The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycle...The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.展开更多
The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high ...The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study, however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific Col1a1–2.3-Cre to ablate both Numb and its homologue Numbl. The trabecular bone mass decreased dramatically while the cortical bone mass was unaffected. Here, the Notch signal was not activated,while the tensin homologue deleted on human chromosome 10(PTEN), which dephosphorylates phosphatidylinositide 3-kinases, was elevated, attenuating protein kinase B(Akt). The ubiquitination assay revealed that NUMB may physiologically promote PTEN ubiquitination in the presence of neural precursor cell-expressed developmentally downregulated protein 4–1. In addition, the deficiency of Numb/Numbl also activated the Hedgehog pathway through GLI1. This process was found to improve the ratio of the receptor activator of nuclear factor-k B ligand to osteoprotegerin, which enhanced the differentiation of osteoclasts and bone resorption. In conclusion, this study provides an insight into new functons of NUMB and NUMBL on bone homeostasis.展开更多
BACKGROUND Staphylococcus aureus bacteraemia(SAB)is among the leading causes of bacteraemia and infectious endocarditis.The frequency of infectious endocarditis(IE)among SAB patients ranges from 5%to 10%-12%.In adults...BACKGROUND Staphylococcus aureus bacteraemia(SAB)is among the leading causes of bacteraemia and infectious endocarditis.The frequency of infectious endocarditis(IE)among SAB patients ranges from 5%to 10%-12%.In adults,the characteristics of epidermolytic hyperkeratosis(EHK)include hyperkeratosis,erosions,and blisters.Patients with inflammatory skin diseases and some diseases involving the epidermis tend to exhibit a disturbed skin barrier and tend to have poor cellmediated immunity.CASE SUMMARY We describe a case of SAB and infective endocarditis in a 43-year-old male who presented with fever of unknown origin and skin diseases.After genetic tests,the skin disease was diagnosed as EHK.CONCLUSION A breached skin barrier secondary to EHK,coupled with inadequate sanitation,likely provided the opportunity for bacterial seeding,leading to IE and deepseated abscess or organ abscess.EHK may be associated with skin infection and multiple risk factors for extracutaneous infections.Patients with EHK should be treated early to minimize their consequences.If patients with EHK present with prolonged fever of unknown origin,IE and organ abscesses should be ruled out,including metastatic spreads.展开更多
Objective Hirschsprung disease(HSCR)is one of the common neurocristopathies in children,which is associated with at least 20 genes and involves a complex regulatory mechanism.Transcriptional regulatory network(TRN)has...Objective Hirschsprung disease(HSCR)is one of the common neurocristopathies in children,which is associated with at least 20 genes and involves a complex regulatory mechanism.Transcriptional regulatory network(TRN)has been commonly reported in regulating gene expression and enteric nervous system development but remains to be investigated in HSCR.This study aimed to identify the potential TRN implicated in the pathogenesis and diagnosis of HSCR.Methods Based on three microarray datasets from the Gene Expression Omnibus database,the multiMiR package was used to investigate the microRNA(miRNA)-target interactions,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Then,we collected transcription factors(TFs)from the TransmiR database to construct the TF-miRNA-mRNA regulatory network and used cytoHubba to identify the key modules.Finally,the receiver operating characteristic(ROC)curve was determined and the integrated diagnostic models were established based on machine learning by the support vector machine method.Results We identified 58 hub differentially expressed microRNAs(DEMis)and 16 differentially expressed mRNAs(DEMs).The robust target genes of DEMis and DEMs mainly enriched in several GO/KEGG terms,including neurogenesis,cell-substrate adhesion,PI3K-Akt,Ras/mitogen-activated protein kinase and Rho/ROCK signaling.Moreover,2 TFs(TP53and TWIST1),4 miRNAs(has-miR-107,has-miR-10b-5p,has-miR-659-3p,and has-miR-371a-5p),and 4 mRNAs(PIM3,CHUK,F2RL1,and CA1)were identified to construct the TF-miRNA-mRNA regulatory network.ROC analysis revealed a strong diagnostic value of the key TRN regulons(all area under the curve values were more than 0.8).Conclusion This study suggests a potential role of the TF-miRNA-mRNA network that can help enrich the connotation of HSCR pathogenesis and diagnosis and provide new horizons for treatment.展开更多
Most existing researches on relation extraction focus on binary flat relations like Bomln relation between a Person and a Location.But a large portion of objective facts de-scribed in natural language are complex,espe...Most existing researches on relation extraction focus on binary flat relations like Bomln relation between a Person and a Location.But a large portion of objective facts de-scribed in natural language are complex,especially in professional documents in fields such as finance and biomedicine that require precise expressions.For example,“the GDP of the United States in 2018 grew 2.9%compared with 2017”describes a growth rate relation between two other relations about the economic index,which is beyond the expressive power of binary flat relations.Thus,we propose the nested relation extraction problem and formulate it as a directed acyclic graph(DAG)structure extraction problem.Then,we propose a solution using the Iterative Neural Network which extracts relations layer by layer.The proposed solution achieves 78.98 and 97.89 FI scores on two nested relation extraction tasks,namely semantic cause-and-efFect relation extraction and formula extraction.Furthermore,we observe that nested relations are usually expressed in long sentences where entities are mentioned repetitively,which makes the annotation difficult and error-prone.Hence,we extend our model to incorporate a mention-insensitive mode that only requires annotations of relations on entity concepts(instead of exact mentions)while preserving most of its performance.Our mention-insensitive model performs better than the mention sensitive model when the random level in mention selection is higher than 0.3.展开更多
Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a mo...Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a more generalized disorder of the connective tissue involving a number of organs.SSc is characterized by the thickening of dermal collagen bundles,fibrosis,and vascular abnormalities in the visceral organs.[1]Despite the differences in their morphologic features and clinical presentation,these two diseases do share some characteristics including endothelial cell dysfunction,T helper 2(Th2)cell dominance during immune activation and excess fibrosis of the skin with similar pathologic findings,leading to the hypothesis that SSc and LSc share an underlying mechanism of pathogensis.Currently,multiple lines of evidence suggest that genetic factors may contribute to SSc susceptibility.展开更多
Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population.Due to irreversible airflow obstruction and progressive...Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population.Due to irreversible airflow obstruction and progressive lung function decline,COPD is characterized by high mortality and disability rates,which imposes a huge economic burden on society.In recent years,the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed.Identifying and intervening in individuals with early COPD,some of whom have few or no symptoms,might halt or reverse the progressive decline in lung function,improve the quality of life,and better their prognosis.However,understanding of early COPD is not yet well established,and there are no unified and feasible diagnostic criteria,which complicates clinical research.In this article,we review evolution of the definition of early COPD over the past 20 years,describe the changes in awareness of this concept,and propose future research directions.展开更多
基金The authors are grateful for support from the National Social Science Fund of China(21AJL015).
文摘The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.
基金provided by Funding of State Key Laboratory of Oral Disease (Sichuan University, SKLOD201702)the National Science Foundation for Excellent Young Scholars of China (81322013)+1 种基金the Innovation Team of Sichuan Province (2015TD0011)Start-up Funding from State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, China (To Peng Liu)
文摘The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study, however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific Col1a1–2.3-Cre to ablate both Numb and its homologue Numbl. The trabecular bone mass decreased dramatically while the cortical bone mass was unaffected. Here, the Notch signal was not activated,while the tensin homologue deleted on human chromosome 10(PTEN), which dephosphorylates phosphatidylinositide 3-kinases, was elevated, attenuating protein kinase B(Akt). The ubiquitination assay revealed that NUMB may physiologically promote PTEN ubiquitination in the presence of neural precursor cell-expressed developmentally downregulated protein 4–1. In addition, the deficiency of Numb/Numbl also activated the Hedgehog pathway through GLI1. This process was found to improve the ratio of the receptor activator of nuclear factor-k B ligand to osteoprotegerin, which enhanced the differentiation of osteoclasts and bone resorption. In conclusion, this study provides an insight into new functons of NUMB and NUMBL on bone homeostasis.
文摘BACKGROUND Staphylococcus aureus bacteraemia(SAB)is among the leading causes of bacteraemia and infectious endocarditis.The frequency of infectious endocarditis(IE)among SAB patients ranges from 5%to 10%-12%.In adults,the characteristics of epidermolytic hyperkeratosis(EHK)include hyperkeratosis,erosions,and blisters.Patients with inflammatory skin diseases and some diseases involving the epidermis tend to exhibit a disturbed skin barrier and tend to have poor cellmediated immunity.CASE SUMMARY We describe a case of SAB and infective endocarditis in a 43-year-old male who presented with fever of unknown origin and skin diseases.After genetic tests,the skin disease was diagnosed as EHK.CONCLUSION A breached skin barrier secondary to EHK,coupled with inadequate sanitation,likely provided the opportunity for bacterial seeding,leading to IE and deepseated abscess or organ abscess.EHK may be associated with skin infection and multiple risk factors for extracutaneous infections.Patients with EHK should be treated early to minimize their consequences.If patients with EHK present with prolonged fever of unknown origin,IE and organ abscesses should be ruled out,including metastatic spreads.
基金supported by grants from the National Natural Science Foundation of China(numbers 82071692,81770513,and 82170531)Xi’an Jiaotong University(number YXJLRH2022053)the General Project of Shaanxi Science and Technology Department(number 2022SF-133/033).
文摘Objective Hirschsprung disease(HSCR)is one of the common neurocristopathies in children,which is associated with at least 20 genes and involves a complex regulatory mechanism.Transcriptional regulatory network(TRN)has been commonly reported in regulating gene expression and enteric nervous system development but remains to be investigated in HSCR.This study aimed to identify the potential TRN implicated in the pathogenesis and diagnosis of HSCR.Methods Based on three microarray datasets from the Gene Expression Omnibus database,the multiMiR package was used to investigate the microRNA(miRNA)-target interactions,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Then,we collected transcription factors(TFs)from the TransmiR database to construct the TF-miRNA-mRNA regulatory network and used cytoHubba to identify the key modules.Finally,the receiver operating characteristic(ROC)curve was determined and the integrated diagnostic models were established based on machine learning by the support vector machine method.Results We identified 58 hub differentially expressed microRNAs(DEMis)and 16 differentially expressed mRNAs(DEMs).The robust target genes of DEMis and DEMs mainly enriched in several GO/KEGG terms,including neurogenesis,cell-substrate adhesion,PI3K-Akt,Ras/mitogen-activated protein kinase and Rho/ROCK signaling.Moreover,2 TFs(TP53and TWIST1),4 miRNAs(has-miR-107,has-miR-10b-5p,has-miR-659-3p,and has-miR-371a-5p),and 4 mRNAs(PIM3,CHUK,F2RL1,and CA1)were identified to construct the TF-miRNA-mRNA regulatory network.ROC analysis revealed a strong diagnostic value of the key TRN regulons(all area under the curve values were more than 0.8).Conclusion This study suggests a potential role of the TF-miRNA-mRNA network that can help enrich the connotation of HSCR pathogenesis and diagnosis and provide new horizons for treatment.
基金supported by the National Key Research and Development Program of China(2017YFB1002104)the National Natural Science Foundation of China(Grant No.U1811461)the Innovation Program of Institute of Computing Technology,CAS。
文摘Most existing researches on relation extraction focus on binary flat relations like Bomln relation between a Person and a Location.But a large portion of objective facts de-scribed in natural language are complex,especially in professional documents in fields such as finance and biomedicine that require precise expressions.For example,“the GDP of the United States in 2018 grew 2.9%compared with 2017”describes a growth rate relation between two other relations about the economic index,which is beyond the expressive power of binary flat relations.Thus,we propose the nested relation extraction problem and formulate it as a directed acyclic graph(DAG)structure extraction problem.Then,we propose a solution using the Iterative Neural Network which extracts relations layer by layer.The proposed solution achieves 78.98 and 97.89 FI scores on two nested relation extraction tasks,namely semantic cause-and-efFect relation extraction and formula extraction.Furthermore,we observe that nested relations are usually expressed in long sentences where entities are mentioned repetitively,which makes the annotation difficult and error-prone.Hence,we extend our model to incorporate a mention-insensitive mode that only requires annotations of relations on entity concepts(instead of exact mentions)while preserving most of its performance.Our mention-insensitive model performs better than the mention sensitive model when the random level in mention selection is higher than 0.3.
文摘Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma(LSc)and systemic sclerosis(SSc).LSc is characterized by sclerotic and pigmented skin lesions,while SSc is a more generalized disorder of the connective tissue involving a number of organs.SSc is characterized by the thickening of dermal collagen bundles,fibrosis,and vascular abnormalities in the visceral organs.[1]Despite the differences in their morphologic features and clinical presentation,these two diseases do share some characteristics including endothelial cell dysfunction,T helper 2(Th2)cell dominance during immune activation and excess fibrosis of the skin with similar pathologic findings,leading to the hypothesis that SSc and LSc share an underlying mechanism of pathogensis.Currently,multiple lines of evidence suggest that genetic factors may contribute to SSc susceptibility.
基金This study was supported by grants from the National Natural Science Foundation of China(Nos.82090014 and 81970037)Capital Health Development Research Project(No.2020-2Z-40917)+1 种基金Dr.Curtis is supported by R01 HL144718,R01 HL144849,and U01 HL137880 from the National Heart,Lung,and Blood Institute,National Institutes of Healthby Merit Review awards I01 CX002377 and I01 CX001562 from the Department of Veterans Affairs.
文摘Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population.Due to irreversible airflow obstruction and progressive lung function decline,COPD is characterized by high mortality and disability rates,which imposes a huge economic burden on society.In recent years,the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed.Identifying and intervening in individuals with early COPD,some of whom have few or no symptoms,might halt or reverse the progressive decline in lung function,improve the quality of life,and better their prognosis.However,understanding of early COPD is not yet well established,and there are no unified and feasible diagnostic criteria,which complicates clinical research.In this article,we review evolution of the definition of early COPD over the past 20 years,describe the changes in awareness of this concept,and propose future research directions.
