Walking is an active and sustainable mode of transportation with numerous health and environmental benefits.However,the growing concern over the increasing number of hit-and-run crashes involving pedestrians poses a s...Walking is an active and sustainable mode of transportation with numerous health and environmental benefits.However,the growing concern over the increasing number of hit-and-run crashes involving pedestrians poses a significant threat to public health.This research investigates the various factors contributing to the severity of injuries sustained by pedestrians in hit-and-run crashes.By analysing data from hit-and-run incidents involving pedestrians in Louisiana,USA between 2017 and 2021,this study examined the complex relationships between contributing factors,pedestrian actions,driver and pedestrian characteristics and injury severity.Bayesian network analysis was employed to unravel the intricate web of variables.Findings showed that the highest probability of pedestrian injury occurred when the driver’s condition was known and normal,without the involvement of alcohol or drugs.Counterfactual scenarios were also examined to explore the potential impact of changing certain variables on crash outcomes.The results highlighted the importance of driver age,driver condition,pedestrian actions and the presence of alcohol or drugs in determining injury severity.This study’s insights offer valuable policy implications for enhancing pedestrian safety and underscore the need for targeted interventions to promote safer and more sustainable transportation systems.展开更多
Gastric cancer is the fifth most common malignancy and third leading cancerrelated cause of death worldwide.Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3%of the world’...Gastric cancer is the fifth most common malignancy and third leading cancerrelated cause of death worldwide.Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3%of the world’s population and represents the main risk factor for the onset of gastric neoplasms.CagA is the most important virulence factor in H.pylori,and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions.Upon translocation and tyrosine phosphorylation,CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways,thereby disrupting cell proliferation,differentiation and apoptosis.All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes.In this sense,once gastric cancer sets in,its perpetuation is independent of the presence of the oncoprotein,characterizing a“hit-and-run”carcinogenic mechanism.Therefore,this review aims to describe H.pylori-and CagA-related oncogenic mechanisms,to update readers and discuss the novelties and perspectives in this field.展开更多
Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer.The cagA gene product,CagA,is delivered into gastric epithelial cells via the bacterial type IV secretio...Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer.The cagA gene product,CagA,is delivered into gastric epithelial cells via the bacterial type IV secretion system.Delivered CagA then undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala(EPIYA)motifs in its C-terminal region and acts as an oncogenic scaffold protein that physically interacts with multiple host signaling proteins in both tyrosine phosphorylation-dependent and-independent manners.Analysis of CagA using in vitro cultured gastric epithelial cells has indicated that the nonphysiological scaffolding actions of CagA cell-autonomously promote the malignant transformation of the cells by endowing the cells with multiple phenotypic cancer hallmarks:sustained proliferation,evasion of growth suppressors,invasiveness,resistance to cell death,and genomic instability.Transgenic expression of CagA in mice leads to in vivo oncogenic action of CagA without any overt inflammation.The in vivo oncogenic activity of CagA is further potentiated in the presence of chronic inflammation.Since Helicobacter pylori infection triggers a proinflammatory response in host cells,a feedforward stimulation loop that augments the oncogenic actions of CagA and inflammation is created in CagA-injected gastric mucosa.Given that Helicobacter pylori is no longer colonized in established gastric cancer lesions,the multistep nature of gastric cancer development should include a“hit-and-run”process of CagA action.Thus,acquisition of genetic and epigenetic alterations that compensate for CagA-directed cancer hallmarks may be required for completion of the“hit-and-run”process of gastric carcinogenesis.展开更多
文摘Walking is an active and sustainable mode of transportation with numerous health and environmental benefits.However,the growing concern over the increasing number of hit-and-run crashes involving pedestrians poses a significant threat to public health.This research investigates the various factors contributing to the severity of injuries sustained by pedestrians in hit-and-run crashes.By analysing data from hit-and-run incidents involving pedestrians in Louisiana,USA between 2017 and 2021,this study examined the complex relationships between contributing factors,pedestrian actions,driver and pedestrian characteristics and injury severity.Bayesian network analysis was employed to unravel the intricate web of variables.Findings showed that the highest probability of pedestrian injury occurred when the driver’s condition was known and normal,without the involvement of alcohol or drugs.Counterfactual scenarios were also examined to explore the potential impact of changing certain variables on crash outcomes.The results highlighted the importance of driver age,driver condition,pedestrian actions and the presence of alcohol or drugs in determining injury severity.This study’s insights offer valuable policy implications for enhancing pedestrian safety and underscore the need for targeted interventions to promote safer and more sustainable transportation systems.
基金Supported by National Council for Scientific and Technological Development,CNPq Brazil.
文摘Gastric cancer is the fifth most common malignancy and third leading cancerrelated cause of death worldwide.Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3%of the world’s population and represents the main risk factor for the onset of gastric neoplasms.CagA is the most important virulence factor in H.pylori,and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions.Upon translocation and tyrosine phosphorylation,CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways,thereby disrupting cell proliferation,differentiation and apoptosis.All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes.In this sense,once gastric cancer sets in,its perpetuation is independent of the presence of the oncoprotein,characterizing a“hit-and-run”carcinogenic mechanism.Therefore,this review aims to describe H.pylori-and CagA-related oncogenic mechanisms,to update readers and discuss the novelties and perspectives in this field.
基金Our studies presented in this review article were supported by Grants-in-Aid for Scientific Research“S”(#16H06373 to M.H.),“A”(#22240085 and#25250016 to M.H.)and“C”(#19K05945 to A.T.-K.)Grants-in-Aid for Innovative Areas(#3205,#22114001,and#22114002 to M.H.)+4 种基金Grants-in-Aid for Japan Society for the Promotion of Science(JSPS)Fellows(#07J03878 to A.T.-K.and#19J12668 to C.T.K.)Grants-in-Aid for Young Scientists“B”(#24700965 and#15K18399 to A.T.-K.)the Graduate Program for Leaders in Life Innovation(GPLLI,to C.T.K.)from the Ministry of Education,Culture,Sports,Science and Technology(MEXT)of Japan,by CREST(#120200000396 to M.H.)Japan Science and Technology Agency,by the Uehara Memorial Foundation(#137 in 2016 to A.T.-K.)by the Max-Planck Society,Germany。
文摘Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer.The cagA gene product,CagA,is delivered into gastric epithelial cells via the bacterial type IV secretion system.Delivered CagA then undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala(EPIYA)motifs in its C-terminal region and acts as an oncogenic scaffold protein that physically interacts with multiple host signaling proteins in both tyrosine phosphorylation-dependent and-independent manners.Analysis of CagA using in vitro cultured gastric epithelial cells has indicated that the nonphysiological scaffolding actions of CagA cell-autonomously promote the malignant transformation of the cells by endowing the cells with multiple phenotypic cancer hallmarks:sustained proliferation,evasion of growth suppressors,invasiveness,resistance to cell death,and genomic instability.Transgenic expression of CagA in mice leads to in vivo oncogenic action of CagA without any overt inflammation.The in vivo oncogenic activity of CagA is further potentiated in the presence of chronic inflammation.Since Helicobacter pylori infection triggers a proinflammatory response in host cells,a feedforward stimulation loop that augments the oncogenic actions of CagA and inflammation is created in CagA-injected gastric mucosa.Given that Helicobacter pylori is no longer colonized in established gastric cancer lesions,the multistep nature of gastric cancer development should include a“hit-and-run”process of CagA action.Thus,acquisition of genetic and epigenetic alterations that compensate for CagA-directed cancer hallmarks may be required for completion of the“hit-and-run”process of gastric carcinogenesis.
