Enhanced patient-based real-time quality control using the graph-based anomaly detection.

OBJECTIVES: Patient-based real-time quality control (PBRTQC) is an alternative tool for laboratories that has gained increasing attention. Despite the progress made by using various algorithms, the problems of data volume imbalance between in-control and out-of-control results, as well as the issue of variation remain challenges. We propose a novel integrated framework using anomaly detection and graph neural network, combining clinical variables and statistical algorithms, to improve the error detection performance of patient-based quality control. METHODS: The testing results of three representative analytes (sodium, potassium, and calcium) and eight independent variables of patients (test date, time, gender, age, department, patient type, and reference interval limits) were collected. Graph-based anomaly detection network was modeled and used to generate control limits. Proportional and random errors were simulated for performance evaluation. Five mainstream PBRTQC statistical algorithms were chosen for comparison. RESULTS: The framework of a patient-based graph anomaly detection network for real-time quality control (PGADQC) was established and proven feasible for error detection. Compared with classic PBRTQC, the PGADQC showed a more balanced performance for both positive and negative biases. For different analytes, the average number of patient samples until error detection (ANPed) of PGADQC decreased variably, and reductions could reach up to approximately 95 % at a small bias of 0.02 taking calcium as an example. CONCLUSIONS: The PGADQC is an effective framework for patient-based quality control, integrating statistical and artificial intelligence algorithms. It improves error detection in a data-driven fashion and provides a new approach for PBRTQC from the data science perspective.

Determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: Succinic acid and lactic acid have been associated with diarrhea in weaned piglets. The level of succinic acid and lactic acid in serum, meat, and intestinal contents is important to elucidate the mechanism of diarrhea in weaned piglets. METHODS: A facile method was developed for the quantification of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS). The serum samples underwent protein precipitation with methanol. The meat and intestinal contents were freeze-dried and homogenized using a tissue grinding apparatus. Methanol-water mixture (80:20, v/v) was used for homogenizing the meat, while water was used for homogenizing the intestinal contents. An additional step of protein precipitation with acetonitrile was required for the intestinal contents. The resulting solution was diluted with water before being analyzed by UHPLC/MS/MS. Separation of succinic acid and lactic acid could be achieved within 3 min using a Kinetic XB-C18 column. RESULTS: The coefficients of variation for peak areas of succinic acid and lactic acid were less than 5.0%. The established method demonstrated good linearity as indicated by correlation coefficients exceeding 0.996. Additionally, satisfactory recoveries ranging from 88.58% to 108.8% were obtained. The detection limits (RS/N = 3) for succinic acid and lactic acid were determined to be 0.75 ng/mL and 0.02 µg/mL, respectively. CONCLUSION: This method exhibited high sensitivity, simplicity in operation, and small sample weight, making it suitable for quantitative determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat. The method developed will provide valuable technical support in studying the metabolic mechanisms of succinic acid and lactic acid in pigs.

Picornavirus VP3 protein induces autophagy through the TP53-BAD-BAX axis to promote viral replication.

Macroautophagy/autophagy and apoptosis are pivotal interconnected host cell responses to viral infection, including picornaviruses. Here, the VP3 proteins of picornaviruses were determined to trigger autophagy, with the autophagic flux being triggered by the TP53-BAD-BAX axis. Using foot-and-mouth disease virus (FMDV) as a model system, we unraveled a novel mechanism of how picornavirus hijacks autophagy to bolster viral replication and enhance pathogenesis. FMDV infection induced both autophagy and apoptosis in vivo and in vitro. FMDV VP3 protein facilitated the phosphorylation and translocation of TP53 from the nucleus into the mitochondria, resulting in BAD-mediated apoptosis and BECN1-mediated autophagy. The amino acid Gly129 in VP3 is essential for its interaction with TP53, and crucial for induction of autophagy and apoptosis. VP3-induced autophagy and apoptosis are both essential for FMDV replication, while, autophagy plays a more important role in VP3-mediated pathogenesis. Mutation of Gly129 to Ala129 in VP3 abrogated the autophagic regulatory function of VP3, which significantly decreased the viral replication and pathogenesis of FMDV. This suggested that VP3-induced autophagy benefits viral replication and pathogenesis. Importantly, this Gly is conserved and showed a common function in various picornaviruses. This study provides insight for developing broad-spectrum antivirals and genetic engineering attenuated vaccines against picornaviruses.Abbreviations: 3-MA, 3-methyladenine; ATG, autophagy related; BAD, BCL2 associated agonist of cell death; BAK1, BCL2 antagonist/killer 1; BAX, BCL2 associated X, apoptosis regulator; BBC3/PUMA, BCL2 binding component 3; BCL2, BCL2 apoptosis regulator; BID, BH3 interacting domain death agonist; BIP-V5, BAX inhibitor peptide V5; CFLAR/FLIP, CASP8 and FADD like apoptosis regulator; CPE, cytopathic effects; CQ, chloroquine; CV, coxsackievirus; DAPK, death associated protein kinase; DRAM, DNA damage regulated autophagy modulator; EV71, enterovirus 71; FMDV, foot-and-mouth disease virus; HAV, hepatitis A virus; KD, knockdown; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MOI, multiplicity of infection; MTOR, mechanistic target of rapamycin kinase; PML, promyelocytic leukemia; PV, poliovirus; SVA, Seneca Valley virus; TCID50, 50% tissue culture infectious doses; TOR, target of rapamycin. TP53/p53, tumor protein p53; WCL, whole-cell lysate.

Room-temperature sulfur doped NiMoO4 with enhanced conductivity and catalytic activity for efficient hydrogen evolution reaction in alkaline media.

Transition metal oxides have been acknowledged for their exceptional water splitting capabilities in alkaline electrolytes, however, their catalytic activity is limited by low conductivity. The introduction of sulfur (S) into nickel molybdate (NiMoO4) at room temperature leads to the formation of sulfur-doped NiMoO4 (S-NiMoO4), thereby significantly enhancing the conductivity and facilitating electron transfer in NiMoO4. Furthermore, the introduction of S effectively modulates the electron density state of NiMoO4 and facilitates the formation of highly active catalytic sites characterized by a significantly reduced hydrogen absorption Gibbs free energy (ΔGH*) value of -0.09 eV. The electrocatalyst S-NiMoO4 exhibits remarkable catalytic performance in promoting the hydrogen evolution reaction (HER), displaying a significantly reduced overpotential of 84 mV at a current density of 10 mA cm-2 and maintaining excellent durability at 68 mA cm-2 for 10 h (h). Furthermore, by utilizing the anodic sulfide oxidation reaction (SOR) instead of the sluggish oxygen evolution reaction (OER), the assembled electrolyzer employing S-NiMoO4 as both the cathode and anode need merely 0.8 V to achieve 105 mA cm-2, while simultaneously producing hydrogen gas (H2) and S monomer. This work paves the way for improving electron transfer and activating active sites of metal oxides, thereby enhancing their HER activity.

Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics.

African swine fever, one of the major viral diseases of swine, poses an imminent threat to the global pig industry. The high-efficient replication of the causative agent African swine fever virus (ASFV) in various organs in pigs greatly contributes to the disease. However, how ASFV manipulates the cell population to drive high-efficient replication of the virus in vivo remains unclear. Here, we found that the spleen reveals the most severe pathological manifestation with the highest viral loads among various organs in pigs during ASFV infection. By using single-cell-RNA-sequencing technology and multiple methods, we determined that macrophages and monocytes are the major cell types infected by ASFV in the spleen, showing high viral-load heterogeneity. A rare subpopulation of immature monocytes represents the major population infected at late infection stage. ASFV causes massive death of macrophages, but shifts its infection into these monocytes which significantly arise after the infection. The apoptosis, interferon response, and antigen-presentation capacity are inhibited in these monocytes which benefits prolonged infection of ASFV in vivo. Until now, the role of immature monocytes as an important target by ASFV has been overlooked due to that they do not express classical monocyte marker CD14. The present study indicates that the shift of viral infection from macrophages to the immature monocytes is critical for maintaining prolonged ASFV infection in vivo. This study sheds light on ASFV tropism, replication, and infection dynamics, and elicited immune response, which may instruct future research on antiviral strategies.

An improved compact-form antisaturation model-free adaptive control algorithm for a class of nonlinear systems with time delays.

To solve the time-delay problem and actuator saturation problem of nonlinear plants in industrial processes, an improved compact-form antisaturation model-free adaptive control (ICF-AS-MFAC) method is proposed in this work. The ICF-AS-MFAC scheme is based on the concept of the pseudo partial derivative (PPD) and adopts equivalent dynamic linearization technology. Then, a tracking differentiator is used to predict the future output of a time-delay system to effectively control the system. Additionally, the concept of the saturation parameter is proposed, and the ICF-AS-MFAC controller is designed to ensure that the control system will not exhibit actuator saturation. The proposed algorithm is more flexible, has faster output responses for time-delay systems, and solves the problem of actuator saturation. The convergence and stability of the proposed method are rigorously proven mathematically. The effectiveness of the proposed method is verified by numerical simulations, and the applicability of the proposed method is verified by a series of experimental results based on double tanks.

Early mesodermal development in the patellogastropod Lottia goshimai.

Mesodermal development is essential to explore the interlineage variations in the development of spiralians. Compared with model mollusks such as Tritia and Crepidula, knowledge about the mesodermal development of other molluscan lineages is limited. Here, we investigated early mesodermal development in the patellogastropod Lottia goshimai, which shows equal cleavage and has a trochophore larva. The endomesoderm derived from the 4d blastomere, that is, the mesodermal bandlets, was situated dorsally and showed a characteristic morphology. Investigations of the potential mesodermal patterning genes revealed that twist1 and snail1 were expressed in a proportion of these endomesodermal tissues, while all of the five genes we investigated (twist1, twist2, snail1, snail2, and mox) were expressed in ventrally located ectomesodermal tissues. Relatively dynamic snail2 expression suggests additional roles in various internalization processes. By tracing snail2 expression in early gastrulae, the 3a211 and 3b211 blastomeres were suggested to be the precursors of the ectomesoderm, which elongated to become internalized before division. These results help to understand the variations in the mesodermal development of different spiralians and explore the different mechanisms by which ectomesodermal cells are internalized, which has important evolutionary implications.

MALDI-TOF-MS for Rapid Screening and Typing of ß-Globin Variant and ß-Thalassemia through Direct Measurements of Intact Globin Chains.

BACKGROUND: Traditional phenotype-based screening for ß-globin variant and ß-thalassemia using hematological parameters is time-consuming with low-resolution detection. Development of a MALDI-TOF-MS assay using alternative markers is needed. METHODS: We constructed a MALDI-TOF-MS-based approach for identifying various ß-globin disorders and classifying thalassemia major (TM) and thalassemia intermedia (TI) patients using 901 training samples with known HBB/HBA genotypes. We then validated the accuracy of population screening and clinical classification in 2 separate cohorts consisting of 16 172 participants and 201 ß-thalassemia patients. Traditional methods were used as controls. Genetic tests were considered the gold standard for testing positive specimens. RESULTS: We established a prediction model for identifying different forms of ß-globin disorders in a single MALDI-TOF-MS test based on δ- to ß-globin, γ- to α-globin, γ- to ß-globin ratios, and/or the abnormal globin-chain patterns. Our validation study yielded comparable results of clinical specificity (99.89% vs 99.71%), and accuracy (99.78% vs 99.16%) between the new assay and traditional methods but higher clinical sensitivity for the new method (97.52% vs 88.01%). The new assay identified 22 additional abnormal hemoglobins in 69 individuals including 9 novel ones, and accurately screened for 9 carriers of deletional hereditary persistence of fetal hemoglobin or δß-thalassemia. TM and TI were well classified in 178 samples out of 201 ß-thalassemia patients. CONCLUSIONS: MALDI-TOF-MS is a highly accurate, predictive tool that could be suitable for large-scale screening and clinical classification of ß-globin disorders.

18F-FDG PET/CT-based radiomics nomogram could predict bone marrow involvement in pediatric neuroblastoma.

OBJECTIVE: To develop and validate an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based radiomics nomogram for non-invasively prediction of bone marrow involvement (BMI) in pediatric neuroblastoma. METHODS: A total of 133 patients with neuroblastoma were retrospectively included and randomized into the training set (n = 93) and test set (n = 40). Radiomics features were extracted from both CT and PET images. The radiomics signature was developed. Independent clinical risk factors were identified using the univariate and multivariate logistic regression analyses to construct the clinical model. The clinical-radiomics model, which integrated the radiomics signature and the independent clinical risk factors, was constructed using multivariate logistic regression analysis and finally presented as a radiomics nomogram. The predictive performance of the clinical-radiomics model was evaluated by receiver operating characteristic curves, calibration curves and decision curve analysis (DCA). RESULTS: Twenty-five radiomics features were selected to construct the radiomics signature. Age at diagnosis, neuron-specific enolase and vanillylmandelic acid were identified as independent predictors to establish the clinical model. In the training set, the clinical-radiomics model outperformed the radiomics model or clinical model (AUC: 0.924 vs. 0.900, 0.875) in predicting the BMI, which was then confirmed in the test set (AUC: 0.925 vs. 0.893, 0.910). The calibration curve and DCA demonstrated that the radiomics nomogram had a good consistency and clinical utility. CONCLUSION: The 18F-FDG PET/CT-based radiomics nomogram which incorporates radiomics signature and independent clinical risk factors could non-invasively predict BMI in pediatric neuroblastoma.

An 18F-FDG PET/CT radiomics nomogram for differentiation of high-risk and non-high-risk patients of the International Neuroblastoma Risk Group Staging System.

PURPOSE: To develop and validate an 18F-FDG PET/CT radiomics nomogram for non-invasive differentiation of high-risk and non-high-risk patients of the International Neuroblastoma Risk Group (INRG) Staging System (INRGSS). METHOD: One hundred thirty-nine neuroblastoma patients were retrospectively enrolled and classified into a training set (n = 84) and validation set (n = 55). Radiomics features were extracted from 18F-FDG PET/CT images, a radiomics signature was constructed, and a radiomics score (Rad score) was calculated. Then, univariate and multivariate logistic regression analyses were used to screen out the independent clinical factors and construct the clinical model. A radiomics nomogram was developed based on the Rad score and independent clinical factors. The performance of the clinical model, Rad score, and nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). RESULTS: Seven radiomics features were selected to build the radiomics signature. The age at diagnosis, the INRG stage, neuron-specific enolase (NSE) and Rad score showed a significant difference between the high-risk and non-high-risk patients. The radiomics nomogram incorporating the Rad score and the above clinical factors demonstrated favorable predictive value for differentiating high-risk from non-high-risk, yielded AUCs of 0.988 and 0.971 in the training and validation sets, respectively. The calibration curves showed that the radiomics nomogram had the goodness of fit, and the DCA demonstrated that the radiomics nomogram was clinically useful. CONCLUSIONS: The radiomics nomogram, which incorporates the Rad score and clinical factors can well predict high-risk and non-high-risk patients of the INRGSS. It may help the disease follow-up and management in clinical practice and assist in personalized and precise treatment of neuroblastoma.