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Background: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. Case presentation: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. Conclusion: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis. [ABSTRACT FROM AUTHOR]

Malignant lymphoma, which impacts the lymphatic system, presents diverse challenges in accurate diagnosis due to its varied subtypes—chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Lymphoma is a form of cancer that begins in the lymphatic system, impacting lymphocytes, which are a specific type of white blood cell. This research addresses these challenges by proposing ensemble and non-ensemble transfer learning models employing pre-trained weights from VGG16, VGG19, DenseNet201, InceptionV3, and Xception. For the ensemble technique, this paper adopts a stack-based ensemble approach. It is a two-level classification approach and best suited for accuracy improvement. Testing on a multiclass dataset of CLL, FL, and MCL reveals exceptional diagnostic accuracy, with DenseNet201, InceptionV3, and Xception exceeding 90% accuracy. The proposed ensemble model, leveraging InceptionV3 and Xception, achieves an outstanding 99% accuracy over 300 epochs, surpassing previous prediction methods. This study demonstrates the feasibility and efficiency of the proposed approach, showcasing its potential in real-world medical applications for precise lymphoma diagnosis. [ABSTRACT FROM AUTHOR]

Epigenetic regulation has been thoroughly investigated in recent years and has emerged as an important aspect of chronic lymphocytic leukemia (CLL) biology. Characteristic aberrant features such as methylation patterns and global DNA hypomethylation were the early findings of the research during the last decades. The investigation in this field led to the identification of a large number of genes where methylation features correlated with important clinical and laboratory parameters. Gene-specific analyses investigated methylation in the gene body enhancer regions as well as promoter regions. The findings included genes and proteins involved in key pathways that play central roles in the pathophysiology of the disease. Τhe application of these findings beyond the theoretical understanding can not only lead to the creation of prognostic and predictive models and scores but also to the design of novel therapeutic agents. The following is a review focusing on the present knowledge about single gene/gene promoter methylation or mRNA expression in CLL cases as well as records of older data that have been published in past papers. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry–Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i–19m were found to elicit potent antiproliferative effects in both BL cell lines EBV−MUTU-1 (chemosensitive) and EBV+ DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC50 values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of small agents targeting the B-cell receptor (BCR) pathway revolutionized the treatment of chronic lymphocytic leukemia (CLL). BCR-dependent leukemic cell proliferation is governed by phosphoinositide 3-kinase (PI3K) signaling. The selective PI3Kδ inhibitor idelalisib and dual PI3Kδ/γ inhibitor duvelisib are currently approved by the Food and Drug Administration and European Medicine Agency (only idelalisib) for CLL treatment. Umbralisib, a selective PI3Kδ and casein kinase-1ε (CK1ε) inhibitor, has a different chemical structure and a more favorable safety profile than other PI3K inhibitors (PiK3is); this has enabled its use in combination regimens in clinical trials in first-line and relapsed/refractory CLL. This paper summarizes the development of PI3Kis, their current role and future perspectives in the treatment of patients with CLL. Phosphoinositide 3-kinases (PI3Ks) signaling regulates key cellular processes, such as growth, survival and apoptosis. Among the three classes of PI3K, class I is the most important for the development, differentiation and activation of B and T cells. Four isoforms are distinguished within class I (PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ). PI3Kδ expression is limited mainly to the B cells and their precursors, and blocking PI3K has been found to promote apoptosis of chronic lymphocytic leukemia (CLL) cells. Idelalisib, a selective PI3Kδ inhibitor, was the first-in-class PI3Ki introduced into CLL treatment. It showed efficacy in patients with del(17p)/TP53 mutation, unmutated IGHV status and refractory/relapsed disease. However, its side effects, such as autoimmune-mediated pneumonitis and colitis, infections and skin changes, limited its widespread use. The dual PI3Kδ/γ inhibitor duvelisib is approved for use in CLL patients but with similar toxicities to idelalisib. Umbralisib, a highly selective inhibitor of PI3Kδ and casein kinase-1ε (CK1ε), was found to be efficient and safe in monotherapy and in combination regimens in phase 3 trials in patients with CLL. Novel PI3Kis are under evaluation in early phase clinical trials. In this paper we present the mechanism of action, efficacy and toxicities of PI3Ki approved in the treatment of CLL and developed in clinical trials. [ABSTRACT FROM AUTHOR]

The most common forms of B-cell malignancy, non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), have seen a drastic shift in the treatment landscape over the last two decades with the introduction of targeted agents. Among them are Bruton's tyrosine kinase (BTK) inhibitors, which have demonstrated excellent efficacy in indolent B-cell NHLs and CLL. Although BTK inhibitors are generally thought to be more tolerable than chemoimmunotherapy, they are associated with a unique safety profile including varying rates of rash, diarrhea, musculoskeletal events, cardiovascular events, and bleeding. Ibrutinib was the first BTK inhibitor to gain a Health Canada indication, followed by second-generation BTK inhibitors acalabrutinib and zanubrutinib, which have better safety profiles compared to ibrutinib, likely due to their improved selectivity for BTK. As BTK inhibitors are oral agents given continuously until disease progression, long-term adverse event (AE) monitoring and management as well as polypharmacy considerations are important for maintaining patient quality of life. This paper intends to serve as a reference for Canadian nurses and pharmacists on dosing, co-administration, and AE management strategies when caring for patients with indolent B-cell NHL or CLL being treated with BTK inhibitors. [ABSTRACT FROM AUTHOR]

Several novel treatments for chronic lymphocytic leukemia (CLL) have been recently approved based on the results of randomized clinical trials. However, real-world evidence (RWE) is also requested before and after drug authorization in order to confirm safety and to provide data for health technology assessments. We conducted a scoping review of the available RWE for targeted treatments of CLL, namely ibrutinib, acalabrutinib, idelalisib, and venetoclax, as well as for chemoimmunotherapy (CIT). In particular, we searched studies published since 1 January 2010 and reported outcomes of the above treatments based on health databases, registries, or phase IV studies, including named-patient programs. We included both full papers and abstracts of studies presented at major meetings. Overall, 110 studies were selected and analyzed: 28,880 patients were treated with ibrutinib, 1424 with idelalisib, 751 with venetoclax, 496 with acalabrutinib, and 14,896 with CIT. Reported discontinuation rates were higher than in clinical trials, while effectiveness could not be indirectly compared with clinical trials since a detailed case mix, including cytogenetic risk factors, was partially available and propensity scores rarely applied. RWE on CLL can help to set realistic outcomes with novel treatments, however, real-world studies should be fostered, and available data shared. [ABSTRACT FROM AUTHOR]

This paper presents a coil-based liquid lens (CLL) with a mature and simple fabrication process. A tunable focal length is achieved by changing the liquid–liquid interface curvature using electrowetting on dielectric (EWOD). The lens cavity is a coil wound or stacked by a particular structure named EWOD wire, which is made by coating a soft insulating dielectric layer on a flexible conductive core. As a result, requirements for different lens designs can be achieved, and coating an insulating dielectric layer in complex cavities is not required. The optical performance of the CLL is measured with a clear aperture of 8 mm, which shows that the tunable range for the focal length is (−∞, −35 mm] ∪ [78 mm, +∞) at a voltage of 0–235 V, and the response time is less than 40 ms. [ABSTRACT FROM AUTHOR]

This paper considers the Riemann–Hilbert problem (RHP) with higher-order poles for the Chen–Lee–Liu equation. By assuming the scattering coefficients have N th order zero points, we obtain expressions of these scattering coefficients, the theta condition, and parallelization conditions between Jost solutions and their derivatives. Based on these parallelization conditions, it yields generalizations of residue conditions, which are essential for solving the RHP with higher-order poles. The explicit formulae for solutions of CLL equation are reconstructed from asymptotic behaviors of the RHP. As an example, we present the second-order pole soliton and illustrate that parameter b 0 plays a principal role to determine the structures of solutions of the CLL equation. [ABSTRACT FROM AUTHOR]

Computational systems to provide studies and diagnoses of non-Hodgkin's lymphomas have been increasingly developed to assist specialists in their decision-making. On the other hand, the approaches have not yet fully explored the sample entropy to assess the disease's characteristics, with indications of the best features and techniques to distinguish the main groups of lymphomas. Herein, we present a method that considers sample entropy signatures to study chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma, involving images after applying multiple segmentation techniques and color normalization models. Texture signatures were defined as feature curves obtained from multiple observations, by associating different parameters. Each signature was calculated for windows of size m and ranged from 1 to 4 (0.06–0.40) tolerance levels (r). The behavior of each signature was determined from the area under the curve, skewness, maximum entropy value and area ratio, representing the signature metrics. This approach aimed to improve the quantitative ability of this descriptor, with new interpretations and associations. Thus, all features were provided for different functions, such as lazy learning, trees, genetic evolution, particle swarm and animal behavior-based approaches. The best association was tested after adding noise levels of 20%, 40% and 80%. The performances achieved with the proposal were accuracy rates between 98.72% and 99.60%. We were able to obtain an accuracy of 98.84% for multi-class classification using only ten features, which is an amount considerably lower than most of the state-of-the-art approaches. The proposed approach presents relevant advances for the investigation of computer-aided diagnosis systems since it provides accurate results and does not require preprocessing steps. Moreover, signature metrics in association with evolutionary approaches, which provided the best results, are among the main contributions of this paper, since the details of the most relevant features with a full understanding of the solutions are useful for the study and pattern recognition of non-Hodgkin's lymphomas. • An experimental analysis dedicated to improving techniques for CAD systems on NHL. • Association of SampEn signatures and different classifiers for evaluating H&E images. • Analyses with multiple segmentation techniques and color normalization models. • Enhancement of the quantitative ability of sample entropy with signature metrics. • Accurate results even after applying different types of noise. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL. [ABSTRACT FROM AUTHOR]

Earlier studies have shown that classification accuracies of Bayesian networks (BNs) obtained by maximizing the conditional log likelihood (CLL) of a class variable, given the feature variables, were higher than those obtained by maximizing the marginal likelihood (ML). However, differences between the performances of the two scores in the earlier studies may be attributed to the fact that they used approximate learning algorithms, not exact ones. This paper compares the classification accuracies of BNs with approximate learning using CLL to those with exact learning using ML. The results demonstrate that the classification accuracies of BNs obtained by maximizing the ML are higher than those obtained by maximizing the CLL for large data. However, the results also demonstrate that the classification accuracies of exact learning BNs using the ML are much worse than those of other methods when the sample size is small and the class variable has numerous parents. To resolve the problem, we propose an exact learning augmented naive Bayes classifier (ANB), which ensures a class variable with no parents. The proposed method is guaranteed to asymptotically estimate the identical class posterior to that of the exactly learned BN. Comparison experiments demonstrated the superior performance of the proposed method. [ABSTRACT FROM AUTHOR]

Simple Summary: This review analyzes the occurrence, clinical characteristics, and prognostic impact and treatment of autoimmune hemolytic anemia (AIHA) in chronic lymphocytic leukemia (CLL). Autoimmune hemolytic anemia is observed in about 10% of CLL. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity, so the different mechanisms are well described in this review which also focuses on drugs associated to CLL-AIHA and on difficulties to diagnose it. There is a comprehensive revision of the main published casistics and then of the treatments; in particular the paper analyzes the main chemo-immunotherapeutic agents used in this setting. Since the therapy depends on the presence and severity of clinical symptoms, disease status, and comorbidities, treatment is nowadays more individualized in CLL and also in CLL-AIHA. Patients not responding to corticosteroids and rituximab are treated with CLL-specific drugs as per current guidelines according to age and comorbidities and new targeted agents against BCR and BCL-2 which can be given orally and have few side effects, are very effective both in progressive CLL and in situations such as AIHA. Chronic lymphocytic leukemia (CLL) patients have a greater predisposition to develop autoimmune complications. The most common of them is autoimmune hemolytic anemia (AIHA) with a frequency of 7–10% of cases. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity. CLL B-cells have damaged apoptosis, produce less immunoglobulins, and could be responsible for antigen presentation and releasing inflammatory cytokines. CLL B-cells can act similar to antigen-presenting cells activating self-reactive T helper cells and may induce T-cell subsets imbalance, favoring autoreactive B-cells which produce anti-red blood cells autoantibodies. Treatment is individualized and it depends on the presence and severity of clinical symptoms, disease status, and comorbidities. Corticosteroids are the standardized first-line treatment; second-line treatment comprises rituximab. Patients not responding to corticosteroids and rituximab should be treated with CLL-specific drugs as per current guidelines according to age and comorbidities. New targeted drugs (BTK inhibitors and anti BCL2) are recently used after or together with steroids to manage AIHA. In the case of cold agglutinin disease, rituximab is preferred, because steroids are ineffective. Management must combine supportive therapies, including vitamins; antibiotics and heparin prophylaxis are indicated in order to minimize infectious and thrombotic risk. [ABSTRACT FROM AUTHOR]