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2,302 results for “B-cells”
Distinct Stromal Cell Populations Define the B-cell Acute Lymphoblastic Leukemia Microenvironment
<p>Processed single-cell RNA-seq from the study </p> <ul> <li>10X Genomics CellRanger output (barcodes.tsv, genes.tsv, matrix.mtx) for each each sample</li> <li>Metadata</li> <li>Seurat object of the integrated scRNAseq dataset</li> <li>Xenium object of the spatial transcriptomic data</li> </ul> <p>Distinct Stromal Cell Populations Define the B-cell Acute Lymphoblastic Leukemia Microenvironment</p> <p>Mauricio N. Ferrao Blanco<sup>1</sup>, Bexultan Kazybay<sup>1</sup>, Mirjam Belderbos<sup>1</sup>, Olaf Heidenreich<sup>1</sup>, Hermann Josef Vormoor<sup>1,2</sup></p> <p><sup>1 </sup>Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands</p> <p><sup>2 </sup>University Medical Center Utrecht, Utrecht, the Netherlands</p> <p><strong>Abstract</strong></p> <p>The bone marrow microenvironment plays a critical role in B-cell acute lymphoblastic leukemia (B-ALL) progression, yet its cellular heterogeneity remains poorly understood. Using single-cell RNA sequencing on patient-derived of bone marrow aspirates from pediatric B-ALL patients, we identified two distinct mesenchymal stromal cell (MSC) populations: early mesenchymal progenitors and adipogenic progenitors. Spatial transcriptomic analysis further revealed the localization of these cell types and identified a third stromal population, osteogenic-lineage cells, exclusively present in the bone biopsy. Functional <em>ex vivo</em> assays using sorted stromal populations derived from B-ALL patient bone marrow aspirates demonstrated that both early mesenchymal and adipogenic progenitors secrete key niche-supportive factors, including CXCL12 and Osteopontin, and support leukemic cell survival and chemoresistance. Transcriptomic profiling revealed that B-ALL cells interact differently with stromal subtypes. Notably, adipogenic progenitors, but not early mesenchymal progenitors, provide support to leukemic cells through interleukin-7 and VCAM1 signaling. Stromal cells from B-ALL patients exhibited an enhanced adipogenic differentiation capacity compared to healthy controls. Moreover, co-culture experiments showed that B-ALL cells induce adipogenic differentiation in healthy MSCs through a cell contact-dependent mechanism. Adipogenic progenitors were also enriched in relapse samples, implicating them in disease progression. These findings highlight the complexity of the B-ALL microenvironment and identify different specialized stromal niches with which the leukemic cells can engage.</p> <p> </p> <p> </p> <p> </p>
spindle cell variant diffuse large B-cell lymphoma (NGS annotation file; high confidence calls) hematolrep-2136295
<p>Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans’ classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response.</p> <p>Carreras J, Kikuti YY, Miyaoka M, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Ito A, Nagase S, Miura H, Roncador G, Colomo L, Hamoudi R, Campo E, Nakamura N. Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma. <em>Hematology Reports</em>. 2023; 15(1):188-200. https://doi.org/10.3390/hematolrep15010020</p>
spindle cell variant diffuse large B-cell lymphoma (hematolrep-2136295)
<p>Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans’ classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response.</p> <p>Carreras J, Kikuti YY, Miyaoka M, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Ito A, Nagase S, Miura H, Roncador G, Colomo L, Hamoudi R, Campo E, Nakamura N. Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma. <em>Hematology Reports</em>. 2023; 15(1):188-200. https://doi.org/10.3390/hematolrep15010020</p>
Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
ClinicalTrials.gov study NCT04436107. IPD Sharing: YES. Countries: 1. Publications: 0.
Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma
ClinicalTrials.gov study NCT03570892. IPD Sharing: YES. Countries: 18. Publications: 3.
Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib
ClinicalTrials.gov study NCT05068440. IPD Sharing: YES. Countries: 1. Publications: 0.
Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy
ClinicalTrials.gov study NCT01077518. IPD Sharing: YES. Countries: 17. Publications: 1.
Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-
ClinicalTrials.gov study NCT00790036. IPD Sharing: UNDECIDED. Countries: 34. Publications: 1.
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic
<p>Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition.</p> <p>Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering.</p> <p>Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed.</p> <p>Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.</p>
Supplementary data for article "Reduced B-cell antigenicity of Omicron lowers host serologic response"
<p>This repository contains five supplementary data files for the research article "<strong>Reduced B-cell antigenicity of Omicron lowers host serologic response</strong>". For more information, please refer to the article preprint https://doi.org/10.1101/2022.02.15.480546 and upcoming article at Cell Reports.</p> <p> </p> <ol> <li><strong>Table_hCoV229E.xlsx:</strong> list of hCoV229E RBD sequences, with associated isolate and collection date identifiers, and ScanNet antigenicity score for reproducing <strong>Figure 3A</strong>. Aligned sequences and templates are also provided.</li> <li><strong>table_artificial_variants.csv</strong>: List of artificial RBD sequences generated by an evolutionary-based sequence generative model for reproducing <strong>Figure 3B</strong>, <strong>Supplementary Figure S6H</strong>.</li> <li><strong>MSA_RBD.fasta:</strong> Multiple Sequence Alignment of RBD sequences and sample weights used for training the sequence generative model used in <strong>Figure 3B</strong>, <strong>Supplementary Figures S2C, S6</strong>.</li> <li><strong>table_antibody_hit_rate_RBD.csv</strong>: Empirical epitope distribution for the RBD, as determined from the Protein Data Bank and raw data for <strong>Supplementary Figure S1</strong>).</li> <li><strong>RBD_virtual_DMS.xlsx</strong>: virtual Deep Mutational Scan performed with ScanNet and the sequence generative model shown in <strong>Supplementary Figure S2</strong>.</li> </ol> <p> </p> <p> </p>
B-cell receptor data from intratumoural B cells in melanoma patients
<p>This record contains data used in the Crescioli et al. analysis of B-cell response in melanoma, specifically analysis concerning high-throughput BCR repertoire.</p> <p>Files:</p> <p>"Visium_all_Aug22_comboDatBoth.txt": IMGT/HighV-Quest output of the high-throughput intratumoural BCR repertoire from n=5 melanoma tumours. In tab-separated text file format.</p> <p>"HV_EB_COV_MEL_comb_Oct22.RDS": A R data object (readable into R with "readRDS(...)") containing combined data from the melanoma (MEL) data with analogous high-throughput BCR repertoire data from healthy volunteers (HV), Ebola convalescent patients (EB) and hospitalised COVID-19 patients (COV). HV, EB and COV data are taken from <a href="https://dx.doi.org/10.5281/zenodo.5146019">https://dx.doi.org/10.5281/zenodo.5146019</a>. Here the sequences are filtered to contain only unique combinations of isotype and IMGT-numbered V-domain DNA sequence (to remove redundancies due to e.g. capturing BCR transcripts from plasma cells).</p> <p>"BM_Master_Light_Useasreftrue_140325_withPepStats_8.csv". IMGT/HighV-Quest output of the Bone Marrow light chain repertoire data. <a href="https://doi.org/10.3389/fimmu.2016.00388">Published in Townsend et al. Front Immunol 7:388 (2016)</a>. Used here for the comparison of gene conversion frequencies against the melanoma light chain repertoire.</p> <p>"BM_Master_Light_Useasreftrue_140325_withPepStats_8_Vgapped.fasta". The IMGT-gapped V-gene sequence from the Townsend et al. (see above) Bone Marrow light chain repertoire data. This is the raw input to BrepConvert. Provided here for this dataset; same sequences for the melanoma/healthy data are already in the RDS object ("HV_EB_COV_MEL_comb_Oct22.RDS").</p> <p>"2_IMGT-gapped-nt-sequences_visa.txt", "2_IMGT-gapped-nt-sequences_visb.txt": Raw output of IMGT/HighV-Quest containing IMGT-gapped nucleotide sequences. These files were parsed to extract the IMGT-gapped V-gene sequence for BrepConvert analysis.</p> <p>"BrepConvert.zip": BrepConvert gene conversion analysis results for Healthy and Melanoma repertoires.</p> <p>See code in <a href="https://github.com/josef0731/melanoma-ig">https://github.com/josef0731/melanoma-ig</a> for ways to use these input files for reproducing the analyses.</p> <p> </p>
Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
ClinicalTrials.gov study NCT02669017. IPD Sharing: NO. Countries: 3. Publications: 3.
Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
ClinicalTrials.gov study NCT02077166. IPD Sharing: YES. Countries: 4. Publications: 2.
A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies
ClinicalTrials.gov study NCT03088878. IPD Sharing: NO. Countries: 1. Publications: 3.
A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia (CLL) Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor The
ClinicalTrials.gov study NCT02141282. IPD Sharing: YES. Countries: 1. Publications: 3.
Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas
ClinicalTrials.gov study NCT02332980. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study of De-immunized DI-Leu16-IL2 Administered Subcutaneously in Participants With B-cell NHL
ClinicalTrials.gov study NCT01874288. IPD Sharing: NO. Countries: 1. Publications: 3.
MLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab +/- Vincristine
ClinicalTrials.gov study NCT01397825. IPD Sharing: Not stated. Countries: 4. Publications: 1.
BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL)
ClinicalTrials.gov study NCT03520920. IPD Sharing: YES. Countries: 1. Publications: 0.
Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma
ClinicalTrials.gov study NCT04002401. IPD Sharing: YES. Countries: 1. Publications: 2.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.