Skin Lesion Analyser: An Efficient Seven-Way Multi-Class Skin Cancer Classification Using MobileNet

Skin cancer, a major form of cancer, is a critical public health problem with 123,000 newly diagnosed melanoma cases and between 2 and 3 million non-melanoma cases worldwide each year. The leading cause of skin cancer is high exposure of skin cells to UV radiation, which can damage the DNA inside skin cells leading to uncontrolled growth of skin cells. Skin cancer is primarily diagnosed visually employing clinical screening, a biopsy, dermoscopic analysis, and histopathological examination. It has been demonstrated that the dermoscopic analysis in the hands of inexperienced dermatologists may cause a reduction in diagnostic accuracy. Early detection and screening of skin cancer have the potential to reduce mortality and morbidity. Previous studies have shown Deep Learning ability to perform better than human experts in several visual recognition tasks. In this paper, we propose an efficient seven-way automated multi-class skin cancer classification system having performance comparable with expert dermatologists. We used a pretrained MobileNet model to train over HAM10000 dataset using transfer learning. The model classifies skin lesion image with a categorical accuracy of 83.1 percent, top2 accuracy of 91.36 percent and top3 accuracy of 95.34 percent. The weighted average of precision, recall, and f1-score were found to be 0.89, 0.83, and 0.83 respectively. The model has been deployed as a web application for public use at (https://saketchaturvedi.github.io). This fast, expansible method holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists.Comment: This is a pre-copyedited version of a contribution published in Advances in Intelligent Systems and Computing, Hassanien A., Bhatnagar R., Darwish A. (eds) published by Chaturvedi S.S., Gupta K., Prasad P.S. The definitive authentication version is available online via https://doi.org/10.1007/978-981-15-3383-9_1

Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma

International audienceMantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab–anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy). On the bench side, several studies aiming to integrate the tumor within its ecosystem highlighted a critical role of the tumor microenvironment (TME) in the expansion and resistance of MCL. This led to important insights into the role of the TME in the management of MCL, including potential targets and biomarkers. Indeed, targeted agents often have a combined mechanism of action on the tumor B cell but also on the tumor microenvironment. The aim of this review is to briefly describe the current knowledge on the biology of the TME in MCL and expose the results of the different therapeutic strategies integrating the TME in this disease

Atypical meningeal localization of classical hairy cell leukemia with an impressive response to rituximab and cladribine association. A case report and literature review

Abstract Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy

Listeria-associated lymphadenitis: a series of 11 consecutive cases and review of the literature

International audienceWe studied 11 cases of culture-proven Listeria-associated lymphadenitis reported to the French National Reference Center for Listeria from 1994 to 2019, and 8 additional published cases. Listeria-associated lymphadenitis is rare but associated with a mortality as high as for invasive listeriosis, and frequently diagnosed with concomitant neoplasia

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

International audienceSpecific and reciprocal interactions with the bone marrow microenvironment (BMM) govern the course of hematological malignancies. Matrix metalloproteinase-9 (MMP-9), secreted by leukemia cells, facilitates tumor progression via remodeling of the extracellular matrix (ECM) of the BMM. Hypothesizing that leukemias may instruct the BMM to degrade the ECM, we show, that MMP-9-deficiency in the BMM prolongs survival of mice with BCR-ABL1-induced B-cell acute lymphoblastic leukemia (B-ALL) compared with controls and reduces leukemia-initiating cells. MMP-9-deficiency in the BMM leads to reduced degradation of proteins of the ECM and reduced invasion of BALL. Using various in vivo and in vitro assays, as well as recipient mice deficient for the receptor for tumor necrosis factor (TNF) α (TNFR1) we demonstrate that BALL cells induce MMP-9-expression in mesenchymal stem cells (MSC) and possibly other cells of the BMM via a release of TNFα. MMP-9-expression in MSC is mediated by activation of nuclear factor kappa B (NF-κB) downstream of TNFR1. Consistently, knockdown of TNF-α in BALL initiating cells or pharmacological inhibition of MMP-9 led to significant prolongation of survival in mice with BALL. In summary, leukemia cell-derived Tnfα induced MMP-9-expression by the BMM promoting BALL progression. Inhibition of MMP-9 may act as an adjunct to existing therapies

Safety and efficacy of temsirolimus in combination with three different immuno-chemotherapy regimens in relapse and refractory mantle cell lymphoma, final results of the T phase IB trial of the LYSA

International audienceMantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients

Malignant histiocytosis with a Langerhans cell subtype: A report on the diagnostic and therapeutic challenge

International audienceNo abstract availabl

Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient cells

In ribosomopathies, the Diamond-Blackfan anemia (DBA) or 5q- syndrome, ribosomal protein (RP) genes are affected by mutation or deletion, resulting in bone marrow erythroid hypoplasia. Unbalanced production of ribosomal subunits leading to a limited ribosome cellular content, regulates translation at the expense of the master erythroid transcription factor GATA1. In RPS14-deficient cells mimicking 5q- syndrome erythroid defects, we show that the transcript length, codon bias of the coding sequence (CDS) and 3'UTR structure are the key determinants of translation. In these cells, short transcripts with a structured 3'UTR and high CAI showed a decreased translation efficiency. Quantitative analysis of the whole proteome confirmed that the post-transcriptional changes depended on the transcript characteristics that governed the translation efficiency in conditions of low ribosome availability. In addition, proteins involved in normal erythroid differentiation share most determinants of translation selectivity. Our findings thus indicate that impaired erythroid maturation due to 5q- syndrome may proceed from a translational selectivity at the expense of the erythroid differentiation program and suggest that an interplay between the CDS and UTRs may regulate mRNA translation