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This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer's and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.
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Encéfalo , População do Leste Asiático , Idoso , Pessoa de Meia-Idade , Humanos , Estudos de Coortes , Encéfalo/diagnóstico por imagem , Córtex Cerebral , Cognição , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.
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Tratamento Farmacológico da COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pandemias , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Neuromorphic computing based on two-dimensional transition-metal dichalcogenides (2D TMDs) has attracted significant attention recently due to their extraordinary properties generated by the atomic-thick layered structure. This study presents sulfur-defect-assisted MoS2 artificial synaptic devices fabricated by a simple sputtering process, followed by a precise sulfur (S) vacancy-engineering process. While the as-sputtered MoS2 film does not show synaptic behavior, the S vacancy-controlled MoS2 film exhibits excellent synapse with remarkable nonvolatile memory characteristics such as a high switching ratio (â¼103), a large memory window, and long retention time (â¼104 s) in addition to synaptic functions such as paired-pulse facilitation (PPF) and long-term potentiation (LTP)/depression (LTD). The synaptic device working mechanism of Schottky barrier height modulation by redistributing S vacancies was systemically analyzed by electrical, physical, and microscopy characterizations. The presented MoS2 synaptic device, based on the precise defect engineering of sputtered MoS2, is a facile, low-cost, complementary metal-oxide semiconductor (CMOS)-compatible, and scalable method and provides a procedural guideline for the design of practical 2D TMD-based neuromorphic computing.
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The advancement of ion transport applications will require the development of functional materials with a high ionic conductivity that is stable, scalable, and micro-patternable. We report unusually high ionic conductivity of Li+, Na+, and K+ in 2D MoS2 nanofilm exceeding 1 S/cm, which is more than 2 orders of magnitude higher when compared to that of conventional solid ionic materials. The high ion conductivity of different cations can be explained by the mitigated activation energy via percolative ion channels in 2H-MoS2, including the 1D ion channel at the grain boundary, as confirmed by modeling and analysis. We obtain field-effect modulation of ion transport with a high on/off ratio. The ion channel is large-scale patternable by conventional lithography, and the thickness can be tuned down to a single atomic layer. The findings yield insight into the ion transport mechanism of van der Waals solid materials and guide the development of future ionic devices owing to the facile and scalable device fabrication with superionic conductivity.
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BACKGROUND/AIMS: Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. METHODS: All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. RESULTS: Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. CONCLUSION: Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.
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Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/diagnóstico , COVID-19/mortalidade , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia Viral/complicações , Sistema Renina-Angiotensina , República da Coreia/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
Established genetic risk factors for Alzheimer's disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal cortical thickness in 2643 Koreans meeting the clinical criteria for AD (n = 209), mild cognitive impairment (n = 1449) or normal cognition (n = 985). A missense variant, rs77359862 (R274W), in the SHANK-associated RH Domain Interactor (SHARPIN) gene was associated with entorhinal cortical thickness (p = 5.0 × 10-9) and hippocampal volume (p = 5.1 × 10-12). It revealed an increased risk of developing AD in the mediation analyses. This variant was also associated with amyloid-ß accumulation (p = 0.03) and measures of memory (p = 1.0 × 10-4) and executive function (p = 0.04). We also found significant association of other SHARPIN variants with hippocampal volume in the Alzheimer's Disease Neuroimaging Initiative (rs3417062, p = 4.1 × 10-6) and AddNeuroMed (rs138412600, p = 5.9 × 10-5) cohorts. Further, molecular dynamics simulations and co-immunoprecipitation indicated that the variant significantly reduced the binding of linear ubiquitination assembly complex proteins, SHPARIN and HOIL-1 Interacting Protein (HOIP), altering the downstream NF-κB signaling pathway. These findings suggest that SHARPIN plays an important role in the pathogenesis of AD.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Proteínas do Tecido Nervoso , UbiquitinasRESUMO
Alloying two-dimensional transition metal dichalcogenides (2D TMDs) is a promising avenue for band gap engineering. In addition, developing a scalable synthesis process is essential for the practical application of these alloys with tunable band gaps in optoelectronic devices. Here, we report the synthesis of optically uniform and scalable single-layer Mo1- xW xS2 alloys by a two-step chemical vapor deposition (CVD) method followed by a laser thinning process. The amount of W content ( x) in the Mo1- xW xS2 alloy is systemically controlled by the co-sputtering technique. The post-laser process allows layer-by-layer thinning of the Mo1- xW xS2 alloys down to a single-layer; such a layer exhibits tunable properties with the optical band gap ranging from 1.871 to 1.971 eV with variation in the W content, x = 0 to 1. Moreover, the predominant exciton complexes, trions, are transitioned to neutral excitons with increasing W concentration; this is attributed to the decrease in excessive charge carriers with an increase in the W content of the alloy. Photoluminescence (PL) and Raman mapping analyses suggest that the laser-thinning of the Mo1- xW xS2 alloys is a self-limiting process caused by heat dissipation to the substrate, resulting in spatially uniform single-layer Mo1- xW xS2 alloy films. Our findings present a promising path for the fabrication of large-scale single-layer 2D TMD alloys and the design of versatile optoelectronic devices.
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In the version of this Article originally published, a technical error in typesetting led to the traces in Fig. 3a being trimmed and made to overlap. The figure has now been corrected with the traces as supplied by the authors; the original and corrected Fig. 3a are shown below. Also, in the last paragraph of the section "Mechanistic study on Li diffusion in MoS2" the authors incorrectly included the term 'high-concentration' in the text "the Li diffusion will be dominated by high-concentration Li migration on the surface of T-MoS2 with a much smaller energy barrier (0.155 eV) to overcome". This term has now been removed from all versions of the Article. Finally, the authors have added an extra figure in the Supplementary Information (Supplementary Fig. 19) to show galvanostatic tests at 1 and 3 mA cm-2 for the MoS2-coated Li symmetric cells. The caption to Fig. 3 of the Article has been amended to reflect this, with the added wording "Galvanostatic tests at 1 and 3 mA cm-2 can be found in Supplementary Fig. 19."
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Among the candidates to replace Li-ion batteries, Li-S cells are an attractive option as their energy density is about five times higher (~2,600 Wh kg-1). The success of Li-S cells depends in large part on the utilization of metallic Li as anode material. Metallic lithium, however, is prone to grow parasitic dendrites and is highly reactive to several electrolytes; moreover, Li-S cells with metallic Li are also susceptible to polysulfides dissolution. Here, we show that ~10-nm-thick two-dimensional (2D) MoS2 can act as a protective layer for Li-metal anodes, greatly improving the performances of Li-S batteries. In particular, we observe stable Li electrodeposition and the suppression of dendrite nucleation sites. The deposition and dissolution process of a symmetric MoS2-coated Li-metal cell operates at a current density of 10 mA cm-2 with low voltage hysteresis and a threefold improvement in cycle life compared with using bare Li-metal. In a Li-S full-cell configuration, using the MoS2-coated Li as anode and a 3D carbon nanotube-sulfur cathode, we obtain a specific energy density of ~589 Wh kg-1 and a Coulombic efficiency of ~98% for over 1,200 cycles at 0.5 C. Our approach could lead to the realization of high energy density and safe Li-metal-based batteries.
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Two-dimensional transition metal dichalcogenides (2D TMDs) have gained great interest due to their unique tunable bandgap as a function of the number of layers. Especially, single-layer tungsten disulfides (WS2) is a direct band gap semiconductor with a gap of 2.1 eV featuring strong photoluminescence and large exciton binding energy. Although synthesis of MoS2 and their layer dependent properties have been studied rigorously, little attention has been paid to the formation of single-layer WS2 and its layer dependent properties. Here we report the scalable synthesis of uniform single-layer WS2 film by a two-step chemical vapor deposition (CVD) method followed by a laser thinning process. The PL intensity increases six-fold, while the PL peak shifts from 1.92 eV to 1.97 eV during the laser thinning from few-layers to single-layer. We find from the analysis of exciton complexes that both a neutral exciton and a trion increases with decreasing WS2 film thickness; however, the neutral exciton is predominant in single-layer WS2. The binding energies of trion and biexciton for single-layer WS2 are experimentally characterized at 35 meV and 60 meV, respectively. The tunable optical properties by precise control of WS2 layers could empower a great deal of flexibility in designing atomically thin optoelectronic devices.
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Two-dimensional (2D) van der Waal (vdW) heterostructures composed of vertically-stacked multiple transition metal dichalcogenides (TMDs) such as molybdenum disulfide (MoS2) and tungsten disulfide (WS2) are envisioned to present unprecedented materials properties unobtainable from any other material systems. Conventional fabrications of these hybrid materials have relied on the low-yield manual exfoliation and stacking of individual 2D TMD layers, which remain impractical for scaled-up applications. Attempts to chemically synthesize these materials have been recently pursued, which are presently limited to randomly and scarcely grown 2D layers with uncontrolled layer numbers on very small areas. Here, we report the chemical vapor deposition (CVD) growth of large-area (>2 cm(2)) patterned 2D vdW heterostructures composed of few layer, vertically-stacked MoS2 and WS2. Detailed structural characterizations by Raman spectroscopy and high-resolution/scanning transmission electron microscopy (HRTEM/STEM) directly evidence the structural integrity of two distinct 2D TMD layers with atomically sharp vdW heterointerfaces. Electrical transport measurements of these materials reveal diode-like behavior with clear current rectification, further confirming the formation of high-quality heterointerfaces. The intrinsic scalability and controllability of the CVD method presented in this study opens up a wide range of opportunities for emerging applications based on the unconventional functionalities of these uniquely structured materials.
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BACKGROUNDS/AIMS: We present our experience of laparoscopic liver resection for various liver diseases. METHODS: From April 2008 to August 2012 in Chungnam National University, 68 of 253 liver resections were performed laparoscopically. During the first year, laparoscopy-assisted liver resection was mainly performed and subsequently totally laparoscopic liver resection was the main operative type. Surgery type for treatment purposes was decided preoperatively. Clinical data were collected retrospectively and analyzed. RESULTS: Preoperatively, 43 patients (63.2%) were diagnosed with benign disease, 19 patients (27.9%) were malignant liver tumors and 6 patients (8.8%) were indeterminate liver tumor but favorable towards malignancy. Anatomical major liver resection was performed in 58 cases (85.3%) and 10 cases (14.7%) were non-anatomical resection. Left hemihepatectomy was performed in 38 cases (55.8%) followed by left lateral sectionectomy in 18 cases (26.5%), and segment IV and IVa segmentectomy, were each in 1 case. Mean operation time was 235.0 minutes (range, 60-470) and 14 patients (18.6%) had intraoperative transfusion. Mean postoperative hospital stay was 10.2 days (range, 4-32). Mean operation time of laparoscopy-assisted left lobectomy was 317 minutes and totally laparoscopic left lobectomy was 281 minutes, but there was no significant statistical difference between these two operation types. There were 11 episodes of postoperative complications in 8 patients. There was no mortality after laparoscopic liver resection. CONCLUSIONS: We concluded that laparoscopic liver resection is a feasible operation, but needs to be carefully conducted in malignant tumors.
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We report a case of Valsalva retinopathy associated with esophagogastroduodenoscopy (EGD) under propofol sedation. A 43-year-old woman who had no previous history of systemic or ocular disease presented with a complaint of decreased vision in her left eye, which developed one day after EGD under propofol sedation. According to the referring physician, the patient had experienced multiple sustained Valsalva maneuvers during EGD. The fundus examination of the left eye showed a large preretinal hemorrhage surrounded by multiple small retinal hemorrhages in the posterior pole. One month later, fundus examination revealed a floating organized vitreous hemorrhage. The pars plana vitrectomy was performed to treat persistent vitreous hemorrhage. One month after vitrectomy, fundus examination showed normal retina and the patient's vision recovered to 20/20. Valsalva maneuver can occur during EGD under sedation, and Valsalva retinopathy should be considered as a possible cause. Valsalva retinopathy should be included in the differential diagnosis when a patient complains of blurred vision following EGD.
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Endoscopia do Sistema Digestório/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Doenças Retinianas/etiologia , Manobra de Valsalva , Adulto , Feminino , HumanosRESUMO
Two-dimensional MoS2 is a promising material for next-generation electronic and optoelectronic devices due to its unique electrical and optical properties including the band gap modulation with film thickness. Although MoS2 has shown excellent properties, wafer-scale production with layer control from single to few layers has yet to be demonstrated. The present study explored the large-scale and thickness-modulated growth of atomically thin MoS2 on Si/SiO2 substrates using a two-step sputtering-CVD method. Our process exhibited wafer-scale fabrication and successful thickness modulation of MoS2 layers from monolayer (0.72 nm) to multilayer (12.69 nm) with high uniformity. Electrical measurements on MoS2 field effect transistors (FETs) revealed a p-type semiconductor behavior with much higher field effect mobility and current on/off ratio as compared to previously reported CVD grown MoS2-FETs and amorphous silicon (a-Si) thin film transistors. Our results show that sputter-CVD is a viable method to synthesize large-area, high-quality, and layer-controlled MoS2 that can be adapted in conventional Si-based microfabrication technology and future flexible, high-temperature, and radiation hard electronics/optoelectronics.