Purpose To validate the diagnostic performance of commercially available, deep learning-based automatic white matter hyperintensity (WMH) segmentation algorithm for classifying the grades of the ...Fazekas scale and differentiating subcortical vascular dementia. Methods This retrospective, observational, single-institution study investigated the diagnostic performance of a deep learning-based automatic WMH volume segmentation to classify the grades of the Fazekas scale and differentiate subcortical vascular dementia. The VUNO Med-DeepBrain was used for the WMH segmentation system. The system for segmentation of WMH was designed with convolutional neural networks, in which the input image was comprised of a pre-processed axial FLAIR image, and the output was a segmented WMH mask and its volume. Patients presented with memory complaint between March 2017 and June 2018 were included and were split into training (March 2017-March 2018, n = 596) and internal validation test set (April 2018-June 2018, n = 204). Results Optimal cut-off values to categorize WMH volume as normal vs. mild/moderate/severe, normal/mild vs. moderate/severe, and normal/mild/moderate vs. severe were 3.4 mL, 9.6 mL, and 17.1 mL, respectively, and the AUC were 0.921, 0.956 and 0.960, respectively. When differentiating normal/mild vs. moderate/severe using WMH volume in the test set, sensitivity, specificity, and accuracy were 96.4%, 89.9%, and 91.7%, respectively. For distinguishing subcortical vascular dementia from others using WMH volume, sensitivity, specificity, and accuracy were 83.3%, 84.3%, and 84.3%, respectively. Conclusion Deep learning-based automatic WMH segmentation may be an accurate and promising method for classifying the grades of the Fazekas scale and differentiating subcortical vascular dementia.
Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) ...structure and function in subjects without overt heart disease.
In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy).
LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e' (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group.
Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease.
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.
Controlling magnetic states by a small current is essential for the next‐generation of energy‐efficient spintronic devices. However, it invariably requires considerable energy to change a magnetic ...ground state of intrinsically quantum nature governed by fundamental Hamiltonian, once stabilized below a phase‐transition temperature. Here, it is reported that, surprisingly, an in‐plane current can tune the magnetic state of the nanometer‐thin van der Waals ferromagnet Fe3GeTe2 from a hard magnetic state to a soft magnetic state. It is a direct demonstration of the current‐induced substantial reduction of the coercive field. This surprising finding is possible because the in‐plane current produces a highly unusual type of gigantic spin–orbit torque for Fe3GeTe2. In addition, a working model of a new nonvolatile magnetic memory based on the principle of the discovery in Fe3GeTe2, controlled by a tiny current, is further demonstrated. The findings open up a new window of exciting opportunities for magnetic van der Waals materials with potentially huge impact on the future development of spintronic and magnetic memory.
Substantial coercivity reduction by the current, larger at least by two orders of magnitude than those in previous reports, is found in the van der Waals ferromagnet Fe3GeTe2. It is theoretically shown to arise from an unusual type of gigantic spin–orbit torque, which itself is directly related to its special symmetries, large Berry curvature, and band topology. A working model of a new robust nonvolatile magnetic memory based on Fe3GeTe2, controlled by a much smaller current, is also produced.
Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen (1O2) and superoxide radical (O2 •–) is considered to trigger cell death pathways associated with protein dysfunction; ...however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm–2) because of the relatively high 1O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes.
Spin current generation through the spin-orbit interaction in non-magnetic materials lies at the heart of spintronics. When the generated spin current is injected to a ferromagnet, it produces ...spin-orbit torque and manipulates magnetization efficiently. Optically generated spin currents are expected to be superior to their electrical counterparts in terms of the manipulation speed. Here we report optical spin-orbit torques in heavy metal/ferromagnet heterostructures. The strong spin-orbit coupling of heavy metals induces photo-excited carriers to be spin-polarized, and their transport from heavy metals to ferromagnets induces a torque on magnetization. Our results demonstrate that heavy metals can generate spin-orbit torque not only electrically but also optically.
Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, ...direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL.
A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity.
Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408-1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823).
Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL.
The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. ...The “dual‐stream model” was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual‐stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal‐directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal‐directed Interaction of Stimulus and Task‐demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices—the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects—with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non‐navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non‐navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.
Scope
Cannabidiol (CBD), the most abundant non‐psychoactive constituent of the plant Cannabis sativa, is known to possess immune modulatory properties. This study investigates the effects of CBD on ...mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice.
Methods and results
Mouse bone marrow‐derived mast cells and human cord‐blood derived mast cells are generated. CBD suppressed antigen‐stimulated mast cell degranulation in a concentration‐dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long‐term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells.
Conclusion
Based on these results, the administration of CBD is a new therapeutic intervention in mast cell‐associated anaphylactic diseases.
The effects of cannabidiol (CBD), the most abundant non‐psychotropic component of marijuana plant (Cannabis sativa) on mast cell degranulation are investigated using mouse and human mast cells. The results suggest that CBD suppresses mast cell degranulation by inhibiting the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization. Consequently, CBD suppresses passive cutaneous anaphylaxis in mice.
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