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Deep dive: How I use robots to survey coral reefs
Prizloncabtagene autoleucel: a new CAR T cell for B-NHL
Prognostic value of circulating HPV cell-free DNA in cervical cancer using liquid biopsy
Genetic subtypes of B-cell acute lymphoblastic leukemia in adults
Abstract B-cell acute lymphoblastic leukemia (B-ALL) is a rare malignancy in adults, with outcomes remaining poor, especially compared with children. Over the past 2 decades, extensive whole-genome studies have identified numerous genetic alterations driving leukemia, leading to the recognition of >20 distinct subtypes that are closely associated with treatment response and prognosis. In pediatric B-ALL, large correlation studies have made genetic classification a central component of risk-adapted treatment strategies. Notably, genetic subtypes are unevenly distributed according to age, and the spectrum of genetic alterations and their prognostic relevance in adult B-ALL have been less extensively studied, with treatment primarily based on the presence or absence of BCR::ABL1 fusion. This review provides an overview of genetic subtypes in adult B-ALL, including recent biological and clinical insights in well-established subtypes as well as data on newly recognized subtypes. Their relevance for risk classification, disease monitoring, and therapeutic management, including in the context of B-cell–directed therapies, is discussed. This review advocates for continuing efforts to further improve our understanding of the biology of adult B-ALL to establish the foundation of future precision medicine in B-ALL.
Application of HEMA-AAm copolymer to achieve faster optical tissue transparency for 2D/3D fluorescence imaging
Classification and risk stratification in T-lineage acute lymphoblastic leukemia
Abstract Cure rates for patients with acute lymphoblastic leukemia (ALL) have improved markedly in recent decades, in part because of risk stratification incorporating leukemia genomics, response to treatment, and clinical features to be able to determine at diagnosis which patients are more likely to relapse or have refractory disease. Although risk stratification is well developed for patients with B-lineage ALL, it remains challenging for those with T-lineage ALL (T-ALL). Prognostic factors validated across clinical trials and real-world data in T-ALL include age, central nervous system involvement, and measurable residual disease (MRD) response. Immunophenotype, including early T-cell precursor ALL, is widely used to classify T-ALL but is not consistently associated with outcome in multivariable risk models. Historically, few genetic alterations have been consistently associated with outcome, but recent comprehensive, large-scale genomic profiling has identified multiple genetic subtypes and alterations associated with outcome independent of MRD. This review highlights ongoing efforts to identify reliable prognostic biomarkers and underscores the potential of genomics-based classification to guide future T-ALL treatment strategies.
Crosslinking a nanocomposite by zirconium sulfate to synthesize a high-durable new-generation polymer gel
Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma
Abstract The success of targeted therapies for hematological malignancies has heralded their potential as both salvage treatment and early treatment lines, reducing the need for high-dose, intensive, and often toxic chemotherapeutic regimens. For young patients with classic Hodgkin lymphoma (cHL), immunotherapies provide the possibility to lessen long-term, treatment-related toxicities. However, suitable therapeutic targets are lacking. By integrating single-cell dissection of the tumor landscape and an in-depth, single-cell–based off-tumor antigen prediction, we identify CD86 as a promising therapeutic target in cHL. CD86 is highly expressed on Hodgkin and Reed-Sternberg cancer cells and cHL-specific tumor-associated macrophages. We reveal CD86–CTLA-4 as a key suppressive pathway in cHL, driving T-cell exhaustion. Cellular therapies targeting CD86 had extraordinary efficacy in vitro and in vivo and were safe in immunocompetent mouse models without compromising bacterial host defense in sepsis models. Our results prove the potential value of anti-CD86 immunotherapies for treating cHL.
Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus
“When I’m 64”: functional shift of aging platelets
Publisher Correction: Sleep and stress in athletes with disabilities around the 2021 Tokyo Paralympic games during the pandemic
CD44-mediated metabolic rewiring is a targetable dependency of IDH-mutant leukemia
Abstract Recurrent isocitrate dehydrogenase (IDH) mutations catalyze nicotinamide adenine dinucleotide phosphate (NADPH)–dependent production of oncometabolite (R)-2-hydroxyglutarate (R-2HG) for tumorigenesis. IDH inhibition provides clinical response in a subset of acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need for more effective IDH-targeting therapies. By comparing transcriptomic alterations in isogenic leukemia cells harboring CRISPR base-edited IDH mutations, we identify the activation of adhesion molecules including CD44, a transmembrane glycoprotein, as a shared feature of IDH-mutant leukemia, consistent with elevated CD44 expression in IDH-mutant AML patients. CD44 is indispensable for IDH-mutant leukemia cells through activating pentose phosphate pathway and inhibiting glycolysis by phosphorylating glucose-6-phosphate dehydrogenase and pyruvate kinase muscle isozyme M2, respectively. This metabolic rewiring ensures efficient NADPH generation for mutant IDH-catalyzed R-2HG production. Combining IDH inhibition with CD44 blockade enhances the elimination of IDH-mutant leukemia cells. Hence, we describe an oncogenic feedforward pathway involving CD44-mediated metabolic rewiring for oncometabolite production, representing a potentially targetable dependency of IDH-mutant malignancies.
Intranasal oxytocin modulates brain activity during emotional processing in children with treatment resistant conduct problems
Abstract One of the most highly replicated neural correlates of Conduct Problems (CP) is amygdala hypoactivity to another person’s fear. We recently reported that this correlate was only observed in boys with persistent CP (i.e. antisocial behaviour that persisted following a gold-standard psychological intervention), suggesting that amygdala hypoactivity to fear could be an important neural signature for treatment-resistant CP, and a putative target for future treatments. Potential treatment candidates include the oxytocin system, as this has been reported to modulate amygdala activity and social behaviour across species. Further, in adults with antisocial personality disorder, intranasal oxytocin improved facial emotion recognition for fearful and happy faces. However, to-date, no-one has studied whether intranasal oxytocin can normalise neural processing differences in children with CP. Twenty boys (mean age 9.85±1.26 years) with persistent CP underwent functional magnetic resonance imaging in a within-subject randomised control design to investigate whether, compared to placebo, a single-dose of intranasal oxytocin could ‘shift’ abnormal neural processing to fear. Oxytocin failed to reduce amygdala hypoactivity to fearful faces, but increased activation in the posterior cingulate cortex / precuneus to happy faces. These findings tentatively suggest that intranasal oxytocin may promote a more neurotypical profile in treatment-resistant CP children, therefore, supporting the merit of investigating oxytocin in further larger clinical studies in this population.
Two strikes, base hit: odronextamab after CAR T cells in LBCL
No hyponatremia despite continuous plasma sodium decline in female runners during a seven stage ultramarathon
iPSCs unlock clues to pediatric AML onset
Adaptive feature interaction enhancement network for text classification
Abstract Text classification aims to establish text distinctions, which face difficulty in capturing global text semantics and local details. To address this issue, we propose an Adaptive Feature Interactive Enhancement Network (AFIENet). Specifically, AFIENet uses two branches to model the text globally and locally. The adaptive segmentation module in the local network can dynamically split the text and capture key phrases, while the global network grasps the overall central semantics. After obtaining the results from the two branches, an interaction gate is designed to evaluate the confidence of the global features and selectively fuse them with the local features effectively. Finally, the interactively enhanced features are re-input into the classifier to improve text classification performance. Experiment results show that our proposed method can effectively enhance the performance of backbone networks such as TextCNN, RNN, and Transformer with fewer parameters. AFIENet achieved an average accuracy of 3.82% and an F1-score of 3.88% improvement across the three datasets when using Transformer as the backbone network. The comparable results to MacBERT that obtained with static word vectors also reflect the applicability of the proposed method.
Aging platelets shift their hemostatic properties to inflammatory functions
Abstract Platelets are crucial players in hemostasis and thrombosis but also contribute to immune regulation and host defense, using different receptors, signaling pathways, and effector functions, respectively. Whether distinct subsets of platelets specialize in these diverse tasks is insufficiently understood. Here, we used a pulse-labeling method in Mus musculus models for tracking in vivo platelet aging and its functional implications. Using in vitro and in vivo assays, we reveal that young, reticulated platelets show heightened responses in the setting of clot formation, with corresponding, increased responses to agonists, adhesion, and retractile function. Unexpectedly, aged platelets lose their hemostatic proficiency but are more prone to react to inflammatory challenge: compared with reticulated platelets, this cohort was more likely to form platelet-leukocyte aggregates and showed increased adhesion to neutrophils in vitro, as well as enhanced bactericidal function. In vivo, this was reflected in increased pulmonary recruitment of aged platelets in an acute lung injury model. Proteomic analyses confirmed the upregulation of immune pathways in this cohort, including enhanced procoagulant function. In mouse models of prolonged platelet half-life, this resulted in increased pulmonary leukocyte infiltration and inflammation upon acute lung injury. Similarly, human platelet concentrates decreased their hemostatic function and elevated their putative immunomodulatory potential in vitro over time, and in a mouse model of platelet transfusion, aged platelet concentrates resulted in augmented inflammation. In summary, we show that platelets exhibit age-dependent phenotypic shifts, allowing them to fulfill their diverse tasks in the vasculature. Because functional alterations of aging platelets extend to platelet concentrates, this may hold important implications for transfusion medicine.