gGATLDA: lncRNA-disease association prediction based on graph-level graph attention network

Background Long non-coding RNAs (lncRNAs) are related to human diseases by regulating gene expression. Identifying lncRNA-disease associations (LDAs) will contribute to diagnose, treatment, and prognosis of diseases. However, the identification of LDAs by the biological experiments is time-consuming, costly and inefficient. Therefore, the development of efficient and high-accuracy computational methods for predicting LDAs is of great significance. Results In this paper, we propose a novel computational method (gGATLDA) to predict LDAs based on graph-level graph attention network. Firstly, we extract the enclosing subgraphs of each lncRNA-disease pair. Secondly, we construct the feature vectors by integrating lncRNA similarity and disease similarity as node attributes in subgraphs. Finally, we train a graph neural network (GNN) model by feeding the subgraphs and feature vectors to it, and use the trained GNN model to predict lncRNA-disease potential association scores. The experimental results show that our method can achieve higher area under the receiver operation characteristic curve (AUC), area under the precision recall curve (AUPR), accuracy and F1-Score than the state-of-the-art methods in five fold cross-validation. Case studies show that our method can effectively identify lncRNAs associated with breast cancer, gastric cancer, prostate cancer, and renal cancer. Conclusion The experimental results indicate that our method is a useful approach for predicting potential LDAs.

Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis

(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.

Downregulated Ferroptosis-Related Gene STEAP3 as a Novel Diagnostic and Prognostic Target for Hepatocellular Carcinoma and Its Roles in Immune Regulation

Ferroptosis, a distinct type of regulated cell death, has been reported to be involved in the tumorigenesis of liver hepatocellular carcinoma (LIHC). However, the precise functions and potential mechanisms of ferroptosis in LIHC were still poorly understood. Herein, we investigated the biological roles of ferroptosis-related gene STEAP3 in LIHC. STEAP3 was previously proved to serve a key regulator in ferroptosis via mediating the iron metabolism. Comprehensive bioinformatics from several databases revealed that STEAP3 was significantly downregulated in LIHC tissues and exhibited the favorable prognostic significance in LIHC patients. The downregulated STEAP3 was further confirmed in two LIHC cells Huh7 and MHCC97H using real-time PCR and western blot. And STEAP3 overexpression significantly inhibited the cell proliferation in Huh7 and MHCC97H cells. In addition, clinical data identified the relationship between STEAP3 expression and several clinicopathological parameters of LIHC patients, including histologic grade, alpha fetal protein (AFP) concentration, etc. Receiver operation characteristic (ROC) curve revealed STEAP3 as a potential diagnostic biomarker for LIHC patients. Moreover, the co-expression network of STEAP3 was explored to gain a better insight into its underlying signaling pathways. Finally, aberrant STEAP3 might participate in varieties of immune-associated signatures in LIHC pathogenesis, including immunostimulators, immunoinhibitors, chemokines, and chemokine receptors. Taken together, these findings could enhance our knowledge regarding the inhibitory roles and underlying biological significance of STEAP3 in LIHC tumorigenesis.

The relationship between sitting balance, trunk control and mobility with predictive for current mobility level in survivors of sub-acute stroke

Objective To investigate the relationship between sitting balance, trunk control, and mobility, as well as whether the sitting balance and trunk control can predict mobility level in sub-acute stroke survivors. Methods This is a observational and cross-sectional study. Fifty-five hemiplegic stroke survivors were participated in this study. The Timed Up and Go Test (TUG) was used to estimate mobility, and the Sitting Balance Scale (SBS) was used to examining sitting balance. The Trunk Impairment Scale (TIS), Trunk Control Test (TCT), and Postural Assessment Scale for Stroke-trunk control (PASS-TC) were used for examining the trunk control. Spearman’s correlation was used to analyze the relationship between TUG, SBS, TIS, TCT, and PASS-TC. Results The TUG is significantly correlated with SBS (r = -0.78), TIS (r = -0.76), TCT (r = -0.65), and PASS-TC (r = -0.67). In addition, the receiver operation characteristic (ROC) curve showed as cut-off value of SBS as >28.5, TIS > 16.5, TCT >82, and PASS-TC >10.5. The area under the ROC curve in each of the four tests is moderately accurate for predicting the mobility of sub-acute stroke survivors (0.84 ~0.90) (0.7 < AUC ≤ 9 (moderate informative)). Implications The SBS showed the highest correlation for mobility using TUG in the hemiplegic stroke survivors. Also, SBS was revealed as the most dominant examination tool predicting the mobility by TUG, it can be explained the sitting postural balance is the variable predicting the mobility in survivors of sub-acute stroke.

Prediction of Unplanned Hospitalizations in Older Patients Treated with Chemotherapy

Purpose: To determine the incidence of unplanned hospitalization (UH) and to identify risk factors for UH in elderly patients with cancer who start chemotherapy. Methods: In all, 493 patients over 70 years starting new chemotherapy regimens were prospectively included. A pre-chemotherapy geriatric assessment was performed, and tumor and treatment variables were collected. The association between these factors and UH was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 37% of patients had at least one episode of UH. Risk factors were the use of combination chemotherapy at standard doses, a MAX2 index ≥1, a Charlson comorbidity score ≥2, albumin level <3.5 g/dL, falls in the past 6 months ≥1, and weight loss >5%. Three risk groups for UH were established according to the score in all patients: 0–1: 17.5%; 2: 34%; and 3–7: 57% (p < 0.001). The area under receiver operation characteristic (ROC) curve was 0.72 (95% CI: 0.67–0.77). Conclusion: This simple tool can help to reduce the incidence of UH in elderly patients with cancer who are scheduled to initiate chemotherapy treatment.

Detection of poststroke oropharyngeal dysphagia with swallowing screening by ultrasonography

There are currently no standard evaluation tools for poststroke neurogenic oropharyngeal dysphagia. We previously suggested calculating the relative movements of the hyoid bone and larynx by ultrasonography to evaluate swallowing movement. Swallowing movement is altered in neurogenic oropharyngeal dysphagia. Therefore, the present study aimed to verify whether an ultrasonographic evaluation of swallowing movement facilitates the detection of neurogenic oropharyngeal dysphagia. Eighteen healthy male elderly participants (the healthy group) and 18 male stroke patients diagnosed with neurogenic oropharyngeal dysphagia (the dysphagia group) were enrolled. Participants swallowed 5 mL of liquid and water with an adjusted viscosity and the movements of the hyoid bone and larynx were visualized by ultrasonography. The results obtained revealed significant differences in laryngeal duration (static phase), laryngeal displacement (elevation phase), and the hyoid bone–laryngeal motion ratio (HL motion ratio) between the two groups. A multiple regression analysis was performed to adjust for confounding factors, and laryngeal duration (static phase) and the HL motion ratios were identified as factors affecting dysphagia. In the receiver operation characteristic curve of the two variations, the area under the curve for laryngeal duration (static phase) was 0.744 and the cut-off was 0.26 sec with 72.2% sensitivity and 88.9% specificity; the area under the curve for the HL motion ratio was 0.951 and the cut-off was 0.56 with 88.9% sensitivity and 88.9% specificity. Therefore, the objective evaluation of hyoid bone and larynx movements during swallowing by ultrasonography facilitated the detection of neurogenic oropharyngeal dysphagia.

Relationship Between Arterial Stiffness and Cardiovascular Risk Scores Predicted by 2 Different Models

Background To investigate the relationship between arterial stiffness and 10-year atherosclerotic cardiovascular disease (ASCVD) risk predicted by models of pooled cohort equations (PCEs) or ASCVD risk in China (China-PAR). Methods A cross-sectional clinical study was carried out, in which clinical data were collected from 1,090 subjects aged 30–75 years who were admitted to a university affiliated hospital from 2016 to 2018. Arterial stiffness was examined by carotid–femoral pulse wave velocity (cfPWV). All subjects were divided into 2 groups: normal arterial stiffness (cfPWV &lt;10 m/second) and elevated arterial stiffness (cfPWV ≥10 m/second). Ten-year ASCVD risk was predicted by either PCE or China-PAR. Results ASCVD risks predicted by 2 models in the elevated arterial stiffness group were higher than those in the normal arterial stiffness group [PCE: 16.5% (8.6%–28.3%) vs. 6.3% (2.7%–12.3%); China-PAR: 8.8% (6.1%–12.4%) vs. 3.9% (2.1%–6.6%), both P &lt; 0.001]. The correlation coefficient between cfPWV and ASCVD risk predicted by China-PAR was greater than that by PCE (0.573 vs. 0.503, z = 5.272, P &lt; 0.001). Multivariate linear regression analysis showed that 10-year ASCVD risk predicted by PCE model (β = 0.475, P &lt; 0.001) and waist circumference (β = 0.092, P = 0.001) correlated with cfPWV. However, when PCE was replaced by China-PAR, only ASCVD risk (β = 0.573, P &lt; 0.001), not waist circumference, was associated with arterial stiffness. Receiver operation characteristic curve showed that the discrimination of 10-year ASCVD risk predicted by China-PAR for arterial stiffness was better than PCE (area under curve 0.814 vs. 0.767, z = 4.992, P &lt; 0.001). A stratification analysis revealed that the better discrimination by China-PAR mainly came from males. Conclusions Ten-year ASCVD risks predicted by either China-PAR or PCE are associated with arterial stiffness. The association is stronger when the risk is predicted by China-PAR, especially in males.

Relationship Between Arterial Stiffness and Cardiovascular Risk Scores Predicted by 2 Different Models

Background To investigate the relationship between arterial stiffness and 10-year atherosclerotic cardiovascular disease (ASCVD) risk predicted by models of pooled cohort equations (PCEs) or ASCVD risk in China (China-PAR). Methods A cross-sectional clinical study was carried out, in which clinical data were collected from 1,090 subjects aged 30–75 years who were admitted to a university affiliated hospital from 2016 to 2018. Arterial stiffness was examined by carotid–femoral pulse wave velocity (cfPWV). All subjects were divided into 2 groups: normal arterial stiffness (cfPWV &lt;10 m/second) and elevated arterial stiffness (cfPWV ≥10 m/second). Ten-year ASCVD risk was predicted by either PCE or China-PAR. Results ASCVD risks predicted by 2 models in the elevated arterial stiffness group were higher than those in the normal arterial stiffness group [PCE: 16.5% (8.6%–28.3%) vs. 6.3% (2.7%–12.3%); China-PAR: 8.8% (6.1%–12.4%) vs. 3.9% (2.1%–6.6%), both P &lt; 0.001]. The correlation coefficient between cfPWV and ASCVD risk predicted by China-PAR was greater than that by PCE (0.573 vs. 0.503, z = 5.272, P &lt; 0.001). Multivariate linear regression analysis showed that 10-year ASCVD risk predicted by PCE model (β = 0.475, P &lt; 0.001) and waist circumference (β = 0.092, P = 0.001) correlated with cfPWV. However, when PCE was replaced by China-PAR, only ASCVD risk (β = 0.573, P &lt; 0.001), not waist circumference, was associated with arterial stiffness. Receiver operation characteristic curve showed that the discrimination of 10-year ASCVD risk predicted by China-PAR for arterial stiffness was better than PCE (area under curve 0.814 vs. 0.767, z = 4.992, P &lt; 0.001). A stratification analysis revealed that the better discrimination by China-PAR mainly came from males. Conclusions Ten-year ASCVD risks predicted by either China-PAR or PCE are associated with arterial stiffness. The association is stronger when the risk is predicted by China-PAR, especially in males.

Association of alpha-fetoprotein levels with liver stiffness measurement in outpatients with chronic hepatitis B

The association between alpha-fetoprotein (AFP) levels with the assessment of liver stiffness (LS) in chronic hepatitis B (CHB) patients were explored. A total of 283 outpatients with CHB were enrolled. Patient age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AFP, platelet (PLT), total bilirubin, direct bilirubin, alkaline phosphatase, albumin, globulin, and albumin/globulin (A/G) levels were associated with LS values in the univariate model (p&lt;0.05). Significant associations between AFP and PLT levels with LS values were observed when both variables were included in the multivariate analysis models. Receiver operation characteristic (ROC) analysis indicated that the combination of AFP and PLT levels could enhance the predictive performance of liver fibrosis (AUC=0.819, p&lt;0.001) and that PLT levels (PLT&lt;100×10^9/L) combined with high AFP levels (AFP&gt;8 ng/mL) significantly increased the prediction of liver fibrosis (OR=11.216). More importantly, LS values of associated with higher AFP levels (AFP &gt;8 ng/mL), independently of higher ALT or AST values, were significantly higher than those of low AFP level groups. In conclusion, in Chinese outpatients with CHB, AFP outperformed ALT and/or AST levels in terms of their association with LS. AFP and PLT levels were independently associated with LS, and their combined assessment could enhance the diagnostic and predictive performance of liver fibrosis among CHB patients.

Do low TB prevalence and lack of BCG Vaccinations Contribute to Emergence Multisystem Inflammatory Syndrome in Children?

Background: Emergence of new multisystem inflammatory syndrome in children (MIS-C) is thought to be associated with COVID-19 pandemic. Covid-19 morbidity and mortality variances among countries have been suggested by previous works to be influenced by BCG and previous latent TB infection (which is reflected by TB prevalence) possibly through inducing heterogeneous immunity against SARS-CoV-2. Aim: To examine influence of BCG status and TB prevalence on variances among countries which report new multisystem inflammatory syndrome in children (MIS-C). Methods: We choose all countries which report MIS-C till 23/6/2020, number of cases for each 10 million inhabitants was examined among 3 categories of countries classified according to BCG program status. TB prevalence, MIS-C no. / 10 million (M) population and Covid- 19 deaths/M are taken as markers. Receiver operation characteristic - (ROC) curve, with some relative indicators such as (sensitivity and specificity rates), estimation area of trade - off between sensitivity and specificity, and cutoff points are used with different studied markers for discriminating different three pairs of countries (which have different BCG practices). Results: BCG vaccinations and high TB prevalence are found to be associated with decrease MIS-C no. and COVID-19 deaths Conclusions: Findings might explain variances in MIS-C incidence and in COVID-19 mortality among countries worldwide. Further studies to confirm this relation and to confirm possible similar relations in Kawasaki disease(KD) in previous epidemics is recommended.