Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b...Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated by infiltrating immune cells(Hauser and Cree, 2020).展开更多
Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose a...Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular networks.Brain vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the brain.This elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing vasculature.Brain capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.展开更多
Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–go...Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.展开更多
Despite significant progress in the Prognostics and Health Management(PHM)domain using pattern learning systems from data,machine learning(ML)still faces challenges related to limited generalization and weak interpret...Despite significant progress in the Prognostics and Health Management(PHM)domain using pattern learning systems from data,machine learning(ML)still faces challenges related to limited generalization and weak interpretability.A promising approach to overcoming these challenges is to embed domain knowledge into the ML pipeline,enhancing the model with additional pattern information.In this paper,we review the latest developments in PHM,encapsulated under the concept of Knowledge Driven Machine Learning(KDML).We propose a hierarchical framework to define KDML in PHM,which includes scientific paradigms,knowledge sources,knowledge representations,and knowledge embedding methods.Using this framework,we examine current research to demonstrate how various forms of knowledge can be integrated into the ML pipeline and provide roadmap to specific usage.Furthermore,we present several case studies that illustrate specific implementations of KDML in the PHM domain,including inductive experience,physical model,and signal processing.We analyze the improvements in generalization capability and interpretability that KDML can achieve.Finally,we discuss the challenges,potential applications,and usage recommendations of KDML in PHM,with a particular focus on the critical need for interpretability to ensure trustworthy deployment of artificial intelligence in PHM.展开更多
Mason Reset(MR),a groundbreaking invention by Clesson E.Mason in 1930 that later became a part of“the universal approach to process control instrumentation”,is revisited in this paper and is shown to consists of thr...Mason Reset(MR),a groundbreaking invention by Clesson E.Mason in 1930 that later became a part of“the universal approach to process control instrumentation”,is revisited in this paper and is shown to consists of three actions:fast(errorcorrection),medium(negative feedback for expanded proportional band)and slow(reset for zero steady-state error).The focus of the paper is on the reset action,generated from a positive feedback loop,and its underlying principles with profound implications to our understanding and practice of automatic control,both basic and advanced.For example,we note that reset control and integral control,contrary to common belief,differ fundamentally in design principle and in practicality.Such difference comes to a head in the event of integrator windup:while reset windup is a problem of actuator saturation,the integrator windup is a runaway situation due to controller instability.In fact,there is no advantage gained in replacing MR with an integrator.In other words,one should not integrate the error directly as in standard PID,since doing so makes the closed-loop system internally unstable.With MR-based control formulated in this paper,there is no such threat of instability and,therefore,no need for any anti-windup mechanisms.Furthermore,the integral control is made scalable in this framework as a tradeoff between the steady-state accuracy and the controller stability.This leads to a novel MR-based control design,scalable in gain and in time to accommodate various process characteristics and design specifications.Simple in construction and transparent in principle,this MR-based control,as a basic framework of design,is readily deployable in scale.展开更多
Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-asso...Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.展开更多
The“obesity paradox”in hepatocellular carcinoma(HCC)suggests patients with obesity may experience better treatment outcomes compared to patients without obesity.Wang et al highlighted this paradox in HCC immunothera...The“obesity paradox”in hepatocellular carcinoma(HCC)suggests patients with obesity may experience better treatment outcomes compared to patients without obesity.Wang et al highlighted this paradox in HCC immunotherapy,demonstrating superior progression-free survival and overall survival in patients with overweight and obesity treated with lenvatinib and camrelizumab,focusing on hepatitis B virus-related HCC.Mechanisms such as better nutritional reserves,leptin-mediated immune modulation,and reduced protein breakdown may explain these outcomes.Obesity’s role in anti-programmed cell death protein-1 therapy appears could have a benefit,while its effects on other treatments,such as anti-vascular endothelial growth factor therapy,may reduce efficacy.Further research is needed to explore how obesity influences the effectiveness of other most common immunotherapies like nivolumab,pembrolizumab,and bevacizumab,and whether weight loss as well as weight-loss related sarcopenia impacts these benefits.展开更多
A biologic drug is a medication produced from or containing components of living organisms.Given the rigorous testing that originator biologics undergo to establish Food and Drug Administration(FDA)Biologics License A...A biologic drug is a medication produced from or containing components of living organisms.Given the rigorous testing that originator biologics undergo to establish Food and Drug Administration(FDA)Biologics License Application(BLA)approval,their subsequent price yields a high burden on healthcare systems(1).Biologics account for 37%of prescription drug spending,despite comprising only 2%of all prescribed medications(2).Biosimilar medicines are designed to have active properties that are“highly similar”to a previously licensed reference product,leading to increased chemistry,manufacturing,and controls(CMC).展开更多
This study investigates the stabilization challenge at the boundaries of a type II thermoelastic network with n-star configuration and terminal masses,which experiences non-uniform bounded external disturbances at its...This study investigates the stabilization challenge at the boundaries of a type II thermoelastic network with n-star configuration and terminal masses,which experiences non-uniform bounded external disturbances at its control boundary.This research employs an advanced active disturbance rejection control framework,incorporating an innovative observer with adaptive gain characteristics for precise disturbance estimation,coupled with a robust feedback control mechanism for disturbance compensation.The theoretical analysis establishes rigorous convergence proofs for the proposed time-dependent extended state observer.Furthermore,this investigation utilizes semigroup theory to validate the closed-loop system’s well-posed.Through comprehensive Lyapunov-based analysis,this study confirms the system’s capability to achieve exponential convergence of tracking errors while effectively mitigating disturbance effects.Extensive numerical experiments corroborate the theoretical findings,demonstrating the control scheme’s practical efficacy.展开更多
The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathog...The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathogens.This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs.Although conventional thought is this is primarily in terms of oral health issues,such as dental caries and gingival disease.The systemic effects of the oral microbiome however,are relevant to both gastrointestinal(GI)disease and non-GI disease.These systemic risks occur for several reasons,including upregulation of cytokines,adhesion cell-like processes,toll-like receptors,reactive oxidative species or generation of mutation inducing DNA changes.Additionally,there is translocation risk of potential active pathogens or their metabolic byproducts.There is a substantial and growing body of evidence that the oral microbiome influences diseases including Barrett’s esophagus,metabolicassociated steatosis liver disease,and GI cancers.Additionally,there is burgeoning evidence of a causal association with systemic inflammatory diseases,including inflammatory bowel disease.This report discusses the most recent evidence of this association and highlights new approaches to potentially enhance our“best practice”strategies for optimal care of patients with inflammatory bowel disease.展开更多
Third-space endoscopy,also known as intramural surgery,represents a major evolution in minimally invasive gastrointestinal interventions.While natural orifice transluminal endoscopic surgery provided early conceptual ...Third-space endoscopy,also known as intramural surgery,represents a major evolution in minimally invasive gastrointestinal interventions.While natural orifice transluminal endoscopic surgery provided early conceptual groundwork,third-space endoscopy builds upon it by maintaining interventions within the submucosal layer,offering improved precision and reduced risk.The creation of a controlled submucosal working space enables precise therapeutic interventions while potentially reducing the morbidity associated with traditional surgical approaches.Among its most impactful applications are the peroral endoscopic myotomy techniques,including cricopharyngeal,esophageal,gastric,and Zenker’s myotomies.These procedures have redefined the management of cricopharyngeal bar,achalasia,gastroparesis,and Zenker’s diverticulum,respectively.These techniques offer durable symptom relief with reduced recovery times.Over the past five years,refinements in technique,advancements in instrumentation,technology,and improved patient selection have expanded indications and enhanced safety.However,challenges remain,including the limited standardization and accessibility to specialized training.This review provides a comprehensive analysis of the evolution,technical refinements,and clinical outcomes of thirdspace endoscopy,with a focus on its expanding role in foregut surgery.By consolidating current evidence and highlighting future directions,we aim to provide a critical perspective on the impact of intramural surgery and its potential to further transform the management of complex gastrointestinal disorders.展开更多
This study was to survey the relationship between semen values and demographics,comorbidities,and recreational substance use in a large cohort of adult men at the University of Chicago Medical Center Department of Uro...This study was to survey the relationship between semen values and demographics,comorbidities,and recreational substance use in a large cohort of adult men at the University of Chicago Medical Center Department of Urology(Chicago,IL,USA).We performed an analysis from January 2013 to December 2023 of semen samples obtained from adult patients at our institution and collected their demographics,comorbid medical conditions,and recreational substance use information.Patients were divided into categories of normozoospermia,oligozoospermia,and azoospermia on the basis of the 5th version of the World Health Organization(WHO)guidelines.Data were analyzed by univariate linear and logistic regression models,after which statistically significant variables were placed into multivariable models.Azoospermia and oligozoospermia were both associated with Caucasian or Black,Indigenous,and People of Color(BIPOC)race(both P<0.001),increasing age(P=0.005 and P<0.001,respectively),anemia(P<0.001 and P=0.02,respectively),lifetime tobacco use(both P<0.001),lifetime alcohol use(P=0.02 and P<0.001,respectively),and lifetime use of at least two recreational substances(P<0.001 and P=0.003,respectively)in multivariable models.Oligospermia was additionally associated with benign prostatic hyperplasia(BPH;P=0.003)in multivariable models.This study suggests that at-risk populations may benefit from additional early screening and workup for infertility.展开更多
This article focuses on financial management issues in mergers and acquisitions(M&A).It provides an indepth analysis of the financial risks and management challenges faced by contemporary businesses during various...This article focuses on financial management issues in mergers and acquisitions(M&A).It provides an indepth analysis of the financial risks and management challenges faced by contemporary businesses during various stages of M&A,such as pre-merger valuation pricing difficulties,unreasonable financing structures,risks in payment method selection,obstacles to financial integration,and lack of risk management.Targeted management strategies are proposed to address these issues.This paper suggests strengthening due diligence and valuation management,optimizing financing structures,rationally selecting payment methods,deepening financial integration,and improving tax planning.These strategies aim to enhance the level of financial management in M&A,promote economic synergies and management effects,help companies quickly achieve M&A goals,and drive sustainable business development.展开更多
This editorial comment on the article by Agidew et al in the recent issue of the World Journal of Clinical Oncology.Breast cancer remains a growing challenge in Ethiopia,where high mortality results from low awareness...This editorial comment on the article by Agidew et al in the recent issue of the World Journal of Clinical Oncology.Breast cancer remains a growing challenge in Ethiopia,where high mortality results from low awareness,delayed diagnosis,and restricted healthcare access.Agidew et al report that women with a family history of breast disease exhibit significantly higher levels of knowledge(83.9%vs 10.5%),more positive attitudes(49%vs 32.1%),and greater engagement in pre-ventive practices(74.1%vs 16.7%).However,with 69%-79%of women living below the poverty line,socioeconomic barriers severely limit preventive actions.Education,income,and community health insurance emerge as key predictors of health behaviors.We propose integrated interventions including deploying co-mmunity-based approaches,culturally tailored education,and artificial intelli-gence-powered education tools,to bridge knowledge gaps and transform aware-ness into action.This multifaceted strategy offers a scalable model for resource-limited settings globally,addressing both individual awareness and structural barriers to improve breast cancer outcomes.展开更多
Direct recycling methods offer a non-destructive way to regenerate degraded cathode material.The materials to be recycled in the industry typically constitute a mixture of various cathode materials extracted from a wi...Direct recycling methods offer a non-destructive way to regenerate degraded cathode material.The materials to be recycled in the industry typically constitute a mixture of various cathode materials extracted from a wide variety of retired lithium-ion batteries.Bridging the gap,a direct recycling method using a low-temperature sintering process is reported.The degraded cathode mixture of LMO(LiMn_(2)O_(4))and NMC(LiNiCoMnO_(2))extracted from retired LIBs was successfully regenerated by the proposed method with a low sintering temperature of 300℃ for 4 h.Advanced characterization tools were utilized to validate the full recovery of the crystal structure in the degraded cathode mixture.After regeneration,LMO/NMC cathode mixture shows an initial capacity of 144.0mAh g^(-1) and a capacity retention of 95.1%at 0.5 C for 250 cycles.The regenerated cathode mixture also shows a capacity of 83 mAh g-1 at 2 C,which is slightly higher compared to the pristine material.As a result of the direct recycling process,the electrochemical performance of degraded cathode mixture is recovered to the same level as the pristine material.Life-cycle assessment results emphasized a 90.4%reduction in energy consumption and a 51%reduction in PM2.5 emissions for lithium-ion battery packs using a direct recycled cathode mixture compared to the pristine material.展开更多
Introduction:Direct-to-consumer(DTC)telemedicine has emerged as an option for transgender patients seeking gender affirming hormone therapy(GAHT).We aimed to characterize the healthcare services provided by DTC teleme...Introduction:Direct-to-consumer(DTC)telemedicine has emerged as an option for transgender patients seeking gender affirming hormone therapy(GAHT).We aimed to characterize the healthcare services provided by DTC telemedicine companies offering GAHT and to compare their costs to a tertiary care center.Methods:We identified DTC telemedicine platforms offering GAHT via internet searches and extracted information from their websites related to evaluation,treatment,monitoring,and cost.Cost of theDTC GAHT was compared to cost for comparable services at a tertiary care center.Results:Six DTC companies were identified.All platforms utilized an informed consent model without prerequisite mental health evaluation for GAHT.Platforms did not provide comprehensive mental health services.All platforms endorsed the use of regular follow up visits throughout the treatment period although interval of laboratory assessment varied.Cost estimates were comparable for uninsured patients and higher compared to those for insured patients.Cost estimates were lowest with private and public insurance at the tertiary center.Conclusions:DTC telemedicine platforms offering GAHT appear to be in line with the recently released World Professional Association for Transgender Health standards of care regarding the laboratory evaluation and monitoring,but it is unclear whether they are compliant with other recommendations.These platforms offer competitive costs for TGD patients without insurance.展开更多
BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qua...BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.展开更多
文摘Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated by infiltrating immune cells(Hauser and Cree, 2020).
基金supported by funding from the National Institutes of Health(R01 NS117510)(to RLM)。
文摘Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular networks.Brain vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the brain.This elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing vasculature.Brain capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.
文摘Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.
基金Supported in part by Science Center for Gas Turbine Project(Project No.P2022-DC-I-003-001)National Natural Science Foundation of China(Grant No.52275130).
文摘Despite significant progress in the Prognostics and Health Management(PHM)domain using pattern learning systems from data,machine learning(ML)still faces challenges related to limited generalization and weak interpretability.A promising approach to overcoming these challenges is to embed domain knowledge into the ML pipeline,enhancing the model with additional pattern information.In this paper,we review the latest developments in PHM,encapsulated under the concept of Knowledge Driven Machine Learning(KDML).We propose a hierarchical framework to define KDML in PHM,which includes scientific paradigms,knowledge sources,knowledge representations,and knowledge embedding methods.Using this framework,we examine current research to demonstrate how various forms of knowledge can be integrated into the ML pipeline and provide roadmap to specific usage.Furthermore,we present several case studies that illustrate specific implementations of KDML in the PHM domain,including inductive experience,physical model,and signal processing.We analyze the improvements in generalization capability and interpretability that KDML can achieve.Finally,we discuss the challenges,potential applications,and usage recommendations of KDML in PHM,with a particular focus on the critical need for interpretability to ensure trustworthy deployment of artificial intelligence in PHM.
文摘Mason Reset(MR),a groundbreaking invention by Clesson E.Mason in 1930 that later became a part of“the universal approach to process control instrumentation”,is revisited in this paper and is shown to consists of three actions:fast(errorcorrection),medium(negative feedback for expanded proportional band)and slow(reset for zero steady-state error).The focus of the paper is on the reset action,generated from a positive feedback loop,and its underlying principles with profound implications to our understanding and practice of automatic control,both basic and advanced.For example,we note that reset control and integral control,contrary to common belief,differ fundamentally in design principle and in practicality.Such difference comes to a head in the event of integrator windup:while reset windup is a problem of actuator saturation,the integrator windup is a runaway situation due to controller instability.In fact,there is no advantage gained in replacing MR with an integrator.In other words,one should not integrate the error directly as in standard PID,since doing so makes the closed-loop system internally unstable.With MR-based control formulated in this paper,there is no such threat of instability and,therefore,no need for any anti-windup mechanisms.Furthermore,the integral control is made scalable in this framework as a tradeoff between the steady-state accuracy and the controller stability.This leads to a novel MR-based control design,scalable in gain and in time to accommodate various process characteristics and design specifications.Simple in construction and transparent in principle,this MR-based control,as a basic framework of design,is readily deployable in scale.
文摘Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.
文摘The“obesity paradox”in hepatocellular carcinoma(HCC)suggests patients with obesity may experience better treatment outcomes compared to patients without obesity.Wang et al highlighted this paradox in HCC immunotherapy,demonstrating superior progression-free survival and overall survival in patients with overweight and obesity treated with lenvatinib and camrelizumab,focusing on hepatitis B virus-related HCC.Mechanisms such as better nutritional reserves,leptin-mediated immune modulation,and reduced protein breakdown may explain these outcomes.Obesity’s role in anti-programmed cell death protein-1 therapy appears could have a benefit,while its effects on other treatments,such as anti-vascular endothelial growth factor therapy,may reduce efficacy.Further research is needed to explore how obesity influences the effectiveness of other most common immunotherapies like nivolumab,pembrolizumab,and bevacizumab,and whether weight loss as well as weight-loss related sarcopenia impacts these benefits.
文摘A biologic drug is a medication produced from or containing components of living organisms.Given the rigorous testing that originator biologics undergo to establish Food and Drug Administration(FDA)Biologics License Application(BLA)approval,their subsequent price yields a high burden on healthcare systems(1).Biologics account for 37%of prescription drug spending,despite comprising only 2%of all prescribed medications(2).Biosimilar medicines are designed to have active properties that are“highly similar”to a previously licensed reference product,leading to increased chemistry,manufacturing,and controls(CMC).
文摘This study investigates the stabilization challenge at the boundaries of a type II thermoelastic network with n-star configuration and terminal masses,which experiences non-uniform bounded external disturbances at its control boundary.This research employs an advanced active disturbance rejection control framework,incorporating an innovative observer with adaptive gain characteristics for precise disturbance estimation,coupled with a robust feedback control mechanism for disturbance compensation.The theoretical analysis establishes rigorous convergence proofs for the proposed time-dependent extended state observer.Furthermore,this investigation utilizes semigroup theory to validate the closed-loop system’s well-posed.Through comprehensive Lyapunov-based analysis,this study confirms the system’s capability to achieve exponential convergence of tracking errors while effectively mitigating disturbance effects.Extensive numerical experiments corroborate the theoretical findings,demonstrating the control scheme’s practical efficacy.
文摘The oral microbiome is the second largest microbial community in the human body after the gut microbiome.It includes an array of fungi,bacteria,amoebae,flagellates,archaea,and viruses,all of which are potential pathogens.This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs.Although conventional thought is this is primarily in terms of oral health issues,such as dental caries and gingival disease.The systemic effects of the oral microbiome however,are relevant to both gastrointestinal(GI)disease and non-GI disease.These systemic risks occur for several reasons,including upregulation of cytokines,adhesion cell-like processes,toll-like receptors,reactive oxidative species or generation of mutation inducing DNA changes.Additionally,there is translocation risk of potential active pathogens or their metabolic byproducts.There is a substantial and growing body of evidence that the oral microbiome influences diseases including Barrett’s esophagus,metabolicassociated steatosis liver disease,and GI cancers.Additionally,there is burgeoning evidence of a causal association with systemic inflammatory diseases,including inflammatory bowel disease.This report discusses the most recent evidence of this association and highlights new approaches to potentially enhance our“best practice”strategies for optimal care of patients with inflammatory bowel disease.
文摘Third-space endoscopy,also known as intramural surgery,represents a major evolution in minimally invasive gastrointestinal interventions.While natural orifice transluminal endoscopic surgery provided early conceptual groundwork,third-space endoscopy builds upon it by maintaining interventions within the submucosal layer,offering improved precision and reduced risk.The creation of a controlled submucosal working space enables precise therapeutic interventions while potentially reducing the morbidity associated with traditional surgical approaches.Among its most impactful applications are the peroral endoscopic myotomy techniques,including cricopharyngeal,esophageal,gastric,and Zenker’s myotomies.These procedures have redefined the management of cricopharyngeal bar,achalasia,gastroparesis,and Zenker’s diverticulum,respectively.These techniques offer durable symptom relief with reduced recovery times.Over the past five years,refinements in technique,advancements in instrumentation,technology,and improved patient selection have expanded indications and enhanced safety.However,challenges remain,including the limited standardization and accessibility to specialized training.This review provides a comprehensive analysis of the evolution,technical refinements,and clinical outcomes of thirdspace endoscopy,with a focus on its expanding role in foregut surgery.By consolidating current evidence and highlighting future directions,we aim to provide a critical perspective on the impact of intramural surgery and its potential to further transform the management of complex gastrointestinal disorders.
文摘This study was to survey the relationship between semen values and demographics,comorbidities,and recreational substance use in a large cohort of adult men at the University of Chicago Medical Center Department of Urology(Chicago,IL,USA).We performed an analysis from January 2013 to December 2023 of semen samples obtained from adult patients at our institution and collected their demographics,comorbid medical conditions,and recreational substance use information.Patients were divided into categories of normozoospermia,oligozoospermia,and azoospermia on the basis of the 5th version of the World Health Organization(WHO)guidelines.Data were analyzed by univariate linear and logistic regression models,after which statistically significant variables were placed into multivariable models.Azoospermia and oligozoospermia were both associated with Caucasian or Black,Indigenous,and People of Color(BIPOC)race(both P<0.001),increasing age(P=0.005 and P<0.001,respectively),anemia(P<0.001 and P=0.02,respectively),lifetime tobacco use(both P<0.001),lifetime alcohol use(P=0.02 and P<0.001,respectively),and lifetime use of at least two recreational substances(P<0.001 and P=0.003,respectively)in multivariable models.Oligospermia was additionally associated with benign prostatic hyperplasia(BPH;P=0.003)in multivariable models.This study suggests that at-risk populations may benefit from additional early screening and workup for infertility.
文摘This article focuses on financial management issues in mergers and acquisitions(M&A).It provides an indepth analysis of the financial risks and management challenges faced by contemporary businesses during various stages of M&A,such as pre-merger valuation pricing difficulties,unreasonable financing structures,risks in payment method selection,obstacles to financial integration,and lack of risk management.Targeted management strategies are proposed to address these issues.This paper suggests strengthening due diligence and valuation management,optimizing financing structures,rationally selecting payment methods,deepening financial integration,and improving tax planning.These strategies aim to enhance the level of financial management in M&A,promote economic synergies and management effects,help companies quickly achieve M&A goals,and drive sustainable business development.
文摘This editorial comment on the article by Agidew et al in the recent issue of the World Journal of Clinical Oncology.Breast cancer remains a growing challenge in Ethiopia,where high mortality results from low awareness,delayed diagnosis,and restricted healthcare access.Agidew et al report that women with a family history of breast disease exhibit significantly higher levels of knowledge(83.9%vs 10.5%),more positive attitudes(49%vs 32.1%),and greater engagement in pre-ventive practices(74.1%vs 16.7%).However,with 69%-79%of women living below the poverty line,socioeconomic barriers severely limit preventive actions.Education,income,and community health insurance emerge as key predictors of health behaviors.We propose integrated interventions including deploying co-mmunity-based approaches,culturally tailored education,and artificial intelli-gence-powered education tools,to bridge knowledge gaps and transform aware-ness into action.This multifaceted strategy offers a scalable model for resource-limited settings globally,addressing both individual awareness and structural barriers to improve breast cancer outcomes.
基金Financial support from the US National Science Foundation(CBET-2101129)is acknowledged.
文摘Direct recycling methods offer a non-destructive way to regenerate degraded cathode material.The materials to be recycled in the industry typically constitute a mixture of various cathode materials extracted from a wide variety of retired lithium-ion batteries.Bridging the gap,a direct recycling method using a low-temperature sintering process is reported.The degraded cathode mixture of LMO(LiMn_(2)O_(4))and NMC(LiNiCoMnO_(2))extracted from retired LIBs was successfully regenerated by the proposed method with a low sintering temperature of 300℃ for 4 h.Advanced characterization tools were utilized to validate the full recovery of the crystal structure in the degraded cathode mixture.After regeneration,LMO/NMC cathode mixture shows an initial capacity of 144.0mAh g^(-1) and a capacity retention of 95.1%at 0.5 C for 250 cycles.The regenerated cathode mixture also shows a capacity of 83 mAh g-1 at 2 C,which is slightly higher compared to the pristine material.As a result of the direct recycling process,the electrochemical performance of degraded cathode mixture is recovered to the same level as the pristine material.Life-cycle assessment results emphasized a 90.4%reduction in energy consumption and a 51%reduction in PM2.5 emissions for lithium-ion battery packs using a direct recycled cathode mixture compared to the pristine material.
文摘Introduction:Direct-to-consumer(DTC)telemedicine has emerged as an option for transgender patients seeking gender affirming hormone therapy(GAHT).We aimed to characterize the healthcare services provided by DTC telemedicine companies offering GAHT and to compare their costs to a tertiary care center.Methods:We identified DTC telemedicine platforms offering GAHT via internet searches and extracted information from their websites related to evaluation,treatment,monitoring,and cost.Cost of theDTC GAHT was compared to cost for comparable services at a tertiary care center.Results:Six DTC companies were identified.All platforms utilized an informed consent model without prerequisite mental health evaluation for GAHT.Platforms did not provide comprehensive mental health services.All platforms endorsed the use of regular follow up visits throughout the treatment period although interval of laboratory assessment varied.Cost estimates were comparable for uninsured patients and higher compared to those for insured patients.Cost estimates were lowest with private and public insurance at the tertiary center.Conclusions:DTC telemedicine platforms offering GAHT appear to be in line with the recently released World Professional Association for Transgender Health standards of care regarding the laboratory evaluation and monitoring,but it is unclear whether they are compliant with other recommendations.These platforms offer competitive costs for TGD patients without insurance.
文摘BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.
