In the intricate landscape of healthcare,vicarious liability looms large,shaping the responsibilities and actions of healthcare practitioners and administrators alike.Illustrated by a poignant scenario of a medication...In the intricate landscape of healthcare,vicarious liability looms large,shaping the responsibilities and actions of healthcare practitioners and administrators alike.Illustrated by a poignant scenario of a medication error,this article navigates the complexities of vicarious liability in healthcare.It explains the legal basis and ramifications of this theory,emphasizing its importance in fostering responsibility,protecting patient welfare,and easing access to justice.The paper explores the practical effects of vicarious responsibility on day-to-day operations,leadership practices,and decision-making processes via the eyes of senior consultants,junior doctors,and hospital administrators.Through comprehensive insights and real-world examples,it underscores the imperative of fostering a culture of accountability,communication,and quality care to navigate the intricate web of liabilities inherent in modern healthcare.展开更多
BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the ...BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.展开更多
BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acu...BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Customer segmentation according to load-shape profiles using smart meter data is an increasingly important application to vital the planning and operation of energy systems and to enable citizens’participation in the...Customer segmentation according to load-shape profiles using smart meter data is an increasingly important application to vital the planning and operation of energy systems and to enable citizens’participation in the energy transition.This study proposes an innovative multi-step clustering procedure to segment customers based on load-shape patterns at the daily and intra-daily time horizons.Smart meter data is split between daily and hourly normalized time series to assess monthly,weekly,daily,and hourly seasonality patterns separately.The dimensionality reduction implicit in the splitting allows a direct approach to clustering raw daily energy time series data.The intraday clustering procedure sequentially identifies representative hourly day-unit profiles for each customer and the entire population.For the first time,a step function approach is applied to reduce time series dimensionality.Customer attributes embedded in surveys are employed to build external clustering validation metrics using Cramer’s V correlation factors and to identify statistically significant determinants of load-shape in energy usage.In addition,a time series features engineering approach is used to extract 16 relevant demand flexibility indicators that characterize customers and corresponding clusters along four different axes:available Energy(E),Temporal patterns(T),Consistency(C),and Variability(V).The methodology is implemented on a real-world electricity consumption dataset of 325 Small and Medium-sized Enterprise(SME)customers,identifying 4 daily and 6 hourly easy-to-interpret,well-defined clusters.The application of the methodology includes selecting key parameters via grid search and a thorough comparison of clustering distances and methods to ensure the robustness of the results.Further research can test the scalability of the methodology to larger datasets from various customer segments(households and large commercial)and locations with different weather and socioeconomic conditions.展开更多
文摘In the intricate landscape of healthcare,vicarious liability looms large,shaping the responsibilities and actions of healthcare practitioners and administrators alike.Illustrated by a poignant scenario of a medication error,this article navigates the complexities of vicarious liability in healthcare.It explains the legal basis and ramifications of this theory,emphasizing its importance in fostering responsibility,protecting patient welfare,and easing access to justice.The paper explores the practical effects of vicarious responsibility on day-to-day operations,leadership practices,and decision-making processes via the eyes of senior consultants,junior doctors,and hospital administrators.Through comprehensive insights and real-world examples,it underscores the imperative of fostering a culture of accountability,communication,and quality care to navigate the intricate web of liabilities inherent in modern healthcare.
基金Supported by General Project of Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0604Chongqing Doctoral"Through Train"Research Program,China,No.CSTB2022BSXM-JCX0045.
文摘BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.
文摘BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the Spanish Ministry of Science and Innovation under Projects PID2022-137680OB-C32 and PID2022-139187OB-I00.
文摘Customer segmentation according to load-shape profiles using smart meter data is an increasingly important application to vital the planning and operation of energy systems and to enable citizens’participation in the energy transition.This study proposes an innovative multi-step clustering procedure to segment customers based on load-shape patterns at the daily and intra-daily time horizons.Smart meter data is split between daily and hourly normalized time series to assess monthly,weekly,daily,and hourly seasonality patterns separately.The dimensionality reduction implicit in the splitting allows a direct approach to clustering raw daily energy time series data.The intraday clustering procedure sequentially identifies representative hourly day-unit profiles for each customer and the entire population.For the first time,a step function approach is applied to reduce time series dimensionality.Customer attributes embedded in surveys are employed to build external clustering validation metrics using Cramer’s V correlation factors and to identify statistically significant determinants of load-shape in energy usage.In addition,a time series features engineering approach is used to extract 16 relevant demand flexibility indicators that characterize customers and corresponding clusters along four different axes:available Energy(E),Temporal patterns(T),Consistency(C),and Variability(V).The methodology is implemented on a real-world electricity consumption dataset of 325 Small and Medium-sized Enterprise(SME)customers,identifying 4 daily and 6 hourly easy-to-interpret,well-defined clusters.The application of the methodology includes selecting key parameters via grid search and a thorough comparison of clustering distances and methods to ensure the robustness of the results.Further research can test the scalability of the methodology to larger datasets from various customer segments(households and large commercial)and locations with different weather and socioeconomic conditions.
