Detecting mental and physical disorders using multi-task learning equipped with knowledge graph attention network.

Mental and physical disorders (MPD) are inextricably linked in many medical cases; psychosomatic diseases can be induced by mental concerns and psychological discomfort can ensue from physiological diseases. However, existing medical informatics studies focus on identifying mental or physical disorders from a unilateral perspective. Consequently, no existing domain knowledge base, corpus, or detection modeling approach considers mental as well as physical aspects concurrently. This paper proposes a joint modeling approach to detect MPD. First, we crawl through online medical consultation records of patients from websites and build an MPD knowledge ontology by extracting the core conceptual features of the text. Based on the ontology, an MPD knowledge graph containing 12,673 nodes and 82,195 relations is obtained using term matching with a domain thesaurus of each concept. Subsequently, an MPD corpus with fine-grained severities (None, Mild, Moderate, Severe, Dangerous) and 8909 records is constructed by formulating MPD classification criteria and a data annotation process under the guidance of domain experts. Taking the knowledge graph and corpus as the dataset, we design a multi-task learning model to detect the MPD severity, in which a knowledge graph attention network (KGAT) is embedded to better extract knowledge features. Experiments are performed to demonstrate the effectiveness of our model. Furthermore, we employ ontology-based and centrality-based methods to discover additional potential inferred knowledge, which can be captured by KGAT so as to improve the prediction performance and interpretability of our model. Our dataset has been made publicly available, so it can be further used as a medical informatics reference in the fields of psychosomatic medicine, psychiatrics, physical co-morbidity, and so on.

Exceptional soft tissue preservation reveals a cnidarian affinity for a Cambrian phosphatic tubicolous enigma.

Exoskeletal dwelling tubes are widespread among extant animals and early fossil assemblages. Exceptional fossils from the Cambrian reveal independent origins of tube dwelling by several clades including cnidarians, lophophorates, annelids, scalidophorans, panarthropods and ambulacrarians. However, most fossil tubes lack preservation of soft parts, making it difficult to understand their affinities and evolutionary significance. Gangtoucunia aspera (Wulongqing Formation, Cambrian Stage 4) was an annulated, gradually expanding phosphatic tube, with occasional attachments of multiple, smaller juveniles and has previously been interpreted as the dwelling tube of a 'worm' (e.g. a scalidophoran), lophophorate or problematicum. Here, we report the first soft tissues from Gangtoucunia that reveal a smooth body with circumoral tentacles and a blind, spacious gut that is partitioned by septa. This is consistent with cnidarian polyps and phylogenetic analysis resolves Gangtoucunia as a total group medusozoan. The tube of Gangtoucunia is phenotypically similar to problematic annulated tubular fossils (e.g. Sphenothallus, Byronia, hyolithelminths), which have been compared to both cnidarians and annelids, and are among the oldest assemblages of skeletal fossils. The cnidarian characters of G. aspera suggest that these early tubular taxa are best interpreted as cnidarians rather than sessile bilaterians in the absence of contrary soft tissue evidence.

Baseline Hemodynamic Impairment and Revascularization Outcome in Newly Diagnosed Adult Moyamoya Disease Determined by Pseudocontinuous Arterial Spin Labeling.

OBJECTIVE: The study aimed to investigate the hemodynamic features and independent predictors of neoangiogenesis after revascularization in moyamoya disease (MMD) by pseudocontinuous arterial spin labeling magnetic resonance imaging (pCASL MRI). METHODS: Thirty-nine MMD patients were categorized into infarction group, hemorrhagic group, and atypical group. All patients underwent combined bypass surgery and pCASL MRI with postlabeling delays (PLD) of 1525 ms and 2525 ms. Absolute CBFMCA (cerebral blood flow in middle cerebral artery territory), relative CBFMCA (CBFMCA 2525 ms/CBFMCA 1525 ms), and spatial coefficient of variation of MCA (CoVMCA) were analyzed. Relationships between CBFMCA and the following clinical parameters were assessed: Suzuki stage, modified Rankin scale (mRS), cerebrovascular accident lesion score, and deep medullary veins score. Potential predictors for favorable neoangiogenesis and hemodynamic changes were explored as well. RESULTS: Preoperative CBFMCA differed among MMD patients with variable clinical presentations, Matsushima stages, modified Rankin Scale scores, CVA scores, and deep medullary vein scores. After bypass surgery, mean CBFMCA increased significantly in the infarction group (P = 0.027) and decreased in the hemorrhagic group (P = 0.043), while spatial CoVMCA was observed to decline in all groups. Higher preoperative relative CBFMCA and spatial CoVMCA were independent predictors for robust neoangiogenesis after bypass. The cutoff value of 0.330 of spatial CoVMCA at long PLD yielded the best sensitivity at 82.1% and specificity at 81.8%. Furthermore, both preoperative relative CBFMCA and spatial CoVMCA showed mild positive correlations with ΔmRS in MMD patients. CONCLUSIONS: pCASL-MRI with multiple PLDs could reflect preoperative hemodynamic impairment and predict the neoangiogenesis after combined bypass surgery in moyamoya patients.

Caveolin-1 Promoted Collateral Vessel Formation in Patients With Moyamoya Disease.

Background: Caveolin-1 (Cav-1) plays pivotal roles in the endothelial function and angiogenesis postischemia. Moyamoya disease (MMD) is characterized by progressive artery stenosis with unknown etiology. We aim to determine whether serum Cav-1 levels of patients with MMD were associated with collateral vessel formation after bypass surgery. Methods: We studied serum Cav-1 levels of 130 patients with MMD (16 with RNF213 p.R4810K mutation and 114 without RNF213 p.R4810K mutation), 15 patients with acute stroke, and 33 healthy controls. Cerebral perfusion and collateral circulation were evaluated preoperation and at 6 months after operation using pseudocontinuous arterial spin labeling MRI (pCASL-MRI) and digital subtraction angiography (DSA), respectively. Endothelial expression of Cav-1 was verified in the superficial temporal artery (STA) wall of patients with MMD by immunofluorescence double staining. We also investigated whether overexpression of Cav-1 affects cell migration and tube formation using human microvascular endothelial cells (HMECs). Results: The serum Cav-1 level of patients with MMD intermediated between the stroke group and healthy controls and it was enhanced after the bypass surgery (681.87 ± 311.63 vs. 832.91 ± 464.41 pg/ml, p = 0.049). By 6 months after bypass surgery, patients with MMD with better collateral compensation manifested higher postoperative/preoperative Cav-1 ratio (rCav-1) than bad compensation patients. Consistently, cerebral blood flow (CBF) determined by pCASL-MRI (nCBFMCA ratio) was positively in line with rCav-1 ratio (r = 0.8615, p < 0.0001). Cav-1 was expressed in the endothelial cells of the STA vessels of patients with MMD. Overexpression of Cav-1 by plasmid transfection in HMECs promoted tube formation and cell migration. Conclusion: This study indicated that Cav-1 may be a potential driver to promote angiogenesis and collateral formation after bypass surgery in patients with MMD, providing a better understanding of MMD pathophysiology and potential non-surgical targets of MMD.

Evaluation of the acute toxic effects of crude oil on intertidal mudskipper (Boleophthalmus pectinirostris) based on antioxidant enzyme activity and the integrated biomarker response.

With the development of marine oil industry, oil spill accidents will inevitably occur, further polluting the intertidal zone and causing biological poisoning. The muddy intertidal zone and Boleophthalmus pectinirostris were selected as the research objects to conduct indoor acute exposure experiments within 48 h of crude oil pollution. Statistical analysis was used to reveal the activity changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in the gills and liver of mudskipper. Then, integrated biomarker response (IBR) indicators were established to comprehensively evaluate the biological toxicity. The results showed that the activities of SOD, CAT and GST in livers were higher than those in gills, and the maximum induction multipliers of SOD, CAT and GPx in livers appeared earlier than those in gills. Both SOD and GPx activities were induced at low pollutant concentrations and inhibited at high pollutant concentrations. For the dose-effect, the change trends of CAT and SOD were roughly inversed. There was substrate competition between GPx and CAT, with opposite trends over time. The activating mechanism of GST was similar to that of GPx, and the activation time was earlier than that of GPx. In terms of dose-effect trends, the IBR showed that the antioxidant enzymes activities in biological tissues were induced by low and inhibited by high pollutant concentrations. Overall, SOD and GPx in gills and CAT and GST in livers of the mudskippers were suitable as representative markers to comprehensively analyze and evaluate the biotoxicity effects of oil pollution in the intertidal zone. The star plots and IBR values obtained after data standardization were consistent with the enzyme activity differences, which can be used as valid supplementary indexes for biotoxicity evaluation. These research findings provide theoretical support for early indicators of biological toxicity after crude oil pollution in intertidal zones.

Low-frequency collective motion of DNA-binding domain defines p53 function.

Most mutations in the DNA-binding domain (DBD) of p53 inactivate or rescue the protein function interacting with the minor groove of DNA. However, how the conformation changes propagating from the mutation sites result in distinct molecular recognition is still not well understood. As the protein mobility is an intrinsic property encrypted in its primary structure, we examined if different structures of wild-type and mutant p53 core domains display any unique patterns of intrinsic mobility. Normal mode calculation was employed to characterize the collective dynamics of DBD in p53 monomer and tetramer as well as their mutants. Intriguingly, the low-frequency collective motions of DBD show similar patterns between the wild-type protein and the rescued mutants. The analysis on atomic backbone fluctuations and low-frequency vibration mode statistics does further support the correlation between the intrinsic collective motion of DBD and the p53 protein function. The mutations in the DBD influence the low-frequency vibration of the p53 tetramer via the change of the collective motions among its four monomers. These findings thus provide new insights for understanding the physical mechanism of p53 protein structure-function relationship and help find the small molecule drug to modulate protein dynamic for disease therapy.

LncRNA-mRNA Co-expression Profiles Relative to Vascular Remodeling in Moyamoya Patients Without RNF213 Mutation.

OBJECTIVE: Moyamoya disease (MMD) is an idiopathic cerebrovascular disease with unknown etiology. Long noncoding RNA (lncRNA) and messenger RNA (mRNA) profiles in MMD remain unknown. In this current study, we aim to investigate lncRNA-mRNA co-expression pattern and their biological functions in superficial temporal artery (STA) of MMD. METHODS: STA of 3 MMD patients without RNF213 mutation and 3 age-matched controls were obtained for transcriptomic RNA sequencing. Bioinformatics analysis was performed to investigate their molecular functions and interactions. Then, differentially expressed genes relative to vascular remodeling were further validated by quantitative real-time polymerase chain reaction and immunofluorescence. WNT5A functions were tested by tube formation assay and wound scratching assay in human microvascular endothelial cells (HMECs). RESULTS: We detected 6235 different lncRNAs and 2065 different mRNAs from the RNA-sequencing between MMD patients and controls (P < 0.05; fold change >2.0). Gene ontology showed that altered mRNAs were enriched for endothelial cell morphogenesis and positive regulation of angiogenesis, which were closely related with vascular remodeling. We then searched 76 altered genes related with vascular remodeling and applied Kyoto Encyclopedia of Genes and Genomes analysis. Integrated analysis of lncRNA-TF-mRNA co-expression networks and gene verifications indicated that molecular including WNT5A, TEK, and GATA2 may contribute to the vascular malformation of MMD. Overexpression of WNT5A in HMECs promoted tube formation and cell migration. CONCLUSIONS: In MMD patients, genes related to vascular remodeling including WNT5A and their regulators were aberrantly disrupted. These results will help elucidate the complicated pathogenic mechanism of MMD and develop potential therapeutic targets facilitating MMD angiogenesis in the future.

Terahertz refractive phenotype of living cells.

Cellular refractive index is a vital phenotypic parameter for understanding the cell functional activities. So far, there remains technical challenges to obtain refractive index of viable cells at the terahertz frequency in which contains rich information closely related to their physiological status. Here we introduce a label-free optical platform for interrogating cellular phenotypes to measure the refractive index of living cells in near-physiological environments by using terahertz spectroscopy with the combination of cellular encapsulation in a confined solution droplet. The key technical feature with cells encapsulated in aqueous droplets allows for keeping cellular viability while eliminating the strong adsorption of solvent water to terahertz signal. The obtained high signal-to-noise ratio enables to differentiate different cell types (e.g., E. coli, stem cell and cancer cell) and their states under stress conditions. The integrating of terahertz spectroscopy to droplet microfluidic further realizes automated and high-through sample preparation and detection, providing a practical toolkit for potential application in cellular health evaluation and phenotypic drug discovery.

The Corrosion Features of Q235B Steel under Immersion Test and Electrochemical Measurements in Desulfurization Solution.

With the continuous tightening marine diesel engines emission standards, removing sulfur oxides (SOX) by sodium hydroxide solution absorption is a highly efficiency and economic method, which has been a hot area of research. The ensuing desulfurization solution is a new corrosive system, the aim of this paper is to ascertain the corrosion feature of Q235B steel in desulfurization solution, which lays a theoretical foundation for industrialization. For this purpose, mass loss, electrochemical techniques and surface analyses were applied. The results of mass loss highlight a reduction in the corrosion rate with 35 days of immersion. Higher exposure time increased the compactness of the corrosion product layer and changed phase composition. These conclusions are supported by surface analyses, such as X-ray diffraction and scanning electron microscope. However, electrochemical results showed that the polarization resistance Rp was fluctuant. Both of Rp and charge transfer resistance Rt reach a maximum after immersing 21 days. In addition, although the sediments attached to the steel surface could inhibit corrosion, pitting corrosion aggravated by hydrolyzation of FeSO4 should be given more attention.