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Breath Biopsy^(®) to Identify Exhaled Volatile Organic compounds Biomarkers for Liver cirrhosis Detection

Journal of clinical and Translational Hepatology 2023年第3期11卷 638-648页

作者： Giuseppe Ferrandino Giovanna De Palo Antonio Murgia Owen Birch Ahmed Tawfike Rob Smith Irene Debiram-Beecham Olga Gandelman Graham Kibble Anne Marie Lydon Alice Groves Agnieszka Smolinska Max Allsworth Billy Boyle Marc P.van der Schee Michael Allison rebecca c.fitzgerald Matthew Hoare Victoria K.Snowdon Owlstone Medical CambridgeUK Department of Oncology University of CambridgeHutchison/MRC Research CentreCambridgeUK Department of Pharmacology and Toxicology School for Nutrition and Translational Research in Metabo-lism(NUTRIM)Maastricht University Medical Centerthe Netherlands Department of Medicine University of CambridgeAddenbrooke’s HospitalCambridgeUK Addenbrookes Hepatology and Liver Transplantation Unit Addenbrookes Hospi-talCambridgeUK MRc cancer Unit Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUK cRUK cambridge Institute CambridgeUK

Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare *** is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease *** previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical ***:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from *** and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(Gc-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOcs)***:A set of 29 breath VOcs differed significantly between cirrhosis and controls.A classification model based on these VOcs had an area under the curve(AUc)of 0.95±0.04 in cross-validated test *** seven best performing VOcs were sufficient to maximize classifica-tion performance.A subset of 11 VOcs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component ***:A set of seven VOcs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.

关键词： Breath Biopsy Non-invasive Biomarker cirrhosis Liver function test.

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Ink-structing the future of vascular tissue engineering:a review of the physiological bioink design

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Bio-Design and Manufacturing 2024年第2期7卷 181-205页

作者： Judith Synofzik Sebastian Heene rebecca Jonczyk cornelia Blume Institute for Technical chemistry Leibniz University Hannover30167 HannoverGermany

Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and *** tissue-engineered structures are intended to integrate with the patient’s *** tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered *** have a specific role,representingthenecessarymedium for printability and vascular cell *** review aims to understand the requirements for the design of vascular ***,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth *** review describes the general structure of vascular walls with wall-speciﬁc cell and extracellular matrix(EcM)components and biomechanical properties and ***,the physiological role of vascular EcM components for their interaction with vascular cells and the mode of interaction is *** currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular *** physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular ***,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are *** concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.

关键词： Vascular wall histology Vascular cells Microenvironment Extracellular matrix cell–matrix interaction Bioink Printability

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Timely completion of multiple life-saving interventions for traumatic haemorrhagic shock: a retrospective cohort study

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Burns & Trauma 2019年第1期7卷 204-212页

作者： Biswadev Mitra Jordan Bade-Boon Mark c.fitzgerald Ben Beck Peter A.cameron National Trauma Research Institute The Alfred Hospital89 Commercial RoadMelbourneVIC 3004Australia Emergency&Trauma centre The Alfred HospitalMelbourneAustralia School of Public Health and Preventive Medicine Monash University MelbourneAustralia Trauma Service The Alfred HospitalMelbourneAustralia Faculty of Medicine Laval University Quebec City QuebecCanada

Background:Early control of haemorrhage and optimisation of physiology are guiding principles of resuscitation after *** outcomes have been previously associated with single,timely *** aim of this study was to assess the association between multiple timely life-saving interventions(LSIs)and outcomes of traumatic haemorrhagic shock ***:A retrospective cohort study was undertaken of injured patients with haemorrhagic shock who presented to Alfered Emergency&Trauma centre between July 01,2010 and July 31,*** studied included chest decompression,control of external haemorrhage,pelvic binder application,transfusion of red cells and coagulation products and surgical control of bleeding through angio-embolisation or operative *** primary exposure variable was timely initiation of≥50%of the indicated *** association between the primary exposure variable and outcome of death at hospital discharge was adjusted for potential confounders using multivariable logistic regression *** association between total pre-hospital times and pre-hospital care times(time from ambulance at scene to trauma centre),in-hospital mortality and timely initiation of≥50%of the indicated interventions were ***:Of the 168 patients,54(32.1%)patients had≥50%of indicated LSI completed within the specified time *** delivery of LSI was independently associated with improved survival to hospital discharge(adjusted odds ratio(OR)for in-hospital death 0.17;95%confidence interval(cI)0.03–0.83;p=0.028).This association was independent of patient age,pre-hospital care time,injury severity score,initial serum lactate levels and *** patients with pre-hospital time of≥2 h,2(3.6%)received timely ***-hospital care times of≥2 h were associated with delayed LSIs and with in-hospital death(unadjusted OR 4.3;95%cI 1.4–13.0).conclusions:Timely completion of LSI when indicated was completed in a small

关键词： Wounds Bundle of care Haemorrhage shock Resuscitation Emergency department Blood products Timely life-saving interventions Trauma Injuries

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Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

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World Journal of Gastroenterology 2010年第45期16卷 5669-5681页

作者： chin-Ann J Ong Pierre Lao-Sirieix rebecca c.fitzgerald MRc cancer cell Unit Hutchison-MRC Research CentreCambridgeCB20XZUnited Kingdom

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.

关键词： Barrett’s esophagus Esophageal adenocar cinoma Esophageal dysplasia Prognosis

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Storylines of family medicine Ⅻ:family medicine and the healthcare system

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Family Medicine and community Health 2024年第S3期12卷 109-118页

作者： William B Ventres Leslie A Stone Jeannette E South-Paul Kendall M campbell Aerial R Petty Hima Ekanadham Kurt c Stange rebecca S Etz William L Miller Robert L Ferrer Marianna Kong Thomas Bodenheimer Roger Strasser Sharon c M Reece Joshua Freeman John M Westfall Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Meharry Medical college NashvilleTennesseeUSA Family Medicine University of Texas Medical Branch at Galveston School of MedicineGalvestonTexasUSA Family Medicine Residency Program New York-Presbyterian Columbia University Medical CenterNew YorkNew YorkUSA center for Family and community Medicine Columbia University Vagelos College of Physicians and SurgeonsNew YorkNew YorkUSA center for community Health Integration Case Western Reserve University School of MedicineClevelandOhioUSA Family Medicine and Population Health Virginia Commonwealth University School of MedicineRichmondVirginiaUSA Family Medicine Lehigh Valley Health NetworkAllentownPennsylvaniaUSA University of South Florida Morsani college of Medicine TampaFloridaUSA Family and community Medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA Family and community Medicine University of California San Francisco School of MedicineSan FranciscoCaliforniaUSA Northern Ontario School of Medicine University SudburyOntarioCanada Family Medicine Baylor Scott and White HealthTempleTexasUSA Family Medicine University of Kansas School of MedicineKansas CityKansasUSA DARTNet Insitute AuroraColoradoUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅻ:Family medicine and the future of the healthcare system’,authors address the following themes:‘Leadership in family medicine’,‘Becoming an academic family physician’,‘Advocare—our call to act’,‘The paradox of primary care and three simple rules’,‘The quadruple aim—melding the patient and the health system’,‘Fit-for-purpose medical workforce’,‘Universal healthcare—coverage for all’,‘The futures of family medicine’and‘The 100th essay.’May readers of these essays feel empowered to be part of family medicine’s exciting future.

关键词： system illustration family

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Frequency of the c677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

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Open Journal of Genetics 2024年第1期14卷 13-25页

作者： N’Guessan-Blao rebecca Yapo Vincent Yayo-Ayé Mireille Adjambri Eusèbe Koné-Koné Fatoumata Sawadogo Duni Hematology and General Biology Unit Faculty of Pharmaceutical and Biological Sciences Department of Biological Sciences Felix Houphouet-Boigny University Abidjan Ivory Coast Laboratory of Biology and Medical Research National Institute of Public Health (INSP) Abidjan Ivory Coast Molecular Biology Unit Center for Diagnosis and Research on AIDS and Other Infectious Diseases (CeDReS) Treichville University Hospital (CHU) Abidjan Ivory Coast

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the c677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PcR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the cOBAS c311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous c677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

关键词： Type 2 Diabetes c677T of MTHFR G20210A Factor V Leiden Thrombosis

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Redefining pandemic preparedness:Multidisciplinary insights from the cERP modelling workshop in infectious diseases,workshop report

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Infectious Disease Modelling 2024年第2期9卷 501-518页

作者： Marta c.Nunes Edward Thommes Holger Fröhlich Antoine Flahault Julien Arino Marc Baguelin Matthew Biggerstaff Gaston Bizel-Bizellot rebecca Borchering Giacomo cacciapaglia Simon cauchemez Alex Barbier--chebbah carsten claussen christine choirat Monica cojocaru catherine commaille-chapus chitin Hon Jude Kong Nicolas Lambert Katharina B.Lauer Thorsten Lehr cédric Mahe Vincent Marechal Adel Mebarki Seyed Moghadas Rene Niehus Lulla Opatowski Francesco Parino Gery Pruvost Andreas Schuppert Rodolphe Thiébaut Andrea Thomas-Bachli cecile Viboud Jianhong Wu Pascal crépey Pascalcrepey center of Excellence in Respiratory Pathogens(cERP) Hospices Civils de Lyon(HCL)and Centre International de Recherche en Infectiologie(CIRI)Équipe SantéPubliqueÉpidémiologie etÉcologieÉvolutive des Maladies Infectieuses(PHE3ID)Inserm U1111CNRS UMR5308ENS de LyonUniversitéClaude Bernard Lyon 1LyonFrance South African Medical Research council Vaccines&Infectious Diseases Analytics Research UnitFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa New Products and Innovation(NPI) Sanofi Vaccines(Global)TorontoOntarioCanada Department of Mathematics and Statistics University of GuelphGuelphOntarioCanada Fraunhofer Institute for Algorithms and Scientific computing(ScAI) Department of BioinformaticsSchloss BirlinghovenSankt AugustinGermany University of Bonn Bonn-Aachen International Center for IT(b-it)BonnGermany Institute of Global Health Faculty of MedicineUniversity of GenevaGenevaSwitzerland and Swiss School of Public HealthZürichSwitzerland Department of Mathematics University of ManitobaWinnipegManitobaCanada MRc centre for Global Infectious Disease Analysis School of Public HealthImperial College LondonLondonUK centre for Mathematical Modelling of Infectious Diseases Department of Infectious Disease EpidemiologyLondon School of Hygiene&Tropical MedicineLondonUK National center for Immunization and Respiratory Diseases(NcIRD) US Centers for Disease Control and Prevention(CDC)AtlantaGAUSA Departement of computational Biology Departement of Global HealthInstitut PasteurParisFrance Institut de Physique des Deux Infinis de Lyon(IP2I) UMR5822IN2P3/CNRSUniversitéClaude Bernard Lyon 1VilleurbanneFrance Mathematical Modelling of Infectious Diseases Unit Institut PasteurUniversitéParis CitéUMR2000 CNRSParisFrance Decision and Bayesian computation Institut PasteurUniversitéParis CitéCNRS UMR 3571France Fraunhofer-Institute for Translational Medicine and Pharmacology HamburgGermany Institute of Global Health Faculty of MedicineUniversity of

In July 2023,the center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the covid-19 *** report summarizes the rich discussions that occurred during the *** workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data,social media,and wastewater *** advancements were noted in the development of predictive models,with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease *** role of open collaboration between various stakeholders in modelling was stressed,advocating for the continuation of such partnerships beyond the pandemic.A major gap identified was the absence of a common international framework for data sharing,which is crucial for global pandemic ***,the workshop underscored the need for robust,adaptable modelling frameworks and the integration of different data sources and collaboration across sectors,as key elements in enhancing future pandemic response and preparedness.

关键词： Modelling covid-19 Infectious diseases Pandemic preparedness Workshop

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Reconciling concepts, theory, and empirical patterns surrounding cascade reinforcement

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current Zoology 2016年第2期62卷 131-134页

作者： rebecca c. FULLER Department of Animal Biology University of Illinois Urbana IL 61801 USA

IntroductionReinforcement is a critically important process in speciation. It has been credited with often completing speciation, and it is unique in that natural selection directly favors the evolution of reproductive isolating barriers. Reinforcement occurs when selection favors increased prezygotic isolation between two lineages in order to avoid maladaptive hybridization in areas of sympatry （Noor 1999; Servedio and Noor 2003; coyne and Orr 2004）.

关键词：调和加固梯级

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Male-driven reproductive and agonistic character displacement in darters and its implications for speciation in allopatry

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current Zoology 2018年第1期64卷 101-113页

作者： Rachel L. MORAN rebecca c. FULLER School of Integrative Biology University of Illinois Champaign IL 61820 USA

Selection against hybridization can cause mating traits to diverge between species in sympatry via reproductive character displacement （RcD）. Additionally, selection against interspecific fighting can cause aggressive traits to diverge between sympatric species via agonistic character displacement （AcD）. By directly affecting conspecific recognition traits, RcD and AcD between species can also incidentally cause divergence in mating and fighting traits among populations within a species [termed cascade RcD （cRcD） and cascade AcD]. Here, we demonstrate patterns consistent with male-driven RcD and AcD in 2 groups of darters （orangethroat darter clade ceasia and rainbow darter Etheostoma caeruleum）. In both groups, males that occur in sympatry （between ceasia and E. caeruleum） have higher levels of preference for mating and fighting with conspecifics over heterospecifics than do males from allopatry. This is consistent with RcD and AcD. We also found patterns consistent with cRcD and cascade AcD among species of ceasia. ceasia males that are sympatric to E. caeruleum （but allopatric to one another） also have heightened preferences for mat- ing and fighting with conspecific versus heterospecific ceasia. In contrast, ceasia males that are allopatric to E. caeruleum readily mate and fight with heterospecific ceasia. We suggest that RcD and AcD between ceasia and E. caeruleum has incidentally led to divergence in mating and fighting traits among ceasia species. This study is unique in that male preferences evolve via both RcD （male preference for conspecific females） and AcD （male preference to fight conspecific males） which leads to subsequent divergence among allopatric lineages.

关键词： agonistic character displacement behavioral isolation cascade reinforcement reinforcement reproductive charac-ter displacement speciation.

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Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals

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cellular & Molecular Immunology 2017年第1期14卷 118-126页

作者： Jelena S Bezbradica rebecca c coll Kate Schroder Institute for Molecular Bioscience (IMB) IMB Centre for Inflammation and Disease Research and Australian Infectious Diseases Research Centre The University of Queensland Brisbane St Lucia Queensland 4072 Australia

Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.

关键词： inflammasome NLRP3 sterile inflammation TNF

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