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Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis

World Journal of Hepatology 2016年第10期8卷 499-508页

作者： Mona Ascha Zeneng Wang Mustafa S Ascha Raed Dweik Nizar N Zein david grove J Mark Brown Stephanie Marshall Rocio Lopez Ibrahim A Hanouneh Department of Gastroenterology and Hepatology Cleveland Clinic Department of Cellular and Molecular Medicine Cleveland Clinic Department of Pulmonary Allergy and Critical Care Medicine/Respiratory Institute Cleveland Clinic Department of Quantitative Health Science Cleveland Clinic Minnesota Gastroenterology Min- neapolis

AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free ***: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53(0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma anal

关键词： Metabolomics Biomarkers Liver disease Model for end-stage liver disease Cirrhosis Alcoholic hepatitis Liver biopsy

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Effects of using headset-delivered virtual reality in road safety research:A systematic review of empirical studies

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Virtual Reality & Intelligent Hardware 2021年第5期3卷 351-368页

作者： Daniel VANKOV david JANKOVSZKY Queensland University of Technology Centre for Accident Research and Road Safety-QueenslandKelvin Grove 4059QueenslandAustralia Asociatia Pentru Tinerii si Studentii din Partium OradeaRomania

To reduce serious crashes,contemporary research leverages opportunities provided by technology.A potentially higher added value to reduce road trauma may be hidden in utilising emerging technologies,such as headset-delivered virtual reality(VR).However,there is no study to analyse the application of such VR in road safety research *** the PRISMA protocol,our study identified 39 papers presented at conferences or published in scholarly *** those sources,we found evidence of VR's applicability in studies involving different road users(drivers,pedestrians,cyclists and passengers).A number of articles were concerned with providing evidence around the potential adverse effects of VR,such as simulator *** work compared VR with conventional *** was also contributing to the emerging field of autonomous ***,few studies leveraged the opportunities that VR presents to positively influence the involved road users'*** on our findings,we identified pathways for future research.

关键词： Empirical evidence Headset Road safety Systematic review Virtual reality

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Education programs for people living with chronic pain:a scoping review

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Frontiers of Nursing 2020年第4期7卷 307-319页

作者： Hai-Ying Wang Carol Grech david Evans Rasika Jayasekara Family Health Golden grove 205 The Golden WayGolden GroveSouth Australia 5125Australia School of Nursing&Midwifery University of South AustraliaAustralia

Objective:The aim of this scoping review was to provide evidence for health practitioners to improve patient education practice for chronic pain ***:A scoping review was guided by Arksey and O’Malley’s(2005)1 five-stage framework,investigated contemporary patient education programs(2007–2018)for chronic pain management in education content,formats of delivery,and tools used for *** analysis and description were used for the outcome ***:Seven quantitative studies were *** content consisted of General information,Cognitive behavior therapy(CBT),Self-management,and Pain neurophysiology(PN).Education delivery formats varied from workbook to workbook,face-toface,online,when given for a group or individual or in a combined *** total,19 tools were reported for the evaluation of the education ***:There is a variety in the education content and the delivery *** majority of programs showed effectiveness in patients’chronic pain management based on their selected evaluation *** review showed that patient education programs can be useful in chronic pain *** effectiveness of patient education programs focuses on the improved patients’physical function and quality of life rather than the cessation of pain only.

关键词： patient education chronic pain management scoping review taxonomy pain patient education

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Modelling ocular ageing in adults with well-controlled type I diabetes

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Advances in Ophthalmology Practice and Research 2022年第2期2卷 11-17页

作者： Jos J.Rozema Adnan Khan david A.Atchison Visual Optics Lab Antwerp(VOLANTIS) Faculty of Medicine and Health SciencesAntwerp UniversityWilrijkBelgium Department of Ophthalmology Antwerp University HospitalEdegemBelgium Research Division Weill Cornell Medicine-QatarDohaQatar Faculty of Health Sciences Khyber Medical UniversityPeshawarPakistan Centre for Vision and Eye Research Queensland University of TechnologyKelvin GroveAustralia

Purpose:To develop a paraxial eye model based on a previously collected cohort of adults with well-controlled type 1 diabetes mellitus(DM1)and a limited range of refractive ***:The study used the previously published biometric data of 72 participants(Age:41.512.4 years)with *** included objective refraction,anterior and posterior corneal radii of curvatures,and internal ***,phakometry was used to determine the lens radii of curvature and lens equivalent indices,from which the lens powers were calculated.A multivariate linear regression was performed for each biometric parameter with respect to current age(Age),the time since the onset of diabetes(Tdb),and current levels of glycated hemoglobin(HbA1c).The vitreous chamber depth was determined from other distances,and lens equivalent index was chosen to balance the *** were compared with an existing model for nondiabetic ***:Some dependent parameters were not affected by the independent variables(spherical equivalent,anterior corneal radius of curvature,central corneal thickness),some were affected by time since onset(the lens radii of curvatures,anterior chamber depth)and others were affected by both age and time since onset(posterior corneal radius of curvature,lens thickness,axial length).None of the dependent parameters were affected by current levels of ***:The proposed model accurately describes the age-related changes in the eyes of people with *** this description the age of diabetes onset plays an important role,especially if the diabetes onset occurred during childhood.

关键词： Diabetes Eye model Refractive error

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Late Miocene ice sheet elevation in the grove Mountains,East Antarctica,inferred from cosmogenic 21 Ne-10Be-26Al

Late Miocene ice sheet elevation in the Grove Mountains,East...

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中国科学院地质与地球物理研究所第十届(2010年度)学术年会

作者： david Fink Institute for Environmental Research Australian Nuclear Science & Technology Organisation Menai NSW2234 Australia

The grove Mountains,lying in the interior of East Antarctica,consist of 64 *** characteristics of the nunataks suggest that past ice sheet elevations have overtopped the summits of the grove *** Ne,Be and Al dating yields surface exposure ages of five bedrock samples taken from the crest of Mount Harding,a typical nunatak in the grove *** multi-nuclide fitting,we have calculated the time that the ice sheet retreated below the crest of Mount Harding;all data point to the late Miocene,～6.3Ma *** results provide the first land-based evidence of the elevation of the East Antarctic Ice Sheet in the grove Mountains in Late Miocene,which reached 2300 m, 200 m higher than the current ice sheet *** higher than current ice sheet elevations during the late Miocene together with contemporaneously higher temperatures in the Southern Ocean suggest that moisture transport plays an important role in ice sheet expansion in the interior of East Antarctica.

关键词： exposure age cosmogenic nuclide grove Mountains Antarctica Late Miocene

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Preliminary study on the erratic exposure ages of grove Mountains,East Antarctica

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Chinese Journal of Polar Science 2009年第1期20卷 15-21页

作者：李广伟刘小汉黄费新孔屏 Fink david 韦利杰方爱民 Institute of Tibetan Plateau Research Chinese Academy of Sciences Graduate University of the Chinese Academy of Sciences Institute of Geology and geophysics Chinese Academy of Sciences Australian Nuclear Science and Technology Organization Menai Institute of Geomechanics Chinese Academy of Geological Sciences

The first study of erratic boulder exposure ages in the grove Mountains, interior Antarctica, indicates the two erratic boulders （060131-1 and 060131-2, collected from a typical nunataks, Zakharoff Ridge in the grove Mountains） have 10 Be minimum exposure ages of 1.24 ±0. 11 Ma, 1.37 ±0. 12 Ma, and ^26Al ages of 0.90 ±0.12 Ma,0.44 ±0.04 Ma, respectively. Meanwhile, another erratic boulder sample 060131-4, coming from vicinal ice surface, has ^10Be and ^26Al minimum exposure ages of 0.47 ±0.3 Ma and 0. 44 ±0.04 Ma, respectively. The exposure ages of the three erratic boulders are nearly similar to the bedrocks with the similar elevation. Thus, using the technique of in situ produced terrestrial cosmogenic nuclides, the ice sheet evolution histories in the grove Mountains reflected by erratic boulder and bedrock exposure ages are basically consistent.

关键词： East Antarctica grove Mountains Zakharoff Ridge, ^10 Be and ^26 AI exposure age erratic boulders.

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The Use of Human Amniotic Membrane for Cartilage Repair: A Sheep Study

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Stem Cell Discovery 2015年第4期5卷 40-47页

作者： Samuel K. Tabet david M. Conner Davis A. Guebert New Mexico Orthopaedic Associates Albuquerque NM USA

Studies show that human amniotic cells’ pluripotentency can be influenced to produce chondrocytes and osteocytes through adding demineralized bone (DMB). Objective: This study evaluates the human amniotic membrane (HAM) mixed with DMB to fill defects in sheep models. We hypothesized this membrane would fill these defects with hyaline-like cartilage with chondrocytes populating the matrix. Design: Six adult sheep were used in this study. One hindquarter knee of each sheep was utilized to make two cartilage defects: one on the femoral condyle and one in the trochlear grove. Three control sheep had unfilled defects. Three sheep received HAM/DMB from a placenta to fill the defects. The membrane was folded so the cellular layer faced the defect and the joint while demineralized bone was placed between the layers. The membranes were fixed to the femur and to the trochlear grove. At six months, the sheep were sacrificed for evaluation. Results: Of the controls, defects did not fill with hyaline or fibrocartilage. In HAM/DMB sheep, 50% of the defects retained the membrane, consistent with other animal models. Membrane defects were examined histologically by a validated scoring system. A strong correlation of little statistical difference between the test and the normal cartilages was observed. The defects that retained membranes had evidence of diffuse chondrocyte-like cell proliferation of stromal matrix similar to hyaline cartilage. Conclusions: HAM/DMB is a potential source of pluripotent cells that can influence chondrogenesis in defects in sheep models. The implications for application in a human model are promising and warrant further study.

关键词： Stem Cell Chondrocytes Amniotic Membrane Pluripotent Demineralized Bone

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东南极格罗夫山萨哈罗夫岭漂砾暴露年龄初探

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极地研究 2009年第4期21卷 265-271页

作者：李广伟刘小汉黄费新孔屏 david Fink 韦利杰方爱民中国科学院青藏高原研究所地球动力学实验室北京100085 中国科学院研究生院北京100049 中国科学院地质与地球物理研究所北京100029 Australian Nuclear Science and Technology Orgnization MenaiNSW 2234Australia 中国地质科学院地质力学研究所北京100081

首次对格罗夫山地区漂砾的暴露年龄进行的研究表明,萨哈罗夫岭冰原岛峰的两块漂砾样品的^(10)Be最小暴露年龄分别为1.24±0.11Ma和1.37±0.12Ma,^(26)Al最小暴露年龄分别为0.90±0.12Ma和0.44±0.04Ma。萨哈罗夫岭附近冰面上的漂砾样品... 详细信息

首次对格罗夫山地区漂砾的暴露年龄进行的研究表明,萨哈罗夫岭冰原岛峰的两块漂砾样品的^(10)Be最小暴露年龄分别为1.24±0.11Ma和1.37±0.12Ma,^(26)Al最小暴露年龄分别为0.90±0.12Ma和0.44±0.04Ma。萨哈罗夫岭附近冰面上的漂砾样品的^(10)Be和^(26)Al最小暴露年龄分别是0.47±0.3Ma和0.44±0.04Ma。考虑到误差,萨哈罗夫岭三块漂砾的最小暴露年龄与相近高程的基岩样品的最小暴露年龄基本一致。因此,在利用原地生成宇宙成因核素测年技术对东南极内陆格罗夫山地区的冰川消涨历史进行研究时,基岩和漂砾暴露年龄所反映出的冰川演化历史是明显吻合的。

关键词：东南极格罗夫山萨哈罗夫岭 ~10Be和~26Al暴露年龄漂砾

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IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion

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Cellular & Molecular Immunology 2021年第9期18卷 2199-2210页

作者： Sadiq Umar Karol Palasiewicz Katrien Van Raemdonck Michael V.Volin Bianca Romay MAsif Amin Ryan K.Zomorrodi Shiva Arami Mark Gonzalez Vikram Rao Brian Zanotti david A.Fox Nadera Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoIL60612USA Department of Medicine Division of RheumatologyUniversity of Illinois at ChicagoChicagoIL60612USA Department of Microbiology and Immunology Midwestern UniversityDowners GroveIL60515USA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMI481096USA Department of Orthopedic Surgery University of Illinois at ChicagoChicagoIL60612USA Pfizer Research CambridgeMA02139USA

Flares of joint inflammation and resistance to currently available biologic therapeutics in rheumatoid arthritis(RA)patients could reflect activation of innate immune ***,we show that a TLR7 GU-rich endogenous ligand,miR-Let7b,potentiates synovitis by amplifying RA monocyte and fibroblast(FLS)***-Let7b ligation to TLR7 in macrophages(MΦs)and FLSs expanded the synovial inflammatory ***,secretion of M1 monokines triggered by miR-Let7b enhanced Th1/Th17 cell *** showed that IRAK4 inhibitor(i)therapy attenuated RA disease activity by blocking TLR7-induced M1 MΦor FLS activation,as well as monokine-modulated Th1/Th17 cell ***4i therapy also disrupted RA osteoclastogenesis,which was amplified by miR-Let7b ligation to joint myeloid ***,the effectiveness of IRAK4i was compared with that of a TNF inhibitor(i)or anti-IL-6R treatment in collagen-induced arthritis(CIA)and miR-Let7b-mediated *** found that TNF or IL-6R blocking therapies mitigated CIA by reducing the infiltration of joint F480+iNOS+MΦs,the expression of certain monokines,and Th1 cell ***,these biologic therapies were unable to alleviate miR-Let7b-induced *** superior efficacy of IRAK4i over anti-TNF or anti-IL-6R therapy in miR-Let7b-induced arthritis or CIA was due to the ability of IRAK4i therapy to restrain the migration of joint F480+iNOS+MΦs,vimentin+fibroblasts,and CD3+T cells,in addition to negating the expression of a wide range of monokines,including IL-12,MIP2,and IRF5 and Th1/Th17 *** conclusion,IRAK4i therapy may provide a promising strategy for RA therapy by disconnecting critical links between inflammatory joint cells.

关键词： TLR7 MΦs RA FLSs osteoclasts T cells IRAK4

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Macrophages are the primary effector cells in IL-7-induced arthritis

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Cellular & Molecular Immunology 2020年第7期17卷 728-740页

作者： Seung-jae Kim Huan J.Chang Michael VVolin Sadiq Umar Katrien Van Raemdonck Aimee Chevalier Karol Palasiewicz John W.Christman Suncica Volkov Shiva Arami Mehrdad Maz Anjali Mehta Ryan K.Zomorrodi david A.Fox Nadera Sweiss Shiva Shahrara Division of Rheumatology Jesse Brown VAMedical CenterChicagoIL 60612USA Department of Medicine Division of RheumatologyUniversity of Illinois at ChicagoChicagoIL 60612USA Department of Microbiology and Immunology Chicago College of Osteopathic MedicineMidwestern UniversityDowners GroveIL 60515USA Pulmonary Critical Care and Sleep MedicineOhio State University Wexner Medical CenterDavis Heart and Lung Research InstituteColumbusOH 43210USA Division of Allergy Clinical Immunology and RheumatologyThe University of Kansas Medical CenterKansas CityKS 66160USA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMI 481096USA

Synovial macrophages are crucial in the development of joint inflammation and bone damage;however, the pathways that controlmacrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined thatelevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highlyresponsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), andtumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine *** local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480^(+)iNOS^(+) cells rather than CD3^(+)T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ ***, in RAG−/− mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lackof IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in theunique F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) subset, with no impact on the F480^(+)Arginase^(+) cell or CD3^(+) T cell frequency. Consistent with thepreclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealedthat IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) cell function, which activates TH-1 cells to amplify myeloid IL-7Rexpression and disease severity.

关键词： myeloid elevated inflammation

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