tbuckley/cabot-search huggingface dataset:
Abstract 12644: Growth Differentiation Factor-15 (GDF-15) for Risk Stratification in Patients After an Acute Coronary Syndrome: Insights From the SOLID-TIMI 52 trial
Authors: Eri Toda Kato, David A Morrow, Christopher P Cannon, Mary Ann Lukas, Andrzej Budaj, Christian W Hamm, Petr Jarolim, KyungAh Im, Jing Zhou, Eugene Braunwald, Michelle L O’Donoghue
Journal: Circulation (2015)

Background: Growth differentiation factor (GDF)-15, a stress responsive cytokine, is associated with the risk of CV events after an acute coronary syndrome (ACS). Unlike other established cardiac biomarkers, the level of GDF-15 remains elevated in sub-acute phase after ACS and gradually decreases over time. We evaluated the prognostic utility of GDF-15 in patients after ACS accounting for established markers and risk predictors. Methods: GDF-15 (R&amp;D Systems) and other established cardiac biomarkers (BNP, hsCRP and hsTnI) were measured at baseline in a randomly selected cohort of 4,968 patients enrolled within 30 days of hospitalization with ACS (median=14d) in SOLID-TIMI 52. Previously defined cutpoints were applied for GDF-15 concentration: &lt;1200 (n=3451), 1200-1800 (n=919), and &gt; 1800 ng/L (n=598). Analyses were adjusted for established risk predictors, days from the ACS event and other markers. MACE was defined as CV death, MI or stroke. Median follow-up was 2.5 years. Results: Patients with higher GDF-15 tended to be older, more likely to have diabetes, hypertension, history of revascularization, and CKD at baseline. Higher baseline levels of GDF-15 identified patients with higher rates of MACE as well as each individual element (p-trend &lt;0.001 for all endpoints, Fig). The rate of MI was ∼2-fold higher in those with GDF-15 concentration &gt;1800ng/L compared to patients with GDF-15 concentration &lt;1200 ng/L. After adjustment for clinical predictors and other markers, GDF-15 was independently associated with the risk of MACE (HR 1.4, 95% CI 1.1-1.7; HR 1.8, 95% CI 1.4-2.3 for GDF-15 1200-1800, &gt;1800, respectively). Individuals with GDF-15 &gt;1800 ng/L had an increased risk of MI (adj HR 1.4, 95% CI 1.1-2.0) and stroke (adj HR 2.3, 95% CI 1.3-3.9). Conclusion: In patients after ACS, GDF-15 concentration is associated with the risk of MACE including MI and stroke independent of traditional risk factors and risk markers.
Abstract 2960: A combined bioinformatics and proteomics approach identifies DNA repair factors regulated by the APC/C
Authors: Marcel A. van Vugt, Rudolf S.N. Fehrmann, Shao-En Ong
Journal: Cancer Research (2011)

Abstract Our genome is constantly challenged by endogenous and exogenous factors that induce a variety of DNA lesions. DNA double strand breaks are considered to most toxic type of DNA damage, and cells have evolved powerful mechanisms that can detect and repair such lesions. Two main mechanisms responsible for repair of DNA double strand breaks are Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). The choice between these two types of DNA double strand break repair is strongly influenced by the cell cycle. Only cells in late S and G2 phase of the cell cycle can employ HR and this differential activity is underscored by a strict requirement for Cdk activity for HR. Mechanisms that enable HR during S-phase have been previously identified, but how exactly HR DNA repair is inactivated during the mitosis-to-G1 transition is poorly understood. Based on the observed strict cell-cycle regulation of HR repair, a role for the mitotic E3 ligase APC/C was suggested. Here we present a combined proteomics and bioinformatics approach to identify APC/C targets and reveal components of DNA double strand break repair that are potential targets of the APC/C. Firstly, proteins were identified that contain evolutionary conserved and sterically accessibly APC/C targeting domains (KEN and D-boxes) using bioinformatics. Within this group of proteins with a known role in DNA repair were highlighted. Subsequently, a quantitative mass-spec approach was used to identify those proteins, whose abundance was readily lost upon mitotic exit. Reassuringly, we could identify many previously identified APC/C targets, that all showed loss of abundance during mitotic exit. We subsequently searched for DNA repair-associated factors that were down-regulated during mitotic exit and among those, we identified multiple topoisomerase subunits as likely APC/C substrates. We could subsequently confirm a role for the APC/C in regulating protein levels of these novel substrates using RNAi-mediated depletion of Cdh1 and live cell microscopy. In conclusion, we here present a novel method to identify APC/C targets and used this approach to uncover novel regulatory aspects of cell cycle-regulated DNA repair. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2960. doi:10.1158/1538-7445.AM2011-2960
Cessation of screening for intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae in a low-endemicity intensive care unit with universal contact precautions
Authors: W. Jalalzaï, M. Boutrot, J. Guinard, A. Guigon, L. Bret, D.-M. Poisson, T. Boulain, F. Barbier
Journal: Clinical Microbiology and Infection (2017)
Abstract 18887: Fetal-Derived Cdx2 Cells in Placenta Are Multipotent Cells With Cardiomyogenic Potential
Authors: Sangeetha Vadakke-Madathil, Amaresh Ranjan, Jesse Yoon, Joseph Tripodi, Koen Raedschelders, Sarah Parker, Vesna Najfeld, Jennifer Van EyK, Hina Chaudhry
Journal: Circulation (2016)

Introduction: Stem cell based therapies for cardiac regeneration are of crucial importance and an ideal cell-type is yet to be established. Placenta is an easily available and rich source of multip...
Abstract 407: Overexpression of the Valosin-containing Protein in vivo Prevents Cardiac Hypertrophy and Heart Failure by Chronic Pressure Overload via Suppressing the Activation of mTORC1 Pathway
Authors: Ning Zhou, Ben Ma, Tristen T Hays, Hongyu Qiu
Journal: Circulation Research (2016)

Aims: Pressure overload induced cardiac hypertrophy is a key risk factor for heart failure. Although several defined interventions result in a significant inhibition of cardiac hypertrophy, the functional consequences are controversial. Identification of novel targets modulating the cardiac hypertrophy without adversely affecting cardiac function is particularly crucial to the treatment of heart failure. Here we test our hypothesis that the valosin-containing protein (VCP) is a novel mediator of cardiac protection against cardiac hypertrophy and heart failure by pressure overload. Methods and Results: Pressure overload was induced by transverse aortic constriction (TAC) in a mouse model to mimic the progression of cardiac hypertrophy and heart failure. Cardiac structure and function were measured by echocardiography and hemodynamic analysis. VCP expression was significantly reduced in wild type (WT) mice after 2 weeks TAC at both the mRNA and protein levels by 40% and 45 % respectively and even more markedly reduced after 5 weeks TAC (68% in mRNA and 73% in protein, all, P &lt;0.01 vs sham). Cardiac overexpression of VCP in a transgenic (TG) mouse did not alter either cardiac structure or function at baseline condition. However, compared to 2 week TAC WT mice, VCP TG mice showed a significant repression of cardiac hypotrophy, evidenced by a significant reduction in the ratio of left ventricle (LV) /tibial length (TL) by 36%, LV posterior wall thickness by 20%, and cardiomyocyte cross sectional area by 39% (all P &lt;0.05 vs WT). After 5 weeks of TAC, while WT mice progressed to cardiac failure, VCP TG mice exhibited preservation of cardiac function in terms of ejection function (EF,72±1% vs 52±4.1% in WT) and Lung weight /TL ratio (8.0±0.8mg/mm vs 9.8±0.8 mg/mm in WT) ( P &lt;0.05 vs WT). Induction of fetal cardiac genes in TAC WT, e.g. ANP and BNP, was significant suppressed in VCP TG mice ( P &lt;0.05 vs WT). TAC induced activation of mammalian target of rapamycin complex 1 (mTORC1), e.g., an increase of phosphorylation of mTOR and S6K1, was significantly blunted in VCP TG mice vs WT after TAC ( P &lt;0.05 vs WT). Conclusion: Overexpression of VCP in vivo prevents the progression of cardiac hypertrophy and dysfunction upon pressure overload by modulating mTORC1 signaling pathways.
A methylation center within intron 1 of RIL predisposes to silencing, and is opposed by a polymorphic Sp1/Sp3 site
Authors: Yanis Boumber, Marcos Estecio, Carmen Tellez, Saira Ahmed, Kazuo Konishi, Jiali Si, Yutaka Kondo, Lanlan Shen, Jean-Pierre Issa
Journal: Cancer Research (2007)

2843   Aberrant promoter methylation is a common feature of cancer, yet the underlying mechanisms of it are not well understood. We have previously reported that the RIL gene is one of the most frequently methylated genes in different cancer types and is a candidate tumor suppressor by functional assays. In search for causes of abnormal methylation of RIL, we designed seven pyrosequencing assays around the transcription start site (TSS) of the gene as well as exon 1 and intron 1. Here we show that in a group of 19 normal colon samples, the region around the transcription start site of the gene (-306 to +168) shows low degrees of methylation (average methylation density, 25.9± 1.9%) and a strong correlation with age (R=0.62, P=0.006 as measured by the sum of Z-scores), whereas the intron 1 region (+370 to +384 has a very high degree of methylation in normal tissues (average methylation density, 85.35± 0.8%) and no correlation with age (R=-0.05, P=0.844). These data suggested that intron 1 contains a putative methylation center for RIL. To test this, we generated reporter constructs with (-589 to +516) and without (-590 to +20) intron 1 (the putative methylation center). Transient transfections of 3T3 cells showed 3.8 to 4.0 fold lower levels of expression for the constructs containing the methylation center, suggesting the presence of a repressor sequence within intron 1. Stable transfection of the constructs without the methylation center resulted in sustained expression, whereas intron-containing constructs showed gradual decline in transcription levels starting from day 37 after transfection, consistent with time-dependednt silencing. RIL has a polymorphic Sp1/Sp3 site in the TSS area that is associated with lower levels of methylation  in vivo . Interestingly, among intron-containing constructs, Sp1+ transgenes were more resistant to time-dependent silencing relative to the Sp1- transgenes, as they showed substantially higher levels of expression (4.1-fold higher expression on day 25 and 23.8-fold higher expression on day 51). Similar data were obtained in the RKO cell line. Our results suggest a model whereby the RIL gene contains a methylation center in the intron region that predisposes its promoter to time-dependent silencing, whereas a naturally-occuring insertional Sp1/Sp3 polymorphic site acts as a barrier, preventing cis-acting spreading of heterochromatin.
Update to CDC’s <i>U.S. Medical Eligibility Criteria for Contraceptive Use, 2016</i>: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection
Authors: Naomi K. Tepper, Jamie W. Krashin, Kathryn M. Curtis, Shanna Cox, Maura K. Whiteman
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

CDC's U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) (first published in 2010 and updated in 2016) provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1), and is adapted from global guidance from the World Health Organization (WHO) and kept up to date based on continual review of published literature (2).* CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception.† After careful review, CDC adopted the updated WHO guidance for inclusion in the U.S. MEC guidance; this guidance states that the advantages of progestin-only injectable contraceptive use (including depot medroxyprogesterone acetate [DMPA]) by women at high risk for HIV infection outweigh the theoretical or proven risks (U.S. MEC category 2). The guidance also includes an accompanying updated clarification, which states that "there continues to be evidence of a possible increased risk of acquiring HIV among progestin-only injectable users. Uncertainty exists about whether this is due to methodological issues with the evidence or a real biological effect. In many settings, unintended pregnancies and/or pregnancy-related morbidity and mortality are common, and progestin-only injectables are among the few types of methods widely available. Women should not be denied the use of progestin-only injectables because of concerns about the possible increased risk. Women considering progestin-only injectables should be advised about these concerns, about the uncertainty over whether there is a causal relationship, and about how to minimize their risk of acquiring HIV." Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1).
Histopathology of Interstitial Lung Abnormalities in the Context of Lung Nodule Resections
Authors: Ezra R. Miller, Rachel K. Putman, Marina Vivero, Yin Hung, Tetsuro Araki, Mizuki Nishino, George R. Washko, Ivan O. Rosas, Hiroto Hatabu, Lynette M. Sholl, Gary M. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Impaired Cognition and the Risk of Parkinson Disease
Authors: Ethan G. Brown, Caroline M. Tanner
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Multiregional Sequencing Reveals Genomic Alterations and Clonal Dynamics in Primary Malignant Melanoma of the Esophagus
Authors: Jingjing Li, Shi Yan, Zhen Liu, Yong Zhou, Yaqi Pan, WenQin Yuan, Mengfei Liu, Qin Tan, Geng Tian, Bin Dong, Hong Cai, Nan Wu, Yang Ke
Journal: Cancer Research (2017)

Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intratumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a patient with PMME. High intratumor heterogeneity was observed in both somatic mutation and copy-number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model. Most putative oncogenic drivers such as BRAF and KRAS mutations as well as CDKN2A biallelic inactivation were observed in trunk clones, whereas clinically actionable mutations such as PIK3CA and JAK1 mutations were detected in branch clones. Ancestor tumor clones evolved into three subclonal clades: clade1 fostered metastatic subclones that carried metastatic features of PIK3CA and ARHGAP26 point mutations as well as chr13 arm-level deletion, clade2 owned branch-specific JAK1 mutations and PTEN deletion, and clade3 was found in two vertical distribution samples below the primary tumor area, highlighting the fact that it is possible for PMME to disseminate by the submucosal longitudinal lymphatic route at an early stage of metastasis. These findings facilitate interpretation of the genetic essence of this rare melanoma subtype as well as the pattern of cancer evolution, thus reinforcing the therapeutic challenges associated with PMME.Significance: This study highlights the use of multiregion exome sequencing and whole genome SNP array genotyping to comprehensively characterize the genetic landscape of a rare type of esophogeal melanoma. Cancer Res; 78(2); 338-47. ©2017 AACR.
Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches
Authors: Enrique Martín-Gayo, Sara González-García, María J. García-León, Alba Murcia-Ceballos, Juan Alcain, Marina García-Peydró, Luis Allende, Belén de Andrés, María L. Gaspar, María L. Toribio
Journal: The Journal of Experimental Medicine (2017)

A key unsolved question regarding the developmental origin of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) resident in the steady-state thymus is whether early thymic progenitors (ETPs) could escape T cell fate constraints imposed normally by a Notch-inductive microenvironment and undergo DC development. By modeling DC generation in bulk and clonal cultures, we show here that Jagged1 (JAG1)-mediated Notch signaling allows human ETPs to undertake a myeloid transcriptional program, resulting in GATA2-dependent generation of CD34+ CD123+ progenitors with restricted pDC, cDC, and monocyte potential, whereas Delta-like1 signaling down-regulates GATA2 and impairs myeloid development. Progressive commitment to the DC lineage also occurs intrathymically, as myeloid-primed CD123+ monocyte/DC and common DC progenitors, equivalent to those previously identified in the bone marrow, are resident in the normal human thymus. The identification of a discrete JAG1+ thymic medullary niche enriched for DC-lineage cells expressing Notch receptors further validates the human thymus as a DC-poietic organ, which provides selective microenvironments permissive for DC development.
Respiratory, Dermal, and Eye Irritation Symptoms Associated with Corexit™ EC9527A/EC9500A following the <i>Deepwater Horizon</i> Oil Spill: Findings from the GuLF STUDY
Authors: Craig J. McGowan, Richard K. Kwok, Lawrence S. Engel, Mark R. Stenzel, Patricia A. Stewart, Dale P. Sandler
Journal: Environmental Health Perspectives (2017)

The large quantities of chemical oil dispersants used in the oil spill response and cleanup (OSRC) work following the
Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms
Authors: S K Balasubramanian, M Aly, Y Nagata, T Bat, B P Przychodzen, C M Hirsch, V Adema, V Visconte, T Kuzmanovic, T Radivoyevitch, A Nazha, S Mukherjee, M A Sekeres, J P Maciejewski
Journal: Leukemia (2017)
HCV carriers with persistently normal aminotransferase levels [2] (multiple letters)
Authors: Claudio Puoti, Lia Bellis, Roberto Castellacci, Fabrizio Montagnese, Nicoletta Bergami, Patrizia Petrone De Luca, Doris B. Strader, Teresa L. Wright, David L. Thomas, Leonard B. Seeff
Journal: Hepatology (2004)
Systemic Antitumor Immunity by PD-1/PD-L1 Inhibition Is Potentiated by Vascular-Targeted Photodynamic Therapy of Primary Tumors
Authors: Matthew J. O'Shaughnessy, Katie S. Murray, Stephen P. La Rosa, Sadna Budhu, Taha Merghoub, Alexander Somma, Sebastien Monette, Kwanghee Kim, Renato Beluco Corradi, Avigdor Scherz, Jonathan A. Coleman
Journal: Clinical Cancer Research (2017)

Purpose: PD-1/PD-L1 pathway inhibition is effective against advanced renal cell carcinoma, although results are variable and may depend on host factors, including the tumor microenvironment. Vascular-targeted photodynamic (VTP) therapy with the photosensitizer WST11 induces a defined local immune response, and we sought to determine whether this could potentiate the local and systemic antitumor response to PD-1 pathway inhibition.Experimental Design: Using an orthotopic Renca murine model of renal cell carcinoma that develops lung metastases, we treated primary renal tumors with either VTP alone, PD-1/PD-L1 antagonistic antibodies alone, or a combination of VTP and antibodies and then examined treatment responses, including immune infiltration in primary and metastatic sites. Modulation of PD-L1 expression by VTP in human xenograft tumors was also assessed.Results: Treatment of renal tumors with VTP in combination with systemic PD-1/PD-L1 pathway inhibition, but neither treatment alone, resulted in regression of primary tumors, prevented growth of lung metastases, and prolonged survival in a preclinical mouse model. Analysis of tumor-infiltrating lymphocytes revealed that treatment effect was associated with increased CD8+:regulatory T cell (Treg) and CD4+FoxP3-:Treg ratios in primary renal tumors and increased T-cell infiltration in sites of lung metastasis. Furthermore, PD-L1 expression is induced following VTP treatment of human renal cell carcinoma xenografts.Conclusions: Our results demonstrate a role for local immune modulation with VTP in combination with PD-1/PD-L1 pathway inhibition for generation of potent local and systemic antitumor responses. This combined modality strategy may be an effective therapy in cancers resistant to PD-1/PD-L1 pathway inhibition alone. Clin Cancer Res; 24(3); 592-9. ©2017 AACR.
Behavior of circulating tumor cells detected by EGF tagged SERS nanoparticles in head and neck cancer patients.
Authors: Jonathan Jay Beitler, Xu Wang, Ximei Qian, Hong Wang, Zhuo Georgia Chen, Fadlo Raja Khuri, Shuming Nie, Dong M Shin
Journal: Journal of Clinical Oncology (2012)

e21161 Background: Quantification of circulating tumor cells(CTCs) is becoming central to the management of metastatic breast, colorectal and prostate cancers and the potential to improve management of head and neck squamous cell cancer (HNSCC) patients is very high. Our group has published our experience with nanotechnology, highly specific, surface-enhanced Raman spectroscopy(SERS) and Epidermal Growth Factor Receptor(EGFR) ligands to identify 7-720 CTCs/ml in 19 samples from HNSCC patients[1]. Our goal here is to understand the clinical behavior of CTCs in HNSCC for selected patients whom we believe our single channel assay has been accurate. Methods: Our methods for detection of CTCs using EGFR ligands have been previously described[1]. After comparing CTCs in 116 patient samples with and without gross disease, we examined 8 patients with decreasing sequential single channel assays of CTCs and no evidence of disease at last follow-up. Results: For 56 samples from patients with no gross disease, the mean CTC was 94/ml. For 61 samples from patients with gross disease the mean CTC was 193/ml (p=0.002). Among our 4 samples where we had initial disease and a non-zero, no evidence of disease, second sample, the absolute and percentage decrease per month in CTC was 121/ml/month(range 43-160) and 17%/month(range 11-25%). The decrease of 121 CTC/ml/month correlated well with 5 out of 6 other data sets. Conclusions: Targeting of EGFR for detection of CTCs in HNSCC patients appears very promising. Among +EGFR HNSCC patients who appear cured, the average decrease in CTC per ml was 121 per month and 17% per month. To further enhance the sensitivity and specificity of detection of CTCs, we are developing 3 SERS nanoparticles (multiplexed SERS) to target specific and distinct targets on the CTC surface while still maintaining a single tube assay system. 1. Wang, X., et al., Detection of circulating tumor cells in human peripheral blood using surface-enhanced Raman scattering nanoparticles. Cancer Research, 2011. 71(5): p. 1526-32.