tbuckley/cabot-search huggingface dataset:
Abstract 13861: Deep Terminal Negativity of P wave in V1 is Associated With Twice Higher Mortality in the Hospital Population
Authors: Larisa G Tereshchenko, Lauren Hawkins, Trevor Feldman, Jiri Sklenar, Charles Henrikson
Journal: Circulation (2015)

Introduction: Easily recognizable ECG sign deep terminal negativity of P wave in V1 (DTNPV1) represents an epiphenomenon of a fibrotic heart, and predicts sudden cardiac death in the general population. Hypothesis: We hypothesized that DTNPV1 is associated with increased mortality in the population comprised from an entire health system ECG database. Methods: We conducted retrospective double-cohort study and screened all 12-lead ECGs over 4 years (2010-2014) at a large hospital system and reviewed medical records to collect baseline clinical characteristics. ECGs from 130,284 individual patients were automatically analyzed in the MUSE ECG database. Children &lt; 18 y were excluded. Two cohorts with different exposures (P-prime in V1), matched by age and sex, were comprised. The DTNPV1 cohort included participants with biphasic P wave in V1 with the amplitude of the terminal negative phase &gt;100 μV. The zero P-prime in V1 cohort was comprised of participants with absent negative terminal deflection of P wave in V1. All-cause mortality served as a primary outcome. Results: Each cohort consisted of 3,435 patients (mean age 58.0±16.2y; 44.8% female). In DTNPV1 cohort mean P prime in V1 amplitude was -119.4±19.6 μV. Over a mean follow-up time of 2.5 years, 7.6% patients in the zero P-prime V1 cohort and 14.3% patients in the DTNPV1 cohort had died (Figure). In Cox regression analysis, DTNPV1 was associated with a two-fold increase in risk of mortality after adjustment for age, sex, coronary artery disease, history of myocardial infarction, chronic obstructive lung disease, diabetes, liver disease, ventricular tachycardia, and atrial fibrillation/flutter [HR 1.94 (1.65-2.28); P&lt;0.001]. Conclusions: DTNPV1 in a population from an entire health system ECG database is independently associated with twice higher risk of all-cause death, as compared to patients without negative deflection of P prime in V1.
Abstract 17709: Framingham Risk Score and Coronary Plaque Characteristics as Assessed by Three-Vessel Optical Coherence Tomography Imaging
Authors: Rocco Vergallo, Haibo Jia, Tsunenari Soeda, Yoshiyasu Minami, Sining Hu, Jinwei Tian, Hang Lee, Luigi M Biasucci, Filippo Crea, Ik-Kyung Jang
Journal: Circulation (2014)

Introduction: Clinical prediction models, such as the Framingham Risk Score (FRS), are useful to identify patients at high risk for future events. However, their association with coronary plaque features is largely unknown. Aim: This study aimed at evaluating the relationship between FRS and coronary plaque features by optical coherence tomography (OCT). Methods: FRS was assessed in 176 patients with coronary artery disease [72 with acute coronary syndrome (ACS), and 104 with stable angina] who underwent 3-vessel OCT imaging. Based on the FRS values, patients were divided into 3 groups: lower FRS (FRS&lt;5%, n=26), intermediate FRS (5%≤FRS&lt;10%, n=105), and higher FRS (FRS≥10%, n=45). Nonculprit coronary plaque features were compared among the 3 groups. Results: A total of 448 nonculprit plaques were identified (lower FRS, n=61; intermediate FRS, n=267; higher FRS, n=120). Compared to the patients with lower and intermediated FRS, those with higher FRS were older (p&lt;0.001), and more likely to have male gender (p&lt;0.001), diabetes (p=0.023), lower HDL-cholesterol (p&lt;0.001) and higher creatinine levels (p=0.023). Compared to the patients with lower FRS, those with higher FRS had greater lipid index (mean lipid arc x lipid length), and tended to have higher prevalence of thin-cap fibroatheroma (TCFA). Patients with higher FRS showed greater prevalence of calcifications compared to those with lower and intermediate FRS. Prevalence of cholesterol crystals was progressively higher across the 3 groups. At multivariate analysis, presentation with ACS (OR, 2.37; 95% CI, 1.27–4.39; p=0.006), and FRS (OR, 1.57 per 5% risk increase; 95% CI, 1.01–2.42, p=0.043) were independent predictors of TCFA. Conclusions: Nonculprit plaques of patients with higher FRS showed greater lipid content, and higher prevalence of calcifications and cholesterol crystals compared to those of patients with lower and intermediate FRS. ACS presentation and FRS were independent predictors of TCFA.
Abstract 8436: Depression and Mortality in Older Adults Undergoing Percutaneous Coronary Intervention
Authors: S. M Gharacholou, Veronique L Roger, Ryan J Lennon, Mark A Frye, Charanjit S Rihal, Mandeep Singh
Journal: Circulation (2011)

Background: Depression is prevalent in adults with cardiovascular disease; however, the association between depression and death in older adults treated with percutaneous coronary intervention (PCI) is not known. Method: We prospectively studied 596 patients 65 years of age or older undergoing PCI at Mayo Clinic (Rochester, MN and Franciscan Skemp Hospital in La Crosse, WI) from October 2005 through September 2008. Depression was assessed using the validated and reliable Center for Epidemiological Studies Depression (CES-D) scale. Patients were categorized into groups by depression symptom severity: none/mild (CES-D &lt;16; referent), moderate (CES-D 16-21), or moderate/severe (CES-D&gt;21). Patients were followed annually for death. Results: Mean age of patients was 75.0±6.4 years; 31% were women, 98.0% were white. There were 461 patients (77.3%) that were not depressed and 135 patients (22.7%) that were depressed; 67 patients (11.3%) had moderate depressive scores (CES-D 16-21) and 68 patients (11.4%) had moderate/severe scores (CES-D &gt;21). Groups were similar with respect to baseline characteristics. After a median follow-up of 36 months, there were 74 deaths, and patients with moderate/severe depressive symptom scores had a higher cumulative incidence of mortality (p = 0.036 by log-rank) (Figure). In multivariable analysis, CES-D score &gt;21 was independently predictive of all-cause mortality (HR 1.90; 95% CI 1.02-3.53; p = 0.043), along with other covariates, including age (HR 1.88; 95% CI 1.31-2.68), comorbidity (Charlson Index) (HR 1.08; 95% CI 1.02-1.15), and diabetes mellitus (HR 2.04; 95% CI 1.26-3.30). Conclusion: Over one-fifth of older adults undergoing PCI met criteria for depression and those with high depressive scores reflecting greater self-perceived depressive symptoms had worse survival. Recognition of depressive symptoms in older adults treated with PCI identifies a cohort at higher risk of adverse outcomes.
Transition to immediate open access publishing under Plan S will be smooth, promise backers
Authors: Jacqui Thornton
Journal: BMJ (2018)

A coalition of research funders has outlined how a new system called Plan S,1 which aims to ensure full and immediate open access science publishing by January 2020, should be implemented.

The guidance2 contains 10 principles that the group, called cOAlition S, says are immovable. But the group is seeking views from stakeholders on implementation in a consultation ending on 1 February 2019.

Plan S aims to establish science publication without paywalls—a system, the coalition says, that will be more transparent, efficient, and fair, fostering a culture that ensures all scholars, and in particular early career researchers, have the opportunity to excel and advance their careers.

So far, 16 funding bodies have signed up to it, mostly national funding agencies of countries including Austria, France, and the UK, but also private funders such as the Bill and Melinda Gates Foundation and Wellcome.

Critics in science publishing have said previously that the move will not support high quality peer review, research publication, and dissemination, while others said that research funding agencies should align rather than act in small groups in ways that are incompatible with each other.3

On 26 …
Abstract 17279: Have the 2013 AHA/ACC Cholesterol Guidelines Affected Clinicians’ Lipid Management Strategies?
Authors: Ann M Navar, Anne C Goldberg, Jennifer G Robinson, Veronique L Roger, Salim S Virani, Peter F Wilson, Joseph Elassal, L. Veronica Lee, Laura E Webb, Michael P Pencina, Eric D Peterson, Tracy Y Wang
Journal: Circulation (2015)

Background: The 2013 ACC/AHA Cholesterol Guidelines departed from prior ATPIII guidelines, recommending statin treatment based on patients’ predicted 10-year ASCVD risk and de-emphasizing LDL-C targets. However, the degree to which these new guidelines have been adopted by clinicians in community practice is unknown. Methods: We surveyed 522 clinicians in 133 cardiology, primary care, and endocrinology practices participating in the Patient and Provider Assessment of Lipid Management (PALM) Registry. Clinicians were asked about their likelihood of prescribing statins in 4 hypothetical patient scenarios. Results: Among responders, 79% were physicians (60% cardiologists, 38% primary care or general practice, 2% endocrinology), 18% were advanced practice providers, and 3% trainees. When queried, 73% of providers reported primarily using the 2013 ACC/AHA Guidelines to guide lipid management. However, only half reported “often” or “always” calculating 10-year ASCVD risk to aid lipid management decisions for primary prevention. When presented with a high 10-year ASCVD risk patient (&gt;15%) with a high LDL-C (150 mg/dL), 92% of providers recommended statins. Similarly, 83% of providers would use statins in a diabetic patient with a LDL-C of 140 mg/dL. Yet, only 37% reported they would prescribe a statin to an older adult (age 70) for whom guidelines recommend statin based on high 10-year ASCVD risk alone (10.1%). And up to 40% would prescribe a statin to a younger (age 40) with a low 10-year risk, but a high LDL (165 mg/dL) who would not otherwise meet criteria for statin therapy under the new guidelines. Cardiologists and non-cardiologists were similarly likely prescribe statins in most scenarios with the exception of to the younger patient with elevated LDL-C were cardiologists used statins more commonly (32% vs. 42%. OR 1.5, 95% CI 1.1-2.2, p=0.02). Conclusion: Initial survey results show that while most clinicians claim adoption of the 2013 ACC/AHA Guidelines, reported practices are not always adherent to these guidelines. Providers do not always calculate 10-year ASCVD risk to guide lipid management and many do not prescribe statins to patients eligible based on 10-year ASCVD risk.
Errors in Programming and Coding Affecting Cohorts Included in the Study Deriving and Validating the PROMISE Minimal-Risk Tool
Authors: Christopher B. Fordyce, Pamela S. Douglas, James E. Udelson
Journal: JAMA Cardiology (2018)

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 Cardiology 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 Cardiology journal
Abstract PR12: Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape
Authors: Chao Lu, Siddhant Jain, Dominik Hoelper, Denise Bechet, Leili Ran, Irene Andrulis, Brendan Dickson, Jacek Majewski, Craig Thompson, Ping Chi, Benjamin Garcia, Nada Jabado, Peter Lewis, C. David Allis
Journal: Clinical Cancer Research (2018)

Abstract Several types of bone/cartilage tumors reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. We find that the H3 lysine 36 to methionine (H3K36M) mutation, identified in &amp;gt;90% of chondroblastomas, impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases, resulting in globally diminished H3K36 methylation. Depletion of H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy H3K36M mutation. Following the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of polycomb target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas where novel K36M/I mutations in H3.1 are identified in rare pediatric cases. This abstract is also being presented as Poster A12. Citation Format: Chao Lu, Siddhant Jain, Dominik Hoelper, Denise Bechet, Leili Ran, Irene Andrulis, Brendan Dickson, Jacek Majewski, Craig Thompson, Ping Chi, Benjamin Garcia, Nada Jabado, Peter Lewis, C. David Allis. Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR12.
Narrative medicine and reflective practice among providers: Connecting personal experiences with professional action for ACP.
Authors: Leslie J. Hinyard, Cara L Wallace, Jennifer E Ohs, April Trees
Journal: Journal of Clinical Oncology (2018)

9 Background: Increasingly, Narrative Medicine (NM) is utilized in clinical experiences. Critical reflection is a core aspect of NM providing the narrative competence to “recognize, absorb, interpret, and honor” the stories of self and other. This study evaluates the effectiveness of a NM workshop to: 1) develop skills in attending and responding to the stories of others as a part of advance care planning (ACP) conversations and 2) reflect on their own stories of loss in relation to professional practice. Developing narrative skills may help overcome barriers to successful ACP with patients and families. Methods: 29 health care professionals completed a continuing education course on NM principles for end-of-life care. Workshop activities included a close reading on a professional’s story of personal loss and a reflective writing exercise sharing one’s own personal story of loss. Small groups debriefed after each exercise. 24 participants (83%) completed post-workshop surveys including closed and open-ended questions. Results: Mean age of participants was 50.3 (SD 14.7), 87% were female, and 92% White. Social workers represented 71% of the sample with clinicians across several specialty areas. Findings indicate 80% of participants strongly agreed the experience of writing about their own experiences of loss helped develop their communication skills and 88% strongly agreed the experience of listening to stories of others helped develop their communication skills and they would use skills from the workshop in practice. Common themes from qualitative analysis included the usefulness of techniques for framing difficult conversations, patient vulnerability, the importance of active listening, and increased empathy for the storyteller. Common themes reflecting on providers’ personal stories of loss included recognition of prior experience on professional interactions and reported improved skills in authentic interactions and increased capacity for empathy. Conclusions: NM competencies have the potential to enhance communication surrounding ACP. Providers find the NM approach to be a useful framework for engaging in difficult conversations about end-of-life.
Synergistic effect of cobalt chloride (CoCl2) and estrogen on hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in endometrial cancer cells in vitro
Authors: Kristin Molitoris, Armina Kazi, Robert Koos
Journal: Cancer Research (2007)

1373  Estrogen (17β-estradiol, E2) rapidly and strongly induces the expression of VEGF, a potent inducer of increased microvascular permeability and angiogenesis, in normal endometrial epithelial cells in rats in vivo. Recent work in our laboratory showed that this effect is mediated through the combined actions of estrogen receptor α (ERα) and HIF-1α, and requires the PI3K/Akt pathway [Kazi A et al., 2005; Kazi A and Koos R, 2007]. Similar to its role in normal endometrial growth, E2-induced, HIF-1α-mediated VEGF expression could contribute to the growth of endometrial carcinomas. Several studies have shown, however, that E2 induces little or no VEGF expression in ERα-positive cancer cells in vitro.One major difference between the in vitro and in vivo situations is that cultured cells are exposed to a high, non-physiological oxygen level (20%), which causes HIF-1α degradation and, consequently, abnormally weak E2 induction of VEGF expression. To determine whether restoring HIF-1α in cultured cancer cells would restore E2-induced VEGF expression, we treated human endometrial cancer cells (ECC-1) with E2 (10 nM) in the absence or presence of CoCl2 (100 :M), which inhibits oxygen-induced HIF-1α degradation. HIF-1α levels were determined using Western blots and VEGF mRNA was measured using real-time RT-PCR. HIF-1α was undetectable in untreated ECC-1 cells, and as expected, E2 treatment alone did not increase VEGF mRNA levels at 2 or 4 h in these cells. HIF-1α was readily detectable, however, in cells 2 and 4 h after of treatment with CoCl2 alone. When cells were treated with both CoCl2 and E2, there was a synergistic increase in both HIF-1α protein and VEGF mRNA levels by 2 and 4 h. As expected, this effect was blocked by the PI3K inhibitors wortmannin and LY294002. Thus, restoring HIF-1α in ECC-1 cells does unmask E2-induced VEGF expression. Interpretation of this result is complicated, however by a recent study [Chachami G et al. 2004] which showed that CoCl2 may also induce HIF-1α expression via activation of the PI3K pathway. Therefore, we treated ECC-1 cells with combinations of CoCl2 and wortmannin (100 nM) or LY294002 (50 µM) and examined HIF-1α protein and VEGF mRNA levels. PI3K inhibitors reduced the CoCl2-induced increases in both, but only by approximately half. This is consistent with CoCl2 both inhibiting HIF-1α degradation, by a mechanism that is not PI3K-dependent, and stimulating HIF-1α expression, which is PI3K-dependent. These studies shed light on the mechanism of action of CoCl2 in the regulation of HIF-1α. This will facilitate its use as a tool to study the pathways involved in the regulation of HIF-1α-dependent genes by E2, such as VEGF, that could contribute to the survival, growth and spread of cancers of the endometrium and other E2-sensitive tissues(supported by NICHD U54 Cooperative Centers Program HD36207).
The Molecular Profiling Lottery: More Accuracy, Less Precision, and No Cost
Authors: Mark J Ratain
Journal: Clinical Cancer Research (2018)

The concept of complete molecular profiling to select investigational treatment options is appealing, theoretically allowing the matching of patients to investigational drugs specifically targeted to molecular features of each patient's cancer. Although some patients do benefit from such a strategy, the vast majority do not.See related article by Tuxen et al., p. 1239.
Exposure to Secondhand Smoke and Arrhythmogenic Cardiac Alternans in a Mouse Model
Authors: Zhen Wang, Lianguo Wang, Srinivas Tapa, Kent E. Pinkerton, Chao-Yin Chen, Crystal M. Ripplinger
Journal: Environmental Health Perspectives (2018)

Background: Epidemiological evidence suggests that a majority of deaths attributed to secondhand smoke (SHS) exposure are cardiovascular related. However, to our knowledge, the impact of SHS on cardiac electrophysiology, Ca2+ handling, and arrhythmia risk has not been studied. Objectives: The purpose of this study was to investigate the impact of an environmentally relevant concentration of SHS on cardiac electrophysiology and indicators of arrhythmia. Methods: Male C57BL/6 mice were exposed to SHS [total suspended particles (THS): 3.0±0.1 mg/m3, nicotine: 0.4±0.2 mg/m3, carbon monoxide: 12.4±1.6 ppm, or filtered air (FA) for 4, 8, or 12 wk (n=4–5/group]. Hearts were excised and Langendorff perfused for dual optical mapping with voltage- and Ca2+-sensitive dyes. Results: At slow pacing rates, SHS exposure did not alter baseline electrophysiological parameters. With increasing pacing frequency, action potential duration (APD), and intracellular Ca2+ alternans magnitude progressively increased in all groups. At 4 and 8 wk, there were no statistical differences in APD or Ca2+ alternans magnitude between SHS and FA groups. At 12 wk, both APD and Ca2+ alternans magnitude were significantly increased in the SHS compared to FA group (p<0.05). SHS exposure did not impact the time constant of Ca2+ transient decay (τ) at any exposure time point. At 12 wk exposure, the recovery of Ca2+ transient amplitude with premature stimuli was slightly (but nonsignificantly) delayed in SHS compared to FA hearts, suggesting that Ca2+ release via ryanodine receptors may be impaired. Conclusions: In male mice, chronic exposure to SHS at levels relevant to social situations in humans increased their susceptibility to cardiac alternans, a known precursor to ventricular arrhythmia. https://doi.org/10.1289/EHP3664