to estimate the subsurface CO 2 distribution, which confirmed that diffusion of the injected CO 2 gas extended to the soil zone where CO 2 was not injected. Additionally, variation in δ 13 C for soil CO 2 was detected at the three soil depths (15, 30, and 60 cm), where the values were -16.1, -20.0, and -22.1‰, respectively. Different δ 13 C values horizontally and vertically indicated that soil heterogeneity led to different CO 2 migration pathways and rates. We suggest that the carbon isotope ratio of CO 2 is an effective tool for concurrently monitoring CO 2 leakage on and under surface in a soil zone if a thorough baseline study is carried out in the field., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A combination of O3S2-macrocycles incorporating different sulfur-to-sulfur separations (S-(CH2)n-S, L1: n = 2, L2: n = 3) and copper(ii) nitrate afforded new types of both monocopper(ii) and dicopper(ii) complexes, respectively. L1 gave a 1D coordination polymer [Cu2(L1)2(NO3)4]n (1) based on a convergent exo-coordination mode while L2 resulted in the formation of a divergent exo/exo-coordinated dicopper(ii) complex, [Cu2(L2ox)4(μ-Cl)](NO3)4 (2), whose shape resembles a four-bladed waterwheel in which in situ oxidized macrocycles (L2ox) act as the blades and a CuII-(μ-Cl)-CuII entity corresponds to the axle shaft. The chloro-bridging ligand is derived from the dichloromethane solvent and its arrangement is held together by C-HCl- H-bonds. Compound 2 shows a weak antiferromagnetic property via the CuII-(μ-Cl)-CuII entity.

The use of lithium (Li) has dramatically increased during the last two decades due to the proliferation of mobile electronic devices and the diversification of electric-powered vehicles. Lithium is also prescribed as a medication against bipolar disorder. While Li can exert a toxic effect on living organisms, few studies have investigated the impact of anthropogenic inputs on Li levels in the environment. Here we report Li concentrations and Li isotope compositions of river, waste and tap water, and industrial products from the metropolitan city of Seoul. Results show that the large increase in population density in Seoul is accompanied by a large enrichment in aqueous Li. Lithium isotopes evidence a major release from Li-rich materials. Water treatment protocols are also shown to be inefficient for Li. Our study therefore highlights the need for a global Li survey and adequate solutions for minimizing their impact on ecosystems and city dwellers.

Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced [Ca 2+ ]i transient and reduced sarcoplasmic reticulum (SR) Ca 2+ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR Ca 2+ -ATPase subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises Ca 2+ signaling by downregulating the expression of DHPR and SERCA proteins., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest., (Copyright © 2019 The Korean Physiological Society and The Korean Society of Pharmacology.)

Objective: To investigate the factors associated with the change in alveolar bone level of mandibular second and third molars after second molar protraction into the space of the missing first molar (L6) or second premolar (LE)., Methods: Fifty-one patients in whom space of the missing L6 or LE was treated with second molar protraction (13 males, 38 females, mean age 19.6 ± 4.7 years) from 2003 to 2015 were included. The alveolar bone level and position and angulation of the mandibular second and third molars were measured in panoramic radiographs at pre-treatment (T1), and after the alignment of the third molars following second molar protraction (T2). Factors associated with alveolar bone loss on the distal aspect of the mandibular second molars were assessed using linear regression analysis., Results: Age at T1 (P < 0.001) and third molar angulation at T1 (P = 0.002) were significant factors for the prediction of alveolar bone level distal to the second molars., Limitation: This study used two-dimensional panoramic radiographs, and we could observe only the interproximal bone level., Conclusions: After second molar protraction into the missing first molar or second premolar space, mandibular second molars may exhibit alveolar bone resorption in the distal root in older patients and in those with mesially tilted third molars before treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Orthodontic Society.)

Sensor-to-sensor variability and high hysteresis of composite-based piezoresistive pressure sensors are two critical issues that need to be solved to enable their practical applicability. In this work, a piezoresistive pressure sensor composed of an elastomer template with uniformly sized and arranged pores, and a chemically grafted conductive polymer film on the surface of the pores is presented. Compared to sensors composed of randomly sized pores, which had a coefficient of variation (CV) in relative resistance change of 69.65%, our sensors exhibit much higher uniformity with a CV of 2.43%. This result is corroborated with finite element simulation, which confirms that with increasing pore size variability, the variability in sensor characteristics also increases. Furthermore, our devices exhibit negligible hysteresis (degree of hysteresis: 2%), owing to the strong chemical bonding between the conductive polymer and the elastomer template, which prevents their relative sliding and displacement, and the porosity of the elastomer that enhances elastic behavior. Such features of the sensor render it highly feasible for various practical applications in the near future., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Microglia, the brain's immune cells, maintain homeostasis and sense pathological changes by continuously surveying the parenchyma with highly motile large processes. Here, we demonstrate that microglia also use thin actin-dependent filopodia that allow fast nanoscale sensing within discrete regions. Filopodia are distinct from large processes by their size, speed, and regulation mechanism. Increasing cyclic AMP (cAMP) by activating norepinephrine G s -coupled receptors, applying nitric oxide, or inhibiting phosphodiesterases rapidly increases filopodia but collapses large processes. Alternatively, G i -coupled P2Y12 receptor activation collapses filopodia but triggers large processes extension with bulbous tips. Similar control of cytoskeletal dynamics and microglial morphology by cAMP is observed in ramified primary microglia, suggesting that filopodia are intrinsically generated sensing structures. Therefore, nanoscale surveillance of brain parenchyma by microglia requires localized cAMP increases that drive filopodia formation. Shifting intracellular cAMP levels controls the polarity of microglial responses to changes in brain homeostasis and alters the scale of immunosurveillance., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

An ultrahigh sensitive capacitive pressure sensor based on a porous pyramid dielectric layer (PPDL) is reported. Compared to that of the conventional pyramid dielectric layer, the sensitivity was drastically increased to 44.5 kPa -1 in the pressure range <100 Pa, an unprecedented sensitivity for capacitive pressure sensors. The enhanced sensitivity is attributed to a lower compressive modulus and larger change in an effective dielectric constant under pressure. By placing the pressure sensors on islands of hard elastomer embedded in a soft elastomer substrate, the sensors exhibited insensitivity to strain. The pressure sensors were also nonresponsive to temperature. Finally, a contact resistance-based pressure sensor is also demonstrated by chemically grafting PPDL with a conductive polymer, which also showed drastically enhanced sensitivity.

Electronic skin are devices that mimic the functionalities of human skin, which require high sensitivity, large dynamic range, high spatial uniformity, low-cost and large-area processability, and the capacity to differentiate various external inputs. We herein introduce a versatile droplet-based microfluidic-assisted emulsion self-assembly process to generate three-dimensional microstructure-based high-performance capacitive and piezoresistive pressure sensors for electronic skin applications. Our technique can generate uniformly sized micropores that are self-assembled in an orderly close-packed manner over a large area, which results in high spatial uniformity. The size of the micropores can easily be tuned from 100 to 500 μm, through which sensitivity and dynamic range were controlled as high as 0.86 kPa -1 and up to 100 kPa. Our device can be printed on curvilinear surfaces and be molded into various shapes. We furthermore demonstrate that by simultaneously utilizing capacitive and piezoresistive pressure sensors, we can distinguish between pressure and temperature, or between pressure and proximity. These demonstrations make our process and sensors highly useful for a wide variety of electronic skin applications.

A qualitative study was conducted to explore nurses' positive experiences in caring for older adults with dementia in South Korea. Researchers collected data through in-depth, face-to-face interviews, and the recorded interviews were analyzed using grounded theory. A total of 33 codes, 12 categories, and 21 sub-categories were derived, and the categories were further analyzed using the paradigm model. A conceptual framework, the Gratified in Caring Model, was developed by integrating and abstracting the core category from nurses' positive experiences, and can be used by nurses to provide effective care and educators to train nurses to care for older adults. Findings also emphasize the need for nurses to collaborate with family members, as collaboration has been found to influence nurses' positive experiences. [Journal of Gerontological Nursing, 45(1), 31-37.]., (Copyright 2019, SLACK Incorporated.)

Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of nonsyndromic hearing loss, deafness nonsyndromic autosomal dominant 2 (DFNA2). We performed whole-exome sequencing for 98 families with hearing loss and found mutations in KCNQ4 in five families. In this study, we characterized two novel mutations in KCNQ4: a missense mutation (c.796G>T; p.Asp266Tyr) and an in-frame deletion mutation (c.259&#95;267del; p.Val87&#95;Asn89del). p.Asp266Tyr located in the channel pore region resulted in early onset and moderate hearing loss, whereas p.Val87&#95;Asn89del located in the N-terminal cytoplasmic region resulted in late onset and high frequency-specific hearing loss. When heterologously expressed in HEK 293 T cells, both mutant proteins did not show defects in protein trafficking to the plasma membrane or in interactions with wild-type (WT) KCNQ4 channels. Patch-clamp analysis demonstrated that both p.Asp266Tyr and p.Val87&#95;Asn89del mutant channels lost conductance and were completely unresponsive to KCNQ activators, such as retigabine, zinc pyrithione, and ML213. Channels assembled from WT-p.Asp266Tyr concatemers, like those from WT-WT concatemers, exhibited conductance and responsiveness to KCNQ activators. However, channels assembled from WT-p.Val87&#95;Asn89del concatemers showed impaired conductance, suggesting that p.Val87&#95;Asn89del caused complete loss-of-function with a strong dominant-negative effect on functional WT channels. Therefore, the main pathological mechanism may be related to loss of K + channel activity, not defects in trafficking.

Increasing attention is being placed on the prevalence of elder abuse and its impact on mental health. This study conducted a survey of 172 elderly people in South Korea to determine the prevalence of elder abuse and the relationships involving elder abuse, depression and posttraumatic stress disorder (PTSD). Participants completed a battery of self-report questionnaires, which included the Korean Geriatric Depression Screening Scale (KGDS) and Impact of Event Scale-Revised Korean version (IES-R-K). Descriptive analyses were conducted to examine the frequency of specific forms of abuse. Logistic regression models were estimated to identify the factors that contributed to risk of abuse exposure and the relationship between exposure and PTSD or depression. The results indicated around 22% of the participants reported abuse exposure, which most commonly included being refused physical contact, verbal threats, and/or being excluded from decision-making about personal issues. Low education and being unmarried, separated or divorced was associated with an increased risk of abuse exposure. There were strong associations between elder abuse and PTSD symptoms, while comparable relationships with depression were weaker and were not robust to the inclusion of control variables. The findings provided empirical support for the relationship between abuse experiences of the elderly and poor mental health and raise important issues for the mental health care of the elderly.

Purpose: Recently, fetal placenta-specific epigenetic regions (FSERs) have been identified for quantification of cell-free fetal DNA (cff-DNA) for non-invasive prenatal testing (NIPT). The aim of this study was to evaluate the efficiencies of a column-based kit and magnetic bead-based kit for quantification of methylated FSERs from maternal plasma., Methods: Maternal plasma was extracted from normal pregnant women within the gestational age of 10~13 weeks (n = 24). Total cell-free DNA (cf-DNA) was extracted using a column-based kit and magnetic bead-based kit from the plasma of the same pregnant woman, respectively. Methylated FSERs were enriched from the extracted total cf-DNA using a methyl-CpG-binding domain-based protein method. The four FSERs were simultaneously quantified by multiplex real-time polymerase chain reaction., Results: Methylated FSERs were detected in all samples extracted from both kits. However, the amplification of FSERs showed significant differences in the extraction efficiency of methylated FSERs between the two extraction methods. The Ct values of methylated FSERs extracted using the column-based kit were significantly lower than those obtained using the magnetic bead-based kit (P < 0.001 for all FSERs). The quantity of methylated FSERs was significantly higher for extracted DNA using the column-based kit than that extracted using the magnetic bead-based kit (P < 0.001 for all FSERs). Time and cost for the process of extraction were similar for the column kit and magnetic bead-based kit., Conclusions: Our findings demonstrate that the column-based kit was more effective than the magnetic bead-based kit for isolation of methylated FSERs from maternal plasma as assessed by FSER detection.