Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding...Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.展开更多
BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the im...BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the impact of bile spillage during primary surgery on the survival of patients with iGBC.METHODS Medical records of patients with iGBC diagnosed between 2000 and 2019 in 27 Dutch secondary centers and 5 tertiary centers were retrospectively reviewed.Patient medical records were assessed.Predictors for overall survival(OS)were determined using multivariable Cox regression.RESULTS Of the 346 included patients with iGBC,138(39.9%)had bile spillage,which was associated with higher American Society of Anesthesiologists classification(P=0.020),cholecystitis(P<0.001),higher tumor stage(P=0.005),and non-radical resection(P<0.001).Bile spillage was associated with poor OS[hazard ratio=1.97,95%confidence interval(CI):1.48-2.63,P<0.001]with a median OS of 12 months(95%CI:7-18 months)vs 34 months(95%CI:14-55 months,P<0.001).In multivariable analysis,spillage was not an independent prognostic factor for survival(hazard ratio=1.21,95%CI:0.84-1.74,P=0.313).CONCLUSION Although bile spillage correlates with prognostic factors,it lacks independent prognostic significance for survival.Patients with an indication for additional treatment should be promptly referred to a specialized hepatopancreatobiliary center,irrespective of whether bile spillage has occurred.展开更多
Organic fertilizers generally come from agricultural co-products. Their valuation is therefore a major issue for sustainable development. The main objective of this study aims to develop an organic fertilizer derived ...Organic fertilizers generally come from agricultural co-products. Their valuation is therefore a major issue for sustainable development. The main objective of this study aims to develop an organic fertilizer derived from moringa leaves and cocoa pod husks that can improve soil quality and plant growth. The experimental design consisted of completely randomized blocks in three repetitions. The experiment was carried out in five treatments: T0: no fertilization, T1: 100% cocoa pods, T2: 75% cocoa pods + 25% Moringa leaves;T3: 50% cocoa pods + 50% Moringa leaves;T4: 25% cocoa pods + 75% Moringa leaves;T5: 100% Moringa leaves. Three doses were applied: 1;2;4 kg/m2. The trial took place over three growing cycles. The results of the soil analysis compared to the control revealed a significant improvement in physicochemical parameters. Variation of pH from (6.1 to 7.2), calcium from (1.4 to 4.13), magnesium from (0.450 to 0.870), potassium from (0.096 to 0.365) cmol+/kg. Carbon and nitrogen were recorded (1.02% to 2.77%) and (0.12% to 2.56%) respectively. The CEC (cation exchange capacity) saw a clear improvement (4.2 to 9.03) cmol+/kg. Concerning the growth parameters, the control plants recorded an average height of (31.19 cm) while those that benefited from the treatments oscillated between (55.51 to 105.57 cm). In terms of production, the best yields are attributed to treatments T3 and T4 with (37.66 t/ha) and (51.176 t/ha) respectively. The T3 and T4 formulations could help improve the fertility of agricultural soils and the yield of market garden products such as eggplant.展开更多
Dill(Anethum graveolens),an annual species,was used to study the impact of metallic pollution potentially spreading fromthe nickel smelter dump in Dolna Streda(Slovakia)by monitoring 55 elements.Despite the proximity ...Dill(Anethum graveolens),an annual species,was used to study the impact of metallic pollution potentially spreading fromthe nickel smelter dump in Dolna Streda(Slovakia)by monitoring 55 elements.Despite the proximity of this dump(1 km),only soil Ni(54.8 mg/kg)or Pb(47.3 mg/kg),but not Cr,Mn,Fe or Co(main elements of the dump’s sludge)was elevated in given garden soil compared to two control sites.Mainly flowers and/or leaves contained significantly higher amounts of Ni,Cr,Pb,Cu,As,Sb,Sn,V,W,and some rare earth elements at the site close to the dump.Correlation between elements in organs and soil was significant mainly in stem or root but the bioaccumulation factor was typically low(<0.02)for most elements.A positive finding was that the 2022/2024 comparison revealed a decline in most elements in dill leaves,even at the dump site,which may reflect a decrease in the content of air PM particles.Soluble phenols were less accumulated in plants close to the nickel smelter dump,but flavonols showed the opposite trend,and free amino acids were positively correlated with many elements in the stem and root.An evaluation of commercial dill samples revealed variability(e.g.,up to 0.7 mg Cd/kg dry weight)but subsequent NCA and PCA analyses clearly separated the dump locality from other samples.However,significant differences in the content of Cd,Ni,Pb,As,and other elements encourage precise control of commercially available dill dry matter.展开更多
Tunnels are a crucial component of urban infrastructure,continuously exposed to various hazards,threats,and stressors.Events such as earthquakes,fires,and floods,along with aging and construction-related disturbances,...Tunnels are a crucial component of urban infrastructure,continuously exposed to various hazards,threats,and stressors.Events such as earthquakes,fires,and floods,along with aging and construction-related disturbances,pose significant challenges to tunnel resilience.Reliable fragility,restoration,and traffic reinstatement models are essential for assessing and quantifying resilience,as they allow infrastructure operators to prioritize maintenance and adapt to evolving threats in complex transportation systems.Although the vulnerability and fragility of tunnels have been widely researched over the last decade,studies focusing on tunnel restoration to quantify resilience remain scarce.This gap prevents operators from implementing proactive and reactive adaptation measures to ensure seamless tunnel functionality.To address this issue,this study presents a novel,fit-for-purpose,damage-level-dependent probabilistic approach for quantifying tunnel recovery.It introduces the first realistic,practice-led restoration models that enable resilience quantification in tunnels.To develop these models,a global expert survey was conducted to establish reinstatement(traffic capacity)and restoration(structural capacity)models tailored to tunnel resilience assessments.A detailed questionnaire was designed to gather expert input on required restoration tasks,their duration,sequencing,and cost.The survey focused primarily on damage induced by seismic events,incorporating idle times and traffic capacity gains over time.The results were then used to generate deterministic and probabilistic reinstatement and restoration models.The deterministic models are intended for practical applications,while the probabilistic models account for epistemic uncertainties and are presented in a reproducible format for further development across different hazards and applications.A case study is included to demonstrate the resilience assessment of a typical tunnel using the newly developed restoration models.The findings will help infrastructure operators and city planners to accurately assess tunnel resilience,enabling informed investment decisions.展开更多
High-energy,short-pulse laser-driven proton–boron(p–11B)fusion has attracted growing interest due to its aneutronic character and potential for clean energy generation.In this study,we report on two experimental cam...High-energy,short-pulse laser-driven proton–boron(p–11B)fusion has attracted growing interest due to its aneutronic character and potential for clean energy generation.In this study,we report on two experimental campaigns carried out at the LFEX laser facility using petawatt-class laser systems(energy~1.2–1.4 kJ,pulse duration 2.7 ps,peak intensity~(2–3)×10^(19)W/cm^(2)).The experiments explored the influence of complex target geometries–including spherical,cylindrical and wedge-shaped configurations–onα-particle yield.Our results demonstrate that spherical targets can enhanceα-particle production by up to two orders of magnitude compared to planar targets of identical composition and also lead to a noticeable shift of theα-particle energy spectrum toward higher values.Furthermore,we implemented a novel diagnostic technique for unambiguousα-particle detection using a CR-39 detector integrated into a Thomson parabola spectrometer.Particle-in-cell simulations performed with the Smilei code provide additional insight into the role of self-generated magnetic fields in modulating particle dynamics.These simulations highlight the critical interplay among target geometry,confinement effects and fusion efficiency.Overall,our findings underscore the potential of optimized target designs to significantly enhance fusion yield andα-particle output in p–11B fusion,with promising implications for the development of laser-drivenα-particle sources and advanced clean energy concepts.展开更多
This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical...This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.展开更多
Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter(LES)to relax,accompanied by the loss of peristalsis in the esophageal body.Although more prevalent in a...Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter(LES)to relax,accompanied by the loss of peristalsis in the esophageal body.Although more prevalent in adults,pediatric achalasia poses unique diagnostic challenges due to its atypical presentation.Peroral Endoscopic Myotomy(POEM)has emerged as a minimally invasive alternative to laparoscopic Heller myotomy for managing achalasia,particularly in children,but its efficacy and safety remain under-investigated.A comprehensive literature review was conducted to assess the role of POEM in pediatric achalasia,focusing on procedure efficacy,clinical outcomes,and safety.Key parameters included pre-and post-procedure Eckardt scores and adverse events.Comparison of outcomes with alternative interventions,such as laparoscopic myotomy and pneumatic dilation were also investigated.Currently,POEM achieves high clinical success in pediatric patients,with significant reduction in post-procedure Eckardt scores and LES pressures.Clinical success rates of up to 90%with durable symptom relief have been observed over follow-up exceeding one year.Common adverse events include mucosal injury,capnoperitoneum,and postoperative reflux.This comprehensive review reveals that POEM is as effective as laparoscopic myotomy but offers shorter hospital stay and reduced recovery time at the cost of a higher complication rate.POEM is an effective treatment for pediatric achalasia,providing durable symptom relief,comparable to traditional interventions.Future research should focus on the identification of pediatric patients that would benefit the most from POEM.展开更多
文摘Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.
文摘BACKGROUND Bile spillage occurs more frequently in patients with incidental gallbladder carcinoma(iGBC)and may be associated with poor survival due to presumed high risk of peritoneal seeding.AIM To investigate the impact of bile spillage during primary surgery on the survival of patients with iGBC.METHODS Medical records of patients with iGBC diagnosed between 2000 and 2019 in 27 Dutch secondary centers and 5 tertiary centers were retrospectively reviewed.Patient medical records were assessed.Predictors for overall survival(OS)were determined using multivariable Cox regression.RESULTS Of the 346 included patients with iGBC,138(39.9%)had bile spillage,which was associated with higher American Society of Anesthesiologists classification(P=0.020),cholecystitis(P<0.001),higher tumor stage(P=0.005),and non-radical resection(P<0.001).Bile spillage was associated with poor OS[hazard ratio=1.97,95%confidence interval(CI):1.48-2.63,P<0.001]with a median OS of 12 months(95%CI:7-18 months)vs 34 months(95%CI:14-55 months,P<0.001).In multivariable analysis,spillage was not an independent prognostic factor for survival(hazard ratio=1.21,95%CI:0.84-1.74,P=0.313).CONCLUSION Although bile spillage correlates with prognostic factors,it lacks independent prognostic significance for survival.Patients with an indication for additional treatment should be promptly referred to a specialized hepatopancreatobiliary center,irrespective of whether bile spillage has occurred.
文摘Organic fertilizers generally come from agricultural co-products. Their valuation is therefore a major issue for sustainable development. The main objective of this study aims to develop an organic fertilizer derived from moringa leaves and cocoa pod husks that can improve soil quality and plant growth. The experimental design consisted of completely randomized blocks in three repetitions. The experiment was carried out in five treatments: T0: no fertilization, T1: 100% cocoa pods, T2: 75% cocoa pods + 25% Moringa leaves;T3: 50% cocoa pods + 50% Moringa leaves;T4: 25% cocoa pods + 75% Moringa leaves;T5: 100% Moringa leaves. Three doses were applied: 1;2;4 kg/m2. The trial took place over three growing cycles. The results of the soil analysis compared to the control revealed a significant improvement in physicochemical parameters. Variation of pH from (6.1 to 7.2), calcium from (1.4 to 4.13), magnesium from (0.450 to 0.870), potassium from (0.096 to 0.365) cmol+/kg. Carbon and nitrogen were recorded (1.02% to 2.77%) and (0.12% to 2.56%) respectively. The CEC (cation exchange capacity) saw a clear improvement (4.2 to 9.03) cmol+/kg. Concerning the growth parameters, the control plants recorded an average height of (31.19 cm) while those that benefited from the treatments oscillated between (55.51 to 105.57 cm). In terms of production, the best yields are attributed to treatments T3 and T4 with (37.66 t/ha) and (51.176 t/ha) respectively. The T3 and T4 formulations could help improve the fertility of agricultural soils and the yield of market garden products such as eggplant.
基金supported by the Slovak grant agency VEGA(project no 1/0003/21)analyses of foreign co-authors also by internal sources(grant no.SGS_2025_001)of their workplaces.
文摘Dill(Anethum graveolens),an annual species,was used to study the impact of metallic pollution potentially spreading fromthe nickel smelter dump in Dolna Streda(Slovakia)by monitoring 55 elements.Despite the proximity of this dump(1 km),only soil Ni(54.8 mg/kg)or Pb(47.3 mg/kg),but not Cr,Mn,Fe or Co(main elements of the dump’s sludge)was elevated in given garden soil compared to two control sites.Mainly flowers and/or leaves contained significantly higher amounts of Ni,Cr,Pb,Cu,As,Sb,Sn,V,W,and some rare earth elements at the site close to the dump.Correlation between elements in organs and soil was significant mainly in stem or root but the bioaccumulation factor was typically low(<0.02)for most elements.A positive finding was that the 2022/2024 comparison revealed a decline in most elements in dill leaves,even at the dump site,which may reflect a decrease in the content of air PM particles.Soluble phenols were less accumulated in plants close to the nickel smelter dump,but flavonols showed the opposite trend,and free amino acids were positively correlated with many elements in the stem and root.An evaluation of commercial dill samples revealed variability(e.g.,up to 0.7 mg Cd/kg dry weight)but subsequent NCA and PCA analyses clearly separated the dump locality from other samples.However,significant differences in the content of Cd,Ni,Pb,As,and other elements encourage precise control of commercially available dill dry matter.
基金support from the National Natural Science Foundation of China(52478410,W2411044,and 52408435)the National Key Research and Development Program of China(2022YFC3800905)+3 种基金Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)the Fundamental Research Funds for the Central UniversitiesDr.Stergios-Aristoteles Mitoulis and Dr.Sotirios Argyroudis acknowledge funding from the UK Research and Innovation(UKRI)under the UK government’s Horizon Europe funding guarantee(EP/Y003586/1,EP/X037665/1)This is the funding guarantee for the European Union's HORIZON-MSCA-2021-SE-01(101086413)“ReCharged-Climate-Aware Resilience for Sustainable Critical and Interdependent Infrastructure Systems Enhanced by Emerging Digital Technologies.”。
文摘Tunnels are a crucial component of urban infrastructure,continuously exposed to various hazards,threats,and stressors.Events such as earthquakes,fires,and floods,along with aging and construction-related disturbances,pose significant challenges to tunnel resilience.Reliable fragility,restoration,and traffic reinstatement models are essential for assessing and quantifying resilience,as they allow infrastructure operators to prioritize maintenance and adapt to evolving threats in complex transportation systems.Although the vulnerability and fragility of tunnels have been widely researched over the last decade,studies focusing on tunnel restoration to quantify resilience remain scarce.This gap prevents operators from implementing proactive and reactive adaptation measures to ensure seamless tunnel functionality.To address this issue,this study presents a novel,fit-for-purpose,damage-level-dependent probabilistic approach for quantifying tunnel recovery.It introduces the first realistic,practice-led restoration models that enable resilience quantification in tunnels.To develop these models,a global expert survey was conducted to establish reinstatement(traffic capacity)and restoration(structural capacity)models tailored to tunnel resilience assessments.A detailed questionnaire was designed to gather expert input on required restoration tasks,their duration,sequencing,and cost.The survey focused primarily on damage induced by seismic events,incorporating idle times and traffic capacity gains over time.The results were then used to generate deterministic and probabilistic reinstatement and restoration models.The deterministic models are intended for practical applications,while the probabilistic models account for epistemic uncertainties and are presented in a reproducible format for further development across different hazards and applications.A case study is included to demonstrate the resilience assessment of a typical tunnel using the newly developed restoration models.The findings will help infrastructure operators and city planners to accurately assess tunnel resilience,enabling informed investment decisions.
基金the framework of the EUROfusion Consortium,funded by the European Union via the Euratom Research and Training Programme(Grant Agreement No.101052200–EUROfusion)Co-authors from Deakin University gratefully thank the Australian Research Council for financial support under the Linkage[LP200301537]+2 种基金supported by COST(European Cooperation in Science and Technology)through Action CA21128 PROBONO(PROton BOron Nuclear Fusion:from energy production to medical applicati Ons)the support of the Czech Science Foundation through Grant No.GACR24-11398Sthe support of HB11 Energy Holdings Pty,Australia,through its collaborative science program。
文摘High-energy,short-pulse laser-driven proton–boron(p–11B)fusion has attracted growing interest due to its aneutronic character and potential for clean energy generation.In this study,we report on two experimental campaigns carried out at the LFEX laser facility using petawatt-class laser systems(energy~1.2–1.4 kJ,pulse duration 2.7 ps,peak intensity~(2–3)×10^(19)W/cm^(2)).The experiments explored the influence of complex target geometries–including spherical,cylindrical and wedge-shaped configurations–onα-particle yield.Our results demonstrate that spherical targets can enhanceα-particle production by up to two orders of magnitude compared to planar targets of identical composition and also lead to a noticeable shift of theα-particle energy spectrum toward higher values.Furthermore,we implemented a novel diagnostic technique for unambiguousα-particle detection using a CR-39 detector integrated into a Thomson parabola spectrometer.Particle-in-cell simulations performed with the Smilei code provide additional insight into the role of self-generated magnetic fields in modulating particle dynamics.These simulations highlight the critical interplay among target geometry,confinement effects and fusion efficiency.Overall,our findings underscore the potential of optimized target designs to significantly enhance fusion yield andα-particle output in p–11B fusion,with promising implications for the development of laser-drivenα-particle sources and advanced clean energy concepts.
文摘This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.
文摘Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter(LES)to relax,accompanied by the loss of peristalsis in the esophageal body.Although more prevalent in adults,pediatric achalasia poses unique diagnostic challenges due to its atypical presentation.Peroral Endoscopic Myotomy(POEM)has emerged as a minimally invasive alternative to laparoscopic Heller myotomy for managing achalasia,particularly in children,but its efficacy and safety remain under-investigated.A comprehensive literature review was conducted to assess the role of POEM in pediatric achalasia,focusing on procedure efficacy,clinical outcomes,and safety.Key parameters included pre-and post-procedure Eckardt scores and adverse events.Comparison of outcomes with alternative interventions,such as laparoscopic myotomy and pneumatic dilation were also investigated.Currently,POEM achieves high clinical success in pediatric patients,with significant reduction in post-procedure Eckardt scores and LES pressures.Clinical success rates of up to 90%with durable symptom relief have been observed over follow-up exceeding one year.Common adverse events include mucosal injury,capnoperitoneum,and postoperative reflux.This comprehensive review reveals that POEM is as effective as laparoscopic myotomy but offers shorter hospital stay and reduced recovery time at the cost of a higher complication rate.POEM is an effective treatment for pediatric achalasia,providing durable symptom relief,comparable to traditional interventions.Future research should focus on the identification of pediatric patients that would benefit the most from POEM.
