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Background: Congestive heart failure (CHF) as a risk of stroke in patients with atrial fibrillation (AF) mainly referred to patients with left ventricular systolic dysfunction. Whether this should include patients with preserved ejection fraction is debatable., Objective: The study aimed to investigate the variation in stroke risk of AF patients with heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) for enhancing risk assessment and subsequent management strategies., Methods: In a longitudinal study using the National Taiwan University Hospital integrated Medical Database, 8358 patients with AF were observed for 10 years (mean follow-up, 3.76 years). The study evaluated the risk of ischemic stroke in patients with differing ejection fractions and CHA 2 DS 2 -VASc score, further using Cox models adjusted for risk factors of AF-related stroke., Results: Patients with HFpEF and HFmrEF had a higher mean CHA 2 DS 2 -VASc score compared with patients with HFrEF (4.30 ± 1.729 vs 4.15 ± 1.736 vs 3.73 ± 1.712; P < .001) and higher risk of stroke during follow-up (hazard ratio [HR], 1.40 [1.161-1.688; P < .001] for HFmrEF; HR, 1.184 [1.075-1.303; P = .001] for HFpEF vs no CHF) after multivariate adjustment). In patients with lower CHA 2 DS 2 -VASc score (0-4), presence of any type of CHF increased ischemic stroke risk (HFrEF HR, 1.568 [1.189-2.068; P = .001]; HFmrEF HR, 1.890 [1.372-2.603; P < .001]; HFpEF HR, 1.800 [1.526-2.123; P < .001] vs no CHF)., Conclusion: After multivariate adjustment, HFpEF and HFmrEF showed a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for C in the CHA 2 DS 2 -VASc score to include patients with HFpEF and HFmrEF. In patients with fewer concomitant stroke risk factors, the presence of any subtype of CHF increases risk for ischemic stroke., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

High-performance poly(lactic acid) (PLA) blend-based composites were fabricated with a poly(ether-block-amide) (PEBA) elastomer acting as the blend counterpart. It was confirmed that a compatibilizer (ADR) enhanced the interaction between PLA and PEBA. Carbon nanotubes (CNTs) and organoclay (30B) were added individually and simultaneously into the blend to produce bionanocomposites. Morphological results showed that CNTs were mainly dispersed in PEBA domains, whereas 30B was mainly localized at the interfacial region of PLA and PEBA phases. The selective localization of added CNTs and 30B led to significant modification of the properties of the compatibilized PLA/PEBA blend. The brittleness and flammability of PLA were evidently improved after forming the bionanocomposites. Differential scanning calorimetry results revealed that CNTs and 30B assisted the crystallization of both PLA and PEBA in the composites, with CNTs providing superior nucleation efficiency to 30B. Thermogravimetric analysis revealed the thermal stability enhancement of the blend after adding CNTs and/or 30B, with up to 16 °C increase at 20 wt% loss with inclusion of 2 phr 30B. Addition of CNTs and/or 30B improved the blend's anti-dripping performance during burning tests, and CNT exhibited better anti-dripping efficiency. Ductility of PLA was drastically improved after forming the compatibilized blend, and further improved with incorporation of CNTs and/or 30B (increased from 9 % for neat PLA to 252 % for the hybrid composite containing CNT/30B). The impact strength of 1 phr CNTs-added composite was about 3 times that of PLA. Rheological properties indicated the (pseudo)network formation of added filler(s), leading to a significant reduction in electrical resistivity, up to six orders of magnitude with addition of 3 phr CNTs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Atrial fibrillation (AF) is a stroke and heart complication riskbut is often overlooked due to subtle symptoms. The accessibility of sphygmomanometers that can detect AF, may play crucial roles in identifying asymptomatic patients. AViTA BPM63B is an automatic blood pressure (BP) monitor for atrial fibrillation detection. This study validated the performance of BPM63B for AF detection using two novel algorithms of time-domain analysis and frequency-domain analysis which evaluate multiple statistics., Methods: The study included 100 subject, with 47 participants being male (47%) and ages ranging from 24 to 89 years (mean ± SD: 59 ± 17 years). Each participant received three consecutive readings from the subject device and a 12-lead ECG assessment. The pulse wave data from subject device was analyzed using the two algorithms. The atrial fibrillation status thus determined was compared to the ECG results interpreted by a physician., Results: Among the 100 participants, 52 patients had chronic atrial fibrillation, along with 48 outpatients exhibiting sinus rhythm or non-atrial fibrillation arrhythmias. Using the time-domain analysis method for atrial fibrillation detection, we achieved a sensitivity of 94.8% [95% confidence interval (CI), 90.08-97.75%] and a specificity of 98.6% (95% CI, 95.07-99.83%). Similarly, utilizing the frequency-domain analysis method resulted in a sensitivity of 91.6% (95% CI, 86.08-95.46%) and specificity of 94.4% (95% CI, 89.35-97.57%)., Conclusions: These findings suggest that AViTA BPM63B, which integrates two novel algorithms for atrial fibrillation diagnosis, demonstrates high sensitivity and specificity. Utilizing the AViTA BPM63B for BP monitoring could aid in the early detection of atrial fibrillation among outpatients in cardiology clinics., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I-V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1-induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, a twin-screw extruder was used to fabricate poly(lactic acid) (PLA)/poly(butylene adipate-co-terephthalate) (PBAT) blends and blend-based nanocomposites with carbon nanotube (CNT) or nanocarbon black (CB) as nanofillers. The fabricated samples were subsequently treated with supercritical carbon dioxide (scCO 2 ) to fabricate the corresponding foams. Bi-phasic morphology and selective distribution of CNTs or CBs in the PBAT phase were observed in the blends/composites through scanning electron microscopy. After the scCO 2 treatment, the selective foaming of the PBAT phase in the prepared blends/composites was confirmed. The cellular structure of PBAT phase in scCO 2 -treated blends is similar to the size/shape of PBAT domains in untreated blends or treated neat PBAT foam. The addition of CNTs or CBs in the blends led to a slight reduction in cell size of the foamed PBAT phase, demonstrating CNT/CB-induced cell nucleation. Differential scanning calorimetry (DSC) results showed that CNTs and CBs played as nucleating agents and increased the initial crystallization temperature up to 14 °C compared with neat PBAT for PBAT in different composites during cooling. The scCO 2 treatment induced the bimodal stability of PBAT crystals in different samples, which melted mainly in two temperature regions in DSC studies. Thermogravimetric analyses revealed that compared with parent blends, the addition of CNTs or CBs increased the temperature at 80 wt.% loss (degradation of PBAT portion) up to 6 °C. The electrical resistivity decreased by more than six orders of magnitude for certain CNT- or CB-added composites compared with the parent blends. The hardness of the blends slightly increased after forming the corresponding composites and then declined after the scCO 2 treatment.

Background: The risk of subsequent myocardial infarction (MI) varies widely in patients with atrial fibrillation (AF). No convenient scoring system currently exists to identify MI in AF. While each element of the CHA2DS2-VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke or thromboembolism [doubled]; vascular disease; age 65-75 years; and sex category) score can increase the likelihood of MI, this retrospective longitudinal study aimed to determine the accuracy of the CHA2DS2-VASc score in predicting subsequent MI risk in AF., Methods: A total of 29,341 patients with AF were enrolled and followed up from January 2010 until the first occurrence of MI or until December 2020. The primary endpoint was the occurrence of subsequent MI., Results: The average age of the study population was 71 years, and 43.2% were male. The mean CHA2DS2-VASc score was found to be higher in patients with AF who had experienced an MI than in those who had not (3.56 ± 1.92 vs. 3.32 ± 1.81, p < 0.001). During the long-term follow-up, the risk of subsequent MI increased by 22% with every one-point increase in the CHA2DS2-VASc score (hazard ratio 1.22, 95% confidence interval 1.19-1.25; p < 0.001). Kaplan-Meier analysis revealed that high CHA2DS2-VASc scores were more likely to experience an MI than those with low CHA2DS2-VASc scores (log-rank p < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of MI in multivariate regression analysis., Conclusion: The CHA 2 DS 2 -VASc score is a valuable predictor of subsequent MI risk in patients with AF., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Conductive polymers (CPs) are typically insoluble in solvents, and devising biocompatible hydrophilic CPs is challenging and imperative to expand the applications of CPs. Herein, sulfated chitosan (SCS) is used as a green dopant instead of toxic poly(styrene sulfonate) (PSS), and SCS:polypyrrole (SCS:PPy) conductive ink is prepared by in situ polymerization. Due to the complex structure between PPy and SCS polyanion, the synthesized SCS:PPy dispersion forms a well-connected electric pathway and confers superior conductivity, dispersion stability, good film-forming ability, and high electrical stability. As proof of our concept, electrochemical sensing utilizing an SCS:PPy-modified screen-printed carbon electrode (SPCE) was performed towards carbendazim (CBZ). The SCS:PPy on the SPCE surface displayed greater sensitivity to CBZ because the conductive complex structure eased the electrocatalytic action of SCS:PPy by dramatically increasing the current intensity of CBZ oxidation and notably ameliorating stability. The sensor unveils the lowest detection value of 1.02 nM with a linear range of 0.05 to 906 μM for sensing trace CBZ by utilizing the pulse voltammetry technique. Interestingly, this senor shows excellent selectivity towards CBZ due to the formation of substantial interactions between SCS:PPy and CBZ, as demonstrated by molecular simulation studies. Furthermore, this sensor can precisely monitor CBZ in actual fruit and river water samples with satisfactory results. This study sheds light on the design and synthesis of sustainable hydrophilic CPs in the fabrication of sensors., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hitherto unreported hybrid nanofillers (CNC:MgO) reinforced chitosan (CTS) based composite (CNC:MgO)/CTS films were synthesized using a solution-casting blend technique and synergistic effect of hybrid nanofiller in terms of properties enhancement were investigated. Optical microscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) technique, fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM) were used to characterize the films. The hybrid nanofiller considerably changed the transparency and color of the CTS films. The tensile strengths of (3 wt%) CNC/CTS, (3 wt%) MgO/CTS, (1:1)(CNC:MgO)/CTS, (1:2)(CNC:MgO)/CTS and (2:1)(CNC:MgO)/CTS films were 27.49 %, 35.60 %, 91.62 %, 38.22 %, and 29.32 % higher than pristine CTS films respectively, while the water vapor permeation were 28.21 %, 30.77 %, 34.62 %, 38.46 %, and 37.44 % lower than pristine CTS film, respectively. Moreover, the CTS composite films exhibited an improvement in overall water barrier properties after incorporating hybrid nanofillers. Our observations suggest that chitosan-based hybrid nanofiller composite films are a good replacement for plastic-based packaging materials within the food industry., 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.)

Dimetridazole (DMZ) is a derivative of nitroimidazole and is a veterinary drug used as an antibiotic to treat bacterial or protozoal infections in poultry. The residues of DMZ cause harmful side effects in human beings. Thus, we have constructed a superior electrocatalyst for DMZ detection. A copper (Cu)-integrated poly(aniline) (PANI) electrocatalyst (PANI-Cu@BSA) was prepared by using a one-step method of biomimetic mineralization and polymerization using bovine serum albumin (BSA) as a stabilizer. Then, the synthesized PANI-Cu@BSA was encapsulated with reduced graphene oxide (rGO) using an ultrasonication method. The PANI-Cu@BSA/rGO nanocomposite had superior water dispersibility, high electrical conductivity, and nanoscale particles. Moreover, a PANI-Cu@BSA/rGO nanocomposite-modified, screen-printed carbon electrode was used for the sensitive electrochemical detection of DMZ. In phosphate buffer solution, the PANI-Cu@BSA/rGO/SPCE displayed a current intensity greater than PANI-Cu@BSA/SPCE, rGO/SPCE, and bare SPCE. This is because PANI-Cu@BSA combined with rGO increases fast electron transfer between the electrode and analyte, and this synergy results in analyte-electrode junctions with extraordinary conductivity and active surface areas. PANI-Cu@BSA/rGO/SPCE had a low detection limit, a high sensitivity, and a linear range of 1.78 nM, 5.96 μA μM -1 cm -2 , and 0.79 to 2057 μM, respectively. The selective examination of DMZ was achieved with interfering molecules, and the PANI-Cu@BSA/rGO/SPCE showed excellent selectivity, stability, repeatability, and practicability.

The search for alternatives to petroleum-based thermoplastic polyamide elastomers (TPAEs) has recently drawn great interest. In this study, a bio-massed TPAE, PA12,36, was synthesized using 1,12-dodecanediamine (DDA) and fatty dimer acid (FDA, Pripol TM 1009) precursors via catalyst and solvent-free melt polycondensation. The molecular structure and molecular weight of the PA12,36 were characterized by 1 H NMR, FTIR, and GPC. PA12,36 displayed a low melting temperature of 85.8 °C, an initial degradation temperature of 425 °C, and a glass-transition temperature of 30.4 °C, whereas it sustained satisfactory tensile strength (10.0 MPa) and superior strain at break (1378%). Furthermore, PA12,36 was foamed by supercritical CO 2 , and the cell size, cell density, and porosity were determined. The entangled long-chained FDA component generated a physically crosslinked network, which promoted the melt viscosity of PA12,36 against elongations of foam cell growth and increased foamability significantly. As a result, uniform structured cellular foams with a cell diameter of 15-24 µm and high cell density (10 11 cells/cm 3 -10 12 cells/cm 3 ) were successfully achieved. The foaming window was widened from 76 to 81 °C, and the expansion ratio was increased from 4.8 to 9.6. Additionally, PA12,36 foam with a physically crosslinked structure presented a better creep shape recovery percentage (92-97.9%) and sturdier dimensional stability. This bio-based PA12,36 foam is a promising candidate to replace petroleum-based thermoplastic elastomer foams for engineering applications, particularly shoe soles.

Background: Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device-related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization., Methods and Results: We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization., Conclusions: We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.

Objective: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia., Methods: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death., Results: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4-18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1-39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6-17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047)., Conclusion: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

A twin-screw extruder was used to fabricate poly(butylene succinate) (PBS)/high-density polyethylene (HDPE) blends (7:3 weight ratio) and blend-based nanocomposites. Carbon nanotubes (CNTs), graphene nanoplatelets (GNPs), and organoclays (15A and 30B) served as the nanofiller, while maleated HDPE (PEgMA) acted as an efficient compatibilizer for the blend. In the composites, individual nanofillers were mostly localized in HDPE domains, but some fillers were also observed at PBS-HDPE interfaces. The sea-island morphology of the compatibilized blend evolved into a pseudo-co-continuous morphology in the composites. Differential scanning calorimetry results confirmed that PEgMA with HDPE evidently accelerated the crystallization of PBS in the blend. The possible nucleation effect of added fillers on PBS crystallization was obscured by the formation of quasi-connected HDPE domains, causing fewer PBS nucleation sites. The presence of nanofillers improved the thermal stability and burning anti-dripping behavior of the parent blend. The anti-dripping efficiency of added fillers followed the sequence CNT > 15A > 30B > GNP. The rigidity of the blend was increased after the formation of nanocomposites. In particular, adding GNP resulted in 19% and 31% increases in the Young's modulus and flexural modulus, respectively. The development of a pseudo-network structure in the composites was confirmed by measurement of rheological properties. The electrical resistivity of the blend was reduced by more than six orders of magnitude at 3 phr CNT loading, demonstrating the achievement of double percolation morphology.

Background: Cardioversion and catheter-based circumferential pulmonary vein isolation (CPVI) are established rhythm control treatment strategies for patients with atrial fibrillation (AF). However, these treatments are contraindicated for AF patients with a left atrial appendage (LAA) thrombus., Methods: We conducted the first-in-man case series study to evaluate the feasibility and safety of performing cardioversion or CPVI in AF patients with LAA thrombus immediately after implantation of LAA Occluder (LAAO) in a combined procedure. In our multi-center LAAO registry of 310 patients, 27 symptomatic and drug-refractory AF patients underwent a combined procedure of LAAO and CPVI, among whom 10 (mean age 68 ± 16 years, 6 men) having anticoagulant-resistant LAA thrombus received a bailout procedure of LAAO implantation first then CPVI, and the other 17 patients without LAA thrombus received CPVI first then LAAO for comparison., Results: The mean CHA 2 DS 2 -VASc score and HAS-BLED score were comparable between these two groups. In patients with LAA thrombus, we put carotid filters and did a no-touch technique, neither advancing the wire and sheath into the LAA nor performing LAA angiography. After LAAO implantation, the connecting cable was still connected to the occluder when cardioversion was performed. During CPVI, the occluder location was registered in the LA geometry by three-dimensional mapping to guide the catheter not to touch the LAAO. The procedure was successful in all the patients without intra-procedural complications. After a mean follow-up of 1.7 ± 0.7 years, there was no device embolization, peri-device leak ≧ 5 mm or stroke event in both groups. The AF recurrence rate was also similar between the two groups (P = 0.697)., Conclusion: We demonstrated that cardioversion or CPVI is doable in symptomatic AF patients with LAA thrombus if LAA was occluded ahead as a bailout procedure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Patients with drug-refractory atrial fibrillation (AF) and pre-existing left atrial appendage occluder (LAAO) device may need pulmonary vein isolation (PVI). In this pioneer study, we investigated the impact of pre-existing LAAO on AF substrates and outcomes of PVI., Methods: From our AF registry, 65 drug-refractory patients with LAAO (72.1±11.4 years old; CHA 2 DS 2 -VASc score 3.7±2.1) were included for PVI. A balanced control group with 124 patients without LAAO receiving PVI (70.9±10.2 years old, CHA 2 DS 2 -VASc 3.6±1.9) were included for comparison., Results: We found PVI is feasible in patients with AF with pre-existing LAAO without new peridevice leak. Two patients with LAAO and one without LAAO had stroke during the procedure (2/65 vs 1/124, p=0.272). Complete isolation of left-sided PVs might not be achieved if the device covered the ridge joining the left atrial (LA) appendage to the body of LA. Local electrogram could be detected over LAAO and there was propagation of conduction over the occluder either under sinus rhythm or under atrial arrhythmia. LAAO might modulate LA substrate and induce peridevice fibrosis, peridevice LA flutter and complex fractionate atrial electrogram. The AF recurrent rate at 1 year was similar between the two groups (9.2% vs 8.8%)., Conclusions: This pioneer study first showed impacts of LAAO on LA substrate and PVI procedure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke., Methods and Results: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank)., Conclusion: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients., Competing Interests: Conflict of interest: None declared, (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Ventricular premature complex (VPC) is a common arrhythmia in clinical practice. VPC could trigger ventricular tachycardia/fibrillation or VPC-induced cardiomyopathy in susceptible patients. Existing screening methods require prolonged monitoring and are limited by cost and low yield when the frequency of VPC is low. Twelve-lead electrocardiogram (ECG) is low cost and widely used. We aimed to identify patients with VPC during normal sinus rhythm (NSR) using artificial intelligence (AI) and machine learning-based ECG reading., Methods: We developed AI-enabled ECG algorithm using a convolutional neural network (CNN) to detect the ECG signature of VPC presented during NSR using standard 12-lead ECGs. A total of 2515 ECG records from 398 patients with VPC were collected. Among them, only ECG records of NSR without VPC (1617 ECG records) were parsed., Results: A total of 753 normal ECG records from 387 patients under NSR were used for comparison. Both image and time-series datasets were parsed for the training process by the CNN models. The computer architectures were optimized to select the best model for the training process. Both the single-input image model (InceptionV3, accuracy: 0.895, 95% confidence interval [CI] 0.683-0.937) and multi-input time-series model (ResNet50V2, accuracy: 0.880, 95% CI 0.646-0.943) yielded satisfactory results for VPC prediction, both of which were better than the single-input time-series model (ResNet50V2, accuracy: 0.840, 95% CI 0.629-0.952)., Conclusions: AI-enabled ECG acquired during NSR permits rapid identification at point of care of individuals with VPC and has the potential to predict VPC episodes automatically rather than traditional long-time monitoring., (© 2022. The Author(s).)

Left atrial appendage (LAA) closure (LAAC) device implantation may be challenging in cases with difficult LAA anatomy. A deflectable sheath to approach multiple LAA positions may be helpful. We used a deflectable sheath to implant LAAC devices in 20 patients and included 60 cases using the standard sheaths for comparison. The procedures were successful in all patients without peri-procedural complications. After a median follow-up of 1.52 (IQR: 0.76-2.33) years, none of the patients in the deflectable sheath group had peri-device leak ≥3 mm and experienced thromboembolic stroke. In the standard sheath group, after follow-up of 2.03 (IQR: 0.87-3.19) years, 2 had peri-device leak ≥3 mm and 1 experienced thromboembolic stroke. We first proved the idea of using a universal steerable sheath for LAAC device implantation in difficult LAA anatomy, which also allows rapid switching of different LAAC devices., Competing Interests: The work was supported by grants from the Ministry of Science and Technology in Taiwan (MOST 109-2314-B-002-244-MY3 and MOST 110-2314-B-002-198 -MY3). The Ministry of Science and Technology had no role in the conduct of this study. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Objective: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, thromboembolic event still occur, and the predictors are unknown., Methods: The first Asian long-term follow-up study consisted of 308 patients with mean age 71.9±9.5 years, mean CHA 2 DS 2 -VASc 4.1 ± 1.8 since 2013. Primary outcome was defined as any type of ischemic stroke/transient ischemic attack (TIA), systemic embolization and cardiovascular death., Results: There was no procedural-related TIA or stroke. After a mean follow-up of 38±16 months, the ischemic stroke/TIA rate was 1.9 and cardiovascular death rate 0.3 per 100 patient-year. The rate of peri-device leak (PDL) was 11.9% and device-related thrombus (DRT) 2.6%. In the multivariable analyses, PDL was the only independent predictor of stroke/TIA (hazard ratio 5.5, p=0.008). CHA 2 DS 2 -VASc score, prior history of stroke, DRT and post-procedural anti-thrombotic regimen/duration were not associated with outcomes. Implantation of Watchman was associated with PDL (odds ratio 4.35, p=0.001)., Conclusions: PDL is the only independent predictor of post-LAAO stroke. The risk of stroke for patients with NVAF may be controllable after LAA is occluded, because PDL is preventable and treatable., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/purpose: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, the long-term outcomes in Asia was generally unknown., Methods and Results: This was a retrospective longitudinal study and a total of 124 patients with contraindications to oral anticoagulants or stroke despite under anticoagulants had been enrolled since 2013. Primary efficacy was defined as any type of stroke/systemic embolization and adverse event as any procedure or anti-thrombotic related complications. Twelve patients were excluded due to thrombus in the LAA or oversize LAA. Watchman was successfully implanted in 55 patients (98%) and ACP/Amulet also 55 patients (98%). During follow-up, the ischemic stroke rate was 1.9 in the Watchman and 1.4 per 100 patient-year in the ACP/Amulet group. There were 2 Watchman patients experiencing intracranial hemorrhage. Device-related thrombus (DRT) was noted in 3 patients (2.7%).There was no patient with peri-device lead ≧5 mm. In those patients receiving only local anesthesia, the follow-up echocardiography showed no significant peri-device leak, malposition of LAAO and DRT., Conclusion: This long-term follow-up study shows that percutaneous closure of LAA is a safe and technically feasible procedure with satisfactory outcomes in Asia. The procedure success rate, efficacy and adverse event were similar to those reported in the Caucasian populations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

This study aimed to develop a program of mindfulness-based stress reduction for military cadets (MBSR-MC). On the basis of a pretest-posttest design, participants were assigned to either a control or an experimental group to examine the effectiveness of MBSR-MC. First, 60 volunteering cadets of National Defense University were randomly assigned to the MBSR-MC group ( n  = 30) and the control group ( n  = 30). In the pretest, all participants were required to complete the Taiwanese version of the Five Facet Mindfulness Questionnaire (T-FFMQ) and a perceived stress scale (PSS). Subsequently, the MBSR-MC group participated in the 8-week MBSR-MC program, whereas the control group did not receive any experimental treatment. One week following the completion of the program, a posttest consisted of the same questions as the pretest was conducted. Statistical analysis showed that (1) Comparing with the control group, the MBSR-MC group showed superior performance in three subscales of T-FFMQ, namely Acting with awareness, Non-judgment, and Non-reactivity. However, no significant difference was found in the remaining two facets: Observing and Describing. (2) The perceived stress score of the MBSR-MC group was significantly lower than that of the control group. Furthermore, an analysis of mediating effect showed that Acting with awareness, Non-judgment, and Non-reactivity were mediating variables of the relationship between MBSR-MC and perceived stress. The aforementioned results indicated that MBSR-MC training significantly increased military cadets' Acting with awareness, Non-judgment, and Non-reactivity, thereby significantly reducing their perceived stress. Therefore, this study supported the effectiveness of the MBSR-MC program on perceived stress.

Background: The advantage of prophylactic cavotricuspid isthmus (CTI) ablation for AF patients without documented atrial flutter is still unclear. The present study aimed to evaluate the role of prophylactic CTI ablation in this population. Methods: A systematic review and meta-analysis study was conducted. The overall effects estimation was conducted using random effects models. The pooled effects were presented as the risk difference and standardised mean difference for dichotomous and continuous outcomes, respectively. Results: A total of 1,476 patients from four studies were included. The risk of atrial tachyarrhythmias following a successful catheter ablation procedure was greater in the pulmonary vein isolation + CTI ablation group than pulmonary vein isolation alone group (34.8% versus 28.2%; risk difference 0.08; 95% CI [0.00-0.17]; p=0.04). Prophylactic CTI ablation was associated with a higher recurrent AF rate (33.8% versus 27.1%; risk difference 0.07; 95% CI [0.01-0.13]; p=0.02). Additional prophylactic CTI ablation to pulmonary vein isolation significantly increased the radio frequency application time (standardised mean difference 0.52; 95% CI [0.04-1.01]; p=0.03). Conclusion: This study suggested that prophylactic CTI ablation was an ineffective and inefficient approach in AF without documented typical atrial flutter patients., Competing Interests: Disclosure: The authors have no conflicts of interest to declare. Data Availability: The data that support the findings of this study are available in the main article and in the supplementary material., (Copyright © 2022, Radcliffe Cardiology.)

Background: Gut microbiome alterations might be considered a metabolic disorder. However, the relationship between the microbiome and acute myocardial infarction (AMI) has not been properly validated. Methods: The feces of 44 subjects (AMI: 19; control: 25) were collected for fecal genomic DNA extraction. The variable region V3−V4 of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. The metabolite amounts were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways. Results: The bacteria were more enriched in the AMI group both in the observed operational taxonomic units (OTUs) and faith phylogenetic diversity (PD) (p-value = 0.01 and <0.001 with 95% CI, individually). The Selenomonadales were less enriched in the AMI group at the family, genus, and species levels (all linear discriminant analysis (LDA) scores > 2). Seleno-compounds were more abundant in the AMI group at the family, genus, and species levels (all LDA scores > 2). Conclusions: This is the first study to demonstrate the association of Selenomonadales and seleno-compounds with the occurrence of AMI. Our findings provide an opportunity to identify a novel approach to prevent and treat AMI.

(1) Background: The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods: We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results: We trained convolutional neural networks (CNN) models to identify patients with significant CAD (>70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions: We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.

Transthoracic, transesophageal, and intracardiac echocardiography are applicable imaging tools used for increasing the accuracy of tumor positioning during transvenous intracardiac tumor biopsy. However, incorporating echo-images in the extremely rare procedures is usually not easy. By using a contralateral catheter for simultaneous contrast injection and tip positioning, we demonstrated tumor biopsy safely and effectively in 4 cases without the guidance of echocardiography.

There has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia-Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy., (© 2021. The Author(s).)

Chitosan (CS)/boron nitride nanoplatelet (BNNP) nanobiocomposite films were successfully prepared. Morphological results showed good dispersion of BNNPs in the CS matrix. After loading with BNNPs, water solubility (WS) and moisture absorption of the CS film decreased. The WS decreased from 41.2 to 27.8% at 7 wt% BNNP loading. Additionally, water vapor permeation decreased from 4.2 × 10 -11 for pure CS film to 2.9 × 10 -11  g m -1 s -1 Pa -1 at 7 wt% BNNP inclusion. The oxygen permeability of CS film decreased by up to 84% at 7 wt% BNNP loading. The composites showed better sodium hydroxide resistance compared with pure CS. Thermal stability of the composites was higher than the pure CS, up to 35 °C increase at 7 wt% BNNP loading. The addition of 5 wt% BNNPs improved Young's modulus by up to 45% compared with pure CS film. Cytotoxicity of the films decreased after loading with BNNPs., (Copyright © 2021. Published by Elsevier B.V.)

Patients with heart failure and preserved ejection fraction (HFpEF) are known to have reduced systolic myocardial velocity (Sm) with impaired accommodation to exercise. We tested the impact of an aldosterone antagonist on Sm at rest and post-exercise. Forty-nine HFpEF patients (65 ± 11 years, 24 male) with HF signs/symptoms, mitral E/Ea (annular early diastolic velocity) > 8, and left ventricular (LV) EF > 50% were randomized to spironolactone (25 mg/day, 25 patients) or the Control. At baseline and 6 months, we analyzed Sm of basal LV segments at rest and after a 6 min treadmill exercise. At 6 months, post-exercise mean Sm in the spironolactone group became greater than that in the Control (9.2 ± 1.6 vs. 8.3 ± 1.0 cm/s, p = 0.021), mainly due to the increment of post-exercise % increase of lateral Sm (44 ± 30 vs. 30 ± 19% at baseline, p = 0.045). Further analyses showed the presence of systolic dyssynchrony (standard deviation of electromechanical delay of 6-basal LV segments > 35 ms) was independently associated with a poorer response to spironolactone, defined as a post-exercise % increase of lateral Sm < 50% (OR = 2.7, 95% CI = 1.8-4.2) and the increment of Ea < 1.5 cm/s (OR = 1.5, 95% CI = 1.1-2.3). Spironolactone could improve exercise accommodation of regional systolic myocardial velocity for HFpEF patients. However, its benefits could be decreased in those with ventricular dyssynchrony. This suggested possible therapeutic impacts from underlying heterogeneity within HFpEF patients.

Researchers have suggested that receiving attribute affirmation (AA) may increase the motivation of students to confront a challenge. However, we posited that to determine whether AA increases the motivation of students to confront a challenging task, we must consider dispositional achievement goals of the students. The participants were 171 junior-high-school students, randomly assigned to an AA or no affirmation condition. The results showed that AA enhanced the tendency to confront a challenging task for students who endorsed low mastery-approach goals (MAGs) and low performance-approach goals (PAGs) simultaneously ( b = 0.5, p = 0.015). The effect was mainly mediated by the increasing state performance-approach goals (SPAGs) in confronting the task (indirect effect = 0.21, 95% CI = 0.04-0.49); however, being attribute-affirmed decreased the tendency to confront the challenging task for students adopting a dominant PAG orientation ( b = -0.76, p = 0.049). In addition, for students adopting a dominant MAG orientation or adopting high MAGs and high PAGs simultaneously, no difference was noted in the tendency to confront the task between participants in the control and attribute-affirmed conditions., 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 Liu, Huang, Yin and Chiu.)

Carbon black (CB), carbon nanotubes (CNTs), and graphene nanoplatelets (GnPs) individually or doubly served as reinforcing fillers in polycarbonate (PC)/poly(vinylidene fluoride) (PVDF)-blend (designated CF)-based nanocomposites. Additionally, organo-montmorillonite (15A) was incorporated simultaneously with the individual carbon fillers to form hybrid filler nanocomposites. Microscopic images confirmed the selective localization of carbon fillers, mainly in the continuous PC phase, while 15A located in the PVDF domains. Differential scanning calorimetry results showed that blending PVDF with PC or forming single/double carbon filler composites resulted in lower PVDF crystallization temperature during cooling. However, PVDF crystallization was promoted by the inclusion of 15A, and the growth of β-form crystals was induced. The rigidity of the CF blend increased after the formation of nanocomposites. Among the three individually added carbon fillers, GnPs improved the CF moduli the most; the simultaneous loading of CNT/GnP resulted in the highest moduli by up to 33%/46% increases in tensile/flexural moduli, respectively, compared with those of the CF blend. Rheological viscosity results showed that adding CNTs increased the complex viscosity of the blend to a greater extent than did adding CB or GnPs, and the viscosity further increased after adding 15A. The electrical resistivity of the blend decreased with the inclusion of carbon fillers, particularly with CNT loading.

Background: Left atrial (LA) size represents atrial fibrillation (AF) burden and has been shown to be a predictor for AF stroke. The CHA 2 DS 2 -VASc score is also a well-established predictor of AF stroke. It is unknown to cardiologists whether these two risk scores are correlated, whether both are independent prognostic predictors and complimentary to each other, or whether one of them is a major determinant of stroke risk for AF patients. Method: A total of 708 patients from the National Taiwan University Atrial Fibrillation Registry were longitudinally followed up for more than 15 years. Left atrial size was measured by M mode of echocardiography. Adverse thromboembolic endpoints during follow-up were defined as ischemic stroke or transient ischemic attack. Results: The mean age was 72.1 ± 12.9 years, with 53% men. Both LA size and CHA 2 DS 2 -VASc score were associated with the risk of stroke in univariate analyses. There was a weak but significant positive correlation between LA size and CHA 2 DS 2 -VASc score ( r = 0.17, P < 0.0001). Patients with higher CHA 2 DS 2 -VASc scores had a higher mean LA size ( P < 0.01 for trend). When combining LA size and CHA 2 DS 2 -VASc score in the multivariable Cox model, only CHA 2 DS 2 -VASc score remained statistically significant [HR 1.39 (1.20-1.63); P < 0.001]. Conclusion: LA size is not an independent predictor of AF stroke, and calculation of CHA 2 DS 2 -VASc score may be an alternative to measurement of echocardiographic LA size when evaluating the risk of stroke for AF patients., 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 Tsai, Huang, Chen, Chang, Chiu, Lin, Lai, Hwang and Tsai.)

Background: Chronic kidney disease (CKD) is a global health burden. Self-management plays a key role in improving modifiable risk factors., Objective: The aim of this study was to evaluate the effectiveness of wearable devices, a health management platform, and social media at improving the self-management of CKD, with the goal of establishing a new self-management intervention model., Methods: In a 90-day prospective experimental study, a total of 60 people with CKD at stages 1-4 were enrolled in the intervention group (n=30) and control group (n=30). All participants were provided with wearable devices that collected exercise-related data. All participants maintained dietary diaries using a smartphone app. All dietary and exercise information was then uploaded to a health management platform. Suggestions about diet and exercise were provided to the intervention group only, and a social media group was created to inspire the participants in the intervention group. Participants' self-efficacy and self-management questionnaire scores, Kidney Disease Quality of Life scores, body composition, and laboratory examinations before and after the intervention were compared between the intervention and control groups., Results: A total of 49 participants completed the study (25 in the intervention group and 24 in the control group); 74% of the participants were men and the mean age was 51.22 years. There were no differences in measured baseline characteristics between the groups except for educational background. After the intervention, the intervention group showed significantly higher scores for self-efficacy (mean 171.28, SD 22.92 vs mean 142.21, SD 26.36; P<.001) and self-management (mean 54.16, SD 6.71 vs mean 47.58, SD 6.42; P=.001). Kidney Disease Quality of Life scores were also higher in the intervention group (mean 293.16, SD 34.21 vs mean 276.37, SD 32.21; P=.02). The number of steps per day increased in the intervention group (9768.56 in week 1 and 11,389.12 in week 12). The estimated glomerular filtration rate (eGFR) of the intervention group was higher than that of the control group (mean 72.47, SD 24.28 vs mean 59.69, SD 22.25 mL/min/1.73m 2 ; P=.03) and the decline in eGFR was significantly slower in the intervention group (-0.56 vs -4.58 mL/min/1.73m 2 ). There were no differences in body composition between groups postintervention., Conclusions: The use of wearable devices, a health management platform, and social media support not only strengthened self-efficacy and self-management but also improved quality of life and a slower eGFR decline in people with CKD at stages 1-4. These results outline a new self-management model to promote healthy lifestyle behaviors for patients with CKD., Trial Registration: ClinicalTrials.gov NCT04617431; https://www.clinicaltrials.gov/ct2/show/NCT04617431., (©Wen-Yi Li, Fu-Chun Chiu, Jyun-Kai Zeng, Yao-Wei Li, Su-Hua Huang, Hui-Chin Yeh, Bor-Wen Cheng, Feng-Jung Yang. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.12.2020.)

Aims: Recently, the spectrum of background mutation in the genes implicated in sudden arrhythmic death syndrome (SADS), has been elucidated in the Caucasian populations. However, this information is largely unknown in the Asian populations., Methods and Results: We assessed the background rare variants (minor allele frequency < 0.01) of major SADS genes in whole genome sequence data of 1514 healthy Taiwanese subjects from the Taiwan Biobank. We found up to 45% of healthy subjects have a rare variant in at least one of the major SADS genes. Around 3.44% of healthy subjects had multiple mutations in one or multiple genes. The background mutation rates in long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy genes were similar, but those in Brugada syndrome (BrS) (SCN5A) and hypertrophic cardiomyopathy (HCM) genes (MYBPC3, MYH7, and TNNT2) were higher, compared to those reported in the Caucasian populations. Furthermore, the rate of incidental pathogenic variant was highest in MYBPC3 gene. Finally, the number of variant was proportional to the exon length of the gene (R2 = 0.486, P = 0.0056) but not related to its functional or evolutionary importance (degree of evolutionary conservation) (R2 = 0.0008, P = 0.9218), suggesting that the mutation was random. The ratio of variant number over exon nucleotide length was highest in MYBPC3, MYH7, and TNNT2 genes., Conclusion: Unique features of background SADS gene mutation in the Asian populations include higher prevalence of incidental variant in HCM, BrS, and long QT 3 (SCN5A) genes. HCM genes have the highest variant number per exon length., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

In this study, green composite films based on cellulose nanocrystal/chitosan (CNC/CS) were fabricated by solution casting. FTIR, XRD, SEM, and TEM characterizations were conducted to determine the structure and morphology of the prepared films. The addition of only 4 wt.% CNC in the CS film improved the tensile strength and Young's modulus by up to 39% and 78%, respectively. Depending on CNC content, the moisture absorption decreased by 34.1-24.2% and the water solubility decreased by 35.7-26.5% for the composite films compared with neat CS film. The water vapor permeation decreased from 3.83 × 10 -11 to 2.41 × 10 -11 gm -1 s -1 Pa -1 in the CS-based films loaded with (0-8 wt.%) CNC. The water and UV barrier properties of the composite films showed better performance than those of neat CS film. Results suggested that CNC/CS nanocomposite films can be used as a sustainable packaging material in the food industry., Competing Interests: The authors declare no conflict of interest.

Polyamide 6 (PA6)/poly(vinylidene fluoride) (PVDF) blend-based nanocomposites were successfully prepared using a twin screw extruder. Carbon nanotube (CNT) and organo-montmorillonite (30B) were used individually and simultaneously as reinforcing nanofillers for the immiscible PA6/PVDF blend. Scanning electron micrographs showed that adding 30B reduced the dispersed domain size of PVDF in the blend, and CNT played a vital role in the formation of a quasi-co-continuous PA6-PVDF morphology. Transmission electron microscopy observation revealed that both fillers were mainly located in the PA6 matrix phase. X-ray diffraction patterns showed that the presence of 30B facilitated the formation of γ-form PA6 crystals in the composites. Differential scanning calorimetry results indicated that the crystallization temperature of PA6 increased after adding CNT into the blend. The inclusion of 30B retarded PA6 nucleation (γ-form crystals growth) upon crystallization. The Young's and flexural moduli of the blend increased after adding CNT and/or 30B. 30B exhibited higher enhancing efficiency compared with CNT. The composite with 2 phr 30B exhibited 21% higher Young's modulus than the blend. Measurements of the rheological properties confirmed the development of a pseudo-network structure in the CNT-loaded composites. Double percolation morphology in the PA6/PVDF blend was achieved with the addition of CNT.

Eco-friendly cellulose nanocrystal/silver/alginate (CNC/Ag/Alg) bionanocomposite films were successfully prepared by blending of CNC with Ag/Alg solution. The CNC was fabricated from cellulose microcrystal (CMC) by acid hydrolysis method. The Ag nanoparticles (AgNPs) were generated by using Alg as a reducing agent through hydrothermal process. AgNPs-included composite films showed characteristic plasmonic effect of the AgNPs with the maximum absorption at 491 nm and they also showed high ultraviolet (UV) barrier properties. The CNC/Ag/Alg composite films were analyzed by using scanning electron microscopy, transmission electron microscopy, optical microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction technique. Depending on the type of nanofillers, tensile strength of the composite films increased by 39-57% and water vapor permeation decreased by 17-36% compared with those of the neat Alg films. The Ag/Alg and CNC/Ag/Alg films showed brown color as detected from the increase of both 'b' and 'a' parameters by colorimeter. The UV and water barrier properties of Alg based composite films were found higher than the Alg films. The obtained results suggested that the prepared composite films can be used in food packaging applications.

This study investigated the relationship between creativity and negative emotion, and the effects of integrating creative insight into the reappraisal process on negative emotions. In Study 1, participants' creativity and baseline anxiety levels were measured; then anxiety was induced, and anxiety levels were reassessed. In Study 2, participants wrote about past negative events and then completed the positive and negative affect schedule. They were split into three groups (insight reappraisal, simple reappraisal, or control groups); each of them received a separate intervention, and then they completed positive and negative affect schedule again. In Study 3, participants were randomly assigned to insight reappraisal or control groups; apart from measuring cognitive changes, the procedures were identical to Study 2. All participants were undergraduate students. Results showed that flexibility, originality, risk-taking, and complexity are negatively correlated with anxiety, and that insight reappraisal can induce insight experience and enhance cognitive changes, and reduce negative emotional responses. Therefore, integrating creative insight into the reappraisal process can enhance its effectiveness in reducing negative emotions.

In this work, κ-carrageenan bionanocomposite films were prepared by solution casting of a mixture of κ-carrageenan, glycerol, and various amounts of cellulose nanocrystals (CNCs, 0-9 wt.%). The structure and morphology of the bionanocomposite films were characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Compared with κ-carrageenan films, the κ-carrageenan bionanocomposite films showed better mechanical and barrier properties (water and UV) and thermal stability. The water contact angle increased from 23.30° to 71.80° and the water vapor permeation decreased from 8.93 gm -1  s -1  Pa -1 to 4.69 × 10 -11  gm -1  s -1  Pa -1 in the κ-carrageenan films loaded with 9-7 wt.% CNCs, respectively. The tensile strength and elongation at break of the films increased from 38.33 ± 3.79 MPa to 52.73 ± 0.70 MPa and from 21.50 ± 3.72% to 28.27 ± 2.39%, respectively, after CNC loading increased from 0 wt.% to 7.0 wt.%. These results indicated that the κ-carrageenan nanocomposite films have potential applications in food packaging., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this study, a graphene nanoplatelet (GNP) was used as a reinforcing filler to prepare poly(vinylidene fluoride) (PVDF)/high density polyethylene (HDPE) blend-based nanocomposites through a melt mixing method. Scanning electron microscopy confirmed that the GNP was mainly distributed within the PVDF matrix phase. X-ray diffraction analysis showed that PVDF and HDPE retained their crystal structure in the blend and composites. Thermogravimetric analysis showed that the addition of GNP enhanced the thermal stability of the blend, which was more evident in a nitrogen environment than in an air environment. Differential scanning calorimetry results showed that GNP facilitated the nucleation of PVDF and HDPE in the composites upon crystallization. The activation energy for non-isothermal crystallization of PVDF increased with increasing GNP loading in the composites. The Avrami n values ranged from 1.9⁻3.8 for isothermal crystallization of PVDF in different samples. The Young's and flexural moduli of the blend improved by more than 20% at 2 phr GNP loading in the composites. The measured rheological properties confirmed the formation of a pseudo-network structure of GNP-PVDF in the composites. The electrical resistivity of the blend reduced by three orders at a 3-phr GNP loading. The PVDF/HDPE blend and composites showed interesting application prospects for electromechanical devices and capacitors.

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK a and lower log D 7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D 7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

The emergence of drug-resistant malaria parasites continues to hamper efforts to control this lethal disease. Dihydroorotate dehydrogenase has recently been validated as a new target for the treatment of malaria, and a selective inhibitor (DSM265) of the Plasmodium enzyme is currently in clinical development. With the goal of identifying a backup compound to DSM265, we explored replacement of the SF 5 -aniline moiety of DSM265 with a series of CF 3 -pyridinyls while maintaining the core triazolopyrimidine scaffold. This effort led to the identification of DSM421, which has improved solubility, lower intrinsic clearance, and increased plasma exposure after oral dosing compared to DSM265, while maintaining a long predicted human half-life. Its improved physical and chemical properties will allow it to be formulated more readily than DSM265. DSM421 showed excellent efficacy in the SCID mouse model of P. falciparum malaria that supports the prediction of a low human dose (<200 mg). Importantly DSM421 showed equal activity against both P. falciparum and P. vivax field isolates, while DSM265 was more active on P. falciparum. DSM421 has the potential to be developed as a single-dose cure or once-weekly chemopreventative for both P. falciparum and P. vivax malaria, leading to its advancement as a preclinical development candidate., Competing Interests: MAP, SAC, PKR, DW and DM hold a pending patent covering DSM421 and related compounds. DW, DM and MJP are paid consultants to MMV.

The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand-androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD 7.4 , aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins.

Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505-5.545, P = 0.001; and OR 2.55, 95% CI = 1.428-4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025-3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD., Competing Interests: The remaining authors have no conflicts of interest to disclose.

We present a series of oxadiazolothiazinones, selective inotropic agents on isolated cardiac tissues, devoid of chronotropy and vasorelaxant activity. Functional and binding data for the precursor of the series (compound 1) let us hypothesize LTCC blocking activity and the existence of a recognition site specific for this scaffold. We synthesized and tested 22 new derivatives: introducing a para-methoxyphenyl at C-8 led to compound 12 (EC50 = 0.022 μM), twice as potent as its para-bromo analogue (1). For 10 analogues, we extended the characterization of the biological properties by including the assessment of metabolic stability in human liver microsomes and cytochrome P450 inhibition potential. We observed that the methoxy group led to active compounds with low metabolic stability and high CYP inhibition, whereas the protective effect of bromine resulted in enhanced metabolic stability and reduced CYP inhibition. Thus, we identified two para-bromo benzothiazino-analogues as candidates for further studies.

Drug-induced toxicity is a leading cause of drug withdrawal from clinical development and clinical use and represents a major impediment to the development of new drugs. The mechanisms underlying drug-induced toxicities are varied; however, metabolic bioactivation to form reactive metabolites has been identified as a major contributor.1,2 These electrophilic species can covalently modify important biological macromolecules and thereby increase the risk of adverse drug reactions or idiosyncratic toxicity. Consequently, screening compounds for their propensity to form reactive metabolites has become an integral part of drug discovery programs. This screening process typically involves identification of structural alerts as well as the generation of reactive metabolites in vitro in subcellular hepatic fractions, followed by trapping the reactive species with nucleophiles and characterization via LC-MS. This article presents evidence for the bioactivation of a series of aminopyrazole derivatives via LC-MS detection of glutathione ethyl ester-trapped reactive intermediates formed in human liver microsomal incubations. These results indicate that the aminopyrazole motif, within specific contexts, may be considered a new structural alert for the potential formation of reactive metabolites.

This paper addresses the trap exploration in amorphous boron-doped ZnO (ZnO:B) films using an asymmetric structure of metal-oxide-metal. In this work, the structure of Ni/ZnO:B/TaN is adopted and the ZnO:B film is deposited by RF magnetron sputtering. The as-deposited ZnO:B film is amorphous and becomes polycrystalline when annealing temperature is above 500 °C. According to the analysis of conduction mechanism in the as-deposited ZnO:B devices, Ohmic conduction is obtained at positive bias voltage because of the Ohmic contact at the TaN/ZnO:B interface. Meanwhile, hopping conduction is obtained at negative bias voltage due to the defective traps in ZnO:B in which the trap energy level is lower than the energy barrier at the Ni/ZnO:B interface. In the hopping conduction, the temperature dependence of I-V characteristics reveals that the higher the temperature, the lower the current. This suggests that no single-level traps, but only multiple-level traps, exist in the amorphous ZnO:B films. Accordingly, the trap energy levels (0.46-0.64 eV) and trap spacing (1.1 nm) in these multiple-level traps are extracted.