Phyllodes tumors are rare fibroepithelial tumors that make up less than 1% of all breast tumors. Malignant phyllodes tumors are associated with a 25% incidence of distant metastasis, which is ...invariably fatal within 24 months. We report successful resection of a solitary pulmonary metastasis in the left chest in a 50-year-old woman 7 years after a right-sided mastectomy for malignant phyllodes tumor.
Extramedullary myeloma (EMM) is an infrequent but well-established manifestation of multiple myeloma (MM), defined as a soft tissue plasma cell neoplasm without bone marrow involvement. Gallbladder ...involvement in EMM, however, is a very rare occurrence, with only 8 cases found in the English medical literature. Here, we present a case of an older adult male with a gallbladder mass in the presence of increasing serum kappa light chains after a normal bone marrow biopsy confirmed the complete remission of a previous MM diagnosis. Histopathologic evaluation of a biopsied sample confirmed the mass as an atypical plasma cell neoplasm. Later in his treatment, he developed several firm, smooth, violaceous skin nodules on the torso, which histopathology confirmed as also being atypical plasma cell neoplasms. We aim to contribute to the medical literature by expanding the pool of information regarding EMM of the gallbladder to support future diagnostic and treatment recommendations.
The Food-Energy–Water (FEW) nexus has been promoted as a tool for improving food, energy, and water resource security via an interdisciplinary approach that acknowledges the inherent synergies and ...tradeoffs involved in managing these resources. Over the past decade discussion of the nexus has increased rapidly, along with research funding and output. However, because the nexus encompasses so many different disciplines, researchers engage with and study the nexus from differing perspectives with distinct motivations and analytical methodologies. Understanding these motivations is critical to understanding the value of a given work. This paper first uses a narrative review to identify the motivations and toolsets of five key perspectives used to view the nexus, including: ecosystem health, waste management, public and private institutional change, stakeholder trust, and the learning process. Then, a systematic review is conducted to examine how publication trends have changed over the past decade, both generally and for each of these perspectives. The Food-Energy-Water nexus is not the first systems-based approach for addressing resource management and critiques of the nexus as a “Buzzword” or simply a reinvention of previous systems are growing in the literature. Challenging authors to explicitly define the role and motivations of their research within the broader category of the FEW nexus can improve the actionability of the research, better allow researchers to build from each other's work, and help reduce the ambiguity surrounding the nexus.
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•FEW nexus can be understood from overlapping perspectives with distinct motivations and toolsets.•Ecosystems, waste management, institutional change, trust, and learning process perspectives•Systematic review of FEW nexus literature found in scopus was performed.•Clarity in defining FEW nexus research motivations improves collaboration and actionability.
The glucocorticoid (GC) receptor (GR), when liganded to GC, activates transcription through direct binding to simple (+)GRE DNA binding sequences (DBS). GC-induced direct repression via GR binding to ...complex “negative” GREs (nGREs) has been reported. However, GR-mediated transrepression was generally ascribed to indirect “tethered” interaction with other DNA-bound factors. We report that GC-induces direct transrepression via the binding of GR to simple DBS (IR nGREs) unrelated to (+)GRE. These DBS act on agonist-liganded GR, promoting the assembly of
cis-acting GR-SMRT/NCoR repressing complexes. IR nGREs are present in over 1000 mouse/human ortholog genes, which are repressed by GC in vivo. Thus variations in the levels of a single ligand can coordinately turn genes on or off depending in their response element DBS, allowing an additional level of regulation in GR signaling. This mechanism suits GR signaling remarkably well, given that adrenal secretion of GC fluctuates in a circadian and stress-related fashion.
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► Distinct response elements mediate direct transrepression by glucocorticoid receptor ► This direct repression, distinct from “tethered” transrepression, controls many genes ► Direct repression is important for homeostasis, circadian and stress functions ► Our discovery paves the way to improved anti-inflammatory glucocorticoids
Correction to: Oncogene (2015) 34, 1698–1708; doi:10.1038/onc.2014.102; published online 21 April 2014 The authors wish to add H Farghaly, originally included in the Acknowledgements, to the ...authorship of this article, published online 21 April 2014. Dr Farghaly was omitted from the byline at final submission due to communication impediments outside the authors’ control during the manuscript review period which were shortly thereafter resolved.
A measurement of direct photon production in {sup 208}Pb+ {sup 208}Pb collisions at 158A GeV has been carried out in the CERN WA98 experiment. The invariant yield of direct photons in central ...collisions is extracted as a function of transverse momentum in the interval 0.5<p{sub T}<4 GeV/c . A significant direct photon signal, compared to statistical and systematical errors, is seen at p{sub T}>1.5 GeV/c . The result constitutes the first observation of direct photons in ultrarelativistic heavy-ion collisions. It could be significant for diagnosis of quark-gluon-plasma formation.
MUC5AC is a secretory mucin aberrantly expressed in various cancers. In lung cancer, MUC5AC is overexpressed in both primary and metastatic lesions; however, its functional role is not well ...understood. The present study was aimed at evaluating mechanistic role of MUC5AC on metastasis of lung cancer cells. Clinically, the overexpression of MUC5AC was observed in lung cancer patient tissues and was associated with poor survival. In addition, the overexpression of Muc5ac was also observed in genetically engineered mouse lung adenocarcinoma tissues (Kras(G12D); Trp53(R172H/+); AdCre) in comparison with normal lung tissues. Our functional studies showed that MUC5AC knockdown resulted in significantly decreased migration in two lung cancer cell lines (A549 and H1437) as compared with scramble cells. Expression of integrins (α5, β1, β3, β4 and β5) was decreased in MUC5AC knockdown cells. As both integrins and MUC5AC have a von Willebrand factor domain, we assessed for possible interaction of MUC5AC and integrins in lung cancer cells. MUC5AC strongly interacted only with integrin β4. The co-localization of MUC5AC and integrin β4 was observed both in A549 lung cancer cells as well as genetically engineered mouse adenocarcinoma tissues. Activated integrins recruit focal adhesion kinase (FAK) that mediates metastatic downstream signaling pathways. Phosphorylation of FAK (Y397) was decreased in MUC5AC knockdown cells. MUC5AC/integrin β4/FAK-mediated lung cancer cell migration was confirmed through experiments utilizing a phosphorylation (Y397)-specific FAK inhibitor. In conclusion, overexpression of MUC5AC is a poor prognostic marker in lung cancer. MUC5AC interacts with integrin β4 that mediates phosphorylation of FAK at Y397 leading to lung cancer cell migration.
Abstract Background Venous thromboembolism (VTE) is a common and potentially fatal complication of arthroplasty. Methods We reviewed randomized trials to determine which anticoagulant has the best ...safety and efficacy in hip/knee arthroplasty patients. We searched PubMed, MEDLINE, and EMBASE through January 2016. Results Compared to enoxaparin (most commonly dosed 40 mg once daily), the relative risk (RR) of VTE was lowest for edoxaban 30 mg once daily (0.49, 95% CI 0.32-0.75), fondaparinux 2.5 mg once daily (0.53, 95% CI 0.45–0.63), and rivaroxaban 10 mg once daily (0.55, 95% CI 0.46-0.66), and highest for dabigatran 150 mg once daily (1.19, 95% CI 0.98-1.44). The RR of major/clinically relevant bleeding was lowest for apixaban 2.5 mg twice daily (0.84, 95% CI 0.70-0.99), and highest for rivaroxaban (1.27, 95% CI 1.01-1.59) and fondaparinux (1.64, 95% CI 0.24–11.35). Fondaparinux was the only agent that was more effective than enoxaparin 30 mg twice daily (VTE RR = 0.58, 95% CI 0.43-0.76). Conclusion With the possible exception of apixaban, newer anticoagulants that lower the risk of post-operative VTE increase bleeding.
Abstract The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing despite a decrease in tobacco use. Almost 20–30% of patients with OPSCC do not have the traditional risk factors ...of smoking and alcohol use and in a vast majority of these patients, the human papilloma virus (HPV) appears to drive the malignant transformation. HPV induced malignant transformation is attributed to two viral oncogenes and their non-structural protein products (E6 and E7). These two proteins appear to affect carcinogenesis by their inhibitory effects on p53 and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a better prognosis compared to their non-HPV counterparts. However, in the absence of strong evidence, standard of care at this time for OPSCC does not differ based on HPV status. Current research is focused on the role of de-escalation of treatment and elucidation of prognostic markers in this unique population. This review focuses on the pathogenesis of HPV mediated OPSCC and details the current evidence in the management of these patients.
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