bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zebrafish ALL Driven By HumanMYCand a New Technique to Biopsy Living Fish
Authors: Park Gilseung , Burroughs-Garcia Jessica , Foster Clay , Sinha Arpan A. , Frazer Kimble John 
Published: November 2020

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; B-lineage ALL (B-ALL) represents ~85% of cases. Transgenic humanMYC(hMYC), an oncogenic transcription factor in many blood cancers, is known to induce T-ALL in zebrafish. Until recently robust zebrafish B-ALL models did not exist, but we discovered fish of this transgenic line develop B-ALL also. To distinguish T-ALL from B-ALL, we use a transgenic marker,lck:GFP, where T-ALL fluoresce brightly while B-ALL fluoresce dimly. To define B- and T-ALL incidence, we monitored &gt;600 fish by serial fluorescent microscopy and found 100% of fish developed ALL (64% T-ALL, 23% B-ALL, both 13%) by 10 months. To find transcriptional programs active in both ALL types, we performed RNA-seq on 10 T- and 14 B-ALL and compared these to T- and B-ALL induced by murineMyc(mMyc). Unexpectedly, we found B-ALL occur in distinct lineages in these related lines, withhMYCB-ALL expressingighzheavy chains, butmMycB-ALLighm. To investigate glucocorticoid responses, a key agent in ALL, we treated fishin vivowith dexamethasone (DXM).hMYCB-ALL were highly DXM-sensitive, but many recurred rapidly after treatment ceased.
Studies lymphocytes or ALL cells from zebrafish typically require fish euthanization; it would be useful to obtain cells without euthanasia. Thus, we developed biopsy techniques in living fish to obtain lymphocytes from the thymus, kidney-marrow, and even scales. We found B and T cells can be obtained from thymus, with B cells abundant in scales. We can also recover ALL cells from scales of fish with B- or T-ALL. Analyses of normal lymphocytes and ALL cells from these anatomic regions prove that GFPhi cells express T cell genes, and GFPlo cells express B cell genes. These novel biopsy methods will permit studies ofex vivosamples from live fish. Overall, these new results and methods expand the utility of zebrafishhMYC-driven ALL, a model of the most important pediatric cancer.

Disclosures
No relevant conflicts of interest to declare.
Multiple Myeloma Course with Renal Insufficiency in Young Patient: Case Report
Authors: Ferreira Hugo Henrique de Freitas , Silva Alessandra Suelen Jardim , Júnior Lenilton Silva DA Silva , Oliveira Gustavo Henrique de Medeiros , Araujo Maria das Graças Pereira , Soares Victor lima , Bahia Frank , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Paiva Aldair Sousa , Cavalcanti Geraldo Barroso 
Published: November 2020

Introduction: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells in the bone marrow (OM). The average age of patients diagnosed with MM is approximately 70 years, being relatively uncommon in younger individuals. Objective: To report a case of a young patient with multiple myeloma. Case Description: A 42-year-old male patient presented with continuous and progressive low back pain for 3 months, associated with adynamia, weight loss (10 kg), episodes of constipation and bleeding in the oral cavity in this period. Examinations at the first appointment revealed moderate anemia (Hb 7.4 g / dL), leukocytosis, thrombocytopenia, hypercalcemia, and altered renal function (Cr 5.9 and Ur 178), chest tomography indicating vertebral fracture in T6, T11, L2 and L4. Referred for specialized follow-up, he performed electrophoresis of serum proteins with the presence of a monoclonal peak in the gamma globulin fraction. The immunofixation test confirmed monoclonality for IgA isotype and Kappa light chain (IgA / Kappa). The myelogram showed plasmacytosis of more than 50% of mononuclear cells in the bone marrow. He developed renal failure (with dosage of creatinine of 10.1 mg/ dL. and urea of 208 mg/dL) and hypercalcemia requiring dialysis therapy on the third day of hospitalization, having undergone chemotherapy with Bortezomib, cyclophosphamide and dexamethasone. During this period, infection by the multisensitive S. aureus in catheter occurred and, despite being treated with specific antibiotic therapy, it evolved with clinical worsening and hemodynamic instability and was referred to the Intensive Care Unit, going to death after 2 days. Conclusion: Young patients with MM may study with more aggressive characteristics. Despite the use of new therapeutic agents, more effective treatment strategies need to be studied more for patients in this age group.

Disclosures
No relevant conflicts of interest to declare.
High-Grade B-Cell Lymphoma,NOS : Does Prognosis End with the Diagnosis? - a Retrospective Analysis
Authors: Karunakaran Parathan , Selvarajan Gangothri , PK Jayachandran , Mehra Nikita , Sundersingh Shirley , Dhanushkodi Manikandan , Rajan Arun Kumar , Kesana Sivasree , Sagar Tenali Gnana , Kannan Krishnarathinam , Radhakrishnan Venkatraman 
Published: November 2020

Background
High-Grade B-cell Lymphoma (HGBL) was a new disease entity proposed in 2016 to define a particularly aggressive subset of DLBCL. It consisted of two entities - HGBL with double hit(DH)/ triple hit(TH) and HGBL,NOS. While the aggressive nature of HGBL with DH/TH is well described, the data on the other subset of HGBL - HGBL,NOS is lacking in literature. We conducted this analysis to study the clinical profile of HGBL,NOS versus DLBCL,NOS.
Methodology
Retrospective, registry-based, single centre analysis of all patients diagnosed between 1.1.2017 till 31.12.2019 with the histopathological diagnosis of (1) DLBCL (2) HGBL,NOS and (3) HGBL with DH/TH.
Results
One hundred and forty four cases were identified, including 109 DLBCL,NOS, 29 HGBL, NOS and 6 cases of HGBL with DH/TH. The comparison of these 3 aggressive lymphoma subsets has been shown in table 1. HGBL,NOS had worse outcome in comparison to DLBCL,NOS (median PFS 20months vs NR, p=0.12) with a median follow up of 19 months. But the multivariate Cox analysis confirmed that DLBCL vs HGBL significantly affected PFS(p&lt;0.005). End of treatment complete remission showed significant(p&lt;0.001) PFS benefit with respect to both subsets. GCB subtype and IPI score significantly(p=0.03) influenced PFS in DLBCL,NOS but not in HGBL NOS. The DA-EPOCH-R arm did significantly (p&lt;0.05) worse than R CHOP arm with respect to DLBCL NOS. For HGBL,NOS the analysis failed to show any significant difference in PFS with respect to different chemotherapeutic regimen delivered (RCHOP/DA EPOCH R/R mini CHOP).
Conclusion
High-grade B-cell lymphoma, NOS is part of the spectrum of aggressive large B -cell lymphomas with prognosis intermediate to DLBCL, NOS and HGBL with DH/TH. The ideal therapeutic regimen for this aggressive lymphoma needs to be addressed prospectively in clinical trials.
Table

Disclosures
No relevant conflicts of interest to declare.
Integrated Analysis of Key Genes for FGFR1 Knockdown in Mantle Cell Lymphoma Cell Line (Z-138)
Authors: Wu Xue , Li Yuan , Chen Baoan 
Published: November 2020

Background:Mantle cell lymphoma (MCL) is the secondary common B cell lymphoma subtype that comprises 6 to 8% of non-Hodgkin's lymphoma, and is closely related to the poor clinical outcomes. Previous studies have focussed on the mechanisms mediating ibrutinib resistance, the first-in-class oral covalent inhibitor of Bruton's tyrosine kinase (BTK). The aims of the this study is to identify key genes related to the FGFR1 Knockdown in Mantle cell lymphoma cell line (Z-138) that has been proved to play a vital role in MCL progression.
Methods:GSE138127 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between vector control and the Knockdown of FGFR1 charactered by ibrutinib resistance. The GO and GSEA were carried out by WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) to do the functional enrichment analysis. The network analysis of protein-protein interactions (PPIs), TF-gene interaction were carried out by Network Analyst 3.0 to identify hub genes. And the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.
Results:In total, 175 DEGs were obtained, of which 87 and 88 were up- and down-regulated, respectively. Three hub genes (CDK1, CCND1) were identified and associated to cell cycle and DNA replication. FOXC1 were identified as the potential Transcription factors in the biological process.
Conclusion:CDK1, CCND1 may affect the cell cycle regulated by FOXC1, and represent the new candidate molecular markers of the occurrence of ibrutinib resistance.
Keywords: Mantle cell lymphoma (MCL), ibrutinib resistance, Network Analyst, Microarray, Protein-protein interactions, Molecular markers

Disclosures
No relevant conflicts of interest to declare.
Importance of Flow Cytometry in the Immunophenotyping Characterization of Mantle Cell Lymphoma in State of Rio Grande Do Norte, Brazil
Authors: Paiva Aldair Sousa , Silva Alessandra Suelen Jardim , Júnior Lenilton Silva DA Silva , Oliveira Gustavo Henrique de Medeiros , Ferreira Hugo Henrique de Freitas , Araujo Maria das Graças Pereira , Soares Victor lima , Bahia Frank , Freitas Rodrigo Villar , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Paiva Hugo Diogenes De Oliveira , Soares Rodolfo DA , Cavalcanti Geraldo Barroso 
Published: November 2020

Introduction:Mantle Cell Lymphoma (MCL) is a disease of a neoplastic nature characterized by proliferation in lymphoid tissues, classified as non-Hodgkin's lymphoma of B lymphocytes (NHBL). The nomenclature derives from the specific pathophysiology of this disease, that proliferates in the marginal area of the mantle of the germinal center of the lymph nodes.Objective:Carry out a detailed assessment of the immunophenotypic profile using the flow cytometry (CF) technique in 26 patients, NHBL to confirm mantle lymphoma.Materials and Methods:Biological samples from 26 patients, these being from peripheral blood (SP) or bone marrow (MO), of patients with suspected MCL were marked with monoclonal antibodies conjugated to fluorochromes and subsequently analyzed by FC.Results:all patients with a confirmed diagnosis of LCM were positive for pan-B antigens CD19, CD20 (strong) and CD22 (strong), CD19+/CD5+ and ciclin-D1 in 100% of cases. In addition to these, CD23, CD56, CD38, CD79b, Ki-67, Bcl-2, FMC-7 and HLA-Dr also obtained positive staining, as well as the immunoglobulin heavy chain (IgH) in all cases, and isotypes of immunoglobulins, IgD, IgG and IgM in most cases, with a predominance of the heavy chain of the lambda light chain in 79% of cases. Antigens related to T lymphocytes such as CD1a, CD2, CD3, CD7, TCR alpha/beta, TCR gamma/delta, CD4 and CD8, as well as antigens related to NK cells (CD16-56) and lymphoid progenitor cells (CD10 and Terminal- deoxynucleotidyl-transferase) were negative, as were CD200, antigens related to hairy cell leukemia (CD103, CD11c and CD123) and multiple myeloma (CD138).Discussion:According to the expression of the antigens, the antibodies were positive for: Cyclin D, CD19, CD20, CD22, CD38, Ki-67, Bcl-2, FMC-7 and CD79b, which are relevant to the diagnosis of this disease. Conclusion: Flow cytometry immunophenotyping is the technique currently used to confirm the diagnosis of neoplasms, such as LCM, which, due to its specific phenotype, helps in the correct selection of treatment.

Disclosures
No relevant conflicts of interest to declare.
Characterization of Abnormal Hemoglobins in the Blood Center of Rio Grande Do Norte, Brazil By High Performance Liquid Chromatography
Authors: Oliveira Gustavo Henrique de Medeiros , Paiva Aldair Sousa , Silva Alessandra Suelen Jardim , Júnior Lenilton Silva DA Silva , Ferreira Hugo Henrique de Freitas , Araujo Maria das Graças Pereira , Soares Victor lima , Bahia Frank , Freitas Rodrigo Villar , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Soares Rodolfo DA , Paiva Hugo Diogenes De Oliveira , Cavalcanti Geraldo Barroso 
Published: November 2020

INTRUDUCTION:In Brazil, blood donation is carried out by healthy people and meets the criteria established in the technical regulation of hemotherapy (Ordinance No. 2,712 / 20013 - Ministry of Health). METHODS It is mandatory to screen donors with hemoglobin S (HbS) and in the Blood Center of Rio Grande do Norte we use High Performance Liquid Chromatography (HPLC) VARIANT II. (Bio-Rad Laboratories, Hercules, CA). This method allows the screening of HbS and analysis of the levels of Glycated Hemoglobin (HbA1c), which is an important indicator of type 2 diabetes.RESULTS AND DISCUSSIONThe present study evaluated 29,098 donors, between 2018-2019, of both genders, aged between 18 and 69 years old. 22,754 (78.2%) are male and 451 (1.55%) have variant hemoglobins. The sickle cell trait (HbAS) was the most frequent among blood donors 372 (1.28%). For the analysis of HbA1c, donors with variant hemoglobins were excluded and we found that 26,910 (92, 48%) are in the normoglycemic group with HbA1c &lt;6%. 1,379 blood donors were classified as pre-diabetic with HbA1c levels between 6 - 6.4%. 766 (2.63%) donors were considered diabetic with HbA1c levels&gt; 6.5%.CONCLUSIONThe frequency of variant hemoglobins is lower in Rio Grande do Norte when compared to other Brazilian states. The prevalence of diabetes found in our study is in accordance with data from the International Diabetes Federation (IDF 2019). Brazilian blood centers could perform a large public health service by screening non-diagnosed cases of diabetes as well as assisting in monitoring donor HbA1c levels, however this notification is not mandatory.

Disclosures
No relevant conflicts of interest to declare.
Frequency of Thrombotic Events in Hospitalized Patients with Sickle Cell Disease
Authors: Inoue Susumu , Anagonye Christina 
Published: November 2020

Background
Thrombosis is one of the most common complications described in patients with sickle cell disease. However, little is known about the prevalence, variety and severity of thrombus particularly in sickle cell patients hospitalized with vaso-occlusive crisis.
Methods
We made a retrospective chart review of patients (age 21 years or older) admitted with sickle cell disease at Hurley Medical Center (Flint, Michigan) and was diagnosed with a thrombotic event between April 2012 and April 2020. To obtain a logistic model, we identified all patients with the the final discharge diagnosis of thrombosis (ICD-9 or ICD-10 code indicating any thrombosis, such as DVT, arterial thrombosis, catheter-related thrombus, pulmonary embolism, and stroke), combined with the diagnosis of sickle cell disease.
Findings
37/137 (27%) sickle cell patients were found to have had at least one thrombotic event during their hospitalization. As predicted, patients with sickle cell disease appeared to have very high frequency of thrombotic complications, though we lack a control group to compare with. Genotypes of sickle cell disease was also measured in this study. Patients with the Hb-SS disease had a much higher rate of this complication(25/68=37%) compared with those with Hb SC disease patients (12/49=24%). There were no thrombotic events reported in patients with Hb S/beta thalassemia+, or 0 patients or in patients with Hb SS with HPFH.
Interpretation
The risk of a thromboembolic event in patients with SCD is high, Sickle cell anemia is a procoagulant condition, which is a risk factor for thrombosis. More research is required to determine if preventive modalities could reduce thrombotic risk.

Disclosures
No relevant conflicts of interest to declare.
Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS
Authors: Stengel Anna , Shahswar Rabia , Haferlach Torsten , Walter Wencke , Hutter Stephan , Meggendorfer Manja , Kern Wolfgang , Haferlach Claudia 
Published: November 2020

AbstractFusion transcripts are frequent genetic abnormalities in myeloid malignancies and are often the basis for risk stratification, minimal residual disease (MRD) monitoring, and targeted therapy. We comprehensively analyzed the fusion transcript landscape in 572 acute myeloid leukemia (AML) and 630 myelodysplastic syndrome (MDS) patients by whole transcriptome sequencing (WTS). Totally, 274 fusion events (131 unique fusions) were identified in 210/572 AML patients (37%). In 16/630 MDS patients, 16 fusion events (15 unique fusions) were detected (3%). In AML, 141 cases comprised entity-defining rearrangements (51% of all detected fusions) and 21 (8%) additional well-known fusions, all detected by WTS (control group). In MDS, only 1 fusion was described previously (NRIP1-MECOM, n = 2). Interestingly, a high number of so-far unreported fusions were found (41% [112/274] in AML, 88% [14/16] in MDS), all validated by cytogenetic and/or whole genome sequencing data. With 1 exception (CTDSP1-CFLAR, n = 2), all novel fusions were observed in 1 patient each. In AML, cases with novel fusions showed concomitantly a high frequency of TP53 mutations (67%) and of a complex karyotype (71%), which was also observed in MDS, but less pronounced (TP53, 26%; complex karyotype, 21%). A functional annotation of genes involved in novel fusions revealed many functional relevant genes (eg, transcription factors; n = 28 in AML, n = 2 in MDS) or enzymes (n = 42 in AML, n = 9 in MDS). Taken together, new genomic alterations leading to fusion transcripts were much more common in AML than in MDS. Any novel fusions might be of use for developing markers (eg, for MRD monitoring), particularly in cases without an entity-defining abnormality.
Four myriapod relatives – but who are sisters? No end to debates on relationships among the four major myriapod subgroups
Authors: Szucsich Nikolaus U. , Bartel Daniela , Blanke Alexander , Böhm Alexander , Donath Alexander , Fukui Makiko , Grove Simon , Liu Shanlin , Macek Oliver , Machida Ryuichiro , Misof Bernhard , Nakagaki Yasutaka , Podsiadlowski Lars , Sekiya Kaoru , Tomizuka Shigekazu , Von Reumont Björn M. , Waterhouse Robert M. , Walzl Manfred , Meng Guanliang , Zhou Xin , Pass Günther , Meusemann Karen 
Published: November 2020

Abstract

Background
Phylogenetic relationships among the myriapod subgroups Chilopoda, Diplopoda, Symphyla and Pauropoda are still not robustly resolved. The first phylogenomic study covering all subgroups resolved phylogenetic relationships congruently to morphological evidence but is in conflict with most previously published phylogenetic trees based on diverse molecular data. Outgroup choice and long-branch attraction effects were stated as possible explanations for these incongruencies. In this study, we addressed these issues by extending the myriapod and outgroup taxon sampling using transcriptome data.

Results
We generated new transcriptome data of 42 panarthropod species, including all four myriapod subgroups and additional outgroup taxa. Our taxon sampling was complemented by published transcriptome and genome data resulting in a supermatrix covering 59 species. We compiled two data sets, the first with a full coverage of genes per species (292 single-copy protein-coding genes), the second with a less stringent coverage (988 genes). We inferred phylogenetic relationships among myriapods using different data types, tree inference, and quartet computation approaches. Our results unambiguously support monophyletic Mandibulata and Myriapoda. Our analyses clearly showed that there is strong signal for a single unrooted topology, but a sensitivity of the position of the internal root on the choice of outgroups. However, we observe strong evidence for a clade Pauropoda+Symphyla, as well as for a clade Chilopoda+Diplopoda.

Conclusions
Our best quartet topology is incongruent with current morphological phylogenies which were supported in another phylogenomic study. AU tests and quartet mapping reject the quartet topology congruent to trees inferred with morphological characters. Moreover, quartet mapping shows that confounding signal present in the data set is sufficient to explain the weak signal for the quartet topology derived from morphological characters. Although outgroup choice affects results, our study could narrow possible trees to derivatives of a single quartet topology. For highly disputed relationships, we propose to apply a series of tests (AU and quartet mapping), since results of such tests allow to narrow down possible relationships and to rule out confounding signal.
Association between plasma leptin/adiponectin ratios with the extent and severity of coronary artery disease
Authors: Rahmani Asghar , Toloueitabar Yaser , Mohsenzadeh Yousef , Hemmati Roholla , Sayehmiri Kourosh , Asadollahi Khairollah 
Published: November 2020

AbstractBackgroundLeptin can have a direct effect on endothelial and vascular smooth muscle cells and high level of leptin is involved in the pathogenesis of atherosclerosis. This study aimed to determine the relationship between leptin/adiponectin (L/A) ratio and the extent and severity of coronary artery disease (CAD).MethodsThis case-control study was conducted in an educational hospital in Ilam, Iran from June 2014 to September 2015. Totally 300 participants including 150 patients with CAD (case group) and 150 healthy individuals (control group) were selected and their plasma leptin, adiponectin and leptin/adiponectin ratio was measured. The extent and severity of coronary artery disease were assayed based on the number of involved vessels and Gensini score (GS) and the relation between scores and L/A findings were compared between cases and controls.ResultsTotally, 300 participants including 150 (42.7% male), mean age 59.5 ± 11.4 years as cases and 150 (50.7% male), mean age 59.8 ± 10.7 as controls were analyzed. Plasma level of leptin and L/A ratio were higher in cases compared to controls, but level of adiponectin was significantly lower in CAD patients than the control group. More number of involved coronary vessels was significantly correlated to higher level of plasma leptin, L/A ratio and lower level of adiponectin among case group. Moreover, adiponectin was negatively and leptin or L/A ratio were positively correlated with number of involved vessels. 7.3% of cases had only one involved vessel, 42.7% had two involved vessels, and 50% of total patients had involved vessels and the mean ± SD of GS in the case group was 23.6 ± 6.9.ConclusionsPlasma levels of leptin, and adiponectin can indicate the extent of coronary artery diseases but leptin may be a better marker of extent of CAD than either L/A ratio or adiponectin separately.