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Hepcidin levels in hereditary hyperferritinemia:Insights into the iron-sensing mechanism in hepatocytes

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World Journal of Gastroenterology 2010年第28期16卷 3541-3545页

作者： Jayantha Arnold Arvind Sangwaiya Vijay Manglam mark thursz Caroline Beaumont Caroline Kannengiesser mark Busbridge Department of Gastroenterology Ealing HospitalLondonUB1 3HWUnited Kingdom Department of Hepatology St Mary's Hospital Imperial College LondonLondonW2 1NYUnited Kingdom Biochemical hormones and Genetics Laboratory Bichat Claude Bernard Hospital46Rue Henri HuchardParis75018France Clinical Chemistry Hammersmith Hospital Imperial College LondonLondonW6 8RFUnited Kingdom

AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 ***:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,*** ferritin was 1716.3± 376μg/*** biopsy in one patient did not show any evidence of iron *** hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/*** was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in *** study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.

关键词： Hereditary hyperferritinemia Hereditary hyperferritinemia cataract syndrome Hepcidin Hepcidin assay Iron-sensing mechanism Iron responsive element Ferritin

Role of monocytes and macrophages in experimental and human acute liver failure

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World Journal of Gastroenterology 2010年第15期16卷 1811-1819页

作者： Lucia A Possamai Charalambos Gustav Antoniades Quentin M Anstee Alberto Quaglia Diego Vergani mark thursz Julia Wendon Antiviral Centre 10th Floor QEQM building St Mary’s Hospital Imperial College London Institute of Liver Studies King’s College Hospital

Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.

关键词： Monocyte Macrophage Acute liver failure Inflammation Monocyte chemoattractant protein-1/ chemokine (C-C motif) receptor-2 Cytokine

Liver function tests and metabolic-associated fatty liver disease:Changes in upper normal limits,does it really matter?

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World Journal of Hepatology 2021年第12期13卷 2104-2112页

作者： Roberta Forlano Benjamin H Mullish Ameet Dhar Robert D Goldin mark thursz Pinelopi Manousou Liver Unit/Department of Metabolism Digestion and ReproductionFaculty of MedicineImperial College LondonLondon W21NYUnited Kingdom Centre for Pathology Department of MedicineImperial College LondonLondon W21NYUnited Kingdom

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be *** To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in *** We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to *** conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for *** UNL of aspartate aminotransferase(AST)was 40 IU/*** Total 436 patients were enrolled;of these,288 underwent liver *** a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASH)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%***,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASH”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASH”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASH-related liver *** the UNL might not be beneficial and imply an increase in healthcare *** stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.

关键词： Metabolic-associated fatty liver disease Liver function tests Alanine aminotransferase Fibrosis Stiffness

Granulocyte colony-stimulating factor as a novel adjunct to improve hepatitis B vaccination

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World Journal of Hepatology 2010年第3期2卷 136-138页

作者： Sudeep Tanwar mark thursz Department of Hepatology Imperial College London St Mary's Hospital

Hepatitis B vaccination is successful in 95% of individuals. In the remainder, despite repeated attempts, immunization often remains unsuccessful. 'Non-response' leaves the individual susceptible to infection. Various strategies have been employed to overcome this. These include the use of adjuncts alongside conventional vaccines which activate immune responses. In this case report we demonstrate the successful use of the hematopoietic growth factor Granulocyte colonystimulating factor (G-CSF) as a vaccine adjunct in an individual who had previously failed conventional vaccination three times. The patient tolerated the regimen without any side effects and achieved a hepatitis B surface antibody titer greater than 100 IU/L. Use of G-CSF as a vaccine adjunct for hepatitis B has not previously been reported and the outcome in this case suggests that the use of G-CSF in this context warrants further exploration.

关键词： Hepatitis B Vaccination Adjunct Granulocyte colony-stimulating factor

Design Improvements and Validation of a Novel Fully 3D Printed Analogue Lumbar Spine Motion Segment

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Journal of Bionic Engineering 2024年第3期21卷 1388-1396页

作者： Siril Teja Dukkipati mark Driscoll Musculoskeletal Biomechanics Research Lab Department of Mechanical EngineeringMcGill University845 Sherbrooke St.W(163)MontréalQCH3A 0C3Canada Orthopaedic Research Lab Montreal General Hospital1650 Cedar Ave(LS1.409)MontréalQCH3G 1A4Canada

Spine biomechanical testing methods in the past few decades have not evolved beyond employing either cadaveric studies or finite element modeling ***,both these approaches may have inherent cost and time *** studies are the present gold standard for spinal implant design and regulatory approval,but they introduce significant variability in measurements across patients,often requiring large sample *** element modeling demands considerable expertise and can be computationally expensive when complex geometry and material nonlinearity are *** analogue spine models could complement these traditional methods as a low-cost and high-fidelity alternative.A fully 3D printable L-S1 analogue spine model with ligaments is developed and validated in this *** stiffness of the model under pure bending loading in flexion-extension,Lateral Bending(LB)and Axial Rotation(AR)is evaluated and compared against historical ex vivo and in silico ***,the effect of interspinous,intertransverse ligaments and the Thoracolumbar Fascia(TLF)on spinal stiffness is evaluated by systematic construction of the *** flexion,model Range of Motion(ROM)was 12.92±0.11°(ex vivo:16.58°,in silico:12.96°)at *** LB,average ROM was 13.67±0.12°at 7.5 Nm(ex vivo:15.21±1.89°,in silico:15.49±0.23°).Similarly,in AR,average ROM was 17.69±2.12°at 7.5Nm(ex vivo:14.12±0.31°,in silico:15.91±0.28°).The addition of interspinous and intertransverse ligaments increased both flexion and LB stiffnesses by approximately 5%.Addition of TLF showed increase in flexion and AR stiffnesses by 29%and 24%,*** novel model can reproduce physiological ROMs with high repeatability and could be a useful open-source tool in spine biomechanics.

关键词： Lumbar spine 3D printing Intervertebral disc Biomechanical testing Spine mechanics

The Wave Front Set Correspondence for Dual Pairs with One Member Compact

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Acta Mathematica Sinica,English Series 2024年第3期40卷 823-869页

作者： mark MCKEE Angela PASQUALE Tomasz PRZEBINDA Hammond Lane ProvidenceUT 84332USA Universite de Lorraine CNRSIECLF-57000 MetzFrance Department of Mathematics University of OklahomaNormanOK 73019USA

Let W be a real symplectic space and(G,G')an irreducible dual pair in Sp(W),in the sense of Howe,with G *** G be the preimage of G in the metaplectic group Sp(W).Given an irreducible unitary representation II of G that occurs in the restriction of the Weil representation to G,let On denote its *** prove that,for a suitable embedding T of Sp(W)in the space of tempered distributions on W,the distribution T(On)admits an asymptotic limit,and the limit is a nilpotent orbital *** an application,we compute the wave front set of II',the representation of G dual to II,by elementary means.

关键词： Reductive dual pairs Howe duality Weil representation wave front set orbital integrals

Is Deep Time Geology Scientific?

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Journal of Earth Science 2024年第2期35卷 700-703页

作者： T.mark Harrison Department of Earth Planetary and Space SciencesUniversity of CaliforniaLos Angeles90095USA

We all know what car mechanics *** maintain and repair our automobiles according to established engineering *** all know what physicians *** maintain and repair our bodies according to established medical *** what is it that I do as a scientist?Indeed,am I a scientist?The answer to these questions depends on what we meant by“science”.

关键词： maintain Deep repair

Normal Crossings Singularities for Symplectic Topology:Structures

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Acta Mathematica Sinica,English Series 2024年第1期40卷 107-160页

作者： Mohammad FARAJZADEH-TEHRANI mark MCLEAN Aleksey ZINGER The University of Iowa MacLean HallIowa CityIA 52241 Department of Mathematics Stony Brook UniversityStony BrookNY 11794

Our previous papers introduce topological notions of normal crossings symplectic divisor and variety,show that they are equivalent,in a suitable sense,to the corresponding geometric notions,and establish a topological smoothability criterion for normal crossings symplectic *** present paper constructs a blowup,a complex line bundle,and a logarithmic tangent bundle naturally associated with a normal crossings symplectic divisor and determines the Chern class of the last *** structures have applications in constructions and analysis of various moduli *** a corollary of the Chern class formula for the logarithmic tangent bundle,we refine Aluffi’s formula for the Chern class of the tangent bundle of the blowup at a complete intersection to account for the torsion and extend it to the blowup at the deepest stratum of an arbitrary normal crossings divisor.

关键词： Normal crossings divisor Chern class Logarithmic tangent bundle

Analysis of the inflection points of height-diameter models

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Forest Ecosystems 2024年第4期11卷 414-422页

作者： Tzeng Yih Lam mark J.Ducey Department of Forest Resources Management Faculty of ForestryThe University of British Columbia2045-2424 Main MallVancouverBCV6T 1Z4 Canada Department of Natural Resources and the Environment University of New Hampshire114 James HallDurhamNH 03824USA

The inflection point is an important feature of sigmoidal height-diameter(H-D)*** is often cited as one of the properties favoring sigmoidal model ***,there are very few studies analyzing the inflection points of H-D *** goals of this study were to theoretically and empirically examine the behaviors of inflection points of six common H-D models with a regional *** six models were the Wykoff(WYK),Schumacher(SCH),Curtis(CUR),HossfeldⅣ(HOS),von Bertalanffy-Richards(VBR),and Gompertz(GPZ)*** models were first fitted in their base forms with tree species as random effects and were then expanded to include functional traits and spatial *** distributions of the estimated inflection points were similar between the two-parameter models WYK,SCH,and CUR,but were different between the threeparameter models HOS,VBR,and *** produced some of the largest inflection *** and VBR produced concave H-D curves without inflection points for 12.7%and 39.7%of the tree *** species or decreasing shade tolerance resulted in larger inflection *** trends in the estimated inflection points of HOS and VBR were entirely opposite across the ***,HOS could produce concave H-D curves for portions of the *** on the studied behaviors,the choice between two-parameter models may not *** recommend comparing seve ral three-parameter model forms for consistency in estimated inflection points before deciding on *** sigmoidal models to have inflection points does not necessarily mean that they will produce fitted curves with *** study highlights the need to integrate analysis of inflection points into modeling H-D relationships.

关键词： Concavity Forest inventory and analysis Generalized height-diameter models Growth functions Height-diameter functions Mixed-effects modeling Points of inflection Species-specific models