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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti marco Zeppieri Mattia Ghidoni Tamara Ius Alessandro Tel marco maria fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and *** stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and *** studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular *** mechanisms can involve different cellular pathways,most of which have been recently reported in the *** progress,targeted therapeutic approaches lack consensus due to GSCs’high *** To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying *** A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,*** search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text *** them,201 were deemed eligible after excluding 168 for various *** temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma *** analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance *** molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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Current status and future perspectives on stem cell transplantation for spinal cord injury

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World Journal of Transplantation 2024年第1期14卷 189-209页

作者： Edoardo Agosti marco Zeppieri Andrea Pagnoni marco maria fontanella Alessandro Fiorindi Tamara Ius Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Department of Medical and Surgical Specialties Radiological Sciencesand Public HealthUniversity of BresciaBrescia 25123BSItaly Neurosurgery Unit Head-Neck and NeuroScience DepartmentUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and *** research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational *** situation prompts inquiries regarding the readiness for clinical *** To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for *** A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,*** search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of *** In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text *** them,236 were deemed eligible after excluding 170 for various *** studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration ***-up durations averaged around 84.4 *** 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to *** improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell *** In

关键词： Spinal cord injury Stem cell therapy Adverse events Functional outcomes Systematic review

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Quantitative comparison of cranial approaches in the anatomy laboratory: A neuronavigation based research method

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World Journal of Methodology 2017年第4期7卷 139-147页

作者： Francesco Doglietto Jimmy Qiu Mayoorendra Ravichandiran Ivan Radovanovic Francesco Belotti Anne Agur Gelareh Zadeh marco maria fontanella Walter Kucharczyk Fred Gentili Neurosurgery Unit Department of Medical and Surgical Specialties Radiological Sciences and Public Health University of Brescia Division of Neuroradiology Departments of Medical Imaging and Surgery University Health Network Division of Ana-tomy Department of Surgery University of Toronto Division of Neurosurgery Toronto Western Hospital Department of Surgery University Health Network

AIM To describe the development and validation of a novel neuronavigation-based method, which allows the quan-tification of the anatomical features that define an approach, as well as real-time visualization of the surgical pyramid. METHODS The method was initially developed with commerciallyavailable hardware for coordinate collection(a digitizer and a frameless navigation system) and software for volume rendering; dedicated neuronavigation software(ApproachV iewer, part of GTx-UHN) was then developed. The accuracy of measurements and the possibility of volumetric rendering of surgical approaches simulated in a phantom were compared among three different methods and commercially-available radiological software. In the anatomy laboratory, ApproachV iewer was applied to the comparative quantitative analysis of multiple neurosurgical approaches and was used by many surgeons who were untrained for the research *** The accuracy of ApproachV iewer is comparable to commercially-available radiological software. In the anatomy laboratory, the method appears versatile. The system can be easily used after brief training. ApproachV iewer allows for real-time evaluation and comparison of surgical approaches, as well as post-dissection analyses of collected data. The accuracy of the method depends on the navigation registration: with a 1-2 mm registration error, it is adequate for evaluation and comparison of most neurosurgical *** This new research method and software allows semiautomated visualization, quantification, and comparison of neurosurgical approaches in the anatomy laboratory.

关键词： Anatomical study Comparison Neurosurgical approach Quantification Research method 3D rendering

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Effect of Milling and Parboiling Processes on Arsenic Species Distribution in Rice Grains

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Rice science 2021年第4期28卷 402-408,I0035-I0037页

作者： maria Chiara fontanella maria Martin Daniele TENNI Gian maria Beone marco Romani Department for Sustainable Food Process Catholic University of Sacred Heart of PiacenzaPiacenza 29100Italy Department of Agricultural Forest and Food SciencesUniversity of TorinoTorino 10095Italy Rice Research Center National Rice BoardCastello d’Agogna 27030Italy

This study identified the role of milling and parboiling on arsenic(As)content and its species in large numbers of rice *** As contents were 108±33μg/kg in polished rice grains(PR),159±46μg/kg in unpolished rice grains(UR),145±42μg/kg in parboiled polished rice grains(PPR)and 145±44μg/kg in parboiled unpolished rice grains(PUR).The percentages of inorganic As(iAs)were 66%±8%in PR and from 72%to 77%in other grain *** polishing process reduced the As content in the rice grains,removing outer part of the UR with high amount of As,whereas the parboiling technique transferred the semimetal content within the *** As and iAs contents were not significantly different in UR,PPR and PUR,homogenizing its distribution inside the *** results allowed to understand how different operations affect As fate and its chemical forms in grains.

关键词： rice arsenic inductively coupled plasma-mass spectrometer milling parboiling laser ablation

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Can neck swelling lead to spinal cord compression?

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World Journal of Clinical Cases 2013年第1期1卷 56-58页

作者： Emanuele Costi Elena Roca Fabio Spanu Federico Nicolosi Giovanni Nodari marco fontanella Pier Paolo Panciani Department of Neuroscience Division of Neurosurgery University of Brescia 25123 Brescia Italy Department of Neuro-science Division of Neurosurgery University of Torino 10126 Torino Italy

Spinal cord compression(SCC) caused by cervical spinal canal invasion of a pulmonary sarcomatoid carcinoma metastasis has never been reported previously. A 59-year-old man, with a history of pulmonary carcinosarcoma, developed over several weeks important neck swelling. Admitted to our division with severe tetraparesis he underwent a cervical spine computed tomography scan that showed a large cervical mass measuring 11 cm × 27 cm × 17 cm with SCC, extending from the occiput to C7. Emergency spinal cord decompression was performed leading to minor neurological improvement. Poor outcome was due to the unusual clinical sign that led to late diagnosis and treatment.

关键词： Carcinosarcoma Spinal cord compression Spine surgery Tetraparesis Pulmonary sarcomatoid carcinoma

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CD44v8-10 is a marker for malignant traits and a potential driver of bone metastasis in a subpopulation of prostate cancer cells

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Cancer Biology & Medicine 2021年第3期18卷 788-807页

作者： Rosaria A.fontanella Silvia Sideri Chiara Di Stefano Angiolina Catizone Silvia Di Agostino Daniela F.Angelini Gisella Guerrera Luca Battistini Giulia Battafarano Andrea Del Fattore Antonio Francesco Campese Fabrizio Padula Paola De Cesaris Antonio Filippini Anna Riccioli Department of Anatomy HistologyForensic Medicine and OrthopaedicsUnit of Histology and Medical EmbryologySapienza UniversityRome 00161Italy Department of Health Sciences School of Medicine-"Magna Graecia"University of Catanzaro Catanzaro 88100Italy IRCCS Fondazione Santa Lucia Rome 00143 Bone Physiopathology Research Unit Genetics and Rare Diseases Research DivisionBambino GesùChildren’s HospitalIRCCSRome 00146Italy Department of Molecular Medicine Sapienza UniversityRome 00161Italy Department of Life Health and Environmental SciencesUniversity of L’AquilaL'Aquila 67100Italy

Objective:Bone metastasis is a clinically important outcome of prostate carcinoma(PC).We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell *** cells,originated from the spontaneous conversion of a CD44-negative subpopulation,stably express the CD44 v8-10 isoform(CD44 v8-10 pos)and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44 v8-10 ***:Flow cytometry,enzyme-linked immunoassay,immunofluorescence,and Western blot were used for phenotypic and immunologic ***-time quantitative polymerase chain reaction and functional assays were used to assess ***:Analysis of epithelial–mesenchymal transition markers showed that CD44 v8-10 pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry,acquiring bone cell phenotypic and behavioral *** of specific si RNA evidenced the ability of CD44 v8-10 variant to confer osteomimetic features,hence the potential to form bone-specific ***,the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a *** we report that CD44 v8-10 pos cells express programmed death ligand 1,a negative regulator of anticancer immunity,and secrete exceptionally high amounts of interleukin-6,favoring osteoclastogenesis and immunosuppression in bone ***,we identified a novel pathway activated by CD44 v8-10,involving tafazzin(TAZ)and likely the Wnt/TAZ axis,known to play a role in upregulating osteomimetic ***:CD44 v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone.A novel link between TAZ and CD44 v8-10 is also shown.

关键词： Metastasis epithelial phenotype EMT MET IL-6 TAZ

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Viticultural Performance of Merlot and Cabernet Sauvignon （Vitis vinifera L.） Cultivated in High Altitude Regions of Southern Brazil

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Journal of Life Sciences 2015年第9期9卷 399-410页

作者： Jaqueline Nogueira Muniz Suzeli Simon Alberto fontanella Brighenti Luciane Isabel Malinovski Carolina Pretto Panceri Gabriella Vanderlinde Juliana Welter Debora Dal Zotto Aparecido Lima da Silva Santa Catarina Federal University Plant Genetic Resources Post Graduate Program Rod. Admar Gonzaga 1346 ItacorubiFlorian6polis 88034-001 SC Brazil Santa Catarina State Agricultural Research and Rural Extension Agency EPAGRI Rua Josd Arafijo Lima 102 CEP S~oJoaquim 88600-000 SC Brazil Santa Catarina Federal University Food Science Post Graduate Program Rod. Admar Gonzaga 1346 CEP FIorian6polis88034-001 SC Brazil Santa Catarina Federal University Agronomy College Rod. Admar Gonzaga 1346 Itaeorubi Florian6polis 88034-001 SC Brazil

Different studies show that the altitude regions of the State of Santa Catarina have great potential for the production of grapevine varieties. The aim of this study was to characterize the phenological development, determine the thermal requirements in degree-days (DD), the index heliothermic (IH) and climatic variables during the vegetative and productive development of varieties Merlot and Cabernet Sauvignon grown in Campo Belo do Sul (27°40′04″ S, 50°44′48″ W, altitude 950 m a. s. l.) and S?o Joaquim (28°15′13″ S, 49°57′02″ W, altitude 1,400 m a. s. l.) during 2012/2013 cycle. Phenological stages evaluated were bud break, full bloom, veraison and maturity. Higher temperatures, global radiation, PAR and lower volumes of rainfall were the main climatic parameters that differentiated Campo Belo do Sul from S?o Joaquim. Due to occurrence of higher temperatures, Campo Belo do Sul presented thermal summation around 40% higher than S?o Joaquim. The low temperatures of S?o Joaquim extended the period of grape ripening and were responsible for the highest levels of titratable acidity and the higher concentrations of anthocyanins and total polyphenols in both varieties. The results show that in the altitude ranges studied (900 and 1400 m), climatic behavior and viticultural performance of Cabernet Sauvignon and Merlot were suitable for producing quality wines.

关键词：高海拔地区葡萄品种赤霞珠栽培表现西南部梅生产潜力发育程度

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干扰素诱导猪繁殖与呼吸综合征病毒候选疫苗引发猪对异源美洲型毒株VR-2385攻毒保护的研究

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中国畜牧兽医 2017年第1期44卷 302-302页

作者： fontanella E 董晓云

通过接种疫苗实现猪对猪繁殖与呼吸综合征病毒（PRRSV）的持续保护仍较困难。最近研究发现干扰素诱导的PRRSV疫苗候选株A2MC2可减毒并可诱导机体产生中和抗体。本研究旨在确定A2MC2第90代毒株（A2P90）保护猪抵抗中毒性PRRSV毒株VR-238... 详细信息

通过接种疫苗实现猪对猪繁殖与呼吸综合征病毒（PRRSV）的持续保护仍较困难。最近研究发现干扰素诱导的PRRSV疫苗候选株A2MC2可减毒并可诱导机体产生中和抗体。本研究旨在确定A2MC2第90代毒株（A2P90）保护猪抵抗中毒性PRRSV毒株VR-2385（与A2MC2核苷酸同源性为92．3％）和高毒性非典型PRRSV毒株MN184（与A2MC2核苷酸同源性为84．5％）的功效。将40只3周龄的猪随机分为5组，包括阴性对照组（未接种疫苗，未攻毒）、VAC—VR2385组（接种疫苗，用VR-2385攻毒）、VR2385组（用VR-2385攻毒）、VAC-MN184组（接种疫苗，用MN184攻毒）和MN184组（用MN184攻毒）。3周龄接种疫苗，8周龄攻毒。接种猪中均未检测到病毒血症，然而，在攻毒时，用ELISA方法检测到15／16接种疫苗的猪出现血清转化。并具有针对同源毒株的中和抗体，其滴度范围为8-128。感染毒株VR-2385导致轻度至中度的临床疾病和病变。攻毒后9d，与VR2385组（用VR-2385攻毒）相比，VAC—VR2385组（接种疫苗，用VR-2385攻毒）PRRSV病毒血症和鼻甲骨纤毛脱落显著降低，肉眼可见的肺脏损伤显著减少，且平均日增重显著增加。无论接种状况如何，用MN184攻毒可导致猪出现中度至严重的临床疾病和病变，然而，与未接种疫苗的猪相比，接种疫苗组猪在攻毒后5d鼻甲骨纤毛脱落显著降低。本试验结果显示，A2P90疫苗株是减毒的，未检测到鼻甲骨纤毛脱落，可提高平均日增重，且通过减少病毒载量和肉眼可见的肺脏损伤对经VR-2385攻毒的猪提供保护。下一步工作将研究不同的疫苗接种和攻毒方案，包括途径、剂量、时间和毒株。

关键词：功效 PRRSV 猪繁殖与呼吸综合征病毒(PRRSV) 疫苗

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Boceprevir or telaprevir in hepatitis C virus chronic infection:The Italian real life experience

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World Journal of Hepatology 2016年第22期8卷 949-956页

作者： Antonio Ascione Luigi Elio Adinolfi Pietro Amoroso Angelo Andriulli Orlando Armignacco Tiziana Ascione Sergio Babudieri Giorgio Barbarini Michele Brogna Francesco Cesario Vincenzo Citro Ernesto Claar Raffaele Cozzolongo Giuseppe D’Adamo Emilio D’Amico Pellegrino Dattolo Massimo De Luca Vincenzo De maria Massimo De Siena Giuseppe De Vita Antonio Di Giacomo Rosanna De marco Giorgio De Stefano Giulio De Stefano Sebastiano Di Salvo Raffaele Di Sarno Nunzia Farella Laura Felicioni Basilio Fimiani Luca fontanella Giuseppe Foti Caterina Furlan Francesca Giancotti Giancarlo Giolitto Tiziana Gravina Barbara Guerrera Roberto Gulminetti Angelo Iacobellis Michele Imparato Angelo Iodice Vincenzo Iovinella Antonio Izzi Alfonso Liberti Pietro Leo Gennaro Lettieri Ileana Luppino Aldo Marrone Ettore Mazzoni Vincenzo Messina Roberto Monarca Vincenzo Narciso Lorenzo Nosotti Adriano maria Pellicelli Alessandro Perrella Guido Piai Antonio Picardi Paola Pierri Grazia Pietromatera Francesco Resta Luca Rinaldi Mario Romano Angelo Rossini Maurizio Russello Grazia Russo Rodolfo Sacco Vincenzo Sangiovanni Antonio Schiano Antonio Sciambra Gaetano Scifo Filomena Simeone Annarita Sullo Pierluigi Tarquini Paolo Tundo Alfredo Vallone Depart-ment of Medicine Center for Liver Diseases "Buon Consiglio" -Fatebenefratelli Hospital Internal Medicine Unit Second University of Naples VI Division of Infectious Diseases Cotugno Hospital AORN "Ospedali dei Colli" Division of Gastro- enterology Casa Sollievo Sofferenza Hospital IRCCS Division of Infectious Diseases Belcolle Hospital IX Division of Infectious Diseases Cotugno Hospital AORN "Ospedali dei Colli" Clinical of Infectious Disease University of Sassari Infectious Disease IRCCS San Matteo Division of Infectious Diseases and Liver Unit "G. Iazzolino" Hospital Division of Infectious Diseases "Annunziata" Hospital Depart-ment of Internal Medicine Umberto I Hospital Internal Medicine Ospedale Evangelico Villa Betania Division of Gastroenterology IRCCS "S.de Bellis" Hospital Internal Medicine Unit Pescara-Penne Hospital Gastroenterology Unit Marcianise Hospital Liver Unit AORN Cardarelli Liver Unit Policlinico "Mater Domini" Service of Medical Day Hospital "Rummo" Hospital Internal Medicine Regina Margherita Hospital Division of Gastroenterology "Annunziata" Hospital Infectious Disease Matera Hospital First Division of Infectious Diseases Cotugno Hospital AORN "Ospedali dei Colli" Division of Infectious Diseases AO Melacrino- Bianchi-Morelli Infectious and Tropical Disease Policlinico Umberto I Division of Infectious Disease Maria SS Addolorata Hospital Division of Infectious Diseases S. Anna and S. Sebastiano Hospital Outpatients Service for Liver Diseases "Loreto Crispi" Hospital V Division of Infectious Diseases Cotugno Hospital AORN "Ospedali dei Colli" Department of Medical Surgical Neurological Geriatric and Metabolic Sciences Second Univer-sity of Naples Liver Unit Policlinico Casilino Medicine and Health Unit for Prisoners Belcolle Hospital Internal Medicine Unit "Ascalesi" Hospital Gastrointestinal and Liver Department National Institute for Health Migration and Poverty Liver Unit Azienda Ospedaliera San Camillo Forlanini VII Division of Infectious Diseases

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

关键词： Boceprevir Telaprevir Chronic hepatitis Antiviral therapy Peg-interferon Ribavirin

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协会是颠覆性领导的完美舞台

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中国社会组织 2019年第8期 34-34页

作者：詹妮弗·方塔内拉国际研究协会

颠覆性领导指的是处于领导地位的人,他们总是在寻找更好的解决办法,以及从整体上改善流程和业务的方法,并且不怕通过改变事情来获得必要的结果,通常在商业环境中使用。那么,颠覆性领导是否能够为协会服务呢?

关键词：领导地位颠覆性协会舞台商业环境

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