RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.

This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.

Review and Updates on Systemic Mastocytosis and Related Entities.

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia.

Composite Lymphoma with Follicular Lymphoma Transformation to Clonally Related Epstein-Barr Virus (EBV) Positive Diffuse Large B-Cell Lymphoma and EBV-PositiveClassic Hodgkin Lymphoma.

While the Epstein-Barr virus (EBV) is known to drive lymphomagenesis, it may rarely contribute to transformation of indolent lymphoma as well. Some EBV-related lymphomas represent a diagnostic challenge with important prognostic and therapeutic implications. We describe a case of follicular lymphoma (FL) transformation to both EBV + diffuse large B-cell lymphoma (DLBCL) and EBV + classic Hodgkin lymphoma (cHL), the latter of which was only identified retrospectively after selective outgrowth during DLBCL therapy.

IGJ and SPATS2L immunohistochemistry sensitively and specifically identify BCR::ABL1+ and BCR::ABL1-like B-acute lymphoblastic leukaemia.

Therapeutic management and prognostication for patients with B-acute lymphoblastic leukaemia (B-ALL) require appropriate disease subclassification. BCR::ABL1-like B-ALL is unique in that it is defined by a gene expression profile similar to BCR::ABL1+ B-ALL rather than a unifying recurrent translocation. Current molecular/cytogenetic techniques to identify this subtype are expensive, not widely accessible, have long turnaround times and/or require an adequate liquid biopsy.

Breakdown of Random-Matrix Universality in Persistent Lotka-Volterra Communities.

The eigenvalue spectrum of a random matrix often only depends on the first and second moments of its elements, but not on the specific distribution from which they are drawn. The validity of this universality principle is often assumed without proof in applications. In this Letter, we offer a pertinent counterexample in the context of the generalized Lotka-Volterra equations.

Gasdermins and pannexin-1 mediate pathways of chemotherapy-induced cell lysis in hematopoietic malignancies.

Pyroptosis is a mechanism of programmed, necrotic cell death mediated by gasdermins, a family of pore-forming proteins. Caspase-1 activates gasdermin D (GSDMD) under inflammatory conditions, whereas caspase-3 activates GSDME under apoptotic conditions, such as those induced by chemotherapy. These pathways are thought to be separate.

Monoclonal B-cell lymphocytosis in the bone marrow: revisiting the criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma.

Monoclonal B-cell lymphocytosis is a clonal B-cell population in the peripheral blood (PB) of <5x10ˆ9/L without extramedullary (EM) disease, often with a chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) phenotype. The degree of bone marrow (BM) involvement is not currently a part of the diagnostic criteria for MBL or CLL/SLL, but CLL-type MBLs in BM can be seen in patients lacking PB lymphocytosis. Data are limited on the outcome of such cases.

Eigenvalues of Random Matrices with Generalized Correlations: A Path Integral Approach.

Random matrix theory allows one to deduce the eigenvalue spectrum of a large matrix given only statistical information about its elements. Such results provide insight into what factors contribute to the stability of complex dynamical systems. In this Letter, we study the eigenvalue spectrum of an ensemble of random matrices with correlations between any pair of elements.

Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential.

Pyroptosis, a lytic form of programmed cell death, both stimulates effective immune responses and causes tissue damage. Gasdermin (GSDM) proteins are a family of pore-forming executors of pyroptosis. While the most-studied member, GSDMD, exerts critical functions in inflammasome biology, emerging evidence demonstrates potential broad relevance for GSDM-mediated pyroptosis across diverse pathologies.

One-Year Mortality and Associated Factors in Patients Receiving Out-of-Hospital Naloxone for Presumed Opioid Overdose.

Study Objective: Out-of-hospital naloxone has been championed as a lifesaving solution during the opioid epidemic. However, the long-term outcomes of out-of-hospital naloxone recipients are unknown. The objectives of this study are to describe the 1-year mortality of presumed opioid overdose victims identified by receiving out-of-hospital naloxone and to determine which patient factors are associated with subsequent mortality.

The impact of phosphatases on proliferative and survival signaling in cancer.

The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role.

3D Anisotropic Thermal Conductivity of Exfoliated Rhenium Disulfide.

ReS represents a different class of 2D materials, which is characterized by low symmetry having 1D metallic chains within the planes and extremely weak interlayer bonding. Here, the thermal conductivity of single-crystalline ReS in a distorted 1T phase is determined at room temperature for the in-plane directions parallel and perpendicular to the Re-chains, and the through-plane direction using time-domain thermoreflectance. ReS is prepared in the form of flakes having thicknesses of 60-450 nm by micromechanical exfoliation, and their crystalline orientations are identified by polarized Raman spectroscopy.

Rapid and Large-Area Characterization of Exfoliated Black Phosphorus Using Third-Harmonic Generation Microscopy.

Black phosphorus (BP) is a layered semiconductor that recently has been the subject of intense research due to its novel electrical and optical properties, which compare favorably to those of graphene and the transition metal dichalcogenides. In particular, BP has a direct bandgap that is thickness-dependent and highly anisotropic, making BP an interesting material for nanoscale optical and optoelectronic applications. Here, we present a study of the anisotropic third-harmonic generation (THG) in exfoliated BP using a fast scanning multiphoton characterization method.

Stable aqueous dispersions of optically and electronically active phosphorene.

Understanding and exploiting the remarkable optical and electronic properties of phosphorene require mass production methods that avoid chemical degradation. Although solution-based strategies have been developed for scalable exfoliation of black phosphorus, these techniques have thus far used anhydrous organic solvents in an effort to minimize exposure to known oxidants, but at the cost of limited exfoliation yield and flake size distribution. Here, we present an alternative phosphorene production method based on surfactant-assisted exfoliation and postprocessing of black phosphorus in deoxygenated water.

Covalent functionalization and passivation of exfoliated black phosphorus via aryl diazonium chemistry.

Functionalization of atomically thin nanomaterials enables the tailoring of their chemical, optical and electronic properties. Exfoliated black phosphorus (BP)-a layered two-dimensional semiconductor-exhibits favourable charge-carrier mobility, tunable bandgap and highly anisotropic properties, but it is chemically reactive and degrades rapidly in ambient conditions. Here we show that covalent aryl diazonium functionalization suppresses the chemical degradation of exfoliated BP even after three weeks of ambient exposure.

Chemically Tailoring Semiconducting Two-Dimensional Transition Metal Dichalcogenides and Black Phosphorus.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDCs) and black phosphorus (BP) have beneficial electronic, optical, and physical properties at the few-layer limit. As atomically thin materials, 2D TMDCs and BP are highly sensitive to their environment and chemical modification, resulting in a strong dependence of their properties on substrate effects, intrinsic defects, and extrinsic adsorbates. Furthermore, the integration of 2D semiconductors into electronic and optoelectronic devices introduces unique challenges at metal-semiconductor and dielectric-semiconductor interfaces.

Probing Out-of-Plane Charge Transport in Black Phosphorus with Graphene-Contacted Vertical Field-Effect Transistors.

Black phosphorus (BP) has recently emerged as a promising narrow band gap layered semiconductor with optoelectronic properties that bridge the gap between semimetallic graphene and wide band gap transition metal dichalcogenides such as MoS2. To date, BP field-effect transistors have utilized a lateral geometry with in-plane transport dominating device characteristics. In contrast, we present here a vertical field-effect transistor geometry based on a graphene/BP van der Waals heterostructure.

Anisotropic Thermal Conductivity of Exfoliated Black Phosphorus.

The anisotropic thermal conductivity of passivated black phosphorus (BP), a reactive two-dimensional material with strong in-plane anisotropy, is ascertained. The room-temperature thermal conductivity for three crystalline axes of exfoliated BP is measured by time-domain thermo-reflectance. The thermal conductivity along the zigzag direction is ≈2.

Acidosis Sensing Receptor GPR65 Correlates with Anti-Apoptotic Bcl-2 Family Member Expression in CLL Cells: Potential Implications for the CLL Microenvironment.

The tumor microenvironment is generally an acidic environment, yet the effect of extracellular acidosis on chronic lymphocytic leukemia (CLL) is not well established. Here we are the first to report that the extracellular acid sensing G-protein coupled receptor, GPR65, is expressed in primary CLL cells where its level correlate strongly with anti-apoptotic Bcl-2 family member levels. GPR65 expression is found normally within the lymphoid lineage and has not been previously reported in CLL.

Metal oxide nanoparticle growth on graphene via chemical activation with atomic oxygen.

Chemically interfacing the inert basal plane of graphene with other materials has limited the development of graphene-based catalysts, composite materials, and devices. Here, we overcome this limitation by chemically activating epitaxial graphene on SiC(0001) using atomic oxygen. Atomic oxygen produces epoxide groups on graphene, which act as reactive nucleation sites for zinc oxide nanoparticle growth using the atomic layer deposition precursor diethyl zinc.

Acidosis blocks CCAAT/enhancer-binding protein homologous protein (CHOP)- and c-Jun-mediated induction of p53-upregulated mediator of apoptosis (PUMA) during amino acid starvation.

Cancer cells must avoid succumbing to a variety of noxious conditions within their surroundings. Acidosis is one such prominent feature of the tumor microenvironment that surprisingly promotes tumor survival and progression. We recently reported that acidosis prevents apoptosis of starved or stressed lymphoma cells through regulation of several Bcl-2 family members (Ryder et al.

Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.

Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.