tbuckley/cabot-search huggingface dataset:
Abstract 24032: Exercise Instigates Apoptosis-inducing Factor Nuclear Translocation and Myocyte Death in Arrhythmogenic Cardiomyopathy
Authors: Stephen P Chelko, Gizem Keceli, Peter Andersen, Nuria Amat-Codina, Jacopo Agrimi, Djahida Bedja, Marcus Stahlberg, Marc Halushka, Cynthia A James, Hugh Calkins, Daniel P Judge, Nazareno Paolocci
Journal: Circulation (2017)

Exercise increases disease penetrance in arrhythmogenic cardiomyopathy (ACM). Yet, how exercise contributes to disease pathogenesis is unclear. Mitochondria potentiate reactive oxygen species (ROS) generation during exercise that are scavenged by antioxidants, such as thioredoxin-2 (Trx2). Here we tested if deficits in Trx2-based ROS buffering act as substrates for exercise-induced cardiac apoptosis in ACM. Homozygote Desmoglein-2 mutant mice ( Dsg2 mut/mut ) model ACM features, thus WT and Dsg2 mut/mut mice were enrolled in a 10 week swimming protocol to evaluate survival and post-effort cardiac function, ROS production by EPR, and mitochondrial ROS-gating protein levels. Survival rate after swimming was 91% (20/22) in WT, but only 60% (15/25) in Dsg2 mut/mut mice (p=0.008). Of the survivors, Dsg2 mut/mut mice displayed cardiac dysfunction (Ejection Fraction 57±4 vs 84±0.4% in WT; n≥14/cohort, P&lt;0.001) and increased bouts of non-sustained VT. Swimming augmented ROS emission in Dsg2 mut/mut right ventricles (RV) than in WT (25±3 vs 15±1 Gauss/total protein [G/tp]; P&lt;0.05) and amplified ROS release from Dsg2 mut/mut left ventricles (LV) (39±5 G/tp vs mutant RV; P&lt;0.05). Isolated mutant mitochondria showed reduced NADH generation and peroxiredoxin-3, Trx2 and Trx2 reductase (Trx2R) protein levels, with impaired Trx2R activity (all P&lt;0.05 vs WT in RV&amp;LV). When mitochondria bound, Apoptosis-Inducing Factor (AIF) acts as a NADH oxidoreductase, yet upon oxidation, AIF translocates to the nucleus and initiates apoptosis. After exercise, Dsg2 mut/mut hearts displayed marked AIF nuclear and chromatin-bound protein levels and increased AIF immunostained nuclei vs WT. Additionally, direct H 2 O 2 exposure or Trx2 inhibition (by auranofin) in Dsg2 mut/mut embryonic stem-cell derived myocytes elevated AIF-nuclear translocation and apoptosis (via AnnexinV/PI FaCS analysis). Our study reveals a novel causal link between exercise-evoked cardiac redox imbalance and aberrant AIF-Trx2 signaling in ACM, which was associated with increased apoptosis, propensity of arrhythmias and sudden cardiac death. These findings offer a new targetable mechanism for preventing one of the most cited, yet poorly understood, pathological phenotypes (apoptosis) in ACM.
Abstract 9444: Study of Natriuretic Peptides Levels in the Left Ventricular Tissue of Patients With Dilated Cardiomyopathy Using RNA-Seq
Authors: Esther Rosello Lleti, Estefania Tarazon Melguizo, Ana Ortega Gutierrez, Micaela Molina Navarro, Luis Almenar Bonet, Antonio Salvador, Miguel Rivera, Manuel Portoles Sanz
Journal: Circulation (2013)

Background: Natriuretic peptides (NPs) levels have been extensively studied in plasma of heart failure (HF) patients. Currently, BNP and proBNP are used for diagnosis and prognosis. Our objective is to evaluate the tissue levels of these peptides and several molecules involved in their processing and biological activity at mRNA level, in the left ventricle of patients with dilated cardiomyopathy (DCM) undergoing heart transplantation. Methods: We analyze the mRNA levels of 14 left ventricular samples from patients with nonischemic DCM undergoing heart transplantation and 7 control subjects (CNT), using massive sequencing, RNAseq, (SOLID 5500XL) and RT-qPCR (ViiATM 7 Real-Time PCR System). Results: ANP and BNP tissue levels are elevated in DCM compared with CNT group (fold change (FC)=37, p&lt;0.01 and FC=26, p&lt;0.05, respectively). CNP was not detected by RNAseq in the left ventricular samples of patients with DCM or in CNT group. NPs receptors (NPR1, NPR2 and NPR3) show no significant differences in mRNA levels between the two study groups. Finally, regarding the enzymes involved in the cleavage of these peptides we observed that corin is significantly decreased in the DCM group compared to CNT (FC=-2.5, p&lt;0.01), while no significant changes are observed in furin. Conclusions: RNA-Seq analysis confirm the presence of ANP in adult ventricular tissue, suggesting that the elevations observed in plasma could be originated in part in the left ventricle. CNP was not detected in cardiac tissue. Changes are specific since there were no modifications in the levels of any of the receptors and only in one of the enzymes involved.
Abstract 17060: Distinct Exercise Blood Pressure Response in Children Born After Hypertensive Pregnancy Predicts Increased Cardiovascular Risk in Adulthood
Authors: Esther F Davis, Adam J Lewandowski, Aye Christina, Wilby Williamson, Rae-Chi Huang, Trevor Mori, John P Newnham, Lawrence J Beilin, Paul Leeson
Journal: Circulation (2017)

Introduction: Offspring of hypertensive pregnancy (HTN) are known to have mild increases in resting blood pressure during childhood but significantly higher rates of hypertension and stroke in adul...
PB1772 TUMOR‐FORMING PLASMACYTOID DENDRITIC CELLS IN ACUTE MYELOMONOCYTIC/MONOCYTIC LEUKEMIA
Authors: L. Zhu, P. Wang, W. Zhang, Q. Li, X. Deng, S. Liu, Y. Liu, P. Kong, J. Rao, X. Zhang
Journal: HemaSphere (2019)

Background: lasmacytoid dendritic cells (PDCs) act as a link between innate and adaptive immunity, PDCs infiltration has been reported in infectious diseases, autoimmune diseases and neoplasms. Our previous work reported PDCs infiltration could occur in AML patients, but the clinical significance of PDC in AML was rarely investigated, based on DC induction from hematopoietic stem cells, myeloid progenitors and monocytes, we presume acute myelomonocytic/monocytic leukemia cases share PDCs phenotypes originally. Aims: To clarify the conception andevaluated the expression of PDCs in bone marrow. Methods: 80 acute myelomonocytic leukemia(AML‐M4) and 83 acute monocytic leukemia (AML‐M5) patients was included in this study for the examination of PDCs expression. Results: 62 cases were positive for PDCs, which were closely associated with cycles of chemotherapy before achieved CR, patients’ WBC count, Hb concentration, platelet count and bone marrow blasts, and the patients with PDC infiltration had a shorter survival time, meanwhile, allo‐HSCT could abrogated the side effects of PDCs on AML patients. Summary/Conclusion: PDC infiltration has a possible role in risk stratification for patients AML‐M4/M5, and our work emphasizes the significance of heterogeneity of AML‐M4/M5.
Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas
Authors: María García-Álvarez, Sara Alonso-Álvarez, Isabel Prieto-Conde, Cristina Jiménez, M. Eugenia Sarasquete, M. Carmen Chillón, Alejandro Medina, Ana Balanzategui, Rebeca Maldonado, Alicia Antón, Noemí Puig, Marta Rodríguez, Oscar Blanco, Pilar Tamayo, Verónica González-Calle, Alejandro Martín, Ramón García-Sanz, Marcos González, M. Dolores Caballero, Miguel Alcoceba
Journal: Blood Cancer Journal (2019)

Abstract Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2–3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable ( IGHV ) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P = 0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P &lt; 0.05), irrespective of the therapy they received. Moreover, IGHV3-30 was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of IGHV3-48 could help predict histological transformation.
PS1235 RED BLOOD CELL GENERATION FROM HUMAN INDUCED PLURIPOTENT STEM CELLS
Authors: E. Varga, M. Hansen, S. Heshusius, P. Burger, T. Wust, M. Hofman, M. von Lindern, E. Van Den Akker
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.
OP0282 OBSTETRIC ANTIPHOSPHOLIPID SYNDROME (OAPS) VS. WITH OBSTETRIC MORBIDITY RELATED WITH ANTIPHOSPHOLIPID ANTIBODIES (OMAPS): A SURVEY OF 1650 CASES FROM EUROAPS REGISTRY
Authors: Jaume Alijotas-Reig, Enrique Esteve-Valverde, Elisa Llurba, Raquel Ferrer-Oliveras, Domingo Ruiz-Hidalgo, Luis Sáez-Comet, Cristina Belizna, Arsene Mekinian, Elmina Lefkou, Gerard Espinosa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The obstetric antiphospholipid syndrome is an autoimmune systemic disorder related to antiphospholipid antibodies and pregnancy morbidity. There exist many patients that do not fulfill the Sydney classification criteria. Those cases may be defined as Obstetric Morbidity related with antiphospholipid antibodies (OMAPS). <h3>Objectives</h3> To compare clinical features, laboratory data and foetal-maternal outcomes, between 1000 women with obstetric antiphospholipid syndrome and 640 women with aPL-related obstetric complications not fulfilling Sydney criteria. <h3>Methods</h3> Retrospective and prospective multicenter study from the European Registry on Obstetric Antiphospholipid Syndrome. <h3>Results</h3> 1650 women with 5251 episodes were included of which 3601 were historical and 1650 were latest episodes. 1000 cases (OAPS group) fulfilled the classification criteria and 650 (OMAPS group) did not. Ten OMAPS cases were excluded because they presented a thrombosis during follow-up. In the OMAPS group, 172/640 (26.87%) did not fulfil Sydney clinical criteria (subgroup A), 179/640 (27.96%) had a low titer and/or non-persistent aPL-positivity but fulfilled clinical criteria (subgroup B), and 289/640 (45.15%) had a medium or high aPL titer but did not fulfil Sydney clinical criteria (subgroup C). <h3>Conclusion</h3> Significant clinical and laboratory differences were found between groups. Foetal-maternal outcomes were similar in both groups when they were treated. The results suggest that we could improve our clinical practice with closed defining and monitoring OMAPS patients. <h3>References</h3> [1] Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002;46:1019-27. [2] Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. Interna-tional consensus statement on an update of the classification criteria for definiteantiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306. [3] Esteve-Valverde E, Ferrer-Oliveras R, Alijotas-Reig J. Obstetric antiphospholipid syndrome. Rev Clin Esp 2016;216:135-45. <h3>Acknowledgement</h3> Amelia Ruffatti, Ariela Hoxha, Angela Tincani, Luca Marozio, Ricard Cervera, Sara de Carolis, Omar Latino, Pier Luigi Meroni, Cecilia Chighizola, Maria Gerosa, Valentina Canti, Karoline Mayer-Pickel, Sara Tabacco, Anna Arnau, Jaume Trapé. <h3>Disclosure of Interests</h3> None declared
A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma
Authors: Shi-Lu Chen, Chris Zhiyi Zhang, Li-Li Liu, Shi-Xun Lu, Ying-Hua Pan, Chun-Hua Wang, Yang-Fan He, Cen-Shan Lin, Xia Yang, Dan Xie, Jing-Ping Yun
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinogenesis is attributed to the reprogramming of cellular metabolism as a consequence of the alteration in metabolite-related gene regulation. Identifying the mechanism of aberrant metabolism is of great potential to provide novel targets for the treatment of hepatocellular carcinoma (HCC). Here, we demonstrated that glycogen synthase 2 (GYS2) restricted tumor growth in hepatitis B virus–related HCC via a negative feedback loop with p53. Expression of GYS2 was significantly downregulated in HCC and correlated with decreased glycogen content and unfavorable patient outcomes. GYS2 overexpression suppressed, whereas GYS2 knockdown facilitated cell proliferation in vitro and tumor growth in vivo via modulating p53 expression. GYS2 competitively bound to MDM2 to prevent p53 from MDM2-mediated ubiquitination and degradation. Furthermore, GYS2 enhanced the p300-induced acetylation of p53 at K373/382, which in turn inhibited the transcription of GYS2 in the support of HBx/HDAC1 complex. In summary, our findings suggest that GYS2 serves as a prognostic factor and functions as a tumor suppressor in HCC. The newly identified HBx/GYS2/p53 axis is responsible for the deregulation of glycogen metabolism and represents a promising therapeutic target for the clinical management of HCC. Significance: We elucidated the clinical significance, biological function, and regulation of the HBx/GYS2/p53 axis, which supplement the understanding of tumor glycogen metabolism and provide potential prognostic and therapeutic targets for HCC treatment.
Hydroxychloroquine dosing in systemic lupus erythematosus: response to ‘Comment on the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakis <i>et al’</i> by Costedoat-Chalumeau <i>et al</i>
Authors: Antonis Fanouriakis, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2019)

We thank Drs Costedoat-Chalumeau, Isenberg and Petri for their interest and insightful comments regarding hydroxychloroquine (HCQ) dosing in systemic lupus erythematosus (SLE).1 The authors outline three major arguments against recommending a lower daily dose for HCQ: (1) the lower dose of 5 mg/kg real weight/day has not proven equal efficacy with the previous 6.5 mg/kg/day, (2) the patient population of the studies that suggest higher rates of HCQ-retinopathy (older patients, mostly with rheumatoid arthritis) does not correspond to the average patient with lupus and (3) established low adherence rates to HCQ reported in some studies, if combined with a lower prescribed dose, may potentially lead to HCQ …
New Sensor and Wearable Technologies to Aid in the Diagnosis and Treatment Monitoring of Parkinson's Disease
Authors: Mariana H.G. Monje, Guglielmo Foffani, José Obeso, Álvaro Sánchez-Ferro
Journal: Annual Review of Biomedical Engineering (2019)

Parkinson's disease (PD) is a degenerative disorder of the brain characterized by the impairment of the nigrostriatal system. This impairment leads to specific motor manifestations (i.e., bradykinesia, tremor, and rigidity) that are assessed through clinical examination, scales, and patient-reported outcomes. New sensor-based and wearable technologies are progressively revolutionizing PD care by objectively measuring these manifestations and improving PD diagnosis and treatment monitoring. However, their use is still limited in clinical practice, perhaps because of the absence of external validation and standards for their continuous use at home. In the near future, these systems will progressively complement traditional tools and revolutionize the way we diagnose and monitor patients with PD.
AB0299 COXITIS DURING CHRONIC INFLAMMATORY RHEUMATISM
Authors: Hedia Ben Abla, Sonia Rekik, Samia Jammali, Soumaya Boussaid, Hela Sahli, Elhem Cheour, Mohamed Elleuch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The occurrence of coxitis in chronic inflammatory rheumatism is a prognostic factor of great importance given the functional repercussions of the involvement of the coxofemoral joint. <h3>Objectives</h3> The aim of this work is to evaluate the prevalence of this lesion in chronic inflammatory rheumatism (PR/JIA/SpA) and to describe the evolution of this disorder according to the pathology. <h3>Methods</h3> Eighty-two patients with chronic inflammatory rheumatism were enrolled. These patients were followed by the rheumatology department rabta since 2004 until March 2018. The clinical demographics, activity scores, treatment background (all our patients in this series were under biotherapy) and the need PTH were identified. <h3>Results</h3> The eighty-two patients were distributed as follows: 36.58% (n = 30) patients with RA, 36.58% (n = 30) SpA and 26.83 (n = 22) JIA. The average age was 48.3 years, 47.6 years and 32.17 years. For the rheumatoid arthritis population 26.67% (n = 8) of the patients had a coxite of which 62.5% (n = 5) was bilateral and 37.5% (n = 3) unilateral. The mean time to discovery of coxite was 11.7 years and the evolution was in 50% (n = 4) to worsening requiring in 3 cases a bilateral PTH and a case of synoviorthesis. In the SpA group, 23.33% (n = 7) of patients had coxitis, of which 57.14% (n = 4) were bilateral and 32.86% (n = 3) unilateral. The average time to discovery was 8.22 years. PTH was performed in 71.43% (n = 5) of patients. For the JIA population, 45.45% (n = 10) of the patients had a coxite of which 80% (n = 8) was bilateral and 20% unilateral. The average time to discovery of this lesion was 14 years, with 60% of cases progressing to an aggravation requiring 40% of the cases for synoviorthesis and 60% for PTH. <h3>Conclusion</h3> SpA is the most common chronic inflammatory rheumatism with cxo-femoral involvement with the most pejorative evolution despite the biological treatment <h3>References</h3> none <h3>Disclosure of Interests</h3> None declared
Florida's breast cancer deaths in the holidays.
Authors: Sandoval Ana, Judith Hurley, Tulay Koru-Sengul, Feng Miao, Stacey Tannenbaum, David J Lee, Margaret M Byrne
Journal: Journal of Clinical Oncology (2013)

e12547 Background: Several studies have been done to determine if there is an increase in the death rate associated with the holiday season or important events. Data has shown that there is an increase in death due to cardiovascular causes but the evidence for cancer related death is non-conclusive. Anecdotal information suggests that women with breast cancer expire more frequently during the Thanksgiving to Christmas holiday season compared with the rest of the year. It is unclear if this constitutes a real finding or if the circumstances connected with the patient’s death makes the dates more memorable. We evaluate if death occurs more frequently during the holiday season (11/15-01/07) for female breast cancer patients. Methods: Data on deaths from female breast cancer patients (n= 34,664) were obtained from linkage of the 1996-2009 Florida Cancer Data System, a population-based cancer registry, to the Florida Agency for Health Care Administration database providing procedure and diagnoses codes. Holiday season was defined as from 11/15-01/07 to create a dichotomous outcome measurement. Clustered logistic regression models were used to predict death during holidays; demographic, clinical, treatment factors and comorbidities were included in adjusted models with race, ethnicity, SES, marital status and presence of depression as the main factors. Results: Deaths (16%) occurred significantly more during the weekends, January-March and November-December. We found a temporal cluster of deaths during the holiday season defined from 11/15-01/07. Overall deaths were significantly more than expected during Thanksgiving and New Year. In the adjusted model, uninsured (OR: 1.24: 95% CI: 1.04-1.47) and been married (OR:1.13; 95%CI:1.03-1.23) were significant predictors of dying during the holiday season. Conclusions: Our results show that there is a seasonal effect on the time of death for Florida breast cancer patients. Marital status and non-insurance were significant predictors of dying during the holiday season.
Abstract 16040: Diagnostic and Prognostic Value of Osteopontin in Acute Congestive Heart Failure
Authors: Michael Behnes, Florian Espeter, Siegfried Lang, Parviz Ahmad-Nejad, Michael Neumaier, Martina Brueckmann, Martin Borggrefe, Ursula Hoffmann
Journal: Circulation (2012)

PURPOSE: Congestive heart failure is characterized by an adverse structural remodeling of the myocardium. Osteopontin (OPN) is a glycoprotein being expressed in cardiomyocytes and fibroblasts. OPN ...