tbuckley/cabot-search huggingface dataset:
Abstract P084: Racial Variation in Stroke Risk by Stroke Risk Factors
Authors: Monik C Jimenez, JoAnn E Manson, Nancy Cook, Ichiro Kawachi, Sylvia Wassertheil-Smoller, Bernhard Haring, Rami Nassir, Jinnie J Rhee, Shawnita Sealy-Jefferson, Kathryn M Rexrode
Journal: Circulation (2017)

Background: Black American adults exhibit a greater risk of stroke and disproportionate burden of stroke risk factors; however, it is unclear whether these stroke risk factors differentially impact stroke risk by race. Methods: In total, 126,018participants of the Women’s Health Initiative (11,389 black women and 114,629 white women), free of stroke and coronary heart disease at baseline (1993-1998), were followed for up to 17 years through 2010. Participants completed baseline clinical exams with standardized measurements of blood pressure and anthropometrics, medication inventory and self-reported questionnaires on socio-demographic, lifestyle/behaviors, diet and medical history. Incident total strokes were updated annually by questionnaire and confirmed by medical records. Multivariable Cox models estimated racial disparities in stroke overall and by across stroke risk factors. Results: We observed 4,344 stroke events over 1,496,314 person-years (py). In age-adjusted analyses, black women exhibited a 47% greater risk of total stroke compared to white women (hazard ratio [HR]=1.47, 95% CI: 1.33-1.63), which was attenuated toward the null (HR=1.05, 95% CI: 0.94-1.17) by further adjustment for stroke risk factors, which may be considered to be on the biological causal pathway. Disparities in stroke were two-fold higher for younger black (50-&lt;60 years) compared to white women, with an incidence rate difference (RD) of 119/100,000 py. These disparities remained statistically significant after adjustment for stroke risk factors. For those 60-&lt;70 years, the risk of stroke was 34% higher among black compared to white women, with a RD of 81/100,000 py No significant variation by other stroke risk factors was observed. Conclusions: Black women exhibited a significantly greater risk of total stroke compared to white women. Importantly, racial disparities were greatest among younger women aged 50-&lt;60 years. Interventions targeted at younger black women may provide the greatest benefit in reducing disparities.
Abstract P225: The Associations of Dietary and Biomarkers of Linoleic Acid Intake and All-cause and Cardiovascular Mortality: A Systematic Review and Meta-analysis
Authors: Jun Li, Marta Guasch-Ferré, Yanping Li, Frank Hu
Journal: Circulation (2018)

Background: Previous studies on intake of linoleic acid (LA), a predominant n-6 fatty acid, and risk of mortality from all-cause and cardiovascular disease (CVD) have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of LA and all-cause and CVD mortality. Methods: We searched MEDLINE and EMBASE databases through June 2017 for prospective cohort studies reporting association of LA (assessed by dietary survey or biomarker in blood or adipose tissue) with all-cause and CVD mortality. In addition, unpublished data from pooling projects were included. We pooled the multivariate-adjusted Hazards ratios (HRs) using random-effect meta-analysis, which allowed for between-study heterogeneity. Results: 27 studies covering 37 prospective cohorts were identified; these included 274,565 individuals with dietary assessment (34,597 all-cause and 10,636 CVD deaths) and 54,794 individuals with biomarker measurements (6,767 all-cause and 5,311 CVD deaths). Comparing the highest category with the lowest, dietary LA intake was associated with a 14% lower risk of all-cause mortality (95% confidence interval [CI], 2%-25%, I 2 =71%) and a 20% lower risk of CVD mortality (95% CI, 13%-26%, I 2 =0). Baseline health status (i.e. general population, CVD/high risk for CVD, or cancer) might be a main source of heterogeneity for the association of dietary LA intake with all-cause mortality. As for biomarkers, 1 SD increment in LA was associated with a 9% lower risk of all-cause mortality (95% CI, 4%-14%, I 2 =61%) and a 10% lower risk of CVD mortality (95% CI, 5%-14%, I 2 =13%). Heterogeneity was presented across tissue types and between genders. Conclusions: In prospective cohort studies, LA intake, assessed by either dietary survey or biomarkers, was inversely associated with all-cause and CVD mortality in a dose-response manner. These data support the current recommendations on polyunsaturated fat intake for prevention of CVD and early death.
Abstract 11709: Klotho, Fibroblast Growth Factor-23, and the Renin-Angiotensin System - An Analysis From the PEACE Trial
Authors: Brian A Bergmark, Jacob A Udell, David A Morrow, Petr Jarolim, Julia F Kuder, Scott D Solomon, Marc A Pfeffer, Eugene Braunwald, Marc S Sabatine
Journal: Circulation (2017)

Introduction: Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system. Hypotheses: Low Klotho concentra...
Single-cell analyses demonstrate that a heme–GATA1 feedback loop regulates red cell differentiation
Authors: Raymond T. Doty, Xiaowei Yan, Christopher Lausted, Adam D. Munday, Zhantao Yang, Danielle Yi, Neda Jabbari, Li Liu, Siobán B. Keel, Qiang Tian, Janis L. Abkowitz
Journal: Blood (2018)
Harnessing copper in cancer to enhance anti-tumor immune response
Authors: F. Voli, L. Lerra, K. Kimpton, F. Saletta, G. Cirillo, M. Kavallaris, O. Vittorio
Journal: Annals of Oncology (2018)

Background: Copper is elevated in tumors and the use of copper-chelating agents is under intense investigation. It has been reported that copper plays a key role in the immune system, but its activity is unclear. Recent advances in immunotherapies have shown great potential for treating several cancers. However, tumors express molecules, such as the Programmed Death Ligand 1 (PD-L1), to prevent immune cell activity. Several anti PD-1/PD-L1 therapies have been approved by the FDA, but concerns have been raised about their safety. Therefore, there is a need for different approaches to target this pathway. Methods: Experiments were performed in 3 neuroblastoma (NB) cell lines SK-N-FI, SH-SY5Y, SK-N-BE(2)C and 2 glioblastoma (GBM) cell lines U87MG, MO59J. PD-L1, T cells markers and Copper transporter1 (CTR1) protein levels were determined using western blot and flow cytometry. Intracellular copper was measured by ICP-MS analysis. In vivo activity of copper-targeting drugs was assessed in NB syngeneic mouse models. Results: Tissue microarrays from NB and GBM patient tumors showed a significant correlation between CTR1 and PD-L1 expression (p = 0.00014 & p = 0.012, respectively). Suppression of CTR1 using siRNAs caused a decrease of intracellular copper which in turn led to a downregulation of PD-L1 expression in NB cells, whereas, addition of copper into the media clearly induced PD-L1 mRNA and protein upregulation. Dextran-Catechin (DC) and TEPA, drugs dysregulating copper homeostasis, downregulated PD-L1 expression in both NB and GBM cells. In vivo studies showed that DC prolonged mouse survival by decreasing tumor size in the NB mouse model. Ex vivo immunohistochemistry staining confirmed that downregulation of CTR1 is associated with reduced PD-L1 expression. In addition, DC treatments showed an increase of tumor-infiltrating CD4+ and CD8+ lymphocytes and activated NK cells in the NB immune-competent mouse model. Conclusions: There is a strong association between PD-L1 expression and intracellular copper levels. Copper dysregulating agents reduce PD-L1 in vitro and in vivo and in turn, promote a significant increase of tumor-infiltrating lymphocytes. This study highlights the potential to enhance tumor immune surveillance by targeting intracellular copper levels. Legal entity responsible for the study: Children's Cancer Institute Australia. Funding: The National Health and Medical Research Council (NHMRC). Disclosure: All authors have declared no conflicts of interest.
Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study
Authors: Savino Sciascia, Jinoos Yazdany, Maria Dall'Era, Roberta Fenoglio, Massimo Radin, Ishita Aggarwal, Maria J Cuadrado, Karen Schreiber, Antonella Barreca, Mauro Papotti, Dario Roccatello
Journal: Annals of the Rheumatic Diseases (2018)

The management of lupus nephritis (LN) and concomitant thrombotic microangiopathy (TMA), with or without antiphospholipid antibodies (aPL), remains controversial, and few studies are available to inform clinical management.1–4 

The purpose of this multicentre retrospective study was to analyse the impact of anticoagulation (vitamin K antagonists (VKAs) and/or heparins) in addition to conventional immunosuppression on kidney outcomes (assessed at 12 months, according to the Kidney Disease: Improving Global Outcomes-KDIGOguidelines5) in patients with biopsy-proven LN and concomitant TMA.

Data source, population and statistical analysis are detailed in the online supplementary material 1. Anticoagulation was considered if given for at least three consecutive months after TMA diagnosis.### Supplementary data

[annrheumdis-2018-214559supp002.docx] 

We retrospectively identified 97 patients with biopsy-proven LN and TMA (2007–2017). See online supplementary table 1 for clinical and demographic characteristics. Laboratory parameters were collected at the time of the biopsy. The mean age of patients was 38.9±15.2 years (13–69) and 85 females (87.6%). Most had proliferative LN (class …
Rendezvous within biloma technique combining percutaneous and endoscopic approaches: a novel biliary recanalization method
Authors: Ayana Okamoto, Kosuke Minaga, Mamoru Takenaka, Tomoe Yoshikawa, Toshimitsu Iwasaki, Masakatsu Tsurusaki, Masatoshi Kudo
Journal: Endoscopy (2018)

Biliary injury and biloma are complications that can occur with hepatobiliary surgery [1]. Endoscopic or percutaneous recanalization for postoperative biliary injury have been reported as minimally invasive treatments [2], but remains challenging for severe biliary stricture [3] [4] [5]. Here, we present a case of biliary injury successfully treated by combining endoscopic and percutaneous approaches within the biloma.
Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12
Authors: Christopher S. Garris, Sean P. Arlauckas, Rainer H. Kohler, Marcel P. Trefny, Seth Garren, Cécile Piot, Camilla Engblom, Christina Pfirschke, Marie Siwicki, Jeremy Gungabeesoon, Gordon J. Freeman, Sarah E. Warren, SuFey Ong, Erica Browning, Christopher G. Twitty, Robert H. Pierce, Mai H. Le, Alain P. Algazi, Adil I. Daud, Sara I. Pai, Alfred Zippelius, Ralph Weissleder, Mikael J. Pittet
Journal: Immunity (2018)
A randomized trial of telephone versus in-person disclosure of BRCA 1/2 results.
Authors: Angela R. Bradbury, Linda J. Patrick-Miller, Brian Egleston, Kyle Smith, Dominique Fetzer, Andrea Forman, Lisa Bealin, Christina Rybak, Kim Rainey, Carol Cherry, Susan Montgomery, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2013)

1538 Background: While some providers use telephone to share genetic test results, there is limited data on the efficacy and impact on patient cognitive and emotional responses. Methods: Patients who completed in-person genetic counseling for BRCA 1/2 testing were randomized to telephone (TD) or in-person (IPD) disclosure. Baseline (BL) and post-disclosure (PD) surveys assessed knowledge, satisfaction and psychological factors. We used T-tests and multiple linear regressions. Results: 179 patients (68% of approached),126 (72%) agreed to be randomized; 36 (28%) declined randomization (Self-select IPD). Patient characteristics did not differ between arms. Change in knowledge, satisfaction and psychological factors did not differ between TD and IPD (Table). Self-select IPD participants had greater declines in depression and state anxiety (Table). In multivariable models, history of cancer was associated with greater declines in general anxiety (coef -1.4, p=0.01). BRCA+ results were associated with greater increases in knowledge (coef 3.2, p 0.02) and state anxiety (coef 12.0, p&lt;0.01), and declines in satisfaction (coef -6.6, p&lt;0.01). Having a mutation in the family was associated with greater declines in intrusive thoughts (coef -4.8, p&lt;0.01). Conclusions: In general,telephone disclosure of BRCA1/2 results does not appear to negativelyimpact psychological outcomes but outcomes among carriers (BRCA+) differ. Larger studies are needed to understand the impact among subgroups and more diverse populations. Some patients preferred in-person communication and had different outcomes, suggesting more data is needed before telephone disclose is universally adopted. [Table: see text]
Abstract 17668: Heart Failure Epidemiology, Risk Factors and Mortality Risk by Gender in Community Cohorts Across Europe
Authors: Christina Magnussen, Teemu Niiranen, Francisco M Ojeda, Francesco Gianfagna, Stefan Blankenberg, Inger Njølstad, Erkki Vartiainen, Susana Sans, Gerard Pasterkamp, Simona Costanzo, Maria Benedetta Donati, Pekka Jousilahti, Allan Linneberg, Tarja Palosaari, Giovanni de Gaetano, Martin Bobak, Hester M den Ruijter, Ellisiv Mathiesen, Torben Jørgensen, Stefan Söderberg, Kari Kuulasmaa, Tanja Zeller, Veikko Salomaa, Licia Iacoviello, Renate B Schnabel
Journal: Circulation (2017)

Introduction: Heart failure (HF) is a global epidemic that is common in aging populations. Hypothesis: There are gender differences in HF epidemiology and risk. Methods: In N=78,877 individuals wit...
Abstract 1623: Coronary Angiodysplasia Associated With Hypertrophic Cardiomyopathy
Authors: Andrea Frustaci, Cristina Chimenti, Giuseppe Critelli, Matteo A Russo, Iacopo Olivotto, Franco Cecchi
Journal: Circulation (2007)

Background :Coronary Angiodysplasia (CA) is a rare congenital anomaly. Its prevalence as well as histological and clinical implications in Hypertrophic Cardiomyopathy (HCM) are unknown. Methods and...
Palliative care for patients with pulmonary fibrosis: symptom relief is essential
Authors: Kathleen Lindell, Ganesh Raghu
Journal: European Respiratory Journal (2018)

<b>Patients with PF-ILD suffer from heavy symptom burden and poor quality of life. Early use of opioids and low dose BDZ in severely ill patients with respiratory comprise may lead to improved symptom control and quality of life for this patient group.</b>http://ow.ly/x50e30mJ6ko
Blinding and Patient-Reported Outcome Completion Rates in US Food and Drug Administration Cancer Trial Submissions, 2007–2017
Authors: Jessica K Roydhouse, Bellinda L King-Kallimanis, Lynn J Howie, Harpreet Singh, Paul G Kluetz
Journal: JNCI Journal of the National Cancer Institute (2018)

Patient-reported outcomes (PROs) are commonly included in submissions to the United States Food and Drug Administration (FDA). Open-label designs are frequent in cancer trials. Between-arm differences in PRO missingness may affect results. We sought to compare PRO completion rates between study arms in randomized open-label and double-blind cancer trials.Randomized, controlled trials for oncology and malignant hematology products submitted to the FDA in fiscal years 2007-2017 were identified using internal FDA databases. Applicant study reports were reviewed to assess PRO use and reporting of completion rates. Completion rates were collected for each PRO and compared between arms. Results were summarized using descriptive statistics.Ninety-six trials for anticancer products from 2007 to 2017 contained PROs. Fifty-one (53.1%) were randomized, controlled trials with useable information on PRO completion. The median completion rate for investigational arms was 89.7% (range = 33.7-100.0%) and 88.2% (range = 11.0-100.0%) for control arms. At six months, seven double-blind trials had gaps of at least 10% in at least one PRO between arms; in four trials, these gaps favored the control arm (median difference = 11.5%, range = 10.0-17.0%). For open-label trials, four trials had such gaps, all of which favored the investigational arm (median difference = 28.5%, range = 10.0-69.0%).Among trials that provided interpretable PRO completion information, completion rates were high. Most trials had comparable completion rates between arms. However, when large between-arm completion rate differences existed, differences favoring the experimental arm were more common in open-label trials compared with double-blind trials. Procedures must be put in place to improve reporting of PRO completion and reduce missingness, particularly in open-label trials.
Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy
Authors: Man Kyu Shim, Jooho Park, Hong Yeol Yoon, Sangmin Lee, Wooram Um, Jong-Ho Kim, Sun-Woong Kang, Joung-Wook Seo, Soo-Wang Hyun, Jae Hyung Park, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim
Journal: Journal of Controlled Release (2018)
Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases
Authors: Ashton A. Connor, Robert E. Denroche, Gun Ho Jang, Mathieu Lemire, Amy Zhang, Michelle Chan-Seng-Yue, Gavin Wilson, Robert C. Grant, Daniele Merico, Ilinca Lungu, John M.S. Bartlett, Dianne Chadwick, Sheng-Ben Liang, Jenna Eagles, Faridah Mbabaali, Jessica K. Miller, Paul Krzyzanowski, Heather Armstrong, Xuemei Luo, Lars G.T. Jorgensen, Joan M. Romero, Prashant Bavi, Sandra E. Fischer, Stefano Serra, Sara Hafezi-Bakhtiari, Derin Caglar, Michael H.A. Roehrl, Sean Cleary, Michael A. Hollingsworth, Gloria M. Petersen, Sarah Thayer, Calvin H.L. Law, Sulaiman Nanji, Talia Golan, Alyssa L. Smith, Ayelet Borgida, Anna Dodd, David Hedley, Bradly G. Wouters, Grainne M. O'Kane, Julie M. Wilson, George Zogopoulos, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger
Journal: Cancer Cell (2019)
Extracellular vesicles enhance the targeted delivery of immunogenic oncolytic adenovirus and paclitaxel in immunocompetent mice
Authors: M. Garofalo, A. Villa, N. Rizzi, L. Kuryk, B. Rinner, V. Cerullo, M. Yliperttula, V. Mazzaferro, P. Ciana
Journal: Journal of Controlled Release (2018)
Mast cell chymase degrades fibrinogen and fibrin
Authors: T. Lipitsä, H. Siiskonen, A. Naukkarinen, I.T. Harvima
Journal: British Journal of Dermatology (2018)

The accumulation of immunoreactants and fibrinoid necrosis of postcapillary vessel walls are common pathological features of cutaneous immune complex vasculitis. In more advanced lesions, these immunoreactants are subject to proteolysis. Mast cell chymase is a powerful enzyme that can degrade several substrates including the extracellular matrix. Heparin can influence the catalytic properties of chymase.To study the effects of recombinant human (rh) chymase on fibrinogen, coagulation and fibrinolysis, and to relate these effects to the pathogenesis of vasculitis.The colocalization of chymase and fibrin in vasculitis specimens was analysed by immunohistochemical double staining. Fibrinogen and fibrin were treated with rh-chymase and the effects were studied in vitro by sodium dodecylsulfate polyacrylamide gel electrophoresis and a variety of clotting and fibrin gel experiments. The effects of rh-chymase on vasculitis cryosections were analysed by direct immunofluorescence.Chymase-positive mast cells were associated with fibrin-positive vessels in vasculitis cryosections. Rh-chymase degraded the alpha-, beta- and gamma-chains of fibrinogen, while heparin enhanced the degradation of the beta-chain. Rh-chymase pretreatment of fibrinogen prolonged thrombin-induced clotting time. Fibrinogen degradation products induced by rh-chymase increased the clotting time of human plasma. Rh-chymase degraded fibrin gel prepared from fibrinogen or human plasma. Immunofluorescence staining positivity of fibrin in vasculitis cryosections decreased after pretreatment with rh-chymase for 24 h, and heparin enhanced this effect.Mast cell chymase may constitute a previously unrecognized endogenous anticoagulant and fibrinolytic enzyme, and may be involved in the clearance of fibrin from vessel walls in aged vasculitis lesions.
Cervical Cancer Screening Access for Women Who Experience Imprisonment in Ontario, Canada
Authors: Fiona G. Kouyoumdjian, Andres McConnon, Emma R. S. Herrington, Kinwah Fung, Aisha Lofters, Stephen W. Hwang
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Women who experience imprisonment have higher rates of cervical cancer. Lack of access to cervical cancer screening in the community or in prison may contribute to increased cervical cancer incidence. <h3>Objectives</h3> To determine cervical cancer screening rates for women in provincial prison in Ontario, Canada, and to compare these data with data for the general population. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used correctional and health administrative data from January 1, 2006, to December 31, 2013. Participants included Ontario women aged 21 to 69 years during the follow-up period with no history of cervical cancer or hysterectomy. Analyses were conducted between July 2017 and September 2018. <h3>Exposures</h3> Women admitted to Ontario provincial prison in 2009 or 2010 and released in 2010 were considered exposed, and women in the general population of Ontario were considered unexposed. <h3>Main Outcomes and Measures</h3> Whether women were overdue for cervical cancer screening at the time of admission to prison or on July 1, 2010, for the general population, defined as not having been screened in the previous 3 years, and whether women who were overdue were still overdue after 3 years. <h3>Results</h3> There were 4553 women in the prison group and 3 647 936 women in the general population group. The median (interquartile range) age was 36 (29-43) years in the prison group and 43 (34-53) years in the general population. Women in the prison group had 2.20 times (95% CI, 2.08-2.33) the odds of being overdue for cervical cancer screening compared with women in the general population after adjusting for neighborhood income quintile, at 53.9% (95% CI, 51.8%-56.1%) compared with 32.9% (95% CI, 32.8%-33.0%) (<i>P</i> &lt; .001). Women in the prison group also had nearly twice the odds of still being overdue at 3 years, with an odds ratio of 1.87 (95% CI, 1.76-1.99) after adjusting for neighborhood income quintile, and rates of still being overdue of 36.2% (95% CI, 34.5%-38.0%) compared with 21.9% (95% CI, 21.8%-21.9%) (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Women who experience imprisonment have worse cervical cancer screening access than women in the general population. Work should be done to promote cervical cancer screening awareness and to improve access to acceptable screening in prison and in the community after prison release.
The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma
Authors: Rabea Wagener, Julian Seufert, Francesco Raimondi, Susanne Bens, Kortine Kleinheinz, Inga Nagel, Janine Altmüller, Holger Thiele, Daniel Hübschmann, Christian W. Kohler, Peter Nürnberg, Rex Au-Yeung, Birgit Burkhardt, Heike Horn, Lorenzo Leoncini, Elaine S. Jaffe, German Ott, Grzegorz Rymkiewicz, Matthias Schlesner, Robert B. Russell, Wolfram Klapper, Reiner Siebert
Journal: Blood (2018)