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

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors

Euclid preparation. XXV. The Euclid Morphology Challenge -- Towards model-fitting photometry for billions of galaxies

The ESA Euclid mission will provide high-quality imaging for about 1.5 billion galaxies. A software pipeline to automatically process and analyse such a huge amount of data in real time is being developed by the Science Ground Segment of the Euclid Consortium; this pipeline will include a model-fitting algorithm, which will provide photometric and morphological estimates of paramount importance for the core science goals of the mission and for legacy science. The Euclid Morphology Challenge is a comparative investigation of the performance of five model-fitting software packages on simulated Euclid data, aimed at providing the baseline to identify the best suited algorithm to be implemented in the pipeline. In this paper we describe the simulated data set, and we discuss the photometry results. A companion paper (Euclid Collaboration: Bretonni\`ere et al. 2022) is focused on the structural and morphological estimates. We created mock Euclid images simulating five fields of view of 0.48 deg2 each in the $I_E$ band of the VIS instrument, each with three realisations of galaxy profiles (single and double S\'ersic, and 'realistic' profiles obtained with a neural network); for one of the fields in the double S\'ersic realisation, we also simulated images for the three near-infrared $Y_E$, $J_E$ and $H_E$ bands of the NISP-P instrument, and five Rubin/LSST optical complementary bands ($u$, $g$, $r$, $i$, and $z$). To analyse the results we created diagnostic plots and defined ad-hoc metrics. Five model-fitting software packages (DeepLeGATo, Galapagos-2, Morfometryka, ProFit, and SourceXtractor++) were compared, all typically providing good results. (cut)Comment: 29 pages, 33 figures. Euclid pre-launch key paper. Companion paper: Bretonniere et al. 202

Euclid preparation: XXVI. the Euclid Morphology Challenge: Towards structural parameters for billions of galaxies

The various Euclid imaging surveys will become a reference for studies of galaxy morphology by delivering imaging over an unprecedented area of 15 000 square degrees with high spatial resolution. In order to understand the capabilities of measuring morphologies from Euclid-detected galaxies and to help implement measurements in the pipeline of the Organisational Unit MER of the Euclid Science Ground Segment, we have conducted the Euclid Morphology Challenge, which we present in two papers. While the companion paper focusses on the analysis of photometry, this paper assesses the accuracy of the parametric galaxy morphology measurements in imaging predicted from within the Euclid Wide Survey. We evaluate the performance of five state-of-the-art surface-brightness-fitting codes, DeepLeGATo, Galapagos-2, Morfometryka, ProFit and SourceXtractor++, on a sample of about 1.5 million simulated galaxies (350 000 above 5σ) resembling reduced observations with the Euclid VIS and NIR instruments. The simulations include analytic Sérsic profiles with one and two components, as well as more realistic galaxies generated with neural networks. We find that, despite some code-specific differences, all methods tend to achieve reliable structural measurements (< 10% scatter on ideal Sérsic simulations) down to an apparent magnitude of about IE = 23 in one component and IE = 21 in two components, which correspond to a signal-to-noise ratio of approximately 1 and 5, respectively. We also show that when tested on non-analytic profiles, the results are typically degraded by a factor of 3, driven by systematics. We conclude that the official Euclid Data Releases will deliver robust structural parameters for at least 400 million galaxies in the Euclid Wide Survey by the end of the mission. We find that a key factor for explaining the different behaviour of the codes at the faint end is the set of adopted priors for the various structural parameters

Euclid preparation XXVI. The Euclid Morphology Challenge. Towards structural parameters for billions of galaxies

The various Euclid imaging surveys will become a reference for studies of galaxy morphology by delivering imaging over an unprecedented area of 15 000 square degrees with high spatial resolution. In order to understand the capabilities of measuring morphologies from Euclid-detected galaxies and to help implement measurements in the pipeline, we have conducted the Euclid Morphology Challenge, which we present in two papers. While the companion paper by Merlin et al. focuses on the analysis of photometry, this paper assesses the accuracy of the parametric galaxy morphology measurements in imaging predicted from within the Euclid Wide Survey. We evaluate the performance of five state-of-the-art surface-brightness-fitting codes DeepLeGATo, Galapagos-2, Morfometryka, Profit and SourceXtractor++ on a sample of about 1.5 million simulated galaxies resembling reduced observations with the Euclid VIS and NIR instruments. The simulations include analytic S\'ersic profiles with one and two components, as well as more realistic galaxies generated with neural networks. We find that, despite some code-specific differences, all methods tend to achieve reliable structural measurements (10% scatter on ideal S\'ersic simulations) down to an apparent magnitude of about 23 in one component and 21 in two components, which correspond to a signal-to-noise ratio of approximately 1 and 5 respectively. We also show that when tested on non-analytic profiles, the results are typically degraded by a factor of 3, driven by systematics. We conclude that the Euclid official Data Releases will deliver robust structural parameters for at least 400 million galaxies in the Euclid Wide Survey by the end of the mission. We find that a key factor for explaining the different behaviour of the codes at the faint end is the set of adopted priors for the various structural parameters.Comment: Accepted by A&A. 30 pages, 23+6 figures, Euclid pre-launch key paper. Companion paper: Euclid Collaboration XXV: Merlin et al. 2022 Minor corrections after journal revie

Genetic redundancies enhance information transfer in noisy regulatory circuits

[EN] Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits.This work has been supported by BFU2015-66894-P (MINECO/FEDER) and GV/2016/079 (GVA) Grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Rodrigo Tarrega, G.; Poyatos, JF. (2016). Genetic redundancies enhance information transfer in noisy regulatory circuits. PLoS Computational Biology. 12(10). https://doi.org/10.1371/journal.pcbi.1005156S121