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Targeting menin: a promising therapeutic strategy for susceptible acute leukemia subtypes

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5141-5142页

作者： pietro di Fazio Department of Visceral Thoracic and Vascular SurgeryPhilipps University of MarburgBaldingerstrasse35043MarburgGermany

Two recent studies published in Nature focused on the clinical efficacy of the menin inhibitor revumenib(SNDX-5613)in KMT2A(histone-lysine N-methyltransferase 2A)-rearranged or NPM1(Nucleophosmin1)-mutant acute myeloid leukemia.1,2 These studies indicate that menin inhibition and its acquired resistance to long-term exposure to revuminib are key points for future treatment,emphasizing the role of menin as a challenging and promising target for the current treatment of leukemia.

关键词： acute clinical therapeutic

Synergy of human platelet lysate and laminin to enhance the neurotrophic effect of human adipose-derived stem cells

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Neural Regeneration Research 2022年第10期17卷 2200-2202页

作者： pietro G di Summa Srinivas Madduri Department of Plastic Reconstructive and Hand SurgeryUniversity Hospital of LausanneUniversity of LausanneLausanneSwitzerland Department of Surgery Bioengineering and NeuroregenerationUniversity of GenevaUniversity Hospital GenevaGenevaSwitzerland

Despite the spontaneous regenerative capacity of the peripheral nervous system,clinical nerve repair often results in poor functional recovery with the high socio-economic *** presence of peripheral nerve injuries and when distal nerve transfers are not possible,nerve autografts,are the solution of choice to cross a critical nerve ***,these are associated with donor site morbidity and offer only suboptimal functional ***,the need to improve the rate of effective regeneration has directed research attention towards stem cell therapy and nerve tissue engineering.

关键词： injuries donor spite

p-Multilevel Preconditioners for HHO discretizations of the Stokes Equations with Static Condensation

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Communications on Applied Mathematics and Computation 2022年第3期4卷 783-822页

作者： Lorenzo Botti Daniele A.di pietro Department of Engineering and Applied Sciences University of BergamoBergamoItaly IMAG Univ MontpellierCNRSMontpellierFrance

We propose a p-multilevel preconditioner for hybrid high-order(HHO)discretizations of the Stokes equation,numerically assess its performance on two variants of the method,and compare with a classical discontinuous Galerkin *** efficient implementa-tion is proposed where coarse level operators are inherited using L2-orthogonal projec-tions defined over mesh faces and the restriction of the fine grid operators is performed recursively and *** h-and k-dependency are investigated tackling two-and three-dimensional problems on standard meshes and graded *** the two HHO for-mulations,featuring discontinuous or hybrid pressure,we study how the combination of p-coarsening and static condensation influences the V-cycle *** particular,two dif-ferent static condensation procedures are considered for the discontinuous pressure HHO variant,resulting in global linear systems with a different number of unknowns and matrix non-zero ***,we show that the efficiency of the solution strategy might be impacted by static condensation options in the case of graded meshes.

关键词： Stokes equations divergence free constraint Hybrid high-order discontinuous Galerkin p-multigrid Static condensation

A time fractional model to represent rainfall process

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Water Science and Engineering 2014年第1期7卷 32-40页

作者： Jacques GOLDER Maminirina JOELSON Marie-Christine NEEL Liliana di pietro Department of Physics University of Avignon Mediterranean Environment and Agro-Hydro System Modelisation Laboratory French National Institute for Agricultural Research

This paper deals with a stochastic representation of the rainfall process. The analysis of a rainfall time series shows that cumulative representation of a rainfall time series can be modeled as a non-Gaussian random walk with a log-normal jump distribution and a time-waiting distribution following a tempered a-stable probability law. Based on the random walk model, a fractional Fokker-Planck equation （FFPE） with tempered a-stable waiting times was obtained. Through the comparison of observed data and simulated results from the random walk model and FFPE model with tempered a-stable waiting times, it can be concluded that the behavior of the rainfall process is globally reproduced, and the FFPE model with tempered a-stable waiting times is more efficient in reproducing the observed behavior.

关键词： rainfall process heavy-tailed probability distribution tempered a-stable probability law log-normal law Hurst exponent continuous time random walk model fractional Fokker-Planck equation

Microglia depletion as a therapeutic strategy:friend or foe in multiple sclerosis models?

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Neural Regeneration Research 2023年第2期18卷 267-272页

作者： Victoria Sofia Berenice Wies Mancini Anabella Ayelen di pietro Laura Andrea Pasquini Universidad de Buenos Aires Facultad de Farmacia y BioquímicaDepartamento de Química BiológicaCátedra de Química Biológica PatológicaBuenos AiresArgentina Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Química y Fisicoquímica Biológicas Prof.Dr.Alejandro C.PaladiniFacultad de Farmacia y BioquímicaBuenos AiresArgentina

M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa *** activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and *** though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor *** can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate *** A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and *** r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the *** colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system ***,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the *** this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of micr

关键词： astrocytes colony-stimulating factor-1 receptor inhibition cuprizone demyelnation microglia multiple sclerosis neurodegeneration

Hepatocellular carcinoma and liver transplant: beyond the Milan criteria and the risk of "short-blanket" syndrome

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 518-521页

作者： Stefano Gitto Stefano di Sandro Paolo Magistri pietro Andreone Fabrizio di Benedetto Department of Experimental and Clinical Medicine University of FlorenceFlorenceItaly Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit AOU di Modena and University of Modena and Reggio EmiliaModenaItaly Internal and Metabolic Medicine AOU di Modena and University of Modena and Reggio EmiliaModenaItaly

Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in the selection of these patients(2).Therefore,basing on MC,the 5-year survival rate after LT could increase to 70%,with a HCC recurrence rate lower than 10%(2).Despite that,too many patients affected by HCC may not benefit from LT due to a tumor stage beyond the selection *** the last two decades,authors and physicians tried to overcome the MC exploring the opportunity to safely transplant patients beyond(3).Notably,the donor shortage and the competition between patients listed due to HCC and those listed for other indications,force physicians in selecting candidates with the best transplant benefit(3).

关键词： beyond listed overcome

Assessing spatial variability and erosion susceptibility of soils in hilly agricultural areas in Southern Italy

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International Soil and Water Conservation Research 2020年第4期8卷 354-362页

作者： Carmen Maria Rosskopf Erika di Iorio Luana Circelli Claudio Colombo pietro P.C.Aucelli University of Molise Department of Biosciences and Territoryc.da Fonte Lappone86090PescheISItaly University of Molise Department of AgriculturalEnvironmental and Food SciencesVia F.De Sanctis186100CampobassoCBItaly University of Napoli"Parthenope" Department of Environmental SciencesCentro Direzionale Isola C/480143NapoliItaly

Soil erosion is one of the main environmental problems in the Mediterranean *** problem is becoming even more important especially in Italy,in the Apennines,where severe erosive processes occur due to the action of concentrated running *** erodibility(K-Factor)of a soil,estimated using the Revised Universal Soil Loss Equation(RUSLE),is a measure of its susceptibility to erosion and depends on several soil properties such as organic matter,texture and permeability and *** assess the spatial variability of soil properties and soil erodibility in hilly agricultural areas and to investigate the relationships between soil features and landscape morphodynamics,a detailed study in Molise region(southern Italy),in a small drainange basin located along its hilly Adriatic flank,was carried *** this catchment,63 topsoil samples(A horizons)were collected and 10 soil profiles,forming a catena crossing 3 land units,were *** calculated K-Factors ranges between 0.012 and 0.048 t ha h ha-1 MJ-1 mm-1 indicating a complex spatial distribution,due to the several local pedological and geomorphological factors affecting soil *** results give clear evidence about the relationships among soil characteristics,soil erodibility and landscape morpho-dynamics(land units).Comparing the soil loss rates estimated for the study area with those reported in literature,a good correspondence can be observed only for the more stable land unit,not characterized by intense erosive *** proposed methodology is suitable to highlight areas characterized by similar morphodynamics features,and comparable soil erodibility,for a more effective spatialization of K factor.

关键词： Hillslope morphodynamics RUSLE equation K factor Mediterranean region Soil catena Land units

Quantitative imaging of the complexity in liquid bubbles’evolution reveals the dynamics of film retraction

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Light(Science & Applications) 2019年第1期8卷 1021-1032页

作者： Biagio Mandracchia Zhe Wang Vincenzo Ferraro Massimiliano Maria Villone Ernesto di Maio Pier Luca Maffettone pietro Ferraro CNR-ISASI Istituto di Scienze Applicate e Sistemi Intelligenti“E.Caianiello”del CNRVia Campi Flegrei 3480078 PozzuoliNapoliItaly College of Applied Sciences Beijing University of Technology100124 BeijingChina dipartimento di Ingegneria Chimica dei Materiali e della Produzione IndustrialeUniversita di Napoli FedericoⅡPiazzale Tecchio 8080125 NapoliItaly

The dynamics and stability of thin liquid films have fascinated scientists over many *** film flows are central to numerous areas of engineering,geophysics,and biophysics and occur over a wide range of lengths,velocities,and liquid property *** spite of many significant developments in this area,we still lack appropriate quantitative experimental tools with the spatial and temporal resolution necessary for a comprehensive study of film *** propose tackling this problem with a holographic technique that combines quantitative phase imaging with a custom setup designed to form and manipulate *** results,gathered on a model aqueous polymeric solution,provide unparalleled insight into bubble dynamics through the combination of a full-field thickness estimation,threedimensional imaging,and a fast acquisition *** unprecedented level of detail offered by the proposed methodology will promote a deeper understanding of the underlying physics of thin film dynamics.

关键词： film dynamics liquid

Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第42期20卷 15518-15531页

作者： Giulia Paolella Claudia Mandato Luca Pierri Marco Poeta Martina di Stasi pietro Vajro Department of Medicine and Surgery University of Salerno Pediatrics of AORN Santobono-Pausilipon ELFID European Laboratory for the Investigation of Food Induced disease

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

关键词： Probiotics Gut-liver axis Intestinal microbiota Barrier function Small intestinal bacterial overgrowth Bacterial translocation Non-alcoholic fatty liver disease