DyGraphformer: Transformer combining dynamic spatio-temporal graph network for multivariate time series forecasting.

Transformer-based models demonstrate tremendous potential for Multivariate Time Series (MTS) forecasting due to their ability to capture long-term temporal dependencies by using the self-attention mechanism. However, effectively modeling the spatial correlation cross series for MTS is a challenge for Transformer. Although Graph Neural Networks (GNN) are competent for modeling spatial dependencies across series, existing methods are based on the assumption of static relationships between variables, which do not align with the time-varying spatial dependencies in real-world series. Therefore, we propose DyGraphformer, which integrates graph convolution into Transformer to assist Transformer in effectively modeling spatial dependencies, while also dynamically inferring time-varying spatial dependencies by combining historical spatial information. In DyGraphformer, decoder module involving complex recursion is abandoned to accelerate model execution. First, the input is embedded using DSW (Dimension Segment Wise) through integrating its position and node level embedding to preserve temporal and spatial information. Then, the time self-attention layer and dynamic graph convolutional layer are constructed to capture temporal dependencies and spatial dependencies of multivariate time series, respectively. The dynamic graph convolutional layer utilizes Gated Recurrent Unit (GRU) to obtain historical spatial dependencies, and integrates the series features of the current time to perform graph structure inference in multiple subspaces. Specifically, to fully utilize the spatio-temporal information at different scales, DyGraphformer performs hierarchical encoder learning for the final forecasting. Extensive experimental results on seven real-world datasets demonstrate DyGraphformer outperforms state-of-the-art baseline methods, with comparisons including Transformer-based and GNN-based methods.

Comprehensive Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Transcriptional Signatures of Macrophages in Intrahepatic Cholestasis of Pregnancy.

Purpose: Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated. Patients and Methods: Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta. Results: In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories showed a gradual progression toward inflammation. Subsequently, we confirmed that cytokine- and chemokine-related signaling pathways were emphasized in macrophages. Within the CXCL signaling pathway, the increased expression of CXCL1 in macrophages can interact with CXCR2 in neutrophils, potentially inducing macrophage infiltration, stimulating neutrophil chemotaxis, and leading to an inflammatory response and cellular damage. Conclusion: In conclusion, we firstly revealed the transcriptional signatures of macrophages in ICP and discovered a tendency toward an inflammatory state. This study also provides new evidence that the CXCL1-CXCR2 axis may play an important role in the pathogenesis of ICP.

Corrigendum: LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

[This corrects the article DOI: 10.3389/fphys.2024.1276722.].

Global research status of intrahepatic cholestasis of pregnancy: A bibliometric analysis of hotspots, bursts, and trends.

Background: Research on intrahepatic cholestasis of pregnancy (ICP) has recently gained attention. However, no bibliometric analysis was performed in the ICP research field. Therefore, the present study aimed to use bibliometric analysis to analyze the current research hotspots and identify global research status in ICP to reference for future research directions. Methods: We comprehensively searched the Web of Science Core Collection (WoSCC) database from its inception to December 31, 2023. Articles and reviews related to ICP were downloaded as plain text file records. We used the VOSviewer and Citespace to perform the bibliometric analysis and visualization. The main bibliometric features were tabulated and calculated. Results: A total of 1092 documents, including 921 original articles and 171 reviews, were identified in WoSCC. These publications were published in 395 journals by 4751 authors from 1250 institutions and 61 countries/regions. The global publication numbers exhibited a gradual upward trend. China, the United States, and the United Kingdom were top contributors to scientific research on ICP. King's College London, London Imperial Coll Sci Technol & Med, and Sichuan University were the most productive institutions. Catherine Williamson had published the most papers and received the most total citations. The most productive journal was Journal of Maternal-Fetal & Neonatal Medicine. The most cited paper was Beuers et al. in the Journal of Hepatology (2009). Citation burst terms showed that "risk factors" and "perinatal outcomes" were hotspots. "Inflammation", "risk factors", "perinatal outcomes", and "bile acid" have gained attention in more recent research. Conclusion: The present study comprehensively summarizes the global research status and research trends in ICP. Our study identifies hotspots, collaborative networks, and trends that will provide new insights and guidance for further research in the field.

LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

Aims: Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis. Methods and materials: Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP. Results: Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90. Conclusion: Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies.

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease. It is characterized by pruritus, abnormal liver function and elevated total bile acid (TBA) levels, increasing the risk of maternal and fetal adverse outcomes. Its etiology remains poorly elucidated. Over the years, various omics techniques, including metabolomics, microbiome, genomics, etc., have emerged with the advancement of bioinformatics, providing a new direction for exploring the pathogenesis, diagnosis and treatment of ICP. In this review, we first summarize the role of bile acids and related components in the pathogenesis of ICP and then further illustrate the results of omics studies.

Predictive value of albumin for intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients.

BACKGROUND: Intravenous immunoglobulin (IVIG) has been the mainstay of treatment for Kawasaki disease (KD) over the past decades. However, 10-20% of KD patients are resistant to IVIG treatment which puts those patients at high risk of coronary artery lesions (CALs). Therefore, it is important to predict whether patients will be resistant to IVIG before the treatment. This study aimed to investigate the risk factors for IVIG non-responsive patients with KD. METHODS: This study enrolled patients diagnosed with KD and divided them into two groups, IVIG responders and IVIG non-responders. We compared the differences in demographics and clinical data between the two groups. Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: In total, 907 KD patients were reviewed, with 841 IVIG responders and 66 IVIG non-responders. Patients in IVIG responders were younger than IVIG non-responders. The length of hospitalization of the IVIG non-responders was significantly longer than IVIG responders. The neutrophils%, C-reaction protein (CRP), and CRP/albumin ratio in IVIG responders were significantly lower than in IVIG non-responders (P < 0.05). The lymphocyte% and Albumin in IVIG responders were significantly higher than in IVIG non-responders. Multivariable logistic regression analysis demonstrated that albumin (OR = 0.881, 95% CI, 0.781 to 0.994, p-value = 0.039) was an independent risk factor for predicting IVIG resistance. The area under the ROC curve was 0.644, with a cut-off of ≤ 33.4 g/L determined by Youden's index. The sensitivity and specificity in predicting IVIG resistance were 40.91% and 83.47%, respectively. CONCLUSION: Albumin can serve as a potential predicting marker for IVIG resistance in KD. A lower albumin level may be useful for identifying KD patients with a high risk of IVIG resistance to guide further therapy strategies.

Association of intraoperative hypotension and severe postoperative complications during non-cardiac surgery in adult patients: A systematic review and meta-analysis.

Background: Intraoperative hypotension (IOH) is a common side effect of non-cardiac surgery that might induce poor postoperative outcomes. The relationship between the IOH and severe postoperative complications is still unclear. Thus, we summarized the existing literature to evaluate whether IOH contributes to developing severe postoperative complications during non-cardiac surgery. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, and the CBM from inception to 15 September 2022. The primary outcomes were 30-day mortality, acute kidney injury (AKI), major adverse cardiac events (myocardial injury or myocardial infarction), postoperative cognitive dysfunction (POCD), and postoperative delirium (POD). Secondary outcomes included surgical-site infection (SSI), stroke, and 1-year mortality. Results: 72 studies (3 randomized; 69 non-randomized) were included in this study. Low-quality evidence showed IOH resulted in an increased risk of 30-day mortality (OR, 1.85; 95% CI, 1.30-2.64; P < .001), AKI (OR, 2.69; 95% CI, 2.15-3.37; P < .001), and stroke (OR, 1.33; 95% CI, 1.21-1.46; P < .001) after non-cardiac surgery than non-IOH. Very low-quality evidence showed IOH was associated with a higher risk of myocardial injury (OR, 2.00; 95% CI, 1.17-3.43; P = .01), myocardial infarction (OR, 2.11; 95% CI, 1.41-3.16; P < .001), and POD (OR, 2.27; 95% CI, 1.53-3.38; P < .001). Very low-quality evidence showed IOH have a similar incidence of POCD (OR, 2.82; 95% CI, 0.83-9.50; P = .10) and 1-year-mortality (OR, 1.66; 95% CI, 0.65-4.20; P = .29) compared with non-IOH in non-cardiac surgery. Conclusion: Our results suggest IOH was associated with an increased risk of severe postoperative complications after non-cardiac surgery than non-IOH. IOH is a potentially avoidable hazard that should be closely monitored during non-cardiac surgery.

The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis.

BACKGROUND: The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients. METHODS: We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1-2 months of follow-up. RESULTS: 27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50-2.15; P < .00001; I2 = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40-0.80; P = .001; I2 = 76%). There was a lower risk of CALs during 1-2 months follow-up for those who started IVIG administration within 10 days from the onset. CONCLUSIONS: Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.

The role of red blood cell distribution width in predicting coronary artery lesions in pediatric patients with kawasaki disease.

Background: Recent studies have shown that red blood cell distribution width (RDW) has emerged as a novel predictor of cardiovascular diseases. We aim to investigate the association between RDW and the risk of coronary artery lesions (CALs) in pediatric patients with Kawasaki disease (KD). Methods: KD patients were classified as the CALs group (patients with CALs) and non-CALs group (patients without CALs). Differences among the groups were analyzed by Mann-Whitney U-test and Chi-square analysis. The independent risk factors of CALs were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the optimal cut-off value. Results: The red blood cell distribution width (RDW) and C-reactive protein were significantly higher in the CALs group than those in the non-CALs group (p < 0.01). Multivariate logistic regression analysis revealed that RDW (OR = 5.2, 95% CI, 4.064 to 6.654) was independent risk factors of CALs in KD patients (p < 0.01). The subgroup analysis also confirmed that the high level of RDW was an independent risk factor for the development of CALs in patients with complete and incomplete KD. The ROC analysis showed the optimal cut-off value of RDW for predicting CALs was >13.86%, with a sensitivity of 75.79% and specificity of 92.81% (AUC = 0.869, 95% CI = 0.844-0.892; p < 0.0001). Conclusions: RDW is an independent predictor with high sensitivity and specificity to predict CALs in KD patients. The elevation in RDW level (>13.86%) may be used as novel biomarkers for early predicting CALs in KD patients during the acute phase.

Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki Disease: a retrospective cohort study.

OBJECTIVE: Since coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD), clinically speaking, early prediction of CALs is crucial. The authors aimed to investigate the predictive value of C-reactive protein (CRP) in predicting CALs in KD patients. METHODS: KD patients were divided into the CALs group and the non-CALs group. The clinical and laboratory parameters were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of CALs. The receiver operating characteristic curve was applied to determine the optimal cut-off value. RESULTS: 851 KD patients who met the inclusion criteria were studied, including 206 in the CALs group and 645 in the non-CALs group. Children in the CALs group had significantly higher CRP levels than the non-CALs group (p < 0.05). Multivariable logistic regression analysis showed that incomplete KD, male, lower hemoglobin, and higher CRP were independent risk factors for predicting CAL (all p < 0.05). The optimal cut-off value of initial serum CRP for predicting CALs was 105.5 mg/L, with a sensitivity of 47.57% and a specificity of 69.61%. In addition, KD patients with high CRP (≥105.5 mg/L) had a higher occurrence of CALs than those with low CRP (<105.5 mg/L) (33% vs 19%, p < 0.001). CONCLUSION: The incidence of CALs was significantly higher in patients with high CRP. CRP is an independent risk factor for CALs formation and may be useful for predicting CALs in KD patients.

A survey on federated learning: challenges and applications.

Federated learning (FL) is a secure distributed machine learning paradigm that addresses the issue of data silos in building a joint model. Its unique distributed training mode and the advantages of security aggregation mechanism are very suitable for various practical applications with strict privacy requirements. However, with the deployment of FL mode into practical application, some bottlenecks appear in the FL training process, which affects the performance and efficiency of the FL model in practical applications. Therefore, more researchers have paid attention to the challenges of FL and sought for various effective research methods to solve these current bottlenecks. And various research achievements of FL have been made to promote the intelligent development of all application areas with privacy restriction. This paper systematically introduces the current researches in FL from five aspects: the basics knowledge of FL, privacy and security protection mechanisms in FL, communication overhead challenges and heterogeneity problems of FL. Furthermore, we make a comprehensive summary of the research in practical applications and prospect the future research directions of FL.

Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki Disease: a retrospective cohort study

Abstract Objective Since coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD), clinically speaking, early prediction of CALs is crucial. The authors aimed to investigate the predictive value of C-reactive protein (CRP) in predicting CALs in KD patients. Methods KD patients were divided into the CALs group and the non-CALs group. The clinical and laboratory parameters were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of CALs. The receiver operating characteristic curve was applied to determine the optimal cut-off value. Results 851 KD patients who met the inclusion criteria were studied, including 206 in the CALs group and 645 in the non-CALs group. Children in the CALs group had significantly higher CRP levels than the non-CALs group (p< 0.05). Multivariable logistic regression analysis showed that incomplete KD, male, lower hemoglobin, and higher CRP were independent risk factors for predicting CAL (all p< 0.05). The optimal cut-off value of initial serum CRP for predicting CALs was 105.5 mg/L, with a sensitivity of 47.57% and a specificity of 69.61%. In addition, KD patients with high CRP (≥105.5 mg/L) had a higher occurrence of CALs than those with low CRP (<105.5 mg/L) (33% vs 19%, p< 0.001). Conclusion The incidence of CALs was significantly higher in patients with high CRP. CRP is an independent risk factor for CALs formation and may be useful for predicting CALs in KD patients.

Status and influencing factors of medication literacy among Chinese caregivers of discharged children with Kawasaki disease.

Background: The information on medication literacy among Chinese caregivers of discharged children with Kawasaki disease (KD) is unknown. We aimed to investigate the status of medication literacy among caregivers of discharged children with KD and evaluate the influencing factors of medication literacy. Methods: From March 2020 to February 2021, 106 caregivers with a KD child were recruited for the present study. We collected the sociodemographic characteristics of the KD caregivers using structured interviews. The medication literacy of the KD caregivers was assessed by the Chinese version of Medication Literacy Assessment. KD patients' demographic and clinical data were obtained from the medical records. The multiple logistic regression was performed to identify factors associated with medication literacy. Results: (1) The average medication literacy score was 4.91 ± 1.51. (2) Most of the Chinese KD caregivers had insufficient medication literacy (≤ 5 scores), and only 39.2% of the caregivers had adequate medication literacy (>5 scores). (3) The multiple logistic regression shows that education level, monthly income, and duration of hospitalization are the independent influencing factors on the medication literacy of KD caregivers. Conclusion: There is preliminary evidence that medication literacy among KD caregivers is low and needs improvement. A higher level of education, higher income, and longer duration of hospitalization were influencing factors of adequate medication literacy.

Landscape and progress of global peptide drugs in obstetrics and gynaecology.

Peptides have gained popularity in the global market during recent years and have been placed between small molecule drugs and biologics. However, little is known about the comprehensive landscape of peptide drugs in obstetrics and gynaecology. Herein, we analysed new peptide drug-related clinical trials in obstetrics and gynaecology registered on ClinicalTrials.gov. The number and percentage were used for statistical analysis, and a time trend analysis was conducted by calculating the annual growth rate. We aimed to provide the first overview of the changing landscape and status of global peptide drugs in this prospective field, including exploring drug targets, the cutting-edge oncotherapy of peptide vaccines and peptide-drug conjugates, and unsolved challenges with oral administration.

The progress of peptide vaccine clinical trials in gynecologic oncology.

Peptide vaccine are a type of immunotherapy that are synthesized according to the amino acid sequence of known or predicted tumor antigen epitopes. They are safe and well tolerated and have shown exciting results in gynecologic oncology. However, no peptide vaccine has yet been licensed in this field. This review examines peptide vaccine clinical trials in gynecology registered on ClinicalTrials.gov through January 1, 2022, analyzes the global progress and current achievements of peptide vaccines in gynecology, and explores the efforts focused on devising new methods to boost immunotherapeutic outcomes, including the use of adjuvants, multi-epitope vaccines, combinations of helper T cell epitopes, personalized peptide vaccines, synthetic long peptides, new peptide delivery, and combination therapy.

Effect of Anesthetics on Functional Connectivity of Developing Brain.

The potential anesthetic neurotoxicity on the neonate is an important focus of research investigation in the field of pediatric anesthesiology. It is essential to understand how these anesthetics may affect the development and growth of neonatal immature and vulnerable brains. Functional magnetic resonance imaging (fMRI) has suggested that using anesthetics result in reduced functional connectivity may consider as core sequence for the neurotoxicity and neurodegenerative changes in the developed brain. Anesthetics either directly impact the primary structures and functions of the brain or indirectly alter the hemodynamic parameters that contribute to cerebral blood flow (CBF) in neonatal patients. We hypothesis that anesthetic agents may either decrease the brain functional connectivity in neonatal patients or animals, which was observed by fMRI. This review will summarize the effect and mechanism of anesthesia on the rapid growth and development infant and neonate brain with fMRI through functional connectivity. It is possible to provide the new mechanism of neuronal injury induced by anesthetics and objective imaging evidence in animal developing brain.