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Commercialization of disruptive innovations:Literature review and proposal for a process framework

International Journal of Innovation Studies 2021年第3期5卷 127-144页

作者： javier nieto cubero Saheed Adebayo Gbadegeshin Carolina Consolación Design Processes Research Group EINACentre Universitari de Disseny I ArtUniversitat Autonoma De Barcelona08017BarcelonaSpain Department of Management and Entrepreneurship Turku School of EconomicsUniversity of Turku20014TurkuFinland Department of Management ETSEBCUniversitat Politecnica De Catalunya08034BarcelonaSpain

The challenges of disruptive innovations have gained significant attention from both academics and practitioners,commercialization being one of the most critical *** the same time,however,it is the less studied area of disruptive ***,this article examined scholarly papers on the commercialization of disruptive innovations through a multidisciplinary systematic literature *** resulted in the analysis of 64 high-quality peer-reviewed academic *** analysis highlighted the commercialization models and main constructs that are affecting the commercialization process:market orientation,market learning,user’s involvement,market configuration,adoption networks and stakeholders,and innovation *** study evidences how commercialization has evolved from a later stage in innovation to influence even the early phases of innovation,characterized in turn by exploration,learning and ecosystem creation ***,the analysis led to a proposition that established an integrated commercialization model for high uncertainty *** model has three phases:1)Concept/value proposition validation,2)Business model validation&Market creation,and 3)Creating sales in the majority ***,the article contributes to a better understanding of commercialization processes in high uncertainty innovations,bridging also the academic-practitioner divide.

关键词： Disruptive innovation Radical innovation Emerging technologies Commercialization process Market creation Scale-up Lean start-up

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Extracellular vesicles in liver disease and beyond

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World Journal of Gastroenterology 2018年第40期24卷 4519-4526页

作者： Laura Morán Francisco javier cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain

Extracellular vesicles(EVs) are membrane-derived vesicles which can be released by different cell types, including hepatocytes, hepatic stellate cells and immune cells in normal and pathological conditions. EVs carry lipids, proteins, coding and non-coding RNAs and mitochondrial DNA causing modifications on the recipient cells. These vesicles are considered potential biomarkers and therapeutic agents for human diagnostic and prognostic due to their function as intercellular mediators of cell-cell communication within the liver and between other organs. However, the development and optimization of methods for EVs isolation is required to characterize their biological functions as well as their potential as a treatment option in the clinic. Nevertheless, many questions remain unanswered related to the function of EVs under physiological and pathological conditions. In the current editorial, the results obtained in different studies that investigated the role of intrahepatic EVs during liver diseases, including drug-induced liver injury, non-alcoholic fatty liver, nonalcoholic steatohepatitis, alcoholic liver disease and hepatocellular carcinoma and extrahepatic EVs in remote organs during pathological events such as pulmonary disease, cardiovascular diseases, neurodegenerative disorders e.g., Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as in immunopathological processes, are discussed. Although much light needs to be shed on the mechanisms of EVs, these membranederived vesicles represent both a novel promising diagnostic, and a therapeutic tool for clinical use that we emphasize in the current editorial.

关键词： Extracellular vesicles microRNA Hepatocytes Drug-induced liver injury Alcoholic liver disease Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Hepatocellular carcinoma

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Dissecting the molecular pathophysiology of drug-induced liver injury

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World Journal of Gastroenterology 2018年第13期24卷 1373-1385页

作者： Hui Ye Leonard J Nelson Manuel Gómez del Moral Eduardo Martínez-Naves Francisco javier cubero Department of Immunology Ophtalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for BioEngineering(Human Liver Tissue Engineering Faraday BuildingThe University of EdinburghThe King BuildingsMayfield RoadEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain

Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.

关键词： signaling pathways acetaminophen Drug-induced liver injury cell death reactive oxygen species

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Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

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World Journal of Gastroenterology 2016年第17期22卷 4397-4402页

作者： Andrés Duarte-Rojo Astrid Ruiz-Margáin Ricardo U Macias-Rodriguez Francisco javier cubero José Estradas-Trujillo Rosa Ma Munoz-Fuentes Aldo Torre University of Arkansas for Medical Sciences Little Rock AR 72205 United States Department of Gastroenterology Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City 14000 Mexico Department of Internal Medicine III University Hospital RWTH Aachen 52074 Aachen Germany Department of Immunology Complutense University School of Medicine 28040 Madrid Spain

AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy (HE).METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy (CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney’s U with Bonferroni adjustment Spearman correlations and area under the ROC were used as ***: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2 (P 0.13 ng/mL as the best cutoff value of S100β for the diagnosis of HE (sensitivity 83.3%, specificity 63.6%).CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE.

关键词： Hepatic encephalopathy S100β protein Astrocyte Psychometric hepatic encephalopathy score Critical flicker frequency

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Link between caries,periodontitis,and pregnancy:The role of personalized oral hygiene

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World Journal of Clinical Cases 2025年第6期13卷 51-57页

作者： Melissa Martínez nieto Martha Leticia De León Rodríguez Francisco javier Alcaraz Baturoni Alma Alicia Soto Chávez Sarah Monserrat LomelíMartínez Periodontics Program Department of Integrated Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Department of Medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810JaliscoMexico Master of Public Health Department of Well-being and SustainableCentro Universitario del NorteUniversidad de GuadalajaraColotlán 46200Mexico

Optimal health during pregnancy is crucial for ensuring the well-being of the mother and the developing *** article is focused on the impact of oral health and the role of personalized oral hygiene management in addressing prevalent dental issues among pregnant women,with particular emphasis on periodontal disease and dental *** the high prevalence of these dental problems and their association with obstetric complications such as pre-term birth and low birth weight,many pregnant women do not receive adequate dental *** gap in care is often due to misconceptions about the safety of dental treat-ments during pregnancy and lack of awareness on the part of healthcare *** of the impacts of oral health and personalization of oral hygiene strategies such as tailored education and support,have proven effective in improving oral health in this *** reductions in the incidence of caries and periodontal disease may be achieved by adapting care to the specific needs of each patient,thereby enhancing maternal and fetal health *** of personalized oral hygiene management into maternal health pro-grams and enhancement of ongoing education for pregnant women and healthcare professionals are essential steps in the reduction of pregnancy-related risks and improvement of maternal and neonatal *** Tip:In this article,we reviewed a recent study on the effects of personalized oral hygiene management on the oral health of pregnant women,as discussed in the article by Men et *** study demonstrated that personalized oral hygiene interventions significantly improved oral health outcomes during pregnancy by reducing the prevalence of dental caries and periodontal *** emphasized the importance of individualized oral care programs that integrate education and tailored support,and we highlighted their significance in enhancing maternal and fetal *** approach underscores the need for

关键词： Pregnancy Periodontal disease Periodontitis Dental caries Oral hygiene

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Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

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World Journal of Gastroenterology 2016年第45期22卷 10064-10070页

作者： Astrid Ruiz-Margáin Ricardo Ulises Macías-Rodríguez javier Ampuero Francisco javier cubero Luis Chi-Cervera Silvia L Ríos-Torres Andrés Duarte-Rojo Ángeles Espinosa-Cuevas Manuel Romero-Gómez Aldo Torre Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán14080 México City México Department of Internal Medicine Ⅲ University Hospital RWTH Aachen52074 Aachen Germany Unit for the Clinical Management of Digestive Diseases Virgen del Rocio-Virgen Macarena University Hospital41009 Sevilla Spain Department of Immunology Complutense University School of Medicine28040 Madrid Spain University of Arkansas for Medical Sciences Little Rock AR 72205 United States Department of Nephrology and Mineral Merabolism Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán México City 14080 México

AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic *** This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic *** Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.

关键词： Malnutrition Hepatic encephalopathy Phase angle Cachexia Prognosis

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Alcoholic liver disease:Utility of animal models

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World Journal of Gastroenterology 2018年第45期24卷 5063-5075页

作者： Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco javier cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for Bioengineering(IBioE) School of EngineeringFaraday BuildingThe University of EdinburghEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Human Anatomy and Embryology Complutense University School of MedicineMadrid 28040Spain Instituto de Neurociencias Consejo Superior de Investigaciones CientíficasUniversidad Miguel HernándezSan Juan de Alicante 03550Spain Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain Department of Genetics Physiology and MicrobiologyFaculty of BiologyUniversidad ComplutenseMadrid 28040Spain Department of Internal Medicine Ⅲ University Hospital RWTH AachenAachen 52062Germany

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

关键词： Steatohepatitis Cirrhosis Hepatocellular carcinoma Alcoholic liver disease Reactive oxygen species

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Transanal Endoscopic Video Assisted Rectal Lesion Resection, New Techniques Addressing Neoplasms

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Surgical Science 2012年第6期3卷 307-309页

作者： Ali Mahmood javier nieto Madhu Ragupathi Prianka Gajula Colorectal Surgical Associates Sugar Land USA Division of Minimally Invasive Surgery Department of Surgery University of Texas at Houston Medical School Houston USA

Early rectal cancer beyond the reach of conventional instruments has resulted in major abdominal and pelvic operations. As visualization is compromised beyond 6 - 8 cm, proximal to the anal verge, there have been several innovations and techniques to address T1 or T2 rectal cancer in the mid to upper rectum. Transanal Endscopic Microsurgery (TEM) was a technique that had garnered some success, however with expensive instrumentation along with limitations in instrument mobility, this technology was not applicable to many patients. Transanal Endoscopic Video Assisted (TEVA) rectal resection offers a cheap and readily accessible media to address early rectal cancer. Any hospital with standard laparoscopic ability is capable to offer TEVA rectal resection. We do advocate appropriate patient selection and advise that there is a learning curve with the increased requirement for technical difficulty. Once mastered, however, this surgical approach does provide yet another tool in the armamentarium of the surgeon.

关键词： Rectal Cancer Minimally Invasive Surgery Endoscopic Surgery

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Auditory function in symptomatic patients recovered from SARS-CoV-2 and unexposed patients:An analytical cross-sectional study

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Journal of Otology 2023年第3期18卷 118-124页

作者： Katherin Andrea Borda Pedraza Sergio Mauricio Moreno Lopez javier Amaya-nieto Liliana Akli Serpa Ginna Paola Saavedra Martínez Mauricio Ernesto Quinche Pardo Alberto Pena Valenzuela Otorhinolaryngology Department Universidad Nacional ColombiaColombia Epidemiology Department Universidad de Los AndesColombia Health Systems and Services Research Group Universidad Nacional de ColombiaBogotaColombia Audiology Department Universidad Nacional de ColombiaColombia Health and Social Protection Ministry Colombia Universidad Nacional Colombia Colombia Otorhinolaryngology Department Universidad Nacional de ColombiaColombia

Objective:To describe audiological symptoms,audiometric profile,and distortion product otoacoustic emission in symptomatic patients recovering from SARS-CoV-2 infection(positive RT-PCR test)and asymptomatic patients(negative RT-PCR test).Methods:An analytical cross-sectional study was conducted using data obtained from clinical charts,physical examination,audiometry,and distortion product otoacoustic emission on 40 patients[case patients(CP)]recovering from SARS-CoV-2 infection diagnosed by a positive RT-PCR test and 22asymptomatic participants with a negative RT-PCR test[non-case(NC)].Results:Sixty-two patients(mean age:31.1 and 28.2 years in the CP and NC groups,respectively)were *** participants were young without significant comorbidities,risk factors for hearing loss or otological ***(5%),tinnitus(17.5%)and aural fullness/hearing loss(35%)were found in the CP group.A statistically significant difference was found in specific frequencies(1000,4000,and 8000 Hz)and pure tone average(low and high conversational frequencies with increased threshold in the PC group compared with the NC group),which was not found in distortion product otoacoustic ***:Audiovestibular symptoms are frequent in symptomatic patients recovering from SARS-CoV-2 ***-CoV-2 infection was consistently associated with an increased audiometric hearing threshold at specific frequencies and low tone average.

关键词： SARS-CoV-2 Cochlear diseases Pure tone audiometry Otoacoustic emissions Hearing loss Otological symptoms

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-Lopez Eduardo Andres-Leon Laura Carmen Terron-Camero Blanca Cano-Gutierrez Jose Manuel Cozar Jose Antonio Lorente Fernando Vazquez-Alonso Luis javier Martinez-Gonzalez Maria Jesus Alvarez-cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC *** increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk ***,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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