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Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

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World Journal of Gastroenterology 2019年第30期25卷 4172-4180页

作者： Francesco Baratta Daniele Pastori Domenico Ferro Giovanna Carluccio giulia tozzi Francesco Angelico Francesco Violi Maria Del Ben Department of Internal Medicine and Medical Specialties Sapienza-University of RomeRome 00155Italy Hepatogastroenterology and Nutrition Unit-Pediatric Department Bambino GesùChildren’s HospitalRome 00156Italy Department of Public Health and Infectious Disease Sapienza-University of RomeRome 00161Italy

Lysosomal acid lipase(LAL)plays a key role in intracellular lipid *** LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage *** liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL *** contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A *** the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the *** with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic *** cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL *** findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of ***,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Lysosomal acid lipase Cirrhosis Wolman disease Cholesterol ester storage disease

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A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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The loaded matrix:neurotrophin-enriched hydrogels for stem cell brain repair in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2315-2316页

作者： giulia Comini Eilis Dowd Pharmacology&Therapeutics University of GalwayGalwayIreland

More than 200 years after Parkinson's disease was first described by the English surgeon whose name would eventually be given to the condition,available treatments remain purely symptomatic,leaving a critical unmet cl... 详细信息

关键词： clinical loaded eventually

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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania Department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico I.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology Service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging *** and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous *** effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory *** mechanisms which underpin the integration of these multisensory signals are the principal topic of the present *** multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older *** emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and *** the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s *** also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older ***,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

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Multilevel Techniques for the Solution of HJB Minimum-Time Control Problems

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Journal of Systems Science & Complexity 2021年第6期34卷 2069-2091页

作者： CIARAMELLA Gabriele FABRINI giulia Department of Mathematics and Statistics University of KonstanzKonstanz 78464Germany

The solution of minimum-time feedback optimal control problems is generally achieved using the dynamic programming approach,in which the value function must be computed on numerical grids with a very large number of *** numerical strategies,such as value iteration(VI)or policy iteration(PI)methods,become very inefficient if the number of grid points is *** is a strong limitation to their use in real-world *** address this problem,the authors present a novel multilevel framework,where classical VI and PI are embedded in a full-approximation storage(FAS)*** fact,the authors will show that VI and PI have excellent smoothing properties,a fact that makes them very suitable for use in multilevel ***,a new smoother is developed by accelerating VI using Anderson’s extrapolation *** effectiveness of our new scheme is demonstrated by several numerical experiments.

关键词： Anderson acceleration FAS Hamilton-Jacobi equation minimum-time problem multi-level acceleration methods policy iteration value iteration

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Tunable ferroelectricity in oxygen-deficient perovskites with Grenier structure

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npj Computational Materials 2023年第1期9卷 118-125页

作者： Yongjin Shin giulia Galli Pritzker School of Molecular Engineering University of ChicagoChicagoIL 60637USA Department of Chemistry University of ChicagoChicagoIL 60637USA Center for Molecular Engineering and Materials Science Division Argonne National LaboratoryLemontIL 60439USA

Using first-principles calculations,we predict that tunable ferroelectricity can be realized in oxide perovskites with the Grenier structure and ordered oxygen ***,we show that R_(1/3)A_(2/3)FeO_(2.67) solids(where R is a rare-earth ion and A an alkaline-earth cation)exhibit polar phases,with a spontaneous polarization tunable by an appropriate choice of R and *** find that larger cations combined with small R elements lead to a maximum in the polarization and to a minimum in the energy barriers required to switch the sign of the *** arises from cooperative distortions of octahedral and tetrahedral units,where a combination of rotational and sliding modes controls the emergence of polarization within three-dimensional connected *** results indicate that polar Grenier phases of oxide perovskites are promising materials for microelectronic applications and,in general,for the study of phenomena emerging from breaking inversion symmetry in solids.

关键词： polarization ferroelectric structure

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Deep convolutional neural network for multi-level non-invasive tunnel lining assessment

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Frontiers of Structural and Civil Engineering 2022年第2期16卷 214-223页

作者： Bernardino CHIAIA giulia MARASCO Salvatore AIELLO Department of Structural Geotechnical and Building EngineeringPolytechnic University of TurinTorino10129Italy

In recent years,great attention has focused on the development of automated procedures for infrastructures *** efforts have aimed at greater speed and reliability compared to traditional methods of assessing structural *** paper proposes a multi-level strategy,designed and implemented on the basis of periodic structural monitoring oriented to a cost-and time-efficient tunnel control *** strategy leverages the high capacity of convolutional neural networks to identify and classify potential critical *** a supervised learning framework,Ground Penetrating Radar(GPR)profiles and the revealed structural phenomena have been used as input and output to train and test such ***-based analysis and integrative investigations involving video-endoscopy,core drilling,jacking and pull-out testing have been exploited to define the structural conditions linked to GPR profiles and to create the *** degree of detail and accuracy achieved in identifying a structural condition is *** a result,this strategy appears of value to infrastructure managers who need to reduce the amount and invasiveness of testing,and thus also to reduce the time and costs associated with inspections made by highly specialized technicians.

关键词： concrete structure GPR damage classification convolutional neural network transfer learning

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Understanding the metal-to-insulator transition in La_(1−x)Sr_(x)CoO_(3−δ) and its applications for neuromorphic computing

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npj Computational Materials 2020年第1期6卷 261-269页

作者： Shenli Zhang giulia Galli Pritzker School of Molecular Engineering The University of ChicagoChicagoILUSA Argonne National Laboratory ArgonneILUSA Department of Chemistry The University of ChicagoChicagoILUSA

Transition metal oxides that exhibit a metal-to-insulator transition(MIT)as a function of oxygen vacancy concentration are promising systems to realize energy-efficient platforms for neuromorphic ***,the current lack of understanding of the microscopic mechanism driving the MIT hinders the realization of effective and stable *** we investigate defective cobaltites and we unravel the structural,electronic,and magnetic changes responsible for the MIT when oxygen vacancies are introduced in the *** show that,contrary to accepted views,cooperative structural distortions instead of local bonding changes are responsible for the MIT,and we describe the subtle interdependence of structural and magnetic ***,we present a model,based on first principles,to predict the required electric bias to drive the transition,showing good agreement with available measurements and providing a paradigm to establish design rules for low-energy cost devices.

关键词： transition insulator hinder

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Vibrationally resolved optical excitations of the nitrogen-vacancy center in diamond

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npj Computational Materials 2022年第1期8卷 2258-2266页

作者： Yu Jin Marco Govoni giulia Galli Department of Chemistry University of ChicagoChicagoIL60637USA Pritzker School of Molecular Engineering University of ChicagoChicagoIL60637USA Materials Science Division and Center for Molecular Engineering Argonne National LaboratoryLemontIL60439USA

A comprehensive description of the optical cycle of spin defects in solids requires the understanding of the electronic and atomistic structure of states with different spin multiplicity,including singlet states which are particularly challenging from a theoretical *** present a general framework,based on spin-flip time-dependent density function theory,to determine the excited state potential energy surfaces of the many-body singlet states of spin defects;we then predict the vibrationally resolved absorption spectrum between singlet shelving states of a prototypical defect,the nitrogen-vacancy center in *** results,which are in very good agreement with experiments,provide an interpretation of the measured spectra and reveal the key role of specific phonons in determining absorption processes,and the notable influence of non-adiabatic *** insights gained from our calculations may be useful in defining strategies to improve infrared-absorption-based magnetometry and optical pumping *** theoretical framework developed here is general and applicable to a variety of other spin defects and materials.

关键词： vacancy resolved singlet

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