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The involvement of genetic factors in the pathogenesis of KC has long been recognized but the identification of variants affecting the underlying protein functions has been challenging. In this study, we selected 34 candidate genes for KC based on previous whole-exome sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls from Belgium, France and Italy. Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests. In our study, we detected enrichment of genetic variation across multiple gene-based tests for the genes COL2A1, COL5A1, TNXB, and ZNF469. The top hit in the single variant association test was obtained for a common variant in the COL12A1 gene. These associations were consistently found across independent subpopulations. Monocrotaline datasheet Interestingly, COL5A1, TNXB, ZNF469 and COL12A1 are all known Ehlers-Danlos Syndrome (EDS) genes. Though the co-occurrence of KC and EDS has been reported previously, this study is the first to demonstrate a consistent role of genetic variants in EDS genes in the etiology of KC. In conclusion, our data show a shared genetic etiology between KC and EDS, and clearly confirm the currently disputed role of ZNF469 in disease susceptibility for KC.To circumvent the von Neumann bottleneck, substantial progress has been made towards in-memory computing with synaptic devices. However, compact nanodevices implementing non-linear activation functions are required for efficient full-hardware implementation of deep neural networks. Here, we present an energy-efficient and compact Mott activation neuron based on vanadium dioxide and its successful integration with a conductive bridge random access memory (CBRAM) crossbar array in hardware. The Mott activation neuron implements the rectified linear unit function in the analogue domain. The neuron devices consume substantially less energy and occupy two orders of magnitude smaller area than those of analogue complementary metal-oxide semiconductor implementations. The LeNet-5 network with Mott activation neurons achieves 98.38% accuracy on the MNIST dataset, close to the ideal software accuracy. We perform large-scale image edge detection using the Mott activation neurons integrated with a CBRAM crossbar array. Our findings provide a solution towards large-scale, highly parallel and energy-efficient in-memory computing systems for neural networks.Timely performing electrocardiography (ECG) is crucial for early detection of ST-elevation myocardial infarction (STEMI). For shortening door-to-ECG time, a chief complaint-based "cardiac triage" protocol comprising (1) raising alert among medical staff with bedside triage tags, and (2) immediate bedside ECG after focused history-taking was implemented at the emergency department (ED) in a single tertiary referral center. All patients diagnosed with STEMI visiting the ED between November 2017 and January 2020 were retrospectively reviewed to investigate the effectiveness of strategy before and after implantation. Analysis of a total of 117 ED patients with STEMI (pre-intervention group, n = 57; post-intervention group, n = 60) showed significant overall improvements in median door-to-ECG time from 5 to 4 min (p = 0.02), achievement rate of door-to-ECG time 10 min for those with initially underestimated disease severity (from 90 to 10%, p less then 0.01) and walk-in (from 29.2 to 8.8%, p = 0.04) were both reduced. In conclusion, a chief complaint-based "cardiac triage" strategy successfully improved the quality of emergency care for STEMI patients through reducing delays in diagnosis and treatment.The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy.This study sought to estimate the association of children's body mass index (BMI) with their social function in Shanghai China. A large population-based cross-sectional study based on a propensity score matching (PSM) analysis was conducted. BMI was compared according to social communication questionnaire (SCQ) classification, and then SCQ score was compared in terms of BMI grouping before and after PSM. A positive SCQ was considered to indicate poor social communication and a negative SCQ was then supposed to be normal. After 13 matching, a total of 7563 children aged 3-12 years were included in analysis. There were statistically significant positive correlation of BMI with SCQ scores for obese females of school age (R2 = 0.043, p less then 0.001) and negative correlation of these two variables for school-aged females with malnutrition (R2 = 0.047, p = 0.027). In conclusion, BMI may be characterized as one of predictive factor for poor social function of these children.Lysine 2-hydroxyisobutyrylation (Khib) is a novel naturally occurring post-translational modification. The system Khib identification at proteomics level has been performed in various species and tissues to characterize the role of Khib in biological activities. However, the study of Khib in plant species is relatively less. In the present study, the first plant root tissues lysine 2-hydroxyisobutyrylome analysis was performed in wheat with antibody immunoprecipitation affinity, high resolution mass spectrometry-based proteomics and bioinformatics analysis. In total, 6328 Khib sites in 2186 proteins were repeatedly identified in three replicates. These Khib proteins showed a wide subcellular location distribution. Function and pathways characterization of these Khib proteins indicated that many cellular functions and metabolism pathways were potentially affected by this modification. Protein and amino acid metabolism related process may be regulated by Khib, especially ribosome activities and proteins biosynthesis process.
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