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Manipulating the Gut Microbiome to Alleviate Steatotic Liver Disease:Current Progress and challenges

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Engineering 2024年第9期40卷 51-60页

作者： Ernesto Saenz Nathally Espinosa Montagut Baohong Wang ch.istoph.stein-th.ringer Kaicen Wang Honglei Weng Matthias Ebert Kai Markus Schneider Lanjuan Li Andreas Teufel Division of Hepatology Division of Clinical BioinformaticsDepartment of Medicine ⅡMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany Clinical Cooperation Unit Healthy Metabolism Center for Preventive Medicine and Digital HealthMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany School of Medicine Universidad de Los AndesBogotá111711Colombia State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Internal MedicineⅠ University Clinic Tuebingen&CoE CMFI(Controlling Microbes to Fight Infections)Tuebingen 72074Germany Department of MedicineⅡ Medical Faculty MannheimHeidelberg UniversityMannheim 68167Germany DKFZ Hector Cancer Institute at the University Medical Center Mannheim 69120Germany Molecular Medicine Partnership Unit European Molecular Biology LaboratoryHeidelberg 69117Germany Department of MedicineⅢ University Hospital RWTH AachenAachen 52074Germany

the prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder *** is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean ***,it is crucial to develop effective therapies for this complex ***,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative *** research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary *** suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.

关键词： Microbiome Fecal microbiota transplantation Metabolic-dysfunction-associated steatotic liver disease Fatty liver

TT viral infection through blood transfusion:retrospective investigation on patients in a prospective study of post-transfusion hepatitis

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World Journal of Gastroenterology 2000年第1期6卷 70-73页

作者： Yang SS Wu ch chen th Huang YY Huang CS Department of Gastroenterology china Medical College TaichungTaiwanChina Cathay General HospitalTaipei and Medical Faculty China Medical CollegeTaichungTaiwanChina Department of Gastroenterology china Medical College TaichungTaiwanChina Department of Laboratory Medicine china Medical College TaichungTaiwanChina

AIM To investigate the role of bloodtransfusion in TT viral infection(TTV).MEthODS We retrospectively studied serumsamples from 192 transfusion recipients whounderwent cardiovascular surgery and bloodtransfusion between July 1991 and June *** had a follow-up every other week for atleast 6 months after *** received blood before screeningdonors for hepatitis C antibody(anti-HCV),and112 recipients received screened *** with alanine aminotransferase level>2.5 times the upper normal limit were testedfor serological markers for viral hepatitis A,B,C,G,Epstein-Barr virus and *** infection was defined by the positivity forserum TTV DNA using the polymerase chainreaction *** Eleven and three patients,whoreceived anti-HCV unscreened and screened'blood,respectively,had serum ALT levels>90 IU/*** patients(HCV and TTV:1;HCV,HGV,and TTV:1;TTV:2;and CMV and TTV:1)were positive for TTV DNA,and four of them hadsero-conversion of TTV *** TTV can be transmitted viablood *** recipients infected byTTV alone may be associated with the ***,whether TTV was the causal agentremains unsettled,and further studies arenecessary to define the role of TTV infection inchronic hepatitis.

关键词： Subject headings blood transfusion TT viral infection hepatitis C antibody viral

ON KARUSH-KUHN-TUCKER POINTS FOR A SMOOthING MEthOD IN SEMI-INFINITE OPTIMIZATION

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Journal of Computational Mathematics 2006年第6期24卷 719-732页

作者： Oliver stein Department o.f Mathematics-C RWTH Aachen University Germany

We study the smoothing method for the solution of generalized semi-infinite optimization problems from （O. stein, G. Still： Solving semi-infinite optimization problems with interior point techniques, SIAM J. Control Optim., 42（2003）, pp. 769-788）. It is shown that Karush-Kuhn-Tucker points of the smoothed problems do not necessarily converge to a Karush-Kuhn-Tucker point of the original problem, as could be expected from results in （F. Facchinei, H. Jiang, L. Qi： A smoothing method for mathematical programs with equilibrium constraints, Math. Program., 85（1999）, pp. 107-134）. Instead, they might merely converge to a Fritz John point. We give, however, different additional assumptions which guarantee convergence to Karush-Kuhn：Tucker points.

关键词： Generalized semi-infinite optimization Stackelberg game Constraint qualifi-cation Smoothing NCP function.

Comparing intellectual and graphical complexities of traditional and image-derived landuse maps

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Science china(Technological Sciences) 2010年第S1期53卷 205-212页

作者： stein Alfred Earth Observation Science International Institute for Geo-Information Science and Earth Observation

Remotely sensed images have become a powerful source for landuse *** far,no quantitative comparison and evaluation exist on the differences between an image-derived landuse map and a traditional landuse *** comparison and evaluation may indicate the possibility for the replacement of a traditional landuse map by an image-derived *** complexity is widely used to describe cartographic representations and map effectiveness from intellectual aspect and graphical *** paper quantifies intellectual and graphical map complexities to explore the differences between these two kinds of *** complexity concerns the meaning or significations contained on a *** complexity concerns spatial characteristics of the graphical content on a *** show that the high graphical complexity of the image-derived landuse map is not harmonized with its low intellectual *** intention of this paper is to encourage realistic cognition of the accuracy and problems existing in image-derived landuse maps.

关键词： landuse map intellectual complexity graphical complexity

Modern developments in image mining

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Science china(Technological Sciences) 2008年第S1期51卷 13-25页

作者： Alfred stein ITC PO Box 6 7500 AA EnschedeNetherlands

this paper presents some new developments in image mining. Image mining con-siders the chain from object identification from remote sensing images through modeling,tracking on a series of images and prediction,towards communication to stakeholders. Attention is given to image mining for vague and uncertain objects. Aspects of up-and down-scaling are addressed. We further consider in this paper both spatial interpolation and decision making. the paper is illustrated with several case studies.

关键词： image mining uncertain objects spatial data quality decision making scale

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 387-400页

作者： Mark N stein Rutgers Cancer Institute of New Jersey Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA. Department of Medicine Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA. Section of Urologic Oncology Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew Brunswick New Jersey USA.

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer （CRPC）, it is possible to detect persistent activation of the androgen receptor （AR） through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17（^-hydroxylase and 17,20-1yase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival （OS） with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone （ACth）, providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-1yase （orteronel, galeterone and VT-464） that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

关键词： androgen synthesis castration-resistant prostate cancer treatment

Use of a multi-temporal grid method to analyze changes in glacier coverage in the Tibetan Plateau

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Progress in Natural Science:Materials International 2009年第7期19卷 861-872页

作者： Alfred stein International Institute for Geo-Information Science and Earth Observation (ITC)

this paper describes a multi-temporal grid method for quantifying changes in glacier coverage. A multi-temporal grid synthesizes spatial, attribute and process components of glacier information by sequentially combining spatial data from satellite images or maps. It enables us to identify glacier retreat and advance areas in individual grid cells for three or more periods of data sets. Discrepancies among the sequential data sets were detected graphically and numerically, including noise from geo-location error, misclassification, or different interpretation results in various pixel resolutions. Noise was detected and corrected to a large extent by visualization of the synthetic grid. the paper compares the results with that from a common method based on individual data sets, focusing on the Mt. Naimona’Nyi and Mt. Qomolangma regions at the northern slopes of the Himalayas. Results show that the identified noise (e.g. by 2.5 km2 in the Mt. Naimona’Nyi region) is much larger than measurement uncertainty calculated by sensor resolution and coregistration error (e.g. by 0.015 km2 in the Mt. Naimona’Nyi region). After noise removal, we notice that glacier recession clearly accelerates. the multi-temporal grid method results in a better quantification of glacier variation. It shows that glaciers in the Himalayas have both retreated and advanced during the last several decades, with retreat dominating and accelerating. Glaciers on the northern slope of Mt. Qomolangma in the middle Himalayas retreat more extensively and faster than those in the Mt. Naimona’Nyi region in the western Himalayas.

关键词： Glacier Multi-temporal grid Mt. Naimona’Nyi Mt. Qomolangma Himalayas Tibetan Plateau

Mitochondrial malfunction in vanishing white matter disease： a disease of the cytosolic translation machinery

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Neural Regeneration Research 2017年第10期12卷 1610-1612页

作者： Orna Elroy-stein Dept of Cell Research and Immunology George S.Wise Faculty of Life Sciences Sagol School of NeuroscienceTel Aviv UniversityIsrael

Vanishing white matter （VWM） disease - a disease of the cytosolic translation machinery： VWM is a recessive genet- ic neurodegenerative disease caused by mutations in any of the five genes encoding the subunits of ... 详细信息

关键词： Mitochondrial malfunction in vanishing white matter disease:a disease of the cytosolic translation machinery ETC

Calcium isotope compositions as a means to trace carbonate recycling

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National Science Review 2022年第6期9卷 8-10页

作者： Shichun Huang stein B.Jacobsen Department of Geoscience University of Nevada Department of Earth and Planetary Sciences Harvard University

Marine carbonates, such as sedimentary carbonates and secondary carbonates formed during marine alteration processes, are returned to the mantle at subduction zones, and their fates regulate the global carbon cycle. S... 详细信息

关键词： Carbonates