Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disea... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disease 2019 (COVID-19) (1), which has become a pandemic since it was discovered in December 2019. Multiple variants of SARS-CoV-2 have subsequently emerged, with some variants of concern (such as Alpha, Beta, Delta, and Omicron) varying in their transmissibility and virulence (2-4). The Alpha variant is more transmissible than the wild-type of SARS-CoV-2 among children (5). A recent study found that children may play an important role in transmission of the Delta variant compared with previously circulating SARS-CoV-2 variants (6). A large cohort study found that individuals aged 10-19 years infected with the Omicron
Background Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency tha... more Background Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency that results in fructose metabolism disorder. The disease prevalence in the Chinese population is unknown, which impedes the formulation of HFI screening and diagnosis strategies. Materials and methods By searching a local cohort (Chinese Children’s Rare Disease Genetic Testing Clinical Collaboration System, CCGT) and public databases (ClinVar and Human Gene Mutation Database) and reviewing HFI-related literature, we manually curated ALDOB pathogenic or likely pathogenic (P/LP) variants according to ACMG guidelines. Allele frequency (AF) information from the local database CCGT and the public databases HuaBiao and gnomAD for ALDOB P/LP variants was used to estimate and the HFI prevalence in the Chinese population and other populations by the Bayesian framework. We collected the genotype and clinical characteristics of HFI patients from the CCGT database and published literature to study gen...
Background: The population of China represents about one sixth of the global population. It is im... more Background: The population of China represents about one sixth of the global population. It is important to create a national database with a large sample size and a sustained collaborative platform. The objective of this study was to introduce the Chinese Neonatal Network (CHNN), a new platform of national collaboration on quality improvement (QI) for short and long-term health outcomes of preterm infants. Methods: The background, participating centers, data collection, and objectives are described. Specific objectives are to: (I) Establish a standardized database of very preterm infants (VPI) with gestational age <32 weeks or birth weight (BW) <1,500 grams. (II) Assess, benchmark and monitor major outcomes of VPI and their risk determinants, as well as inter-institutional variations. (III) Implement the Evidencebased Practice for Improving Quality (EPIQ) program to improve quality of care and outcomes. (IV) Conduct collaborative research, including epidemiologic, clinical and health services studies and randomized controlled trials. This study is collaboratively funded by Canadian Institute of Health Research and the Children's Hospital of Fudan University. Results: The CHNN collaboration acts as a platform that member neonatal intensive care units (NICUs) can access for evidence on implementing practice improvements, learning activities, and research collaborations. There were 58 participating centers in 2018, which was expanded to be 79 in 2021. CHNN has published 2 annual reports to describe the outcomes and care practices of VPI in 2019 and 2020, and conducted an internal audit of data quality. Conclusions: The knowledge generated will be available nationally and worldwide with a definite national impact and a likely global impact.
The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2 infected children aged ... more The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2 infected children aged 6-14 years: a cohort study. Ann Transl Med 2022.
Background and purpose: Neonatal hyperbilirubinemia, also known as neonatal jaundice, is a common... more Background and purpose: Neonatal hyperbilirubinemia, also known as neonatal jaundice, is a common and frequent clinical condition with a complex etiology that can lead to brain damage in severe cases. Early recognition of hyperbilirubinemia and timely intervention and treatment can help reduce the occurrence of sequelae. This study was conducted to identify whether the gut microbiota composition can distinguish neonates with hyperbilirubinemia. Methods: Meconium samples were collected from 69 neonates with neonatal jaundice (NJ) and 69 age- and sex-matched neonates without clinically significant jaundice (healthy controls; HCs) for 16S rRNA gene sequencing and microbiome analysis. Results: Compared with HCs, the Chao 1 richness index of the gut microbiota was significantly decreased in the NJ group. The relative abundance of the probiotic gut bacterium, Lactobacillus, was significantly lower in the NJ group than in the HC group, whereas the abundances of potentially harmful gut bact...
ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, ... more ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples ...
Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but r... more Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and methods We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the h...
The rapid growth of digital images motivates individuals and organizations to upload their images... more The rapid growth of digital images motivates individuals and organizations to upload their images to the cloud server. To preserve the privacy, image owners would prefer to encrypt the images before uploading, but it would strongly limit the efficient usage of images. Plenty of existing schemes on privacy-preserving Content-Based Image Retrieval (PPCBIR) try to seek the balance between security and retrieval ability. However, compared to the advanced technologies in CBIR like Convolutional Neural Network (CNN), the existing PPCBIR schemes are far deficient in both accuracy and efficiency. With more cloud service providers, the collaborative secure image retrieval service provided by multiple cloud servers becomes possible. In this paper, inspired by additive secret sharing technology, we propose a series of additive secure computing protocols on numbers and matrices with better efficiency, and then show their application in PPCBIR. Specifically, we extract CNN features, decrease the dimension of features and build the index securely with the help of our protocols, which include the full process of image retrieval in plaintext domain. The experiments and security analysis demonstrate the efficiency, accuracy and security of our scheme.
Background: Serious games are potential alternatives for supplementing traditional simulation-bas... more Background: Serious games are potential alternatives for supplementing traditional simulation-based education for neonatal resuscitation training. However, evidence regarding the benefits of using serious games to improve long-term knowledge retention of neonatal resuscitation in undergraduate medical students is lacking.Objective: We designed a serious computer game “NEOGAMES” to train undergraduate medical students in neonatal resuscitation in a cost-friendly and accessible way and to examine whether serious game-based training improves long-term knowledge retention in medical students.Methods: “NEOGAMES” consists of a screen with images of an incubator, a baby, visual objects, anatomy, action cards, monitors, real-time feedback, and emotional components. Undergraduate medical students from Shanghai Medical College of Fudan University were invited to participate and were allocated to a game group or a control group. Participants in the game group played the game before the trainin...
BackgroundAn early and accurate evaluation of the risk of bronchopulmonary dysplasia (BPD) in pre... more BackgroundAn early and accurate evaluation of the risk of bronchopulmonary dysplasia (BPD) in premature infants is pivotal in implementing preventive strategies. The risk prediction models nowadays for BPD risk that included only clinical factors but without genetic factors are either too complex without practicability or provide poor-to-moderate discrimination. We aim to identify the role of genetic factors in BPD risk prediction early and accurately.MethodsExome sequencing was performed in a cohort of 245 premature infants (gestational age <32 weeks), with 131 BPD infants and 114 infants without BPD as controls. A gene burden test was performed to find risk genes with loss-of-function mutations or missense mutations over-represented in BPD and severe BPD (sBPD) patients, with risk gene sets (RGS) defined as BPD–RGS and sBPD–RGS, respectively. We then developed two predictive models for the risk of BPD and sBPD by integrating patient clinical and genetic features. The performanc...
Additional file 1 Table S1. Stability results of PAK3 and variant, produced by Molecular Operatin... more Additional file 1 Table S1. Stability results of PAK3 and variant, produced by Molecular Operating Environment (MOE). Table S2. The summary of variants consistent with the inheritance model other than the PAK3 gene in this family from the trio-WES data.
Acrylonitrile butadiene styrene (ABS) is a common thermoplastic polymer used in engineering, elec... more Acrylonitrile butadiene styrene (ABS) is a common thermoplastic polymer used in engineering, electrical, textile, and automotive industries. ABS has good impact resistance and toughness but suffers from low flexural modulus and strength. Typically, ABS is mixed with other materials to create a composite with better properties. In this work, graphite was exfoliated into graphene nanoflakes (GNFs) within ABS in concentrations of 1, 5, and 20 wt.% GNFs followed by injection molding to fabricate GNF-ABS specimens for testing. The morphology and structure of the GNF-ABS composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy. And X-ray photoemission spectroscopy (XPS). The mechanical properties in flexure and electrical conductivity of the GNF-ABS composites were also determined. Results show that GNF particles created within ABS are multilayer graphene, and that increasing GNF concentration increases flexural modulus and streng...
X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylati... more X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. Only two patients from one family have been diagnosed with XMEN in China. In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. Five patients developed EBV viremia, and one patient developed non-Hodgkin’s lymphoma. Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammat...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disea... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disease 2019 (COVID-19) (1), which has become a pandemic since it was discovered in December 2019. Multiple variants of SARS-CoV-2 have subsequently emerged, with some variants of concern (such as Alpha, Beta, Delta, and Omicron) varying in their transmissibility and virulence (2-4). The Alpha variant is more transmissible than the wild-type of SARS-CoV-2 among children (5). A recent study found that children may play an important role in transmission of the Delta variant compared with previously circulating SARS-CoV-2 variants (6). A large cohort study found that individuals aged 10-19 years infected with the Omicron
Background Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency tha... more Background Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency that results in fructose metabolism disorder. The disease prevalence in the Chinese population is unknown, which impedes the formulation of HFI screening and diagnosis strategies. Materials and methods By searching a local cohort (Chinese Children’s Rare Disease Genetic Testing Clinical Collaboration System, CCGT) and public databases (ClinVar and Human Gene Mutation Database) and reviewing HFI-related literature, we manually curated ALDOB pathogenic or likely pathogenic (P/LP) variants according to ACMG guidelines. Allele frequency (AF) information from the local database CCGT and the public databases HuaBiao and gnomAD for ALDOB P/LP variants was used to estimate and the HFI prevalence in the Chinese population and other populations by the Bayesian framework. We collected the genotype and clinical characteristics of HFI patients from the CCGT database and published literature to study gen...
Background: The population of China represents about one sixth of the global population. It is im... more Background: The population of China represents about one sixth of the global population. It is important to create a national database with a large sample size and a sustained collaborative platform. The objective of this study was to introduce the Chinese Neonatal Network (CHNN), a new platform of national collaboration on quality improvement (QI) for short and long-term health outcomes of preterm infants. Methods: The background, participating centers, data collection, and objectives are described. Specific objectives are to: (I) Establish a standardized database of very preterm infants (VPI) with gestational age <32 weeks or birth weight (BW) <1,500 grams. (II) Assess, benchmark and monitor major outcomes of VPI and their risk determinants, as well as inter-institutional variations. (III) Implement the Evidencebased Practice for Improving Quality (EPIQ) program to improve quality of care and outcomes. (IV) Conduct collaborative research, including epidemiologic, clinical and health services studies and randomized controlled trials. This study is collaboratively funded by Canadian Institute of Health Research and the Children's Hospital of Fudan University. Results: The CHNN collaboration acts as a platform that member neonatal intensive care units (NICUs) can access for evidence on implementing practice improvements, learning activities, and research collaborations. There were 58 participating centers in 2018, which was expanded to be 79 in 2021. CHNN has published 2 annual reports to describe the outcomes and care practices of VPI in 2019 and 2020, and conducted an internal audit of data quality. Conclusions: The knowledge generated will be available nationally and worldwide with a definite national impact and a likely global impact.
The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2 infected children aged ... more The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2 infected children aged 6-14 years: a cohort study. Ann Transl Med 2022.
Background and purpose: Neonatal hyperbilirubinemia, also known as neonatal jaundice, is a common... more Background and purpose: Neonatal hyperbilirubinemia, also known as neonatal jaundice, is a common and frequent clinical condition with a complex etiology that can lead to brain damage in severe cases. Early recognition of hyperbilirubinemia and timely intervention and treatment can help reduce the occurrence of sequelae. This study was conducted to identify whether the gut microbiota composition can distinguish neonates with hyperbilirubinemia. Methods: Meconium samples were collected from 69 neonates with neonatal jaundice (NJ) and 69 age- and sex-matched neonates without clinically significant jaundice (healthy controls; HCs) for 16S rRNA gene sequencing and microbiome analysis. Results: Compared with HCs, the Chao 1 richness index of the gut microbiota was significantly decreased in the NJ group. The relative abundance of the probiotic gut bacterium, Lactobacillus, was significantly lower in the NJ group than in the HC group, whereas the abundances of potentially harmful gut bact...
ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, ... more ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples ...
Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but r... more Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and methods We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the h...
The rapid growth of digital images motivates individuals and organizations to upload their images... more The rapid growth of digital images motivates individuals and organizations to upload their images to the cloud server. To preserve the privacy, image owners would prefer to encrypt the images before uploading, but it would strongly limit the efficient usage of images. Plenty of existing schemes on privacy-preserving Content-Based Image Retrieval (PPCBIR) try to seek the balance between security and retrieval ability. However, compared to the advanced technologies in CBIR like Convolutional Neural Network (CNN), the existing PPCBIR schemes are far deficient in both accuracy and efficiency. With more cloud service providers, the collaborative secure image retrieval service provided by multiple cloud servers becomes possible. In this paper, inspired by additive secret sharing technology, we propose a series of additive secure computing protocols on numbers and matrices with better efficiency, and then show their application in PPCBIR. Specifically, we extract CNN features, decrease the dimension of features and build the index securely with the help of our protocols, which include the full process of image retrieval in plaintext domain. The experiments and security analysis demonstrate the efficiency, accuracy and security of our scheme.
Background: Serious games are potential alternatives for supplementing traditional simulation-bas... more Background: Serious games are potential alternatives for supplementing traditional simulation-based education for neonatal resuscitation training. However, evidence regarding the benefits of using serious games to improve long-term knowledge retention of neonatal resuscitation in undergraduate medical students is lacking.Objective: We designed a serious computer game “NEOGAMES” to train undergraduate medical students in neonatal resuscitation in a cost-friendly and accessible way and to examine whether serious game-based training improves long-term knowledge retention in medical students.Methods: “NEOGAMES” consists of a screen with images of an incubator, a baby, visual objects, anatomy, action cards, monitors, real-time feedback, and emotional components. Undergraduate medical students from Shanghai Medical College of Fudan University were invited to participate and were allocated to a game group or a control group. Participants in the game group played the game before the trainin...
BackgroundAn early and accurate evaluation of the risk of bronchopulmonary dysplasia (BPD) in pre... more BackgroundAn early and accurate evaluation of the risk of bronchopulmonary dysplasia (BPD) in premature infants is pivotal in implementing preventive strategies. The risk prediction models nowadays for BPD risk that included only clinical factors but without genetic factors are either too complex without practicability or provide poor-to-moderate discrimination. We aim to identify the role of genetic factors in BPD risk prediction early and accurately.MethodsExome sequencing was performed in a cohort of 245 premature infants (gestational age <32 weeks), with 131 BPD infants and 114 infants without BPD as controls. A gene burden test was performed to find risk genes with loss-of-function mutations or missense mutations over-represented in BPD and severe BPD (sBPD) patients, with risk gene sets (RGS) defined as BPD–RGS and sBPD–RGS, respectively. We then developed two predictive models for the risk of BPD and sBPD by integrating patient clinical and genetic features. The performanc...
Additional file 1 Table S1. Stability results of PAK3 and variant, produced by Molecular Operatin... more Additional file 1 Table S1. Stability results of PAK3 and variant, produced by Molecular Operating Environment (MOE). Table S2. The summary of variants consistent with the inheritance model other than the PAK3 gene in this family from the trio-WES data.
Acrylonitrile butadiene styrene (ABS) is a common thermoplastic polymer used in engineering, elec... more Acrylonitrile butadiene styrene (ABS) is a common thermoplastic polymer used in engineering, electrical, textile, and automotive industries. ABS has good impact resistance and toughness but suffers from low flexural modulus and strength. Typically, ABS is mixed with other materials to create a composite with better properties. In this work, graphite was exfoliated into graphene nanoflakes (GNFs) within ABS in concentrations of 1, 5, and 20 wt.% GNFs followed by injection molding to fabricate GNF-ABS specimens for testing. The morphology and structure of the GNF-ABS composites were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy. And X-ray photoemission spectroscopy (XPS). The mechanical properties in flexure and electrical conductivity of the GNF-ABS composites were also determined. Results show that GNF particles created within ABS are multilayer graphene, and that increasing GNF concentration increases flexural modulus and streng...
X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylati... more X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is a primary immunodeficiency caused by loss-of-function variants in the MAGT1 gene. Only two patients from one family have been diagnosed with XMEN in China. In this study, we retrospectively analyzed the genetic, clinical, and immunological characteristics of six pediatric patients in a Chinese cohort. Medical records were retrieved, immunological phenotypes were assessed, and infectious microbes in patients were detected. Six male patients (mean age, 6.3 years) from five unrelated families were genetically diagnosed as XMEN. Five patients presented with a major complaint of elevated liver enzymes, while one patient was referred for recurrent fever, cough and skin rash. Five patients developed EBV viremia, and one patient developed non-Hodgkin’s lymphoma. Histopathological findings from liver biopsy tissues showed variable hepatic steatosis, fibrosis, inflammat...
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