tbuckley/cabot-search huggingface dataset:
CD4 CAR T Cells Mediate CD8-like Cytotoxic Anti-Leukemic Effects Resulting in Leukemic Clearance and Are Less Susceptible to Attenuation By Endogenous TCR Activation Than CD8 CAR T Cells
Authors: Yinmeng Yang, Tasha Lin, Elad Jacoby, Haiying Qin, Elizabeth Grier Gardner, Christopher Daniel Chien, Daniel W. Lee, Terry J. Fry
Journal: Blood (2015)
PB1677 SIXTEEN YEAR'S EXPERIENCE OF THE EORTC 58951 PROTOCOL FOR THE TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN THE SOUTH OF TUNISIA
Authors: I. Frikha, I. Turki, M. Medhaffer, N. Louati, M. Chaari, S. Hdijji, M. Charfi, O. Kassar, F. Kallel, M. Ghorbel, H. Mnif, M. Elloumi
Journal: HemaSphere (2019)

Background: Childhood acute lymphoblastic leukemia (ALL) is an hematologic malignancies with high rate of cure. We report the experience of the clinical hematology department of Sfax‐Tunisia for the treatment of childhood ALL with the EORTC 58951 protocol. Aims: We report in this study the experience of the clinical hematology department of Sfax‐Tunisia for the treatment of childhood ALL with the EORTC 58951 protocol. Methods: From January 2000 to December 2015, we retrospectively studied the outcome of all childhood ALL treated with the EORTC 58951 pediatric protocol. For those patients we studied the leukemia characteristics (sex ratio, white blood cell counts WBC, blast's phenotype, cytogenetic abnormalities) and response to treatment: response to prophase, remission rate, risk group stratification, treatment related mortality (TRM) (induction and post induction death) and survival (overall survival OS, event free survival EFS and disease free survival DFS). Results: From January 2000 to December 2015, 193 children were treated with the EORTC 58951 protocol. Median age was 6 years (range: 13 months to 15 years). Sex ratio M/F was 1.47. WBC counts less than 10 G/l, from 10 to 100 G/L and more than 100 G/L were observed respectively in 42, 42 and 16% of cases. The blast's phenotype was B in 71% and T in 29%. Cytogenetic abnormalities were noted in 38% of cases. A good response to prophase was noted in 83% and complete remission in 96% of cases. The EORTC risk group stratification was Low Risk (LR) in 6%, Average Risk1 (AR1) in 46%, Average Risk2 (AR2) in 23.5% and Very High Risk (VHR) in 24.5%. TRM was 10.5%: induction rate death was 6% and post‐induction rate death was 4.5%. Nine patients from VHR group with familial donor underwent allograft. The relapse rate was 28% of all patients in remission; 8% for LR group, 32% for AR1 group, 18% for AR2 group and 44% for VHR group. At 5 years of follow up, OS and EFS were 66 and 60 respectively and DFS was 70%. Summary/Conclusion: At diagnosis, childhood ALL in our study had poor characteristics particularly higher rate of T phenotype of blasts, higher rate of leukocytosis more than 100 G/L, higher rate of VHR therapeutic group and higher rate of cortico‐resistant regarding occidental series. Despite the acceptable results concerning remission rate but survival rates remain lower than those observed in the literature, this is explained mainly by the high rate of relapse (28% vs ∼15%). It can be improved our results by detecting high risk patient with MRD study especially for AR1 risk group and doing allograft for VHR patients.
Containing medical expenditure: lessons from reform of Beijing public hospitals
Authors: Xiaoyun Liu, Jin Xu, Beibei Yuan, Xiaochen Ma, Hai Fang, Qingyue Meng
Journal: BMJ (2019)

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Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses
Authors: Tyler M. Sharp, Marc Fischer, Jorge L. Muñoz-Jordán, Gabriela Paz-Bailey, J. Erin Staples, Christopher J. Gregory, Stephen H. Waterman
Journal: MMWR Recommendations and Reports (2019)

Dengue and Zika viruses are closely related mosquitoborne flaviviruses with similar transmission cycles, distribution throughout the tropics and subtropics, and disease manifestations including fever, rash, myalgia, and arthralgia. For patients with suspected dengue or Zika virus disease, nucleic acid amplification tests (NAATs) are the preferred method of diagnosis. Immunoglobulin M (IgM) antibody testing can identify additional infections and remains an important tool for the diagnosis of these diseases, but interpreting the results is complicated by cross-reactivity, and determining the specific timing of infection can be difficult. These limitations are a particular challenge for pregnant women in determining whether Zika virus infection occurred during or before the pregnancy.This report summarizes existing and new guidance on dengue and Zika virus diagnostic testing for patients with a clinically compatible illness who live in or recently traveled to an area where there is risk for infection with both viruses. CDC recommendations for screening of asymptomatic pregnant women with possible Zika virus exposure are unchanged. For symptomatic nonpregnant persons, dengue and Zika virus NAATs should be performed on serum collected ≤7 days after symptom onset. Dengue and Zika virus IgM antibody testing should be performed on NAAT-negative serum specimens or serum collected >7 days after onset of symptoms. For symptomatic pregnant women, serum and urine specimens should be collected as soon as possible within 12 weeks of symptom onset for concurrent dengue and Zika virus NAATs and IgM antibody testing. Positive IgM antibody test results with negative NAAT results should be confirmed by neutralizing antibody tests when clinically or epidemiologically indicated, including for all pregnant women. Data on the epidemiology of viruses known to be circulating at the location of exposure and clinical findings should be considered when deciding which tests to perform and for interpreting results.Patients with clinically suspected dengue should receive appropriate management to monitor and treat shock and hemorrhage. Women with laboratory evidence of possible Zika virus infection during pregnancy and their infants should be evaluated and managed for possible adverse outcomes. Dengue and Zika virus disease are nationally notifiable conditions, and cases should be reported to public health authorities.
Abstract 13236: Elevated Serum Proprotein Convertase Subtilisin/Kexin Type 9 Level Independently Predicts Long-Term Cardiovascular Outcomes in Patients With Chronic Coronary Artery Disease
Authors: Aiko Sakamoto, Nobukazu Ishizaka, Masae Uehara, Jiro Ando, Issei Komuro
Journal: Circulation (2016)

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) may directly promote atherosclerosis. However, the long-term impact of elevated serum PCSK9 levels on the risk of cardiovascular events has not been fully elucidated. We therefore analyzed the association of serum PCSK9 levels with major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD). Methods: Serum PCSK9 levels were measured in 306 patients (171 men; mean age, 68.3 ± 10.5 years) who underwent coronary computed tomography (CT) angiography. Furthermore, 174 patients who were judged to have obstructive CAD were followed-up for a median period of 1584 days (interquartile range [IR] 1334-1790). MACE was defined as death, acute coronary syndrome, and cerebral stroke. Results: Serum levels of PCSK9 were higher in women (268 ng/mL, IR 211-325) than in men (218 ng/mL, IR 175-284, P&lt;0.001). In age- and gender-adjusted logistic regression analysis, serum PCSK9 levels had a significant association with obstructive CAD (odds ratio 1.63 per 100 ng/mL increase, 95% confidence interval [CI] 1.21-2.19, P=0.001). Among patients with obstructive CAD, 14 patients developed MACE during the follow-up period. Patients in the highest tertile of PCSK9 (≥288 ng/mL) had a significantly higher risk of MACE than those in the lower tertiles (log-rank, P=0.005). In Cox regression analysis using age, gender, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, smoking, and vulnerable coronary plaque characteristics assessed by CT, including low-density plaque, positive remodeling, and spotty calcification, as covariates, serum PCSK9 level was an independent predictor of MACE (hazard ratio 2.03 per 100 ng/mL increase, 95% CI 1.13-3.62, P=0.017). Conclusions: Baseline serum PCSK9 level significantly predicted MACE, as well as present coronary stenosis, independent of traditional cardiovascular risk factors and vulnerable plaques.
OP0323 USEFULNESS OF UNIVERSAL ANTINUCLEAR ANTIBODIES TESTING IN EARLY ARTHRITIS REFERRALS
Authors: Mariana Luis, Luisa Brites, Ana Rita Prata, Tânia Santiago, José Antonio P. Da Silva, Catia Duarte
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The CHUC Early Arthritis Clinic, founded in 2011, intends to provide a prompt response to patients with recent onset of symptoms suggestive of an inflammatory rheumatic disease (IRD). By research protocol, all patients are screened at baseline for the presence of antinuclear antibodies (ANA). An analysis was performed to evaluate the usefulness of universal ANA testing in these patients. <h3>Objectives</h3> To evaluate the prevalence and clinical correlates of ANA positivity in early arthritis referrals. <h3>Methods</h3> A retrospective study of consecutive patients referred to the Early Arthritis Clinic between 2011 and 2018 was conducted. Referral is based on the fulfillment of specific criteria: presence of arthritis or clinically suspected arthralgia beginning in the previous 12 months plus suggestive laboratorial abnormalities (rheumatoid factor, C-reactive protein or erythrocyte sedimentation rate). ANA titer (positive= ≥1:160) and cellular staining patterns were assessed by indirect immunofluorescence (Hep-2 cells). Positive (PPV) and negative predictive values (NPV) of an ANA positive test for the diagnosis of an IRD or an ANA-related rheumatic disease (ARD) were determined, along with PPV for the other referral criteria. <h3>Results</h3> 207 patients were included in the analysis (64.3% female, aged 53.9 ± 18.2 years). The diagnosis of an IRD was confirmed by the rheumatologist in 61.4% of cases, including 11.8% cases of ARD. The most prevalent diagnosis was rheumatoid arthritis (21.7%), followed by unclassified arthritis (8.7%), psoriatic arthritis, osteoarthritis and fibromyalgia (6.8% each). The prevalence of ANA positivity in our cohort was 64.2%, most frequently in low titration (1:160 in 33.8%, 1:320 in 19.3%, 1:640 in 8.7% and 1:1280 in 2.4%) and with a dense fine speckled pattern (45.1%). ANA-positive patients were older (53.7 ± 17.9 versus 47.9 ± 18.5, p=0.05), more likely to have an IRD (72.9% versus 40.5%, p&lt;0.001) but not an ARD (9.0% versus 4.1%, p=0.186). PPV for ARD was 9.0% for the 1:160 cut-off titration and 15.6% for the 1:320. Squeeze test (PPV 13.5%), erythrocyte sedimentation rate (PPV 9.9%) and rheumatoid factor (PPV 20.0%), as referral criteria, all performed better at predicting an ARD, compared to an ANA positive testing. <h3>Conclusion</h3> Early Arthritis Clinic referred cohort has a high prevalence of IRD but a low prevalence of ARD which explains the poor predictive value of ANA in this setting, especially when considering lower titters and when compared with specific referral criteria. Thus, universal ANA testing in Early Arthritis Clinic referrals seems unjustified, given its costs and added value. Studies designed to optimize the use of ANA in this context are warranted. <h3>Disclosure of Interests</h3> None declared
NAD(P)H Quinone Dehydrogenase 1 Ablation Inhibits Activation of the Phosphoinositide 3‐Kinase/Akt Serine/Threonine Kinase and Mitogen‐Activated Protein Kinase/Extracellular Signal‐Regulated Kinase Pathways and Blocks Metabolic Adaptation in Hepatocellular Carcinoma
Authors: Manali Dimri, Ashley Humphries, Archana Laknaur, Sawsan Elattar, Tae Jin Lee, Ashok Sharma, Ravindra Kolhe, Ande Satyanarayana
Journal: Hepatology (2019)

Cancer cells undergo metabolic adaptation to sustain uncontrolled proliferation. Aerobic glycolysis and glutaminolysis are two of the most essential characteristics of cancer metabolic reprogramming. Hyperactivated phosphoinositide 3‐kinase (PI3K)/Akt serine/threonine kinase (Akt) and mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK) signaling pathways play central roles in cancer cell metabolic adaptation given that their downstream effectors, such as Akt and c‐Myc, control most of the glycolytic and glutaminolysis genes. Here, we report that the cytosolic flavoprotein, NAD(P)H quinone dehydrogenase 1 (Nqo1), is strongly overexpressed in mouse and human hepatocellular carcinoma (HCC). Knockdown of Nqo1 enhanced activity of the serine/threonine phosphatase, protein phosphatase 2A, which operates at the intersection of the PI3K/Akt and MAPK/ERK pathways and dephosphorylates and inactivates pyruvate dehydrogenase kinase 1, Akt, Raf, mitogen‐activated protein kinase kinase, and ERK1/2. Nqo1 ablation also induced the expression of phosphatase and tensin homolog, a dual protein/lipid phosphatase that blocks PI3K/Akt signaling, through the ERK/cAMP‐responsive element‐binding protein/c‐Jun pathway. Together, Nqo1 ablation triggered simultaneous inhibition of the PI3K/Akt and MAPK/ERK pathways, suppressed the expression of glycolysis and glutaminolysis genes and blocked metabolic adaptation in liver cancer cells. Conversely, Nqo1 overexpression caused hyperactivation of the PI3K/Akt and MAPK/ERK pathways and promoted metabolic adaptation. Conclusion: In conclusion, Nqo1 functions as an upstream activator of both the PI3K/Akt and MAPK/ERK pathways in liver cancer cells, and Nqo1 ablation blocked metabolic adaptation and inhibited liver cancer cell proliferation and HCC growth in mice. Therefore, our results suggest that Nqo1 may function as a therapeutic target to inhibit liver cancer cell proliferation and inhibit HCC.
Contribution of Gene Regulatory Networks to Heritability of Coronary Artery Disease
Authors: Lingyao Zeng, Husain A. Talukdar, Simon Koplev, Chiara Giannarelli, Torbjörn Ivert, Li-Ming Gan, Arno Ruusalepp, Eric E. Schadt, Jason C. Kovacic, Aldons J. Lusis, Tom Michoel, Heribert Schunkert, Johan L.M. Björkegren
Journal: Journal of the American College of Cardiology (2019)
Abstract 14267: Clinical Characteristics of Patients With Out-of-hospital Cardiac Arrest Caused by Ventricular Fibrillation due to Acute Coronary Syndromes Who Responded to Extracorporeal Cardiopulmonary Resuscitation
Authors: Hayato Hosoda, Yoshio Tahara, Takahiro Nakashima, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Naoto Morimura, Ken Nagao, Yasufumi Asai, Hiroyuki Yokota, Mamoru Hase, Takahiro Atsumi, Tetsuya Sakamoto
Journal: Circulation (2015)

Background: Extracorporeal cardiopulmonary resuscitation (ECRP) have been reported to be effective in patients with out-of-hospital cardiac arrest (OHCA) associated with an initial rhythm of ventricular fibrillation (VF) caused by acute coronary syndromes (ACS) refractory to conventional cardiopulmonary resuscitation (CPR). However, the clinical characteristics of patients who best respond to ECRP remain unclear. Methods: Between 2008 and 2012, we prospectively collected Utstein-style data at 46 institutions on 454 consecutive patients with OHCA aged 20 to 74 years had an initial rhythm of VF and arrived at the hospital within 45 minutes after the onset of cardiac arrest. They did not respond to conventional CPR given for more than 15 minutes after hospital arrival and received combination therapy with ECPR, percutaneous coronary intervention (PCI), intra-aortic balloon pumping (IABP), and therapeutic hypothermia (TH). ACS was diagnosed on emergency coronary angiography or clinical course in 133 patients. These patients were classified according to whether neurologic outcomes at 6 months, i.e., good outcome group (cerebral performance category [CPC] = 1 to 2) or poor outcome group (CPC = 3 to 5). Demographic characteristics were compared between two groups. Results: Among the 133 ACS patients given ECPR, good neurologic outcomes at 6 months in 14 (11%) patients, but not in 119 (89%) patients. There were no significant differences of age, the rate of witnessed arrest, bystander CPR, TH and time from hospital arrival to PCPS start between the 2 groups. Good outcome group had a shorter time from cardiac arrest to hospital arrival (24.9± 8.6 vs. 29.5± 10.1 min, p=0.03) and time from cardiac arrest to PCPS start (44 ± 8.8 vs. 53.7 ± 15.9 min, p=0.01) than poor outcome group. Conclusions: Our results suggest that shortening the interval from cardiac arrest until PCPS start, especially until hospital arrival, may improve neurologic outcomes in patients with refractory VF caused by ACS.
Measuring the reproducibility and quality of Hi-C data
Authors: Galip Gürkan Yardımcı, Hakan Ozadam, Michael E. G. Sauria, Oana Ursu, Koon-Kiu Yan, Tao Yang, Abhijit Chakraborty, Arya Kaul, Bryan R. Lajoie, Fan Song, Ye Zhan, Ferhat Ay, Mark Gerstein, Anshul Kundaje, Qunhua Li, James Taylor, Feng Yue, Job Dekker, William S. Noble
Journal: Genome biology (2019)

Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study. Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise and sparsity through simulations, we demonstrate the deficiencies of performing simple correlation analysis on pairs of matrices, and we show that methods developed specifically for Hi-C data produce better measures of reproducibility. We also show how to use established measures, such as the ratio of intra- to interchromosomal interactions, and novel ones, such as QuASAR-QC, to identify low-quality experiments. In this work, we assess reproducibility and quality measures by varying sequencing depth, resolution and noise levels in Hi-C data from 13 cell lines, with two biological replicates each, as well as 176 simulated matrices. Through this extensive validation and benchmarking of Hi-C data, we describe best practices for reproducibility and quality assessment of Hi-C experiments. We make all software publicly available at http://github.com/kundajelab/3DChromatin_ReplicateQC to facilitate adoption in the community.
PF336 EVALUATION OF THROMBOPOIETIN‐RECEPTOR AGONISTS (TPO‐RAS) «STOP‐THERAPY» IN IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)
Authors: O. Vinogradova, M. Pankrashkina, N. Tkachenko, M. Chernikov, L. Mukha, V. Perova, Y. Kobzev, D. Shikhbabaeva, V. Ptushkin
Journal: HemaSphere (2019)

Background: For a number of years, it has been shown that TPO‐RAs are a highly effective therapy of ITP. Still, there are few published guidelines/recommendations addressing the management of ITP patients (pts) on TPO‐RAs after they achieve continuous remission. Aims: To evaluate the TPO‐RAs «stop‐therapy» in ITP pts with complete response (CR) to TPO‐RAs. Methods: We analyzed data of TPO‐RA «stop‐therapy» in patients with CR. Primary endpoints of the study were the duration and type of response (CR, partial – PR, minor – MR, and loss of response) after TPO‐RAs had been stopped. Secondary endpoints included types of response (CR, PR, MR) after TPO‐RAs had been resumed in those pts who relapsed. Results: 194 ITP pts treated at Moscow City Hematology Center (Botkin Hospital) in 2014–2018 were administered TPO‐ARs: (romiplostim (R): n = 123; eltrombopag (E): n = 71). 106 pts (55%) achieved CR (platelets &gt;100х10 9 /l)(R: n = 79 (64%); E: n = 27 (38%). 28 pts in continuous CR (≥3 months (mo) had TPO‐RA stopped: (R: n = 19; E: n = 9). Group R (GR) comprised of 4 males and 15 females, with median age (Mе) age at the time of diagnosis of 51 (range 1 ‐ 69) years, and Me follow‐up time from the time of diagnosis was 108 (9 ‐ 483) mo. Group E (GE) included 1 male and 8 females with Me age of 54 (range 12 ‐ 75) years and Me follow‐up time from the time of diagnosis of 74 (27 ‐ 228) mo. Me stop‐therapy length was 69 (range 20 ‐ 276) weeks in GR, and 38 (range 13 ‐ 131) weeks in GE. At the time of analysis, CR was maintained in 5 (26%) GR pts, and in 1 (11%) GE pt. PR was seen in 7 (37%) GR pts and in 2 (23%) GE pts; and MR in 5 (26%) GR pts and in 1 (11%) GE pt. 2 (11%) GR pts and 5 (55%) GE pts did not respond to TPO‐RAs. TPO‐RAs were resumed in 2 GR and 2 GE pts who relapsed (7 pts have relapsed altogether), and 1 PR and 1 MR in each group were achieved. Summary/Conclusion: Our data adds to the growing body of evidence that ITP pts maintain remission after TPO‐RAs are stopped. This may possibly represent a change in therapeutic approach to these patients who usually require continuous maintenance therapy. Longer follow‐up and larger number of pts enrolled in the study are required to fully assess benefits of such approach.
Abstract 15960: First Results From a Digital Mass Screening for Atrial Fibrillation Using a Smartphone Application
Authors: Tine Proesmans, Dieter Nuyens, Pieter Vandervoort, Hugo Van Herendael, Maximo Rivero-Ayerza
Journal: Circulation (2018)

Introduction: Opportunistic screening for atrial fibrillation, recommended in every patient 65 and older, remains challenging due to its time consuming nature, logistical needs, and reliance on sca...