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Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo

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Bone Research 2019年第4期7卷 388-398页

作者： Marietta Landgraf christoph ALahr Alvaro Sanchez-Herrero christoph Meinert Ali Shokoohmand Pamela MPollock Dietmar WHutmacher Abbas Shafiee Jacqui AMcGovern Centre in Regenerative Medicine Institute of Health and Biomedical InnovationQueensland University of TechnologyBrisbaneAustralia School of Biomedical Science Institute of Health and Biomedical InnovationTranslational Research InstituteQueensland University of TechnologyBrisbaneAustralia Australian Research Council(ARC)Training Centre in Additive Biomanufacturing Queensland University of TechnologyBrisbaneAustralia UQ Diamantina Institute Translational Research InstituteThe University of QueenslandBrisbaneQLDAustralia

Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered *** significant effort,there is no animal model capable of recapitulating the complexity of PCa bone *** humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and *** humanized tissueengineered bone construct(hTEBC)was created within NOD-scid IL2rgnull(NSG)mice and was used for the study of experimental PC3-Luc bone *** was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine *** translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies,the non-species-specific bisphosphonate zoledronic acid(ZA)or the human-specific antibody Denosumab,both targeting Receptor Activator of Nuclear Factor Kappa-Β***,but not Denosumab,significantly decreased metastases in hTEBCs,but not murine *** results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human ***,it will enable the development of new effective antimetastatic treatments.

关键词： metastasis PC3 drugs

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Towards a better understanding of antimicrobial resistance dissemination:what can be learnt from studying model conjugative plasmids?

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Military Medical Research 2022年第5期9卷 592-602页

作者： Zhen Shen christoph M.Tang Guang-Yu Liu Sir William Dunn School of Pathology University of OxfordOxfordOX13REUK Department of Laboratory Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China

Bacteria can evolve rapidly by acquiring new traits such as virulence,metabolic properties,and most importantly,antimicrobial resistance,through horizontal gene transfer(HGT).Multidrug resistance in bacteria,especially in Gram-negative organisms,has become a global public health threat often through the spread of mobile genetic *** represents a major form of HGT and involves the transfer of DNA from a donor bacterium to a recipient by direct *** plasmids,a major vehicle for the dissemination of antimicrobial resistance,are selfish elements capable of mediating their own transmission through *** spread to and survive in a new bacterial host,conjugative plasmids have evolved mechanisms to circumvent both host defense systems and compete with co-resident *** mechanisms have mostly been studied in model plasmids such as the F plasmid,rather than in conjugative plasmids that confer antimicrobial resistance(AMR)in important human pathogens.A better understanding of these mechanisms is crucial for predicting the flow of antimicrobial resistance-conferring conjugative plasmids among bacterial populations and guiding the rational design of strategies to halt the spread of antimicrobial ***,we review mechanisms employed by conjugative plasmids that promote their transmission and establishment in Gram-negative bacteria,by following the life cycle of conjugative plasmids.

关键词： Horizontal gene transfer Antimicrobial resistance Conjugative plasmids Type IV secretion system Restriction-modification systems SOS response Entry exclusion Fertility inhibition

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Resections for colorectal liver metastasis: the breakthrough of laparoscopic surgery?

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 548-550页

作者： Mohammad Abu Hilal christoph Kuemmerli Department of Surgery Istituto Fondazione PoliambulanzaBresciaItaly Department of Surgery University Hospital Southampton NHS Foundation TrustSouthamptonUK

Liver resection is still considered the treatment of choice for colorectal liver metastasis(CRLMs)with 5-year survival rates of 40–58%when associated with modern regimes of chemotherapy.

关键词： metastasis colorectal chemotherapy

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Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients

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World Journal of Gastroenterology 2010年第43期16卷 5447-5451页

作者： Sylvia Brost Paul Schnitzler Wolfgang Stremmel christoph Eisenbach Department of Gastroenterology and Infectious Diseases University of Heidelberg Department of Infectious Diseases Virology University of Heidelberg

AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response.

关键词： Hepatitis B virus Entecavir Immunosuppression Hepatitis B surface antigen Seroconversion

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Neural correlates of the Heidelberg Music Therapy: indicators for the regeneration of auditory cortex in tinnitus patients?

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Neural Regeneration Research 2015年第9期10卷 1373-1375页

作者： christoph M.Krick Heike Argstatter Department of Neuroradiology Saarland University Hospital German Center for Music Therapy Research (Viktor Dulger Institute) DZM

Tinnitus, the phenomenon of ringing or buzzing in the ears without an external sound source is one of the most commonly reported symptoms in otorhinolaryngology and affects 10 - 15% of the general population. Models have been developed to account for neural basis of tinnitus, its pathogenesis and its consequences on mental health （deRidder et al., 2013）. In most cases tinnitus onset follows a partial hearing impairment. Peripheral sensory deprivation due to cochlear damages may prompt increased neuronal activity in the central auditory system in order to adapt the neural sensitivity to the reduced sensory inputs. This central gain could over amplify the ＂neural noise＂ and thus trigger a homeostatic down-regulation of inhib- itory synapses in the auditory cortical map leading to specific reorganization of the cortical representation of the tinnitus percept. Dysfunctional feedback connections from limbic regions to auditory brain areas, interacting at the thalamic level, may account for the psychological impairment.

关键词： indicators for the regeneration of auditory cortex in tinnitus patients Neural correlates of the Heidelberg Music Therapy PTC

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Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients

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World Journal of Gastroenterology 2007年第3期13卷 421-425页

作者： christoph Elsing Sabine Harenberg Wolfgang Stremmel Thomas Herrmann Department of Gastroenterology St. Elisabeth Hospital Dorsten Germany Department of Gastroenterology University of Heidelberg Germany

AIM： To evaluate plasma levels of nitrite/nitrate （NOx）, soluble Pas （spas） antigen, tumor necrosis factor alpha （TNF-α） and interleukin-6 （IL-6） in patients with compensated and acute decompensated cirrhosis and to evaluate mediators causing acute decompensation in liver cirrhosis, METHODS： This prospective study was conducted in the medical intensive care unit of an academic tertiary center, Fifty-five patients with acute decompensation （gastrointestinal hemorrhage, encephalopathy, hydropic decompensation） and twenty-five patients with compensated liver drrhosis were included, Blood samples were taken for analyses of spas, Nox, IL-6, TNF-α, Liver enzymes and kidney functions were also tested, RESULTS： In patients with acute decompensation, plasma spas levels were higher than in non-decompensated patients （15305 ± 4646 vs 12458± 4322 pg/mL, P 〈 0.05）. This was also true for the subgroup of patients with alcoholic liver cirrhosis （P 〈 0.05）. The other mediators were not different and none of the parameters predicted survival, except for ALT （alanine-aminotransferase）. In patients with portal-hypertension-induced acute hemorrhage, NOx levels were significantly lower than in patients with other forms of decompensation （70.8 ± 48.3 vs 112.9 ± 74.9 pg/mL, P 〈 0.05）. When NOx levels were normalized to creatinine levels, the difference disappeared. IL-6, TNF-α and spas were not different between bleeders and non-bleeders. In decompensated patients spas, IL-6 and NOx levels correlated positively with creatinine levels, while IL-6 levels were dependent on Child class. CONCLUSION： In acute decompensated cirrhotic patients sPas is increased, suggesting a role of apoptosis in this process and patients with acute bleeding have lower NOx levels, However, in this acute complex clinical situation, kidney function seems to have a predominant influence on mediator levels,

关键词： Variceal hemorrhage Liver cirrhosis Cytokine Nitrite/nitrate Soluble Fas

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Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea

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World Journal of Gastroenterology 2014年第42期20卷 15837-15844页

作者： christoph G Dietrich Tanja Kottmann Manuela Alavi Department of Medicine Bethlehem Hospital Teaching Hospital of Aachen University RWTH Private Institute of Medical Statistics

AIM: To investigate the effect of Lactobacillus-containing commercially available probiotic formulations in Germany during antibiotic treatment with an analysis of cost-efficiency.

关键词： Antibiotics-associated diarrhea Probiotics Lactobacillus casei

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Replacing Stirrups of Self-Compacting Concrete Beams with Steel Fibers

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Transactions of Tianjin University 2010年第6期16卷 411-416页

作者：尤志国丁一宁 NIEDEREGGER christoph State Key Laboratory of Coastal and Offshore Engineering Dalian University of Technology Faculty of Civil Engineering University of Innsbruck

Based on the investigation of fiber influence on workability of self-compacting concrete (SCC), tests were carried out on two series of SCC rectangular simply supported beams, which were made of hooked steel fibers reinforced concrete with or without stirrups, subjected to four-point symmetrically placed vertical loads. The major test variables are steel fiber contents and stirrup ratios. The results indicate that the ultimate load significantly increases with the increase of fiber content; the addition of ...

关键词： steel fiber self-compacting concrete beam ultimate shear strength failure mode workability

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Selected Recent Applications of Sparse Grids

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Numerical Mathematics(Theory,Methods and Applications) 2015年第1期8卷 47-77页

作者： Benjamin Peherstorfer christoph Kowitz Dirk Pfluger Hans-Joachim Bungartz Scientific Computing Group Dept.of Computer ScienceBoltzmannstr.385748 GarchingGermany Institutefor Advanced Study Technische UniversitätMünchenLichtenbergstr.2a85748 GarchingGermany Institute for Parallel and Distributed Systems University of StuttgartUni-versitätsstr.3870569 StuttgartGermany

Sparse grids have become a versatile tool for a vast range of applications reaching from interpolation and numerical quadrature to data-driven problems and uncertainty *** review four selected real-world applications of sparse grids:financial product pricing with the Black-Scholes model,interactive explo-ration of simulation data with sparse-grid-based surrogate models,analysis of simu-lation data through sparse grid data mining methods,and stability investigations of plasma turbulence simulations.

关键词： Sparse grids hierarchical decomposition adaptivity combination technique

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Screening for nonalcoholic fatty liver disease-when,who and how?

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World Journal of Gastroenterology 2021年第35期27卷 5803-5821页

作者： christoph G Dietrich Monika Rau Andreas Geier Department of Internal Medicine Bethlehem Health CenterStolberg 52222Germany Department of Internal Medicine II University Hospital WürzburgWürzburg 97080Germany Department of Medicine II University Hospital WürzburgWürzburg 97080Germany

Nonalcoholic fatty liver disease(NAFLD)is becoming a frequent liver disease,especially in patients with metabolic syndrome and especially in Western *** of NAFLD comprise progressive fibrosis,cirrhosis and hepatocellular *** also represents an independent risk factor for cardiovascular disease,extrahepatic neoplasia and other organ damage,such as renal *** the epidemiological importance of the disease,new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis,NAFLD should be subject to screening programs,at least in countries with a high prevalence of the *** review discusses prerequisites for screening,cost-effectiveness,current guideline recommendations,suitability of techniques for screening and propositions for the following questions:Who should be screened?Who should perform screening?How should screening be performed?It is time for a screening program in patients at risk for NAFLD.

关键词： Screening Nonalcoholic fatty liver disease Diabetes Liver fibrosis Cirrhosis

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