tbuckley/cabot-search huggingface dataset:
SP0018 WHAT YOU SHOULDN'T MISS FROM THE HPR PROGRAMME AS A CLINICIAN
Authors: Maria Bergström
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> As a health professional, the EULAR congress is the place where I can get access to new and fresh rheumatology research of good quality. My presentation will take you through the possibilities the congress offers clinicians when it comes to different topics within the area of rheumatology. Further, my aim and hope is to give you a sense of what is in store for you during this year9s EULAR congress. People with rheumatic diseases today live their lives to a great extent having the diagnosis affecting their everyday life. The ability to work, interact with others or engaging in activities they want to, can be limited. So what do we need to know about them in order to provide the best possible treatment and rehabilitation? As a health professional clinician, I look forward to finding some of the answers to this during this congress. During the EULAR congress, we as health professionals have the possibility to contribute to and acquire research of good quality in rheumatology, on our way to give our patients the best possible treatment. Also, we have the possibility to contribute to the patientshealth, and I look forward to sessions touching health topics such as exercise. The quality of research and the variety of topics during this EULAR congress can give us a bigger set of tools to work with when we get back to our patients and continue our path towards the best possible treatment and health for this big and important group of patients. I hope that this session can provide an overview of what this years9 congress can offer from a clinical perspective. <h3>Disclosure of Interests:</h3> None declared
Molecular Evolution in Large Steps—Codon Substitutions under Positive Selection
Authors: Qingjian Chen, Ziwen He, Ao Lan, Xu Shen, Haijun Wen, Chung-I Wu
Journal: Molecular Biology and Evolution (2019)

Molecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1-bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of AAs, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the ten pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the ten pairs are shared between Drosophila and Hominoids, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.
PB2310 OUTPATIENT FOLLOW-UP IS ASSOCIATED WITH REDUCED EMERGENCY DEPARTMENT VISITS IN PATIENTS WITH SICKLE CELL DISEASE – A RETROSPECTIVE COHORT STUDY FROM RIYADH, SAUDI ARABIA
Authors: R. Saleh, L. Alhmaly, R. Vishwakarma, I. Kamran, M. Damlaj, A. Alaskar, G. E. Gmati
Journal: HemaSphere (2019)

Background: Pain is the main source of distress in patients with sickle cell disease (SCD), which affects up to 2.6% of the population in Saudi Arabia. Unmanageable pain often termed “crises” may prompt unexpected visits to the emergency department (ED) or other acute healthcare facilities. One study from the Eastern province in Saudi Arabia reported that 64% of SCD patients present to the ED more than three times over a 6-month period. Outpatient follow-up may have a role in preventing ED visits, but this has not been fully explored in Saudi Arabia. Aims: The study aimed to assess the relation between outpatient follow-up and future ED visits due to painful crises in SCD patients. Methods: This is a retrospective, observational study that utilized data from the electronic medical record system at King Abdulaziz Medical City, National Guard Health Affairs in Riyadh. Medical records were searched to identify patients with a labeled diagnosis of sickle cell disease or vaso-occlusive crisis. The study included adult SCD patients who presented at least once to the ED due to a painful crisis between January 2016 and December 2017. Patients’ characteristics and data on each visit were obtained from physicians’ documentation and test results. The time between ED visits due to painful crises was set as the outcome variable. Cox regression analysis with random effects model (frailty model) was used to determine the effect of outpatient follow-up at 15 days, 30 days, and 90 days on the time to next ED visit. Baseline characteristics and previous history of sickle cell complication (acute chest syndrome, avascular necrosis, osteomyelitis, and priapism) were included in the model. Results: Eighty SCD patients (56% male gender, mean age 25.8 ± 10.4 years, 13% sickle-thalassemia trait, 36% previous history of complication) presented a total of 463 times to the ED due to painful crises. Fifty-four percent of these visits required admission and resulted in a total length of stay of 1,474 hospital days and 49 ICU days. Fifteen percent of visits were associated with a documented infection and 8% of visits were associated with a complication – acute chest syndrome, avascular necrosis, osteomyelitis, or priapism. Attendance to a hematology outpatient clinic within 30 days from discharge significantly reduced the hazard of an ED visit due to painful crisis compared to no follow-up (HR = 0.70, CI95% 0.52–0.94, p = 0.02). Summary/Conclusion: Appropriate outpatient referral at discharge may be associated with decreased ED visits. These benchmark results invite further investigation into the effects of outpatient management on preventing painful crises in SCD patients.
PB1982 AN IN VITRO STUDY OF THE INTERACTIONS BETWEEN THE CELL BASED CANCER VACCINE DCP‐001 AND ANTIGEN PRESENTING CELLS
Authors: S.K. Singh, M.‐J. van Lierop, J. Kaspers, R. Bos, A. Kamermans, H.E. de Vries, E.H. Manting
Journal: HemaSphere (2019)

Background: DCP‐001 is a whole cell‐based vaccine derived from the DCOne® human myelomonocytic leukemic cell line. DCOne cells endogenously express known and unknown tumour‐associated antigens. In the DCP‐001 manufacturing process, DCOne cells are differentiated and matured into cells with a mature dendritic cell phenotype. A phase I clinical trial demonstrated that the vaccine is safe and induces local and systemic cellular and humoral immune responses. DCP‐001 is currently studied in an international Phase II trial in AML patients ineligible for HSCT. Aims: To study the role of the interaction of whole cell‐based vaccine DCP‐001 with host immune cells. Methods: DCP‐001 and antigen presenting cell interaction studies were performed using flow cytometry and confocal microscopy. Cytokine/chemokine analyses were performed using luminex technology. Results: The strong immunogenicity of DCP‐001 is demonstrated by the broad range of chemokines and pro‐inflammatory cytokines released upon co‐culture of DCP‐001 with human peripheral blood mononuclear cells. Using different methods, we further demonstrate that antigen presenting cells efficiently process DCP‐001 through phagocytosis. Summary/Conclusion: These in vitro data suggest that in vivo , upon intradermal injection, DCP‐001 induces a strong inflammatory response, and is ingested by both resident as well as attracted host's APC, which subsequently prime tumour‐reactive T cells.
PB2388 A STUDY TO COMPARE HPC DETERMINED ON THE SYSMEX XN-9000 WITH FLOWCYTOMETRIC CD34 COUNT IN PERIPHERAL BLOOD AND IN THE HARVESTED PERIPHERAL BLOOD STEM CELL GRAFT FROM AUTOLOGOUS AND ALLOGENIC DONORS
Authors: S. Mishra, U. Kulkarni, N. Mathews, R. V, S. C. Nair, B. George, D. J. Mammen
Journal: HemaSphere (2019)

Background: Hematopoietic stem cell transplantation is the current standard of curative care for all hemato-lymphoid malignancies as well as of many non-malignant conditions like marrow failure syndromes, inborn errors of metabolism and immune-deficiency syndromes. A successful bone marrow transplant requires a minimum of 2-3 × 10^6 cells/kg patient body weight of CD 34+ cells in the product being transfused. CD34+ cell count in the peripheral blood has the best predictive value for the stem cell yield in the apheresis bag. The major disadvantages of this are the turn-around time and the cost, besides requiring specialized flow cytometric analysis equipment and trained operators. HPC (Hemtopoietic Progenitor Cells) is a parameter which is measured by automated platforms of Sysmex XN series. Aims: This study aimed to find the reliability of HPC determined on the Sysmex XN-9000 in comparison with flowcytometric CD34 count in peripheral blood and in the harvested peripheral blood stem cell graft from autologous and allogenic donors. Methods: 102 autologous and allogeneic donors were enrolled in our study after due consent. TLC (Total Leukocyte Count), MNC (Mononuclear cell count), HPC & CD34 assay were done in both the peripheral blood prior to apheresis and the harvest product post-apheresis. Sysmex-XN 9000 was used for TLC, MNC and HPC assay. Slides were stained by automated slider stainer and evaluated by the investigator. CD34 Assay was done in flowcytometer using ISH-AGE single platform protocol. Statistical analysis was done using SPSS 16.0. Results: 67 allogenic and 35 autologous donors were enrolled. 45% were females and 55% males. Correlation between HPC and CD34 was found to be .887 with p value <0.01 in peripheral blood and .847 with p value <0.01 in the harvest product. On the other hand TLC had a correlation of .424 and .520 in peripheral blood and harvest respectively. MNC had a poor correlation with poor statistical significance. Summary/Conclusion: So, we conclude that HPC is, cheaper and robust method, which is comparable to CD34 in predicting harvest product's adequacy.
PS1234 APPLICATION OF FLOW SOM TO CLASSICAL FLOW CYTOMETRY: UNSUPERVISED ANALYSIS OF HEMATOPOIESIS AND HEMATOLOGICAL MALIGNANCIES
Authors: F. Lacombe, B. Dupont, J.‐P. Vial, N. Lechevalier, M.C. Béné
Journal: HemaSphere (2019)

Background: Multiparameter flow cytometry (MFC) is an essential tool for the diagnosis and follow‐up of hematological malignancies. Numerous panels have been devised that best allow to achieve these goals. However, analysis of MFC graphs still heavily relies on the expertise of biologists and on specifically well adapted cascade‐gating strategies. Because of the development of mass cytometry, which generates data in a multidimensional environment of up to 50 dimensions, new strategies have been developed, that could be applied to classical MFC. Aims: In this study, the capacities of a rapid new tool for multidimensional analysis, FlowSOM (self‐organizing maps) have been combined to a classical MFC analysis tool, Kaluza ® , for the identification of normal and diseased human bone marrow (BM) cell subpopulations. Methods: Normal BM samples collected during bone surgery were analyzed in MFC with four antibody panels adapted to the exploration of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. The listmode files obtained were merged and submitted to FlowSOM analysis, using R packages, which yielded trees of 100 nodes defining normal BM cell subsets. FlowSOM parameters were then transferred to Kaluza ® for a bidimensional representation of the trees within which selected navigation could be performed with Kaluza ® tools. In a second part of the study, the same stainings were performed on myelodysplastic or leukemic (AML or ALL) samples (diagnosis or follow‐up), which were submitted to FlowSOM together with the reference merged BM. Results: Node‐by‐node selection allowed for a precise definition of each of the unsupervised subsets generated by the software. This disclosed a selective segregation of delicate subsets such as non‐classical monocytes, hematogones or stem cells. Direct simultaneous comparison of diseased samples and normal BM allowed for a precise definition of abnormal cells (blasts) at diagnosis, and their immediate recognition as minimal residual disease in follow‐up samples. Summary/Conclusion: Flow SOM appears as a new and efficient tool for a rapid identification of BM cell subsets, highlighting differences from normal BM in dysplastic of leukemic samples. The node‐by‐node approach facilitates the definition of abnormal cells and their quantification, supervision intervening only after the generation of subsets delineated by artificial intelligence.
PB2002 IMPACT OF AUTOIMMUNE CYTOPENIAS ON THE CLINICAL COURSE AND SURVIVAL OF HODGKIN LYMPHOMA
Authors: L. Pinczés, R. Szabó, Z. Miltényi, Á. Illés
Journal: HemaSphere (2019)

Background: Autoimmune cytopenias (AICP), namely autoimmune hemolytic anemia (AIHA) and autoimmune thrombocytopenia (AITP) often complicate the course of malignant lymphomas. The incidence and clinical significance of AICPs associated with Hodgkin lymphoma (HL) have not been thoroughly defined. Aims: Our aim was to retrospectively assess the incidence, clinical features and response to treatment of HL‐associated autoimmune phenomena. Methods: Five hundred and sixty‐five HL patients were diagnosed and treated at the University of Debrecen between 1990 and 2017. We compared the clinicopathological characteristics of HL patients developing AICPs with those who had no clinical evidence of autoimmune events. We considered an AICP to be a disease‐defining event if it led to diagnosis or revealed disease progression, relapse or secondary malignancy. Statistical analysis was performed using Fisher's exact test. Results: We identified 8 cases of AIHA and 8 cases of AITP among 14 patients altogether, one of them presented with Evans syndrome. Two AICPs preceded the diagnosis of HL, 2 of them developed simultaneously with the disease and 11 AICPs occurred during follow‐up after first line therapy. During more than 5000 person‐years of follow‐up, the incidence of AICPs in HL patients was 2,8%. Eighty‐one percent of AICPs required treatment, 77% of these patients responded well to intravenous steroid. Treatment of the underlying lymphoma with ABVD combination chemotherapy resulted in the effective control of both the underlying disease and the immune condition, in most cases, where AICPs were identified at the presentation of HL. Almost half of the AICPs (46%) were disease‐defining events: 5 cases led to the diagnosis of HL or indicated relapse and 2 events revealed secondary malignancies. AICPs were more frequently observed in patients with advanced stage disease at initial diagnosis (p &lt; 0.004). The association of HL and AICPs had no effect on long‐term overall‐ (OS) and progression‐free survival, however, short‐term (1 year) mortality of HL patients experiencing AICPs was significantly elevated (p &lt; 0.022) compared to the majority of patients, who did not have AICPs. Also, the OS rate of HL patients with AICPs at initial diagnosis was significantly lower (p = 0.033) compared to patients developing AICPs during follow‐up. Summary/Conclusion: While AICPs are rare complications of HL, these events can imply clinical significance. Those HL patients who experienced AICPs had a particular disease‐related profile. These cytopenias show a good response to steroid treatment. This large series of consecutive, unselected patients demonstrate that the association of HL and AICPs may increase short‐term mortality. Our results emphasize the importance of taking into consideration the possibility of an underlying hematological malignancy in newly diagnosed AIHA/AITP cases.
PB2120 THE IMPACT OF DEPTH OF RESPONSE BEFORE AND AFTER AUTOLOGOUS STEM CELL TRANSPLANT FOR MULTIPLE MYELOMA PATIENTS
Authors: S. Durão, J. Vieira, F. Velosa, M. Neves, J. Infante, A. Alho, E. Espada, H. Martins, S. Valle, F. Lourenço, R. Moreno, D. Alves, M. J. Costa, B. Polo, C. Lopes, C. Martins, J. Forjaz Lacerda, G. Esteves, J. Raposo
Journal: HemaSphere (2019)

Background: Over the last decade there has been an improvement on the outcome of multiple myeloma (MM) patients. In patients eligible for high‐dose chemotherapy and autologous stem cell transplant (ASCT), the inclusion of bortezomib in induction chemotherapy (ICT) has significantly delayed disease progression. Several studies have shown that achieving a complete response (CR) after ASCT is a predictive factor for disease control, leading to improved progression‐free survival (PFS) and overall survival (OS). Aims: Assessing the impact of depth of response before and after ASCT on PFS in a population of MM patients treated with ICT including bortezomib and identifying predictive/protective factors for disease progression. Methods Retrospective study of MM patients admitted for ASCT between January 2015 and December 2017 treated in first line with VCd (bortezomib, cyclophosphamide, and dexamethasone) or VTd (bortezomib, thalidomide and dexamethasone). Demographic (gender, age), clinical and biological variables at diagnosis were collected, as well as response obtained before and at D + 100 after ASCT, and time elapsed between ASCT and disease progression. Statistical analysis was performed using STATA software (V13). Results: A total of 53 MM patients in the first line setting were included in this study. 43.4% were male; median age at diagnosis was 60 years old (IQR, 40‐72). Both groups (VCd and VTd) had similar baseline characteristics. Median follow‐up after induction chemotherapy was 20.6 months. PFS of patients who achieved CR or very good partial response (VGPR) post‐induction was 73.7%, versus 60% in patients who achieved partial response (PR) or lower (log‐rank p = 0.07). Looking at different variables that could modify the time between ASCT and disease progression, we observed that ISS stage 3 is an independent predictive factor for disease progression (HR 3.1; p = 0.014), and obtaining CR/VGPR at D + 100 post‐ASCT is an independent protective factor against disease progression (HR 0.2; p = 0.004). Summary/Conclusion: Despite the relatively short follow‐up period, in this population of transplant‐eligible MM patients, we have demonstrated that the depth of response after induction chemotherapy (VGPR/CR) is critical for a greater PFS, and that a profound reduction in tumor burden (VGPR/CR) after ASCT allows for prolonged disease control. However, ISS stage 3 is a risk factor for disease progression regardless of the obtained response.
Cancer‐associated thrombosis (CAT)
Authors: John‐Bjarne Hansen
Journal: HemaSphere (2019)

Learning goals Extended knowledge of pathophysiological mechanisms in cancer-related VTE may lead to targeted prevention in the future. Even though unprovoked VTE is associated with occult cancer, extensive cancer screening in these patients have not lead to detection of earlier stage cancers or improved prognosis. Recent RCTs comparing LMWHs and DOACs for treatment of cancer-related VTE have shown that DOAC treatment had less VTE recurrences and higher incidences of major bleedings. The clinical implications are uncertain. Introduction Venous thromboembolism (VTE) is often the first sign of cancer, and cancer patients have a 4-7 fold higher risk of VTE compared to the general population. The VTE risk in cancer is dependent on cancer type and severity. Extended knowledge on mechanisms of cancer-related VTE would potentially lead to targeted prevention. Even though the underlying mechanisms of thrombosis risk in cancer is only partly known, tissue factor (TF), cancer cell-derived microvesicles (MV), and podoplanin, a sialoglycoprotein upregulated in several cancer cells able to induce platelet activation, are important actors in the pathophysiology of cancer-related VTE. As 5% to 10% of unprovoked VTE events are diagnosed with cancer during the following year, it has been assumed that extensive cancer screening would lead to earlier cancer diagnosis and improved prognosis. However, many studies have failed to show that extensive screening leads to detection of earlier stage cancers and improved cancer prognosis. Furthermore, clinical scores have been developed, but are not yet validated for clinical practice. Currently, guidelines recommend LMWHs for treatment of cancer-related VTE. Two independent RCTs have recently reported less VTE recurrences and higher incidences of major bleeding by DOACs compared to LMWHs for treatment of cancer-related VTE. The clinical implications are uncertain.
Comparison of gene expression of mesenchymal stem cells from the umbilical cord and from the bone marrow
Authors: Rodrigo A. Panepucci, Jorge L. C. Siufi, Wilson Araújo da Silva Júnior, Rodrigo Proto-Siqueira, Vanderson Rocha, Dimas Tadeu Covas, Marco Antônio Zago
Journal: Blood (2003)
Mash: fast genome and metagenome distance estimation using MinHash
Authors: Brian D. Ondov, Todd J. Treangen, Páll Melsted, Adam B. Mallonee, Nicholas H. Bergman, Sergey Koren, Adam M. Phillippy
Journal: Genome biology (2016)

Mash extends the MinHash dimensionality-reduction technique to include a pairwise mutation distance and P value significance test, enabling the efficient clustering and search of massive sequence collections. Mash reduces large sequences and sequence sets to small, representative sketches, from which global mutation distances can be rapidly estimated. We demonstrate several use cases, including the clustering of all 54,118 NCBI RefSeq genomes in 33 CPU h; real-time database search using assembled or unassembled Illumina, Pacific Biosciences, and Oxford Nanopore data; and the scalable clustering of hundreds of metagenomic samples by composition. Mash is freely released under a BSD license ( https://github.com/marbl/mash ).
Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma
Authors: Xiyue Zhao, Xiaoyu Liu, Pengcheng Zhang, Yiran Liu, Wei Ran, Ying Cai, Junyang Wang, Yihui Zhai, Guanru Wang, Yaping Ding, Yaping Li
Journal: Acta Pharmaceutica Sinica B (2019)

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.
IFN-γ upregulates membranous and soluble PD-L1 in mesothelioma cells: potential implications for the clinical response to PD-1/PD-L1 blockade
Authors: Maria Pia Pistillo, Roberta Carosio, Barbara Banelli, Anna Morabito, Luca Mastracci, Paola Ferro, Serena Varesano, Roberta Venè, Alessandro Poggi, Silvio Roncella
Journal: Cellular and Molecular Immunology (2019)