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Genetic analysis of congenital adrenal hyperplasia (CAH) has been challenging because of high homology between CYP21A2 and its pseudogene CYP21A1P. This study aimed to evaluate the clinical utility of long-read sequencing (LRS) in diagnosis of CAH attributable to 21-hydroxylase deficiency by comparing with multiplex ligation-dependent probe amplification plus Sanger sequencing. In this retrospective study, 69 samples, including 49 probands from 47 families with high-risk of CAH, were enrolled and blindly subjected to detection of CAH by LRS. The genotype results were compared with control methods, and discordant samples were validated by additional Sanger sequencing. LRS successfully identified biallelic variants of CYP21A2 in the 39 probands diagnosed as having CAH. The remaining 10 probands were not patients with CAH. Additionally, LRS directly identified two pathogenic single-nucleotide variations (SNVs; c.293-13C/A>G and c.955C>T) in the presence of interference caused by nearby insertions/deletions (indels). The cis-trans configuration of two or more SNVs and indels identified in 18 samples was directly determined by LRS without family analysis. Eight CYP21A1P/A2 or TNXA/B deletion chimeras, composed of five subtypes, were identified; and the junction sites were precisely determined. Moreover, LRS determined the exact genotype in two probands who had three heterozygous SNVs/indels and duplication, which could not be clarified by control methods. These findings highlight that LRS could assist in more accurate genotype imputation and more precise CAH diagnosis.
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INTRODUCTION: This study explored the feasibility of a supporting catheter combined with modified end-to-side anastomosis in the operation of radio-cephalic arteriovenous fistula (RC-AVF) and evaluated the clinical application value of this technique. METHODS: Sixty patients underwent RC-AVF operations in our hospital from January 2022 to June 2022. All the patients were treated with modified end-to-side AVF anastomosis and divided into the control group or the test group depending on whether a supporting catheter was applied. The clinical data of 60 cases were analysed retrospectively. Intraoperative related indices, the first time the fistula was used, the success rate of first puncture, the blood flow of first dialysis, the maturity condition of fistula, the size of anastomosis, the diameter of radial artery and drainage vein, the blood flow of brachial artery 8 weeks after operation and the incidence of complications within 6 months after operation were compared between the two groups. RESULTS: Compared with that in the control group, the time spent on the vascular anastomosis in the test group was significantly shortened (p<0.05). The blood flow of the first dialysis, the size of the anastomosis, the diameter of the drainage vein, the blood flow of the brachial artery 8 weeks after the operation and the incidence of complications within 6 months after operation were significantly different between the two groups (p<0.05). CONCLUSION: In the RC-AVF operation, using a supporting catheter can not only increase operation efficiency by reducing surgical injury and difficulty of vascular anastomosis, but also improve postoperative prognosis. RC-AVF is worth promoting in clinical practice.
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Spiking neural networks (SNNs), as the brain-inspired neural networks, encode information in spatio-temporal dynamics. They have the potential to serve as low-power alternatives to artificial neural networks (ANNs) due to their sparse and event-driven nature. However, existing SNN-based models for pixel-level semantic segmentation tasks suffer from poor performance and high memory overhead, failing to fully exploit the computational effectiveness and efficiency of SNNs. To address these challenges, we propose the multi-scale and full spike segmentation network (MFS-Seg), which is based on the deep direct trained SNN and represents the first attempt to train a deep SNN with surrogate gradients for semantic segmentation. Specifically, we design an efficient fully-spike residual block (EFS-Res) to alleviate representation issues caused by spiking noise on different channels. EFS-Res utilizes depthwise separable convolution to improve the distributions of spiking feature maps. The visualization shows that our model can effectively extract the edge features of segmented objects. Furthermore, it can significantly reduce the memory overhead and energy consumption of the network. In addition, we theoretically analyze and prove that EFS-Res can avoid the degradation problem based on block dynamical isometry theory. Experimental results on the Camvid dataset, the DDD17 dataset, and the DSEC-Semantic dataset show that our model achieves comparable performance to the mainstream UNet network with up to 31× fewer parameters, while significantly reducing power consumption by over 13×. Overall, our MFS-Seg model demonstrates promising results in terms of performance, memory efficiency, and energy consumption, showcasing the potential of deep SNNs for semantic segmentation tasks. Our code is available in https://github.com/BICLab/MFS-Seg.
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Redes Neurales de la Computación , Semántica , Humanos , Potenciales de Acción/fisiología , Modelos Neurológicos , Neuronas/fisiología , Aprendizaje Profundo , AlgoritmosRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.
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Antígeno 2 del Estroma de la Médula Ósea , Proteínas Ligadas a GPI , Interferón-alfa , Neoplasias Pancreáticas , Macrófagos Asociados a Tumores , Animales , Femenino , Humanos , Ratones , Antígenos CD/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Proteínas Ligadas a GPI/metabolismo , Tolerancia Inmunológica , Interferón-alfa/metabolismo , Ratones Endogámicos C57BL , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Transducción de Señal , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/patologíaRESUMEN
Thiol amino acids, with great physiological significance, are unstable, and have small molecular weights, as well as very low endogenous concentrations. Therefore, to quantitatively and directly analyze them using liquid chromatography-tandem mass spectrometry is difficult. To overcome these problems, we aimed to prepare a thiol-free amino acid plasm matrix as blank sample to reduce the background for the first time. Using compounds with maleimide group that react with classical thiols to generate water-insoluble products. Reducing agents Tris(2-carboxyethyl)phosphine (TCEP) was applied to cooperate with bismaleimide (DM) for elimination of thiol amino acids from plasma 10 min at room temperature and pH 7. Further, the residual TCEP from plasma were removed using an anion exchange resin within 10 min. Methodological validation analysis revealed good performance in linearity, precision, extraction recovery (≥ 82 %), and stability (except oxidized glutathione). This quantitative analysis was successfully applied to blood samples of 9 people in good health. This study provides a foundation for the development of accurate and rigorous quantitative analysis methods targeting thiol amino acids in different body fluids or tissues. Moreover, it paves the way toward realizing several clinical applications.
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Aminoácidos , Fosfinas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Aminoácidos/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida con Espectrometría de Masas , Compuestos de SulfhidriloRESUMEN
Tumor micronecrosis is a pathological feature that reflects malignant biological behavior in hepatocellular carcinoma (HCC). However, whether micronecrosis can optimize HCC staging systems remains unilluminated. A total of 1632 HCC patients who underwent curative hepatectomy in four institutions from January 2014 to December 2021 were enrolled in this study. Independent prognostic factors were identified, and optimized staging models were established using a training cohort (n = 934). The performance of optimized staging models was validated using an external cohort consisting of cases from three other institutions (n = 232). In addition, patients from our prospectively collected database (n = 379) tested the application effectiveness of the models. Harrel's c-statistics and the corrected Akaike information criterion (AICc) were used to assess the performance of staging models. In most of Barcelona Clinic Liver Cancer (BCLC) and tumor (T) stages, HCC patients with tumor micronecrosis showed poorer prognosis than those without. Tumor micronecrosis, microvascular invasion, multiple tumors and tumor size >2 cm were independent prognostic-related factors. The BCLC and T staging models incorporating tumor micronecrosis showed better performance than the original systems (c-statistic, 0.712 and 0.711 vs. 0.664 and 0.679; AICc, 2314.8 and 2322.3 vs. 2338.2 and 2338.1; respectively). Furthermore, the external validation cohort confirmed that the optimized staging models had improved efficiency compared with the original ones. Moreover, the prospective cohort demonstrated the applicability of the optimized staging systems. Tumor micronecrosis plays a stage-ascending role in HCC patients. The BCLC and T staging systems incorporating tumor micronecrosis can improve the prognosis stratification efficiency of patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Estudios Prospectivos , Estadificación de Neoplasias , PronósticoRESUMEN
End-stage renal disease (ESRD) is associated with vascular and neuronal dysfunction, causing neurovascular coupling (NVC) dysfunction, but how NVC dysfunction acts on the mechanism of cognitive impairment in ESRD patients from local to remote is still poorly understood. We recruited 48 ESRD patients and 35 demographically matched healthy controls to scan resting-state functional MRI and arterial spin labeling, then investigated the four types of NVC between amplitude of low-frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, degree centrality, and cerebral blood perfusion (CBF), and associated functional networks. Our results indicated that ESRD patients showed NVC dysfunction in global gray matter and multiple brain regions due to the mismatch between CBF and neural activity, and associated disrupted functional connectivity (FC) within sensorimotor network (SMN), visual network (VN), default mode network (DMN), salience network (SN), and disrupted FC between them with limbic network (LN), while increased FC between SMN and DMN. Anemia may affect the NVC of middle occipital gyrus and precuneus, and increased pulse pressure may result in disrupted FC with SMN. The NVC dysfunction of the right precuneus, middle frontal gyrus, and parahippocampal gyrus and the FC between the right angular gyrus and the right anterior cingulate gyrus may reflect cognitive impairment in ESRD patients. Our study confirmed that ESRD patients may exist NVC dysfunction and disrupted functional integration in SMN, VN, DMN, SN and LN, serving as one of the mechanisms of cognitive impairment. Anemia and increased pulse pressure may be related risk factors.
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Anemia , Disfunción Cognitiva , Fallo Renal Crónico , Acoplamiento Neurovascular , Humanos , Disfunción Cognitiva/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Individuals exhibit considerable variability in their capacity to learn and retain new information, including novel vocabulary. Prior research has established the importance of vigilance and electroencephalogram (EEG) alpha rhythm in the learning process. However, the interplay between vigilant attention, EEG alpha oscillations, and an individual's word learning ability (WLA) remains elusive. To address this knowledge gap, here we conducted two experiments with a total of 140 young and middle-aged adults who underwent resting EEG recordings prior to completing a paired-associate word learning task and a psychomotor vigilance test (PVT). The results of both experiments consistently revealed significant positive correlations between WLA and resting EEG alpha oscillations in the occipital and frontal regions. Furthermore, the association between resting EEG alpha oscillations and WLA was mediated by vigilant attention, as measured by the PVT. These findings provide compelling evidence supporting the crucial role of vigilant attention in linking EEG alpha oscillations to an individual's learning ability.
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BACKGROUND: Heat shock factor (HSF), a typical class of transcription factors in plants, has played an essential role in plant growth and developmental stages, signal transduction, and response to biotic and abiotic stresses. The HSF genes families has been identified and characterized in many species through leveraging whole genome sequencing (WGS). However, the identification and systematic analysis of HSF family genes in Rye is limited. RESULTS: In this study, 31 HSF genes were identified in Rye, which were unevenly distributed on seven chromosomes. Based on the homology of A. thaliana, we analyzed the number of conserved domains and gene structures of ScHSF genes that were classified into seven subfamilies. To better understand the developmental mechanisms of ScHSF family during evolution, we selected one monocotyledon (Arabidopsis thaliana) and five (Triticum aestivum L., Hordeum vulgare L., Oryza sativa L., Zea mays L., and Aegilops tauschii Coss.) specific representative dicotyledons associated with Rye for comparative homology mapping. The results showed that fragment replication events modulated the expansion of the ScHSF genes family. In addition, interactions between ScHSF proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of ScHSF expression was complex. A total of 15 representative genes were targeted from seven subfamilies to characterize their gene expression responses in different tissues, fruit developmental stages, three hormones, and six different abiotic stresses. CONCLUSIONS: This study demonstrated that ScHSF genes, especially ScHSF1 and ScHSF3, played a key role in Rye development and its response to various hormones and abiotic stresses. These results provided new insights into the evolution of HSF genes in Rye, which could help the success of molecular breeding in Rye.
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Aegilops , Arabidopsis , Secale/genética , Filogenia , Respuesta al Choque TérmicoRESUMEN
Uniparental disomy (UPD) is when all or part of the homologous chromosomes are inherited from only one of the two parents. Currently, UPD has been reported to occur for almost all chromosomes. In this study, we report two cases of UPD for chromosome 2 (UPD2) encountered during prenatal diagnosis. The ultrasound findings of the fetuses from two unrelated families showed intrauterine growth restriction. The karyotype analyses were normal. The two fetuses both had complete paternal chromosome 2 uniparental disomy detected by whole-exome sequencing, but their clinical outcomes were significantly different, with fetal arrest in case 1 and birth in case 2. In this report, we analyzed and discussed the phenotypes of the fetuses in these two cases and reviewed the literature on UPD2.
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Background: The heterogeneity of hepatocellular carcinoma (HCC) leads to the unsatisfying predictive performance of current staging systems. HCC patients with pathological tumor micronecrosis have an immunosuppressive microenvironment. We aimed to develop novel prognostic models by integrating micronecrosis to predict the survival of HCC patients after hepatectomy more precisely. Methods: We enrolled 765 HCC patients receiving curative hepatic resection. They were randomly divided into a training cohort (n= 536) and a validation cohort (n = 229). We developed two prognostic models for postoperative recurrence-free survival (RFS) and overall survival (OS) based on independent factors identified through multivariate Cox regression analyses. The predictive performance was assessed using the Harrell concordance index (C-index) and the time-dependent area under the receiver operating characteristic curve, compared with six conventional staging systems. Results: The RFS and OS nomograms were developed based on tumor micronecrosis, tumor size, albumin-bilirubin grade, tumor number and prothrombin time. The C-indexes for the RFS nomogram and OS nomogram were respectively 0.66 (95% CI, 0.62-0.69) and 0.74 (95% CI, 0.69-0.79) in the training cohort, which was significantly better than those of the six common staging systems (0.52-0.61 for RFS and 0.53-0.63 for OS). The results were further confirmed in the validation group, with the C-indexes being 0.66 and 0.77 for the RFS and OS nomograms, respectively. Conclusion: The two nomograms could more accurately predict RFS and OS in HCC patients receiving curative hepatic resection, thereby aiding in formulating personalized postoperative follow-up plans.
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BACKGROUND: Over the years, the detection rate of pancreatic cystic neoplasms (PCNs) has significantly increased; however, the differential diagnosis and identification of high-risk PCNs remain challenging. We sought to investigate whether chromosomal instability (CIN) features in cell-free DNA in the cystic fluid of PCNs could help to identify high-risk PCNs. METHODS: Pancreatic cystic fluid samples from 102 patients with PCNs were intraoperatively collected for detection of CIN using an ultrasensitive chromosomal aneuploidy detector. Clinical and imaging data were retrospectively collected, and statistical analysis was performed to assess the potential role of CIN in clinical practice. RESULTS: CIN was investigated in a total of 100 patients. Sixteen of 26 serous cystic cystadenomas (SCAs) harbored deletions of chr3p and/or chr6p, whereas low rates of CIN were detected in mucinous cystic neoplasms. Most malignant PCNs presented with more than one type of CIN; amplification of chr1q and chr8q found in nine and seven of 11 malignant PCNs (81.8% and 63.6%), respectively, could aid in distinguishing high-risk IPMNs from low-risk ones, with a higher sensitivity than imaging. A combination of the mural nodule imaging feature and amplification of chr1q and chr8q achieved a sensitivity of 70.0% and a specificity of 82.4% in identifying high-risk IPMNs. CONCLUSIONS: Our work revealed the distinct CIN signature of different types of PCNs. Deletions of chr3p and chr6p defined a subtype of SCAs. Gains of chr1q and chr8q were associated with insidious malignant PCNs and helped identify high-risk IPMNs.
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Cistadenoma Seroso , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Páncreas/patología , Neoplasias Pancreáticas/cirugía , Quiste Pancreático/genética , Quiste Pancreático/diagnóstico , Cistadenoma Seroso/genética , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/patología , GenómicaRESUMEN
OBJECTIVE: To investigate the molecular diagnosis of hemoglobin variants in Z region by Capillary electrophoresis in Central Guangxi, Southern China, and analyze their distribution and phenotypic characteristics, to provide a reference for clinical consultation and prenatal diagnosis for couples. METHODS: A total of 23,709 subjects were collected for blood routine analysis, hemoglobin analysis, and common α- and ß-globin gene loci in Chinese population. The hemoglobin electrophoresis components were divided into Zone 1-Zone 15 (Z1-Z15) by Capillary zone electrophoresis (CE). For samples not clearly detected by the conventional technology, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) were used. Single-molecule real-time (SMRT) sequencing technology was used to analyze rare-type genes in a sample with a structural variation. RESULTS: Ten rare hemoglobin variants distributed in Z region were detected in 23,709 samples, including Hb Cibeles, which was reported for the first time in Asia; Hb J-Broussais, Hb G-Honolulu and J-Wenchang-Wuming, they were first reported in Guangxi; 1 case of Hb Anti-Lepore Liuzhou, which was a newly discovered hemoglobin variant; hemoglobin variants Hb G-Siriraj, Hb Handsworth, Hb Q-Thailand, Hb Ube-2, Hb NewYork were also detected. CONCLUSION: There are a few studies on rare hemoglobin variants in Z region in Southern China. Ten rare hemoglobin variants were found in this study. The hematological phenotype and component content of hemoglobin variants are related to the occurrence of thalassemia. This study enriched the data of rare hemoglobin variants in Southern China and provided a comprehensive data basis for prenatal diagnosis of hemoglobin variants in this area.
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Hemoglobinas Anormales , Talasemia , Humanos , China/epidemiología , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/análisis , Fenotipo , Pueblo AsiaticoRESUMEN
OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.
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Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Biomarcadores de Tumor , Neoplasias PancreáticasRESUMEN
This study investigated universal and language-specific phonological awareness in reading development among Chinese early adolescent students. Seventy-six children participated in this study and completed a series of reading tasks at two data collection points across Grades 5 and 6. In Grade 5, universal phonological awareness (syllable, onset, rhyme, and phoneme awareness), language-specific phonological awareness (tone awareness) as well as character recognition and production measurements were administered to the participants. Lexical inferencing ability was measured in Grade 6. Character recognition and lexical inference were coded as the outcome variables. Subsequent multiple regression analyses showed that Time 1 (Grade 5) language-universal onset and phoneme awareness predicted character recognition and production at Time 1. More strikingly, the study demonstrated that language-specific tone awareness exerted a longitudinal effect on later lexical inferencing ability after controlling for age and nonverbal intelligence. Results underscored both the universality and language specificity of phonological awareness and provided empirical evidence to substantiate the facilitative role of early language-specific psycholinguistic grain size in later reading performance.
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Pueblos del Este de Asia , Lectura , Niño , Humanos , Adolescente , Fonética , Lenguaje , ConcienciaciónRESUMEN
Traffic speed prediction is an essential part of urban transportation systems that contributes to minimizing the environmental pollution caused by vehicle emissions. The existing traffic speed prediction studies have achieved good results, but some challenges remain. Most previously developed methods only account for road network characteristics such as distance while ignoring road directions and time patterns, resulting in lower traffic speed prediction accuracy. To address this issue, we propose a novel model that utilizes multigraph and cross-attention fusion (MGCAF) mechanisms for traffic speed prediction. We construct three graphs for distances, position relationships, and temporal correlations to adequately capture road network properties. Furthermore, to adaptively aggregate multigraph features, a multigraph attention mechanism is embedded into the network framework, enabling it to better connect the traffic features between the temporal and spatial domains. Experiments are performed on real-world datasets, and the results demonstrate that our method achieves positive performance and outperforms other baselines.
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Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Emisiones de Vehículos/análisis , Proyectos de InvestigaciónRESUMEN
Objectives: Our study aims to determine the patterns of renal oxygenation changes and microstructural changes by BOLD and DTI with deteriorating kidney function in patients with diabetic kidney disease (DKD). Methods: Seventy-two patients with type 2 diabetes mellitus (DM) and twenty healthy controls (HCs) underwent laboratory examinations, and renal BOLD and DTI images were obtained on a 3T-MRI machine. R2 ∗ , fractional anisotropy (FA), and average diffusion coefficient (ADC) values were evaluated. DM patients were divided into three subgroups (Group-DI/DII/DIII, based on urinary albumin-creatinine ratio (UACR)) and a nondiabetic kidney disease group (Group-NDKD). D-value and MCR of R2 ∗ and FA were proposed to evaluate the differentiation between medulla and cortex of the individual kidney among HCs and three subgroups for reducing individual differences. Comparisons were made between NDKD and kidney function-matched DKD patients. Correlations between MRI parameters and renal clinical indices were analyzed. Results: Compared with Group-HC/DI, medullary R2 ∗ and FA values were significantly different in Group-DII/III. The D-value of R2 ∗ and FA in Group-III were significantly smaller than that in Group-HC. However, only MCR of R2 ∗ in Group-III was significantly smaller than that in HCs. Medullary R2 ∗ and FA were negatively associated with serum creatinine (SCr) and cystatin C (Cys C) and positively associated with eGFR. Conclusions: With renal function declining, BOLD and DTI could capture alterations including the first rising and then falling medullary R2 ∗ , continuously declining medullary FA, and apparent cortex-medullary differentiation in DKD patients. The MRI parameters showed renal changes accompanied by varying degrees of albuminuria, sharing common involvement in DKD and NDKD patients, but it was hard to distinguish between them. BOLD seemed more sensitive than DTI in identifying renal cortex-medullary differentiation.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Albúminas , Creatinina , Cistatina C , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Humanos , Riñón/diagnóstico por imagen , Riñón/fisiología , Imagen por Resonancia Magnética/métodosRESUMEN
Foxtail millet (Setaria italica) is rich in nutrients and extremely beneficial to human health. We identified and comprehensively analyzed 89 MADS-box genes in the foxtail millet genome. According to the classification of MADS-box genes in Arabidopsis thaliana and rice, the SiMADS-box genes were divided into M-type (37) and MIKC-type (52). During evolution, the differentiation of MIKC-type MADS-box genes occurred before that of monocotyledons and dicotyledons. The SiMADS-box gene structure has undergone much differentiation, and the number of introns in the MIKC-type subfamily is much greater than that in the M-type subfamily. Analysis of gene duplication events revealed that MIKC-type MADS-box gene segmental duplication accounted for the vast majority of gene duplication events, and MIKC-type MADS-box genes played a major role in the amplification of SiMADS-box genes. Collinearity analysis showed highest collinearity between foxtail millet and maize MADS-box genes. Analysis of tissue-specific expression showed that SiMADS-box genes are highly expressed throughout the grain-filling process. Expression analysis of SiMADS-box genes under eight different abiotic stresses revealed many stress-tolerant genes, with induced expression of SiMADS33 and SiMADS78 under various stresses warranting further attention. Further, some SiMADS-box proteins may interact under external stress. This study provides insights for MADS-box gene mining and molecular breeding of foxtail millet in the future.
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Setaria (Planta) , Duplicación de Gen , Regulación de la Expresión Génica de las Plantas , Humanos , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Estrés Fisiológico/genéticaRESUMEN
BACKGROUND: GRAS transcription factors perform indispensable functions in various biological processes, such as plant growth, fruit development, and biotic and abiotic stress responses. The development of whole-genome sequencing has allowed the GRAS gene family to be identified and characterized in many species. However, thorough in-depth identification or systematic analysis of GRAS family genes in foxtail millet has not been conducted. RESULTS: In this study, 57 GRAS genes of foxtail millet (SiGRASs) were identified and renamed according to the chromosomal distribution of the SiGRAS genes. Based on the number of conserved domains and gene structure, the SiGRAS genes were divided into 13 subfamilies via phylogenetic tree analysis. The GRAS genes were unevenly distributed on nine chromosomes, and members of the same subfamily had similar gene structures and motif compositions. Genetic structure analysis showed that most SiGRAS genes lacked introns. Some SiGRAS genes were derived from gene duplication events, and segmental duplications may have contributed more to GRAS gene family expansion than tandem duplications. Quantitative polymerase chain reaction showed significant differences in the expression of SiGRAS genes in different tissues and stages of fruits development, which indicated the complexity of the physiological functions of SiGRAS. In addition, exogenous paclobutrazol treatment significantly altered the transcription levels of DELLA subfamily members, downregulated the gibberellin content, and decreased the plant height of foxtail millet, while it increased the fruit weight. In addition, SiGRAS13 and SiGRAS25 may have the potential for genetic improvement and functional gene research in foxtail millet. CONCLUSIONS: Collectively, this study will be helpful for further analysing the biological function of SiGRAS. Our results may contribute to improving the genetic breeding of foxtail millet.