tbuckley/cabot-search huggingface dataset:
Heavy and Light Chain Monitoring in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment
Authors: Noemi Puig, Teresa Contreras, Bruno Paiva, María Teresa Cedena, José J Pérez, Irene Aires, Cristina Agullo, Joaquin Martinez-Lopez, Paula Rodriguez Otero, Veronica Gonzalez De La Calle, Marta Sonia Gonzalez, Albert Oriol, Norma C. Gutierrez, Rafael Rios, Laura Rosiñol, Miguel Angel Alvarez, Maria Jose Calasanz, Joan Bargay, Ana Pilar Gonzalez, Adrián Alegre, Fernando Escalante, Rafael Martínez, Javier de la Rubia, Ana Isabel Teruel, Felipe De Arriba, Luis Palomera, Miguel-Teodoro Hernández, Javier López, Jesús Martín, Aránzazu García Mateo, Enrique M. Ocio, Ramón García-Sanz, Joan Bladé, Juan Jose Lahuerta, Jesus F. San-Miguel, Maria-Victoria Mateos
Journal: Blood (2019)
xCell: digitally portraying the tissue cellular heterogeneity landscape
Authors: Dvir Aran, Zicheng Hu, Atul J. Butte
Journal: Genome biology (2017)

Tissues are complex milieus consisting of numerous cell types. Several recent methods have attempted to enumerate cell subsets from transcriptomes. However, the available methods have used limited sources for training and give only a partial portrayal of the full cellular landscape. Here we present xCell, a novel gene signature-based method, and use it to infer 64 immune and stromal cell types. We harmonized 1822 pure human cell type transcriptomes from various sources and employed a curve fitting approach for linear comparison of cell types and introduced a novel spillover compensation technique for separating them. Using extensive in silico analyses and comparison to cytometry immunophenotyping, we show that xCell outperforms other methods. xCell is available at http://xCell.ucsf.edu/ .
SP0034 RA-MAP. PATIENT STRATIFICATION IN RA
Authors: John Isaacs
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> When we assess rheumatoid arthritis in the clinic we quantify inflammation. Apart from measuring auto-antibodies we do not assess the immune system.[ <h3>Objectives:</h3> The MRC/ABPI RA-MAP study was an academia-industry consortium designed to characterise the immune dysregulation that presents clinically as RA<sup>1</sup>. Key questions were: o Are there baseline immune markers of prognosis/therapeutic response? o What is the molecular signature of the disease state (is there an immune correlate of inflammation)? o Can 'RA" be defined in terms of immune dysregulation and are there distinct subtypes? <h3>Methods:</h3> RA-MAP was a systems immunology analysis of 275 patients with seropositive, treatment-naive early RA (the TACERA cohort). Patients were assessed at baseline and every 3 months for up to 18 months. At each visit, clinical samples were collected for transcriptomic (blood), proteomic (blood) and metabolomic (blood and urine) analyses. Peripheral blood mononuclear cells were characterised by flow cytometry. Clinical and demographic information was collected at each visit. Primary analyses addressed the key questions by seeking associations between immune parameters and disease activity or disease state. <h3>Results:</h3> Latent class analysis of clinical data revealed three main disease trajectories<sup>2</sup>. Transcriptomic and systems approaches highlighted at least two subtypes of seropositive RA. Proteomic analyses also supported multiple RA subtypes. Metabolomic analyses revealed prognostic baseline signatures. Flow cytometry revealed a reduction in peripheral blood mononuclear cell complexity as disease became less active. Combinatorial analyses of different datasets is currently underway. <h3>Conclusion:</h3> RA-MAP has provided important insights into the immunological and molecular heterogeneity of RA. Our findings require replication and validation, and some analyses are ongoing. RA is the consequence of dysregulated immunity characterized by distinct molecular 'endotypes'. <h3>References:</h3> [1] Cope AP, et al. The RA-MAP Consortium: a working model for academia-industry collaboration. Nat Rev Rheumatol 2018;14:53-60. doi: 10.1038/nrrheum.2017.200 [2] Tom BDM, et al. Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data. RMD Open 2018;4:e000721. doi:10.1136/rmdopen-2018-000721 <h3>Disclosure of Interests:</h3> John Isaacs Grant/research support from: Pfizer, Grant/research support from: Pfizer, Consultant for: Abbvie, Pfizer, Roche, Galvani, Merck, Gilead, Eli Lilly, Amgen, Janssen, Celltrion, NAPP, Consultant for: Abbvie, Pfizer, Roche, Galvani, Merck, Gilead, Eli Lilly, Amgen, Janssen, Celltrion, NAPP, Speakers bureau: Abbvie, Pfizer, Eli Lilly, Speakers bureau: Abbvie, Pfizer, Eli Lilly
PF275 NAT10 UPREGULATION INDICATES A POOR PROGNOSIS IN ACUTE MYELOID LEUKEMIA
Authors: P. Liang, R. Hu, Z. Liu, M. Miao, H. Jiang, C. Li
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) is a series of hematologic malignancies with high morbidity and mortality. It is characterized by impaired differentiation, excessive proliferation, and apoptosis escape. N ‐acetyltransferase 10 (NAT10) is a transcriptional activator of telomerase reverse transcriptase (hTERT)[1]. It has acyltransferase domain and participates in microtubule acetylation, rRNA modification, DNA damage response, and cytokinesis[2–5]. NAT10 was upregulated in various kinds of tumors such as hepatocellular carcinoma, colorectal cancer, ovarian cancer and melanoma[6–9]. NAT10 upregulation is associated with poor prognosis. This study investigated NAT10 expression in AML patients and its correlation with clinical characteristics, chemotherapy response and prognosis. Aims: N ‐acetyltransferase 10 (NAT10) is considered as an oncogene in many tumors. This study investigated the NAT10 expression in Chinese acute myeloid leukemia patients and evaluated the predictive significance of NAT10 with a single‐center retrospective study. Methods: We collected bone marrow samples of 48 newly diagnosed acute myeloid leukemia patients and 20 benign controls in our center. NAT10 mRNA expression levels were detected by Real‐time qPCR. Clinical data was obtained from inpatient medical records. Results: AML patients had higher NAT10 expression level than the normal controls ( P &lt; 0.01). NPM1‐mutant patients had higher NAT10 expression level than NPM1‐wt patients. NAT10 expression level was higher in non‐remission group than that of overall remission group ( P &lt; 0.05). High NAT10 expression indicated a poor progress free survival and overall survival. Summary/Conclusion: The results support NAT10 as a potential prognostic and therapeutic biomarker for acute myeloid leukemia. image
Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque
Authors: Diego A. Espinoza, Xing Fan, Di Yang, Stefan F. Cordes, Lauren L. Truitt, Katherine R. Calvo, Idalia M. Yabe, Selami Demirci, Kristin J. Hope, So Gun Hong, Allen Krouse, Mark Metzger, Aylin Bonifacino, Rong Lu, Naoya Uchida, John F. Tisdale, Xiaolin Wu, Suk See DeRavin, Harry L. Malech, Robert E. Donahue, Chuanfeng Wu, Cynthia E. Dunbar
Journal: Molecular Therapy (2019)

Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, in contrast to retroviral vectors, are not associated with insertion site-associated malignant clonal expansions and, thus, are considered safer. Here, however, we present a case of markedly abnormal dysplastic clonal hematopoiesis affecting the erythroid, myeloid, and megakaryocytic lineages in a rhesus macaque transplanted with HSPCs that were transduced with a LV containing a strong retroviral murine stem cell virus (MSCV) constitutive promoter-enhancer in the LTR. Nine insertions were mapped in the abnormal clone, resulting in overexpression and aberrant splicing of several genes of interest, including the cytokine stem cell factor and the transcription factor PLAG1. This case represents the first clear link between lentiviral insertion-induced clonal expansion and a clinically abnormal transformed phenotype following transduction of normal primate or human HSPCs, which is concerning, and suggests that strong constitutive promoters should not be included in LVs.
Abstract 103: Is All Ventricular Fibrillation the Same? A Comparison of Ischemically Induced and Electrically Induced Ventricular Fibrillation in a Porcine Cardiac Arrest and Resuscitation Model
Authors: James T Niemann, John Rosborough, Scott Youngquist, Jay Thomas, Roger Lewis
Journal: Circulation (2006)

Background: The standard porcine model for the study of cardiac arrest and resuscitation utilizes electrical induction of VF. Reported restoration of spontaneous circulation (ROSC) and survival rat...
AB0809 A STUDY TO COMPARE ARTICULAR CARTILAGE VOLUME IN HEALTHY AND OSTEOARTHRITIC KNEE AND ITS CORRELATION WITH CLINICO – RADIOLOGICAL SEVERITY
Authors: Sudeepti Srivastava, Rajeswar Nath Srivastava, Amar Chandra Sharma
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Knee Osteoarthritis (KOA) is a persistent debilitating disease characterized by loss of articular cartilage. Known to be a disease of elderly, it may not be necessarily so, as the loss in articular cartilage volume (ACV) begins early but detected very late on X-rays and by that time no therapy works and joint replacement is the only answer. <h3>Objectives</h3> To determine the role of ACV in early diagnosis of KOA, which may not only monitor disease progression from a very early stage, it may also open a gateway to slow down or stop the structural changes involved in KOA. <h3>Methods</h3> 60 Cases and equal number of age, sex matched controls were recruited. Each subject had MRI of the reference knee. ACV was measured manually by means of image processing on an independent workstation using semi-automated machine GE Signa. VAS for knee pain and WOMAC for pain, stiffness and disability were recorded for clinical severity and X-rays for radiological severity by KL grading. <h3>Results</h3> With age, a statistically significant inverse correlation of ACV was found in both healthy and osteoarthritis knees. Height, weight and BMI were independent of ACV in healthy knee. In KOA, a significant positive correlation of ACV was observed with height, a significant inverse correlation with WOMAC scores and significant difference with sub- scales of WOMAC index (pain, stiffness and physical function). The statistical difference in ACV between the two categories of WOMAC scores (&lt;32 and &gt;32) was significant. <h3>Conclusion</h3> This study concluded that ACV is significantly lower in osteoarthritis knee as compared to healthy adult knee. This study also found that KOA in females occurs at an early age and progresses slowly whereas in males occurs late and progresses rapidly. ACV may become one of the most promising tools for early diagnosis of KOA and in monitoring disease progression. <h3>Reference</h3> [1] Beary JF III. Joint structure modification in osteoarthritis: development of SMOAD drugs. CurrRheumatol Rep2001;3:506-512. <h3>Disclosure of Interests</h3> None declared
THU0328 DO PATIENTS WITH SYSTEMIC SCLEROSIS HAVE ULTRASONOGRAPHIC MODIFICATIONS OF SALIVARY GLANDS SUGGESTIVE OF SJOGREN SYNDROM?
Authors: Marion Couderc, Anne Tournadre, Sylvain Mathieu, Martin Soubrier, Jean-Jacques Dubost
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Modifications in ultrasonographic aspect of major salivary glands have been reported in patients with primary Sjogren Syndrom (pSS) with good diagnostic accuracy. Sicca symptoms are frequently observed in Systemic sclerosis (SSc). <h3>Objectives</h3> To assess the ultrasonographic echostructure of major salivary glands in patients with SSc and compare the modifications with those of patients with pSS or controls with sicca symptoms. <h3>Methods</h3> We performed a monocentre case-control study between 2014 and 2017 in the universitary hospital of Clermont-Ferrand (France). Patients with SSc and pSS were fullfilling the American College of Rheumatology/European League against Rheumatism (ACR/EULAR) 2013 and the ACR 2012 classification criteria respectively. Controls patients were complaining of sicca symtoms but did not meet the ACR 2012 criteria. Bilateral parotid and submandibular glands ultrasound (US) were performed in all patients by the same operator blinded to the diagnosis. Inhomogeneity of each of the 4 major salivary glands in B-Mode was graded using the Jousse-Joulin scoring system (scale of 0 to 4) as previously described.[1] The highest grade among the 4 glands was retained as suggestive of Sjogren Syndrom if ≥ 2. <h3>Results</h3> A total of 108 patients were included: SSc (n=25), pSS (n=48) and controls (n=35). Among the 48 patients with pSS, 12 were receiving hydroxychloroquine, 4 an immunosuppressor, 77% had antinuclear antibodies at a significant level (≥1/640), 26 (54%) anti-SSA antibodies, 14 (29%) anti-SSB antibodies, 40/45 (89%) had a labial salivary biopsy suggestive of pSS (Chisholm and Mason score ≥3). Comparing the pSS and the control groups, performance of a US echostructure grade ≥ 2 for the diagnosis of pSS was good: Se=75%, Sp=91.4%, positive predictive value= 92.3%, negative predictive value= 72.7%. Among the 25 SSc patients, 7 had immunosuppressor therapy, 8 had a localized SSc. Shirmer's test ≤ 5 mm in 5 minutes was present in 9/18 (53%), unstimulated salvary flow ≤ 0.1 mL/minute in 8/14 (57.1%). In the SSc group, 12 patients had an US echostructure grade 0, 6 grade 1, and 7 patients (28%) had an US echostructure grade of ≥ 2: US score=3 (n=5), US score=4 (n=2). Anti-SSA antibodies were found in 1/7 patients with an US echostructure grade ≥ 2 and 2/18 patients with US echostructure grade 0 or 1. <h3>Conclusion</h3> Nearly one third of patients with SSc have US echostructure changes suggestive of Sjogren Syndrom regardless of the presence of anti-SSA antibodies. <h3>References</h3> [1] - Cornec D, Jousse-Joulin S, Pers JO, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013;65:216-25. <h3>Disclosure of Interests</h3> None declared
Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis
Authors: Meng Li, Ying-Ling Chiang, Costas A. Lyssiotis, Matthew R. Teater, Jun Young Hong, Hao Shen, Ling Wang, Jing Hu, Hui Jing, Zhengming Chen, Neeraj Jain, Cihangir Duy, Sucharita J. Mistry, Leandro Cerchietti, Justin R. Cross, Lewis C. Cantley, Michael R. Green, Hening Lin, Ari M. Melnick
Journal: Cancer Cell (2019)

Diffuse large B cell lymphomas (DLBCLs) are genetically heterogeneous and highly proliferative neoplasms derived from germinal center (GC) B cells. Here, we show that DLBCLs are dependent on mitochondrial lysine deacetylase SIRT3 for proliferation, survival, self-renewal, and tumor growth in vivo regardless of disease subtype and genetics. SIRT3 knockout attenuated B cell lymphomagenesis in VavP-Bcl2 mice without affecting normal GC formation. Mechanistically, SIRT3 depletion impaired glutamine flux to the TCA cycle via glutamate dehydrogenase and reduction in acetyl-CoA pools, which in turn induce autophagy and cell death. We developed a mitochondrial-targeted class I sirtuin inhibitor, YC8-02, which phenocopied the effects of SIRT3 depletion and killed DLBCL cells. SIRT3 is thus a metabolic non-oncogene addiction and therapeutic target for DLBCLs.
Хронический атрофический гастрит: факторы риска и их взаимосвязь с выраженностью морфологических изменений слизистой оболочки желудка
Authors: L.M. Mosiychuk, L.V. Demeshkina, I.V. Kushnirenko, O.V. Simonova, O.P. Petishko, E.V. Zyhalo
Journal: GASTROENTEROLOGY (2019)

Актуальность. Хронический атрофический гастрит (ХАГ) относится к предраковым заболеваниям желудка, на фоне которого часто наблюдаются кишечная метаплазия и дисплазия, а также чаще, чем у здоровых лиц, может возникать рак желудка. Цель исследования: изучить факторы риска ХАГ и их взаимосвязь с выраженностью морфологических изменений слизистой оболочки желудка. Материалы и методы. Под наблюдением находились 120 пациентов с ХАГ. Все больные проходили эндоскопическое (с функцией NBI), морфологическое обследование и анкетирование с помощью анкеты, которая была разработана для больных с ХАГ с целью изучения факторов риска. Результаты. Были определены значимые факторы развития предраковых изменений слизистой оболочки желудка, среди которых на первый план выступили показатели, которые характеризуют острый (r = 0,593) и хронический стресс (r = 0,544), употребление чрезмерного количества жареных (r = 0,636), копченых (r = 0,512) и маринованных (r = 0,591) продуктов, возраст (r = 0,639), ІІ группа крови (r = 0,651), онконаследственность (r = 0,533), наличие дуоденогастрального рефлюкса (r = 0,524) и патологии щитовидной железы (r = 0,522). По результатам эндоскопического и морфологического исследований выявлено уменьшение частоты Helicobacter pylori-инфицирования по мере роста перестроечных изменений слизистой оболочки желудка (атрофия — метаплазия — дисплазия). Выводы. Установлено возможное влияние таких факторов риска, как стресс, возраст, группа крови, наследственность, употребление чрезмерного количества жареных, копченых и маринованных продуктов, заболевания щитовидной железы и наличие дуоденогастрального рефлюкса на развитие ХАГ.
Abstract 16483: TFEB Rescues Advanced aB-Crystallin Mutation-Induced Cardiomyopathy by Normalizing Desmin Localization
Authors: Kartik Mani, Xiucui Ma, Haiyan Liu, Atilla Kovacs, Ivor J Benjamin, Joesph A Hill, Abhinav Diwan
Journal: Circulation (2017)

Introduction: Mutations in αB-Crystallin result in fatal proteotoxic cardiomyopathy with desmin mis-localization to protein aggregates. Induction of autophagy prior to development of protein aggreg...
Current status and applications of genome-scale metabolic models
Authors: Changdai Gu, Gi Bae Kim, Won Jun Kim, Hyun Uk Kim, Sang Yup Lee
Journal: Genome biology (2019)

Genome-scale metabolic models (GEMs) computationally describe gene-protein-reaction associations for entire metabolic genes in an organism, and can be simulated to predict metabolic fluxes for various systems-level metabolic studies. Since the first GEM for Haemophilus influenzae was reported in 1999, advances have been made to develop and simulate GEMs for an increasing number of organisms across bacteria, archaea, and eukarya. Here, we review current reconstructed GEMs and discuss their applications, including strain development for chemicals and materials production, drug targeting in pathogens, prediction of enzyme functions, pan-reactome analysis, modeling interactions among multiple cells or organisms, and understanding human diseases.
Case 19-2019: A 38-Year-Old Woman with Abdominal Pain and Fever
Authors: Hamed Khalili, Aileen O’Shea, Gregory K. Robbins, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2019)

A 38-year-old woman with a history of Crohn's disease was admitted to the hospital because of abdominal pain and fever. She reported 7 months of progressive symptoms despite treatment with adalimumab, infliximab, and glucocorticoid therapy. A diagnosis was made.
Abstract 15803: The Creatinine to Uromodulin Ratio in Serum Predicts Major Cardiovascular Events Independently From the Presence of Type 2 Diabetes
Authors: Andreas Leiherer, Axel Muendlein, Christoph H Saely, Janine Ebner, Eva-Maria Brandtner, Alexandra Schuler, Peter Schwerzler, Arthur Mader, Karl-Martin Ebner, Peter Fraunberger, Heinz Drexel
Journal: Circulation (2017)

Introduction: Low concentrations of the kidney protein uromodulin are associated with type 2 diabetes (T2DM) and with chronic kidney disease (CKD). The serum creatinine to uromodulin ratio recently...
VASC: Dimension Reduction and Visualization of Single-Cell RNA-Seq Data by Deep Variational Autoencoder
Authors: Dongfang Wang, Jin Gu
Journal: Genomics Proteomics & Bioinformatics (2018)

Single-cell RNA sequencing (scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell sub-populations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data (VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.
PB1802 INCREASED RISK OF HIP FRACTURES IN YOUNG WOMEN WITH LYMPHOMA, RESULTS FROM A SWEDISH POPULATION BASED STUDY
Authors: P. Johansson, C. Lewerin, H. Kristjansdottir, H. Johansson, D. Mellström
Journal: HemaSphere (2019)

Background: Blood cancer is the third most common cancer in Sweden and lymphoma is the most common of hematologic malignancies. A significant proportion of lymphoma patients are cured and others are living many years with disease. Bone loss has been noted in lymphoma patients. However, the incidence of fracture, the most devastating outcome of osteoporosis, and in particular hip fracture is not known in this group of patients. Aims: To determine the risk of hip fracture in patients with lymphoma diagnosed between 1995 and 2015 Methods: We conducted a retrospective population based cohort study of Swedish lymphoma patients older than age 18 years, diagnosed from 1995 to the end of 2015 to determine the risk of hip fracture. Patients were identified from the National Cancer Register and from inpatient registers including all Swedish hospitals. They were followed up to 22 years (mean follow up 5.5 years). Fracture risk in lymphoma patients was compared with the Swedish population registry during the same time of period and adjusted for age, sex and calendar year. Results: 37236 lymphoma patients were identified (45% women). 2.2 % of the men and 4.7% of women developed a hip‐fracture, in mean time 4.9 years after they were diagnosed with lymphoma. The incidence of hip‐fracture was higher in women than in men, increased by age and decreased by calendar year. The risk (hazard ratio‐HR) for hip fracture was increased in lymphoma patients compared with the Swedish general population, especially in younger women. The HR was 2.80 (95% CI 1.95‐4.03) in females aged 40 years in 2016 and for men corresponding HR was 1.70 (95% CI 1.44‐2.00). There was a trend to lower HR with increasing calendar year and older age. However, in elderly men (80 years of age) the risk for hip fracture was even lower, HR 0.83 (95% CI 0.81‐0.85) compared with the Swedish population. No differences between hip fracture incidence in patients with Hodgkin lymphoma or diffuse large B‐cell lymphoma compared with other lymphomas was noted (p&gt;0.30). In multivariate analysis, unmarried men had a two times higher risk for hip‐fracture compared with men with other marital status with lymphoma (HR; 2.02 95% CI 1.63‐2.50). Summary/Conclusion: We conclude that lymphoma patients, especially younger women, are at higher risk of hip fracture than the general population independently image