554 research outputs found

    Intrinsic motivation as a double-edged sword: Investigating effects on well-being and the role of flex place practices as moderator to buffer adverse effects

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    Ensuring employee well-being is a crucial task for organizations. While previous research has mainly focused on positive effects of intrinsic motivation, in this study, we took a more comprehensive view on intrinsic motivation and work-related well-being. More specifically, building on conservation of resources theory, we focused on two facets of work-related well-being (job satisfaction and emotional exhaustion) and examined direct (beneficial) and indirect (adverse) effects on well-being via detachment as an inconsistent mediation model. Furthermore, we took a closer look at how the use of flex place practices (FPPs), giving employees the opportunity to choose from where to work, can attenuate potential adverse effects of high intrinsic motivation. We collected data from 408 employees of a European manufacturer at two points of measurement, the first one before and the second one after the introduction of FPPs. Results showed that intrinsic motivation had a positive direct effect on changes in well-being, and an adverse indirect effect on changes in well-being via reduced detachment. For employees using FPPs, this adverse indirect effect was dissolved. This research is among the first to explore potential downsides of intrinsic motivation and the role of FPPs in the functioning of intrinsic motivation

    Genomic markers of panitumumab resistance including ERBB2/ HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC).

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    A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6 mg/kg IV q2weeks. Of 34 panitumumab-treated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders. A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities. This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy

    Strategies for the delay of surgery in the management of resectable hepatobiliary malignancies during the COVID-19 pandemic

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    Objective: We aimed to review data about delaying strategies for the management of hepatobiliary cancers requiring surgery during the covid-19 pandemic. Background: Given the covid-19 pandemic, many jurisdictions, to spare resources, have limited access to operating rooms for elective surgical activity, including cancer, thus forcing deferral or cancellation of cancer surgeries. Surgery for hepatobiliary cancer is high-risk and particularly resource-intensive. Surgeons must critically appraise which patients will benefit most from surgery and which ones have other therapeutic options to delay surgery. Little guidance is currently available about potential delaying strategies for hepatobiliary cancers when surgery is not possible. Methods: An international multidisciplinary panel reviewed the available literature to summarize data relating to standard-of-care surgical management and possible mitigating strategies to be used as a bridge to surgery for colorectal liver metastases, hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma. Results: Outcomes of surgery during the covid-19 pandemic are reviewed. Resource requirements are summarized, including logistics and adverse effects profiles for hepatectomy and delaying strategies using systemic, percutaneous and radiation ablative, and liver embolic therapies. For each cancer type, the long-term oncologic outcomes of hepatectomy and the clinical tools that can be used to prognosticate for individual patients are detailed. Conclusions: There are a variety of delaying strategies to consider if availability of operating rooms decreases. This review summarizes available data to provide guidance about possible delaying strategies depending on patient, resource, institution, and systems factors. Multidisciplinary team discussions should be leveraged to consider patient- and tumour-specific information for each individual case.publishedVersio

    Who is in the driver's seat in 8p12 amplifications? ZNF703 in luminal B breast tumors

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    Two recent reports identify ZNF703 as an oncogene driving selection of frequent chromosome 8p12 amplifications in luminal B breast tumors. The estrogen-responsive ZNF703 gene encodes a transcriptional cofactor that, when overexpressed, induces cell proliferation and interferes with transforming growth factor beta signaling. In MCF7 cells, increased ZNF703 expression results in activation of genes involved in stem cell self-renewal - while in primary human mammary epithelial cells, ZNF703 increases the ratio of luminal to basal progenitors. Expression of the murine homolog of ZNF703 reduces cell adhesion and promotes metastasis. ZNF703 overexpression thus alters regulation of proliferation and differentiation in luminal B tumors

    5-teilige Sonderausgabe des KOBV-Newsletters – 24. bis 30. Oktober 2016

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    An der internationalen Open-Access-Woche 2016 vom 24.-28. Oktober war der KOBV erstmalig mit einem Online „Publishing Event“ beteiligt. An fünf aufeinanderfolgenden Tagen erschien täglich eine Sonderausgabe des KOBV- Newsletters zu ausgewählten Open-Access-Themen. Die einzelnen Beiträge sind in dieser Sonderedition als Online-Reader zusammengestellt. Der aktuelle Diskussionsstand zum jeweiligen Thema wird von Expertinnen und Experten in kurzen Übersichtsartikeln vorgestellt und mit Praxistipps ergänzt. Zielgruppe sind vor allem Bibliothekare und Bibliothekarinnen, die sich einen schnellen Überblick zu Open Access verschaffen wollen

    Light-Activatable Assembled Nanoparticles to Improve Tumor-Penetration and Eradicate Metastasis in Triple Negative Breast Cancer

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    Triple‐negative breast cancer (TNBC) is a kind of aggressive malignancy with fast metastatic behavior. Herein, a nanosystem loaded with a near‐infrared (NIR) agent is developed to achieve chemo‐photothermal combination therapy for inhibiting tumor growth and metastasis in TNBC. The NIR agent of ultrasmall sized copper sulfide nanodots with strong NIR light‐absorbing capability is entrapped into the doxorubicin‐contained temperature‐sensitive polymer‐based nanosystem by a self‐assembled method. The temperature sensitive nanoclusters (TSNCs) can significantly enhance the drug penetration depth and significantly kill the cancer cells under the near‐infrared laser irradiation. Importantly, it is plausible that the tumor penetrating nanosystem combined with NIR laser irradiation can prevent lung and liver metastasis via extermination of the cancer stem cells. The in vivo characteristics, evaluated by photoacoustic imaging, pharmacokinetics, and biodistribution, confirm their feasibility for tumor treatment owing to their long blood circulation time and high tumor uptake. Thanks to the high tumor uptake and highly potent antitumor efficacy, the doxorubicin‐induced cardiotoxicity can be avoided when the TSNC is used. Taken together, it is believed that the nanosystem has excellent potential for clinical translation.Peer reviewe

    Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women

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    Purpose: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. Methods: A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher’s exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. Results: 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % ≤40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. Conclusion: Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics

    What are the Red flags to aid the early detection of metastatic bone disease as a cause of back pain?

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    Existing high performance work system (HPWS) research has rarely considered cultural influences. This study investigates the relationships between guanxi, HPWS and employee attitudes in China. A data set consisting of 226 employees in a Chinese state-owned enterprise in the railway sector was used to test the hypotheses. Using structural equation modelling as an analytical tool, we found that guanxi was positively related to HPWS and trust. Similar to research in the Western context, HPWS was found to be positively related to trust and job satisfaction. Moreover, the results also revealed that HPWS mediated between guanxi and both trust and job satisfaction. Theoretical and practical implications are both discussed

    Are Metastases from Metastases Clinical Relevant? Computer Modelling of Cancer Spread in a Case of Hepatocellular Carcinoma

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    Background: Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. Methods: The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. Results: The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient’s death. Conclusion: The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e.
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