An ion‐based synaptic transistor (synaptor) is designed to emulate a biological synapse using controlled ion movements. However, developing a solid‐state electrolyte that can facilitate ion movement ...while achieving large‐scale integration remains challenging. Here, a bio‐inspired organic synaptor (BioSyn) with an in situ ion‐doped polyelectrolyte (i‐IDOPE) is demonstrated. At the molecular scale, a polyelectrolyte containing the tert‐amine cation, inspired by the neurotransmitter acetylcholine is synthesized using initiated chemical vapor deposition (iCVD) with in situ doping, a one‐step vapor‐phase deposition used to fabricate solid‐state electrolytes. This method results in an ultrathin, but highly uniform and conformal solid‐state electrolyte layer compatible with large‐scale integration, a form that is not previously attainable. At a synapse scale, synapse functionality is replicated, including short‐term and long‐term synaptic plasticity (STSP and LTSP), along with a transformation from STSP to LTSP regulated by pre‐synaptic voltage spikes. On a system scale, a reflex in a peripheral nervous system is mimicked by mounting the BioSyns on various substrates such as rigid glass, flexible polyethylene naphthalate, and stretchable poly(styrene‐ethylene‐butylene‐styrene) for a decentralized processing unit. Finally, a classification accuracy of 90.6% is achieved through semi‐empirical simulations of MNIST pattern recognition, incorporating the measured LTSP characteristics from the BioSyns.
A high‐performance solid‐state electrolyte containing mobile tert‐amine cations is designed and synthesized. The electrolyte to modulate synaptic weights is deposited and doped simultaneously with iCVD, using an in situ process that permits large‐scale integration. Bio‐inspired organic synaptic transistors are fabricated on rigid, flexible, and stretchable substrates. Short‐ and long‐term synaptic plasticity and their transformability are verified.
The aim of this clinical trial was to assess the efficacy and safety of low‐dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a ...2‐week placebo run‐in period, 176 patients were randomized to seven treatment groups (placebo, quarter‐dose combination, third‐dose combination, half‐dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter‐dose and half‐dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP‐lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third‐dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third‐dose group showed similar results with regard to the BP‐lowering effect as the quarter‐dose and half‐dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low‐dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP‐lowering effect in patients with essential hypertension without any safety concerns.
Objectives
To evaluate the diagnostic performance of attenuation imaging (ATI) in the detection of hepatic steatosis compared with a histopathology gold standard.
Methods
We prospectively enrolled ...108 consecutive patients (35 males; median age, 54.0 years) who underwent percutaneous liver biopsy for evaluation of diffuse liver disease between January 2018 and November 2018 in a tertiary academic center. Grayscale ultrasound examination with ATI was performed just before biopsy, and an attenuation coefficient (AC) was obtained from each patient. The degree of hepatic steatosis, fibrosis stage, and necroinflammatory activity were assessed on histopathologic examination. The significant factor associated with the AC was found by a linear regression analysis, and the diagnostic performance of the AC for the classification into each hepatic steatosis stage was evaluated by receiver operating characteristic (ROC) analysis.
Results
The distribution of hepatic steatosis grade on histopathology was 53/11/22/16/6 for none/mild (< 10%)/mild (≥ 10%)/moderate/severe steatosis, respectively. The area under the ROC curve, sensitivity, specificity, and optimal cutoff AC value for detection of hepatic steatosis ranged from 0.843–0.926, 74.5–100.0%, 77.4–82.8%, and 0.635–0.745, respectively. Multivariate analysis revealed that the degree of steatosis was the only significant determinant factor for the AC.
Conclusions
The AC from ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis. The degree of steatosis was the only significant factor affecting the AC, whereas fibrosis and inflammation were not.
Key Points
• Attenuation imaging (ATI) is based on two-dimensional grayscale ultrasound images that can incorporate into routine ultrasound examinations with less than 2 min of acquisition time.
• ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with an area under the ROC curves ranging from 0.843 to 0.926, and there was no technical failure in this study indicating high applicability of this technique.
• The degree of hepatic steatosis was the only significant factor affecting the result of ATI examination.
Background and purpose
The purpose was to assess the effect of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on diphasic dyskinesia in patients with Parkinson disease (PD) and to ...assess the factors associated with the remission of diphasic dyskinesia.
Methods
Medical records for PD patients who underwent bilateral STN DBS at the Movement Disorder Center of Seoul National University Hospital from March 2005 to November 2016 were reviewed. Patients were evaluated preoperatively and at 3, 6 and 12 months after surgery, and annually thereafter. The presence of peak‐dose dyskinesia and diphasic dyskinesia is based on the interview and examination of patients at baseline and at each follow‐up.
Results
Amongst 202 patients who underwent STN DBS, 66 patients who had diphasic dyskinesia preoperatively were included in the analysis. Diphasic dyskinesia disappeared in 49 (74%) after surgery. In 27 (55.1%) patients whose diphasic dyskinesia disappeared after DBS, peak‐dose and diphasic dyskinesia disappeared persistently from as early as 3 months postoperatively. Age at onset was younger and disease duration at surgery was longer in patients whose diphasic dyskinesia persisted compared with patients whose diphasic dyskinesia disappeared. Multivariate Cox regression analysis demonstrated that patients with greater postoperative decrease of dopaminergic medications were more likely to have remission of diphasic dyskinesia.
Conclusion
This study showed that bilateral STN DBS is effective in controlling diphasic dyskinesia and should be considered in PD patients with diphasic dyskinesia.
This study showed that bilateral STN DBS is effective in controlling diphasic dyskinesia and should be considered in PD patients with diphasic dyskinesia.
Background
Stratification of patients who undergo curative resection for early gastric cancer (EGC) is warranted due to the heterogeneity in the risk of developing extragastric recurrence (EGR). ...Therefore, we aimed to stratify the need for postoperative surveillance for EGR detection in patients with EGC by developing a model for predicting EGR-free survival.
Methods
This retrospective cohort study included patients who underwent postoperative surveillance after curative resection of EGC (
n
= 4149). Cox proportional hazard models were used to identify predictors to build a model for predicting EGR-free survival. Bootstrap-corrected c-index and calibration plots were used for internal and external (
n
= 2148) validations.
Results
A risk-scoring system was constructed using variables significantly associated with EGR-free survival: pathologic T stage (pT1bsm1, hazard ratio HR 4.928; pT1bsm2, HR 5.235; pT1bsm3, HR 7.748) and N stage (pN1, HR 4.056; pN2, HR 9.075; pN3, HR 30.659). Patients were dichotomized into a very-low-risk group or a low-or-greater-risk group. The 5-year EGR-free survival rates differed between the two groups (99.9 vs. 97.3%). The discriminative performance of the model was 0.851 (Uno’s c-index) and 0.751 in the internal and external cohorts, respectively. The calibration slope was 0.916 and 1.131 in the internal and external cohorts, respectively.
Conclusions
Our model for predicting EGR-free survival based on the pathologic T and N stages may be useful for stratifying patients who have undergone curative surgery for EGC. The results suggest that patients in the very-low-risk group may be spared from postoperative surveillance considering their extremely high EGR-free survival rate.
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human ...pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.
Compact but precise feature‐extracting ability is core to processing complex computational tasks in neuromorphic hardware. Physical reservoir computing (RC) offers a robust framework to map temporal ...data into a high‐dimensional space using the time dynamics of a material system, such as a volatile memristor. However, conventional physical RC systems have limited dynamics for the given material properties, restricting the methods to increase their dimensionality. This study proposes an integrated temporal kernel composed of a 2‐memristor and 1‐capacitor (2M1C) using a W/HfO2/TiN memristor and TiN/ZrO2/Al2O3/ZrO2/TiN capacitor to achieve higher dimensionality and tunable dynamics. The kernel elements are carefully designed and fabricated into an integrated array, of which performances are evaluated under diverse conditions. By optimizing the time dynamics of the 2M1C kernel, each memristor simultaneously extracts complementary information from input signals. The MNIST benchmark digit classification task achieves a high accuracy of 94.3% with a (196×10) single‐layer network. Analog input mapping ability is tested with a Mackey‐Glass time series prediction, and the system records a normalized root mean square error of 0.04 with a 20×1 readout network, the smallest readout network ever used for Mackey‐Glass prediction in RC. These performances demonstrate its high potential for efficient temporal data analysis.
An integrated temporal kernel using two memristors and one capacitor is fabricated. This kernel extracts complementary features from the input, ultimately processing MNIST images at 8‐bit to achieve an accuracy of 94.3%. Excellent prediction performance for the Mackey‐Glass time series is verified with NRMSE of 0.04 in minimal network size (20 × 1).
Hf
Zr
O
(x ∼ 0.5-0.7) has been the leading candidate of ferroelectric materials with a fluorite crystal structure showing highly promising compatibility with complementary metal oxide semiconductor ...devices. Despite the notable improvement in device performance and processing techniques, the origin of its ferroelectric crystalline phase (space group: Pca2
) formation has not been clearly elucidated. Several recent experimental and theoretical studies evidently showed that the interface and grain boundary energies of the higher symmetry phases (orthorhombic and tetragonal) contribute to the stabilization of the metastable non-centrosymmetric orthorhombic phase or tetragonal phase. However, there was a clear quantitative discrepancy between the theoretical expectation and experiment results, suggesting that the thermodynamic model may not provide the full explanation. This work, therefore, focuses on the phase transition kinetics during the cooling step after the crystallization annealing. It was found that the large activation barrier for the transition from the tetragonal/orthorhombic to the monoclinic phase, which is the stable phase at room temperature, suppresses the phase transition, and thus, plays a critical role in the emergence of ferroelectricity.
Abstract
Study Objectives
We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with ...video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD).
Methods
The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures.
Results
Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered “much or very much improved” on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman’s rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements).
Conclusions
Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.
Graphical Abstract
The unexpected ferroelectric properties of nanoscale hafnia-zirconia are considered to be promising for a wealth of applications including ferroelectric memory, field effect transistors, and ...energy-related applications. However, the reason why the unexpected ferroelectric Pca2
phase can be stabilized has not been clearly understood although numerous extensive theoretical and experimental results have been reported recently. The ferroelectric orthorhombic phase is not a stable phase under processing conditions from the viewpoint of bulk free energy. Although the possibility of stabilization of the ferroelectric phase due to the surface energy effect has been theoretically suggested, such a theoretical model has not been systematically compared with actual experimental results. In this study, the experimental observations on polymorphism in nanoscale HfO
-ZrO
solid solution thin films of a wide range of film compositions and thicknesses are comprehensively related to the theoretical predictions based on a thermodynamic surface energy model. The theoretical model can semi-quantitatively explain the experimental results on the phase-evolution, but there were non-negligible discrepancies between the two results. To understand these discrepancies, various factors such as the film stress, the role of a TiN capping layer, and the kinetics of crystallization are systematically studied. This work also reports on the evolution of electrical properties of the film, i.e. dielectric, ferroelectric, anti-ferroelectric, and morphotropic phase changes, as a function of the film composition and thickness. The in-depth analyses of the phase change are expected to provide an important guideline for subsequent studies.
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