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Myelodysplastic syndromes (MDS) and Waldenstrom's macroglobulinemia (WM) are rarely synchronous. Ineffective myelopoiesis/hematopoiesis with clonal unilineage or multilineage dysplasia and cytopenias characterize MDS. Despite a myeloid origin, MDS can sometimes lead to decreased production, abnormal apoptosis or dysmaturation of B cells, and the development of lymphoma. WM includes bone marrow involvement by lymphoplasmacytic lymphoma (LPL) secreting monoclonal immunoglobulin M (IgM) with somatic mutation (L265P) of myeloid differentiation primary response 88 gene (MYD88) in 80–90%, or various mutations of C-terminal domain of the C-X-C chemokine receptor type 4 (CXCR4) gene in 20–40% of cases. A unique, progressive case of concurrent MDS and WM with several somatic mutations (some unreported before) and a novel balanced reciprocal translocation between chromosomes 10 and 13 is presented below. [ABSTRACT FROM AUTHOR]

Standard treatment regimens for the management of patients with refractory splenic marginal zone lymphoma (SMZL) are currently unavailable. Here, we report a case of SMZL, which, after failing multiple therapeutics, demonstrated an impressive clinical response to combined Venetoclax and Velcade (V2), a treatment combination currently being investigated in the setting of refractory multiple myeloma. We also report a unique histopathology and mutational profile that may have important implications for the characterization and prognosis of SMZL. [ABSTRACT FROM AUTHOR]

Modern law makes currency a creature of the state and ultimately the value of its currency depends on the public's trust in that state. While some nations are more capable than others at instilling public trust in the stability of their monetary institutions, it is nonetheless impossible for any legal system to make the precommitments necessary to completely isolate the governance of its money supply from political pressure. This proposition is true not only today, where nearly all government institutions manage their money supply in the form of central banking, but also true of past private banking regimes circulating their notes under the shadow of public law. However, bitcoin represents a potential third currency regime far more resistant to state control because it mints currency units that exist in no physical place, places a numerical ceiling on the number of units that can be created, and relies on scientific principles from cryptography to guarantee that ceiling and verify any person-to-person transfer. The trust required is not in any government but in the decentralized order of those who verify bitcoin transactions and those who create the software these verifiers choose to run on their connected computers. This Article explores the fundamental structure of bitcoin, first by demystifying it as a technology, and second by showing how its decentralized order contrasts with other currency regimes. Unlike governments that use the power of law to compel action, bitcoin relies on a system of built-in incentives to encourage behavior that benefits not only those seeking to use bitcoin, but also bitcoin miners--those who voluntarily undertake the task of maintaining the payment network. While currently bitcoin is too volatile to compete with all but the worst government-issued currencies, the qualities of this system may give bitcoin a long-term advantage over many currencies. As the bitcoin ecosystem continues to grow, its nonlegal order can help it climb the rungs of stability created by distrust in government. The technology underpinning bitcoin is the next point of innovation in the digital age--the same era that has already seen software create institutional disruption from Amazon, Facebook, and Uber, among many others. As bitcoin gains in popularity, it offers a platform for other kinds of technological alternatives to traditional legal regimes, like smart contracts. Bitcoin's order without currency law will facilitate other forms of order with less law. This is a propitious time for fundamental examination of bitcoin. Despite experiencing significant speculation and volatility throughout late 2017 and early 2018, its ten-year history demonstrates a downward trend in volatility and an upward trend in market capitalization. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite its high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer. One strategy is to co-deliver cytotoxic chemotherapy agents using biocompatible nanoparticles (NPs) which can limit off-target tissue toxicity and improve therapeutic efficacy. Herein, we report the development of dual-drug loaded nanoformulations that improve the efficacy of CRT for NSCLC by co-encapsulation of cisplatin (CP) and PTX in PLGA–PEG NPs. Mice bearing NSCLC xenografts were administered with dual-drug loaded NPs during CRT, which showed greater inhibition of tumor growth than free drug combinations or combinations of single-drug loaded NPs. These results indicate that using a NP co-delivery strategy for this common CRT regimen may improve clinical responses in NSCLC patients. [ABSTRACT FROM AUTHOR]

Stem cells reside in 'niches', where support cells provide critical signalling for tissue renewal. Culture methods mimic niche conditions and support the growth of stem cells in vitro. However, current functional assays preclude statistically meaningful studies of clonal stem cells, stem cell-niche interactions, and genetic analysis of single cells and their organoid progeny. Here, we describe a 'microraft array' (MRA) that facilitates high-throughput clonogenic culture and computational identification of single intestinal stem cells (ISCs) and niche cells. We use MRAs to demonstrate that Paneth cells, a known ISC niche component, enhance organoid formation in a contact-dependent manner. MRAs facilitate retrieval of early enteroids for quantitative PCR to correlate functional properties, such as enteroid morphology, with differences in gene expression. MRAs have broad applicability to assaying stem cell-niche interactions and organoid development, and serve as a high-throughput culture platform to interrogate gene expression at early stages of stem cell fate choices. [ABSTRACT FROM AUTHOR]