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Level of education and mortality after radical prostatectomy

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Asian Journal of Andrology 2017年第2期19卷 173-177页

作者： Michael Froehner Rainer Koch Stefan propping Dorothea Liebeheim Matthias Hfibler Gustavo B Baretton Oliver W Hakenberg manfred p wirth Department of Urology University Hospital 'Carl Gustav Carus' Technische Universit~t Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Medical Statistics and Biometry University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Anesthesiology University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of pathology University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Urology University of Rostock Ernst-Heydemann-Strasse 6 D-18055 Rostock Germany

Estimating the risk of competing mortality is of importance in men with early prostate cancer to choose the most appropriate way of management and to avoid over- or under-treatment. In this study, we investigated the impact of the level of education in this context. The study sample consisted of 2630 patients with complete data on level of education （college, university degree, master craftsmen, comparable profession, or others）, histopathological tumor stage （organ confined or extracapsular）, lymph node status （negative or positive）, and prostatectomy specimen Gleason score （〈7, 7, or 8-10） who underwent radical prostatectomy between 1992 and 2007. Overall, prostate cancer-specific, competing, and second cancer-related mortalities were study endpoints. Cox proportional hazard models for competing risks were used to study combined effects of the variables on these endpoints. A higher level of education was independently associated with decreased overall mortality after radical prostatectomy （hazard ratio [HR]： 0.75, 95% confidence interval [95% CI]： 0.62-0.91, p = 0.0037）. The mortality difference was attributable to decreased second cancer mortality （HR： 0.59, 95% Ch 0.40-0.85, p = 0.0052） and noncancer mortality （HR： 0.73, 95% Ch 0.55-0.98, p = 0.0345） but not to differences in prostate cancer-specific mortality （HR： 1.16, 95% Ch 0.79-1.69, p = 0.4536 in the full model）. In conclusion, the level of education might serve as an independent prognostic parameter supplementary to age, comorbidity, and smoking status to estimate the risk of competing mortality and to choose optimal treatment for men with early prostate cancer who are candidates for radical prostatectomy.

关键词： comorbidity competing risk analysis level of education life expectancy mortality proportional hazards model prostate cancer radical prostatectomy smoking socioeconomic status

Single-cell trajectories of melanoma cell resistance to targeted treatment

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Cancer Biology & Medicine 2022年第1期19卷 56-73页

作者： Maria Schmidt Lena Sünke Mortensen Henry Loeffler-wirth Corinna Kosnopfel Knut Krohn Hans Binder manfred Kunz Interdisciplinary Centre for Bioinformatics University of LeipzigLeipzig 04107Germany Department of Dermatology Venereology and AllergologyUniversity of WürzburgWürzburg 97074Germany Core Unit DNA Technologies Medical FacultyUniversity of LeipzigLeipzig 04103Germany Department of Dermatology Venereology and AllergologyUniversity of Leipzig Medical CenterLeipzig 04103Germany

Objective:Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant melanoma.Recent developments in single-cell sequencing technology have provided deeper insights into these mechanisms.Methods:Here,we analyzed a BRAFV600 E-mutant melanoma cell line by single-cell RNA-seq under various conditions:cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or trametinib.Dimensionality reduction by t-distributed stochastic neighbor embedding and self-organizing maps identified distinct trajectories of resistance development clearly separating the 4 treatment conditions in cell and gene state space.Results:Trajectories associated with resistance to single-agent treatment involved cell cycle,extracellular matrix,and de-differentiation programs.In contrast,shifts detected in double-resistant cells primarily affected translation and mitogen-activated protein kinase pathway reactivation,with a small subpopulation showing markers of pluripotency.These findings were validated in pseudotime analyses and RNA velocity measurements.Conclusions:The single-cell transcriptomic analyses reported here employed a spectrum of bioinformatics methods to identify mechanisms of melanoma resistance to single-and double-agent treatments.This study deepens our understanding of treatmentinduced cellular reprogramming and plasticity in melanoma cells and identifies targets of potential relevance to the management of treatment resistance.

关键词： Melanoma single-cell transcriptome sequencing treatment response

Relationship of Isokinetic Leg press Force with Jumping performance and 1RM in the Squat

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Journal of Science in Sport and Exercise 2022年第2期4卷 180-187页

作者： Sebastian Möck Stefan Erlewein Christoph Mickel Klaus wirth Department of Exercise Science Olympic Training and Testing Center of HessenOtto-Fleck-Schneise 460528 Frankfurt am MainGermany Institute of Applied Training Science LeipzigGermany Athlyzer GmbH Frankfurt am MainGermany Sport and Exercise Sciences University of Applied Sciences Wiener NeustadtWiener NeustadtAustria

purpose Muscle strength and power are important requirements in many sports.The correlation of jumping performance as manifestation of muscle power and squatting one-repetition maximum(1RM)has been shown in several investigations.Correlations with maximum force in a linear isokinetic leg press are still pending.Since different testing devices produce different relationships and rotational isokinetic measurements show conflicting results,further evidence is needed.Methods We investigated the correlation of isokinetic leg press force at 0.1 m/s and 0.7 m/s with squat 1RM and jumping performance in different vertical jumps.Results The results show medium to strong,significant correlations for isokinetic force at 0.1 m/s with squat-and counter-movement-jump performance,whereas isokinetic force at 0.7 m/s showed strong,significant correlations for both jumping tests.Drop jump performance(dropping heights:20,30,40,and 50 cm,respectively)reveals weak to medium,significant correlations with isokinetic force at 0.1 m/s and weak,significant correlations with isokinetic force at 0.7 m/s.Squat 1RM displays strong relationships to isokinetic force with greater coefficients regarding higher movement speed in the isokinetic condition.Conclusion The maximum strength of the leg extensors displays a basic requirement for vertical jumping with great motion in knee-and hip-joints and should be considered in training programs.For vertical jumps that are mainly generated via ankle motion,maximum strength of knee-and hip-extensors plays an indirect role to guarantee for performance-enhancing mechanisms.Additionally,in strength testing,different manifestations of strength performance should carefully be taken into account.

关键词： Isokinetics Diagnostics performance Resistance Training

Current treatment options and response rates in children with chronic hepatitis C

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World Journal of Gastroenterology 2012年第2期18卷 99-104页

作者： Stefan wirth Helios Medical Centre Wuppertal Department of PediatricsWitten-Herdecke UniversityD-42283 WuppertalGermany

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (pEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous pEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or pEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients.Stratified for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of pEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

关键词：丙型肝炎病毒治疗方案慢性感染儿童利巴韦林传播模式基因型干扰素

Boosting T cell immunity against cytomegalovirus:a potential strategy combating human aging and age-related diseases

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4417-4418页

作者： Matthias wirth Walburgis Brenner Oliver H.Kramer Department of Hematology Oncology and Cancer ImmunologyCampus Benjamin FranklinCharite-Universitatsmedizin Berlincorporate member of Freie Universitat Berlin and Humboldt-Universitat zu BerlinBerlinGermany University Medical Center Gottingen Department of GeneralVisceral and Pediatric SurgeryGottingenGermany German Cancer Consortium(DKTK) German Cancer Research Center(DKFZ)HeidelbergGermany Clinic for Obstetrics and Women's Health University Medical CenterJohannes Gutenberg University MainzLangenbeckstr.155131 MainzGermany Department of Toxicology University Medical CenterMainzGermany

In a recent publication in Cell,Hasegawa and colleagues reveal that cytotoxic CD4-positive cytotoxic T lymphocytes(CD4+CTLs)eliminate senescent fibroblasts with a surface expression of the immunologically important human leukocyte antigen class Il(HLA-)and the human cytomegalovirus glycoprotein B(HCMV-gB).1 This implies that a virome-immune cell interaction controls the fate of human skin cells that are linked to the aging process and associated diseases.

关键词： immunity cytomegalovirus cytotoxic

Interaction phenomena between liquid droplets and hot particles—Captured via high-speed camera

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particuology 2009年第4期7卷 260-263页

作者： Sebastian Gehrke Karl-Ernst wirth Institute of particle Technology Cauerstrasse 4Erlangen 91058Germany

The interaction of evaporating droplets and hot catalyst particles plays a major role in heterogeneously catalysed reactions. The liquid feed is injected into a gas-solid flow and is mixed with the catalyst. The interaction phenomena determine the evaporation time which should be minimised to keep the reactor vessel small. First measurements with a bed of fixed hot FCC-particles （fluid catalytic cracking） and two model fluids have been conducted. The interactions of ethanol and water droplets with the hot bed surface were captured via a high-speed camera. While the ethanol droplet developed a stable steam cushion due to Leidenfrost phenomena, water showed intense interaction and steam explosions which induced repulsion and atomisation of the droplet.

关键词： particle-droplet-interaction Leidenfrost phenomenon Direct heat transfer Liquid-feed-injection

Affairs happen---to whom？ A study on extrapair paternity in common nightingales

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Current Zoology 2017年第4期63卷 421-431页

作者： Conny LANDGRAF Kerstin WILHELM Jutta wirth Michael WEISS Silke KIppER Leibniz Institute for Zoo and Wildlife Research (IZW) Alfred-Kowalke-StraBe 17 10315 Berlin Germany Animal Behavior Group Free University of Berlin TakustraBe 6 14195 Berlin Germany Institute of Evolutionary Ecology and Conservation Genomics University of UIm Albert Einstein Allee 11 89069 UIm Germany Behavioural Ecology Group Department of Animal Sciences Wageningen University De Elst 1 6708 WD Wageningen The Netherlands Department of Exposition Unit Epidemiology Statistics and Mathematical Modelling Federal Institute for Risk Assessment (BfR) Max-Dohrn-Str. 8-10 10589 Berlin Germany Chair of Zoology School of Life Sciences Weihenstephan Technische Universitat Munchen LieseI-Beckmann-StraBe 4 85350 Freising Germany

Most birds engage in extrapair copulations despite great differences across and within species. Besides cost and benefit considerations of the two sex environmental factors have been found to alter mating strategies within or between populations and/or over time. For socially monogamous species, the main advantage that females might gain from mating with multiple males is probably increasing their offspring's genetic fitness. Since male (genetic) quality is mostly not directly measurable for female birds, (extrapair) mate choice is based on male secondary traits. In passerines male song is such a sexual ornament indicating male phenotypic and/or genetic quality and song repertoires seem to affect female mate choice in a number of species. Yet their role in extrapair mating behavior is not well understood. In this study, we investigated the proportion of extrapair paternity (Epp) in a population of common nightingales . We found that Epp rate was rather high (21.5% of all offspring tested) for a species without sexual dimorphism and high levels of paternal care. Furthermore, the occurrence of Epp was strongly related to the spatial distribution of male territories with males settling in densely occupied areas having higher proportions of extrapair young within their own brood. Also, song repertoire size affected Epp: here larger repertoires of social mates were negatively related to the probability of being cuckolded. When directly comparing repertoires sizes of social and extrapair mates, extrapair mates tended to have larger repertoires. We finally discuss our results as a hint for a flexible mating strategy in nightingales where several factors-including ecological as well as male song features-need to be considered when studying reproductive behavior in monogamous species with complex song.

关键词：亲子鉴定夜莺一夫一妻制交配策略 Epp 种内差异环境因素直接测量

Epigenetic modulations rendering cell-to-cell variability and phenotypic metastability

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Journal of Genetics and Genomics 2016年第8期43卷 503-511页

作者： Shawal Spencer Agustina Gugliotta Natascha Godecke Hansjorg Hauser Dagmar wirth Model Systems for Infection and Immunity Helmholtz Centre for Infection ResearchBraunschweig 38124Germany Experimental Hematology Hannover Medical SchoolHannover 30625Germany cell culture laboratory faculty of biochemistry and biological sciencesnational university of the littoralSanta Fe 3000Argentina

Tumor cells display phenotypic plasticity and heterogeneity due to genetic and epigenetic variations which limit the predictability of therapeutic interventions. Chromatin modifications can arise stochas- tically but can also be a consequence of environmental influences such as the microenvironment of cancer cells. A better understanding of the impact and dynamics of epigenetic modulation at defined chromosomal sites is required to get access to the underlying mechanisms. We investigated the epige- netic modulations leading to cell-to-cell heterogeneity in a tumor cell line model. To this end, we analyzed expression variance in 80 genetically uniform cell populations having a single-copy reporter randomly integrated in the genorne. Single-cell analysis showed high intraclonal heterogeneity. Epige- netic characterization revealed that expression heterogeneity was accompanied by differential histone marks whereas contribution of DNA methylation could be excluded. Strikingly, some clones revealed a highly dynamic, stochastically altered chromatin state of the transgene cassette which was accompanied with a metastable expression pattern. In contrast, other clones represented a robust chromatin state of the transgene cassette with a stable expression pattern. Together, these results elucidate locus-specific epigenetic modulation in gene expression that contributes to phenotypic heterogeneity of cells and might account for cellular plasticity.

关键词： lntraclonal heterogeneityEpigenetic regulationDNA methylationDifferential histone marksMetastable expression

Comparisons of electrical and optical properties between graphene and silicene A review

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Chinese physics B 2018年第2期27卷 299-313页

作者： wirth-Lima A J Silva M G Sombra A S B Laboratory of Telecommunications and Materials Science and Engineering-www.locem.ufc.br-Fortaleza CearaBrazil Department of physics Science CenterFederal University of Ceara(U.F C.)-FortalezaCear4Brazil State University of Vale do Acarau SobralCeardBrasil

Two-dimensional （2D） metamaterials are considered to be of enormous relevance to the progress of all exact sciences. Since the discovery of graphene, researchers have increasingly investigated in depth the details of electrical/optical proper- ties pertinent to other 2D metamaterials, including those relating to the silicene. In this review are included the details and comparisons of the atomic structures, energy diagram bands, substrates, charge densities, charge mobilities, conductivities, absorptions, electrical permittivities, dispersion relations of the wave vectors, and supported electromagnetic modes related to graphene and silicene. Hence, this review can help readers to acquire, recover or increase the necessary technological basis for the development of more specific studies on graphene and silicene.

关键词： graphene silicene electrical/optical properties