Patients with atrial fibrillation are known to have a high risk of mortality. There is a paucity of population-based studies about the impact of atrial fibrillation on the mortality risk stratified ...by age, sex, and detailed causes of death.
A total of 15,411 patients with atrial fibrillation from the Korean National Health Insurance Service-National Sample Cohort were enrolled, and causes of death were identified according to codes of the 10th revision of the International Classification of Diseases.
From 2002 to 2013, a total of 4,479 (29%) deaths were confirmed, and the crude mortality rate for all-cause death was 63.3 per 1,000 patient-years. Patients with atrial fibrillation had a 3.7-fold increased risk of all-cause death compared with the general population. The standardized mortality ratio for all-cause death was the highest in young patients and decreased with increasing age (standardized mortality ratio 21.93, 95% confidence interval 7.60-26.26 in patients aged <20 years; standardized mortality ratio 2.77, 95% confidence interval 2.63-2.91 in patients aged ≥80 years). Women with atrial fibrillation exhibited a greater excess mortality risk than men (standardized mortality ratio 3.81, 95% confidence interval 3.65-3.98 in women; standardized mortality ratio 3.35, 95% confidence interval 3.21-3.48 in men). Cardiovascular disease was the leading cause of death (38.5%), and cerebral infarction was the most common specific disease. Patients with atrial fibrillation had an about 5 times increased risk of death due to cardiovascular disease compared with the general population.
Patients with atrial fibrillation had a 4 times increased risk of mortality compared with the general population. However, the impact of atrial fibrillation on mortality decreased with age and in men. Cerebral infarction was the most common cause of death, and more attention should be paid to reducing the risk of stroke.
Nanocarbon materials, such as graphene and carbon nanotubes (CNTs), have attracted considerable attention as the main or supplementary components in various optoelectronics boosting the device ...performance and improving the process conditions. Specifically, their application to perovskite solar cells, which are among the most promising photovoltaic devices acknowledged for eco‐friendly energy generation, has significantly impacted the current standing of metal halide perovskite‐based devices. The uniqueness of the nanocarbon applications can be attributed to their outstanding optical, electrical, chemical and mechanical properties, which conventional materials do not possess. This review overviews past and present reports on graphene‐ and CNT‐incorporated perovskite solar cells. Versatile roles and various synthetic methodologies of the applied nanocarbons in perovskite solar cells, including the material growth methods and sources, and functions as transparent electrodes, charge‐transporting layers, interfacial layers, additives and encapsulants, are categorized and graphically illustrated. The discussion expands from single‐junction to tandem applications with silicon solar cells, where the nanocarbon materials also play an equally important yet divergent function. Applications of each graphene and CNTs to the silicon‐perovskite tandem solar cells are interpreted in terms of what roles they play and how they solve the conventional problems. This review serves as the guideline for the photovoltaics researchers in advancing devices using nanocarbons.
The overview and outlook on graphene‐ and carbon nanotube‐applied perovskite solar cells for both single‐junction and tandem applications in this review provide an insight to research strategies for nanocarbons and optoelectronics. The versatile roles and synthesis methods of applied nanocarbons in perovskite solar cells open a gateway to next‐generation energy harvesting devices in terms of both performance and functionality.
We sought to evaluate the clinical implication of LAE based on left atrial anterior-posterior (LA AP) dimension or LA volume index (LAVI) in Korean patients with atrial fibrillation (AF). We enrolled ...8159 AF patients from the CODE-AF registry. The primary outcome was rate of stroke or systemic embolism (SSE). The prevalence of mild, moderate, and severe LAE by LA AP dimension was 30.6%, 18.5%, and 21.4%, and by LAVI (available in 5808 patients) was 15.7%, 12.5% and 37.8%, respectively. Compared with no or mild LAE, patients with significant LAE (moderate to severe LAE, n = 3258, 39.9%) were associated with a higher rate of SSE (2.5% vs. 1.4%, P = 0.001). Multivariable analysis suggested presence of significant LAE by LA AP dimension was associated with a higher risk of SSE in the overall population (HR 1.57, 95% CI: 1.14-2.17, P = 0.005) and in patients using anticoagulants (n = 5836, HR 1.79, 95% CI: 1.23-2.63, P = 0.002). Patients with significant LAE by LAVI were also at higher risk of SSE (HR 1.58, 95% CI: 1.09-2.29, P = 0.017). In conclusion, significant LAE by LA dimension or LAVI was present in 39.9% and 50.2% of AF patients, respectively, and was associated with a higher rate of SSE.
Mechanically resilient optoelectronic devices are relevant for a wide range of applications, including portable and wearable devices. Perovskite thin film‐based devices are a suitable choice for ...designing such resilient systems as it demonstrates high performance while preserving moderate mechanical compliance. Yet its mechanical property can be improved further by integrating the energy dissipation system and self‐healing ability into the thin film. Copolymers containing Lewis‐base functional groups, elastomer chains, and cyclic linkages are synthesized and introduced into the perovskite precursor. The polymers impart multifunctional effect of controlled crystal growth, defect passivation, protection against moisture, mechanical energy dissipation, and self‐recoverability. The polymer‐added perovskite solar cells are shown to provide a power conversion efficiency of 23.25% (a steady‐state efficiency of 22.61%), due to the strong coordinative covalent interaction between the polymer and the perovskite. An operational lifetime of solar cells under harsh conditions is also substantially extended by the polymer incorporation. Furthermore, the interchain hydrogen‐bond strength controlled by the cyclic linkage, and hybrid cross‐linked network formed within the thin film significantly improves the mechanical stability and self‐recoverability of the thin film. As a result, the devices demonstrate robustness under 2000 cyclic flex tests at a bending radius of 1 mm.
Newly designed copolymers with multi‐functionalities are synthesized and incorporated in perovskite solar cells to simultaneously improve device efficiency, stability, and mechanical resilience. The polymers form a hybrid cross‐linked network composed of mixed physical and chemical bonds within the perovskite thin film, which provides controlled crystal growth and surface defect passivation, as well as effective energy dissipation and self‐healing behaviors during and after mechanical deformation of devices.
Dithiocarbonate‐based non‐hygroscopic polymers with a glass transition temperature (Tg) and polydispersity index (PDI) of ≈4 °C and 1, respectively, are synthesized through living cationic ...ring‐opening polymerization. These liquid‐state polymers are characterized by monodispersity based on the low Tg and PDI, rendering remarkable miscibility with the perovskite precursors without aggregation. Accordingly, these polymers are added to perovskite solar cells (PSCs) to enhance their power conversion efficiency (PCE). The PCE of reference PSCs increases from 19.70% to 23.52% after direct addition of the synthesized polymer. This efficiency improvement is attributed to the considerable increases in short‐circuit current density (JSC) and fill factor (FF), resulting from the augmented size and defect passivation of perovskite crystals induced by added polymers. In fact, the PCE and JSC of the devices measured in the laboratory and the certification center are the highest among the reported polymer‐added PSCs, thanks to the great miscibility of the new polymers leading to the large amount addition which enables more thorough passivation among the grain boundaries. The improvement in open‐circuit voltage falls short as compared to that in JSC and FF, ascribed to the relatively moderate interaction strength between perovskite materials and dithiocarbonate groups.
Liquid‐state dithiocarbonate‐based polymers with monodispersity render exceptionally high performance when used as additives for perovskite solar cells. The dithiocarbonate‐based polymers are synthesized by connecting five‐membered cyclic dithiocarbonates through the living cationic ring opening polymerization. The resulting devices exhibit efficiencies of 23.5% and 22.0% during the laboratory and certified measurement, respectively, which are the highest among the perovskite solar cells containing polymers.
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse ...aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.
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•Reduced blood flow with age is due to loss of endothelial NAD+-SIRT1 activity•NAD+ and H2S control muscle angiogenesis and increase endurance in old mice•The NAD precursor NMN mimics and augments exercise by inhibiting NICD-Notch•Neovascularization is as important as mitochondria for rejuvenating muscle
Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice.
Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, there are currently no clinical guidelines for LC surveillance in IPF. This study aimed to ...investigate the cumulative incidence and survival outcomes of LC in IPF. Using the National Health Insurance Service database, including medical information on people aged ≥ 40 years between 2011 and 2016, we identified IPF patients and confirmed the presence of comorbid LC. Patients diagnosed with IPF in 2011 were washed out, and mortality data were analyzed from 2012 to 2018. A total of 7277 newly diagnosed IPF patients were identified among Korean citizens aged ≥ 40 years (about 50 million people) between 2011 and 2016. Their average age was 71.5 years and 72.8% of them were male. The prevalence of LC in the IPF cases was 6.4%. The cumulative incidence rates of LC in IPF patients who did not have LC at the time of IPF diagnosis were 1.7%, 4.7%, and 7.0%, at 1, 3, and 5 years, respectively. The median time from IPF diagnosis to LC development was 16.3 (Interquartile range, 8.2-28.8) months. The survival rate was significantly lower in the IPF with LC group than the IPF without LC group (P < 0.001). We concluded that IPF increases LC risk, and LC weakens survival outcomes in IPF. Close surveillance for LC development is mandatory for patients with IPF.
Lung cancer is one of the most common reasons for cancer-induced mortality across the globe, despite major advancements in the treatment strategies including radiotherapy and chemotherapy. Existing ...reports suggest that CXCR4 is frequently expressed by malignant tumor and is imperative for vascularization, tumor growth, cell migration, and metastasis pertaining to poor prognosis. In this study, we infer that CXCR4 confers resistance to ionizing radiation (IR) in nonsmall cell lung cancer (NSCLC) cells. Further, on the basis of colony forming ability, one finds that drug-resistant A549/GR cells with improved CXCR4 expression exhibited more resistance to IR than A549 cells evidenced along with a reduction in the formation of γ-H2AX foci after IR. Transfection of shRNA against CXCR4 or treatment of pharmacological inhibitor (AMD3100) both led to sensitization of A549/GR cells towards IR. Conversely, the overexpression of CXCR4 in A549 and H460 cell lines was found to improve clonogenic survival, and reduce the formation of γ-H2AX foci after IR. CXCR4 expression was further correlated with STAT3 activation, and suppression of STAT3 activity with siSTAT3 or a specific inhibitor (WP1066) significantly stymied the colony-forming ability and increased γ-H2AX foci formation in A549/GR cells, indicating that CXCR4-mediated STAT3 signaling plays an important role for IR resistance in NSCLC cells. Finally, CXCR4/STAT3 signaling was mediated with the upregulation of Slug and downregulation of the same with siRNA, which heightened IR sensitivity in NSCLC cells. Our data collectively suggests that CXCR4/STAT3/Slug axis is paramount for IR resistance of NSCLC cells, and can be regarded as a therapeutic target to enhance the IR sensitivity of this devastating cancer.
This study has dual research objectives: 1) to evaluate the land use characteristics of the pedestrian catchment areas (PCA) of subway stations in the Seoul metropolitan area (SMA) in terms of ...transit-oriented development (TOD) principles and 2) to investigate the influence of each PCA's land use characteristics on station-level ridership. The major findings can be summarized as follows. First, the built environments of subway PCAs in Seoul were found to be compatible with TOD principles in terms of density and diversity. They have declining density gradients of population and employment that extend outward from a station and have a high level of mixed-use land.
Second, population and employment densities, land use mix diversity, and intermodal connectivity all have a positive impact on subway ridership, but differ in their spatial ranges. In particular, the influence spans of residential and commercial development patterns (population density and the proportion of commercial land) and mixed land use on ridership were limited to only the core and primary PCAs. Consequently, with respect to TOD in a compact city like Seoul, we recommend that a PCA be defined to encompass a radius of 600m.
•To investigate the relationship between built environments and transit ridership in Seoul.•Built environments of subway PCAs were found to be compatible with TOD principles in terms of density and diversity.•Population and employment densities, land use mix, and intermodal connectivity have a positive impact on ridership.•We recommend that a PCA be define to encompass a radius of 600 m.
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•Pluripotent stem cell (PSC)-derived expandable human hepatocyte-like liver organoids were generated.•PSC-derived human hepatic organoids are capable of long-term expansion with ...competent liver functionality.•PSC-derived human hepatic organoids provide a robust hepatic model for toxicity prediction and drug screening.
The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids have not been developed.
We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. The organoids were applied to screening platforms for the prediction of toxicity and the evaluation of drugs that target hepatic steatosis through real-time monitoring of cellular bioenergetics and high-content analyses.
Our organoids were morphologically indistinguishable from adult liver tissue-derived epithelial organoids and exhibited self-renewal. With further maturation, their molecular features approximated those of liver tissue, although these features were lacking in 2D differentiated hepatocytes. Our organoids preserved mature liver properties, including serum protein production, drug metabolism and detoxifying functions, active mitochondrial bioenergetics, and regenerative and inflammatory responses. The organoids exhibited significant toxic responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis.
Our organoids exhibit self-renewal (expandable and further able to differentiate) while maintaining their mature hepatic characteristics over long-term culture. These organoids may provide a versatile and valuable platform for physiologically and pathologically relevant hepatic models in the context of personalized medicine.
A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.
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