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Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

World Journal of Gastrointestinal Oncology 2024年第1期16卷 234-243页

作者： João Gramaça Isabel Gomes Fernandes carolina Trabulo Joana gon.alves Rita Gameiro dos Santos Adriano Baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical Oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKGROUNd In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational *** RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT *** the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR *** SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May *** the time of cell-free dNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and *** neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

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Solar-driven CO_(2) conversion to methane and methanol using different nanostructured Cu_(2)O-based catalysts modified with Au nanoparticles

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Journal of Energy Chemistry 2024年第4期91卷 287-298页

作者： João Angelo Lima Perini Lilian d.Moura Torquato Juliana Fde Brito Gustavo A.Andolpho Mateus A.gon.alves Leonardo d.de Angelis Lucas d.Germano Susana I.Córdoba de Torresi Teodorico C.Ramalho Maria V.Boldrin Zanoni São Paulo State University(UNESP) Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil National Institute of Alternative Technologies for detection Toxicological Evaluation and Removal of Micropollutants and Radioactive Substances(INCT-DATREM)São Paulo State University(UNESP)Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil Laboratory of Molecular Modelling Department of ChemistryNatural Sciences InstituteFederal University of LavrasLavrasMG 37200-900Brazil department of Chemistry Faculty of ScienceUniversity of Hradec KrálovéHradec Králové50003Czech Republic Instituto de Química Universidade de São PauloAv.Prof.Lineu Prestes 74805508-080São PauloSPBrazil

This work describes the use of TiO_(2)nanotubes-based electrodes(TNT)modified with Cu_(2)O nanostructures and gold nanoparticles for the photoelectroreduction of CO_(2)to produce value-added compounds.A thin layer of polydopamine was used as both an adherent agent and an electron transfer mediator,due to itsπ-conjugated electron *** highest production yield was achieved using a TNT@PdA/Nc/Au40%electrode,with Faradaic efficiencies of 47.4%(110.5μM cm^(-2))and 27.8%(50.4μM cm^(-2))for methanol and methane,*** performance of the photoelectrodes was shown to be Cu_(2)O facet-dependent,with cubic structures leading to greater conversion of CO_(2)to methanol(43%)and methane(27%),compared to the octahedral morphology,while a higher percentage of metallic gold on the nanostructured Cu_(2)O surface was mainly important for *** functional theory(dFT)calculations supported these findings,attributing the superior photoelectrocatalytic performance of the TNT@PdA/Nc/Au40%electrode for CH4generation to the formation of an OCH3intermediate bonded to Au *** using isotope-labeling and analysis by gas chromatograph-mass(GC-MS)demonstrated that13CO_(2)was the source for photoelectrocatalytic generation of13CH3OH and13CH313CH2OH.

关键词： Cu_(2)O nanocubes Photoelectrocatalysis Polydopamine CO_(2) photoelectroreduction dFT calculations

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Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

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World Journal of Hepatology 2024年第5期16卷 832-842页

作者： Elisa carolina Lange Pabulo Henrique Rampelotto Larisse Longo Laura Bainy Rodrigues de Freitas carolina Uribe-Cruz Mario Reis Alvares-da-Silva Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Bioinformatics and Biostatistics Core Facility Universidade Federal do Rio Grande do SulPorto Alegre 91501-970Brazil Graduate Program in Biological Sciences:Pharmacology and Therapeutics Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007RSBrazil Conselho Nacional de desenvolvimento Científico e Tecnológico(CNPq)researcher Brasília 71605-001Brazil

BACKGROUNd Metabolic-dysfunction associated steatotic liver disease(MASLd)is a hepatic manifestation of metabolic *** suggest ornithine aspartate(LOLA)as drug *** To analyze the influence of LOLA intake on gut microbiota using a nutritional model of *** Adult male Sprague dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLd(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were *** fecal dNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™*** Alpha and beta diversity metrics were comparable between MASLd and LOLA.3 OTUs were differentially abundant between MASLd and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides *** functional prediction provided two different metabolic profiles between MASLd and *** 9 pathways differentially abundant in MASLd are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides *** 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA *** Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLd,it was associated with changes in specific gut microbes and their related metabolic pathways.

关键词： Animal model Gut microbiota Metabolic-associated steatotic liver disease Metabolic prediction Ornithine aspartate

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A discussion about the limitations of the Eurocode’s high-speed load model for railway bridges

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Railway Engineering Science 2024年第2期32卷 211-228页

作者： gonçalo Ferreira Pedro Montenegro JoséRui Pinto António Abel Henriques Rui Calçada CONSTRUCT-LESE Faculty of EngineeringUniversity of PortoRua Dr.Roberto Frias4200-465 PortoPortugal CONSTRUCT-LABEST Faculty of EngineeringUniversity of PortoRua Dr.Roberto Frias4200-465 PortoPortugal

High-speed railway bridges are subjected to normative limitations concerning maximum permissible deck *** the design of these structures,the European norm EN 1991-2 introduces the high-speed load model(HSLM)—a set of point loads intended to include the effects of existing high-speed ***,the evolution of current trains and the recent development of new load models motivate a discussion regarding the limits of validity of the *** this study,a large number of randomly generated load models of articulated,conventional,and regular trains are tested and compared with the envelope of HSLM *** each type of train,two sets of 100,000 load models are considered:one abiding by the limits of the EN 1991-2 and another considering wider *** comparison is achieved using both a bridge-independent metric(train signatures)and dynamic analyses on a case study bridge(the Canelas bridge of the Portuguese Railway Network).For the latter,a methodology to decrease the computational cost of moving loads analysis is *** show that some theoretical load models constructed within the stipulated limits of the norm can lead to effects not covered by the *** is especially noted in conventional trains,where there is a relation with larger distances between centres of adjacent vehicle bogies.

关键词： High-speed load model dynamic analysis High-speed railways Train signature Railway bridges deck acceleration

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung gon Kim Jun Young Choi department of Brain Science Ajou University School of MedicineSuwonSouth Korea department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea department of Neurology Ajou University School of MedicineSuwonSouth Korea department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a dNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(Ad).However,some older adult people with Ad pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to Ad offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged Ad *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic Ad mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Obtaining 2d Soil Geotechnical Profiles from Cokriging Interpolation of Sample data and Electrical Resistivity Tomography (ERT)—Applications in Mass Movements Studies

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International Journal of Geosciences 2024年第7期15卷 525-548页

作者： Cassiano Antonio Bortolozo Noel Howley Andy Legg Tristan Pryer danielle Silva de Paula Tatiana Sussel gon.alves Mendes daniel Metodiev Marcio Roberto Magalhães de Andrade Silvio Jorge Coelho Simões Maiconn Vinicius de Moraes Marcio Augusto Ernesto de Moraes Luana Albertani Pampuch Rodolfo Moreda Mendes Harideva Marturano Egas Institute of Science and Technology So Paulo State University (UNESP) So Jos dos Campos Brazil Cemaden-National Center for Monitoring and Early Warning of Natural disasters General Coordination of Research and Development So Jos dos Campos Brazil Institute for Mathematical Innovation University of Bath Bath UK department of Mathematical Sciences University of Bath Bath UK

Brazil annually faces significant challenges with mass movements, particularly in areas with poorly constructed housing, inadequate engineering, and lacking sanitation infrastructure. Campos do Jordão, in São Paulo state, is a city currently grappling with these issues. This paper details a study conducted within a pilot area in Campos do Jordão, where geophysical surveys and geotechnical borehole data were integrated. The geophysical surveys provided 2d profiles, and samples were collected to analyse soil moisture and plasticity. These datasets were combined using a Cokriging-based model to produce an accurate representation of the subsurface conditions. The enhanced modelling of subsurface variability facilitates a deeper understanding of soil behavior, which can be used to improve landslide risk assessments. This approach is innovative, particularly within the international context where similar studies often do not address the complexities associated with urban planning deficits such as those observed in some areas of Brazil. These conditions, including the lack of proper sanitation and irregular housing, significantly influence the geological stability of the region, adding layers of complexity to subsurface assessments. Adapting geotechnical evaluation methods to local challenges offers the potential to increase the efficacy and relevance of geological risk management in regions with similar socio-economic and urban characteristics.

关键词： Mass Movements Geophysics ERT Geotechnical Surveys Campos do Jordão Cokriging

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Exercise training improves long-term memory in obese mice

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Life Metabolism 2024年第1期3卷 37-50页

作者： Oliver K.Fuller Casey L.Egan Tina L.Robinson Nimna Perera Heidy K.Latchman Lauren V.Terry Emma d.McLennan carolina Chavez Emma L.Burrows John W.Scott Robyn M.Murphy Henriette van Praag Martin Whitham Mark A.Febbraio Monash Institute of Pharmaceutical Sciences Monash UniversityMelbourneVictoria3052Australia La Trobe Institute for Molecular Science La Trobe UniversityMelbourneVictoria3086Australia Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVictoria3052Australia department of Biomedical Sciences Charles E.Schmidt College of Medicineand Stiles-Nicholson Brain InstituteFlorida Atlantic UniversityJupiterFL 33458United States College of Life and Environmental Sciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom

Obesity has been linked to a range of pathologies,including *** contrast,regular physical activity is associated with the prevention or reduced progression of ***,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully ***,we investigated whether any detrimental effects of high-fat diet(HFd)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BdNF)could be mitigated by voluntary exercise training in male C57Bl/6 ***-induced impairment of motor function was not reversed by ***,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.

关键词： obesity exercise cognition

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Evidence-Based Complementary and Alternative Medicine Effects of Capybara Oil on Cardiac Remodeling of C57bl/6 Mice

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Journal of Biosciences and Medicines 2024年第5期12卷 213-232页

作者： Rafael M. Almeida Wagner d. Giannetti Guilherme R. Silveira carolina R. Castilho Renata V. Lisboa Bianca T. Ciambarella Rodrigo N. Ferreira Jorge José de Carvalho Laboratory of Ultrastructure and Tissue Biology Institute of Biology State University of Rio de Janeiro Rio de Janeiro Brazil Higher Education Center of Valenç a Dom Andr&#233 Arcoverde Educational Foundation Valen&#231a Brazil

Cardiovascular diseases are the main cause of morbidity and mortality in the world, and obesity and the metabolic syndrome are risk factors for its development. One of the therapies to reduce cardiovascular risk is the use of polyunsaturated fatty acids. In Brazil, a source of such acid is the oil extracted from the fat of the capybara. The objective of this work is to study the effects of the capybara oil on lipid and glucose metabolism, as well as its effects on the adipose tissue and cardiac remodeling. We assessed the effects of capybara oil treatment on body mass, lipid and carbohydrate metabolism, systolic blood pressure, adipose tissue and cardiac remodeling, and performed an ultrastructural evaluation of the myocardium in C57Bl/6 mice treated with high-fat diet. Treatment with capybara oil reduced total cholesterol and triglyceride levels, systolic blood pressure, visceral and subcutaneous adipose tissue, and adipocyte diameter. In addition, cardiac remodeling was attenuated, preserving cardiomyocytes, increasing vascularization, reducing cardiomyocyte hypertrophy and the extracellular matrix, and preserving the morphological integrity of mitochondria. Capybara oil has several beneficial effects on the cardiovascular and metabolic system, and further studies are needed to better understand its role in the prevention or treatment of cardiovascular diseases.

关键词： Capybara Oil Cardiac Remodeling Polyunsaturated Fatty Acids Obesity Metabolic Syndrome

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Utility of plasma d-dimer for diagnosis of venous thromboembolism after hepatectomy

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World Journal of Clinical Cases 2024年第2期12卷 276-284页

作者： Taiichiro Miyake Hiroaki Yanagimoto daisuke Tsugawa Masayuki Akita Riki Asakura Keisuke Arai Toshihiko Yoshida Shinichi So Jun Ishida Takeshi Urade Yoshihide Nanno Kenji Fukushima Hidetoshi gon Shohei Komatsu Sadaki Asari Hirochika Toyama Masahiro Kido Tetsuo Ajiki Takumi Fukumoto division of Hepato-Biliary-Pancreatic Surgery Department of SurgeryKobe University Graduate School of MedicineKobe 650-0017HyogoJapan

BACKGROUNd Venous thromboembolism(VTE)is a potentially fatal complication of *** use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative ***,we hypothesized that monitoring plasma d-dimer could be useful in the early diagnosis of VTE after *** To evaluate the utility of monitoring plasma d-dimer levels in the early diagnosis of VTE after *** The medical records of patients who underwent hepatectomy at our institution between January 2017 and december 2020 were retrospectively *** were divided into two groups according to whether or not they developed VTE after hepatectomy,as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower *** factors,including demographic data and perioperative d-dimer values,were compared between the two *** operating characteristic curve analysis was performed to determine the d-dimer cutoff *** and multivariate analyses were performed using logistic regression analysis to identify significant *** In total,234 patients who underwent hepatectomy were,of whom(5.6%)were diagnosed with VTE following hepatectomy.A comparison between the two groups showed significant differences in operative time(529 vs 403 min,P=0.0274)and blood loss(530 vs 138 mL,P=0.0067).The d-dimer levels on postoperative days(POd)1,3,5,7 were significantly higher in the VTE group than in the non-VTE *** the multivariate analysis,intraoperative blood loss of>275 mL[odds ratio(OR)=5.32,95%confidence interval(CI):1.05-27.0,P=0.044]and plasma d-dimer levels on POd 5≥21μg/mL(OR=10.1,95%CI:2.04-50.1,P=0.0046)were independent risk factors for VTE after *** Monitoring of plasma d-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the

关键词： Hepatectomy Malignant tumor Postoperative complication d-dimer Early diagnosis Venous thromboembolism

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