We propose to use segment graph convolutional and recurrent neural networks (Seg-GCRNs), which use only word embedding and sentence syntactic dependencies, to classify relations from clinical notes ...without manual feature engineering. In this study, the relations between 2 medical concepts are classified by simultaneously learning representations of text segments in the context of sentence syntactic dependency: preceding, concept1, middle, concept2, and succeeding segments. Seg-GCRN was systematically evaluated on the i2b2/VA relation classification challenge datasets. Experiments show that Seg-GCRN attains state-of-the-art micro-averaged F-measure for all 3 relation categories: 0.692 for classifying medical treatment-problem relations, 0.827 for medical test-problem relations, and 0.741 for medical problem-medical problem relations. Comparison with the previous state-of-the-art segment convolutional neural network (Seg-CNN) suggests that adding syntactic dependency information helps refine medical word embedding and improves concept relation classification without manual feature engineering. Seg-GCRN can be trained efficiently for the i2b2/VA dataset on a GPU platform.
Although high serum levels of galactose-deficient IgA1 (an important biomarker of IgA nephropathy (IgAN)) are found in most patients with IgAN, their relationship to disease severity and progression ...remains unclear. To help clarify this we prospectively enrolled 275 patients with IgAN and followed them for a median of 47 months (range 12–96 months). Serum galactose–deficient IgA1 was measured at the time of diagnosis using a lectin-based ELISA, and renal survival was modeled using the Cox proportional hazards method. The serum levels of galactose-deficient IgA1 were higher in patients with IgAN compared to those in healthy controls. Importantly, in adjusted analysis, higher levels of galactose-deficient IgA1 were independently associated with a greater risk of deterioration in renal function with a hazard ratio of 1.44 per standard deviation of the natural log–transformed galactose-deficient IgA1 concentration. In reference to the first quartile, the risk of kidney failure increased such that the hazard ratio for the second quartile was 2.47, 3.86 for the third, and 4.76 for the fourth quartile of the galactose-deficient IgA1 concentration. Hence, elevated serum levels of galactose-deficient IgA1 are associated with a poor prognosis in IgAN.
Forest-canopy closure (FCC) reflects the coverage of the forest tree canopy, which is one of the most important indicators of forest structure and a core parameter in forest resources investigation. ...In recent years, the rapid development of UAV LiDAR and photogrammetry technology has provided effective support for FCC estimation. However, affected by factors such as different tree species and different stand densities, it is difficult to estimate FCC accurately based on the single-tree canopy-contour method in complex forest regions. Thus, this study proposes a method for estimating FCC accurately using algorithm integration with an optimal window size for treetop detection and an optimal algorithm for crown-boundary extraction using UAV LiDAR data in various scenes. The research results show that: (1) The FCC estimation accuracy was improved using the method proposed in this study. The accuracy of FCC in a camphor pine forest (Pinus sylvestris var. mongolica Litv.) was 89.11%, with an improvement of 6.77–11.25% compared to the results obtained from other combined conditions. The FCC accuracy for white birch (White birch platyphylla Suk) was about 87.53%, with an increase of 3.25–8.42%. (2) The size of the window used for treetop detection is closely related to tree species and stand density. With the same forest-stand density, the treetop-detection window size of camphor pine was larger than that of white birch. The optimal window size of camphor pine was between 5 × 5~11 × 11 (corresponding 2.5~5.5 m), while that of white birch was between 3 × 3~7 × 7 (corresponding 1.5~3.5 m). (3) There are significant differences in the optimal-canopy-outline extraction algorithms for different scenarios. With a medium forest-stand density, the marker-controlled watershed (MCW) algorithm has the best tree-crown extraction effect. The region-growing (RG) method has better extraction results in the sparse areas of camphor pine and the dense areas of white birch. The Voronoi tessellation (VT) algorithm is more suitable for the dense areas of camphor pine and the sparse regions of white birch. The method proposed in this study provides a reference for FCC estimation using high-resolution remote-sensing images in complex forest areas containing various scenes.
We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up ...in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10⁻²⁶ and 4.84 × 10⁻⁹ and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.
IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation ...in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹⁰), with heterogeneity detected only at the PSMB9/TAP1 locus (I² = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻⁴). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²⁸). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.
•A more precise and robust solution to locate the atrial fibrillation lesion.•An improvement for the inverse solution in electrocardiographic imaging.•A multi-scale solution based on uniform phase ...empirical mode decomposition.•Better reconstructed cardiac potential, even for disturbed body surface ECG signals.
Current techniques used for solving the inverse problem in Electrocardiographic imaging (ECGI) to locate atrial fibrillation (AF) drivers are far from dependable and accurate. Given that body surface electrocardiographic signals (ECGs) are composed of numerous components, separation promises to be a powerful solution for the inverse operation, extracting sections with more specific components from the whole and processing them in a unique way. Therefore, this work proposes a multi-scale time–frequency domain solution based on uniform phase empirical mode decomposition (UPEMD_MSTFDS). We first utilize UPEMD to decompose the complete ECGs. Then we obtain the final solution by applying the second-order Tikhonov algorithms (Tikhonov) and truncated singular value decomposition (TSVD) to the different decomposed signal parts. To evaluate the accuracy and robustness of UPEMD_MSTFDS, two simulated datasets with or without random respiratory interference, namely baseline wander (BW), are employed. Quantitative results show that the detection accuracy of UPEMD_MSTFDS is improved by more than 10% on the first dataset including simple AF (SAF) and complex AF (CAF) when compared to popular inverse algorithms except for Bayesian maximum a posteriori estimation (Bayes). In the same condition but with BW, the weighted under-estimation indicator of UPEMD_MSTFDS drops by more than 70%, and the weighted over-estimation indicator corresponding to SAF with BW and CAF with BW drop to 39.99% and 57.03%, respectively. Moreover, both the driver and domain frequency maps computed by UPEMD_MSTFDS are most similar to the real ones of the other dataset, demonstrating that UPEMD_MSTFDS is apparently superior to existing algorithms.
Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic ...factors involved in its determination are not known. We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8). These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1. We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians. Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians. Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1. By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells. Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive ...factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR HR = 0.96(0.95-0.97), serum albumin HR = 0.47(0.32-0.68), hemoglobin HR = 0.79(0.72-0.88), and SBP HR = 1.02(1.00-1.03). Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification.
Circulation of Sb in an Sn refining system strongly affects the production process. In this study, an innovative multi-stage vacuum separation process was developed and successfully applied on an ...industrial scale. Our results indicate that Sn–Sb alloys can be completely separated by vacuum evaporation. In this study, we used single-factor experiments to investigate the effects of distillation temperature and time on several factors, such as the Sn content in the residue, Sb content in the volatile matter, separation rate, and direct recovery rate of Sb from high-Sb crude Sn. The purity of the obtained Sn and Sb products was above 99%, and the recovery rate of the metal was above 99% under the optimal distillation conditions of 1673 K and 150 min. In addition, we suggest that Sn volatilization occurs due to the presence of SbSn intermetallic compounds. A two-stage vacuum-separation process for high-Sb crude Sn was developed for industrial production. Continuous production data showed that the direct yields of Sn and Sb were 72.99% and 71.15%, respectively. The total power consumption of this process was as low as 1086 kWh/t, which is better than the corresponding parameters of other treatment processes.
Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, ...and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.
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