tbuckley/cabot-search huggingface dataset:
R-CHOP14 As a Standard of Care in Primary Mediastinal B Cell Lymphoma: A 10-YEARS Experience of Lysa Centers
Authors: Vincent Camus, Alina Berriolo-Riedinger, Justine Lequesne, David Tonnelet, Pierre Decazes, Cédric Rossi, Pierre Sesques, Corinne Haioun, Eric Durot, Alexandre Willaume, Martin Gauthier, Marie-Pierre Moles, Chloe Antier, Julien Lazarovici, Helene Monjanel, Sophie Bernard, Magalie Tardy, Caroline Besson, Laure Lebras, Choquet Sylvain, Katell Le Du, Christophe Bonnet, Sarah Bailly, Damaj Gandhi Laurent, Kamel Laribi, Herve Maisonneuve, Roch Houot, Adrien Chauchet, Fabrice Jardin, Stephanie Becker, Herve Tilly
Journal: Blood (2020)
Role of Postoperative Radiotherapy in Nonmetastatic Head and Neck Adenoid Cystic Carcinoma
Authors: Yue Chen, Zi-Qi Zheng, Fo-Ping Chen, Jian-Ye Yan, Xiao-Dan Huang, Feng Li, Ying Sun, Guan-Qun Zhou
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Head and neck adenoid cystic carcinoma (ACC) is a rare malignant tumor that is prone to local recurrence. The NCCN Guidelines for Head and Neck Cancers recommend that all patients with ACC receive postoperative radiotherapy (PORT). However, whether PORT can improve local control and which patients can benefit from PORT are unknown. This study aimed to assess the role of PORT and provide individualized suggestions for postoperative therapy in patients with ACC. Patients and Methods: We retrospectively reviewed patients with nonmetastatic head and neck ACC who underwent surgery with or without PORT. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict local recurrence-free survival (LRFS). The survival outcome was compared between non-PORT and PORT groups. Results: A total of 319 patients were included. PORT was identified as a prognostic factor for LRFS in univariate ( P =.01) and multivariate analysis ( P &lt;.01). However, it did not improve distant metastasis-free survival, disease-free survival, or overall survival in univariate analysis. RPA categorized patients into 3 prognostic groups: low-risk (negative margin, T1–T2, primary location = major or minor salivary gland), intermediate-risk (negative margin, T1–T2, primary location = other locations instead of a major or minor salivary gland; negative margin, T3–T4; positive margin, without bone invasion), and high-risk (positive margin, with bone invasion). Significant LRFS improvements in the PORT group were observed among intermediate-risk ( P &lt;.01) and high-risk patients ( P &lt;.05). LRFS improvements among low-risk patients were relatively insignificant ( P =.10). Conclusions: PORT was shown to be a positive prognostic factor for improved LRFS in ACC. Furthermore, PORT could significantly improve LRFS in intermediate-risk and high-risk patients with ACC, but whether low-risk patients could benefit from PORT needs further study.
Frank Martin Hull
Authors: Emma Miller
Journal: BMJ (2020)

After qualifying, completing house jobs, and doing a short service commission in the Royal Navy, Frank Martin Hull, always known as Robin, entered rural general practice in Wellesbourne, Warwickshire in 1960.

In 1973 he took a sabbatical from the practice as visiting professor in general practice at the University of North Carolina, Chapel Hill, USA.

On returning to the practice, alongside his clinical work, …
Abstract 394: Nicotinamide Phosphoribosyltransferase (Nampt) Potentiates Antioxidant Defense in Diastolic Heart Failure Associated With Diabetes
Authors: Shinichi Oka, Jaemin Byun, Chun-yang Huang, Nobushige Imai, Guersom Ralda, Peiyong Zhai, Xiaoyong Xu, Yoshiyuki Ikeda, Wataru Mizushima, Toshihide Kashihara, Junichi Sadoshima
Journal: Circulation Research (2020)

More than half of diabetic patients develop diastolic heart failure. Nampt is a rate-limiting enzyme for NAD synthesis. Phosphorylation of NAD by NAD kinase (NADK) generates NAD phosphate (NADP), which is in turn converted to NADPH and provides the GSH and thioredoxin (Trx) systems with a reducing power. Whether Nampt is protective against diabetic cardiomyopathy (DCM) and, if so, whether NADK mediates the salutary function of Nampt are unknown. We employed mice with cardiac-specific Nampt overexpression (Nampt-cTG) and a mouse model of DCM induced by high fat diet (HFD) consumption. HFD-induced diastolic dysfunction, indicated by an elevated end-diastolic pressure-volume relationship (EDPVR), was ameliorated in Nampt-cTG mice (EDPVR: wild-type mice (WT) Normal Diet (ND): 0.045; WT HFD (1 month): 0.136; Nampt-cTG: 0.042: Nampt-cTG HFD: 0.055*, p&lt;0.05 vs WT HFD). The protective effect was abolished by thionicotinamide, an NADK inhibitor (EDPVR: Nampt-cKO HFD with thionicotinamide 0.12*, p&lt;0.05 vs Nampt-cKO HFD). Nampt overexpression also attenuated HFD-induced increases in GSSG/GSH and oxidation of Trx1 substrates, including peroxiredoxin 1 (Prdx1). Nampt overexpression upregulated not only NAD(H) (1.5 fold) but also NADP(H) (1.3 fold) in the heart and in cardiomyocytes. Nampt-induced NADPH upregulation was abolished in the presence of NADK knockdown. Nampt attenuated H 2 O 2 -induced oxidation of Trx1 substrates in an NADK-dependent manner in cardiomyocytes. Nampt overexpression inhibited H 2 O 2 -induced cell death, an effect that was attenuated in the presence of NADK inhibition. Systemic Nampt heterozygous knockout promoted HFD-induced diastolic dysfunction and oxidative stress in the heart in vivo . These results suggest that Nampt protects the heart against diastolic dysfunction through upregulation of the reducing system, which occurs through NADK-dependent upregulation of the reducing equivalent, namely NADPH.
Abstract 487: Dihyrosphingosine 1 Phosphate Mediates Collagen Synthesis in Cardiac Fibroblasts Throught Pi3k/akt- Mtor Signalling Pathway
Authors: Ruth R Magaye, Feby Sevira, Xin Xiong, Bernard Flynn, Bing Wang
Journal: Circulation Research (2020)

Background: Cardiac fibrosis is one of the hallmarks of cardiac remodelling in cardiomyopathies such as heart Failure (HF). Dyslipidemia plays a role in the progression of HF. The sphingolipid, dihydrosphingosine 1 phosphate (dhS1P) has been shown to bind to high density lipids in plasma. Unlike its analog, spingosine 1 phosphate (S1P), the role of dhS1P in cardiac fibrosis is not known. The aim of this study is to determine the role dhS1P plays in cardiac fibrosis through the PI3K/Akt- mTOR pathway. Method: Neonatal rat cardiac fibroblasts (NCF) were isolated from 1-2 day old pups with enzymic digestion. After pre-treating with the PI3K inhibitor, Wortmannin (W, 0.1 - 10.0μM), cells were stimulated with dhS1P for 48 hours. NCF collagen synthesis was determined by 3H-proline incorporation. NCF were also treated for protein and gene expression analysis. Results: Exogenous addition of 3 μM dhS1P stimulated significant increase in collagen synthesis (p&lt;0.005) which was dose dependently inhibited by W (p &lt; 0.0001, Fig. 1A). Western blot analysis showed that W reduced Akt, mTOR, and S6 activation in the presence of dhS1P. dhS1P also increased protein levels of TGFβ, Coll 1 and TIMP1. W reduced dhS1P elevated TIMP1, and SK1, but not TGFβ1 gene expression (Fig. 1B). Conclusion: Our study demonstrates for the first time that dhS1P can cause cardiac cellular fibrosis via PI3K/Akt- mTOR pathway. Its inhibition may represent a novel therapeutic strategy for cardiac fibrosis.
Prostate Cancer Grade and Stage Misclassification in Active Surveillance Candidates: Black Versus White Patients
Authors: Lara Franziska Stolzenbach, Giuseppe Rosiello, Angela Pecoraro, Carlotta Palumbo, Stefano Luzzago, Marina Deuker, Zhe Tian, Anne-Sophie Knipper, Raisa Pompe, Kevin C. Zorn, Shahrokh F. Shariat, Felix K.H. Chun, Markus Graefen, Fred Saad, Pierre I. Karakiewicz
Journal: Journal of the National Comprehensive Cancer Network (2020)

Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void.Within the SEER database (2010-2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used.Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = -1.5%; P=.05) in those with favorable intermediate risk.Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.
Adenosine Base Editing of γ-Globin Promoters Induces Fetal Hemoglobin and Inhibit Erythroid Sickling
Authors: Thiyagaraj Mayuranathan, Jonathan S. Yen, Gregory A. Newby, Yu Yao, Shaina N. Porter, Kaitly J. Woodard, Jingjing Zhang, Kalin Mayberry, Akshay Sharma, Shondra M. preutt-Miller, John F. Tisdale, Shengdar Q. Tsai, David R. Liu, Mitchell J. Weiss
Journal: Blood (2020)
Prospective Multicentric Observational Study of COVID19 in Oncohematological Patients in the Catalonia Region: The Opposite Effect of Steroids on Survival
Authors: Alberto Mussetti, Clara Maluquer, Cristian Tebe Cordomi, Maria Condom, Kevin Molina-Mata, Juan Antonio Marin Jimenez, Jose Carlos Tapia Tapia, Javier Gavira Diaz, Margarita Majem Tarruella, Felip Falgas, Laia Llobera Rius, Roser Fort Culillas, Lucia Llavata Martí, Miriam Moreno, Susana Vives, Rosa Coll, Silvia Martin Batista, Carme Talarn, Miguel Sagüés, Ali Bazarbachi, Ramon Salazar, Anna Sureda Balari
Journal: Blood (2020)
Single Cell Transcriptomic Evolution and Resistance Mechanisms of BTK and BCL-2 Inhibition in Mantle Cell Lymphoma
Authors: Vivian Changying Jiang, Shaojun Zhang, Junwei Lian, Yuanxin Wang, Rongjia Zhang, Yang Liu, Joseph McIntosh, Guangchun Han, Ruiping Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Hun Lee, Raphael Eric Steiner, Jorge Enrique Romaguera, Preetesh Jain, Krystle Nomie, Andy Futreal, Linghua Wang, Michael Wang
Journal: Blood (2020)
Machine Leaning Algorithm on Chemotherapeutic Drug Resistance Related Gene Classifier in Acute Myeloid Leukemia
Authors: Yang Song, Yannan Jia, Guangji Zhang, Shuning Wei, Yan Li, Yimin Hu, Qishan Hao, Zhe Wang, Qiuyun Fang, Zheng Tian, Shangzhu Li, Min Wang, Jianxiang Wang, Yingchang Mi
Journal: Blood (2020)
Prognostic and Therapeutic Implications of Mutant <i>TP53</i> Variant Allelic Frequency in Adults with Newly Diagnosed <i>TP53</i>-Mutated Acute Myeloid Leukemia
Authors: Nicholas J. Short, Guillermo Montalban-Bravo, Hyunsoo Hwang, Jing Ning, Miguel Franquiz, Rashmi Kanagal-Shamanna, Keyur Patel, Courtney D. Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Koichi Takahashi, Marina Konopleva, Naval Daver, Elias Jabbour, Musa Yilmaz, Ghayas C. Issa, Michael Andreeff, Tapan M. Kadia
Journal: Blood (2020)
Nx-2127, a Degrader of BTK and IMiD Neosubstrates, for the Treatment of B-Cell Malignancies
Authors: Daniel W Robbins, Aileen Kelly, May Tan, Joel McIntosh, Jeffrey Wu, Zef Konst, Daisuke Kato, Ge Peng, Jeff Mihalic, Dahlia Weiss, Luz Perez, Jennifer Tung, Anna Kolobova, Sasha Borodovsky, Ryan Rountree, Austin Tenn-McClellan, Mark Noviski, Jordan Ye, Steve Basham, Timothy Ingallinera, Jenny McKinnell, Dane E Karr, Janine Powers, Cristiana Guiducci, Arthur Sands
Journal: Blood (2020)
Real-world experience with caplacizumab in the management of acute TTP
Authors: Tina Dutt, Rebecca J. Shaw, Matthew Stubbs, Jun Yong, Benjamin Bailiff, Tanya Cranfield, Maeve P. Crowley, Michael Desborough, Toby A. Eyre, Richard Gooding, John Grainger, John Hanley, Joanna Haughton, Joannes Hermans, Quentin Hill, Louise Humphrey, Gillian Lowe, Hamish Lyall, Muhammad Mohsin, Phillip L. R. Nicolson, Nicole Priddee, Alexandros Rampotas, Rachel Rayment, Susan Rhodes, Alice Taylor, William Thomas, Oliver Tomkins, Joost J. Van Veen, Steven Lane, Cheng-Hock Toh, Marie Scully
Journal: Blood (2020)
Congenital Adrenal Hyperplasia
Authors: Phyllis W. Speiser, Perrin C. White
Journal: New England Journal of Medicine (2003)

Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90 percent of cases. This article discusses the molecular mechanisms, diagnosis, and management of this disease and highlights new developments, including genotype–phenotype correlations, gene-specific prenatal diagnosis, and prenatal therapy.
Ophthalmic Immune-Related Adverse Events after Anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology Intelligent Research in Sight Registry
Authors: Michel M. Sun, Scott P. Kelly, Apoorva L. Mylavarapu, BS, Gary N. Holland, Anne L. Coleman, Fei Yu, Stephen Hsu, MS, Flora Lum, Lynn K. Gordon
Journal: Ophthalmology (2020)
Perceptions of Patient Disease Burden and Management Approaches of Systemic Mastocytosis (SM) By Healthcare Providers: Results from the TouchStone SM Survey
Authors: Ruben A. Mesa, Erin M. Sullivan, David Dubinsky, Brittany Carroll, Valerie M. Slee, Susan Jennings, Celeste Finnerty, Linda Bohannon, Susan Mathias, Mariana Castells
Journal: Blood (2020)
CAR-T cells and TRUCKs that recognize an EBNA-3C-derived epitope presented on HLA-B*35 control Epstein-Barr virus-associated lymphoproliferation
Authors: Anna Christina Dragon, Katharina Zimmermann, Thomas Nerreter, Deborah Sandfort, Julia Lahrberg, Stephan Klöß, Christina Kloth, Caroline Mangare, Agnes Bonifacius, Sabine Tischer-Zimmermann, Rainer Blasczyk, Britta Maecker-Kolhoff, Barbara Uchanska-Ziegler, Hinrich Abken, Axel Schambach, Michael Hudecek, Britta Eiz-Vesper
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunosuppressive therapy or T-cell depletion in transplant patients can cause uncontrolled growth of Epstein-Barr virus (EBV)-infected B cells resulting in post-transplant lymphoproliferative disease (PTLD). Current treatment options do not distinguish between healthy and malignant B cells and are thereby often limited by severe side effects in the already immunocompromised patients. To specifically target EBV-infected B cells, we developed a novel peptide-selective chimeric antigen receptor (CAR) based on the monoclonal antibody TÜ165 which recognizes an Epstein-Barr nuclear antigen (EBNA)−3C-derived peptide in HLA-B*35 context in a T-cell receptor (TCR)-like manner. In order to attract additional immune cells to proximity of PTLD cells, based on the TÜ165 CAR, we moreover generated T cells redirected for universal cytokine-mediated killing (TRUCKs), which induce interleukin (IL)-12 release on target contact. Methods TÜ165-based CAR-T cells (CAR-Ts) and TRUCKs with inducible IL-12 expression in an all-in-one construct were generated. Functionality of the engineered cells was assessed in co-cultures with EBNA-3C-peptide-loaded, HLA-B*35-expressing K562 cells and EBV-infected B cells as PTLD model. IL-12, secreted by TRUCKs on target contact, was further tested for its chemoattractive and activating potential towards monocytes and natural killer (NK) cells. Results After co-cultivation with EBV target cells, TÜ165 CAR-Ts and TRUCKs showed an increased activation marker expression (CD137, CD25) and release of proinflammatory cytokines (interferon-γ and tumor necrosis factor-α). Moreover, TÜ165 CAR-Ts and TRUCKs released apoptosis-inducing mediators (granzyme B and perforin) and were capable to specifically lyse EBV-positive target cells. Live cell imaging revealed a specific attraction of TÜ165 CAR-Ts around EBNA-3C-peptide-loaded target cells. Of note, TÜ165 TRUCKs with inducible IL-12 showed highly improved effector functions and additionally led to recruitment of monocyte and NK cell lines. Conclusions Our results demonstrate that TÜ165 CAR-Ts recognize EBV peptide/HLA complexes in a TCR-like manner and thereby allow for recognizing an intracellular EBV target. TÜ165 TRUCKs equipped with inducible IL-12 expression responded even more effectively and released IL-12 recruited additional immune cells which are generally missing in proximity of lymphoproliferation in immunocompromised PTLD patients. This suggests a new and promising strategy to specifically target EBV-infected cells while sparing and mobilizing healthy immune cells and thereby enable control of EBV-associated lymphoproliferation.
Low Rate of Thrombosis in Mexican Patients with COVID-19 Infection. a Benefit of Higher Doses Anticoagulants or a Sub Diagnosis?
Authors: Félix Gibrant Marquez, Santiago Riviello-Goya, Angel Gabriel Vargas Ruiz, Edgar Ortíz Brizuela, Fernando Gil López, Alfredo Gutierrez Marín, María Fernanda Gonzalez Lara, Alfredo Ponce de Léon Garduño, José Sifuentes Osornio, Juan Rangel-Patiño
Journal: Blood (2020)
Abstract IA24: Dissecting glioblastoma by single cell RNA-seq
Authors: Toshi Hara, Rony Chanoch, Mario Suva, Itay Tirosh
Journal: Cancer Research (2020)

Abstract Glioblastoma is an incurable malignancy that remains poorly understood. By large-scale single cell RNA-seq and follow up experiments we found that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct steps of neural development, are influenced by the tumor microenvironment, and exhibit plasticity. Importantly, we show that while each glioblastoma contains similar cellular states, their relative frequency varies between tumors and is influenced by chromosomal aberrations as well as by the tumor microenvironment. In particular, we demonstrate that macrophages induce a transition of glioblastoma cells into mesenchymal-like (MES-like) states. This effect is mediated, both in vitro and in vivo, by macrophage-derived ligands that interact with receptors on glioblastoma cells. Finally, we show that MES-like glioblastoma states is associated with altered T cells cytotoxicity and response to immunotherapies. Overall, this work dissects the cellular diversity and interactions within the glioblastoma microenvironment, with potential implications for therapies. Citation Format: Toshi Hara, Rony Chanoch, Mario Suva, Itay Tirosh. Dissecting glioblastoma by single cell RNA-seq [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA24.
Preliminary Results of an Ongoing Phase 1 Dose Escalation Study of the Novel Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with B-Cell Non-Hodgkin Lymphoma
Authors: Nirav N. Shah, Ahmad H. Mattour, Leslie L. Popplewell, Charalambos Andreadis, Jason M. Melear, Alexander I. Spira, Jonah Shulman, Sudhir Manda, John M. Burke, Saurabh Chhabra, Jeff P Sharman, Amrita Krishnan, Nina Shah, Clifford DiLea, Jason Kuriakose, Craig Jerome Berman, Shannon L. Matheny, John P. Leonard, Arturo Molina
Journal: Blood (2020)
Common Adaptive Strategies Underlie Within-Host Evolution of Bacterial Pathogens
Authors: Yair E Gatt, Hanah Margalit
Journal: Molecular Biology and Evolution (2020)

Within-host adaptation is a hallmark of chronic bacterial infections, involving substantial genomic changes. Recent large-scale genomic data from prolonged infections allow the examination of adaptive strategies employed by different pathogens and open the door to investigate whether they converge toward similar strategies. Here, we compiled extensive data of whole-genome sequences of bacterial isolates belonging to miscellaneous species sampled at sequential time points during clinical infections. Analysis of these data revealed that different species share some common adaptive strategies, achieved by mutating various genes. Although the same genes were often mutated in several strains within a species, different genes related to the same pathway, structure, or function were changed in other species utilizing the same adaptive strategy (e.g., mutating flagellar genes). Strategies exploited by various bacterial species were often predicted to be driven by the host immune system, a powerful selective pressure that is not species specific. Remarkably, we find adaptive strategies identified previously within single species to be ubiquitous. Two striking examples are shifts from siderophore-based to heme-based iron scavenging (previously shown for Pseudomonas aeruginosa) and changes in glycerol-phosphate metabolism (previously shown to decrease sensitivity to antibiotics in Mycobacterium tuberculosis). Virulence factors were often adaptively affected in different species, indicating shifts from acute to chronic virulence and virulence attenuation during infection. Our study presents a global view on common within-host adaptive strategies employed by different bacterial species and provides a rich resource for further studying these processes.
Molecular targeting therapies for neuroblastoma: Progress and challenges
Authors: Atif Zafar, Wei Wang, Gang Liu, Xinjie Wang, Wa Xian, Frank McKeon, Jennifer Foster, Jia Zhou, Ruiwen Zhang
Journal: Medicinal Research Reviews (2020)

There is an urgent need to identify novel therapies for childhood cancers. Neuroblastoma is the most common pediatric solid tumor, and accounts for ~15% of childhood cancer-related mortality. Neuroblastomas exhibit genetic, morphological and clinical heterogeneity, which limits the efficacy of existing treatment modalities. Gaining detailed knowledge of the molecular signatures and genetic variations involved in the pathogenesis of neuroblastoma is necessary to develop safer and more effective treatments for this devastating disease. Recent studies with advanced high-throughput "omics" techniques have revealed numerous genetic/genomic alterations and dysfunctional pathways that drive the onset, growth, progression, and resistance of neuroblastoma to therapy. A variety of molecular signatures are being evaluated to better understand the disease, with many of them being used as targets to develop new treatments for neuroblastoma patients. In this review, we have summarized the contemporary understanding of the molecular pathways and genetic aberrations, such as those in MYCN, BIRC5, PHOX2B, and LIN28B, involved in the pathogenesis of neuroblastoma, and provide a comprehensive overview of the molecular targeted therapies under preclinical and clinical investigations, particularly those targeting ALK signaling, MDM2, PI3K/Akt/mTOR and RAS-MAPK pathways, as well as epigenetic regulators. We also give insights on the use of combination therapies involving novel agents that target various pathways. Further, we discuss the future directions that would help identify novel targets and therapeutics and improve the currently available therapies, enhancing the treatment outcomes and survival of patients with neuroblastoma.