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Hyun Ho Shin,1,* Junyoung Park,2,* Yeo-Jin Kim,3 Donghyeon Kim,2 Eun-Jung Jin,2,4 Ji Hyun Ryu1,3,4 1Department of Chemical Engineering, Wonkwang, University, Iksan, Jeonbuk, 54538, Republic of Korea; 2Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 3Department of Carbon Convergence Engineering, Smart Convergence Materials Analysis Center, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 4Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea*These authors contributed equally to this workCorrespondence: Ji Hyun Ryu, Department of Carbon Convergence Engineering, Iksan, Jeonbuk, 54538, Republic of Korea, Email jhryu4816@wku.ac.kr Eun-Jung Jin, Department of Biological Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea, Email jineunjung@wku.ac.krIntroduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects.Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1β (IL-1β) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated.Results: CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1β was reduced through the upregulation of PPAR.Conclusion: CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1β via increasing PPAR. Keywords: polycaprolactone nanofibers, gallic acid-conjugated chitosan, compound K, hydrophilic coating, adhesive material, cartilage regeneration

Background: Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to id

The direction and magnitude of association between maternal exposure to ambient air pollutants across gestational windows and offspring risk of autism spectrum disorders (ASD) remains unclear. We sought to evaluate the time-varying effects of prenatal air pollutant exposure on ASD. We conducted a matched case-control study of singleton term children born in Ontario, Canada from 1-Apr-2012 to 31-Dec-2016. Provincial birth registry data were linked with applied behavioural analysis services and ambient air pollutant datasets to ascertain prenatal exposure to nitrogen dioxide (NO 2 ), ground-level ozone (O 3 ), fine particulate matter (PM 2.5 ), and ASD diagnoses. Covariate balance between cases and controls was established using coarsened exact matching. Conditional logistic regression was used to assess the association between prenatal air pollutant exposure and ASD. Distributed lag non-linear models (DLNM) were used to examine the effects of single-pollutant exposure by prenatal week. Sensitivity analyses were conducted to assess the impact of exposure period on the observed findings. The final sample included 1589 ASD cases and 7563 controls. Compared to controls, cases were more likely to be born to mothers living in urban areas, delivered by Caesarean section, and assigned male sex at birth. NO 2 was a consistent and significant contributor to ASD risk after accounting for co-exposure to O 3 , PM 2.5 and covariates. The odds ratio per interquartile range increase was 2.1 (95%CI 1.8-2.3) pre-conception, 2.2 (2.0-2.5) for the 1st trimester, 2.2 (1.9-2.5) for the 2nd trimester, and 2.1 (1.9-2.4) for the 3rd trimester. In contrast, findings for O 3 and PM 2.5 with ASD were inconsistent. Findings from DLNM and sensitivity analyses were similar. Exposure to NO 2 before and during pregnancy was significantly associated with ASD in offspring. The relationship between prenatal O 3 and PM 2.5 exposure and ASD remains unclear. Further investigation into the combined effects of multi-pollutant exposure on child neurodevelopment is warranted., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms., Methods: A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF-GSE complex extract at ratios of 1:1, 1:2, and 2:1., Results: Treatment with the SJF-GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48-72 mg/g sophoricoside and 8-12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles., Conclusions: The SJF-GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD., (© 2024. The Author(s).)

Background: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years)., Methods: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE))., Results: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution., Conclusions: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Bacteriophages, also known as phages, are viruses that replicate in bacteria and archaea. Phages were initially discovered as antimicrobial agents, and they have been used as therapeutic agents for bacterial infection in a process known as "phage therapy." Recently, phages have been investigated as functional nanomaterials in a variety of areas, as they can function not only as therapeutic agents but also as biosensors and tissue regenerative materials. Phages are nontoxic to humans, and they possess self-assembled nanostructures and functional properties. Additionally, phages can be easily genetically modified to display specific peptides or to screen for functional peptides via phage display. Here, we demonstrated the application of phage nanomaterials in the context of tissue engineering, sensing, and probing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Heo, Kim and Shin.)

Background: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis., Methods: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC)., Results: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m 2 , preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning., Conclusions: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success., Level of Evidence: Level III, retrospective cohort study., (© 2024. The Author(s).)

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Attention toward the preventive effects of postbiotics on metabolic diseases has increased because of greater stability and safety over probiotics. However, studies regarding the bioactive effects of postbiotics, especially from probiotic Bacillus strains, are relatively limited. The anti-obesity effects of the cell-free culture supernatant of Bacillus velezensis KMU01 (CFS- B.vele ) were evaluated using high-fat-diet (HFD)-induced mice. HFD-induced mice (n = 8 per group) received equal volumes of (1) CFS- B.vele (114 mg/kg) in PBS, (2) Xenical in PBS, or (3) PBS alone by oral gavage daily for 13 weeks. The results demonstrated that CFS- B.vele changed the gut microbiota and showed anti-obesity effects in HFD-induced obese mice. The elevated Firmicutes/Bacteroidota ratio induced by HFD was decreased in the CFS- B.vele group compared to the other groups ( p  < 0.05). The CFS- B.vele intervention led to the enrichment of SCFA-producers, such as Roseburia and Eubacterium , in the cecum, suggesting their potential involvement in the amelioration of obesity. Due to these changes, the various obesity-related biomarkers (body weight, fat in tissue, white adipose tissue weight and size, serum LDL-cholesterol level, hepatic lipid accumulation, and adipogenesis/lipogenesis-related gene/protein expression) were improved. Our findings suggest that CFS- B.vele has potential as a novel anti-obesity agent through modulation of the gut microbiota., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Moon-Hee Sung reports financial support was provided by Korea Ministry of Small and Medium Enterprises and Startups. Moon Hee Sung reports financial support was provided by Korea 10.13039/501100003624Ministry of Agriculture, Food and Rural Affairs., (© 2024 The Authors. Published by Elsevier Ltd.)

Copper (Cu) is a widely used catalyst for the nitrate reduction reaction (NO 3 RR), but its susceptibility to surface oxidation and complex electrochemical conditions hinders the identification of active sites. Here, we employed electropolished metallic Cu with a predominant (100) surface and compared it to native oxide-covered Cu. The electropolished Cu surface rapidly oxidized after exposure to either air or electrolyte solutions. However, this oxide was reduced below 0.1 V vs. RHE, thus returning to the metallic Cu before NO 3 RR. It was distinguished from the native oxide on Cu, which remained during NO 3 RR. Fast NO 3 - and NO reduction on the metallic Cu delivered 91.5 ± 3.7% faradaic efficiency for NH 3 at -0.4 V vs. RHE. In contrast, the native oxide on Cu formed undesired products and low NH 3 yield. Operando shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) analysis revealed the adsorbed NO 3 - , NO 2 , and NO species on the electropolished Cu as the intermediates of NH 3 . Low overpotential NO 3 - and NO adsorptions and favorable NO reduction are key to increased NH 3 productivity over Cu samples, which was consistent with the DFT calculation on Cu(100)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The occurrence of leakage from anastomotic sites is a significant issue given its potential undesirable complications. The management of anastomotic leakage after gastrointestinal surgery is particularly crucial because it is directly associated with mortality and morbidity in patients. If adhesive materials could be used to support suturing in surgical procedures, many complications caused by leakage from the anastomosis sites could be prevented. In this study, we have developed self-healing, shear-thinning, tissue-adhesive, carbon-black-containing, gallic acid-conjugated chitosan (CB/Chi-gallol) hydrogels as sealing materials to be used with suturing. The addition of CB into Chi-gallol solution resulted in the formation of a crosslinked hydrogel with instantaneous solidification. In addition, these CB/Chi-gallol hydrogels showed enhancement of the elastic modulus (G') values with increased CB concentration. Furthermore, these hydrogels exhibited excellent self-healing, shear-thinning, and tissue-adhesive properties. Notably, the hydrogels successfully sealed the incision site with suturing, resulting in a significant increase in the bursting pressure. The proposed self-healing and adhesive hydrogels are potentially useful in versatile biomedical applications, particularly as suture support materials for surgical procedures.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors.)

Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration; however, challenges related to drug recovery, validation, and efficient drug delivery remain. For instance, compound K (CK) is a major metabolite of ginsenosides that is known to protect against joint degeneration by inhibiting the production of inflammatory cytokines and the activation of immune cells. However, its effects on cartilage degradation and tissue regeneration remain unclear. Additionally, tissue-adhesive drug delivery depots that stably adhere to cartilage defects are required for CK delivery. In this study, CK-loaded adhesive patches were reported to seal cartilage defects and deliver CK to defect sites, preventing cartilage degradation and accelerating cartilage tissue regeneration. Adhesive patches are stable and suitable for application in surgical procedures under physiological conditions and show excellent adhesiveness to cartilage surfaces. In addition, there were no significant differences in the adhesive polymeric networks before and after CK loading. CK-loaded hydrocaffeic acid-conjugated chitosan patches significantly inhibited the stimulation of cartilage-degrading enzymes and apoptosis in osteoarthritic cartilage by releasing CK in cartilage defects. Additionally, the NFkB signaling pathway of released CK from the adhesive patches in the treatment of osteoarthritis is revealed. Thus, the CK-loaded adhesive patches are expected to significantly contribute to cartilage regeneration., (© The Author(s) 2023. Published by Oxford University Press.)

Most of the existing epidemiological studies have investigated adverse health effects of multiple air pollutants for a limited number of cities, thus the evidence of the health impacts is limited and it is challenging to compare these results because of different modeling approaches and potential publication bias. In this paper, we expand the number of Canadian cities, with the use of the most recent available health data. A multi-pollutant model in a case-crossover design is used to investigate the short-term impacts of air pollution on various health outcomes in 47 Canadian main cities, comparing three age groups (all-age, senior (age 66+), non-senior). The main findings are that a 14 ppb increase of O 3 was associated with a 0.17%-2.78% (0.62%-1.46%) increase in the odds of all-age respiratory mortality (hospitalization). A 12.8 ppb increase of NO 2 was associated with a 0.57%-1.47% (0.68%-1.86%) increase in the odds of all-age (non-senior) respiratory hospitalization. A 7.6 μgm -3 increase of PM 2.5 was associated with a 0.19%-0.69% (0.33%-1.1%) increase in the odds of all-age (non-senior) respiratory hospitalization., 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., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The coxsackievirus and adenovirus receptor (CAR) is very well known as an epithelial tight junction and cardiac intercalated disc protein; it mediates attachment and infection via the coxsackievirus B3 (CVB3) and type 5 adenovirus. Macrophages play important roles in early immunity during viral infections. However, the role of CAR in macrophages is not well studied in relation to CVB3 infection. In this study, the function of CAR was observed in the Raw264.7 mouse macrophage cell line. CAR expression was stimulated by treatment with lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α). In thioglycollate-induced peritonitis, the peritoneal macrophage was activated and CAR expression was increased. The macrophage-specific CAR conditional knockout mice (KO) were generated from lysozyme Cre mice. The expression of inflammatory cytokine (IL-1β and TNF-α) was attenuated in the KO mice's peritoneal macrophage after LPS treatment. In addition, the virus was not replicated in CAR-deleted macrophages. The organ virus replication was not significantly different in both wild-type (WT) and KO mice at days three and seven post-infection (p.i). However, the inflammatory M1 polarity genes (IL-1β, IL-6, TNF-α and MCP-1) were significantly increased, with increased rates of myocarditis in the heart of KO mice compared to those of WT mice. In contrast, type1 interferon (IFN-α and β) was significantly decreased in the heart of KO mice. Serum chemokine CXCL-11 was increased in the KO mice at day three p.i. compared to the WT mice. The attenuation of IFN-α and β in macrophage CAR deletion induced higher levels of CXCL-11 and more increased CD4 and CD8 T cells in KO mice hearts compared to those of WT mice at day seven p.i. These results demonstrate that macrophage-specific CAR deletion increased the macrophage M1 polarity and myocarditis in CVB3 infection. In addition, chemokine CXCL-11 expression was increased, and stimulated CD4 and CD8 T cell activity. Macrophage CAR may be important for the regulation of innate-immunity-induced local inflammation in CVB3 infection.

Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing., (© 2023. The Author(s).)

Background: A total of 8,303 individuals (4.3%) with adverse reactions (n=191,860) after vaccination developed serious conditions or died. Such health developments could cause people not vaccinated yet or waiting for a booster shot to become fearful of the vaccination., Methods: The 3-month (July-September 2021) clinical data of 41 patients from the family medicine department of a single medical center were analyzed retrospectively to determine risk factors and to investigate the clinical course to identify the cause of symptoms in detail., Results: A significant number of older adults aged over 50 years reported experiencing general weakness (P=0.026) but fewer incidences of fever than patients aged 50 years or younger (P=0.011). Eighteen of the 41 patients were requested to visit more than twice or consult a specialist. In 14 patients, the symptoms were explained by other medical causes., Conclusion: The primary physician has a pivotal role in thoroughly evaluating patients who complain of adverse effects after vaccination, considering the broad multitude of symptoms and medical conditions presented. To thoroughly evaluate and appropriately advise patients with adverse reactions to their chosen vaccine, taking detailed medical history and nutritional counseling are required to identify possible underlying causes, resolve symptoms, and educate them on self-care and regarding vaccines.

PBL plays a critical role in the atmosphere by transferring heat, moisture, and momentum. The warm PBL has a distinct diurnal cycle including daytime convective mixing layer (ML) and nighttime residual layer developments. Thus, for PBL characterization and process study, simultaneous determinations of PBL height (PBLH) and ML height (MLH) are necessary. Here, new approaches are developed to provide reliable PBLH and MLH to characterize warm PBL evolution. The approaches use Raman lidar (RL) water vapor mixing ratio (WVMR) and Doppler lidar (DL) vertical velocity measurements at the Southern Great Plains (SGP) atmospheric observatory, which was established by the Atmospheric Radiation Measurement (ARM) user facility. Compared with widely used lidar aerosol measurements for PBLH, WVMR is a better trace for PBL vertical mixing. For PBLH, the approach classifies PBL water vapor structures into a few general patterns, then uses a slope method and dynamic threshold method to determine PBLH. For MLH, wavelet analysis is used to re-construct 2-D variance from DL vertical wind velocity measurements according to the turbulence eddy size to minimize the impacts of gravity wave and eddy size on variance calculations; then, a dynamic threshold method is used to determine MLH. Remotely-sensed PBLHs and MLHs are compared with radiosonde measurements based on the Richardson number method. Good agreements between them confirm that the proposed new algorithms are reliable for PBLH and MLH characterization. The algorithms are applied to warm seasons' RL and ML measurements at the SGP site for five years to study warm season PBL structure and processes. The weekly composited diurnal evolutions of PBLHs and MLHs in warm climate were provided to illustrate diurnal and seasonal PBL evolutions. This reliable PBLH and MLH dataset will be valuable for PBL process study, model evolution, and PBL parameterization improvement.

Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice's survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and β), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Establishing an appropriate disease model that mimics the complexities of human cardiovascular disease is critical for evaluating the clinical efficacy and translation success. The multifaceted and complex nature of human ischemic heart disease is difficult to recapitulate in animal models. This difficulty is often compounded by the methodological biases introduced in animal studies. Considerable variations across animal species, modifications made in surgical procedures, and inadequate randomization, sample size calculation, blinding, and heterogeneity of animal models used often produce preclinical cardiovascular research that looks promising but is irreproducible and not translatable. Moreover, many published papers are not transparent enough for other investigators to verify the feasibility of the studies and the therapeutics' efficacy. Unfortunately, successful translation of these innovative therapies in such a closed and biased research is difficult. This review discusses some challenges in current preclinical myocardial infarction research, focusing on the following three major inhibitors for its successful translation: Inappropriate disease model, frequent modifications to surgical procedures, and insufficient reporting transparency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shin, Shin and Shudo.)

Coxsackievirus and adenovirus receptor (CAR) is present in epithelial and vascular endothelial cell junctions. We have previously shown a hemorrhagic phenotype in germ-line CAR knock-out mouse embryos; we have also found that CAR interacts with ZO-1 and β-catenin. However, the role of CAR in vascular endothelial junction permeability has not been proven. To understand the roles of CAR in the vascular endothelial junctions, we generated endothelium-specific CAR knockout (CAR-eKO) mice. In the absence of CAR, the endothelial cell layer showed an increase in transmembrane electrical resistance (TER, Ω) and coxsackievirus permeability. Evans blue dye and 70 kDa dextran-FITC were delivered by tail vein injection. We observed increased vascular permeability in the hearts of adult CAR-eKO mice compare with wild-type (WT) mice. There was a marked increase in monocyte and macrophage penetration into the peritoneal cavity caused by thioglycolate-induced peritonitis. We found that CAR ablation in endothelial cells was not significantly increased coxsackievirus B3 (CVB3) induced myocarditis in murine model. However, tissue virus titers were significantly higher in CAR-eKO mice compared with WT. Moreover, CVB3 was detected in the brain of CAR-eKO mice. Endothelial CAR deletion affects the expression of major endothelial junction proteins, such as cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1) in the cultured endothelial cells as well as liver vessel. We suggest that CAR expression is required for normal vascular permeability and endothelial tight junction homeostasis. Furthermore, CVB3 organ penetration and myocarditis severities were dependent on the endothelial CAR level.

Background: The risk of tick-borne diseases is decreased by increasing awareness and knowledge through prevention education. The aim of the present study was to evaluate the effect of long-lasting permethrin impregnated (LLPI) socks for tick bites., Methods: A randomized open label study was conducted to determine the effectiveness of LLPI socks for prevention of tick bites among 367 adults living in a rural area. Participants completed questionnaires at the start of follow-up (July 2014) and at the end of follow-up (December 2014), and tick bites were reported., Results: A total of 332 subjects completed the follow-up survey. The tick bite rate of the two groups was not significantly different (3.6% vs. 3.1%). But the tick bite rate of lower extremities of subjects wearing LLPI socks was significantly lower compared to that of subjects wearing general socks., Conclusion: The tick bite rate was not different between the two groups, but the tick bite rate of lower extremities of LLPI was significantly lower than general groups. Further study is needed to investigate the effect of LLPI clothes with larger populations., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Objective: To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality., Methods: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill., Results: Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant., Conclusions: For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497)., Competing Interests: The authors have declared that no competing interests exist.

Background: Hospitalization and mortality (H-M) have been linked to air pollution separately. However, previous studies have not adequately compared whether air pollution is a stronger risk factor for hospitalization or mortality. This study aimed to investigate differences in H-M risk from short-term ozone and PM 2.5 exposures, and determine whether differences are modified by season, age, and sex., Methods: Daily ozone, PM 2.5 , temperature, and all-cause H-M counts (ICD-10, A00-R99) were collected for 22-24 Canadian cities for up to 29 years. Generalized additive Poisson models were employed to estimate associations between each pollutant and health outcome, which were compared across season (warm, cold, or year-round), age (all ages or seniors > 65), and sex., Results: Overall, ozone and PM 2.5 showed higher season-specific risk of mortality than hospitalization: warm-season ozone: 0.54% (95% credible interval, 0.20, 0.85) vs. 0.14% (0.02, 0.27) per 10 ppb; and year-round PM 2.5 : 0.90% (0.33, 1.41) vs. 0.29% (0.03, 0.56) per 10 μg/m 3 . While age showed little H-M difference, sex appeared to be a modifier of H-M risk. While females had higher mortality risk, males had higher hospitalization risk: for females, ozone 0.87% (0.36, 1.35) vs. -0.03% (-0.18, 0.11) and PM 2.5 1.19% (0.40, 1.90) vs. 0.19% (-0.10, 0.47); and for males ozone 0.20% (-0.28, 0.65) vs. 0.35% (0.18, 0.51)., Conclusion: This study found H-M differences attributable to ozone and PM 2.5 , suggesting that both are stronger risk factors for mortality than hospitalization. In addition, there were clear H-M differences by sex: specifically, females showed higher mortality risk and males showed higher hospitalization risk., 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., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

The combination therapy based on multifunctional nanocomposites has been considered as a promising approach to improve cancer therapeutic efficacy. Herein, we report targeted multi-functional poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites for synergistic chemo-photothermal therapy toward breast cancer cells. To increase the transition temperature, acrylic acid (AAc) was added in synthetic process of PNIPAM, showing that the intrinsic lower critical solution temperature was changed to 42 °C . To generate the photothermal effect under near-infrared (NIR) laser irradiation (808 nm), polypyrrole (ppy) nanoparticles were uniformly decorated in PNIPAM-AAc. Folic acid (FA), as a cancer targeting ligand, was successfully conjugated on the surplus carboxyl groups in PNIPAM network. The drug release of PNIPAM-ppy-FA nanocomposites was efficiently triggered in response to the temperature change by NIR laser irradiation. We also confirmed that PNIPAM-ppy-FA was internalized to MDA-MB-231 breast cancer cells by folate-receptor-mediated endocytosis and significantly enhanced cancer therapeutic efficacy with combination treatment of chemo-photothermal effects. Therefore, our work encourages further exploration of multi-functional nanocarrier agents for synergistic therapeutic approaches to different types of cancer cells.

Background: Findings from previous studies on the association between exposure to fine particulate matter (PM 2.5 ) and the risk of infant mortality were inconsistent. Thus, two main objectives of our study were to examine the association between exposure to PM 2.5 and specified infant mortality and to identify critical trimesters., Methods: We retrospectively created a birth cohort of singleton full-term infants born in South Korea between 2010 and 2015 using national birth and infant mortality data. The specified causes of infant mortality were circulatory and respiratory diseases, perinatal conditions, congenital anomalies, and sudden infant death syndrome. We performed 1:10 propensity score matching for various exposure windows: each trimester, prenatal, and postnatal (up to age 1). Conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while accounting for gestational age, birth weight, maternal education level, season of birth, and regions (metropolitan areas/provinces). We also conducted sex-stratified analyses and used different matching ratios for sensitivity analyses., Results: A total of 2,501,836 births and 761 deaths (0.03%) were identified in the birth cohort. We found an increased risk of infant mortality per 10 µg/m 3 increase in PM 2.5 exposure during the prenatal period (OR: 1.29, 95% CI: 1.07-1.55). Exposure in the 1st and 2nd trimesters was linked to an elevated risk (OR: 1.19, 95% CI: 1.02-1.37; OR: 1.21, 95% CI: 1.04-1.40). However, no association was shown in the third trimester. PM 2.5 exposure in the 1st and 2nd trimesters was associated with elevated male infant mortality, but did not reach statistical significance in female infants. The use of different matching ratios did not significantly affect the results., Conclusion: The study findings suggest that exposure to PM 2.5 could affect infant mortality differently by the timing of exposure and sex, which suggests a relation to fetal development. However, further investigations are warranted., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Nitrogen dioxide (NO 2 ) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO 2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO 2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies., Methods: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I 2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill., Results: Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO 2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052-1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016-1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant., Conclusions: We concluded that there is a likely causal relationship between short term NO 2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.

Aims: Coxsackievirus B3 (CVB3) is known to be an important cause of myocarditis and dilated cardiomyopathy. Enterovirus-2C (E2C) is a viral RNA helicase. It inhibits host protein synthesis. Based on these facts, we hypothesize that the inhibition of 2C may suppress virus replication and prevent enterovirus-mediated cardiomyopathy., Methods and Results: We generated a chemically modified enterovirus-2C inhibitor (E2CI). From the in vitro assay, E2CI was showed strong antiviral effects. For in vivo testing, mice were treated with E2CI intraperitoneally injected daily for three consecutive days at a dose of 8mg/kg per day, after CVB3 post-infection (p.i) (CVB3 + E2CI, n = 33). For the infected controls (CVB3 only, n = 35), mice were injected with PBS (phosphate buffered saline) in a DBA/2 strain to establish chronic myocarditis. The four-week survival rate of E2CI-treated mice was significantly higher than that of controls (92% vs. 71%; p < 0.05). Virus titers and myocardial damage were significantly reduced in the E2CI treated group. In addition, echocardiography indicated that E2CI administration dramatically maintained mouse heart function compared to control at day 28 p.i chronic stage (LVIDD, 3.1 ± 0.08 vs. 3.9 ± 0.09, p < 0.01; LVDS, 2.0 ± 0.07 vs. 2.5 ± 0.07, p < 0.001; FS, 34.8 ± 1.6% vs. 28.5 ± 1.5%; EF, 67. 9 ± 2.9% vs. 54.7 ± 4.7%, p < 0.05; CVB3 + E2CI, n = 6 vs. CVB3, n = 4). Moreover, E2CI is effectively worked in human iPS (induced pluripotent stem cell) derived cardiomyocytes., Conclusion: Enterovirus-2C inhibitor (E2CI) was significantly reduced viral replication, chronic myocardium damage, and CVB3-induced mortality in DBA/2 mice. These results suggested that E2CI is a novel therapeutic agent for the treatment of enterovirus-mediated diseases., Competing Interests: The authors declare no conflict of interest.

Background: The number of children diagnosed with autism spectrum disorder (ASD) has been increasing. Previous studies suggested potential association between pregnancy air pollution exposure and ASD. This systematic review and meta-analysis is intended to summarize the association between maternal exposure to outdoor air pollution and ASD in children by trimester based on recent studies., Methods: A systematic literature search in 3 databases (Medline, Embase, and Web of Science) was performed using subject headings related to ASD and air pollution since 2007. Eligible studies were screened and evaluated based on predetermined criteria. For meta-analyses, the studies were grouped by air pollutant and exposure time (prenatal period and trimesters). Within-group studies were standardized by log odds ratio (OR) and then combined by three meta-analysis methods: frequentist fixed and random effects models, and Bayesian random effects model., Results: Initial search identified 1564 papers, of which 25 studies remained for final analysis after duplicates and ineligible studies were removed. Of the 25 studies, 13, 14, 12, and 7 studies investigated ASD in children associated with PM 2.5 , PM 10 , NO 2 , and ozone, respectively. The frequentist and Bayesian random effects models resulted in different statistical significance. For prenatal period, frequentist meta-analysis returned significant pooled ORs with 95% confidence intervals, 1.06(1.01,1.11) for PM 2.5 and 1.02(1.01,1.04) for NO 2 , whereas Bayesian meta-analysis showed similar ORs with wider 95% posterior intervals, 1.06(1.00,1.13) for PM 2.5 and 1.02(1.00,1.05) for NO 2 . Third trimester appeared to have higher pooled ORs for PM 2.5 , PM 10 , and ozone, but patterns in the time-varying associations over the trimester were inconsistent., Conclusions: For positive association between maternal exposure to ambient air pollution and ASD in children, there is some evidence for PM 2.5 , weak evidence for NO 2 and little evidence for PM 10 and ozone. However, patterns in associations over trimesters were inconsistent among studies and among air pollutants., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Objective: Postmenopausal women show a more atherogenic lipid profile and elevated cardiovascular risk compared to premenopausal women. The aim of this study was to investigate the efficacy and safety of high-dose atorvastatin on the improvement of the blood lipid profile of postmenopausal women in Korea., Methods: This study is a prospective, open-label, single-arm clinical trial that was conducted in 3 teaching hospitals. Postmenopausal women with a moderate-to-high cardiovascular risk, according to guidelines from the Korean Society of Lipid & Atherosclerosis, were enrolled. Participants were administered 20 mg of atorvastatin daily for the first 8 weeks, and if the targeted low-density lipoprotein cholesterol (LDL-C) level was not achieved, the dose was increased to 40 mg for the second 8 weeks. The primary endpoint was percentage change of LDL-C from baseline after 16 weeks of drug administration., Results: Forty-four women were enrolled, 28 of whom (75.6%) had diabetes mellitus. By the end of treatment period (16 weeks) all patients had achieved LDL-C target levels, with 33 (94.2%) of the participants achieving it after only 8 weeks of administration. After 16 weeks, LDL-C decreased by 45.8±16.7% ( p <0.001) from the baseline, and total cholesterol (33.2±10.9%; p <0.001), triglyceride (24.2±37.5%; p =0.001), and apolipoprotein B (34.9±15.6%; p <0.001) also significantly decreased. Blood glucose and liver enzyme levels slightly increased, but none of the participants developed serious adverse events that would cause them to prematurely withdraw from the clinical trial., Conclusion: 20 and 40 mg atorvastatin was effective and safe for treating dyslipidemia in postmenopausal Korean women with moderate-to-high cardiovascular risk., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2020 The Korean Society of Lipid and Atherosclerosis.)

The aim of this study was to assess the potential of a prone chest CT for the evaluation of esophageal cancer, as compared with a routine supine chest CT. 69 patients (67±18 years old) with pathologically confirmed esophageal cancers underwent MDCT in the supine and prone positions. The supine CT was performed first, followed by the prone position. Localization and staging of individual esophageal lesions on both the prone and supine CTs were assessed by two thoracic radiologists, using a scoring system that consisted of three confidence scales, and the results were correlated with the endoscopic and surgical findings. The mean confidence score for the detection of esophageal cancer was higher in the prone position (2.58±0.74) than that in the supine position (2.42±0.83) with statistical significance (p=0.002). The mean confidence score for predicting local invasion in the selected patients (n=18) who underwent esophagectomy was also higher in the prone position (2.39±0.85) than that in the supine position (2.06±0.73) with statistical significance (p=0.01). In 10 of 11 cases that showed definitive determination for periesophageal infiltration or adjacent organ invasion on the prone CT (score 3), the corresponding findings were also observed in the post-operative evaluations. In conclusion, prone chest CT for evaluating esophageal cancer could have advantages in regards to the localization of esophageal cancer and predicting local invasion compared to that of routine supine CT and can improve the diagnostic accuracy of chest CTs., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2020.)

Recently, 3D-stacked dynamic random access memory (DRAM) has become a promising solution for ultra-high capacity and high-bandwidth memory implementations. However, it also suffers from memory wall problems due to long latency, such as with typical 2D-DRAMs. Although there are various cache management techniques and latency hiding schemes to reduce DRAM access time, in a high-performance system using high-capacity 3D-stacked DRAM, it is ultimately essential to reduce the latency of the DRAM itself. To solve this problem, various asymmetric in-DRAM cache structures have recently been proposed, which are more attractive for high-capacity DRAMs because they can be implemented at a lower cost in 3D-stacked DRAMs. However, most research mainly focuses on the architecture of the in-DRAM cache itself and does not pay much attention to proper management methods. In this paper, we propose two new management algorithms for the in-DRAM caches to achieve a low-latency and low-power 3D-stacked DRAM device. Through the computing system simulation, we demonstrate the improvement of energy delay product up to 67%.

Background : An oil refinery in Oakville, Canada, closed over 2004⁻2005, providing an opportunity for a natural experiment to examine the effects on oil refinery-related air pollution and residents' health. Methods : Environmental and health data were collected for the 16 years around the refinery closure. Toronto (2.5 million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were used as control and reference populations, respectively, for Oakville (160,000 persons). We compared sulfur dioxide and age- and season-standardized hospitalizations, considering potential factors such as changes in demographics, socio-economics, drug prescriptions, and environmental variables. Results : The closure of the refinery eliminated 6000 tons/year of SO₂ emissions, with an observed reduction of 20% in wind direction-adjusted ambient concentrations in Oakville. After accounting for trends, a decrease in cold-season peak-centered respiratory hospitalizations was observed for Oakville (reduction of 2.2 cases/1000 persons per year, p = 0.0006 ) but not in Toronto (p = 0.856) and the GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post closure appeared to have no observed link to known confounders or effect modifiers. Conclusion : The refinery closure allowed an assessment of the change in community health. This natural experiment provides evidence that a reduction in emissions was associated with improvements in population health. This study design addresses the impact of a removed source of air pollution.

The Air Health Trend Indicator is designed to estimate the public health risk related to short-term exposure to air pollution and to detect trends in the annual health risks. Daily ozone, circulatory hospitalizations and weather data for 24 cities (about 54% of Canadians) for 17 years (1996⁻2012) were used. This study examined three circulatory causes: ischemic heart disease (IHD, 40% of cases), other heart disease (OHD, 31%) and cerebrovascular disease (CEV, 14%). A Bayesian hierarchical model using a 7-year estimator was employed to find trends in the annual national associations by season, lag of effect, sex and age group (≤65 vs. >65). Warm season 1-day lagged ozone returned higher national risk per 10 ppb: 0.4% (95% credible interval, -0.3⁻1.1%) for IHD, 0.4% (-0.2⁻1.0%) for OHD, and 0.2% (-0.8⁻1.2%) for CEV. Overall mixed trends in annual associations were observed for IHD and CEV, but a decreasing trend for OHD. While little age effect was identified, some sex-specific difference was detected, with males seemingly more vulnerable to ozone for CEV, although this finding needs further investigation. The study findings could reduce a knowledge gap by identifying trends in risk over time as well as sub-populations susceptible to ozone by age and sex.

The purpose of the study is to assess poststroke muscle structural alterations by examining muscular electrical conductivity and inherent electrophysiological properties. In particular, muscle impedance and compound muscle action potentials (CMAP) were measured from the hypothenar muscle bilaterally using the electrical impedance myography and the electrophysiological techniques, respectively. Significant changes of muscle impedance were observed in the paretic muscle compared with the contralateral side (resistance: paretic: 27.54 ± 0.97 Ω, contralateral: 25.46 ± 0.91 Ω, p  < 0.05; phase angle: paretic: 8.81 ± 0.61°, contralateral: 10.79 ± 0.69°, p  < 0.05). In addition, impedance changes correlated moderately with the CMAP amplitude in the paretic hand (phase angle: r  = 0.66, p  < 0.05; reactance: r  = 0.58, p  < 0.05). The study discloses significant muscle rearrangements as a result of fiber loss or atrophy, fat infiltration or impaired membrane integrity in chronic stroke.

The total dinoflagellate cyst community and the cysts of Cochlodinium polykrikoides in the surface sediments of South Sea (Tongyeong coast), South Korea, were analysed using next-generation sequencing (NGS) and morphological approaches. Dinoflagellate cysts can be highly abundant (111-4,087 cysts g -1 dry weight) and have diverse species composition. A total of 35 taxa of dinoflagellate cysts representing 16 genera, 21 species (including four unconfirmed species), and 14 complex species were identified by NGS analysis. Cysts of Scrippsiella spp (mostly Scrippsiella trochoidea) were the most dominant and Polykrikos schwartzii, Pentapharsodinium dalei, Ensiculifera carinata, and Alexandrium catenella/tamarense were common. Thus, a combination of NGS and morphological analysis is effective for studying the cyst communities present in a given environment. Although C. polykrikoides developed massive blooms during 2013-2014, microscopy revealed low density of their cysts, whereas no cysts were detected by NGS. However, the vegetative C. polykrikoides not appeared during 2015-2017 in spite of the observation of C. polykrikoides cysts. This suggests that the C. polykrikoides blooms were not due to development of their cysts but to other factors such as currents transporting them to a marine environment suitable for their growth.

Micrometer-resolution mass spectrometric imaging of live hippocampal tissue is achieved with a highly efficient desorption of biomolecules using a 532 nm continuous wave laser and gold nanoparticles or graphene oxide as an energy transporter, which enables clear identification of the distributions of monoacylglycerol, adenine, cholesterol, sphingosine and ceramide., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Despite the importance of understanding the bloom mechanisms that influence cyanobacterial toxin production, the dynamics of toxic Microcystis subpopulations are largely unknown. Here, we quantified both toxic and entire (i.e., toxic and non-toxic) Microcystis populations based on the microcystin synthetase E (mcyE) and 16S ribosomal RNA genes. Samples were collected from pelagic water and sediments twice per week from October to December 2011, and we investigated the effects of physicochemical factors (pH, water temperature, dissolved oxygen, nutrients, etc.) and biological factors (ciliates and zooplankton) on the abundance of toxic and non-toxic Microcystis. During the study period, Microcystis blooms were composed of toxic and non-toxic subpopulations. Resting stage Microcystis in sediment may be closely linked to Microcystis populations in pelagic water and may contribute to the toxic subpopulation composition in surface Microcystis blooms. In pelagic water, the toxic and entire Microcystis population had a significant positive correlation with the pH and water temperature (p < 0.05). However, their responses to changes in environmental factors were thought to be distinct. The ratio of the toxic to non-toxic Microcystis subpopulations was significantly (p < 0.05) enhanced by a lower pH and water temperature and an increase in protozoan grazers, reflecting environmental stresses. These results suggest that the toxic and non-toxic subpopulations of Microcystis have distinct tolerance levels against these stressors. The intracellular microcystin (MC) concentration was positively associated with the abundance of the mcyE-positive Microcystis. By comparison, the MC concentration in pelagic water body (extracellular) increased when Microcystis was lysed due to environmental stresses.

Background: The rising prevalence of atopic diseases implies a strong influence of environmental determinants. Epidemiological studies have identified several early life exposures that appear to influence the risk of developing atopic sensitization, but the combined influence of these exposures is unknown. We sought to estimate the proportion of atopy that could be attributed to common childhood exposures associated with atopic sensitization in adolescence and young adulthood., Methods: Atopic sensitization was measured by skin-prick tests for common aeroallergens in a population-based New Zealand birth cohort at ages 13 and 32 years. The independent effects of previously identified risk and protective factors for atopic sensitization were assessed using multiple logistic regression. Population attributable fractions were calculated for atopic sensitization in childhood and adulthood., Results: Tobacco smoke exposure, dog and cat ownership, nail-biting and thumb-sucking, attending pre-school day care, and household crowding were associated with a lower risk of atopic sensitization whereas breastfeeding was associated with a higher risk. Population attributable fractions for combined effects of these environmental factors suggest that they may account for 58% of atopic sensitization at age 13 and 49% at age 32 years., Conclusions: A substantial proportion of atopic sensitization appears to be attributable to common childhood environmental and lifestyle factors, and the influence of these exposures persists into adulthood. The absolute risks attributable to these exposures will be different in other cohorts and we cannot assume that these associations are necessarily causal. Nevertheless, the findings suggest that identifiable childhood environmental factors contribute substantially to atopic sensitization., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)