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Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

World Journal of Gastroenterology 2016年第17期22卷 4321-4329页

作者： Markus Alexander Küper Sebastian Trütschel Jürgen Weinreich Alfred Konigsrainer stefan beckert Department of General Visceral and Transplant Surgery University of Tubingen 72076 Tubingen Germany BG Trauma Center University of Tubingen D-72076 Tubingen Germany

AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic ***: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were ***: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly

关键词： Wound healing Everolimus Human growth hormone Immunosuppression mTOR-inhibitor Growth hormone Anastomotic healing

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Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?

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World Journal of Gastroenterology 2012年第38期18卷 5317-5320页

作者： Ingmar Knigsrainer stefan beckert Department of General Visceral and Transplant Surgery Tübingen University HospitalD-72076 Tübingen Germany

Peritoneal surface malignancies are generally associated with poor prognosis. In daily clinical routine, systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC). The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality. Given these findings, new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity. In addition, personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology. These days, every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies. Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients, our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.

关键词： Peritoneal carcinomatosis Hyperthermic intraperitoneal chemotherapy Cytoreductive surgery

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Experience after 100 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

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World Journal of Gastroenterology 2012年第17期18卷 2061-2066页

作者： Ingmar Knigsrainer Derek Zieker Jrg Glatzle Olivia Lauk Julia Klimek Stephan Symons Bjrn Brücher stefan beckert Alfred Knigsrainer Department of Surgery University of TübingenHoppeSeyler-Strasse 3D-72076 TübingenGermany Center for Bioinformatics Tübingen Sand 14D-72076 TübingenGermany

AIM:To investigate perioperative patient morbidity/mortality and outcome after cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC).METHODS:Of 150 patients 100 were treated with cytoreductive surgery and HIPEC and retrospectively *** and postoperative follow-up data were *** mass index(BMI),age and peritoneal carcinomatosis index(PCI) were chosen as selection criteria with regard to tumor-free survival and perioperative morbidity for this multimodal ***:CRS with HIPEC was successfully performed in 100 out of 150 *** patients were excluded because of intraoperative *** PCI was 17(1-39).In 89% a radical resection(CC0/CC1) was *** patient died postoperatively due to multiorgan *** PCI,age nor BMI was a risk factor for postoperative complications/outcome according to the DINDO *** 9% Re-CRS with HIPEC was performed during the follow-up ***:Patient selection remains the most important *** PCI,age nor BMI alone should be an exclusion criterion for this multimodal therapy.

关键词： Peritoneal carcinomatosis Single-center experience Hyperthermic intraoperative chemotherapy Complications Risk assessment Selection criteria

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Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第3期7卷 434-439页

作者： Philipp Horvath stefan beckert Florian Struller Alfred Konigsrainer Ingmar Konigsrainer Department of General Visceral and Transplant SurgeryUniversity of TübingenCom-prehensive Cancer Center

AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were ***: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols

关键词： Pseudomyxoma peritonei Mitomycin C Oxaliplatin Hyperthermic intraperitoneal chemotherapy Postoperative leukopenia

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Nature:研究发现杀死抗药细菌的新靶点

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现代生物医学进展 2017年第8期17卷 I0003-I0004页

作者： Paul Huter, Claudia Müller, Bertrand beckert, stefan Arenz, Otto Berninghausen, Roland Beckmann Daniel N. Wilson Bertrand beckert Daniel N. Wilson Gene Center Department of Biochemistry and Center for integrated Protein Science Munich (CiPSM) Ludwig-Maximilians-Universität München Feodor-Lynen-Strasse 25 81377 Munich Germany Institute for Biochemistry and Molecular Biology University of Hamburg Martin-Luther-King-Pl. 6 20146 Hamburg Germany

德国科学家最近阐明了一个细菌回收mRNA上停滞核糖体的新机制，当mRNA上缺少终止密码子就会导致核糖体无法从mRNA上脱离。参与该过程的蛋白为未来开发新抗生素药物提供了潜在靶点。

关键词：靶点细菌抗药 mRNA 德国科学家终止密码子抗生素药物核糖体

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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves stefan Przyborski Department of Biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

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BEV-Locator:an end-to-end visual semantic localization network using multi-view images

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Science China(Information Sciences) 2025年第2期68卷 134-150页

作者： Zhihuang ZHANG Meng XU Wenqiang ZHOU Tao PENG Liang LI stefan POSLAD School of Vehicle and Mobility Tsinghua University School of Information Technology & Management University of International Business and Economics Qcraft Inc. School of Electronic Engineering and Computer Science Queen Mary University of London

Accurate localization ability is fundamental in autonomous driving. Traditional visual localization frameworks approach the semantic map-matching problem with geometric models, which rely on complex parameter tuning and thus hinder large-scale deployment. In this paper, we propose BEV-Locator: an end-to-end visual semantic localization neural network using multi-view camera images. Specifically, a visual BEV(bird-eye-view) encoder extracts and flattens the multi-view images into BEV space. While the semantic map features are structurally embedded as map query sequences. Then a cross-model transformer associates the BEV features and semantic map queries. The localization information of ego-car is recursively queried out by cross-attention modules. Finally, the ego pose can be inferred by decoding the transformer outputs. This end-to-end model speaks to its broad applicability across different driving environments, including high-speed scenarios. We evaluate the proposed method in large-scale nuScenes and Qcraft datasets. The experimental results show that the BEV-Locator is capable of estimating the vehicle poses under versatile scenarios, which effectively associates the cross-model information from multi-view images and global semantic maps. The experiments report satisfactory accuracy with mean absolute errors of 0.052 m, 0.135 m and 0.251° in lateral, longitudinal translation and heading angle degree.

关键词： visual localization semantic map bird-eye-view transformer pose estimation

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Influence of symmetric and asymmetric rolling on texture evolution of work-hardened AA 5xxx aluminium alloy

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Transactions of Nonferrous Metals Society of China 2025年第1期35卷 30-44页

作者： MatjažGODEC stefan ZAEFFERER Jakob KRANER Črtomir DONIK Irena PAULIN Institute of Metals and Technology Lepi pot 111000LjubljanaSlovenia Max-Planck-Institut für Eisenforschung Max-Planck-Strasse 140237 DüsseldorfGermany Impol 2000 d.d. Partizanska cesta 382310 Slovenska BistricaSlovenia

The textures and microstructures of hot-and cold-rolled sheets of an AA 5454 aluminium alloy were studied,with special attention paid to comparing the texture development for the symmetric and asymmetric cold *** electron microscopy with electron-backscatter diffraction was used to monitor the development of the microstructure in the differently deformed and additionally annealed *** of the formations and transformations of individual texture components occurring during the rolling processes were observed and *** average grain sizes,textures and mechanical properties were correlated and explained for the symmetric and asymmetric cold-rolled *** asymmetric rolling is beneficial in terms of deep drawability because it reduces the planar anisotropy of the annealed material due to the decrease of the Cube,Goss,rotated-Cube and η-fibre texture components and at the same time strengthens X1-and X2-fibre texture components which are shear texture components and improve deep *** the asymmetric cold rolling,the temperature increases due to friction,triggering recrystallisation processes and leading to larger *** is also confirmed that asymmetric cold rolling uses less rolling force and consequently less energy to produce a final material with better formability,particularly earing.

关键词： crystallographic texture EBSD aluminium alloy symmetric/asymmetric rolling anisotropy

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Advanced hepatocellular carcinoma treatment strategies:Are transarterial approaches leading the way?

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 22-27页

作者： stefan Patauner Giovanni Scotton Francesca Notte Antonio Frena Department of General and Pediatric Surgery Bolzano Central Hospital-SABESBolzano 39100Trentino-Alto AdigeItaly

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with advanced stages posing significant treatment ***-though hepatic arterial infusion chemotherapy(HAIC)has emerged as a promising modality for treating advanced HCC,particularly in Asian clinical practice,its adoption in Western medicine remains limited due to a lack of large-scale randomized controlled *** editorial reviews and comments on the meta-analysis conducted by Zhou et al,which evaluates the efficacy and safety of HAIC and its combination strategies for advanced *** authors performed a comprehensive meta-analysis of various clinical trials and cohort studies comparing HAIC and its combinations to other first-line treatments,such as sorafenib and transarterial chemoembolization(TACE).In this work,HAIC showed significantly better results regarding overall survival and progression-free survival compared to sorafenib or TACE alone and their *** in combination with lenvatinib,ablation,programmed cell death 1 inhibitors,and radiotherapy further enhanced patient outcomes,indicating a synergistic *** editorial focuses on the critical role of multimodal treatment strategies in managing advanced *** advocates for a paradigm shift towards integrated treatment approaches to enhance survival rates and improve the quality of life in patients with advanced HCC.

关键词： Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Transarterial chemoembolization Sorafenib Combined therapy

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The Influence of Major Climatic Elements on the Devastated Geo-Hydrological Disasters: A Case of Hanang Disaster of 3rd December 2023 in Tanzania

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Atmospheric and Climate Sciences 2025年第1期15卷 106-125页

作者： Asnath Alberto Malekela stefan Sieber Jafari Swalehe Chobo Joseph Ndunguru Department of Geography and History Mwalimu Nyerere Memorial Academy Dar es Salaam Tanzania Leibniz Centre for Agricultural Landscape Research (ZALF) Mncheberg Germany Department of Agricultural Economics Humboldt University of Berlin Berlin Germany Department of Climatology and Climate Change Tanzania Meteorological Authority Dar es Salaam Tanzania

Changes in major climatic elements such as temperature, precipitation and wind distribution have triggered weather-related and geophysical disasters. In recent years, the globe has experienced an increased number of floods and landslide events which are said to be the most common among other natural disasters. This study examines the influence of climatic elements on the geo-hydrological disaster which occurred in Hanang district-Tanzania on 3rd December 2023. The study used the primary data collected from 182 respondents. Also, the trend analysis (1981-2023) was conducted using average rainfall from 7 meteorological stations in the study area. Annual and seasonal rainfall as well as a number of rainy days were analyzed. The calculated rainfall data were then used to compute the dimensions of the standardized precipitation anomalies (SPA) which is designated as SPA = (P − P*)/σp. Besides, the temperature was analysed to investigate its trend and trend anomaly. Also, the wind rose statistics for the annual, March to May (MAM) and October to December (OND) for the climatology period of 1991-2020 were analysed so as to examine its contribution to rainfall distribution in Hanang district. The examination of annual rainfall data indicates an upward trend in precipitation levels, accompanied by notable variability in rainfall patterns, including seasonal anomalies and deviations from historical averages. The combination of elevated rainfall, anomalies in rainfall patterns, and potentially unfavourable terrain characteristics may have contributed to devastated geo-hydrological disaster risk. However, future research is recommended that could focus on integrating rainfall and temperature data with comprehensive geo-hydrological susceptibility assessments, considering factors such as terrain stability, land cover and land use practices.

关键词： Climate Elements Climate Change Landslides Floods Geo-Hydrological Disasters

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