Search

Background: The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. Methods: This study included 226 migraineurs and 452 age‐ and sex‐matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP–SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. Results: The RASGRP2‐rs2230414 GT genotype was associated with decreased migraine risk compared with the wild‐type GG genotype [ORadj (95% CI): 0.674(0.458–0.989)]. PIK3R1‐rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004–2.083)]. The CACNA1H‐rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068–2.281)]. One significant two‐way SNP–SNP interaction was found (PRKCA rs2228945‐BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. Conclusions: This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway‐related gene polymorphisms and migraine risk. [ABSTRACT FROM AUTHOR]

Aim: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. Methods: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. Results: Twenty‐eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light‐chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL‐λ, one with AL‐κ and two with ATTR. Group 2 included 15 patients with AL‐λ and two patients with AL‐κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. Conclusions: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis. [ABSTRACT FROM AUTHOR]

Spin-transfer torque magnetic random access memory (MRAM) devices have considerable potential for high-performance computing applications; however, progress in this field has been hindered by difficulties in etching the magnetic tunnel junction (MTJ). One notable issue is electrical shorting caused by the accumulation of etching by-products on MTJ surfaces. Attempts to resolve these issues led to the development of step-MTJs, in which etching does not proceed beyond the MgO barrier; however, the resulting devices suffer from poor scalability and unpredictable shunting paths due to asymmetric electrode structures. This paper outlines the fabrication of pillar-shaped MTJs via a four-step etching process involving reactive-ion etching, ion-beam etching, oxygen exposure, and ion-trimming. The respective steps can be cross-tuned to optimize the shape of the pillars, prevent sidewall redeposition, and remove undesired shunting paths in order to enhance MTJ performance. In experiments, the proposed pillar-MTJs outperformed step-MTJs in key metrics, including tunneling magnetoresistance, coercivity, and switching efficiency. The proposed pillar-MTJs also enable the fabrication of MRAM cells with smaller cell sizes than spin–orbit torque devices and require no external field differing from voltage-controlled magnetic anisotropy devices. [ABSTRACT FROM AUTHOR]

This brief presents a comprehensive analysis of the output-dependent modulation (ODM) in a current-steering digital-to-analog converter (CS-DAC) based on the differential-quad switching (DQS) structure. A mathematical model is proposed to accurately describe ODM, which is categorized into two types: output transition errors and boundary effect errors. A novel approach of adding isolation devices is introduced and reinterpreted to mitigate the effect of ODM. The simulation results indicate that the inclusion of isolation devices efficiently suppresses the odd harmonics at mid-to-high frequency by a value that is 13 dB lower than before. Experimental validation is conducted on a 16-bit 250 MS/s CS-DAC fabricated in a 180 nm process. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. Methods: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. Results: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1–90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. Conclusions: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk. [ABSTRACT FROM AUTHOR]