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Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

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World Journal of Gastroenterology 2019年第27期25卷 3503-3526页

作者： alexandre loktionov DiagNodus Ltd Babraham Research Campus

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

关键词： Eosinophils Eosinophilopoiesis Gut lamina propria Colorectal mucus Normal human small intestine Normal human colon Inflammatory bowel disease Crohn’s disease Ulcerative colitis Colorectal cancer

Biomarkers for detecting colorectal cancer non-invasively: DNA,RNA or proteins?

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World Journal of Gastrointestinal Oncology 2020年第2期12卷 124-148页

作者： alexandre loktionov Diag Nodus Ltd Babraham Research Campus

Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area prom

关键词： Colorectal cancer screening Biomarkers Non-invasive testing Stool Colorectal mucus Blood

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 purposes.Among 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 work.The numerical model is developed in a non-linear framework accounting for the strain rate effect on the mechanical responses of the lattice structure.Four geometries,i.e.,cubic body centered cell,octet cell,rhombic-dodecahedron and truncated cuboctahedron 2+,are investigated.Specifically,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 investigated.The 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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Severe dengue in the intensive care unit

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Journal of Intensive Medicine 2024年第1期4卷 16-33页

作者： alexandre Mestre Tejo Debora Toshie Hamasaki Letícia Mattos Menezes Yeh-Li Ho Intensive Care Unit Department of Intensive Medicine of the Cancer Institute of the State of São PauloHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloBrazil Transfusion Medicine and Cell Therapy Department A.C.Camargo Cancer CenterSão PauloBrazil Intensive Care Unit of Infectious Disease Department Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloBrazil

Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%of patients can develop severe disease.Although the mechanisms are yet not fully comprehended,immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients:increased vascular permeability that may shock and thrombocytopenia,and coagulopathy that can induce hemorrhage.The risk factors of severe disease include previous infection by a different serotype,specific genotypes associated with more efficient replication,certain genetic polymorphisms,and comorbidities such as diabetes,obesity,and cardiovascular disease.The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality.This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.

关键词： Severe dengue Intensive care units Shock Pathogenesis Diagnosis Management

Assimilation of GOES-R Geostationary Lightning Mapper Flash Extent Density Data in GSI 3DVar, EnKF, and Hybrid En3DVar for the Analysis and Short-Term Forecast of a Supercell Storm Case

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Advances in Atmospheric Sciences 2024年第2期41卷 263-277页

作者： Rong KONG Ming XUE Edward R.MANSELL Chengsi LIU alexandre O.FIERRO Center for Analysis and Prediction of Storms Norman Oklahoma 73072U.S.A University of Oklahoma Norman Oklahoma 73072U.S.A NOAA/National Severe Storms Laboratory NormanOklahoma 73072U.S A.4Zentralanstalt für Meteorologie und Geodynamik Department of Forecasting Models-ZAMGVienna 1190Austria

Capabilities to assimilate Geostationary Operational Environmental Satellite “R-series ”(GOES-R) Geostationary Lightning Mapper(GLM) flash extent density(FED) data within the operational Gridpoint Statistical Interpolation ensemble Kalman filter(GSI-EnKF) framework were previously developed and tested with a mesoscale convective system(MCS) case. In this study, such capabilities are further developed to assimilate GOES GLM FED data within the GSI ensemble-variational(EnVar) hybrid data assimilation(DA) framework. The results of assimilating the GLM FED data using 3DVar, and pure En3DVar(PEn3DVar, using 100% ensemble covariance and no static covariance) are compared with those of EnKF/DfEnKF for a supercell storm case. The focus of this study is to validate the correctness and evaluate the performance of the new implementation rather than comparing the performance of FED DA among different DA schemes. Only the results of 3DVar and pEn3DVar are examined and compared with EnKF/DfEnKF. Assimilation of a single FED observation shows that the magnitude and horizontal extent of the analysis increments from PEn3DVar are generally larger than from EnKF, which is mainly caused by using different localization strategies in EnFK/DfEnKF and PEn3DVar as well as the integration limits of the graupel mass in the observation operator. Overall, the forecast performance of PEn3DVar is comparable to EnKF/DfEnKF, suggesting correct implementation.

关键词： GOES-R lightning data assimilation EnKF EnVar

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Cerebral and muscle tissue oxygenation during exercise in healthy adults: A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 459-471,F0003页

作者： Diego Orcioli-Silva Victor Spiandor Beretta Paulo Cezar Rocha Santos Felipe Marroni Rasteiro Anita Brum Marostegan Rodrigo Vitorio Claudio alexandre Gobatto Fulvia Barros Manchado-Gobatto Laboratory of Applied Sport Physiology(LAFAE) School of Applied Sciences(FCA)University of Campinas(UNICAMP)Limeira 13484-350Brazil Posture and Gait Studies Laboratory(LEPLO) Institute of BiosciencesSao Paulo State University(UNESP)Rio Claro 13506-900Brazil Physical Education Department School of Technology and SciencesSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Department of Computer Science&Applied Mathematics Weizmann Institute of ScienceRehovot 7610001Israel Center of Advanced Technologies in Rehabilitation Sheba Medical CenterRamat Gan 5265601Israel Department of Sport Exercise and RehabilitationNorthumbria UniversityNewcastle upon Tyne NE18STUK

Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise.Since this technology has been growing and is now successfully used in laboratory and sports settings,this systematic review aimed to synthesize the evidence and enhance an integrative understanding of bloodﬂow adjustments and oxygen(O_(2))changes(i.e.,the balance between O_(2) delivery and O_(2) consumption)within the cerebral and muscle systems during exercise.Methods:A systematic review was conducted using PubMed,Embase,Scopus,and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise.This review considered manuscripts written in English and available before February 9,2023.Each step of screening involved evaluation by 2 inde-pendent authors,with disagreements resolved by a third author.The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.Results:Twenty studies were included,of which 80%had good methodological quality,and involved 290 young or middle-aged adults.Different types of exercises were used to assess cerebral and muscle hemodynamic changes,such as cycling(n=11),treadmill(n=1),knee extension(n=5),isometric contraction of biceps brachii(n=3),and duet swim routines(n=1).The cerebral hemodynamics anal-ysis was focused on the frontal cortex(n=20),while in the muscle,the analysis involved vastus lateralis(n=18),gastrocnemius(n=3),biceps brachii(n=5),deltoid(n=1),and intercostal muscle(n=1).Overall,muscle deoxygenation increases during exercise,reaching a plateau in voluntary exhaustion,while in the brain,oxyhemoglobin concentration increases with exercise intensity,reaching a plateau or declining at the exhaustion point.Conclusion:Muscle and cerebral oxygenation respond differently to exercise,with muscle increasing O_(2) utilization and cerebral tissue

关键词： Near-infrared spectroscopy Hemodynamic Blood flow Brain Muscle metabolism

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The impact of heterogeneity and pore network characteristics on single and multi-phase fluid propagation in complex porous media:An X-ray computed tomography study

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Petroleum Science 2024年第3期21卷 1719-1738页

作者： Shohreh Iraji Tales Rodrigues De Almeida Eddy Ruidiaz Munoz Mateus Basso alexandre Campane Vidal Department of Mechanical Engineering (FEM) State University of Campinas (UNICAMP) Department of Geology and Natural Resources Geosciences Institute (IG) State University of Campinas (UNICAMP) LRAP/COPPE/COPPETEC/UFRJ Center of Energy and Petroleum Studies (CEPETRO) State University of Campinas (UNICAMP)

This study investigates the impact of pore network characteristics on fluid flow through complex and heterogeneous porous media, providing insights into the factors affecting fluid propagation in such systems. Specifically, high-resolution or micro X-ray computed tomography(CT) imaging techniques were utilized to examine outcrop stromatolite samples of the Lagoa Salgada, considered flow analogous to the Brazilian Pre-salt carbonate reservoirs. The petrophysical results comprised two distinct stromatolite depositional facies, the columnar and the fine-grained facies. By generating pore network model(PNM), the study quantified the relationship between key features of the porous system, including pore and throat radius, throat length, coordination number, shape factor, and pore volume. The study found that the less dense pore network of the columnar sample is typically characterized by larger pores and wider and longer throats but with a weaker connection of throats to pores. Both facies exhibited less variability in the radius of the pores and throats in comparison to throat length. Additionally, a series of core flooding experiments coupled with medical CT scanning was designed and conducted in the plug samples to assess flow propagation and saturation fields. The study revealed that the heterogeneity and presence of disconnected or dead-end pores significantly impacted the flow patterns and saturation.Two-phase flow patterns and oil saturation distribution reveal a preferential and heterogeneous displacement that mainly swept displaced fluid in some regions of plugs and bypassed it in others. The relation between saturation profiles, porosity profiles, and the number of fluid flow patterns for the samples was evident. Only for the columnar plug sample was the enhancement in recovery factor after shifting to lower salinity water injection(SB) observed.

关键词： Pore network model Heterogeneous porous media Flow patterns Dead-end pores

Simulated rainfall in Brazil:An alternative for assesment of soil surface processes and an opportunity for technological development

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International Soil and Water Conservation Research 2024年第1期12卷 29-42页

作者： Camila Calazans da Silva Luz Wilk Sampaio de Almeida Adilson Pacheco de Souza Nivaldo Schultz Jamil alexandre Ayach Anache Daniel Fonseca de Carvalho Postgraduate Program in Agronomy-Soil Sciences Federal Rural University of Rio de JaneiroSeropédicaRJBrazil Agronomy Department Federal Institute of EducationScience and Technology of RondôniaAriquemesROBrazil Federal University of Mato Grosso SinopMTBrazil Federal Rural University of Rio de Janeiro SeropédicaRJBrazil Federal University of Mato Grosso do Sul Campo GrandeMSBrazil

Rainfall simulators(RS)have been used,above all,to evaluate hydrological processes related to soil water infiltration,surface runoff and soil erosion.They allow repeatability of rain application with different precipitation intensities in field and/or laboratory conditions and should produce events with physical characteristics similar to natural rain.In this manuscript,we carried out a bibliometric and scientometric analysis of studies with simulated rainfall in Brazil to assess the temporal evolution of publications,the main topics addressed and the degree of technological development of the equipment.We searched for the terms“rainfall simulator”OR“simulated rainfall”AND“Brazil”in the Scopus,Web of Science,SciELO and Google Scholar databases.We found 143 articles published in the last 37 years(1985-2022).Our findings indicate that the main research areas covered in papers are soil erosion(57.34%),soil water infiltration(24.47%),nutrient losses(9.8%)and RS development and calibration/assessment(8.39%).In recent years,the number of published papers in international high-impact factor journals has increased.Most of the papers(49.65%)refer to studies carried out by institutions located in the south and southeast regions of Brazil.Moreover,there is a large gap of studies on simulated rainfall in other regions of Brazil,where important biomes such as the Cerrado,Amazon,Caatinga,and their transitions are located.This study informs research priorities on soil erosion under simulated rainfall and provides a bibliographic database that can assist in more detailed future analyses.

关键词： Rainfall simulator Soil and water losses Soil water infiltration Bibliometrics Scientific review

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 139-145页

作者： Wellington Andraus Francisco Tustumi alexandre Chagas Santana Rafael Soares Nunes Pinheiro Daniel Reis Waisberg Liliana Ducatti Lopes Rubens Macedo Arantes Vinicius Rocha Santos Rodrigo Bronze de Martino Luiz Augusto Carneiro D’Albuquerque Department of Gastroenterology Transplantation UnitUniversidade de São PauloSão PauloBrazil

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for bette

关键词： Liver transplantation Cholangiocarcinoma Liver neoplasms

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