To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD).
A comprehensive literature search was ...conducted up to October 31, 2022, in PubMed, Embase, Cochrane Library, Web of Science, and Scopus Database. To evaluate the diagnostic value, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Q∗ index were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was used to verify the robustness of the findings.
A total seven studies with 248,853 newborns was included in our meta-analysis. The pooled SEN and SPE were 1.00 (95% confidence interval CI: 0.89∼1.00) and 1.00 (95% CI: 1.00 to 1.00), respectively; the PLR and NLR were 1004.59 (95% CI: 251.37∼4014.91) and 0.13 (95% CI: 0.05∼0.34), respectively; the DOR was 877.96 (95% CI: 983.24∼78,366.32); the AUC and Q index were 0.8683 and 0.9326, respectively. Sensitivity analysis showed that two studies had an impact on the pooled results and mainly contributed to the heterogeneity.
CK-MM test demonstrated high accuracy in newborn screening for DMD and may be a valuable alternative in the early diagnosis of the disease followed by confirmatory genetic testing.
In the quantum noise stream cipher (QNSC) system, the low-order plaintext is encrypted by pre-shared keys into high-order ciphertext. However, high-speed optical communication systems have a huge ...demand for pre-shared keys. On the other hand, the separation of the secure communications sub-system from the secure key distribution (SKD) sub-system increases potential security risks and introduces additional resources overhead. In this letter, we propose an artificial amplitude noise-based SKD scheme (AAN-SKD) in QAM/QNSC to generate secret key for legal parties accordingly. The two orthogonal PAM symbols are superimposed to generate QAM symbols. Thus, the AAN-SKD can also be implemented in PAM modulation. In addition, the data transmission and AAN-SKD are completed in the same channel. Experimental results indicate that the key generation rate and key consistency ratio of the proposed scheme can reach 188.22 Mbit/s and 91%, respectively. Compared with quantum key distribution, the AAN-SKD has the advantage of lower cost, better compatibility, and a higher key rate.
We investigate the state of art technologies of integrated sensing and communication in optical transmission system. A detailed comparison is conducted among the available solutions. Meanwhile, the ...potential research directions and challenges are also discussed.
How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to a protumoral M2-like phenotype during the development of pancreatic ductal adenocarcinoma (PDA) remains to ...be elucidated. We thus conducted a study by employing a PDA-macrophage co-culture system, an "orthotopic" PDA syngeneic mouse model, and human PDA specimens, together with macrophages derived from GARP knockout mice and multiple analytic tools including whole-genome RNA sequencing, DNA methylation arrays, multiplex immunohistochemistry, metabolism measurement, and invasion/metastasis assessment. Our study showed that PDA tumor cells, through direct cell-cell contact, induce DNA methylation and downregulation of a panel of glucose metabolism and OXPHOS genes selectively in M1-like macrophages, leading to a suppressed glucose metabolic status in M1-like but not in M2-like macrophages. Following the interaction with PDA tumor cells, M1-like macrophages are reprogrammed phenotypically to M2-like macrophages. The interaction between M1-like macrophages and PDA cells is mediated by GARP and integrin αV/β8, respectively. Blocking either GARP or integrin would suppress tumor-induced DNA methylation in Nqo-1 gene and the reprogramming of M1-like macrophages. Glucose-response genes such as Il-10 are subsequently activated in tumor-educated M1-like macrophages. Partly through Il-10 and its receptor Il-10R on tumor cells, M1-like macrophages functionally acquire a pro-cancerous capability. Both exogenous M1-like and M2-like macrophages promote metastasis in a mouse model of PDA while such a role of M1-like macrophages is dependent on DNA methylation. Our results suggest that PDA cells are able to reprogram M1-like macrophages metabolically and functionally through a GARP-dependent and DNA methylation-mediated mechanism to adopt a pro-cancerous fate.
Abstract
Genetic leukoencephalopathies (gLEs) are a highly heterogeneous group of rare genetic disorders. The spectrum of gLEs varies among patients of different ages. Distinct from the relatively ...more abundant studies of gLEs in children, only a few studies that explore the spectrum of adult gLEs have been published, and it should be noted that the majority of these excluded certain gLEs. Thus, to date, no large study has been designed and conducted to characterize the genetic and phenotypic spectra of gLEs in adult patients.
We recruited a consecutive series of 309 adult patients clinically suspected of gLEs from Beijing Tiantan Hospital between January 2014 and December 2021. Whole-exome sequencing, mitochondrial DNA sequencing and repeat analysis of NOTCH2NLC, FMR1, DMPK and ZNF9 were performed for patients. We describe the genetic and phenotypic spectra of the set of patients with a genetically confirmed diagnosis and summarize their clinical and radiological characteristics.
A total of 201 patients (65%) were genetically diagnosed, while 108 patients (35%) remained undiagnosed. The most frequent diseases were leukoencephalopathies related to NOTCH3 (25%), NOTCH2NLC (19%), ABCD1 (9%), CSF1R (7%) and HTRA1 (5%). Based on a previously proposed pathological classification, the gLEs in our cohort were divided into leukovasculopathies (35%), leuko-axonopathies (31%), myelin disorders (21%), microgliopathies (7%) and astrocytopathies (6%). Patients with NOTCH3 mutations accounted for 70% of the leukovasculopathies, followed by HTRA1 (13%) and COL4A1/2 (9%). The leuko-axonopathies contained the richest variety of associated genes, of which NOTCH2NLC comprised 62%. Among myelin disorders, demyelinating leukoencephalopathies (61%)—mainly adrenoleukodystrophy and Krabbe disease—accounted for the majority, while hypomyelinating leukoencephalopathies (2%) were rare. CSF1R was the only mutated gene detected in microgliopathy patients. Leukoencephalopathy with vanishing white matter disease due to mutations in EIF2B2-5 accounted for half of the astrocytopathies.
We characterized the genetic and phenotypic spectra of adult gLEs in a large Chinese cohort. The most frequently mutated genes were NOTCH3, NOTCH2NLC, ABCD1, CSF1R and HTRA1.
Wu et al. describe the clinical and radiological features of genetic leukoencephalopathies in a large cohort of 309 adults, and find that the most frequently mutated genes are NOTCH3 (25%), NOTCH2NLC (19%), ABCD1 (9%), CSF1R (7%) and HTRA1 (5%).
Chlorpyrifos (CPF) is associated with depression, cognitive dysfunction, and other neurological disorders. Increasing evidence has suggested that the gut microbiota plays a vital role in regulating ...the development of depression. However, it is unknown whether gut microbiota is associated with CPF-related depression. This study aimed to explore the effect of CPF on depressive-like behavior in mice and investigated the role of gut microbiota in this behavior. In our study, we selected fifty male C57BL/6 J mice for the model and subjected them to CPF poisoning by gavage for 14 days. The depressive-like behaviors of mice were assessed by the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Furthermore, we selected the high-dose group (CPF10) with obvious changes in depressive-like behaviors for the hippocampus and colon histopathological analysis, examined the changes in the gut microbiota by 16 S rRNA sequencing, screened the different microbiota among groups by linear discriminant analysis effect size (LEfSe), analyzed the correlation between intestinal bacteria and depression-like behavior indicators by Spearman analysis, and evaluated the predictive ability of different bacteria to CPF-induced depressive-like behavior using the receiver operator characteristic (ROC) curve. The results showed that CPF caused depressive-like behaviors with pathological changes in the hippocampus and colon. CPF induced changes in gut microbiota, including 49 differential bacteria. Among the top 10 abundant bacteria, Actinobacteria and Deferribacteres were increased, and Cyanobacteria, Patescibacteria and Verrucomicrobia were decreased at the phylum level. Muribaculum, Ruminococcaceae.UCG.014 and uncultured Bacteroides bacterium were decreased at the genus level. Correlation analysis demonstrated that 18 differentially abundant bacteria were correlated with CPF-induced depression. ROC curves revealed that Deferribacteres, Mucispirillum, Rikenella and GCA900066575 are potential biomarkers for depression caused by CPF. These findings will provide an experimental basis for the neurological health of the pesticide-exposed population.
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•Chlorpyrifos can lead to depressive-like neurobehavior in mice.•The gut microbiota may be associated with chlorpyrifos-related depression.•Four bacteria may be potential biomarkers for the chlorpyrifos-related depression.
Metastasis occurs in the majority of pancreatic ductal adenocarcinoma (PDAC) patients at diagnosis or following resection. Patients with liver metastasis and those with lung metastasis have ...significantly different prognosis. Here, we sought to understand how cancer-associated fibroblasts (CAFs) play roles in the development of organ-specific metastasis.
PDAC tumor cell lines established from the primary tumors with liver and lung metastasis potentials, respectively, in Kras/p53 mutation conditional knock-in (KPC) mice were co-cultured with matched CAFs or mouse mesenchymal stem cells. CAFs were isolated from metastases and subjected to DNA methylation and whole transcriptomic RNA sequencing analysis.
The ability of mouse PDAC tumor cell lines in developing liver or lung-specific metastases was demonstrated in orthotopic models. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induced the methylation of metabolism genes including NQO1 and ALDH1a3 and subsequent downregulated mRNA expression of a broader group of metabolism genes in CAFs. DNA methylation and downregulation of metabolism genes in CAFs in liver metastasis, but not those in lung metastasis, appeared to be regulated by DNA methyltransferase. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induce inflammatory CAF (iCAF) signatures. CAFs from liver metastasis demonstrated a more homogenous iCAF phenotype, whereas CAFs from lung metastasis maintained the heterogeneity.
PDAC with organ-specific metastatic potentials has different capacities in inducing methylation of metabolism genes in CAFs, modulating CAF phenotypes, and resulting in different levels of heterogeneity of CAFs in different metastatic niches.
Abstract One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the ...slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca 2+ influx induces T cell membrane-proximal external Ca 2+ concentration (Ca 2+ ex ) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca 2+ threshold for inducing αLβ2 activation, triggering rapid αLβ2 activation and T cell arrest before occurrence of αLβ2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLβ2 but not Ca 2+ ex drop-triggered αLβ2 quick activation. Blocking Ca 2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. Ca 2+ ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.
Spiking neural networks (SNNs) are considered an attractive option for edge-side applications due to their sparse, asynchronous and event-driven characteristics. However, the application of SNNs to ...object detection tasks faces challenges in achieving good detection accuracy and high detection speed. To overcome the aforementioned challenges, we propose an end-to-end Trainable Spiking-YOLO (Tr-Spiking-YOLO) for low-latency and high-performance object detection. We evaluate our model on not only frame-based PASCAL VOC dataset but also event-based GEN1 Automotive Detection dataset, and investigate the impacts of different decoding methods on detection performance. The experimental results show that our model achieves competitive/better performance in terms of accuracy, latency and energy consumption compared to similar artificial neural network (ANN) and conversion-based SNN object detection model. Furthermore, when deployed on an edge device, our model achieves a processing speed of approximately from 14 to 39 FPS while maintaining a desirable mean Average Precision (mAP), which is capable of real-time detection on resource-constrained platforms.
The silica frustules of diatom are regarded as an important physical defense against predation. While the biogenic silica content of diatoms is a major factor controlling the ingestion rate of ...copepods, how it affects the three‐dimensional structure and the mechanical properties of the frustules, and consequently copepod grazing, has not been studied. In this study, the diatoms Thalassiosira weissflogii and Amphora coffeaeformis were grown under different light intensities to manipulate their cellular biogenic silica contents. This manipulation generated diatom cells with distinct nano‐structures and mechanical strengths. The diatoms were then fed to the copepod Paracalanus pravus to test the effect of biogenic silica contents on copepod feeding. We demonstrated that the copepods preferred the low‐silica cells of T. weissflogii, but showed a preference for the high‐silica cells of A. coffeaeformis. Atomic force microscopy and X‐ray photoelectron spectroscopy analyses revealed that the chemical composition and mechanical properties of diatom frustules varied with silica contents. High silica containing T. weissflogii had higher frustule elasticity and hardness. In contrast, A. coffeaeformis containing more biogenic silica had lower frustule elasticity but silica level had little effect on the hardness of the frustule. Our results indicate that the nano‐structure and chemical properties of the frustules determine the mechanical strength of the diatom frustules. This nanoscale study improves our understanding of the relationship between diatom biogenic silica content and copepod grazing in marine planktonic food webs.
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