Numerical simulations of cyclic voltammetry for lithium-ion intercalation in nanosized systems: Finiteness of diffusion versus electrode kinetics

The voltammetric behavior of Li+ intercalation/deintercalation in/from LiMn2O4 thin films and single particles is simulated, supporting very recent experimental results. Experiments and calculations both show that particle size and geometry are crucial for the electrochemical response. A remarkable outcome of this research is that higher potential sweep rates, of the order of several millivolts per second, may be used to characterize nanoparticles by voltammetry sweeps, as compared with macroscopic systems. This is in line with previous conclusions drawn for related single particle systems using kinetic Monte Carlo simulations. The impact of electrode kinetics and finite space diffusion on the reversibility of the process and the finiteness of the diffusion in ion Li / LiMn2O4 (de)intercalation is also discussed in terms of preexisting modeling.Fil: Gavilán Arriazu, Edgardo Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Mercer, M.P.. Lancaster University; Reino UnidoFil: Pinto, Oscar Alejandro. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Oviedo, Oscar Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Barraco Diaz, Daniel Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Hoster, H. E.. Lancaster University; Reino UnidoFil: Leiva, Ezequiel Pedro M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Engendering Unprecedented Activation of Oxygen Evolution via Rational Pinning of Ni Oxidation State in Prototypical Perovskite:Close Juxtaposition of Synthetic Approach and Theoretical Conception

Rational optimization of the OER activity of catalysts based on LaNiO3 oxide is achieved by maximizing the presence of trivalent Ni in the surface structure. DFT investigations of the LaNiO3 catalyst and surface structures related to it predict an improvement in the OER activity for these materials to levels comparable with the top of the OER volcano if the La content is minimized while the oxidation state of Ni is maintained. These theoretically predicted structures of high intrinsic OER activity can be prepared by a templated spray-freeze freeze-drying synthesis followed by a simple postsynthesis exfoliation-like treatment in acidic media. These nanocrystalline LaNiO3-related materials confirm the theoretical predictions, showing a dramatic improvement in OER activity. The exfoliated surfaces remain stable in OER catalysis, as shown by an in-operando ICP-OES study. The unprecedented OER activation of the synthesized LaNiO3-based materials is related to a close juxtaposition of the theoretical conception of ideal structural motifs and the ability to engender such motifs using a unique synthetic procedure, both principally related to stabilization and pinning of the Ni oxidation state within the local coordination environment of the perovskite structure. © 2021 American Chemical Society. All rights reserved

Treatment of Older Patients With Mantle Cell Lymphoma (MCL):Long-Term Follow-Up of the Randomized European MCL Elderly Trial

PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients

Ki-67 as a prognostic marker in mantle cell lymphoma—consensus guidelines of the pathology panel of the European MCL Network

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given

A Chitinase from Aeromonas veronii CD3 with the Potential to Control Myxozoan Disease

Background: The class Myxosporea encompasses about 2,400 species, most of which are parasites of fish and cause serious damage in aquaculture. Due to the concerns about food safety issues and limited knowledge of Myxozoa life cycle and fish immune system, no chemicals, antibiotics or immune modulators are available to control myxozoa infection. Therefore, little can be done once Myxozoa establishment has occurred. Methodology/Principal Findings: In this paper we isolated Aeromonas veronii CD3 with significant myxospore shell valvedegrading ability from pond sediment. A 3,057-bp full-length chitinase gene was consequently cloned, and the corresponding mature, recombinant chitinase (ChiCD3) produced by Escherichia coli had substantial chitinase activity. The deduced sequence of ChiCD3 contained one catalytic domain, two chitin-binding domains, and one putative signal peptide. ChiCD3 had an optimal activity at 50uC and pH 6.0, and retained more than 50 % of its optimal activity under warm water aquaculture conditions (,30uC and pH,7.0). After incubation with ChiCD3, 38.064.8 % of the myxospores had damaged shell valves, whereas myxospores incubated with commercially available chitinases remained intact. Conclusion/Significance: This study reveals a new strategy to control myxozoan disease. ChiCD3 that has capacity to damage the shell valve of myxospores can be supplemented into fish feed and used to control Myxozoa-induced disease

Treatment of Older Patients with Mantle-Cell Lymphoma

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom

Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma : A Study by the Lunenburg Lymphoma Biomarker Consortium

PURPOSE: MYC rearrangement (MYC-R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC-R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene. METHODS: The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC, BCL2, BCL6, and IG heavy and light chain loci was used, and results were correlated with clinical outcomes. RESULTS: A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC-R. MYC-R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC-R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001). CONCLUSION: The negative prognostic impact of MYC-R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further