tbuckley/cabot-search huggingface dataset:
Abstract MP58: Racial Residential Segregation is Associated With Worse Cardiovascular Health in African American Adults: The Jackson Heart Study
Authors: Sharrelle Barber, Kiarri Kershaw, Xu Wang, Mario Sims, Julianne Nelson, Ana V Diez-Roux
Journal: Circulation (2018)

Introduction: Racial residential segregation results in increased exposure to adverse neighborhood environments for African Americans; however, the impact of segregation on ideal cardiovascular health (CVH) has not been examined in large, socioeconomically diverse African American samples. Using a novel spatial measure of neighborhood-level racial residential segregation, we examined the association between segregation and ideal CVH in the Jackson Heart Study (JHS). Hypothesis: Racial residential segregation will be associated with worse cardiovascular health among African American adults. Methods: The sample included 4,354 men and women ages 21-93 from the baseline exam of the JHS (2000-2004). Racial residential segregation was assessed at the census-tract level. Data on racial composition (% African American) from the 2000 US Census was used to calculate the local G i * statistic- a spatially-weighted z-score that represents how much a neighborhood’s racial/ethnic composition deviates from the larger metropolitan area. Ideal CVH was assessed using the AHA Life’s Simple Seven (LS7) index which includes 3 behavioral (nutrition, physical activity, and smoking) and 4 biological (systolic BP, glucose, BMI, and cholesterol) metrics of CVH. Multivariable regression models were used to test associations between segregation and the LS7 index continuously (range: 0-14) and categorically (Inadequate: 0-4; Average: 5-9; and Optimal: 10-14). Covariates included age, sex, income, education, and insurance status. Results: The average LS7 summary score was 7.03 (±2.1) and was lowest in the most racially segregated neighborhood environments (High Segregation: 6.88 ±2.1 vs. Low Segregation: 7.55 ±2.1). The prevalence of inadequate CVH was higher in racially segregated neighborhoods (12.3%) compared to neighborhoods that were the least segregated (6.9%). After adjusting for key socio-demographic characteristics, racial residential segregation was inversely associated with ideal CVH (B=-0.041 ±0.02, p=0.0146). Moreover, a 1-SD unit increase in segregation was associated with a 6% increased odds of having inadequate CVH (OR: 1.06, 95% CI: 1.00-1.12, p=0.0461). Conclusion: In conclusion, African Americans in racially segregated neighborhoods are less likely to achieve ideal CVH even after accounting for individual-level factors. Policies aimed at restricting housing segregation/discrimination and/or structural interventions designed to improve neighborhood environments may be viable strategies to improving CVH in this at-risk population.
Abstract 15782: Heart Failure Following Myocardial Infarction: Risk Factors and Trends in Incidence
Authors: Jennifer Wellings, Davit Sargsyan, John B Kostis, Jeanne M Dobrzynski, William J Kostis
Journal: Circulation (2016)

Introduction: Application of new therapeutic modalities have resulted in a decrease in the mortality rate following myocardial infarction (MI), but heart failure (HF) remains a frequent complicatio...
Efficacy and safety of Her2-targeted chimeric antigen receptor (CAR) T cells using MyD88/CD40 costimulation and iCaspase-9 suicide switch.
Authors: Aaron E Foster, Jeannette Crisostomo, Peter Chang, Pei-Yi Lin, Aruna Mahendravada, An Lu, Mariam Khalil, Sunandan Saha, Kevin Mark Slawin, David M Spencer
Journal: Journal of Clinical Oncology (2016)

3050 Background: Efficacy of chimeric antigen receptor T cells (CAR-T) is dependent on their in vivo survival and expansion following adoptive transfer. Here, we show that constitutive expression of the MyD88/CD40 (MC) fusion protein dramatically enhances CAR-T proliferation resulting in improved antitumor efficacy against Her2+ solid tumors. Importantly, CAR-T cell levels and cytokine-related toxicity can be controlled by graduated administration of rimiducid to activate the inducible iCaspase-9 (iC9) suicide gene without detriment to tumor control. Methods: T cells were modified with a tricistronic retrovirus encoding iC9, a Her2-specific CAR (Her2.ζ) and constitutively active MC (iC9-Her2.ζ-MC), or control vectors (iC9-Her2.ζ and iC9-Her2.CD28.ζ) and compared for cytotoxicity, cytokine production and proliferation in coculture assays against Her2+ breast (SK-BR-3), ovarian (A2780, SKOV-3), gastric (N87, Kato III, SNU-1) and pancreatic (HPAC) cancer cell lines. CAR-T efficacy was assessed in NSG mice engrafted with tumor cell lines followed by i.t. or i.v. injection of T cells. Rimiducid was given i.p. at 0.5 mg/kg. Results: Her2-redirected T cells showed that in vitro, MC costimulation resulted in increased IL-2 production ( > 65-fold compared to iC9-Her2.CD28.ζ) which corresponded to enhanced proliferation and tumor elimination. In tumor xenograft models, iC9-Her2.ζ-MC CAR-T cells were more effective at eliminating large Her2+ tumors compared to conventional CAR-T constructs (Her2.ζ and Her2.28.ζ). Bioluminescent imaging also showed robust engraftment and proliferation of CAR-T cells co-expressing MC. Importantly, cytokine-related toxicity could be completely resolved while maintaining anti-tumor efficacy by partial elimination of iC9-Her2.ζ-MC CAR-T cells through systemic administration of rimiducid. Conclusions: MC represents a broadly applicable, potent T cell costimulatory signaling molecule in CAR-T cells, resulting in higher IL-2 production, improved survival and greater proliferative capacity. CARs containing MC demonstrate enhanced efficacy in vivo while retaining the safety profile through the iC9 suicide gene.
Pure β-ParticleEmitting Stents Inhibit Neointima Formation in Rabbits
Authors: ChristophHehrlein, MarcStintz, RalfKinscherf, KlausSchlösser, EhrhardHuttel, LudwigFriedrich, PeterFehsenfeld, WolfgangKübler
Journal: Circulation (1996)

Background Considerable experimental evidence exists that neointimal hyperplasia after angioplasty is inhibited by γ-irradiation of the treated arteries. A β-particle radiation is absorbed in tissue within a shorter distance away from the source than γ-radiation and may be more suitable for localized vessel irradiation. This study outlines a method to implant a β-particle–emitting radioisotope (32P; half-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventional stents in a rabbit model. Methods and Results 32P was produced by irradiation of red amorphous phophorus (31P) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept apart from 31P in a mass separator. The radioisotope was tightly fixed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 μCi were chosen for the study. Four and 12 weeks after placement of conventio...
FRI0522 Vitamin d supplementation improves depression in knee osteoarthritis patients over 24 months
Authors: S. Zheng, L. Tu, F. Cicuttini, W. Han, Z. Zhu, B. Antony, A. Wluka, T. Winzenberg, D. Aitken, L. Blizzard, G. Jones, C. Ding
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although depression is prevalent in osteoarthritis (OA) patients and the positive association between vitamin D deficiency and depression has been demonstrated, no study has examined the effect of vitamin D supplementation on depression in OA patients. <h3>Objectives</h3> To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depression in patients with knee OA and vitamin D deficiency. <h3>Methods</h3> Participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 50,000IU vitamin D<sub>3</sub> (n=209) or placebo (n=204) monthly for 24 months. Serum 25-hydroxyvitamin D [25(OH)D] was measured at baseline, month 3 and 24. Depression was measured using the patient health questionnaire (PHQ-9), and knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) at baseline, month 3, 6, 12 and 24. Multilevel mixed-effect models were used to estimate the association between exposures and outcomes adjusting for potential confounders. <h3>Results</h3> Over 24 months, 340 participants (82.3% retention rate) completed the study. The prevalence and incidence of depression were 25.4% and 11.2%, respectively. Depression improved more in the vitamin D supplementation group (β: −0.45, 95% CI: −0.84 to −0.07) compared to the placebo group (β: 0.21, 95% CI: −0.19 to 0.61) (p<i>=</i>0.02) and in those participants who maintained vitamin D sufficiency (β: −0.44, 95% CI: −0.88 to −0.00) compared to those who did not maintain sufficiency (β: 0.40, 95% CI: −0.18 to 0.97) (p=0.02) over 24 months. <h3>Conclusions</h3> These findings suggest that vitamin D supplementation and maintaining sufficient vitamin D levels over 24 months may have beneficial effects on depression in patients with knee OA. <h3>References</h3> [1] Stubbs B, Aluko Y, Myint PK, et al. Prevalence of depressive symptoms and anxiety in osteoarthritis: a systematic review and meta-analysis. Age Ageing2016;45(2):228–35. doi:10.1093/ageing/afw001 [2] Anglin RE, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry2013;202:100–7. doi:10.1192/bjp.bp.111.106666 <h3>Acknowledgements</h3> We specially thank the participants who made this study possible, and we gratefully acknowledge the role of Vitamin D Effect on Osteoarthritis Study staff and volunteers in collecting the data. <h3>Disclosure of Interest</h3> None declared
Patterns of healthcare utilisation for respiratory complications of adults with neuromuscular disease: a population study
Authors: Louise Rose, Douglas McKim, David Leasa, Mika Nonoyama, Anu Tandon, Yu Qing Bai, Reshma Amin, Sherri Katz, Roger Goldstein, Andrea Gershon
Journal: European Respiratory Journal (2018)

Our objective was to quantify health service utilisation including monitoring and treatment of respiratory complications for adults with neuromuscular disease (NMD), identifying practice variation and adherence to guideline recommendations at a population level.We conducted a population-based longitudinal cohort study (2003-2015) of adults with NMD using hospital diagnostic and health insurance billing codes within administrative health databases.We identified 185 586 adults with NMD. Mean age 52 years, 59% female. 41 173 (22%) went to an emergency department for respiratory complications on average 1.6 times every 3 years; 14 947 (8%) individuals were admitted to hospital 1.4 times every 3 years. Outpatient respiratory specialist visits occurred for 64 084 (35%) with four visits every 3 years, although substantial variation in visit frequency was found. 157 285 (85%) went to the emergency department (all-cause) almost 4 times every 3 years, 100 052 (54%) were admitted to hospital. Individuals with amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) had more emergency department visits compared with other types of NMD (p<0.0001).One-third of adults with NMD received respiratory specialist care at a frequency recommended by professional guidelines, although substantial variation exists. Emergent healthcare utilisation was substantial, emphasising the burden of NMD on the healthcare system and urgent need to improve community and social supports, particularly for ALS/MND patients.
Cross-genetic determination of maternal and neonatal immune mediators during pregnancy
Authors: Michela Traglia, Lisa A. Croen, Karen L. Jones, Luke S. Heuer, Robert Yolken, Martin Kharrazi, Gerald N. DeLorenze, Paul Ashwood, Judy Van de Water, Lauren A. Weiss
Journal: Genome Medicine (2018)

The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.
Pain distress: the negative emotion associated with procedures in ICU patients
Authors: Kathleen A. Puntillo, Adeline Max, Jean-Francois Timsit, Stephane Ruckly, Gerald Chanques, Gemma Robleda, Ferran Roche-Campo, Jordi Mancebo, Jigeeshu V. Divatia, Marcio Soares, Daniela C. Ionescu, Ioana M. Grintescu, Salvatore Maurizio Maggiore, Katerina Rusinova, Radoslaw Owczuk, Ingrid Egerod, Elizabeth D. E. Papathanassoglou, Maria Kyranou, Gavin M. Joynt, Gaston Burghi, Ross C. Freebairn, Kwok M. Ho, Anne Kaarlola, Rik T. Gerritsen, Jozef Kesecioglu, Miroslav M. S. Sulaj, Michelle Norrenberg, Dominique D. Benoit, Myriam S. G. Seha, Akram Hennein, Fernando J. Pereira, Julie S. Benbenishty, Fekri Abroug, Andrew Aquilina, Julia R. C. Monte, Youzhong An, Elie Azoulay
Journal: Intensive Care Medicine (2018)
The biological significance of histone modifiers in multiple myeloma: clinical applications
Authors: Hiroto Ohguchi, Teru Hideshima, Kenneth C. Anderson
Journal: Blood Cancer Journal (2018)

Multiple myeloma (MM) is a clonal plasma cell disorder that is characterized by a variety of genetic alterations. Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non-coding RNAs in the biology of MM. Post-translational modifications of histone, such as methylation and acetylation, contribute to chromatin dynamics, and are modulated by histone modifying enzymes, and dysregulation of these enzymes is implicated in the pathogenesis of cancers, including MM. Histone modifiers also have non-histone substrates and enzymatically independent roles, which are also involved in tumorigenesis. Here we review and provide comprehensive insight into the biologic significance of histone methyl- and acetyl-modifiers in MM, and further provide an overview of the clinical applications of histone modifier inhibitors, especially histone deacetylase inhibitors. These findings underline the emerging roles of histone modifiers in the pathogenesis of MM, and further highlight the possibility of novel epigenetic therapies in MM.
Global Impact of 2017 American Heart Association/American College of Cardiology Hypertension Guidelines
Authors: Kazuomi Kario
Journal: Circulation (2018)

he 2017 American Heart Association/American College of Cardiology (AHA/ ACC) guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults were recently released. 1The core concept in these guidelines is earlier and tighter BP control over 24 hours, with the aim of providing more sustained target organ protection and cardiovascular disease prevention.These guidelines lower the threshold of hypertension diagnosis and target BP levels to 130/80 mm Hg.This direction of strict BP control with a new definition and universal target goal for hypertension will be the topic of debate among the guideline developing committee members of the Japanese Society of Hypertension. 2
Algorithms for left atrial wall segmentation and thickness – Evaluation on an open-source CT and MRI image database
Authors: Rashed Karim, Lauren-Emma Blake, Jiro Inoue, Qian Tao, Shuman Jia, R. James Housden, Pranav Bhagirath, Jean-Luc Duval, Marta Varela, Jonathan M. Behar, Loïc Cadour, Rob J. van der Geest, Hubert Cochet, Maria Drangova, Maxime Sermesant, Reza Razavi, Oleg Aslanidi, Ronak Rajani, Kawal Rhode
Journal: Medical Image Analysis (2018)

Structural changes to the wall of the left atrium are known to occur with conditions that predispose to Atrial fibrillation. Imaging studies have demonstrated that these changes may be detected non-invasively. An important indicator of this structural change is the wall's thickness. Present studies have commonly measured the wall thickness at few discrete locations. Dense measurements with computer algorithms may be possible on cardiac scans of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The task is challenging as the atrial wall is a thin tissue and the imaging resolution is a limiting factor. It is unclear how accurate algorithms may get and how they compare in this new emerging area. We approached this problem of comparability with the Segmentation of Left Atrial Wall for Thickness (SLAWT) challenge organised in conjunction with MICCAI 2016 conference. This manuscript presents the algorithms that had participated and evaluation strategies for comparing them on the challenge image database that is now open-source. The image database consisted of cardiac CT (n=10) and MRI (n=10) of healthy and diseased subjects. A total of 6 algorithms were evaluated with different metrics, with 3 algorithms in each modality. Segmentation of the wall with algorithms was found to be feasible in both modalities. There was generally a lack of accuracy in the algorithms and inter-rater differences showed that algorithms could do better. Benchmarks were determined and algorithms were ranked to allow future algorithms to be ranked alongside the state-of-the-art techniques presented in this work. A mean atlas was also constructed from both modalities to illustrate the variation in thickness within this small cohort.
Abstract 11405: The Association of Co-Morbid Symptoms of Depression and Anxiety With All-Cause Mortality in Patients With Heart Failure
Authors: Abdullah Alhurani, Rebecca Dekker, Mona Abed, Amani Khalil, Kyoung Suk Lee, Gia Mudd-Martin, Martha Biddle, Terry Lennie, Debra K Moser
Journal: Circulation (2014)

Introduction: Depression or anxiety are associated with survival in heart failure (HF); however, whether co-morbid symptoms of anxiety and depression are associated with survival in patients with HF is unknown. Hypothesis: Co-morbid symptoms of depression and anxiety are more strongly associated with all-cause mortality in patients with HF compared to those with anxiety or depression alone. Methods: A total of 1,260 HF patients participated and were followed for mortality outcomes for 12 months. The Patient Health Questionnaire (PHQ-9) and Brief Symptom Inventory-anxiety subscale (BSI) were used to measure symptoms of depression and anxiety. Cox regression analysis was used to determine whether co-morbid symptoms of depression and anxiety independently predicted all-cause mortality controlling for age,gender, ethnicity, and NYHA class. Depression and anxiety were treated first as continuous level variables, then as categorical variables using standard published cut points. Patients were divided into four groups based on the presence of anxiety and depression symptoms: 1) neither anxiety nor depression, 2) depression alone, 3) anxiety alone, and 4) co-morbid depression and anxiety Results: When entered as continuous variables, the interaction between anxiety and depression (HR 1.02; 95% CI: 1.01-1.03; p = 0.002) was a significant predictor of all-cause mortality. When entered as a categorical variable, co-morbid symptoms of depression and anxiety (versus the other three groups) independently predicted all-cause mortality (HR 2.59; 95% CI: 1.49-4.49; p = 0.001). Conclusions: To improve mortality outcomes in patient with HF, attention must be paid by healthcare providers to the assessment and management of co-morbid symptoms of depression and anxiety.
Abstract 15736: Nasal Nitric Oxide and Systemic Nitric Oxide Reserve Stratification of Surgically Palliated Congenital Heart Disease
Authors: Phillip S Adams, Caroline Hogan, Nicholas Krehel, Maliha Zahid, Omar Khalifa, Cameron Dezfulian, Cecilia W Lo
Journal: Circulation (2017)

Introduction: Nitric oxide (NO) plays an important role in vasoregulation. Oxygen is both a substrate for NO production and a determinant of the half-life of nitrite (pNO2-), a vascular storage for...
Early vs deferred endovenous ablation reduced time to ulcer healing in venous leg ulcers with varicose veins
Authors: Alexander Gallus
Journal: Annals of Internal Medicine (2018)

ACP Journal Club21 August 2018Early vs deferred endovenous ablation reduced time to ulcer healing in venous leg ulcers with varicose veinsAlexander Gallus, MB BS, FRACP, FRCP(C)Alexander Gallus, MB BS, FRACP, FRCP(C)Flinders University and Medical Center, Adelaide, South Australia, Australia (A.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-4-018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGohel MS, Heatley F, Liu X, et al; EVRA Trial Investigators. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14. https://pubmed.ncbi.nlm.nih.gov/29688123Clinical Impact RatingsGIM/FP/GP: Dermatology: References1 Nelzén O. Fifty percent reduction in venous ulcer prevalence is achievable—Swedish experience. J Vasc Surg. 2010;52:39S-44S. [PMID: 21069938] Google Scholar2 Singer AJ, Tassiopoulos A, Kirsner RS. Evaluation and management of lower-extremity ulcers. N Engl J Med. 2017;377:1559-67. [PMID: 29045216] Google Scholar3 Lal BK. Venous ulcers of the lower extremity: definition, epidemiology, and economic and social burdens. Semin Vasc Surg. 2015;28:3-5. [PMID: 26358303] Google Scholar4 Gohel MS, Barwell JR, Taylor M, et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ. 2007;335:83. [PMID: 17545185] Google Scholar Author, Article, and Disclosure InformationAffiliations: Flinders University and Medical Center, Adelaide, South Australia, Australia (A.G.)This article was published at Annals.org on 7 August 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA retrospective cohort study comparing two treatments for active venous leg ulcers 21 August 2018Volume 169, Issue 4Page: JC18KeywordsPatientsPregnancyQuality of lifeQuestionnairesRandomized trialsResearch assessmentSkin graftingUlcersUltrasound imagingVeins ePublished: 21 August 2018 Issue Published: 21 August 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...