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Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

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World Journal of Gastroenterology 2024年第14期30卷 1982-1989页

作者： Julieta Trinks maría F Mascardi Adrián Gadano Sebastián marciano Instituto de Medicina Traslacional e Ingeniería Biomédica-Consejo nacional de Investigaciones Científicas y Técnicas-Instituto Universitario del Hospital Italiano-Hospital Italiano de Buenos Aires Ciudad Autónoma de Buenos Aires C1199ACLArgentina Consejo nacional de Investigaciones Científicas y Técnicas Ciudad Autónoma de Buenos Aires C1425FQBArgentina Liver Unit Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina Department of Research Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

关键词： Metabolic dysfunction-associated steatotic liver disease non-alcoholic steatohepatitis Biomarker Risk stratification Omics

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez maría Fernanda González Ana maría Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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neural Regeneration Research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier Ramos Laboratorio de neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRnAs or lncRnA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán maría Dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and Liver Transplantation Unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.

关键词： Machine learning Liver surgery Artificial intelligence Random forest Prediction model

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The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1042-1048页

作者： maría Ximena núñez Andrea Acosta-Ortega Guillermo Raul Vera-Duarte Catalina Gómez-Duarte Unit of Cornea Cataract and Refractive SurgeryVision Sana Research GroupClínica de Oftalmología de CaliFaculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Faculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Hospital de ClínicasNational University of AsunciónAsunción 111421Paraguay

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)ofn the lower eyelid of each eye,and non-invasive tear break-up time(nI-TBUT)ndomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with Pnalysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,nIBUT,and OSDI.There was a significant difference between ILux®and MMGE(Pnth in MGS,nI-BUT,and OSDI scores.no adverse events were reported.COnCLUSIOn:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

关键词： meibomian gland dysfunction ILux® ocular surface dry eye

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Experimental implementation of phase triplicator gratings in a spatial light modulator

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Chinese Optics Letters 2024年第2期22卷 64-69页

作者：高尚 maría del mar Sánchez-López Ignacio Moreno Instituto de Bioingeniería Universidad Miguel HernándezElche 03202Spain Departamento de Física Aplicada Universidad Miguel HernándezElche 03202Spain Departamento de Ciencia de Materiales Óptica y Tec.Electr´onicaUniversidad Miguel HernándezElche 03202Spain

In this work,we compare different methods for implementing a triplicator,a phase grating that generates three equiintense diffraction orders.The design with optimal efficiency features a continuous phase profile,which cannot be easily reproduced,and is typically affected by quantization.We compare its performance with binary and sinusoidal phase profiles.We also analyze the effect of quantizing the phase levels.Finally,a random approach is adopted to eliminate the additional harmonic orders.In all cases,a liquid-crystal-on-silicon spatial light modulator is employed to experimentally verify and compare the different approaches.

关键词： diffraction gratings phase modulation triplicator spatial light modulators

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From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： Juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio maría del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean Gabriel Gonzáles-Yovera maría Alejandra Quispe-Flores Luis Alberto Concepción-Urteaga Alejandro Román-González José Paz-Ibarra marcio José Concepción-Zavaleta non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

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Tracking the change in Spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： Paula Fernández González maría José Presno Manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this century.In this paper we pursue two objectives.First,we analyze the evolution of GHG emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining factors.Second,we propose several actions specifically oriented to more tightly controlling the level of emissions.Our results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita effect.We detected somewhat different patterns among the various sectors analyzed.While the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of industry.The carbonization effect was revealed as crucial in the commerce sector.The above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in emissions.Additional efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition Spain GHG emissions

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Experimental model standardizing polyvinyl alcohol hydrogel to simulate endoscopic ultrasound and endoscopic ultrasoundelastography

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World Journal of Gastroenterology 2020年第34期26卷 5169-5180页

作者： Elymir S Galvis-García Sergio Sobrino-Cossío Arturo Reding-Bernal yesica contreras-marín Karina Solórzano-Acevedo Patricia González-Zavala Rosa M Quispe-Siccha Unidad de Endoscopía Gastrointestinal Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Unidad de Endoscopia y Fisiología Digestiva HospitalÁngeles del PedregalMexico 10700Mexico Dirección de Investigación Hospital General de México“Dr.Eduardo Liceaga”Mexico 06720Mexico Unidad Profesional Interdisciplinaria de Biotecnología and Unidad de Investigación y Desarrollo Tecnológico Instituto Politécnico Nacional and Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Instituto de Investigaciones en Materiales and Unidad de Investigación y Desarrollo Tecnológico Universidad Nacional Autónoma de México and Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Unidad de Investigación y Desarrollo Tecnológico Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico

BACKGROUnD Endoscopic ultrasound(EUS)and endoscopic ultrasound elastography(EUS-E)simulation lessens the learning curve;however,models lack realism,diminishing competitiveness.AIM To standardize the mechanical properties of polyvinyl alcohol(PVA)hydrogel for simulating organs and digestive lesions.METHODS PVA hydrogel(Sigma Aldrich,degree of hydrolysis 99%)for simulating EUS/EUS-E lesions was investigated in Unidad de Investigación y Desarrollo Tecnológico at Hospital General de México“Dr.Eduardo Liceaga”,Mexico City.We evaluated physical,contrast,elasticity and deformation coefficient characteristics in lesions,applying Kappa’s concordance and satisfaction questionnaire(Likert 4-points).RESULTS PVA hydrogel showed stable mechanical properties.Density depended on molecular weight(MW)and concentration(C).PVA bblocks with the greatest density showed lowest tensile strength(r=-0.8,P=0.01).Lesions were EUSgraphically visible.Homogeneous and heterogeneous examples were created from PVA blocks or PVA phantoms,exceeding(MW2=146000-186000,C9=15%and C10=20%)with a density under(MW1=85000-124000,C1=7%and C2=9%).We calculated elasticity and deformation parameters of solid(blue)areas,contrasting with the norm(Kappa=0.8;high degree of satisfaction).COnCLUSIOn PVA hydrogels were appropriate for simulating organs and digestive lesions using EUS/EUS-E,facilitating practice and reducing risk.Repetition amplified skills,while reducing the learning curve.

关键词： Endoscopic ultrasound simulators in endoscopy Polyvinyl alcohol Endoscopic ultrasound Endoscopic ultrasound elastography Strain Elasticity

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-martínez mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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