Changes in the epidemiology and clinical characteristics of viral gastroenteritis among hospitalized children in the Mainland of China: a retrospective study from 2016 to 2020.

BACKGROUND: Acute gastroenteritis (AGE) causes significant morbidity in children worldwide; however, the disease burden of children hospitalized with viral gastroenteritis in China has been rarely described. Through this study, we analyzed the data of hospitalized children with viral gastroenteritis to explore the changes in the epidemiology and clinical characteristics of viral gastroenteritis in the mainland of China. METHODS: Data were extracted from Futang Children's Medical Development Research Center (FRCPD), between 2016 and 2020, across 27 hospitals in 7 regions. The demographics, geographic distribution, pathogenic examination results, complications, hospital admission date, length of hospital stays, hospitalization charges and outcomes were collected and analyzed. RESULTS: Viral etiological agents included rotavirus (RV), adenovirus (ADV), norovirus (NV) and coxsackievirus (CV) that were detected in 25,274 (89.6%), 1,047 (3.7%), 441 (1.5%) and 83 (0.3%) cases. There was a higher prevalence of RV and NV infection among children younger than 3 years of age. RV and NV had the highest detection rates in winter, while ADV in summer. Children with viral gastroenteritis were often accompanied by other diseases, such as myocardial diseases (10.98-31.04%), upper respiratory tract diseases (1.20-20.15%), and seizures (2.41-14.51%). Among those cases, the co-infection rate with other pathogens was 6.28%, with Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), and influenza virus (FLU) being the most common pathogens. The median length of stay was 5 days, and the median cost of hospitalization corresponded to587 US dollars. CONCLUSIONS: This finding suggests that viral gastroenteritis, especially those caused by RV, is a prevalent illness among younger children. Co-infections and the presence of other diseases are common. The seasonality and regional variation of viral etiological agents highlight the need for targeted prevention and control measures. Although viral gastroenteritis rarely leads to death, it also results in a significant economic burden on healthcare systems.

Precise Design of TiO2@CoOx Heterostructure via Atomic Layer Deposition for Synergistic Sono-Chemodynamic Oncotherapy.

Sonodynamic therapy (SDT), a tumor treatment modality with high tissue penetration and low side effects, is able to selectively kill tumor cells by producing cytotoxic reactive oxygen species (ROS) with ultrasound-triggered sonosensitizers. N-type inorganic semiconductor TiO2 has low ROS quantum yields under ultrasound irradiation and inadequate anti-tumor activity. Herein, by using atomic layer deposition (ALD) to create a heterojunction between porous TiO2 and CoOx, the sonodynamic therapy efficiency of TiO2 can be improved. Compared to conventional techniques, the high controllability of ALD allows for the delicate loading of CoOx nanoparticles into TiO2 pores, resulting in the precise tuning of the interfaces and energy band structures and ultimately optimal SDT properties. In addition, CoOx exhibits a cascade of H2O2→O2→·O2 - in response to the tumor microenvironment, which not only mitigates hypoxia during the SDT process, but also contributes to the effect of chemodynamic therapy (CDT). Correspondingly, the synergistic CDT/SDT treatment is successful in inhibiting tumor growth. Thus, ALD provides new avenues for catalytic tumor therapy and other pharmaceutical applications.

Investigation of the causal relationship between Interleukin-6 signaling and gastrointestinal tract cancers: A Mendelian randomization study.

BACKGROUND: Observational studies indicate that interleukin-6(IL-6) has been associated with gastrointestinal tract cancers. However, the causal association is still confusing. Thus, we aimed to putative the causality between IL-6 signaling and gastrointestinal tract cancers. METHODS: We conducted a two-sample Mendelian randomization analysis to assess the causal effects. Two groups of IL-6 signaling-related single nucleotide polymorphisms were chosen from two Genome-wide association studies. Summary-level data for gastrointestinal tract cancers including esophageal, gastric, and colorectal cancer, were obtained from the FinnGen consortium and UK Biobank study. We also performed survival analysis to explore the prognostic value of IL-6 in gastrointestinal tract cancers. RESULTS: Genetically predicted plasma sIL6R level, which inhibits IL-6 Signaling, was associated with a reduced risk of gastric cancer in FinnGen. In the combined analysis of the two sources, genetically predicted sIL6R was associated with a decreased risk of gastric cancer (OR = 0.943, 95%CI: 0.904,0.983, p = 0.006). Survival analysis results indicated the prognostic value of IL-6 in gastric cancer. CONCLUSIONS: These results present evidence indicating that genetically-determined reduced IL-6 signaling lowers the risk of gastric cancer, which may provide potential prevention and therapeutic strategies for gastric cancer. Additionally, IL-6 may be a prognostic biomarker for gastric cancer.

Exploiting predatory bacteria as biocontrol agents across ecosystems.

Predatory bacteria have been increasingly known for their ubiquity in environments and great functional potentials in controlling unwanted microorganisms. Fundamental understanding of the predation mechanisms, population dynamics, and interaction patterns underlying bacterial predation is required for wise exploitation of predatory bacteria for enhancing ecoenvironmental, animal, and human health. Here, we review the recent achievements on applying predatory bacteria in different systems as biocontrol agents and living antibiotics as well as new findings in their phylogenetic diversity and predation mechanisms. We finally propose critical issues that deserve priority research and highlight the necessity to combine classic culture-based and advanced culture-independent approaches to push research frontiers of bacterial predation across ecosystems for promising biocontrol and therapy strategies towards a sustainable ecoenvironment and health.

Multimodal imaging and photothermal/chemodynamic therapy of cervical cancer using GSH-responsive MoS2@MnO2 theranostic nanoparticles.

The development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS2) core coated with Manganese dioxide (MnO2), which possessed a good photothermal effect and could produce Fenton-like Mn2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH2) to improve their biocompatibility, resulting in the formation of MoS2@MnO2-PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS2@MnO2-PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.

Cobind: quantitative analysis of the genomic overlaps.

Motivation: Analyzing the overlap between two sets of genomic intervals is a frequent task in the field of bioinformatics. Typically, this is accomplished by counting the number (or proportion) of overlapped regions, which applies an arbitrary threshold to determine if two genomic intervals are overlapped. By making binary calls but disregarding the magnitude of the overlap, such an approach often leads to biased, non-reproducible, and incomparable results. Results: We developed the cobind package, which incorporates six statistical measures: the Jaccard coefficient, Sørensen-Dice coefficient, Szymkiewicz-Simpson coefficient, collocation coefficient, pointwise mutual information (PMI), and normalized PMI. These measures allow for a quantitative assessment of the collocation strength between two sets of genomic intervals. To demonstrate the effectiveness of these methods, we applied them to analyze CTCF's binding sites identified from ChIP-seq, cancer-specific open-chromatin regions (OCRs) identified from ATAC-seq of 17 cancer types, and oligodendrocytes-specific OCRs identified from scATAC-seq. Our results indicated that these new approaches effectively re-discover CTCF's cofactors, as well as cancer-specific and oligodendrocytes-specific master regulators implicated in disease and cell type development. Availability and implementation: The cobind package is implemented in Python and freely available at https://cobind.readthedocs.io/en/latest/.

Spatial-temporal data-augmentation-based functional brain network analysis for brain disorders identification.

Introduction: Due to the lack of devices and the difficulty of gathering patients, the small sample size is one of the most challenging problems in functional brain network (FBN) analysis. Previous studies have attempted to solve this problem of sample limitation through data augmentation methods, such as sample transformation and noise addition. However, these methods ignore the unique spatial-temporal information of functional magnetic resonance imaging (fMRI) data, which is essential for FBN analysis. Methods: To address this issue, we propose a spatial-temporal data-augmentation-based classification (STDAC) scheme that can fuse the spatial-temporal information, increase the samples, while improving the classification performance. Firstly, we propose a spatial augmentation module utilizing the spatial prior knowledge, which was ignored by previous augmentation methods. Secondly, we design a temporal augmentation module by random discontinuous sampling period, which can generate more samples than former approaches. Finally, a tensor fusion method is used to combine the features from the above two modules, which can make efficient use of spatial-temporal information of fMRI simultaneously. Besides, we apply our scheme to different types of classifiers to verify the generalization performance. To evaluate the effectiveness of our proposed scheme, we conduct extensive experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and REST-meta-MDD Project (MDD) dataset. Results: Experimental results show that the proposed scheme achieves superior classification accuracy (ADNI: 82.942%, MDD: 63.406%) and feature interpretation on the benchmark datasets. Discussion: The proposed STDAC scheme, utilizing both spatial and temporal information, can generate more diverse samples than former augmentation methods for brain disorder classification and analysis.

Pediatric deep venous thrombosis associated with Staphylococcus aureus osteomyelitis.

INTRODUCTION: Our objective was to evaluate clinical features of children with deep venous thrombosis (DVT) and acute hematogenous osteomyelitis (AHO) caused by Staphylococcus aureus. METHODOLOGY: We analyzed 4 years of medical records of patients with AHO and DVT caused by Staphylococcus aureus (S. aureus) and compared clinical and biochemical characteristics of AHO with and without DVT, as well as patients whose DVT dissolved in ≥ 3 weeks. RESULTS: DVT was found in 19/87 AHO individuals (22%). The median age was 9 years (range: 0.5-15 years). 74% (14/19) patients were boys. Methicillin-susceptible Staphylococcus aureus (MSSA) was present in 58% (11/19) cases. The femoral vein and common femoral vein were the two most damaged veins (9 cases each). Anticoagulation therapy with low molecular weight heparin was given to 18 (95%) patients. Within 3 weeks of anticoagulation, 7/13 (54%) with available data had completely resolved DVT. There was no rehospitalization due to bleeding or recurrent DVT. Patients with DVT were found to be older and had increased levels of C-reactive protein, procalcitonin, D-dimer, positive blood culture, incidence of intensive care unit admission, multifocal rate, and length of hospital stay. We did not find clinical difference between patients whose DVT dissolved within 3 weeks and those with > 3 weeks. CONCLUSIONS: Over 20% of patients with S. aureus AHO developed DVT. MSSA accounted for more than half of the cases. DVT was completely resolved in more than half of the cases after 3 weeks of anticoagulant medication, with no sequelae.

Three-Dimensional Strawlike MoSe2-Ni(Fe)Se Electrocatalysts for Overall Water Splitting.

The development of efficient and low-cost transition-metal electrocatalysts is of great significance for hydrogen production from water splitting. Herein, we synthesized three-dimensional strawlike MoSe2-NiSe composed of microrods on nickel foam (NF) by a one-step hydrothermal reaction. The as-prepared MoSe2-NiSe/NF exhibited effective hydrogen evolution reaction (HER) activity (low overpotential of 79 mV at 10 mA cm-2 and stability of 21 h in 1 M KOH), benefiting from the large electrochemically active area provided by strawlike structures, proper Se content, and synergistic effect of active phases. The enhanced oxygen evolution reaction (OER) activity (the low overpotential of 217 mV at 10 mA cm-2 and maintaining stability for 47 h in 1 M KOH) was further observed for Fe-doped MoSe2-NiSe/NF (MoSe2-NiFeSe/NF) prepared by facile soaking, which can be mainly ascribed to optimized active phases formed on the OER process after Fe doping. The two-electrode system (MoSe2-NiSe/NF||MoSe2-NiFeSe/NF) requires a low cell voltage of 1.54 V to obtain a current density of 10 mA cm-2 in 1 M KOH, which provides an interesting idea for constructing an effective overall water splitting system.

Comparison of cytokine level changes in gingival crevicular fluid between the aligner and pendulum appliance during early molar distalization : A single-center, prospective, observational study.

PURPOSE: There is currently a lack of evidence pertaining to gingival crevicular fluid cytokine levels in patients treated with the pendulum appliance. This study aimed to compare changes in cytokine secretion levels in gingival crevicular fluid (GFC) between the aligner and pendulum appliance in patients undergoing molar distalization. METHODS: GFC samples were collected from 28 participants with asymmetrical dental class II malocclusion who were undergoing molar distalization using aligners or pendulum appliances. An enzyme-linked immunosorbent assay was used to detect cytokine secretion levels during asymmetrical molar distalization for up to 14 days. Periodontal health indices and tooth movements were also assessed. RESULTS: No significant difference was found for the distalization distance between the two appliances. The Silness and Loe Plaque Index and Lobene Modified Gingival Index increased in the pendulum group but not in the aligner group at 14 days. Interleukin-1ß and tumor necrosis factor­α were upregulated in both groups. In the pendulum group, receptor activator of nuclear factor kappa­Β ligand and osteoprotegerin secretion levels were significantly upregulated and downregulated, respectively; smaller changes in these two cytokines were observed in the aligner group. CONCLUSIONS: Pendulum appliances exert stronger forces than aligners, which cause more changes in the secretion of inflammatory mediators in young patients.

Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study.

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study. Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above. Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method. Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis. Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.

Clinical characteristics of central nervous system candidiasis due to Candida albicans in children: a single-center experience.

BACKGROUND: Central nervous system candidiasis due to Candida albicans (CNSC) in children is easily misdiagnosed and is associated with poor outcomes and a high mortality rate. There is no big data research or systematic review of CNSC. METHODS: Patients diagnosed as CNSC with positive culture results of Candida albicans in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2019 were included. Patients receiving immunosuppressive therapy or transplantation, or with malignant tumours were excluded. We analysed the clinical characteristics, follow-up results, drug susceptibility tests and whole-exome sequencing (WES) results. RESULTS: Thirty-three definitive patients were enrolled, including 22 males and 11 females. Twenty-five patients suffered from CNSC when they were less than 1 year old, and a total of 29 patients had high-risk factors. The main clinical manifestations were fever, convulsions, and positive neurological signs. Twenty-two patients had CNS infections alone, and 11 patients had CNS infections combined with invasive infections involving multiple sites. Twenty-seven cases had a positive CSF and/or blood culture at our hospital. All strains were susceptible to fluconazole, and 2 strains had intermediate susceptibility to voriconazole. As for amphotericin B, all the strains were wild type (WT). WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before. CONCLUSION: CNSC mostly existed in children younger than 1 year old, who all had underlying risk factors. CNSC patients with onset at an older age or with recurrent superficial fungal infections might have primary immunodeficiency.

High-throughput sequencing unravels the cell heterogeneity of cerebrospinal fluid in the bacterial meningitis of children.

Bacterial meningitis (BM) is a common life-threatening infection in children that occurs in the central nervous system (CNS). The cytologic examination of cerebrospinal fluid (CSF) is a key parameter in the diagnosis of BM, but the heterogeneity of cells in the CSF has not been elucidated, which limits the current understanding of BM neuroinflammation. In this study, CSF samples were collected from a number of BM patients who were in different stages of disease progression. Single-cell RNA-sequencing (scRNA-seq), with additional bulk transcriptome sequencing, was conducted to decipher the characteristics of CSF cells in BM progression. A total of 18 immune cell clusters in CSF were identified, including two neutrophils, two monocytes, one macrophage, four myeloid dendritic cells, five T cells, one natural killer cell, one B cell, one plasmacytoid dendritic cell, and one plasma cell subtype. Their population profiles and dynamics in the initial onset, remission, and recovery stages during BM progression were also characterized, which showed decreased proportions of myeloid cells and increased proportions of lymphoid cells with disease progression. One novel neutrophil subtype, FFAR2+TNFAIP6+ neutrophils, and one novel monocyte subtype, THBS1+IL1B+ monocytes, were discovered, and their quantity changes positively correlated with the intensity of the inflammatory response in the CSF during BM. In addition, the CSF of BM patients with unsatisfactory therapeutic responses presented with different cell heterogeneity compared to the CSF of BM patients with satisfactory therapeutic responses, and their CSF featured altered intercellular communications and increased proportions of type II myeloid dendritic cells and plasmacytoid dendritic cells. Moreover, the bulk transcriptome profiles of autologous CSF cells and peripheral blood leukocytes of BM patients showed that the immune cells in these two physiological compartments exhibited distinct immune responses under different onset conditions. In particular, the CSF cells showed a high expression of macrophage characteristic genes and a low expression of platelet characteristic genes compared with peripheral blood leukocytes. Our study conducted an in-depth exploration of the characteristics of CSF cells in BM progression, which provided novel insights into immune cell engagement in acute CNS infection.

Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China.

OBJECTIVE: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes. DESIGN: A retrospective study. SETTING: Beijing Children's Hospital. PARTICIPANTS: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017. INTERVENTIONS: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated. PRIMARY AND SECONDARY OUTCOME MEASURES: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05). RESULTS: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old. CONCLUSIONS: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.

Multi-band network fusion for Alzheimer's disease identification with functional MRI.

Introduction: The analysis of functional brain networks (FBNs) has become a promising and powerful tool for auxiliary diagnosis of brain diseases, such as Alzheimer's disease (AD) and its prodromal stage. Previous studies usually estimate FBNs using full band Blood Oxygen Level Dependent (BOLD) signal. However, a single band is not sufficient to capture the diagnostic and prognostic information contained in multiple frequency bands. Method: To address this issue, we propose a novel multi-band network fusion framework (MBNF) to combine the various information (e.g., the diversification of structural features) of multi-band FBNs. We first decompose the BOLD signal adaptively into two frequency bands named high-frequency band and low-frequency band by the ensemble empirical mode decomposition (EEMD). Then the similarity network fusion (SNF) is performed to blend two networks constructed by two frequency bands together into a multi-band fusion network. In addition, we extract the features of the fused network towards a better classification performance. Result: To verify the validity of the scheme, we conduct our MBNF method on the public ADNI database for identifying subjects with AD/MCI from normal controls. Discussion: Experimental results demonstrate that the proposed scheme extracts rich multi-band network features and biomarker information, and also achieves better classification accuracy.

Computational framework for generating large panoramic super-resolution images from localization microscopy.

Combining super-resolution localization microscopy with pathology creates new opportunities for biomedical researches. This combination requires a suitable image mosaic method for generating a panoramic image from many overlapping super-resolution images. However, current image mosaic methods are not suitable for this purpose. Here we proposed a computational framework and developed an image mosaic method called NanoStitcher. We generated ground truth datasets and defined criteria to evaluate this computational framework. We used both simulated and experimental datasets to prove that NanoStitcher exhibits better performance than two representative image mosaic methods. This study is helpful for the mature of super-resolution digital pathology.

Clinical characteristics and effectiveness of antiviral agents in hospitalized children with infectious mononucleosis in China: A multicenter retrospective study.

IMPORTANCE: The clinical characteristics of infectious mononucleosis (IM) in Chinese children have not been evaluated in multicenter studies, and the effectiveness of antiviral treatment are controversial. OBJECTIVE: To investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients. METHODS: Hospitalized patients with IM were enrolled between 2018 and 2020 in five children's hospitals in China. The clinical characteristics were compared among four age groups: <3 years, 3-<6 years, 6-<10 years, and ≥10 years. The clinical characteristics of IM and effectiveness of antiviral therapy were compared among patients receiving acyclovir (ACV), ganciclovir (GCV), and no antiviral therapy (i.e., non-antiviral group). RESULTS: In total, 499 patients were analyzed; most patients were 3-<6 years of age. The most common symptoms and signs included fever (100%), lymphadenopathy (98.6%), pharyngitis (86.4%), eyelid edema (76.8%), and snoring (72.9%). There were significant differences in rash, hepatomegaly, and liver dysfunction among the four age groups. Patients aged < 3 years had a lower incidence of liver dysfunction and a higher incidence of rash. Among the 499 patients, 50.1% were treated with GCV, 26.3% were treated with ACV, and 23.6% received no antiviral therapy. Compared with the non-antiviral group, patients in the ACV and GCV groups had longer durations of fever (P < 0.001). There were no significant differences in the incidences of complications among the three treatment groups. INTERPRETATION: The incidence of IM in Chinese children peaked at 3-<6 years of age. Clinical features of IM varied according to age. Patients receiving antiviral therapy exhibited more serious clinical manifestations than did patients without antiviral therapy. The effectiveness of antiviral therapy for IM requires further analysis.