Richter syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Two pathologic variants of RS are recognized: namely, the diffuse large B-cell ...lymphoma (DLBCL) variant and the rare Hodgkin lymphoma (HL) variant. Histologic documentation is mandatory to diagnose RS. The clinical suspicion of RS should be based on clinical signs and symptoms. Differential diagnosis between CLL progression and RS and choice of the biopsy site may take advantage of positron emission tomography/computed tomography. Molecular lesions of regulators of proliferation (CDKN2A, NOTCH1, MYC) and apoptosis (TP53) overall associate with ∼90% of DLBCL-type RS, whereas the biology of the HL-type RS is largely unknown. The prognosis of the DLBCL-type RS is unfavorable; the outcome of HL-type RS appears to be better. The most important RS prognostic factor is the clonal relationship between the CLL and the aggressive lymphoma clones, with clonally unrelated RS having a better prognosis. Rituximab-containing combination chemotherapy for DLBCL is the most widely used treatment in DLBCL-type RS. Fit patients who respond to induction therapy should be offered stem cell transplantation (SCT) to prolong survival. Adriamycin, bleomycin, vinblastine, and dacarbazine is the preferred regimen for the HL-type RS, and SCT consolidation is less used in this condition.
Background Surface tensiometry consented to characterize the surface free energy of geomaterials in an integrated and non-destructive way.
A new surface tensiometry tool, based on the contact angle ...measurement of Polyperfluoromethylisopropyl Ether (TVS mud index), has thus developed in the early 2000s. The TVS mud index was for the first time employed from 2005 to 2010 for surface tensiometry characterization of peloids for pelotherapy from Abano Terme and Montegrotto Terme (Pa-dova, Italy). We aim to report the surface tensiometry application in the thermal field, and show the potentialities of TVS mud index as a marker for the non invasive quality control of the peloids and their maturation process.
Methods The determination of the typical chemical-mineralogical characteristics of a Euganean Thermal Mud (ETM) and their surface tensiometry allowed us to demonstrate the link between the chemical data from X-ray fluorescence (XRF) analysis and they performed using a tensiometer to assess the quality of the peloid and its biological maturation process.
Results The liquid test Polyperfluoromethylisopropyl Ether-based demonstrated the link between variations in volume elements and surface free energy of muddy matrices. The research results here showed that the TVS mud index is linked to the chemical pattern of peloids.
Conclusions The research work implemented in the period 2005-2010 showed the potentialities of surface tensiometry in the assessment of peloids for pelotherapy using Polyperfluoromethylisopropyl Ether as a liquid test.
Lymphoplasmacytic lymphoma (LPL) is a distinct B-cell lymphoproliferative disorder primarily characterized by bone marrow infiltration of lymphoplasmacytic cells. When LPL produces a serum monoclonal ...immunoglobulin of the IgM class, it is termed Waldenström macroglobulinemia (WM). The differential diagnosis between LPL and other types of morphologically similar B-cell tumors that may also have plasmacytic differentiation and/or secretion of IgM paraproteins is not always clear-cut based solely on the pathologic and phenotypic features of the tumor. Although the current treatments for LPL/WM are initially effective in inducing responses in most patients, they are not curative and show decreasing efficacy with repeated administrations, ultimately resulting in the selection of a chemoresistant clone. Next-generation sequencing studies have identified somatic mutations of MYD88, a key component of the Toll-like receptor signaling machinery, in ∼90% of LPL/WM. Deregulated MYD88 signaling promoted by mutations sustains tumor cell survival in LPL/WM, demonstrating that they are gain-of-function driver events in this lymphoma. This review discusses the molecular and biological mechanisms underlying MYD88 mutations in LPL/WM, the role of MYD88 mutations as molecular biomarker for the refinement of diagnosis and the improvement classification of LPL/WM, and novel targeted therapeutic strategies for LPL/WM based on the pharmacological manipulation of MYD88 signaling to which this lymphoma is addicted.
Most patients enrolled in Stilgenbauer and colleagues' study3 had previously received immunochemotherapy, whereas only five had received kinase inhibitors. ...the population studied might not have ...been completely representative of the typical patient population with relapsed or refractory and TP53-disrupted chronic lymphocytic leukaemia that hemato-oncologists will have to treat in the future.
Convolutional neural networks (CNNs) have revolutionized the world of computer vision over the last few years, pushing image classification beyond human accuracy. The computational effort of today's ...CNNs requires power-hungry parallel processors or GP-GPUs. Recent developments in CNN accelerators for system-on-chip integration have reduced energy consumption significantly. Unfortunately, even these highly optimized devices are above the power envelope imposed by mobile and deeply embedded applications and face hard limitations caused by CNN weight I/O and storage. This prevents the adoption of CNNs in future ultralow power Internet of Things end-nodes for near-sensor analytics. Recent algorithmic and theoretical advancements enable competitive classification accuracy even when limiting CNNs to binary (+1/-1) weights during training. These new findings bring major optimization opportunities in the arithmetic core by removing the need for expensive multiplications, as well as reducing I/O bandwidth and storage. In this paper, we present an accelerator optimized for binary-weight CNNs that achieves 1.5 TOp/s at 1.2 V on a core area of only 1.33 million gate equivalent (MGE) or 1.9 mm 2 and with a power dissipation of 895 μW in UMC 65-nm technology at 0.6 V. Our accelerator significantly outperforms the state-of-the-art in terms of energy and area efficiency achieving 61.2 TOp/s/W@0.6 V and 1.1 TOp/s/MGE@1.2 V, respectively.
This paper presents Mr.Wolf, a parallel ultra-low power (PULP) system on chip (SoC) featuring a hierarchical architecture with a small (12 kgates) microcontroller (MCU) class RISC-V core augmented ...with an autonomous IO subsystem for efficient data transfer from a wide set of peripherals. The small core can offload compute-intensive kernels to an eight-core floating-point capable of processing engine available on demand. The proposed SoC, implemented in a 40-nm LP CMOS technology, features a 108-<inline-formula> <tex-math notation="LaTeX">\mu \text{W} </tex-math></inline-formula> fully retentive memory (512 kB). The IO subsystem is capable of transferring up to 1.6 Gbit/s from external devices to the memory in less than 2.5 mW. The eight-core compute cluster achieves a peak performance of 850 million of 32-bit integer multiply and accumulate per second (MMAC/s) and 500 million of 32-bit floating-point multiply and accumulate per second (MFMAC/s) −1 GFlop/s-with an energy efficiency up to 15 MMAC/s/mW and 9 MFMAC/s/mW. These building blocks are supported by aggressive on-chip power conversion and management, enabling energy-proportional heterogeneous computing for always-on IoT end nodes improving performance by several orders of magnitude with respect to traditional single-core MCUs within a power envelope of 153 mW. We demonstrated the capabilities of the proposed SoC on a wide set of near-sensor processing kernels showing that Mr.Wolf can deliver performance up to 16.4 GOp/s with energy efficiency up to 274 MOp/s/mW on real-life applications, paving the way for always-on data analytics on high-bandwidth sensors at the edge of the Internet of Things.
Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation ...and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.
Richter transformation (RT), defined as the development of an aggressive lymphoma on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), represents a clinical unmet ...need because of its dismal prognosis. An increasing body of knowledge in the field of RT is arising from the recent development of preclinical models depicting the biology underlying this aggressive disease. Consistently, new therapeutic strategies based on a genetic
are exploring actionable pathogenic pathways to improve the outcome of patients in this setting. In this review, we summarize the current understandings on RT biology and the available treatment options.
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