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Protease-activated receptor 2 (PAR2) has garnered attention as a potential therapeutic target in breast cancer. PAR2 is implicated in the activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) via G protein and beta-arrestin pathways, contributing to the proliferation and metastasis of breast cancer cells. Despite the recognized role of PAR2 in breast cancer progression, clinically effective PAR2 antagonists remain elusive. To address this unmet clinical need, we synthesized and evaluated a series of novel compounds that target the orthosteric site of PAR2. Using in silico docking simulations, we identified compound 9a, an optimized derivative of compound 1a ((S)-N-(1-(benzylamino)-1-oxo-3-phenylpropan-2-yl)benzamide), which exhibited enhanced PAR2 antagonistic activity. Subsequent molecular dynamics simulations comparing 9a with the partial agonist 9d revealed that variations in ligand-induced conformational changes and interactions dictated whether the compound acted as an antagonist or agonist of PAR2. The results of this study suggest that further development of 9a could contribute to the advancement of PAR2 antagonists as potential therapeutic agents for breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To describe the rate, timing, and pattern of changes in advance directives (ADs) of do not resuscitate (DNR) and do not hospitalize (DNH) orders among new admissions to nursing homes (NHs)., Design: A retrospective cohort study., Setting and Participants: Admissions to all publicly funded NHs in Ontario, Canada, between January 1, 2013, and December 31, 2017., Methods: Residents were followed until discharged from incident NH stay, death, or were still present at the end of study (December 31, 2019). They were categorized into 3 mutually exclusive baseline composite AD groups: Full Code, DNR Only, and DNR+DNH. We used Poisson regression models to estimate the incidence rate ratios of AD change between different AD groups and different decision makers for personal care, adjusted for baseline clinical and sociodemographic variables., Results: A total of 102,541 NH residents were eligible for inclusion. Residents with at least 1 AD change accounted for 46% of Full Code, 30% of DNR Only, and 25% of DNR+DNH group. Median time to first AD change ranged between 26 and 55 weeks. For Full Code and DNR Only residents, the most frequent change was to an AD 1 level lower in aggressiveness or intervention, whereas for DNR+DNH residents the most frequent change was to DNR Only. About 16% of residents had 2 or more AD changes during their stay. After controlling for covariates, residents with a DNR-only order or DNR+DNH orders at admission and those with a surrogate decision maker were associated with lower AD change rates., Conclusions and Implications: Measuring AD adherence rates that are documented only at a particular time often underestimates the dynamics of AD changes during a resident's stay and results in an inaccurate measure of the effectiveness of AD on resident care. There should be more frequent reviews of ADs as they are quite dynamic. Mandatory review after an acute change in a resident's health would ensure that ADs are current., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A rigid fluorophore unit of Julolidine/coumarin fused with an indolium-conjugated system was built for the immediate and effective recognition of cyanide ions in a 90 % aq. DMSO solution. The probes are capable of displaying better sensitivity/selectivity for the cyanide ion over a wide range of other interfering ions. The probe JI showed an instant colorimetric variation, whereas the modified probe JCI showed both colorimetric and fluorimetric variation with cyanide ion. The observed detection limit values indicated excellent sensitivity of the probe to the cyanide ion. HRMS and 1 H NMR studies confirmed that the mechanism of detection of CN - is via the nucleophilic attack on the electron-deficient indolium moiety of the molecule. Moreover, the probes are well proficient in selective recognition of cyanide in various real time applications (test strips, electronic sensor kit, food and water sample analysis)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort., Patients and Methods: Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1., Results: A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis., Conclusions: Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients., Competing Interests: Disclosure IM reports consultancy fees from AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, EMD Serono, F-Star, Genmab, Gossamer Bio, Lilly, Merck Sharp & Dohme, Numab, PharmaMar, Roche, Tusk Therapeutics, Highlight Therapeutics, Alligator Bioscience, Genentech, CatalYm GmbH, BioLineRx, Boston Pharma, Janssen, HotSpot Therapeutics, Inc., ImmuneSensor Therapeutics, Inc., and Monopteros Therapeutics; honoraria from Alligator Biosciences, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Lilly, Roche/Genentech, Tusk Therapeutics, Moderna, and CatalYm GmbH; travel support from Bristol Myers Squibb, Incyte, Merck Sharp & Dohme, and Roche/Genentech; and research grants from Alligator Biosciences, Bristol Myers Squibb, AstraZeneca, Genmab, Pfizer, and Roche/Genentech. TY reports consultancy fees from AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme Oncology. YKK reports consulting fees from ALX Oncology, Amgen, Blueprint, Bristol Myers Squibb, Daehwa, MacroGenics, Merck, Novartis, Roche, Surface Oncology, and Zymeworks. TYK is the founder of IMBdx, Inc. and has received research funds from Bayer Korea. AS reports consulting role at Bayer, Bristol Myers Squibb, Eisai, Gilead Sciences, Incyte, Merck Sharp & Dohme, Pfizer, Sanofi, and Servier; and speakers’ bureau participation for AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Eisai, Gilead Sciences, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Servier, and Takeda. BS reports consultancy fees from Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Eisai, Eli Lilly, Incyte, Ipsen, Novartis, Roche, Sirtex Medical, Terumo; speaker fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Incyte, Ipsen, Roche, Sirtex Medical, and Terumo; and research grants (to institution) from Bristol Myers Squibb and Sirtex Medical. MK reports consultancy fees from Chugai, Roche, Eisai, and AstraZeneca; speaker fees from Eli Lilly, Bayer, Eisai, Chugai, Takeda, and AstraZeneca; research grants (to institution) from Taiho, Otsuka, EA Pharma, AbbVie, Eisai, Chugai, GE Healthcare, and Ono Pharmaceutical Company. AM reports consulting role at Bayer, Eisai, Merck Sharp & Dohme, Roche, and Sirtex Medical; and speakers’ bureau participation for Bayer, Boston Biologics, Eisai, Merck Sharp & Dohme. FT reports consultancy role for Ipsen, Eisai, and Roche. JK reports consultancy fees from AstraZeneca, Ibsen, Taiho, and Hoffman-La Roche; and research support from AstraZeneca, Merck, Ibsen, and Roche. ARH reports consulting role at Eisai, Genentech/Roche, and Merck; speakers’ bureau participation for Bristol Myers Squibb, Eisai, and Exelixis; and research grants from Genentech and Merck. BER reports research grants from AstraZeneca, Bristol Myers Squibb, EUSA Pharmaceuticals, Exelixis, Merck, Novartis, and Xencor; consulting fees from AstraZeneca, Bristol Myers Squibb, Deciphera, Ipsen, NeoGenomics, Roche, and Seagen; and advisory role at Exelixis. HYL reports honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Medarex, Eisai, and MSD Oncology; consulting role at AstraZeneca, Bayer, Bristol Myers Squibb, and Eisai; and speakers’ bureau participation for Bayer. SS, JY, JN, and MT report being employees of and owning stock in Bristol Myers Squibb. CH reports honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Ono Pharmaceuticals, Eisai, Ipsen, Merck Sharp & Dohme, Novartis, PharmaEngine, Roche, and TTY Biopharm. ABEK reports consultancy fees from ABL Bio, Agenus, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Eisai, Exelixis, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, Qurient, Roche, Senti Biosciences, Servier, and Tallac Therapeutics; honoraria from ABL Bio, Agenus, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Eisai, Exelixis, EMD Serono, Gilead Sciences, Merck, Roche/Genentech, QED Therapeutics, Qurient, Roche, Senti Biosciences, Servier, and Tallac Therapeutics; and research grants from AstraZeneca, Astex Pharmaceuticals, and Fulgent Genetics. All other authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to investigate the mediating effect of distress on the relationship between stigma and quality of life (QOL) in lung cancer patients, and to explore the moderated mediating effect of social support., Methods: A total of 184 individuals diagnosed with primary lung cancer participated in the study. Data on general and disease-related characteristics, stigma, distress, QOL, and social support were collected using a comprehensive structured questionnaire. Medical records were also utilized for an in-depth analysis of disease-related attributes. The data were meticulously analyzed using the SPSS PROCESS macro ver. 3.4 for detailed insights., Results: The findings elucidated a clear pathway whereby stigma negatively impacted patients' QOL through the mediating effect of distress. Interestingly, the extent of this impact was significantly influenced by the presence of friendship support, underscoring its unique moderated mediating role. Conversely, support from family and health care professionals did not demonstrate a significant influence in this context., Conclusions: These findings underscore the importance of addressing stigma and distress to improve the QOL of lung cancer patients. The study highlights the pivotal role of friendship support in moderating this relationship, suggesting the need for tailored interventions to strengthen social networks. These insights provide valuable guidance for developing more nuanced and effective patient support strategies in oncology care., (© 2024 The Author(s).)

Background: Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described., Methods: We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6 years without having undergone Fontan procedure. The primary outcome was heart failure events, defined as heart transplant listing or death attributable to heart failure. Symptomatic heart failure for participants surviving 10 or more years was also assessed utilizing the Pediatric Quality of Life Inventory (PedsQL)., Results: Of the 345 participants who underwent a Fontan operation or survived to 6 years without Fontan, 25 (7.2%) had a heart failure event before the age of 12 years. Among these, 21 were listed for heart transplant, and 4 died from heart failure. Nineteen participants underwent heart transplant, all of whom survived to age 12 years. Factors associated with a heart failure event included longer Norwood hospital length of stay, aortic atresia, and no Fontan operation by age 6 years. Assessment of heart failure symptoms at 12 years of age revealed that 24 (12.2%) of 196 PedsQL respondents "often" or "almost always" had difficulty walking more than one block., Conclusions: Heart failure events occur in over 5% of children with palliated HLHS between preschool age and adolescence. Outcomes for children listed for transplant are excellent. However, a substantial portion of palliated HLHS children have significant symptoms of heart failure at 12 years of age., (Copyright © 2023. Published by Elsevier Inc.)

Multifunctional membranes S7P0.7, S7P3.0, and dual membranes composed of soya protein isolate (SPI) and polyethylene oxide (PEO) were produced for wound dressing applications. The internal structure of the membranes was confirmed by scanning electron microscopy (SEM) to be homogeneous and coarser with a porous-like network. S7P3.0 showed the tensile strength of 0.78 ± 0.04 MPa. In the absence of antibiotics, the dual membrane (combination of S7P0.7 and S7P3.0) exhibited potential antibacterial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. Hemolysis quantitative data presented in the image demonstrates that all samples exhibited hemolysis levels below 5 %. Dual membrane showed 77.93 ± 9.5 % blood uptake which reflects its absorption capacity. The combination of S7P0.7 and S7P3.0 influenced the dual membrane's antibacterial, biocompatibility, and good hemolytic potentials. The dual membranes' promising histology features after implantation suggest they could be used as wound dressings., 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.)

Over the last few decades, pollution levels in aquatic environments due to heavy metal ions and micro/nanoplastics have increased owing to industrial development, causing adverse effects on microorganisms. Adsorbent-based filtration is a well-developed technique for removing contaminants from aquatic environments. However, this technique should be improved from the perspectives of eco-friendliness and cost-effectiveness, as commercial adsorbents require energy-intensive synthesis and post-processing with chelating agents. In this study, an eco-friendly filtration system was developed. This system employs biodegradable, natural materials, such as diatomite to remove metal ions and micro/nanoplastics and polycaprolactone (PCL) to make the free-form shapes. The filter removes metal ions via adsorption and micro/nanoplastics via physical size filtration and adsorption. This PCL-bound diatomite filter was fabricated from a mixture of acetone, PCL, and diatomite, varying its size, thickness, shape, and stacking number for a particular objective and usage. The adsorption capacity, kinetics, and permeation flux of the membrane were measured, and the stacking number of the membranes were optimized to maximize the removal efficiency of the target contaminants. This filter is completely biodegradable, as indicated by the degradation of the PCL binder within 60 days in water, without any treatment. The degradable, eco-friendly PCL-bound diatomite filter is a low-cost and sustainable component that can be utilized in various applications, especially potable drinking water production from river in developing country and filtering the micro/nanoplastics from the commercially bottled drinking water in daily life., Competing Interests: Declaration of competing interest The authors declare no competing financial interest. This article has patent issued to Korea Institute of Machinery and Materials, which is published at KR102551040B1., (Copyright © 2023. Published by Elsevier B.V.)

Since the Geostationary Ocean Color Imager (GOCI) was successfully launched in 2010, the GOCI Yonsei aerosol retrieval (YAER) algorithm has been continuously updated to retrieve hourly aerosol optical properties. GOCI-II has 4 more channels including UV, finer spatial resolution (250 m), and daily full disk coverage as compared to GOCI, and was launched in February 2020, onboard the GEO-KOMPSAT-2B (GK-2B) satellite. In this study, we extended the YAER algorithm to GOCI-II data based on its improved performance in many aspects and present the first results of aerosol optical properties retrieved from GOCI-II data. Utilizing the overlapping period between the GOCI-II and GOCI in geostationary Earth orbit, we present GOCI-II aerosol retrievals for high aerosol-loading cases over East Asia and show that these have a consistent spatial distribution with those from GOCI. Furthermore, GOCI-II provides AOD at an even higher spatial resolution, revealing finer changes in aerosol concentrations. Validation results for one year data show that the GOCI-II AOD has a correlation coefficient of 0.83 and a ratio within the expected error (EE) of 59.4 % when compared with the aerosol robotic network (AERONET) data. We compared statistical metrics for the GOCI and GOCI-II AODs to assess the consistency between the two datasets. In addition, it was found that there is a strong correlation between the two datasets from the comparison of gridded GOCI and GOCI-II AOD products. It is expected that data from GOCI-II will continue long-term aerosol records with high accuracy that can be used to address air-quality issues over East Asia., 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 B.V. All rights reserved.)

Ganglioside GM3 is a simple monosialoganglioside (NeuAc-Gal-Glc-ceramide) that modulates cell adhesion, proliferation, and differentiation. Previously, we reported isolation of GM3-binding vascular endothelial growth factor receptor and transforming growth factor-β receptor by the T7 phage display method (Chung et al., 2009; Kim et al., 2013). To further identify novel proteins interacting with GM3, we extended the T7 phage display method in this study. After T7 phage display biopanning combined with immobilized biotin-labeled 3'-sialyllactose prepared on a streptavidin-coated microplate, we isolated 100 candidate sequences from the human lung cDNA library. The most frequently detected clones from the blast analysis were the human nucleolar and coiled-body phosphoprotein 1 (NOLC1) sequences. We initially identified NOLC1 as a molecule that possibly binds to GM3 and confirmed this binding ability using the glutathione S-transferase fusion protein. Herein, we report another GM3-interacting protein, NOLC1, that can be isolated by the T7 phage display method. These results are expected to be helpful for elucidating the functional roles of ganglioside GM3 with NOLC1. When human breast cancer MCF-7 cells were examined for subcellular localization of NOLC1, immunofluorescence of NOLC1 was observed in the intracellular region. In addition, NOLC1 expression was increased in the nucleolus after treatment with the anticancer drug doxorubicin. GM3 and NOLC1 levels in the doxorubicin-treated MCF-7 cells were correlated, indicating possible associations between GM3 and NOLC1. Therefore, direct interactions between carbohydrates and cellular proteins can pave the path for new signaling phenomena in biology., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Accurate gait detection is crucial in utilizing the ample health information embedded in it. Vision-based approaches for gait detection have emerged as an alternative to the exacting sensor-based approaches, but their application has been rather limited due to complicated feature engineering processes and heavy reliance on lateral views. Thus, this study aimed to find a simple vision-based approach that is view-independent and accurate. A total of 22 participants performed six different actions representing standard and peculiar gaits, and the videos acquired from these actions were used as the input of the deep learning networks. Four networks, including a 2D convolutional neural network and an attention-based deep learning network, were trained with standard gaits, and their detection performance for both standard and peculiar gaits was assessed using measures including F 1 -scores. While all networks achieved remarkable detection performance, the CNN-Transformer network achieved the best performance for both standard and peculiar gaits. Little deviation by the speed of actions or view angles was found. The study is expected to contribute to the wider application of vision-based approaches in gait detection and gait-based health monitoring both at home and in clinical settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyung-Ryoul Mun reports financial support was provided by Korea Institute of Science and Technology., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite significant advancements made in cardiovascular stents, restenosis, thrombosis, biocompatibility, and clinical complications remain a matter of concern. Herein, we report a biodegradable Mg alloy stent with a dual effect of the drug (Paclitaxel) and growth factor (VEGF) release. To mitigate the fast degradation of Mg alloy, inorganic and organic coatings were formed on the alloy surface. The optimized hierarchal sequence of the coating was the first layer consisting of magnesium fluoride, followed by poly(l-lactide) and hydroxyapatite coating, and finally sealed by a polycaprolactone layer (MgC). PLLA and HAp were used to increase the adhesion strength and biocompatibility of the coating. Paclitaxel and VEGF were loaded in the final PCL layer (Mg-C/PTX-VEGF). As compared to bare Mg alloy (28 % weight loss), our MgC system showed (3.1 % weight loss) successful decrease in the degradation rate. Further, the in vitro biocompatibility illustrated the highly biocompatible nature of our drug and growth factor-loaded system. The in vivo results displayed that the drug loading decreased the inflammation and neointimal hyperplasia as indicated by the α-SMA and CD-68 antibody staining. The growth factor helped in the endothelialization which was established by the FLKI and ICAM antibody staining of the tissue., 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. Published by Elsevier B.V.)

Introduction: Selecting a patient-specific sequencing strategy to maximize survival outcomes is a clinically unmet need for patients with castration-resistant prostate cancer (CRPC). We developed and validated an artificial intelligence-based decision support system (DSS) to guide optimal sequencing strategy selection., Patients and Methods: Clinicopathological data of 46 covariates were retrospectively collected from 801 patients diagnosed with CRPC at 2 high-volume institutions between February 2004 and March 2021. Cox-proportional hazards regression survival (Cox) modeling in extreme gradient boosting (XGB) was used to perform survival analysis for cancer-specific mortality (CSM) and overall mortality (OM) according to the use of abiraterone acetate, cabazitaxel, docetaxel, and enzalutamide. The models were further stratified into first-, second-, and third-line models that each provided CSM and OM estimates for each line of treatment. The performances of the XGB models were compared with those of the Cox models and random survival forest (RSF) models in terms of Harrell's C-index., Results: The XGB models showed greater predictive performance for CSM and OM compared to the RSF and Cox models. C-indices of 0.827, 0.807, and 0.748 were achieved for CSM in the first-, second-, and third-lines of treatment, respectively, while C-indices of 0.822, 0.813, and 0.729 were achieved for OM regarding each line of treatment, respectively. An online DSS was developed to provide visualization of individualized survival outcomes according to each line of sequencing strategy., Conclusion: Our DSS can be used in clinical practice by physicians and patients as a visualized tool to guide the sequencing strategy of CRPC agents., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Natural biopolymers have attracted considerable attention in a variety of biomedical applications. Herein, tempo-oxidized-cellulose nanofibers (T) were incorporated into sodium alginate/chitosan (A/C) to reinforce the physicochemical properties and further modified with decellularized skin extracellular matrix (E). A unique ACTE aerogel was successfully prepared, and its nontoxic behavior was validated using mouse fibroblast L929 cells. In vitro hemolysis results revealed excellent platelet adhesion and fibrin network formation abilities of the obtained aerogel. A high speed of homeostasis was attained based on the quick clotting in <60 s. Skin regeneration in vivo experiments were conducted using the ACT1E0 and ACT1E10 groups. In comparison to ACT1E0 samples, ACT1E10 samples demonstrated enhanced skin wound healing with increased neo-epithelialization, increased collagen deposition, and extracellular matrix remodeling. ACT1E10 was found to be a promising aerogel for skin defect regeneration due to its improved wound-healing ability., 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.)

Various health-related effects of long-chain (LC) ω-3 PUFAs, EPA, and DHA have been suggested. LC ω-3 PUFAs reduce TG concentrations and have anti-inflammatory, immunomodulatory, antiplatelet, and vascular protective effects. Controversially, they might help in restoring glucose homeostasis via the gut microbiota. However, previous studies have not shown the clear benefits of LC ω-3 PUFAs for CVDs. REDUCE-IT and STRENGTH-representative randomized controlled trials (RCTs) that examined whether LC ω-3 PUFAs would prevent major adverse cardiovascular (CV) events (MACE)-showed conflicting results with differences in the types, doses, or comparators of LC ω-3 PUFAs and study populations. Therefore, we performed a meta-analysis using major RCTs to address this inconsistency and assess the clinical and biological effects of LC ω-3 PUFAs. We included RCTs that involved ≥500 participants with ≥1 y follow-up. Of 17 studies involving 143,410 people, LC ω-3 PUFA supplementation showed beneficial effects on CV death (RR: 0.94; 95% CI: 0.88, 0.99; P = 0.029) and fatal or nonfatal MI (RR: 0.83; 95% CI: 0.72, 0.95; P = 0.010). RCTs on EPA alone showed better results for 3-point MACE, CV death, and fatal or nonfatal MI. However, the benefits were not found for fatal or nonfatal stroke, all-cause mortality, and hospitalization for heart failure. Of note, studies of both the EPA/DHA combination and EPA alone showed a significant increase in risk of new-onset atrial fibrillation. Thus, well-designed studies are needed to investigate the underlying mechanisms involved in the distinct effects of EPA compared with DHA on cardiometabolic diseases. This review discusses the potential benefits and safety of LC ω-3 PUFAs from a cardiometabolic perspective focusing on recent updates and controversies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Giselleligne is the world's first multiphasic gel product that evenly surrounds particles. In the current study, Giselleligne was compared with other existing fillers to evaluate their clinical use, safety, and ability to improve midface volume deficits of Asian individuals., Methods: A comparative experiment was conducted to gain an understanding of the physical properties of Giselleligne, which is a multilayered hyaluronic acid filler, and to compare its properties with those of existing hyaluronic acid fillers. The primary outcome of this study was a Midface Volume Deficit Scale (MFVDS) score improvement at 24 weeks after the procedure. The secondary outcomes were as follows: MFVDS score improvement after the procedure; MFVDS score changes after the procedure; Global Esthetic Improvement Scale (GAIS) scores as evaluated by the operator after the procedure; the operator's satisfaction with the product; evaluation of the GAIS scores by the patient after the procedure; and pain level of the patient on the day of the procedure., Results: Giselleligne exhibited properties that are expected to result in significantly superior clinical outcomes compared to existing products. Giselleligne was superior not only to the existing products but also in terms of global esthetic improvement, effect duration, and operator satisfaction. Furthermore, Giselleligne was found significantly safer than the existing products., Conclusion: Giselleligne is a safer, more user-friendly, and more effective alternative to existing products for improving the midfacial volume., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Emerging evidence supports an association between heat exposure and acute kidney injury (AKI). However, there is a paucity of studies on the association between cold exposure and AKI., Objective: We aimed to investigate the associations of cold exposure with hospital admission and mortality due to AKI and to explore whether these associations were influenced by age and sex., Methods: Information on daily counts of hospital admission and mortality due to AKI in 16 regions of Korea during the cold seasons (2010-2019) was obtained from the National Health Insurance Service (a single national insurer providing universal health coverage) and Statistics Korea. Daily mean temperature and relative humidity were calculated from hourly data obtained from 94 monitoring systems operated by the Korean Meteorological Administration. Associations of low temperatures (<10th percentile of daily mean temperature) and cold spells (≥2 consecutive days with <5th percentile of daily mean temperature) up to 21 days with AKI were estimated using quasi-Poisson regression models adjusted for potential confounders (e.g., relative humidity and air pollutants) with distributed lag models and univariate meta-regression models., Results: Low temperatures were associated with hospital admission due to AKI [relative risk (RR) = 1.12, 95 % confidence interval (CI): 1.09, 1.16]. Cold spells were associated with hospital admission (RR = 1.87, 95 % CI: 1.46, 2.39) and mortality due to AKI (RR = 4.84, 95 % CI: 1.30, 17.98). These associations were stronger among individuals aged ≥65 years than among those aged <65 years., Conclusion: Our results underscore the need for the general population, particularly the elderly, physicians, and other healthcare providers to be more vigilant to cold exposure, given the risk of AKI. Government agencies need to develop specific strategies for the prevention and early detection of cold exposure-related AKI., 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 Elsevier B.V. All rights reserved.)

Background: We analyzed the FGF/FGFR and co-alteration cancer landscape, hypothesizing that combination therapy might be useful in the presence of co-drivers., Materials and Methods: We describe FGF/FGFR-altered pathways, prognosis, and co-alterations [cBioPortal (N = 7574)] and therapeutic outcomes [University of California San Diego Molecular Tumor Board (MTB) (N = 16)]., Results: Patients whose cancers harbored FGF/FGFR alterations (N = 1074) versus those without them (N = 6500) had shorter overall survival (OS) (median: 23.1 versus 26.4 months, P = 0.038) (cBioPortal). Only 6.1% (65/1074 patients) had no pathogenic co-alterations accompanying FGF/FGFR axis abnormalities. The most frequently co-altered pathways/genes involved: TP53 (70%); cell cycle (58%); PI3K (55%); and receptor tyrosine kinases and mitogen-activated protein kinase (MAPK) (65%). Harboring alterations in both FGF/FGFR and in the TP53 pathway or in the cell cycle pathway correlated with shorter OS (versus FGF/FGFR-altered without those co-altered signals) (P = 0.0001 and 0.0065). Four of 16 fibroblast growth factor receptor (FGFR) inhibitor-treated patients presented at MTB attained durable partial responses (PRs) (9, 12, 22+, and 52+ months); an additional two, stable disease (SD) of ≥6 months (13+ and 15 months) [clinical benefit rate (SD ≥ 6 months/PR) = 38%]. Importantly, six patients with cyclin pathway co-alterations received the CDK4/6 inhibitor palbociclib (75 mg p.o. 3 weeks on, 1 week off) and the multikinase FGFR inhibitor lenvatinib (10 mg p.o. daily); three (50%) achieved a PR [9 (ovarian), 12 (biliary), and 52+ months (osteosarcoma)]. Palbociclib and lenvatinib were tolerated well., Conclusions: FGF/FGFR alterations portend a poor prognosis and are frequently accompanied by pathogenic co-aberrations. Malignancies harboring co-alterations that activate both cyclin and FGFR pathways can be co-targeted by CDK4/6 and FGFR inhibitors., (Published by Elsevier Ltd.)

With the rising environmental concern, sustainable chemistry should be accomplished by considering technical, economic, and environmental factors that guarantee the successful implementation of new alternative products. Hence, we performed the integrated techno-economic and life cycle assessment for two-step solvothermal liquefaction (two-pot synthesis) and simplified solvothermal liquefaction (one-pot synthesis) based on experiment results. Based on the itemized cost estimation, the unit biopolyol production costs obtained from the two-pot synthesis and one-pot synthesis were 10.0 $ kg -1 and 2.89 $ kg -1 , respectively. To provide techno-economic guidelines for biopolyol production, profitability analysis, and uncertainty analysis were used to identify the economic feasibility of the proposed processes. In addition, the life cycle assessment results indicated that biopolyol production via the two-pot synthesis leads to a slightly lower greenhouse gas emission compared with the one-pot synthesis, which further required the use of an analytic hierarchy process to determine the best process for biopolyol production depending on the different weight points in the economic and environmental aspects. From these results, we can provide the technical performance, economic feasibility, and environmental impact of lab-scale biopolyol production from silvergrass residue, a low-cost waste of biomass saccharification., 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 Elsevier B.V. All rights reserved.)

The waste solvent is unavoidably generated from the high solvent dependable processes. One of them is the semiconductor industry. The waste solvent is frequently incinerated to eliminate hazardous waste and this practice raises the issue of environmental and treatment costs. Thus, recovery of waste solvent is a substantial environmental mitigation option. This study explores the recovery of multicomponent waste solvents from the semiconductor industry. To achieve a greener and energy-efficient process, the recovery process is proposed through investigation of mixture thermodynamic behavior, process design, optimization, economics, and integration of renewable energy for environmental advantages. Herein, Distillation, a practical technology option for solvent recovery, with green solvent for extractive distillation and a new approach using renewable energy in waste solvent recovery are explored. As the result, waste solvent recovery by distillation with conventional energy exhibits bold advantages to cost and lower carbon process compared to waste disposal. The integration of renewable energy with about 37 % share of conventional energy as the backup indicates the highest annual cost-saving and reduces about 89.4 % of annual carbon emission compared to carbon emission from waste disposal., 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 Elsevier B.V. All rights reserved.)

We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure-activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of saponin-based coronavirus cell entry inhibitors. These findings enabled us to develop minimal saponin-based antiviral agents that are equipotent to the originally discovered platycodin D. We found that our saponin-based antiviral agents inhibited both the endosomal and transmembrane protease serine 2-mediated cell surface viral entries. Cell fusion assay experiment revealed that our newly developed compounds inhibit the SARS-CoV-2 entry by blocking the fusion between the viral and host cell membranes. The effectiveness of the newly developed antiviral agents over various SARS-CoV-2 variants hints at the broad-spectrum antiviral efficacy of saponin-based therapeutics against future coronavirus variants., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Climate change is predicted to increase the frequency, intensity, and duration of extreme cold events in the mid-latitudes. However, although diabetes is one of the most critical metabolic diseases due to its high and increasing prevalence worldwide, few studies have investigated the short-term association between cold exposure and diabetes-related outcomes., Objective: The aim of this study was to investigate the associations between cold spells and their characteristics (intensity, duration, and seasonal timing) and hospital admission and mortality due to diabetes., Methods: This study used claims data from the National Health Insurance Service and cause-specific mortality data from Statistics Korea (2010-2019). Cold spells were defined as ≥2 consecutive days with a daily mean temperature lower than the region-specific 5th percentile during the cold season (November-March). Quasi-Poisson regressions combined with distributed lag models were used to assess the associations between exposures and outcomes in 16 regions across the Republic of Korea. Meta-analyses were conducted to pool the region-specific estimates., Results: Exposure to cold spells was associated with an increased risk of hospital admission [relative risk (RR) = 1.45, 95% confidence interval (CI): 1.26, 1.66] and mortality (RR = 2.02, 95% CI: 1.37, 2.99) due to diabetes. The association between cold spells and hospital admission due to diabetes was stronger for cold spells that were more intense, longer, and occurred later during the cold season. The association between cold spells and diabetes-related mortality was stronger for more intense and longer cold spells., Conclusion: This study emphasizes the importance of developing effective interventions against cold spells, including education on the dangers of cold spells and early alarm systems. Further studies are needed to create real-world interventions and evaluate their effectiveness in improving diabetes-related outcomes., 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 Elsevier B.V. All rights reserved.)

Nutrient enrichment can alleviate productivity limitations and thus substantially increase carbon (C) uptake in northern coniferous forests. Yet, factors controlling stand-to-stand variation of forest ecosystem responses to nutrient enrichment remain unclear. We used five long-term (13 years) nutrient-enrichment experiments across Sweden, where nitrogen (N), phosphorus, and potassium were applied annually to young Norway spruce forests that varied in their baseline ecosystem properties. We measured tree biomass and soil C and N stocks, litterfall C inputs, soil CO 2 efflux, and shifts in composition and biomass of soil microbial communities to understand the links between above and belowground responses to nutrient enrichment. We found that the strongest responses in tree biomass occurred when baseline site productivity was lowest. High increases in tree biomass C stocks were generally balanced by weaker responses in organic soil C stocks. The average ecosystem C-N response rate was 35 kg C kg -1 N added, with a nearly five-fold greater response rate in tree biomass than in soil. The positive nutrient enrichment effects on ecosystem C sinks were driven by a 95% increase in tree biomass C stocks, 150% increase in litter production, 67% increase in organic layer C stocks, and a 46% reduction in soil CO 2 efflux accompanied by compositional changes in soil microbial communities. Our results show that ecosystem C uptake in spruce forests in northern Europe can be substantially enhanced by nutrient enrichment; however, the strength of the responses and whether the enhancement occurs mainly in tree biomass or soils are dependent on baseline forest productivity., 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.)

Objective: This study aimed to compare how children with overweight or obesity and their parents perceive the obesity-related terms used by healthcare professionals and investigate the factors associated with these perceptions., Methods: Children and adolescents aged 8-16 years with overweight or obesity (n = 192) and their parents participated in the cross-sectional study by responding to a 5-point Likert-scale questionnaire on 10 obesity-related terms, including "chubby," "weight problem," "weight," "overweight," "BMI," "obese," "heavy," "fleshy," "fat," and "severely obese.", Results: For both children and parents, "chubby" was the most desirable term (mean ± standard deviation: 3.50 ± 1.12 and 2.95 ± 0.83, respectively), and "severely obese" was the least acceptable term (2.83 ± 1.17 and 2.02 ± 1.02, respectively). Although the parents preferred all the terms less than the children did (p < 0.001), "weight problem" was considered most motivating for a child to lose weight (3.93 ± 0.94). Among children, older age and a larger self-perceived body size were associated with a more positive response towards obesity-related terms, whereas having internalized or externalized problems were negatively associated with these terms. Parents with a history of cardiovascular disease considered "severely obese" (β = -0.419, [95% CI: -0.739, -0.099]) and "fat" (β = -0.457, [95% CI: -0.750, -0.164]) less desirable., Conclusions: Children and adolescents had a higher preference for obesity-related terms than their parents and preferred that healthcare professionals use euphemistic terms such as "chubby," or neutral terms such as "weight problem." Children with larger self-perceived body sizes or older age had a higher preference for obesity-related words. The terms used by healthcare professionals to describe excess weight must be motivating and respectful for all family members participating in the treatment., 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 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies., Patients and Methods: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected., Results: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies., Conclusions: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: This study examined whether a pilot workshop focused on maternal mortality had an impact on pharmacy students' confidence, comfort, and knowledge regarding preeclampsia, postpartum depression and opioid poisoning., Educational Activity and Setting: The two-hour workshop included lecture, video, discussion and case studies. P1-P3 student pharmacists completed pre- and post-surveys measuring confidence (N = 5) and comfort (N = 15) using a 5-point Likert type scale (1 = strongly disagree to 5 = strongly agree), as well as knowledge with 12 true/false statements. Data were analyzed using paired t-tests and McNemar's tests, as well as Cronbach's alphas for scale reliability., Findings: The majority of participants (N = 27) were 18-25 years (85.2%), female (74.1%) and Asian (51.9%). Overall confidence and comfort increased significantly (p < .001) from pre- to post-intervention regarding: 1) preeclampsia (2.5 ± 0.9 to 4.5 ± 0.5); 2) postpartum depression (3.3 ± 0.8 to 4.5 ± 0.5); 3) opioids (3.5 ± 0.9 to 4.7 ± 0.5); 4) maternal mortality risk factors (2.1 ± 0.7 to 4.5 ± 0.5); and 5) pharmacist services related to maternal mortality prevention (2.0 ± 0.7 to 4.5 ± 0.5). Knowledge significantly (p < .05) improved on the majority (83.3%) of items. Scale reliabilities were ≥ 0.8., Summary: Incorporating maternal mortality training in colleges/schools of pharmacy curricula may have a positive impact on pharmacists' counseling and screening of patients at risk for maternal mortality in practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: In May 2020, The Communicable Diseases Network of Australia (CDNA) case definition introduced serological criteria to support the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present findings that support the utility of SARS-CoV-2-specific serology for public health investigations., Methods: From 24 January to 31 July 2020, the following information was collected from individuals with positive SARS-CoV-2-specific immunofluorescence antibody tests: history of contact with COVID-19 cases; recent travel; symptoms consistent with COVID-19; and SARS-CoV-2 nucleic acid testing (NAT) results. Individuals were classified as confirmed or probable by CDNA criteria or additionally as possible (SARS-CoV-2-specific IgG positive with compatible symptoms or epidemiologic risk) or indeterminate (SARS-CoV-2-specific IgA/IgM positive only) cases., Results: A total of 10,595 individuals were tested in the six-month period. Of these, 9.8% (1,037) individuals had positive SARS-CoV-2-specific serology of which 566 (53.6%) were NAT-confirmed COVID-19 cases and 286 (27.6%) were part of a cruise ship outbreak sero-survey. The remaining 185 individuals (NAT negative) were individually classified as serologically confirmed (4, 0.4%), probable (72, 6.9%) possible (66, 6.4%) and indeterminate (38, 3.7%) cases. Maternal antibody transfer was inferred in one infant and four were unclassified., Conclusion: SARS-CoV-2-specific serology is a key diagnostic tool for retrospective identification of COVID-19 infection. Implications for public health: SARS-CoV-2 specific serology can enhance the ability to find cases, link missing cases in clusters of infection and identify the epidemiological extent of SARS-CoV-2 outbreaks. A combination of epidemiological criteria, clinical criteria and a quantitative serological test can be used as an adjunct to classify SARS-CoV-2 cases. Our study confirms the low level of community transmission in NSW during the first year of the COVID-19 pandemic., (© 2021 The Authors.)

Polyhydroxyalkanoates (PHAs) are biopolyesters synthesized by microorganisms as intracellular energy reservoirs under stressful environmental conditions. PHA synthase (PhaC) is the key enzyme responsible for PHA biosynthesis, but the importance of its N- and C-terminal ends still remains elusive. Six plasmid constructs expressing truncation variants of Aquitalea sp. USM4 PhaC (PhaC1 As ) were generated and heterologously expressed in Cupriavidus necator PHB - 4. Removal of the first six residues at the N-terminus enabled the modulation of PHA composition without altering the PHA content in cells. Meanwhile, deletion of 13 amino acids from the C-terminus greatly affected the catalytic activity of PhaC1 As , retaining only 1.1-7.4% of the total activity. Truncation(s) at the N- and/or C-terminus of PhaC1 As gradually diminished the incorporation of comonomer units, and revealed that the N-terminal region is essential for PhaC1 As dimerization whereas the C-terminal region is required for stabilization. Notably, transmission electron microscopy analysis showed that PhaC modification affected the morphology of intracellular PHA granules, which until now is only known to be regulated by phasins. This study provided substantial evidence and highlighted the significance of both the N- and C-termini of PhaC1 As in regulating intracellular granule morphology, activity, substrate specificity, dimerization and stability of the synthase., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To develop a lung nodule management strategy combining the Lung CT Screening Reporting and Data System (Lung-RADS) with an artificial intelligence (AI) malignancy risk score and determine its impact on follow-up investigations and associated costs in a baseline lung cancer screening population., Materials and Methods: Secondary analysis was undertaken of a data set consisting of AI malignancy risk scores and Lung-RADS classifications from six radiologists for 192 baseline low-dose CT studies. Low-dose CT studies were weighted to model a representative cohort of 3,197 baseline screening patients. An AI risk score threshold was defined to match average sensitivity of six radiologists applying Lung-RADS. Cases initially Lung-RADS category 1 or 2 with a high AI risk score were upgraded to category 3, and cases initially category 3 or higher with a low AI risk score were downgraded to category 2. Follow-up investigations resulting from Lung-RADS and the AI-informed management strategy were determined. Investigation costs were based on the 2019 US Medicare Physician Fee Schedule., Results: The AI-informed management strategy achieved sensitivity and specificity of 91% and 96%, respectively. Average sensitivity and specificity of six radiologists using Lung-RADS only was 91% and 66%, respectively. Using the AI-informed management strategy, 41 (0.2%) category 1 or 2 classifications were upgraded to category 3, and 5,750 (30%) category 3 or higher classifications were downgraded to category 2. Minimum net cost savings using the AI-informed management strategy was estimated to be $72 per patient screened., Conclusion: Using an AI risk score combined with Lung-RADS at baseline lung cancer screening may result in fewer follow-up investigations and substantial cost savings., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) are a versatile source of carbon nanoarchitectures in gas sensing applications (Torad et al., 2019). Herein, several types of nanoporous carbons (NPCs) have been prepared by in-situ carbothermal treatment of zeolitic imidazolate frameworks (ZIFs) under different inert atmospheres to achieve a highly sensitive discrimination of vaporized aromatic compounds. In this study, we demonstrate how different carbonization conditions under the flow of N 2 or H 2 gases affect the surface area and the degree of graphitization of the resulting NPCs polyhedrons, and their consequent effect on the sensing performance in terms of sensitivity and selectivity toward toxic volatile hydrocarbons. A growth of carbon nanotubes (CNTs) is observed on the surface of polyhedral NPCs after careful carbonization of ZIF crystals under H 2 atmosphere. The fabricated quartz crystal microbalance (QCM) sensor with CNT-containing NPCs demonstrates increased sensitivity and selectivity towards toxic volatile aromatic hydrocarbons over the aliphatic analogues, suggesting the rich growth of hairy graphitic-like CNTs on the surface of carbon framework act as highly selective sensing antennae for vapor molecular discrimination of toxic aromatic hydrocarbons. Despite of increased selectivity towards volatile aromatic compounds, however, the surface area of CNT-rich NPCs derived from hybrid ZIFs and ZIF-67 is greatly sacrificed as compared to CNT-free NPCs from ZIF-8 polyhedron. In the case of Co-containing ZIF-67, the rich growth of hair-like CNTs, which is induced by the presence of Co, is observed during carbothermal reduction under a flow of H 2 gas, thus allowing ultra-selective detection of aromatic hydrocarbons in the vapor phase, such as benzene (C 6 H 6 ) and toluene (C 6 H 5 CH 3 ) over their aliphatic analogue, c-hexane (c-C 6 H 12 ) of same molecular mass, size and vapor pressure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC., Patients and Methods: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m 2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146)., Results: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable., Conclusions: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Data generated and analyzed during this study are on file at the Samsung Medical Center, and are not publicly available. Data can be shared upon request., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Children spend a significant amount of their day in preschool; thus, environmental quality at preschools may have an impact on children's health. In the present study, we analyzed polycyclic aromatic compounds (PACs), including PAHs, alkylated PAHs and oxygenated PAHs (OPAHs), in indoor and outdoor air particulate matter (PM 10 ) and indoor dust at preschools in Stockholm, Sweden. There were significant correlations between PAC levels in outdoor and indoor PM 10 , with in general higher PAC levels outdoors. Fluoranthene and pyrene were detected at highest levels in all sample types, although phenanthrene and methylated phenanthrene derivatives also were found at high levels in indoor dust. In addition, the highly carcinogenic PAHs 7H-benzo[c]fluorene, 7,12-dimethylbenz[a]anthracene, benz[j]aceanthrylene, and dibenzo[a,l]pyrene were detected in some samples. Benzanthrone was the most prevalent OPAH in PM 10 samples and 9,10-anthraquinone in indoor dust. Based on diagnostic ratios and Positive Matrix Factorization we identified vehicle emission and biomass burning as important PAC sources for all samples analyzed. However, poor correlation between PAC levels in indoor PM 10 and indoor dust suggested additional sources for the latter. Measuring activation of DNA damage signaling in human cells exposed to organic extracts of the samples indicated substantial genotoxic potential of outdoor PM 10 and indoor dust. Determination of benzo[a]pyrene equivalents demonstrated that the highly potent PAHs benz[j]aceanthrylene and dibenz[a,h]anthracene contributed more than 20% to the total carcinogenic potency of the samples. We conclude that PAC levels at Stockholm preschools are relatively low but that outdoor air quality may impact on the indoor environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Emergence delirium (ED) in children after general anaesthesia causes significant distress in patients, their family members, and clinicians; however, electroencephalogram (EEG) markers predicting ED have not been fully investigated., Methods: This prospective, single-centre observational study enrolled children aged 2-10 yr old under sevoflurane anaesthesia. ED was assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or 5 criteria. The relative power of low-frequency (delta and theta) and high-frequency (alpha and beta) EEG waves during the emergence period was compared between the children with and without ED. The linear relationships between the relative power and peak Paediatric Assessment of Emergence Delirium (PAED) score were investigated., Results: Among the 60 patients, 22 developed ED (ED group), whereas the other 38 did not (non-ED group). The relative power of the delta wave was higher (mean [standard deviation], 0.579 [0.083] vs 0.453 [0.090], respectively, P<0.001) in the ED group, whereas that of the alpha and beta waves was lower in the ED group, than in the non-ED group (0.155 [0.063] vs 0.218 [0.088], P=0.005 and 0.114 [0.069] vs 0.186 [0.070], P<0.001, respectively). The areas under the receiver operating characteristic curves of the relative power of the delta wave, low-to-high frequency power ratio, and delta-to-alpha ratio were 0.837 (95% confidence interval, 0.737-0.938), 0.835 (0.735-0.934), and 0.768 (0.649-0.887), respectively. The relative power of the delta wave and the two ratios had a positive linear relationship with the peak PAED scores., Conclusions: Paediatric patients developing ED have increased low-frequency (delta) frontal EEG activity with reduced high-frequency (alpha and beta) activity during emergence from general anaesthesia., Clinical Trial Registration: NCT03797274., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of β- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, comprehensive studies on the effect of α-amino acid with (R)-configuration in the S1' pocket has not been reported yet. We selected ZJ-43 (1) and DCIBzL (5) as templates and synthesized their analogues with (S)- or (R)-configuration in the P1 and P1' regions. The PSMA-inhibitory activities of compounds with altered chirality in the P1' region were dropped dramatically, with their IC 50 values changing from nM to μM ranges. The compounds with (S)-configuration at both P1 and P1' regions were more potent than the others. The findings of this study may provide insights regarding the structural modification of PSMA inhibitor in the S1' binding pocket., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Recognition of childhood epilepsy has improved worldwide. Children with epilepsy require immediate healthcare evaluation and monitoring. The interval between the onset of the first seizures and pediatric neurology assessment may influence the epilepsy outcome at follow-up assessments. This study aimed to assess the quality of medical care for children with first seizure onset and determine the impact of pediatric neurology clinic waiting times on epilepsy outcomes., Methods: This was a retrospective cohort study based on chart reviews and included patients who underwent their first seizure evaluation at the Royal University Hospital in Saskatoon, Canada between January 1, 2012 and December 31, 2015. Waiting time (the time interval between seizure onset and the first clinical assessment) and baseline factors were examined in relation to epilepsy outcome on follow-up., Results: Of a total 1157 patients evaluated for epilepsy for the period 2012-2015, 197 patients had unprovoked seizures and were eligible for this study. The mean age of the patients at seizure onset was 5.6 (±5.1) years. The mean waiting time was 4.33 months and the mean follow-up time was 20.9 months. Shorter waiting times in the clinic led to a more favourable seizure outcome. Of the 197 assessed at the last seizure assessment, 132 (67 %) patients had a favourable epilepsy outcome with no seizures at follow-up appointments and 65 (33 %) showed an unfavourable epilepsy outcome with persistent seizures at follow-up appointments., Conclusion: Early assessment of first seizure onset is crucial for the management of children with epilepsy. Waiting time and other factors may influence epilepsy outcome, and represent opportunities to improve standard medical care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front β-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Few data on the association between height and the risk of sudden cardiac death (SCD) in Asian populations are available., Objective: The purpose of this study was to assess the risk of SCD as related to height both in a representative Korean population and in specific subgroups., Methods: This is a retrospective cohort study of 410,119 Koreans age ≥20 years from the Korean National Health Insurance Service-National Sample Cohort, who underwent a national health examination. SCD cases were adjudicated based on information within the claims database. Cox proportional hazard models were applied to estimate hazard ratios and 95% confidence intervals for the association between height and SCD. Potential mediators included demographic factors, health-related habits, and specific cardiovascular comorbidities., Results: During an 8.45-year follow-up period, a total of 1341 SCDs occurred. Various factors, including short stature, were identified as risk factors for SCD. Multivariable regression analysis revealed that a 10-cm increase in height was associated with a 14% decreased risk for SCD. This relationship remained significant among the elderly, postmenopausal women, and individuals without cardiovascular disease., Conclusion: Our results indicate that short stature is a significant risk factor for SCD in a Korean population, thus supporting previously published findings correlating height to SCD risk in non-Asian populations., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Although increased height is associated with a risk of atrial fibrillation (AF), the mechanism is not well understood. We aimed to explore whether this association varies with metabolic conditions., Methods and Results: We used the database from the 14-year Korea National Health Insurance Service-National Sample Cohort. The data of 368,206 adults older than 20 years who received a health check-up were analyzed to explore the association of height and AF risk. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of height with the risk of AF. During the median follow up duration of 8.46 years, 2641 (0.72%) patients were diagnosed with AF at 3,070,724 person-years. Overall, greater height was significantly associated with AF risk (HR per 5 cm, 1.22; 95% CI, 1.03-1.05). The association did not vary with age, sex, obesity, hypertension, and diabetes., Conclusion: Metabolic conditions do not affect the higher risk of AF in tall people., Competing Interests: Declaration of competing interest There are no potential conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Developing natural preservatives for wood protection is of great interest in sustainable construction and green building industries. This study was designed to determine the feasibility of using methyl-β-cyclodextrin-essential oils (MβCD-EOs) complexes as potential bio-based preservatives for wood protection. Four essential oils (EOs) with proven antifungal properties, eugenol (EG), trans-cinnamaldehyde (CN), thymol (TM) and carvacrol (CV), were complexed with methyl-β-cyclodextrin (MβCD) by a co-precipitation method. The inclusion of EOs in MβCD and the corresponding inclusion yield of the MβCD-EOs complexes were determined by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and ultraviolet-visible spectroscopy (UV/Vis), respectively. The maximum inclusion yields in MβCD-EG, MβCD-CN, MβCD-CV, and MβCD-TM were estimated to be almost 100%. MβCD-EOs complexes were impregnated into southern pine wood blocks and exposed to two brown rot fungi, Gloeophyllum trabeum and Postia placenta, following procedures described in AWPA Standard E22 and E10. The penetration of MβCD-EOs complexes in wood was confirmed by fluorescence microscopic analysis after the selective dyeing of EOs encapsulated in MβCD. In comparison to the control wood samples, MβCD-EOs complexes treated wood exhibited a significant reduction in the mass loss from 16-36% to 2-18%, accompanied by improvement in radial compression strength loss from 81-92% to 29-67% after four-week fungi exposure., (Copyright © 2020 Elsevier B.V. All rights reserved.)