Introduction to Dr.Karl Golnik Karl Golnik,MD,MEd(Figure 1)is a neuro-ophthalmologist at the University of Cincinnati Gardner Neuroscience Institute;a professor of ophthalmology at the Cincinnati Eye Institute and the...Introduction to Dr.Karl Golnik Karl Golnik,MD,MEd(Figure 1)is a neuro-ophthalmologist at the University of Cincinnati Gardner Neuroscience Institute;a professor of ophthalmology at the Cincinnati Eye Institute and the University of Cincinnati;and professor of Ophthalmology at the University of Louisville.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn...Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.展开更多
Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS)...Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).展开更多
Facilitated transport membranes for post-combustion carbon capture are one of the technologies to achieve efficient and large-scale capture.The central principle is to utilize the affinity of CO_(2) for the carrier to...Facilitated transport membranes for post-combustion carbon capture are one of the technologies to achieve efficient and large-scale capture.The central principle is to utilize the affinity of CO_(2) for the carrier to achieve efficient separation and to break the Robson upper bound.This paper reviews the progress of facilitated transport membranes research regarding polymer materials,principles,and problems faced at this stage.Firstly,we briefly introduce the transport mechanism of the facilitated transport membranes.Then the research progress of several major polymers used for facilitated transport membranes for CO_(2)/N_(2) separation was presented in the past five years.Additionally,we analyze the primary challenges of facilitated transport membranes,including the influence of water,the effect of temperature,the saturation effect of the carrier,and the process configuration.Finally,we also delve into the challenges and competitiveness of facilitated transport membranes.展开更多
Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic...Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).展开更多
BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the leading cause of chronic liver disease in children,affecting up to 38%with obesity of children.With the global shift from non-alcoholic fatty l...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the leading cause of chronic liver disease in children,affecting up to 38%with obesity of children.With the global shift from non-alcoholic fatty liver disease(NAFLD)to MASLD using affirmative criteria(hepatic steatosis plus≥1 cardiometabolic risk factor)and approximately 99%concordance in pediatrics,the development of non-invasive fibrosis tools is accelerating.Yao et al report a machine-learning“chronic MASLD with fibrosis(CH-MASLD-Fib)”score for advanced fibrosis with area under the receiver operating characteristic curve(AUROC)of 0.92.While timely,we urge caution.First,high accuracy from a single-center cohort signals overfitting:Complex models can learn cohort-specific noise and fail to generalize.Consistent with this,established pediatric scores(NAFLD fibrosis score,fibrosis-4,pediatric NAFLD fibrosis score)perform modestly(AUROC:Approximately 0.6-0.7),and aspartate aminotransferase-to-platelet ratio index is variable,raising concern that CH-MASLD-Fib’s result reflects a statistical artifact.Second,MASLD epidemiology varies by ethnicity(highest in Hispanic,lower in Black children);a model derived in a mono-ethnic Chinese cohort may misclassify other populations.Third,clinical utility and cost-effectiveness are unproven;dependence on specialized assays(e.g.,bile acids,cholinesterase)would limit access and increase cost.We recommend external validation in multi-ethnic cohorts,head-to-head comparisons with simple serum indices and elastography,and formal economic analyses.Until then,clinical judgment anchored in readily available markers and judicious,targeted liver biopsy remains paramount.展开更多
BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with A...BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.展开更多
Chemotherapy-related cardiac dysfunction(CTRCD)remains a major barrier to optimal cancer survivorship,threatening quality of life and long-term outcomes.Contemporary guidelines emphasize early detection through multim...Chemotherapy-related cardiac dysfunction(CTRCD)remains a major barrier to optimal cancer survivorship,threatening quality of life and long-term outcomes.Contemporary guidelines emphasize early detection through multimodal strategies,including echocardiographic global longitudinal strain(GLS)and cardiac biomarkers,but their real-world uptake is inconsistent.In this issue,Méndez-Toro et al present a retrospective cohort from Colombia that highlights this gap,reporting a CTRCD incidence of 8.8%in high-risk oncology patients.Although the authors observed clear declines in left ventricular ejection fraction and GLS among affected patients,less than 40%underwent end-of-treatment echocardiography and only one-quarter had biomarker surveillance.The study underscores three critical lessons:Multimodal monitoring is under-utilized,reported incidence likely underestimates the true burden,and low-and middle-income countries face unique challenges in implementing structured cardio-oncology programs.These findings demand a shift from sporadic monitoring to pragmatic,risk-adapted protocols that can translate early detection into meaningful cardioprotection.展开更多
Images obtained from hyperspectral sensors provide information about the target area that extends beyond the visible portions of the electromagnetic spectrum.However,due to sensor limitations and imperfections during ...Images obtained from hyperspectral sensors provide information about the target area that extends beyond the visible portions of the electromagnetic spectrum.However,due to sensor limitations and imperfections during the image acquisition and transmission phases,noise is introduced into the acquired image,which can have a negative impact on downstream analyses such as classification,target tracking,and spectral unmixing.Noise in hyperspectral images(HSI)is modelled as a combination from several sources,including Gaussian/impulse noise,stripes,and deadlines.An HSI restoration method for such a mixed noise model is proposed.First,a joint optimisation framework is proposed for recovering hyperspectral data corrupted by mixed Gaussian-impulse noise by estimating both the clean data as well as the sparse/impulse noise levels.Second,a hyper-Laplacian prior is used along both the spatial and spectral dimensions to express sparsity in clean image gradients.Third,to model the sparse nature of impulse noise,anℓ_(1)−norm over the impulse noise gradient is used.Because the proposed methodology employs two distinct priors,the authors refer to it as the hyperspectral dual prior(HySpDualP)denoiser.To the best of authors'knowledge,this joint optimisation framework is the first attempt in this direction.To handle the non-smooth and nonconvex nature of the generalℓ_(p)−norm-based regularisation term,a generalised shrinkage/thresholding(GST)solver is employed.Finally,an efficient split-Bregman approach is used to solve the resulting optimisation problem.Experimental results on synthetic data and real HSI datacube obtained from hyperspectral sensors demonstrate that the authors’proposed model outperforms state-of-the-art methods,both visually and in terms of various image quality assessment metrics.展开更多
In response to the increasing global energy demand and environmental pollution,microgrids have emerged as an innovative solution by integrating distributed energy resources(DERs),energy storage systems,and loads to im...In response to the increasing global energy demand and environmental pollution,microgrids have emerged as an innovative solution by integrating distributed energy resources(DERs),energy storage systems,and loads to improve energy efficiency and reliability.This study proposes a novel hybrid optimization algorithm,DE-HHO,combining differential evolution(DE)and Harris Hawks optimization(HHO)to address microgrid scheduling issues.The proposed method adopts a multi-objective optimization framework that simultaneously minimizes operational costs and environmental impacts.The DE-HHO algorithm demonstrates significant advantages in convergence speed and global search capability through the analysis of wind,solar,micro-gas turbine,and battery models.Comprehensive simulation tests show that DE-HHO converges rapidly within 10 iterations and achieves a 4.5%reduction in total cost compared to PSO and a 5.4%reduction compared to HHO.Specifically,DE-HHO attains an optimal total cost of$20,221.37,outperforming PSO($21,184.45)and HHO($21,372.24).The maximum cost obtained by DE-HHO is$23,420.55,with a mean of$21,615.77,indicating stability and cost control capabilities.These results highlight the effectiveness of DE-HHO in reducing operational costs and enhancing system stability for efficient and sustainable microgrid operation.展开更多
This study evaluates the dynamics of trace metals impacts on the ecosystems of the Bartlett Pond, a small shallow wetland pond located in Laredo, Texas by analyzing sediment samples taken from four quadrants of the po...This study evaluates the dynamics of trace metals impacts on the ecosystems of the Bartlett Pond, a small shallow wetland pond located in Laredo, Texas by analyzing sediment samples taken from four quadrants of the pond. The concentrations of trace elements in sediment samples are highest for iron (Fe), followed by chromium (Cr), then lead (Pb), with lower concentration of antimony (Sb), cobalt (Co), arsenic (As), cadmium (Cd), and the lowest concentration being thallium (Tl) within Bartlett Pond. The sediment quality of the pond is acceptable for organisms and the environment as trace element concentrations (e.g. As, Cd, Cr, and Pb) are within the probable effect concentration (PEC) of National Ocean and Atmospheric Administration (NOAA) guidelines although the PEC values for Co, Fe, Sb and Tl are not given. Bivariate and multivariate correlation analysis shows that most trace elements exhibit a strong positive correlation among them indicating the same anthropogenic sources and biogeochemical processes control these trace elements concentrations within the pond. We provided a comprehensive snapshot of trace element concentrations in sediments through descriptive analysis, laying the foundation for future environmental risk assessments. Correlation analysis of eight trace elements helped identify relationships, offering insights into pollution sources and potential health impacts. Additionally, univariate and multivariate predictive analyses generated numerous models, extending beyond the interpretation of partial and full regression coefficients. We also included graphical analyses of trace element variations, which are critical for understanding environmental processes and geochemical patterns. These findings advance our understanding about trace metals dynamics in sediments and may be a valuable reference for ecosystems and environmental management of different landscapes.展开更多
The Late Paleozoic marked Earth’s most recent icehouse–greenhouse transition,providing valuable insights into future climate and environmental changes.Although the aridification of the North China Craton(NCC)during ...The Late Paleozoic marked Earth’s most recent icehouse–greenhouse transition,providing valuable insights into future climate and environmental changes.Although the aridification of the North China Craton(NCC)during the Late Paleozoic is well established,its pattern and causes remain unclear.Here,we identify four aridification intervals from the late Gzhelian to Lopingian by analyzing continuous records of elemental climate proxies(MgO/CaO,Sr/Cu),a volcanism proxy(Hg/TOC),and spore–pollen assemblages.Interval I(∼303–295 Ma),during which the NCC was located at low paleolatitudes,was characterized by humid conditions and a predominance of ferns,associated with weak volcanism.Interval II(∼295–286 Ma)was subhumid,with increasing gymnosperm presence,and significant climate fluctuations linked to volcanism.CO_(2) emissions from the Tarim LIP and Panjal Traps drove aridification from the late Asselian to late Artinskian,contributing to the decline of the Late Paleozoic Ice Age.As a result,aridification in the NCC lagged behind that of Pangea.Interval III(∼286–280.98 Ma)marked the transition to subarid conditions and the onset of dominance by gymnosperms,associated with a rapid northward drift of the NCC and an increase in atmosphericρCO_(2).Interval IV(∼259.51–251.902 Ma),separated from the underlying Interval III by a major regional unconformity(∼280.98–259.51),coincided with global aridification and intensified volcanism.These findings highlight the significant influences of both tectonic plate motion and volcanism on the climate evolution of the NCC,with shifts in the dominant controlling factors through time.This study provides new insights into the distinct trajectories of global and regional climate dynamics.展开更多
文摘Introduction to Dr.Karl Golnik Karl Golnik,MD,MEd(Figure 1)is a neuro-ophthalmologist at the University of Cincinnati Gardner Neuroscience Institute;a professor of ophthalmology at the Cincinnati Eye Institute and the University of Cincinnati;and professor of Ophthalmology at the University of Louisville.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金supported by NIH grants,Nos.R01NS125074,R01AG083164,R01NS107365,and R21NS127177(to YL),1F31NS129204-01A1(to KW)and Albert Ryan Fellowship(to KW).
文摘Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.
基金supported by NIH grants(R01NS125074,R01AG083164,and R21NS127177)(to YL).
文摘Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).
文摘Facilitated transport membranes for post-combustion carbon capture are one of the technologies to achieve efficient and large-scale capture.The central principle is to utilize the affinity of CO_(2) for the carrier to achieve efficient separation and to break the Robson upper bound.This paper reviews the progress of facilitated transport membranes research regarding polymer materials,principles,and problems faced at this stage.Firstly,we briefly introduce the transport mechanism of the facilitated transport membranes.Then the research progress of several major polymers used for facilitated transport membranes for CO_(2)/N_(2) separation was presented in the past five years.Additionally,we analyze the primary challenges of facilitated transport membranes,including the influence of water,the effect of temperature,the saturation effect of the carrier,and the process configuration.Finally,we also delve into the challenges and competitiveness of facilitated transport membranes.
文摘Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).
基金Supported by the University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the leading cause of chronic liver disease in children,affecting up to 38%with obesity of children.With the global shift from non-alcoholic fatty liver disease(NAFLD)to MASLD using affirmative criteria(hepatic steatosis plus≥1 cardiometabolic risk factor)and approximately 99%concordance in pediatrics,the development of non-invasive fibrosis tools is accelerating.Yao et al report a machine-learning“chronic MASLD with fibrosis(CH-MASLD-Fib)”score for advanced fibrosis with area under the receiver operating characteristic curve(AUROC)of 0.92.While timely,we urge caution.First,high accuracy from a single-center cohort signals overfitting:Complex models can learn cohort-specific noise and fail to generalize.Consistent with this,established pediatric scores(NAFLD fibrosis score,fibrosis-4,pediatric NAFLD fibrosis score)perform modestly(AUROC:Approximately 0.6-0.7),and aspartate aminotransferase-to-platelet ratio index is variable,raising concern that CH-MASLD-Fib’s result reflects a statistical artifact.Second,MASLD epidemiology varies by ethnicity(highest in Hispanic,lower in Black children);a model derived in a mono-ethnic Chinese cohort may misclassify other populations.Third,clinical utility and cost-effectiveness are unproven;dependence on specialized assays(e.g.,bile acids,cholinesterase)would limit access and increase cost.We recommend external validation in multi-ethnic cohorts,head-to-head comparisons with simple serum indices and elastography,and formal economic analyses.Until then,clinical judgment anchored in readily available markers and judicious,targeted liver biopsy remains paramount.
文摘BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.
文摘Chemotherapy-related cardiac dysfunction(CTRCD)remains a major barrier to optimal cancer survivorship,threatening quality of life and long-term outcomes.Contemporary guidelines emphasize early detection through multimodal strategies,including echocardiographic global longitudinal strain(GLS)and cardiac biomarkers,but their real-world uptake is inconsistent.In this issue,Méndez-Toro et al present a retrospective cohort from Colombia that highlights this gap,reporting a CTRCD incidence of 8.8%in high-risk oncology patients.Although the authors observed clear declines in left ventricular ejection fraction and GLS among affected patients,less than 40%underwent end-of-treatment echocardiography and only one-quarter had biomarker surveillance.The study underscores three critical lessons:Multimodal monitoring is under-utilized,reported incidence likely underestimates the true burden,and low-and middle-income countries face unique challenges in implementing structured cardio-oncology programs.These findings demand a shift from sporadic monitoring to pragmatic,risk-adapted protocols that can translate early detection into meaningful cardioprotection.
文摘Images obtained from hyperspectral sensors provide information about the target area that extends beyond the visible portions of the electromagnetic spectrum.However,due to sensor limitations and imperfections during the image acquisition and transmission phases,noise is introduced into the acquired image,which can have a negative impact on downstream analyses such as classification,target tracking,and spectral unmixing.Noise in hyperspectral images(HSI)is modelled as a combination from several sources,including Gaussian/impulse noise,stripes,and deadlines.An HSI restoration method for such a mixed noise model is proposed.First,a joint optimisation framework is proposed for recovering hyperspectral data corrupted by mixed Gaussian-impulse noise by estimating both the clean data as well as the sparse/impulse noise levels.Second,a hyper-Laplacian prior is used along both the spatial and spectral dimensions to express sparsity in clean image gradients.Third,to model the sparse nature of impulse noise,anℓ_(1)−norm over the impulse noise gradient is used.Because the proposed methodology employs two distinct priors,the authors refer to it as the hyperspectral dual prior(HySpDualP)denoiser.To the best of authors'knowledge,this joint optimisation framework is the first attempt in this direction.To handle the non-smooth and nonconvex nature of the generalℓ_(p)−norm-based regularisation term,a generalised shrinkage/thresholding(GST)solver is employed.Finally,an efficient split-Bregman approach is used to solve the resulting optimisation problem.Experimental results on synthetic data and real HSI datacube obtained from hyperspectral sensors demonstrate that the authors’proposed model outperforms state-of-the-art methods,both visually and in terms of various image quality assessment metrics.
文摘In response to the increasing global energy demand and environmental pollution,microgrids have emerged as an innovative solution by integrating distributed energy resources(DERs),energy storage systems,and loads to improve energy efficiency and reliability.This study proposes a novel hybrid optimization algorithm,DE-HHO,combining differential evolution(DE)and Harris Hawks optimization(HHO)to address microgrid scheduling issues.The proposed method adopts a multi-objective optimization framework that simultaneously minimizes operational costs and environmental impacts.The DE-HHO algorithm demonstrates significant advantages in convergence speed and global search capability through the analysis of wind,solar,micro-gas turbine,and battery models.Comprehensive simulation tests show that DE-HHO converges rapidly within 10 iterations and achieves a 4.5%reduction in total cost compared to PSO and a 5.4%reduction compared to HHO.Specifically,DE-HHO attains an optimal total cost of$20,221.37,outperforming PSO($21,184.45)and HHO($21,372.24).The maximum cost obtained by DE-HHO is$23,420.55,with a mean of$21,615.77,indicating stability and cost control capabilities.These results highlight the effectiveness of DE-HHO in reducing operational costs and enhancing system stability for efficient and sustainable microgrid operation.
文摘This study evaluates the dynamics of trace metals impacts on the ecosystems of the Bartlett Pond, a small shallow wetland pond located in Laredo, Texas by analyzing sediment samples taken from four quadrants of the pond. The concentrations of trace elements in sediment samples are highest for iron (Fe), followed by chromium (Cr), then lead (Pb), with lower concentration of antimony (Sb), cobalt (Co), arsenic (As), cadmium (Cd), and the lowest concentration being thallium (Tl) within Bartlett Pond. The sediment quality of the pond is acceptable for organisms and the environment as trace element concentrations (e.g. As, Cd, Cr, and Pb) are within the probable effect concentration (PEC) of National Ocean and Atmospheric Administration (NOAA) guidelines although the PEC values for Co, Fe, Sb and Tl are not given. Bivariate and multivariate correlation analysis shows that most trace elements exhibit a strong positive correlation among them indicating the same anthropogenic sources and biogeochemical processes control these trace elements concentrations within the pond. We provided a comprehensive snapshot of trace element concentrations in sediments through descriptive analysis, laying the foundation for future environmental risk assessments. Correlation analysis of eight trace elements helped identify relationships, offering insights into pollution sources and potential health impacts. Additionally, univariate and multivariate predictive analyses generated numerous models, extending beyond the interpretation of partial and full regression coefficients. We also included graphical analyses of trace element variations, which are critical for understanding environmental processes and geochemical patterns. These findings advance our understanding about trace metals dynamics in sediments and may be a valuable reference for ecosystems and environmental management of different landscapes.
基金financially supported by CNPC Innovation Found(2021DQ02-1003)the Fundamental Research Funds for the Central Universities(Ph.D.Top Innovative Talents Fund of CUMTB)(BBJ2025043).
文摘The Late Paleozoic marked Earth’s most recent icehouse–greenhouse transition,providing valuable insights into future climate and environmental changes.Although the aridification of the North China Craton(NCC)during the Late Paleozoic is well established,its pattern and causes remain unclear.Here,we identify four aridification intervals from the late Gzhelian to Lopingian by analyzing continuous records of elemental climate proxies(MgO/CaO,Sr/Cu),a volcanism proxy(Hg/TOC),and spore–pollen assemblages.Interval I(∼303–295 Ma),during which the NCC was located at low paleolatitudes,was characterized by humid conditions and a predominance of ferns,associated with weak volcanism.Interval II(∼295–286 Ma)was subhumid,with increasing gymnosperm presence,and significant climate fluctuations linked to volcanism.CO_(2) emissions from the Tarim LIP and Panjal Traps drove aridification from the late Asselian to late Artinskian,contributing to the decline of the Late Paleozoic Ice Age.As a result,aridification in the NCC lagged behind that of Pangea.Interval III(∼286–280.98 Ma)marked the transition to subarid conditions and the onset of dominance by gymnosperms,associated with a rapid northward drift of the NCC and an increase in atmosphericρCO_(2).Interval IV(∼259.51–251.902 Ma),separated from the underlying Interval III by a major regional unconformity(∼280.98–259.51),coincided with global aridification and intensified volcanism.These findings highlight the significant influences of both tectonic plate motion and volcanism on the climate evolution of the NCC,with shifts in the dominant controlling factors through time.This study provides new insights into the distinct trajectories of global and regional climate dynamics.
