Revealing Distance-Dependent Synergy between MnCo2O4 and Co-N-C in Boosting the Oxygen Reduction Reaction.

Synergistic effects have been applied to a variety of hybrid electrocatalysts to improve their activity and selectivity. Understanding the synergistic mechanism is crucial for the rational design of these types of catalysts. Here, we synthesize a MnCo2O4/Co-N-C hybrid electrocatalyst for the oxygen reduction reaction (ORR) and systematically investigate the synergy between MnCo2O4 nanoparticles and Co-N-C support. Theoretical simulations reveal that the synergy is closely related to the distance between active sites. For a pair of remote active sites, the ORR proceeds through the known 2e- + 2e- relay catalysis while the direct 4e- ORR occurs on a pair of adjacent active sites. Therefore, the formation of the undesired byproduct (H2O2) is inhibited at the interface region between MnCo2O4 and Co-N-C. This synergistic effect is further verified on an anion-exchange membrane fuel cell. The findings deepen the understanding of synergistic catalysis and will provide guidance for the rational design of hybrid electrocatalysts.

CanCHD Study of Hematopoietic Cancers in Children With and Without Genetic Syndromes.

BACKGROUND: Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population-based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD. METHODS AND RESULTS: Data sources were the Canadian CHD database, a nationwide database on CHD (1999-2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan-Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0-17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person-years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7-15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11-2.76) among children with a syndrome and 0.79% (95% CI, 0.72-0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia. CONCLUSIONS: This is the first large population-based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk-stratified policy recommendations for cancer surveillance in children with CHD.

Short-term influence of polytetrafluoroethylene micro/nano-plastics on the inhibition of copper and/or ciprofloxacin on the nitrifying sludge activities based on concentration addition and independent action models.

Short-term influence of polytetrafluoroethylene micro/nano-plastics (PTFE-MPs/NPs) on the inhibition of copper (Cu2+) and/or ciprofloxacin (CIP) on the nitrifying sludge activities was explored based on concentration addition (CA) and independent action (IA) models. The half maximal inhibitory concentration (IC50) of Cu2+, CIP, PTFE-MPs (3 µm), and PTFE-NPs (800 nm) on the specific ammonium oxidation rate (SAOR) of nitrifying sludge was 64.57, 51.29, 102.33 and 93.33 mg L-1, respectively, while those on the specific nitrite oxidation rate (SNOR) of nitrifying sludge were 77.62, 32.36, 104.70 and 97.72 mg L-1, respectively. Among the five binary mixtures and two ternary mixtures composed by Cu2+, CIP, and/or PTFE-MPs/NPs, it was found that the two joint inhibitory actions from ternary mixtures on the SAOR and SNOR of the sludge showed time-dependent characteristics by analyzing of CA and IA models, while the five combined inhibitory effects from different binary mixtures did not all have time-dependent features. The two joint inhibition actions from diverse ternary mixtures on the SAOR at the exposure time of 60 min and on the SNOR at 90 min showed always concentration-dependent features, while the combined inhibitions with concentration-dependent characteristics had never been observed in the binary Cu2+ and PTFE-NPs mixtures at different exposure time. The Cu2+, CIP, and PTFE-MPs mixtures (or Cu2+, CIP, and PTFE-NPs mixtures) had synergistic actions on the SAOR at 90 min and antagonistic effects on the SNOR at 60 min based on CA and IA models, and these combined inhibitions did not exhibit concentration-dependent characteristics. In contrast, the joint inhibitory effects (on the SAOR and SNOR) with concentration-dependent features were found in the binary mixtures of CIP and PTFE-MPs at different exposure time, and the join inhibition changed from synergism to antagonism as the increasing concentration of mixed CIP and PTFE-MPs. This study provides novel perspectives for understanding the combined influence of plastic particles with different sizes, antibiotics, and heavy metals on the biological wastewater treatment process.

Study on the Sliding Tribological Behavior of Oleic Acid-Modified MoS2 under Boundary Lubrication.

The effects of MoS2 and MoS2 modified by adding oleic acid (OA) on the friction properties of lithium-based grease under boundary lubrication conditions are studied by molecular dynamics (MD) simulation and experiment. A rough wall boundary lubrication MD model with peaks and grooves is established to simulate the mechanical properties and lubrication effects of three lubrication systems on rough walls for the relative shear velocity between the two solid walls of 5 m/s at 500 MPa. The stress, wear amount, friction force, normal pressure, and friction heat of the friction surface are quantitively calculated. Simultaneously, a Retc friction and wear testing machine is used to measure the friction coefficient under different concentrations of additives and different pressures. The results show that the grease added with MoS2 can reduce friction, wear, and the temperature between friction pairs. However, under high pressure and shear, MoS2 can easily agglomerate and accumulate in the pits, reducing the lubricating effect. At the same time, since OA-modified MoS2 can reduce agglomeration, the modified MoS2 is adsorbed on the metal wall surface, forming a stable lubricant film. The main contributions of this article can be found in combining MD simulation and experimentation, establishing the connection between micronano structures and macroscopic properties, exploring the mechanism of the influence of wall roughness and particle size on the friction performance of lubricating oil, and providing a theory for predicting and developing high-performance new lubricating grease.

Severe Fontan-Associated Liver Disease and Its Association With Mortality.

Background Data are rare about the incidence of severe Fontan-associated liver disease (FALD) and its association with mortality. We sought to: (1) estimate the probability of developing severe FALD in patients who undergo the Fontan procedure (Fontan patients), compared with severe liver complications in patients with a ventricular septal defect; (2) assess the severe FALD-mortality association; and (3) identify risk factors for developing severe FALD. Methods and Results Using the Quebec Congenital Heart Disease database, a total of 512 Fontan patients and 10 232 patients with a ventricular septal defect were identified. Kaplan-Meier curves demonstrated significantly higher cumulative risk of severe FALD in Fontan patients (11.95% and 52.24% at 10 and 35 years, respectively), than the risk of severe liver complications in patients with a ventricular septal defect (0.50% and 2.75%, respectively). At 5 years, the cumulative risk of death was 12.60% in patients with severe FALD versus 3.70% in Fontan patients without FALD (log-rank P=0.0171). Cox proportional hazard models identified significant associations between the development of severe FALD and congestive heart failure and supraventricular tachycardia, with hazard ratios (HRs) of 2.36 (95% CI, 1.38-4.02) and 2.45 (95% CI, 1.37-4.39), respectively. More recent Fontan completion was related to reduced risks of severe FALD, with an HR of 0.95 (95% CI, 0.93-0.97) for each more recent year. Conclusions This large-scale population-based study documents that severe FALD in Fontan patients was associated with a >3-fold increase in mortality. The risk of FALD is time-dependent and can reach >50% by 35 years after the Fontan operation. Conditions promoting poor Fontan hemodynamics were associated with severe FALD development.

Research Progress and Molecular Mechanisms of Endothelial Cells Inflammation in Vascular-Related Diseases.

Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases.

OCMR: A comprehensive framework for optical chemical molecular recognition.

Artificial intelligence (AI) has achieved significant progress in the field of drug discovery. AI-based tools have been used in all aspects of drug discovery, including chemical structure recognition. We propose a chemical structure recognition framework, Optical Chemical Molecular Recognition (OCMR), to improve the data extraction capability in practical scenarios compared with the rule-based and end-to-end deep learning models. The proposed OCMR framework enhances the recognition performances via the integration of local information in the topology of molecular graphs. OCMR handles complex tasks like non-canonical drawing and atomic group abbreviation and substantially improves the current state-of-the-art results on multiple public benchmark datasets and one internally curated dataset.

Long-term exposure of polytetrafluoroethylene-nanoplastics on the nitrogen removal and extracellular polymeric substances in sequencing batch reactor.

The impact of polytetrafluoroethylene-nanoplastics (PTFE-NPs) on biological sewage disposal was delved, containing nitrogen remotion, microbiological activity and composition of extracellular polymer (EPS). The addition of PTFE-NPs reduced the removal efficiencies of chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N) by 3.43 % and 2.35 %, respectively. In comparison with no PTFE-NPs, the specific oxygen uptake rate (SOUR), specific ammonia oxidation rate (SAOR), specific nitrite oxidation rate (SNOR) and specific nitrate reduction rate (SNRR) decreased by 65.26 %, 65.24 %, 41.77 % and 54.56 %, respectively. The PTFE-NPs inhibited the activities of nitrobacteria and denitrobacteria. It was worth noting that, nitrite oxidized bacterium was more resistant to adverse environments than ammonia oxidizing bacterium. Compared with no PTFE-NPs, the reactive oxygen species (ROS) content and lactate dehydrogenase (LDH) grew by 130 % and 50 % under PTFE-NPs pressure. The appearance of PTFE-NPs affected the normal function of microorganisms by inducing endocellular oxidative stress and destroying the completeness of the cytomembrane. The protein (PN) and polysaccharide (PS) levels in loosely bound EPS (LB-EPS) and tightly bound EPS (TB -EPS) increased by 4.96, 0.70, 3.07 and 0.71 mg g-1 VSS, under PTFE-NPs. Meanwhile, the PN/PS ratios of LB-EPS and TB -EPS increased from 6.18 and 6.41-11.04 and 9.29, respectively. The LB-EPS might provide sufficient binding sites for PTFE-NPs adsorption due to its loose and porous structure. The defense mechanism of bacteria against PTFE-NPs was mainly the PN in loosely bound EPS. Moreover, the functional groups referred to the complexation of EPS with PTFE-NPs were mainly related to N-H, CO, and C-N in proteins and O-H in polysaccharides.

Field-applied biochar-based MgO and sepiolite composites possess CO2 capture potential and alter organic C mineralization and C-cycling bacterial structure in fertilized soils.

Agricultural soils contribute a significant amount of anthropogenic CO2 emission, a greenhouse gas of global environmental concern. Hence, discovering sustainable materials that can capture CO2 in cultivated soils is paramount. Since the effect of biochar on C mineralization/retention in fertilized soils is unclear, we produced biochar-based MgO and sepiolite-nanocomposites with CO2 capture potential. The field-scale impacts of the modified-biochars were evaluated on net C exchange rate (NCER) periodically for 3 months in fertilized plots. The effects of the modified-biochar on organic-C mineralization, the activities, and dynamics of C-cycling-related 16S rRNA which are unknown, were investigated. Results revealed an initial rapid and higher cumulative CO2 emission from the sole fertilizer treatment (F). Unlike the biochar treatment (BF), the successful incorporation of MgO/Mg(OH)2 nanoparticles into the matrix and surface of biochar, and the potential formation of MgCO3 with soil CO2, mitigated CO2 emission, especially in the MgO-modified biochar (MgOBF), compared to the sepiolite-biochar treatment (SBF). Compared to F and BF, the higher C retention as MgCO3 in the modified biochar treatments led to an increase in cellulase activity, stimulation of key C-cycling-related bacteria, and the expression of genes associated with starch, sucrose, amino sugar, nucleotide sugar, ascorbate, aldarate, cellulose, and chitin degradation, thus, increasing organic C mineralization. Among the modified-biochar treatments, higher C mineralization was recorded in SBF, resulting in increased cumulative CO2 emission, despite its initial capture for up to 42 days. However, MgOBF was effective in capturing soil-derived CO2, despite the increased C mineralization compared to biochar. The changes in soil moisture and temperature significantly regulated NCER. Also, the modified biochars positively influenced the distribution of C-cycling-related bacteria by improving soil pH and available nutrients. Among the modified biochars, the observed higher mitigation effect of MgOBF on NCER indicated that it could be preferably applied in agricultural soils.

Re-exploring α-Cyano-4-Hydroxycinnamic Acid as a Reactive Matrix for Selective Detection of Glutathione via MALDI-MS.

Herein, we re-explored α-cyano-4-hydroxycinnamic acid (CHCA) as a reactive matrix for selective and sensitive analysis of glutathione (GSH) by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). CHCA efficiently reacted with GSH, and the resulting CHCA-GSH conjugate was readily detected by MALDI-MS without interferences. The detection limit of the CHCA-GSH conjugate decreased to 200 pmol µL-1, which was 2 orders of magnitude lower than that of pure GSH.Forapplication, CHCA was successfully applied for the detection of GSH, present in HepG2 cell lysates. The results demonstrated detection advantages of simple, high-throughput, and selective and screening of GSH in biological samples by MALDI-MS.

A dual-mode reactive matrix for sensitive and quantitative analysis of carbohydrates by MALDI-TOF MS.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a widely used tool for the analysis of carbohydrates. However, the detection of carbohydrates by MALDI-TOF MS is often limited by the unsatisfactory ionization efficiency, instability and the matrix interference in low molecular weight region. Here, we demonstrate that a reactive matrix, 2-hydrazinoquinoline (2-HQ), can be used to detect neutral, sialic and low molecular weight carbohydrates sensitively both in the positive and negative ion mode. Since 2-HQ reacts efficiently with the reducing end of carbohydrate to form stable hydrazone, the ionization efficiency of derived carbohydrates is significantly enhanced. Using 2-HQ, the sensitivity for analyzing glycans has been improved 10-fold and 100-fold compared with those using 3-aminquinoline (3-AQ) and 2,5-dihydroxybenzoic acid (DHB) as matrix, respectively. Moreover, quantitative analysis of neutral, acidic and low molecular weight carbohydrates has been achieved because of the good reproducibility by using 2-HQ as matrix. As a result, up to 50 glycans in a single sample spot of human fresh serum without any prior purification and enrichment have been successfully detected. Therefore, 2-HQ as a new reactive matrix has shown great potentials in widespread applications for sensitive, selective, quantitative, high speed and high throughput analysis of carbohydrates in complex samples by MALDI-TOF MS.

Neurocognitive disorders amongst patients with congenital heart disease undergoing procedures in childhood.

BACKGROUND: Amongst children with congenital heart disease (CHD), earlier age of repair improves cardiovascular outcomes. The effects of early intervention on neurodevelopment remains unclear. We assessed the association between early life repair, cardiopulmonary bypass (CPB) and the incidence of neurocognitive disorders (NCD) amongst CHD patients. METHODS: We created two retrospective cohorts from the Quebec CHD Database; with data from 1988 to 2010. Complexity of reparative procedures for CHD lesions were used as the proxy of CPB exposure with more complex procedure means longer exposure to CPB. Study Population 1 included pediatric patients with a single reparative procedure and compared patients with complex (long CBP) versus isolated shunt (short CBP) lesions. To assess the effects of CPB alone in Study Population 2 we compared patients with isolated atrial septal defects (ASD) who had surgical (short CBP) versus percutaneous (no CBP) repairs. The primary endpoint for both cohorts was development of an NCD. RESULTS: In Study population 1, 1174 patients underwent complex surgical repair and 1620 had a shunt closure. The incidence of NCDs was 2.45/100 person-years in the complex surgery group, and 2.08/100 person-years in the shunt closure group. The following were associated with increased risk of developing a NCD: surgical complexity (Hazard Ratio [HR] = 1.20, 95% Confidence Interval [CI]: 1.01-1.42), younger age at intervention (AAI) (HR = 1.20, 95% CI: 1.16-1.25), male sex (HR = 1.91, 95% CI: 1.61-2.27), and later calendar year at intervention (HR = 1.06, 95% CI: 1.04-1.07). Study population 2 had 527 isolated ASD patients; 202 underwent surgical repair and 325 had percutaneous closure. The incidence of NCDs was not statistically different between groups. Male sex (HR = 1.77, 95% CI: 1.08-2.89) and younger AAI (HR = 1.15, 95% CI: 1.06-1.25) were associated with increased NCD risk. CONCLUSION: Increased surgical complexity, male sex and younger AAI were associated with increased risk of NCDs in pediatric CHD patients. Surveillance protocols should be considered to identify NCDs in CHD patients after cardiac intervention.

Recurrent disease progression networks for modelling risk trajectory of heart failure.

MOTIVATION: Recurrent neural networks (RNN) are powerful frameworks to model medical time series records. Recent studies showed improved accuracy of predicting future medical events (e.g., readmission, mortality) by leveraging large amount of high-dimensional data. However, very few studies have explored the ability of RNN in predicting long-term trajectories of recurrent events, which is more informative than predicting one single event in directing medical intervention. METHODS: In this study, we focus on heart failure (HF) which is the leading cause of death among cardiovascular diseases. We present a novel RNN framework named Deep Heart-failure Trajectory Model (DHTM) for modelling the long-term trajectories of recurrent HF. DHTM auto-regressively predicts the future HF onsets of each patient and uses the predicted HF as input to predict the HF event at the next time point. Furthermore, we propose an augmented DHTM named DHTM+C (where "C" stands for co-morbidities), which jointly predicts both the HF and a set of acute co-morbidities diagnoses. To efficiently train the DHTM+C model, we devised a novel RNN architecture to model disease progression implicated in the co-morbidities. RESULTS: Our deep learning models confers higher prediction accuracy for both the next-step HF prediction and the HF trajectory prediction compared to the baseline non-neural network models and the baseline RNN model. Compared to DHTM, DHTM+C is able to output higher probability of HF for high-risk patients, even in cases where it is only given less than 2 years of data to predict over 5 years of trajectory. We illustrated multiple non-trivial real patient examples of complex HF trajectories, indicating a promising path for creating highly accurate and scalable longitudinal deep learning models for modeling the chronic disease.

Risk prediction models for heart failure admissions in adults with congenital heart disease.

BACKGROUND: Heart failure (HF) is the leading cause of death in adult patients with congenital heart disease (ACHD). No risk prediction model exists for HF hospitalization (HFH) for ACHD patients. We aimed to develop a clinically relevant one-year risk prediction system to identify ACHD patients at high risk for HFH. METHODS: Data source was the Quebec CHD Database. A retrospective cohort including all ACHD patients aged 18-64 (1995-2010) was constructed for assessing the cumulative risk of HFH adjusting for competing risk of death. To identify one-year predictors of incident HFH, multivariable logistic regressions were employed to a nested case-control sample of all ACHD patients aged 18-64 in 2009. The final model was used to create a risk score system based on adjusted odds ratios. RESULTS: The cohort included 29,991 ACHD patients followed for 648,457 person-years. The cumulative HFH risk by age 65 was 12.58%. The case-control sample comprised 26,420 subjects, of whom 189 had HFHs. Significant one-year predictors were age ≥ 50, male sex, CHD lesion severity, recent 12-month HFH history, pulmonary arterial hypertension, chronic kidney disease, coronary artery disease, systemic arterial hypertension, and diabetes mellitus. The created risk score ranged from 0 to 19. The corresponding HFH risk rose rapidly beyond a score of 8. The risk scoring system demonstrated excellent prediction performance. CONCLUSIONS: One eighth of ACHD population experienced HFH before age 65. Age, sex, CHD lesion severity, recent 12-month HFH history, and comorbidities constructed a risk prediction model that successfully identified patients at high risk for HFH.

TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells.

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.

Diagnostic value of VDBP and miR-155-5p in diabetic nephropathy and the correlation with urinary microalbumin.

This study explored the diagnostic and therapeutic significance of vitamin D binding protein (VDBP) and miR-155-5p for diabetic nephropathy and the correlation with urinary microalbumin. A total of 145 patients with type 2 diabetes who attended the Hwamei hospital were selected as research objects and assigned to diabetic nephropathy group (DN group) and diabetes group according to whether they suffered from diabetic nephropathy (DN). The expression levels of urine VDBP and serum miR-155-5p in the two groups were detected, and the correlation between urinary microalbumin (mAlb), serum cystatin C (Cys C) and 24-h urinary protein was analyzed. The predictive value of single and joint detection of urinary VDBP and serum miR-155-5p for DN onset and poor prognosis was analyzed. In DN patients, urine VDBP and serum miR-155-5p were highly expressed, and urine VDBP, serum miR-155-5p and mAlb, Cys C and 24-h urine protein were positively correlated (P<0.05). Moreover, the joint detection of urine VDBP and serum miR-155-5p was more valuable in diagnosis and poor prognosis prediction of DN patients than its single detection. Urine VDBP and serum miR-155-5p have good diagnostic value for DN, but their joint diagnostic value is higher, and their expression levels are all related to mAlb of DN patients, which may be used as new biological indicators for diagnosis and disease assessment.

Inferring multimodal latent topics from electronic health records.

Electronic health records (EHR) are rich heterogeneous collections of patient health information, whose broad adoption provides clinicians and researchers unprecedented opportunities for health informatics, disease-risk prediction, actionable clinical recommendations, and precision medicine. However, EHRs present several modeling challenges, including highly sparse data matrices, noisy irregular clinical notes, arbitrary biases in billing code assignment, diagnosis-driven lab tests, and heterogeneous data types. To address these challenges, we present MixEHR, a multi-view Bayesian topic model. We demonstrate MixEHR on MIMIC-III, Mayo Clinic Bipolar Disorder, and Quebec Congenital Heart Disease EHR datasets. Qualitatively, MixEHR disease topics reveal meaningful combinations of clinical features across heterogeneous data types. Quantitatively, we observe superior prediction accuracy of diagnostic codes and lab test imputations compared to the state-of-art methods. We leverage the inferred patient topic mixtures to classify target diseases and predict mortality of patients in critical conditions. In all comparison, MixEHR confers competitive performance and reveals meaningful disease-related topics.

Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Tumor necrosis factor receptor superfamily 19 (TNFRSF19) is a transmembrane protein involved in tumorigenesis. RAB43 is a small molecule GTP-binding protein contributing to the occurrence and development of tumors. However, TNFRSF19/RAB43 dysregulation and their role in hepatocellular carcinoma cells are unknown. Herein, we found that TNFRSF19 and RAB43 were downregulated in hepatocellular carcinoma tissues. TNFRSF19/RAB43 overexpression suppressed, whereas TNFRSF19/RAB43 knockdown promoted cell proliferation and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells. Previously, using deep sequencing technology, a new miRNA, miR-HCC3, was identified and found to suppress the expression of TNFRSF19 and RAB43 by binding to their 3'untranslated regions (3'UTRs) directly. miR-HCC3 was upregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent noncancerous tissues and promoted proliferation and epithelial-mesenchymal transition in HCC cells. Furthermore, TNFRSF19/RAB43 suppressed but miR-HCC3 promoted tumor growth in vivo. Collectively, our results indicated that downregulation of TNFRSF19 and RAB43 by miR-HCC3 contributes to oncogenic activities in HCC, which sheds light on tumorigenesis and might provide potential therapeutic targets for HCC.