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Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner

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Cellular & Molecular Immunology 2021年第2期18卷 415-426页

作者： Morten Orebo Holmström Rasmus Erik Johansson Mortensen Angelos Michail Pavlidis Evelina Martinenaite Stine Emilie Weis-Banke Mia Aaboe-Jørgensen Simone Kloch Bendtsen Özcan Met Ayako Wakatsuki Pedersen marco donia Inge Marie Svane Mads Hald Andersen Department of Oncology National Center for Cancer Immune TherapyCopenhagen University HospitalHerlevDenmark IO Biotech ApS CopenhagenDenmark Institute for Immunology and Microbiology Copenhagen UniversityCopenhagenDenmark

Transforming growth factor-beta(TGFβ)is a highly potent immunosuppressive *** TGFβis a tumor suppressor in early/premalignant cancer lesions,the cytokine has several tumor-promoting effects in advanced cancer;abrogation of the antitumor immune response is one of the most important tumor-promoting *** several immunoregulatory mechanisms have recently been shown to be targets of specific T cells,we hypothesized that TGFβis targeted by naturally occurring specific T cells and thus could be a potential target for immunomodulatory cancer ***,we tested healthy donor and cancer patient T cells for spontaneous T-cell responses specifically targeting 3820-mer epitopes derived from TGFβ*** identified numerous CD4^(+)and CD8^(+)T-cell responses against several epitopes in TGFβ.Additionally,several ex vivo responses were *** enriching specific T cells from different donors,we produced highly specific cultures specific to several TGFβ-derived *** CD8^(+)T-cell clones specific for both a 20-mer epitope and a 9-mer HLA-A2 restricted killed epitope peptide were pulsed in HLA-A2+target cells and killed the HLA-A2+cancer cell lines THP-1 and ***,stimulation of THP-1 cancer cells with cytokines that increased TGFβexpression increased the fraction of killed *** conclusion,we have shown that healthy donors and cancer patients harbor CD4^(+)and CD8^(+)T cells specific for TGFβ-derived epitopes and that cytotoxic T cells with specificity toward TGFβ-derived epitopes are able to recognize and kill cancer cell lines in a TGFβ-dependent manner.

关键词： Immune regulation TGFbeta cancer T cells adaptive immunity

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Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:Delphi consensus study

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World Journal of Gastroenterology 2024年第18期30卷 2467-2478页

作者： Edda Battaglia Luciano Bertolusso marco Del Prete marco Monzani marco Astegiano Gastroenterology Unit ASLTO4Ivrea 10015TurinItaly General Practitioner ASL CN2Alba-Bra 12051CuneoItaly Specialist in Nephrology International Academy of Physiological Regulating Medicine Milan 20100Italy Specialist in Endocrinology Territorial Social and Health Authority of BrianzaMonza 20900Italy Gastroenterology Specialist Retired from Gastroenterology and Hepatology UnitAOU Cittàdella Salute e della ScienzaTurin 10123Italy

BACKGROUND Gastro-esophageal reflux disease(GERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by ***,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for ***,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse *** effective and safe alternative pharmacological tool for GERD is *** the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus *** To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi *** The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of *** Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:Gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)GERD disease;and(2)GERD *** for each of these topics were then formulated and *** Delphi process involved two rounds of questioning submitted to the panel experts using an online *** According to their routinary GERD practice and current clinical evidence,the panel members provided feedback to each questionnaire *** experts evaluated 15 statements and reached consensus on all *** statements regarding the GERD disease showed high levels of

关键词： Gastro-esophageal reflux disease Proton Pump Inhibitors Consensus Nux vomica-Heel Overlapping Decalage

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Microglia out of place—mapping macrophages across the developing human body

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Cellular & Molecular Immunology 2024年第3期21卷 210-212页

作者： Roman Sankowski marco Prinz Institute of Neuropathology Faculty of MedicineUniversity of FreiburgFreiburgGermany Signalling Research Centres BIOsS and CIBSs University of FreiburgFreiburgGermany

Macrophages(MΦs)are versatile cells found in every *** the body,they work tirelessly to maintain *** this end,they are instructed by their respective niches to express organ-specific genes and proteins,resulting in a variety of cell morphologies and highly specialized functions across different tissues[1].A recent study by Wang et *** single-cell RNA sequencing to comprehensively profile human MΦphenotypes across 19 organs between postconception weeks(PCW)4 and 26[2].This study revealed a surprising diversity of these cells and suggests new avenues of research.

关键词： organs instru

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Potential and progress of studying mountain biodiversity by means of butterfly genetics and genomics

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Journal of Genetics and Genomics 2024年第3期51卷 292-301页

作者： Shuting Wang marco Girardello Wei Zhang State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China cE3c-Centre for Ecology Evolution and Environmental Changes/Azorean Biodiversity GroupFaculdade de Ciencias Agrarias e do AmbienteUniversidade dos Açores9700-042 Angra do HeroísmoTerceiraPortugal

Mountains are rich in biodiversity,and butterflies are species-rich and have a good ecological and evolutionary research *** review addresses the potential and progress of studying mountain biodiversity using butterflies as a *** discuss the uniqueness of mountain ecosystems,factors influencing the distribution of mountain butterflies,representative genetic and evolutionary models in butterfly research,and evolutionary studies of mountain biodiversity involving butterfly genetics and ***,we demonstrate the necessity of studying mountain butterflies and propose future *** review provides insights for studying the biodiversity of mountain butterflies as well as a summary of research methods for reference.

关键词： Mountain ecosystem Butterfly Biodiversity Adaptation Genomics Genetics

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Current status of magnetic resonance imaging radiomics in hepatocellular carcinoma:A quantitative review with Radiomics Quality Score

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World Journal of Gastroenterology 2024年第4期30卷 381-417页

作者： Valentina Brancato marco Cerrone Nunzia Garbino marco Salvatore Carlo Cavaliere Department of Information Technology IRCCS SYNLAB SDNNaples 80143Italy Department of Radiology IRCCS SYNLAB SDNNaples 80143Italy

BACKGROUND Radiomics is a promising tool that may increase the value of magnetic resonance imaging(MRI)for different tasks related to the management of patients with hepatocellular carcinoma(HCC).However,its implementation in clinical practice is still far,with many issues related to the methodological quality of radiomic *** To systematically review the current status of MRI radiomic studies concerning HCC using the Radiomics Quality Score(RQS).METHODS A systematic literature search of PubMed,Google Scholar,and Web of Science databases was performed to identify original articles focusing on the use of MRI radiomics for HCC management published between 2017 and *** methodological quality of radiomic studies was assessed using the RQS ***’s correlation(ρ)analysis was performed to explore if RQS was correlated with journal metrics and characteristics of the *** level of statistical significance was set at P<*** One hundred and twenty-seven articles were included,of which 43 focused on HCC prognosis,39 on prediction of pathological findings,16 on prediction of the expression of molecular markers outcomes,18 had a diagnostic purpose,and 11 had multiple *** mean RQS was 8±6.22,and the corresponding percentage was 24.15%±15.25%(ranging from 0.0% to 58.33%).RQS was positively correlated with journal impact factor(IF;ρ=0.36,P=2.98×10^(-5)),5-years IF(ρ=0.33,P=1.56×10^(-4)),number of patients included in the study(ρ=0.51,P<9.37×10^(-10))and number of radiomics features extracted in the study(ρ=0.59,P<4.59×10^(-13)),and time of publication(ρ=-0.23,P<0.0072).CONCLUSION Although MRI radiomics in HCC represents a promising tool to develop adequate personalized treatment as a noninvasive approach in HCC patients,our study revealed that studies in this field still lack the quality required to allow its introduction into clinical practice.

关键词： Hepatocellular carcinoma Systematic review Magnetic resonance imaging Radiomics Radiomics quality score

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Influence of manufacturing process-induced geometrical defects on the energy absorption capacity of polymer lattice structures

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Defence Technology（防务技术） 2024年第5期35卷 47-59页

作者： Alexandre Riot Enrico Panettieri Antonio Cosculluela marco Montemurro Universite de Bordeaux Arts et Metiers Institute of TechnologyCNRSINRABordeaux INPHESAM UniversiteI2M UMR 5295F-33405 TalenceFrance French Atomic Energy Commission Route des GargailsCedexF-33114Le BarpFrance

Modern additive manufacturing processes enable fabricating architected cellular materials of complex shape,which can be used for different *** them,lattice structures are increasingly used in applications requiring a compromise among lightness and suited mechanical properties,like improved energy absorption capacity and specific stiffness-to-weight and strength-to-weight ratios.A dedicated modeling strategy to assess the energy absorption capacity of lattice structures under uni-axial compression loading is presented in this *** numerical model is developed in a non-linear framework accounting for the strain rate effect on the mechanical responses of the lattice *** geometries,i.e.,cubic body centered cell,octet cell,rhombic-dodecahedron and truncated cuboctahedron 2+,are ***,the influence of the relative density of the representative volume element of each geometry,the strain-rate dependency of the bulk material and of the presence of the manufacturing process-induced geometrical imperfections on the energy absorption capacity of the lattice structure is *** main outcome of this study points out the importance of correctly integrating geometrical imperfections into the modeling strategy when shock absorption applications are aimed for.

关键词： Lattice structures Architected cellular materials Dynamic simulation Energy absorption Geometrical imperfection Additive manufacturing

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Inhibition of tubulin detyrosination:a novel strategy to promote central nervous system regeneration

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Neural Regeneration Research 2024年第12期19卷 2557-2558页

作者： Charlotte Zeitler marco Leibinger Dietmar Fischer Center of Pharmacology Institute for PharmacologyMedical Faculty and University of CologneCologneGermany

The adult mammalian central nervous system(CNS) coordinates essential functions such as sensation,movement,autonomic control,thought processes,and ***,injuries or diseases of the CNS are often associated with devastating and permanent functional impairments because damaged axons normally fail to *** insufficient neuron-intrinsic growth capacity and an inhibitory environment at the injury site are the leading causes of this regenerative failure.

关键词： injuries sensation diseases

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Sex-specifc seasonal variations of wild boar distance traveled and home range size

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Current Zoology 2024年第3期70卷 284-290页

作者： Silvia Cavazza Rudy Brogi marco Apollonio Department of Veterinary Medicine University of Sassarivia Vienna 2I-07100 SassariItaly

Distance traveled and home range size describe how animals move in *** seasonal variations of these parameters are important to comprehensively understand animal ecology and its connection with reproductive behavior and energy *** usually estimate the distance traveled as the sum of the straight-line displacements between sampled positions,but this approach is sensitive to the sampling frequency and does not account for the tortuosity of the animal’s *** means of the continuous-time movement modeling which takes into account autocorrelation and tortuosity of movement data,we estimated the distance traveled and monthly home range size of 28 wild boar Sus scrofa and modeled their inter-sexual seasonal *** traveled longer distances and used larger home ranges than females,particularly during the rut in autumn-winter,consistently with the different biological cycles of males and *** enlarged their home ranges during the rut but traveled constant average distances along the year,whereas females traveled shorter distances in correspondence with the peak of food resources and birth periods but exhibited constant home range size across *** differences between the seasonal variation patterns of distance traveled and home range size,observed in both sexes,revealed the complex relationship between these two aspects of spatial behavior and the great opportunity of including both distance traveled and home range size in behavioral ecology *** provided a detailed analysis of wild boar spatial behavior and its relationships with the reproductive cycles of males and females,promoting a deeper comprehension of their behavioral ecology.

关键词： continuous-time ctmm daily range movements spatial behavior Sus scrofa

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Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma:A Western perspective

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World Journal of Gastroenterology 2024年第31期30卷 3635-3639页

作者： marco Biolato Maurizio Pompili Department of Medical and Surgical Sciences CEMAD Digestive Disease CenterFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Department of Translational Medicine and Surgery Catholic University of Sacred HeartRome 00168LazioItaly

Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial *** strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently *** a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety *** results of this study raise several controversial points regarding their applicability in the Western *** the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone ***,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

关键词： Chemotherapeutic drugs Lipiodol Post-embolization syndrome Prevention Prophylaxis

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Optimal orbit transfer of single-tether E-sail with inertially fixed spin axis

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Astrodynamics 2024年第2期8卷 285-295页

作者： Alessandro A.Quarta marco Bassetto Giovanni Mengali Department of Civil and Industrial Engineering University of PisaPisa I-56122Italy

This study analyzes the optimal transfer trajectory of a spacecraft propelled by a spinstabilized electric solar wind sail(E-sail)with a single conducting tether and a spin axis with a fixed direction in an inertial(heliocentric)reference *** approach proposed in this study is useful for rapidly analyzing the optimal transfer trajectories of the current generation of small spacecraft designed to obtain in-situ evidence of the E-sail propulsion *** this context,starting with the recently proposed thrust model for a single-tether E-sail,this study discusses the optimal control law and performance in a typical two-dimensional interplanetary transfer by considering the(binary)state of the onboard electron emitter as the single control *** resulting spacecraft heliocentric trajectory is a succession of Keplerian arcs alternated with propelled arcs,that is,the phases in which the electron emitter is switched *** particular,numerical simulations demonstrated that a single-tether E-sail with an inertially fixed spin axis can perform a classical mission scenario as a circle-to-circle two-dimensional transfer by suitably varying a single control parameter.

关键词： electric solar wind sail(E-sail) single conducting tether fixed inertial spin axis trajectory optimization circle-to-circle coplanar transfer

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