Genetic Variants of PICALM rs541458 Modulate Brain Spontaneous Activity in Older Adults With Amnestic Mild Cognitive Impairment

Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI).Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF).Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = −0.543, p = 0.030).Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients

CondSeg: Ellipse Estimation of Pupil and Iris via Conditioned Segmentation

Parsing of eye components (i.e. pupil, iris and sclera) is fundamental for eye tracking and gaze estimation for AR/VR products. Mainstream approaches tackle this problem as a multi-class segmentation task, providing only visible part of pupil/iris, other methods regress elliptical parameters using human-annotated full pupil/iris parameters. In this paper, we consider two priors: projected full pupil/iris circle can be modelled with ellipses (ellipse prior), and the visibility of pupil/iris is controlled by openness of eye-region (condition prior), and design a novel method CondSeg to estimate elliptical parameters of pupil/iris directly from segmentation labels, without explicitly annotating full ellipses, and use eye-region mask to control the visibility of estimated pupil/iris ellipses. Conditioned segmentation loss is used to optimize the parameters by transforming parameterized ellipses into pixel-wise soft masks in a differentiable way. Our method is tested on public datasets (OpenEDS-2019/-2020) and shows competitive results on segmentation metrics, and provides accurate elliptical parameters for further applications of eye tracking simultaneously

LRDNet: A lightweight and efficient network with refined dual attention decorder for real-time semantic segmentation

Most of the current popular semantic segmentation convolutional networks are focus on accuracy and require large amount of computation, which is using complex models. In order to realize real-time performance in practical applications, such as embedded systems and mobile devices, lightweight semantic segmentation has become a new need, where the network model should keep good accuracy in very limited computing budget. In this paper, we propose a lightweight network with the refined dual attention decorder (termed LRDNet) for better balance between computational speed and segmentation accuracy. In the encoding part of LRDNet, we offer an asymmetric module based on the residual network for lightweight and efficiency. In this module, a combination of decomposition convolution and deep convolution is used to improve the efficiency of feature extraction. In the decoding part of LRDNet, we use a refined dual attention mechanism to reduce the complexity of the entire network. Our network attained precise real-time segmentation results on Cityscapes, CamVid datasets. Without additional processing and pretraining, the LRDNet model achieves 70.1 Mean IoU in the Cityscapes test set. With a parameter value below 0.66 M, it can be up to 77 FPS

Diagnostic value of isolated plasma biomarkers and its combination in neurodegenerative dementias: A multicenter cohort study

Plasma amyloid-β (Aβ), phosphorylated tau-181 (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) potentially aid in the diagnosis of neurodegenerative dementias. We aim to conduct a comprehensive comparison between different biomarkers and their combination, which is lacking, in a multicenter Chinese dementia cohort consisting of Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP)

Performance of the human papillomavirus E6/E7 mRNA assay in the primary screening of cervical cancer: opportunistic screening in Fujian, China

Purpose: A high-risk human papillomavirus E6/E7 mRNA (HR-HPV mRNA) assay is widely used in cervical cancer screening in China. However, it is still unclear whether stand-alone HR-HPV mRNA testing is sufficient for primary screening. The purpose of this study was to investigate the feasibility of a stand-alone HR-HPV mRNA assay for primary screening of cervical cancer. Methods: Women aged 21 and older were recruited in Fujian Province, China, from January 2020 to January 2022. Cervical exfoliated cells were collected for cervical cytology and HR-HPV mRNA assays, and women with positive results on either assay were referred for colposcopy. The screening effectiveness of the assay was calculated based on the cervical histology. When comparing the efficacy of the different screening strategies, only women aged 25 and older were included. Results: A total of 9927 women were recruited. This study identified 217 cases of high-grade squamous intraepithelial disease or worse (HSIL+). The overall age-specific HR-HPV infection rate showed a U-shaped distribution. The sensitivity of the HR-HPV mRNA assay to identify CIN2+ and CIN3+ was 97.2% and 97.9%, respectively, which was significantly higher than that of cytology (82.9% and 88.6%, P<0.001 and 0.002). The sensitivity of the HR-HPV mRNA primary screening strategy to identify CIN2+ and CIN3+ was 92.2% and 94.3%, respectively, which was similar to the co-testing strategy (P=0.336 and 0.394) and higher than the cytology primary screening (P=0.002 and 0.048). In addition, the HR-HPV primary screening strategy had a lower referral rate for colposcopy than cytology primary screening (5.4% vs 6.6%, P<0.001), and the screening cost was lower than co-testing ($29,594.3 per 1000 screened women vs$55,140 per 1000 screened women, P<0.001). Conclusion: In conclusion, the detection of CIN2+/CIN3+ by HR-HPV mRNA is both specific and sensitive. It may be suitable for primary screening of cervical cancer in China

Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer

Background: Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected through inflammatory responses or the tumor microenvironment. However, further exploration of the inflammatory response-related genes that have prognostic value, microenvironment infiltration, and chemotherapeutic therapies in CC is needed.Methods: The clinical data and mRNA expression profiles of CC patients were downloaded from a public database for this study. In the TCGA cohort, a multigene prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) and Cox analyses. CC patients from the GEO cohort were used for validation. K‒M analysis was used to compare overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors of OS. The immune cell infiltration and immune-related functional score were calculated by single-sample gene set enrichment analysis (GSEA). Immunohistochemistry was utilized to validate the protein expression of prognostic genes in CC tissues.Results: A genetic signature model associated with the inflammatory response was built by LASSO Cox regression analysis. Patients in the high-risk group had a significantly lower OS rate. The predictive ability of the prognostic genes was evaluated by means of receiver operating characteristic (ROC) curve analysis. The risk score was confirmed to be an independent predictor of OS by univariate and multivariate Cox analyses. The immune status differed between the high-risk and low-risk groups, and the cancer-related pathways were enriched in the high-risk group according to functional analysis. The risk score was significantly related to tumor stage and immune infiltration type. The expression levels of five prognostic genes (LCK, GCH1, TNFRSF9, ITGA5, and SLC7A1) were positively related to sensitivity to antitumor drugs. Additionally, the expression of prognostic genes was significantly different between CC tissues and myoma patient cervix (non-tumorous) tissues in the separate sample cohort.Conclusion: A model consisting of 5 inflammation-related genes can be used to predict prognosis and influence immune status in CC patients. Furthermore, the inhibition or enhancement of these genes may become a novel alternative therapy

Fire-Needle Moxibustion for the Treatment of Knee Osteoarthritis: A Meta-Analysis

Objectives. The aim of this study was to evaluate the effectiveness of fire-needle moxibustion as an intervention in the treatment of knee osteoarthritis (KOA). Methods. An updated meta-analysis of randomized controlled trials (RCTs) on fire-needle moxibustion in treating KOA was conducted by searching PubMed, Embase, the Cochrane Library, Web of Science, Wanfang database, and the Chinese Medical Database (CNKI) since their inception through March 2016. The meta-analysis was performed using RevMan 5.3. Results. Thirteen RCTs were identified in the systematic study which consisted of 1179 participants. Fire-needle moxibustion treatment group had a statistical significance on recovery rate as well as recovery and marked-improvement rate compared with control group. Subgroup analysis indicated that there was significant difference between fire-needle moxibustion group and control group. However, GRADE analysis indicated that the quality of evidence for all outcomes was relatively low. Only two of 13 studies reported adverse reactions (difficulty in movement and intolerance of cold). Conclusion. This meta-analysis suggests that fire-needle moxibustion is more effective than control group in symptom management of KOA. Further high quality trials should be conducted to evaluate the effectiveness of fire-needle moxibustion on KOA

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG