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- Hoshino, Ayuko, et al.
(author)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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In: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Journal article (peer-reviewed)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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- Eichhorst, B., et al.
(author)
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First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
- 2023
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In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 388:19, s. 1739-1754
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Journal article (peer-reviewed)abstract
- Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity,
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- Franco, Irene, et al.
(author)
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Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.
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- Joszai, R., et al.
(author)
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Metal-metal bond or isolated metal centers? Interaction of Hg(CN)(2) with square planar transition metal cyanides
- 2005
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 44:26, s. 9643-9651
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Journal article (peer-reviewed)abstract
- Three adducts have been prepared from Hg(CN)(2) and square planar M-II(CN)(4)(2-) transition metal cyanides (M = Pt, Pd, or Ni, with d(8) electron shell) as solids. The structure of the compounds K2PtHg(CN)(6)center dot 2H(2)O (1), Na2PdHg(CN)(6)center dot 2H(2)O (2), and K2NiHg(CN)(6)center dot 2H(2)O (3) have been studied by single-crystal X-ray diffraction, XPS, Raman spectroscopy, and luminescence spectroscopy in the solid state. The structure of K2PtHg(CN)(6)center dot 2H(2)O consists of one-dimensional wires. No CN- bridges occur between the heterometallic centers. The wires are strictly linear, and the Pt(II) and Hg(II) centers alternate. The distance d(Hg-Pt) is relatively short, 3.460 angstrom. Time-resolved luminescence spectra indicate that Hg(CN)2 units incorporated into the structure act as electron traps and shorten the lifetime of both the short-lived and longer-lived exited states in 1 compared to K-2[Pt(CN)(4)]center dot 2H(2)O. The structures of Na2PdHg(CN)(6)center dot 2H(2)O and K2NiHg(CN)(6)center dot 2H(2)O can be considered as double salts; the lack of heterometallophilic interaction between the remote Hg(II) and Pd(II) atoms, d(Hg-Pd) = 4.92 angstrom, and Hg(II) and Ni(II) atoms, d(Hg-Ni) = 4.61 angstrom, is apparent. Electron binding energy values of the metallic centers measured by XPS show that there is no electron transfer between the metal ions in the three adducts. In solution, experimental findings clearly indicate the lack of metal-metal bond formation in all studied Hg-II-CN--M-II(CN)(4)(2-) systems (M = Pt, Pd, or Ni).
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- Mirioglu, Safak, et al.
(author)
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Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group
- 2024
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In: Nephrology, Dialysis and Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 39:4, s. 569-580
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Journal article (peer-reviewed)abstract
- The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field. 10.1093/ndt/gfae025 Video Watch the video of this contribution at https://academic.oup.com/ndt/pages/author_videos gfae025Media1 6346336829112
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- Mukherjee, S.D., et al.
(author)
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Critical parameters for parallel interconnects using VCSEL arrays and fiber image guides
- 2002
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In: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 4942, s. 292-305
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Conference paper (other academic/artistic)abstract
- Several thousand glass optical fibers fused together is routinely used as fiber image guides for medical and other image remoting applications. Fiber image guides also offer possibility for flexible optical interconnect links with potentially thousands of bi-directional parallel channels with data rates as high as 10 Gbps per channel, leading to more than Tera bits per second aggregate data transfer rates. A fair number of fiber image guide based link demonstrations using vertical cavity surface emitting lasers have been reported. However, little is known about designable parameters and optimization paradigms for applications to massively parallel optical interconnects. This paper discusses critical optical parameters that characterize a massively parallel link. Experimental characterizations were carried out to explore some of the fundamental interactions between single-mode 850 nm VCSELs and fiber image guides having different numerical apertures, 0.25, 0.55 and 1.00. Preliminary optical simulation results are given. Finally, potential directions for further experimental and analytical explorations, and for applicability into designable link systems are suggested.
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- Pöhls, Henrich C., et al.
(author)
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RERUM : Building a reliable IoT upon privacy- and security- enabled smart objects
- 2014
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In: 2014 IEEE Wireless Communications and Networking Conference Workshops (WCNCW). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781479930869 ; , s. 122-127
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Conference paper (peer-reviewed)abstract
- The Internet of Things (IoT) provides a platform for the interconnection of a plethora of smart objects. It has been widely accepted for providing Information and Communication Technologies (ICT) applications in many ￜsmartￜ environments, such as cities, buildings, metering, and even agriculture. For several reasons though such applications have yet to achieve wide adoption; a major hurdle is the lack of user trust in the IoT and its role in everyday activities. RERUM, a recently started FP7 European Union project. aims to develop a framework which will allow IoT applications to consider security and privacy mechanisms early in their design phase, ensuring a configurable balance between reliability (requiring secure, trustworthy and precise data) and privacy (requiring data minimization for private information, like location). The RERUM framework will comprise an architecture, built upon novel network protocols and interfaces as well as the design of smart objects hardware. To highlight the challenges and evaluate the framework, RERUM will employ several Smart City application scenarios, which will be deployed and evaluated in real-world testbeds in two Smart Cities participating in the project. Here we detail the key technologies RERUM will investigate over the coming three years to reach its vision for IoT security, privacy and trust.
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- Rullman, E., et al.
(author)
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A single bout of exercise activates matrix metalloproteinase in human skeletal muscle
- 2007
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 102:6, s. 2346-2351
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Journal article (peer-reviewed)abstract
- The aims of this study were 1) to characterize changes in matrix metalloproteinase (NIMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and NIMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.
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