tbuckley/cabot-search huggingface dataset:
Abstract 18811: The Influence of Early Revascularization With Percutaneous Coronary Intervention in Older Adults (≥75 years) With ST-Elevation Myocardial Infarction and Cardiogenic Shock
Authors: Abdulla A Damluji, Rahul Chaudhary, Mohammed S Al-Damluji, Mauricio G Cohen, Carol Berkower, Gary Gerstenblith, Jeremy Walston, Mauro Moscucci
Journal: Circulation (2017)

Background: Older adults (≥ 75 years) carry an increased risk of mortality after STEMI complicated by cardiogenic shock. The influence of PCI in older adults with STEMI and shock remains largely un...
Global, regional, and national burden of suicide mortality 1990 to 2016: systematic analysis for the Global Burden of Disease Study 2016
Authors: Mohsen Naghavi
Journal: BMJ (2019)

Abstract Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Evaluation of T Cell and Monocyte Immune Subsets in the Stem Cell Product of Patients Developing Engraftment Syndrome Following Autologous Stem Cell Transplantation for Multiple Myeloma and Lymphoma
Authors: Dante B. Descalzi-Montoya, Zheng Yang, Kira Goldgirsh, Rena Feinman, David S Siegel, Noa Biran, David H. Vesole, Andre Goy, Tatyana A. Feldman, Lori A. Leslie, Scott D. Rowley, Alan P Skarbnik, Phyllis McKiernan, Melissa Baker, Michele L. Donato, Robert Korngold
Journal: Blood (2018)
Abstract 19749: Cardiac-specific Deletion of Caveolin-3 Delays Repolarization and Increases Susceptibility to Ventricular Arrhythmia
Authors: Yogananda S Markandeya, Li Feng, Vignesh Ramchandran, Ravi Vaidyanathan, Jabe Best, Martin L Lea, Alexis Keefe, Matthew M Kalscheur, Thomas O’Hara, Lee L Eckhardt, Jonathan C Makielski, Natalia A Trayanova, Ravi C Balijepalli, Timothy J Kamp
Journal: Circulation (2015)

Caveolin-3 (Cav-3) is an essential scaffolding protein for formation of caveolae in muscle cells. Cav-3 is part of a macromolecular complex including several ion channels. Mutations in Cav-3 have been associated with the inherited long QT syndrome as well as a variety of skeletal myopathies. To investigate the role of Cav-3 in heart and whether loss of function of Cav-3 explains the long QT phenotype, we generated cardiac-specific, inducible Cre-lox Cav-3 knockout mice. 8 week old mice were treated with tamoxifen in the chow to induce cardiac-specific recombination. Western blot analysis and transmitted electron microscopy demonstrated a graded loss of Cav-3 and caveolae in Cav-3 KO heterozygous mice (Cav-3-/+), Cav-3 KO homozygous mice (Cav-3-/-) relative to the littermate controls mice (WT). Echocardiography revealed no significant difference in %EF, %FS, LV chamber dimensions, and LV wall thickness between the different genotypes. Histopathological examination demonstrated no significant difference in HW/BW ratio, cardiac structure or fibrosis comparing Cav-3-/- and WT mice. Telemetry ECG recordings revealed a significant increase in QTc interval Cav-3-/- (68.5±7 ms) compared to WT (54.83±6 ms). Whole cell patch clamp analysis from isolated ventricular myocytes indicated a progressive increase in action potential duration (APD) with loss of Cav-3: WT (APD50: 4.7 ± 1ms; APD90: 28.0±3 ms; n=9); Cav-3-/+(APD50: 10.3±2 ms; APD90: 42.4±3 ms; n=13), Cav-3-/- (APD50: 32.4±6ms; APD90: 97.4±7ms; n=12). Whole cell voltage clamp measurements from Cav-3-/- revealed increased late INa, decrease in ICa,L, Ito,Iss current density without altering peak INa compared to WT cells, and these current changes were adequate to explain the increased APD based on computational representation using the Morotti et al. mouse ventricular cell model. Intracardiac programmed electrical stimulation (ventricular burst pacing) induced VT/Vfib in 8 out of 9 Cav3-/- but none of WT mice (0/5). Our results demonstrate that loss of Cav-3 and caveolae in adult mice does not alter cardiac structure or contractile function but leads to prolonged APD, an increased in QTc, and increased susceptibility to ventricular arrhythmias.
Ensuring that ambulance services are used only for genuine emergencies
Authors: Vikas Wadhwa, Penny Gaskell
Journal: BMJ (2019)

Ambulance services have always been intended for those with life threatening or serious medical illness or injury.1 But over time they have been increasingly used for non-urgent and even social reasons. In natural disasters or emergencies, capacity can be so constrained as to contribute to adverse outcomes and preventable deaths. This happened in November 2016 in Melbourne, Victoria, when an …
Omega-3 fatty acids induce TGF-β1 expression in epithelial ovarian cancer
Authors: Arun Sharma, Jennifer Belna, Jennifer Logan, Jean Hurteau
Journal: Cancer Research (2005)

6091  Background: Ovarian cancer is often asymptomatic in its early stages and most patients have widespread disease at the time of diagnosis. Epithelial ovarian cancer is the most common form of ovarian cancer with a long-term survival rate of approximately 30%. Measures used to prevent this disease are somewhat invasive or have the potential for significant side effects. Omega-3 fatty acids (OM-3FAs) are a non-toxic supplement that we have previously shown to reduce the proliferative capacity of immortalized epithelial ovarian cancer cell lines accompanied with the down-regulation of pro-angiogenic molecules, such as VEGF. In this study, we show that OM-3FAs also have the ability to up-regulate the pleiotropic anti-proliferative molecule TGF-β1 in vitro. Aim: To study the effects of OM-3FAs as a possible non-toxic chemo-preventative/treatment modality for epithelial ovarian cancer through the TGF-β1 signaling pathway. Methods: 8x106 cells/T75 flask of the epithelial ovarian cancer cell lines OVCAR3, SKOV3, Hey, HeyC2, and HeyA8 were plated in appropriate culture media and incubated at 370C at 5% CO2 overnight. An OM-3FA emulsion (or control media alone) at either 100μM or 150μM was then added to corresponding flasks and incubated from 24-72 hrs at 24hr increments. An ELISA assay for TGF-β1 (RandD Systems, MN) was then performed according to manufacturer’s instructions. Results: After treatment with the OM-3FA emulsion, TGF-β1 expression was dramatically up-regulated in the following manner: Hey cell line was 7% greater than control at 24hrs and 32% greater than control at 48hrs with 150μM OM-3FAs; HeyA8 cell line was 17% greater than control at 24hrs and 33% greater than control at 48hrs with 100μM OM-3FAs; HeyC2 cell line was 8% greater than control at 48hrs and was 35% greater than control at 72hrs with 100μM OM-3FAs. SKOV3 cell line was 5% greater than control at 72hrs with 150μM OM-3FAs. TGF-β1 expression was not effected in the OVCAR3 cell line (n=3). Conclusion: OM-3FAs have recently been shown to reduce the carcinogenic potential in a number of different cancers. Although a mechanism of action has not been delineated, one know molecule, TGF-β1, acts as a key molecule for cellular growth inhibition with anti-angiogenic capabilities. By studying the effects of OM-3FA on epithelial ovarian cancer cells, we have demonstrated that OM-3FAs can induce expression of TGF-β1from 5-33% greater than a control population further limiting the growth potential of these epithelial ovarian cell lines in vitro. This data further suggests that there are definitive growth suppressive mechanisms that may play a role in the down regulation of other molecular pathways that are responsible for uncontrolled cellular proliferation. Ongoing studies will address the anti-angiogenic effects of TGF-β1 through the SMAD family of proteins and thrombospondin receptor signaling pathways.
Reply to J. Wang et al
Authors: David M. Kurtz, Florian Scherer, Michael C. Jin, Joanne Soo, Alexander F.M. Craig, Mohammad S. Esfahani, Jacob J. Chabon, Henning Stehr, Chih Long Liu, Robert Tibshirani, Lauren S. Maeda, Neel K. Gupta, Michael S. Khodadoust, Ranjana H. Advani, Aaron M. Newman, Ulrich Dührsen, Andreas Hüttmann, Michel Meignan, Olivier Casasnovas, Jason R. Westin, Mark Roschewski, Wyndham H. Wilson, Gianluca Gaidano, Davide Rossi, Maximilian Diehn, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2019)
Abstract 18705: BRCA2 is a Novel Regulator of Endothelial Cell Function and Apoptosis
Authors: Pratiek N Matkar, Wei J Cao, Mohammed Al-Omran, Subodh Verma, Howard Leong-Poi, Krishna K Singh
Journal: Circulation (2015)

Background: Germ-line mutations in the tumor suppressor gene BRCA2 (breast cancer 2, early onset) predispose carriers not only to breast cancer, but also to other cancers. BRCA2 plays crucial role in the genome integrity maintenance and is central to DNA-damage repair. BRCA2-associated DNA-damage responses are not only specific to cancer syndromes but also represent a common pathophysiological basis for diverse cardiovascular diseases (CVDs). These observations led us to hypothesize that BRCA2 is an essential regulator of endothelial function and apoptosis following genotoxic stress. Methods: To elucidate the role of BRCA2 in endothelial cells, we silenced BRCA2 in the human umbilical vein endothelial cells (ECs) and measured the indices of EC function; tube formation and proliferation, DNA-damage/repair and apoptosis by qPCR, immunoblotting and immunofluorescence following doxorubicin (Dox) treatment. Results: We confirmed the basal expression and successful silencing of BRCA2 in ECs at transcript and protein levels by qPCR and immunoblotting, respectively. Genotoxic stress in the form of Dox exacerbated DNA-damage in BRCA2-silenced ECs as evident by increased expression and activation of DNA double-stranded breaks (DSBs) marker H2A.X and reduced RAD51-foci formation, an essential regulator of DSB repair. Increased DSBs were associated with significantly increased expression and activation of p53, and increased expression of p53-upregulated modulator of apoptosis PUMA. Elevated levels of DNA-damage and p53 were further associated with significantly increased Dox-induced apoptosis in BRCA2-silenced ECs as measured by immunoblotting for cleaved-caspase-3 and TUNEL-staining.Key indices of endothelial function, including tube formation and proliferation, were significantly reduced following Dox-treatment in BRCA2-deficient ECs, which was accompanied with significantly increased expression of cell cycle inhibitor, p21 at transcript and protein levels. Conclusion: Our data for the first time, show an entirely novel role of BRCA2 as a regulator of endothelium, and provide important clues regarding a potential susceptibility of BRCA2 mutation carriers to anthracycline-induced CVDs, a cornerstone of chemotherapy for cancer.
Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell
Authors: Nazish Sayed, Mohamed Ameen, Joseph C Wu
Journal: Cardiovascular Research (2019)

Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure. Certain risk factors may predispose an individual to experiencing adverse cardiovascular effects, and when unexpected cardiotoxicity occurs, it is generally managed with supportive care. Animal models of chemotherapy-induced cardiotoxicity have provided some mechanistic insights, but the precise mechanisms by which these drugs affect the heart remains unknown. Moreover, the genetic rationale as to why some patients are more susceptible to developing cardiotoxicity has yet to be determined. Many genome-wide association studies have identified genomic variants that could be associated with chemotherapy-induced cardiotoxicity, but the lack of validation has made these studies more speculative rather than definitive. With the advent of human induced pluripotent stem cell (iPSC) technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. Furthermore, it allows us to conduct validation studies to confirm the role of genomic variants in human diseases. In this review, we discuss the role of iPSCs in modelling chemotherapy-induced cardiotoxicity.
Abstract P1-15-24: Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy
Authors: M Ramos, C Arce, F Lara, A Alvarado, N Castañeda
Journal: Cancer Research (2019)

Abstract Background: Among patients with locally advanced breast cancer (LABC), preoperative systemic treatment is the standard of care; approximately 80% of the patients treated with neoadjuvant chemotherapy present partial or complete clinical response, however there are patients who progress during this therapy or at the end of it, the tumors remain inoperable, this confers a worse prognosis, with an increase in the rates of metastasis and decrease overall survival. The benefit of concomitant chemoradiotherapy in local control is controversial. The objective of this trial is to analyze the efficacy of local control and survival in patients with locally advanced breast cancer who received systemic treatment plus chemoradiotherapy or radiotherapy alone preoperatively. Patients and Methods Prospective, randomized, open label trial; patients with LABC whom after neoadjuvant chemotherapy based con anthracyclines and taxanes have disease progression or inoperable disease. Arm A (standard) received radiotherapy (RT) 50 Gy in 25 fractions or chemoradiotherapy (CRT)(gemcitabine 100 mg/m2 plus cisplatin 30 mg/m2) weekly during radiation. The primary endpoint was local recurrence. Secondary end points included systemic recurrence, overall survival and -surgical complications. Statistical analysis was done with SPSS v 20.0, groups comparison was done with X2, survival was analyzed with Kaplan-meier method and comparison among groups with log-rank. Proportional Cox model associate clinical variables with recurrence and death. Local ethics committee approves the trial. Results: 78 patients were included, median follow-up was 116 months (110-121) at this time, 37 patients had recurrence (local, systemic or both) of which 18 were treated with CRT vs 19 RT alone (51.4 vs 44.2%, p=0.34). Higher rates of local recurrence were in RT alone 63.1% vs 38.9% with chemoradiotherapy with significance difference (p=0.004). There were no differences in disease free survival (p=0.542) and overall survival was found (p=0.303), 57.1 vs 53.5% respectively. Proportion of surgical complications were similar 71.4% for CRT vs 69.8% for RT (p=0.848). However hematological and gastrointestinal toxicity were more prevalent in patients treated with CRT p&amp;lt;0.005 Conclusion: Chemoradiotherapy it´s a feasible option to reduce the risk of local recurrence, however without any additional benefit to improve the recurrence-free survival or overall survival. Surgical complications are still the same. Citation Format: Ramos M, Arce C, Lara F, Alvarado A, Castañeda N. Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-24.
Hematopoeitic Cell Transplant - Comorbidity Index (HCT-CI) Score Is a Useful Tool for Predicting Induction Mortality and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia Patients
Authors: Neeraj Y Saini, Jan Cerny, Vanessa Furtado, Imran Puthawala, Angela Desmond, Muthalagu Ramanathan, Rajneesh Nath
Journal: Blood (2018)
Representation of Women Among Physician Authors of Perspective-Type Articles in High-Impact Dermatology Journals
Authors: Allison R. Larson, Julie A. Poorman, Julie K. Silver
Journal: JAMA Dermatology (2019)

This cross-sectional, descriptive study analyzes the number of women among physician first authors of articles published in the Journal of the American Academy of Dermatology and JAMA Dermatology across a 5-year period.
Proceedings of the British Thoracic Society. 1985 summer meeting. 3-5 July, York. Abstracts.
Authors: M Burr, J Mullins, T Merret, Nch Stott, S Ruffles, J Ayres, A Watson, H Joyce, F Holland, N Pride, Ida Johnston, S Patel, H Anderson, H Lambert, J Warner, J Banks, P Jenkins
Journal: Thorax (1985)

Asthmatics aged 15-60 years, currently receiving treatment, were identified from a register maintained by a group practice in Cardiff.Seventy-two patients were identified and may be taken to represent the spectrum of treated asthma in the community.Each patient was matched with a control, of the same age and sex, registered with the same general practitioners.Patients and controls were investigated for evidence of allergy to moulds and other allergens.Nineteen of the asthmatics (26%o) and nine of the controls (12.501o) reported visible mould on the inside walls of their homes.The commonest moulds found in the asthmatics' houses were Penicillium (13 asthmatics), Cladosporium (12), Stemphyllium (5), and Cephalosporium (4); seven other moulds were also found.Eight asthmatics and one control had a positive skin test reaction (weal 3 mm or more) to one of five moulds.IgE antibodies to common moulds were found (with RAST assay) much more frequently in the asthmatics than in the controls, often to the same moulds that were found in the corresponding houses.Exposure to visible indoor mould may be a contributory factor to the disease in a proportion of asthmatics.What are the symptoms of asthma and their importance?CMB HIGGS, P JONES, AR TANSER, G LASZLO Chest Unit, Royal United Hospital, Bath In outpatient studies of asthma it is usual to record a standard set of symptoms - cough (C), wheeze (W), tightness (T), breathlessness (B) + nocturnal waking (N), limitation of daily activity (A).But are these the symptoms of asthma, are they what patients use to judge the severity of their asthma, and does each symptom increase as asthma worsens?Fifty-six patients with asthma (31 male), aged 18-74 years, were asked, "What symptoms do you experience with your asthma?" and "Which do you use to judge the severity of your asthma?"They were then asked specifically whether they experienced and used for assessment C, W, T, B, and chest/back pain (P).The occurence of symptoms was B 95%, W 88%, T 86%, C 48%, P 36%, A 16%, N 13% plus others (panic 11%o, sputum 7%).The symptoms used to judge asthma were B 75%, T 70%, W 52%, C 30%, P 30%, A 16%, N 13% plus others (loss of inhaler response 5%, fast pulse rate 4%).Some volunteered that as asthma permitted selected children to hold and adminster their own inhalers.Only 10% of schools employed teachers with any training about asthma or other illnesses, and this usually from voluntary courses.Concern was expressed by teachers over their ignorance about asthma and its treatment, and 89%o of schools considered further information desirable.
Abstract 16808: Outcomes Following Implantable Cardioverter-Defibrillator Generator Replacement in Patients With Recovered Left Ventricular Systolic Function: Insights From the NCDR
Authors: Isac C Thomas, Yongfei Wang, VIncent Y See, Karl E Minges, Jeptha Curtis, Jonathan C Hsu
Journal: Circulation (2017)

Introduction: Some heart failure (HF) patients with a primary prevention implantable cardioverter-defibrillator (ICD) experience recovery of left ventricular (LV) systolic function by the end of their ICD generator battery life. The decision to proceed with generator replacement in this setting is informed by limited data. We sought to examine adverse outcomes following ICD generator replacement among patients with recovered LV systolic function. Methods: We studied patients undergoing primary-prevention ICD generator replacement enrolled in the NCDR ICD Registry between 2006-2009 with linked Medicare outcomes data. Using Cox regression models, we assessed the association of LV Ejection Fraction (EF) with periprocedural events as well as hospital readmission and mortality over three years of follow-up among patients with reduced (≤35%), partially-recovered (>35% and ≤50%), and recovered (>50%) LVEF. Results: Of 26,197 patients undergoing primary prevention generator replacement, 7.3% had recovered and 17....