tbuckley/cabot-search huggingface dataset:
SAT0513 ASSOCIATION OF SERUM OMENTIN LEVELS WITH COLCHICINE RESISTANCE IN FAMILIAL MEDITERRANEAN FEVER
Authors: S. Can Sandikci, A. Omma, C. Yucel, T. Omma
Journal: Annals of the Rheumatic Diseases (2020)

Background: Omentin is an anti-inflammatory adipokine, which plays important roles in the adjustments of glucose metabolism, cardiovascular homeostasis, atherosclerosis (1). Objectives: To investigate the omentin levels in Familial Mediterranean fever (FMF) patients and to assess the association with markers of subclinical inflammation in FMF patients such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Methods: This cross-sectional study included 54 consecutive adult FMF patients (27 male, 27 female) and 28 healthy individuals (16 male, 12 female). The demographic and clinical features and MEFV gene mutations were recorded. The FMF patients were separated into 3 groups: 1) attack-free group, 2) active attack group and 3) colchicine-resistant group. Serum omentin levels were compared between the FMF patients and the healthy control group. Results: Serum omentin and SAA levels were higher in the study group than in the control group (108.05(19.97-343.22) vs. 199.5(42.98-339.41) p&lt;0.05, 3.69(1.18-22.75) vs. 1.31(0.95-3.16) p&lt;0.001) (Table 1). When the FMF patients were examined as separate groups, serum omentin values were lower in the colchicine resistant group than in the groups without resistance (Table 2). The correlation analysis showed a negative correlation between omentin and SAA levels (r = -0.240, p = 0.030). Table 1. Laboratory results of the FMF and the control group Variables FMF patients (n=54 ) Control (n=28 ) P value Omentin, pg/mL 108.05(19.97-343.22) 199.5(42.98-339.41) 0.03 SAA, ng/mL 3.7 (1.18-22.75) 1.31(0.95-3.16) &lt;0.001 ESR, mm/h 15(2-68) 12(7-17) &lt;0.001 CRP, mg/L 12(1-194) 2.5(1-8) &lt;0.001 Variables were given as median (IQR). Calculated using Mann-Whitney U test for non-normal distribution. FMF=Familial Mediterranean fever, SAA=serum amyloid A, ESR=erythrocyte sedimentation rate, CRP=C-reactive protein, IQR=interquartile range. Table 2. Laboratory results of FMF patients with and without colchicine resistance Variables With resistance (n=16 ) Without resistance (n=38 ) P value Omentin, pg/mL 76.64(19.77-224.33) 186.47(28.41-343.21) 0.006 SAA, ng/mL 3.69(1.18-22.75) 3.77(1.18-21.49) 0.784 ESR, mm/h 25.5(2-68) 15(2-60) 0.835 CRP, mg/L 11(1-67) 19(1-194) 0.111 Variables were given as median (IQR). Calculated using Mann-Whitney U test for non-normal distribution. FMF=Familial Mediterranean fever, SAA=serum amyloid A, ESR=erythrocyte sedimentation rate, CRP=C-reactive protein, IQR=interquartile range.FOM Conclusion: FMF patients with colchicine resistance are associated with decreased omentin concentrations, probably mediated by inflammation-driven mechanisms. References: [1]Yue J, Chen J, Wu Q, Liu X, Li M, Li Z, Gao Y. Serum levels of omentin-1 association with early diagnosis, lesion volume and severity of acute ischemic stroke. Cytokine. 2018;111:518–522. Disclosure of Interests: None declared
COVID-19: Once upon a time in Portugal
Authors: F. Guimarães, J.C. Winck
Journal: Pulmonology (2020)

Once upon a time in Portugal A brief atlas of ongoing pandemic Portuguese research Once upon a time. . . . . .a novel coronavirus was described in China.The new year 2020 had just arrived full of hope and promise.Portugal was preparing to defend its European Football Champion title.And China was far far away.Suddenly, something changed.The virus had a name, as did the disease it caused.The cases were spreading fast and arrived in Europe.Now, the threat was real.Portugal was panicking with suspected cases and the scientific community was warning of a lack of preparedness.And it arrived indeed on March 2nd.
Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves
Authors: Raj R. Makkar, Philipp Blanke, Jonathon Leipsic, Vinod Thourani, Tarun Chakravarty, David Brown, Alfredo Trento, Robert Guyton, Vasilis Babaliaros, Mathew Williams, Hasan Jilaihawi, Susheel Kodali, Isaac George, Michael Lu, James M. McCabe, John Friedman, Richard Smalling, Shing Chiu Wong, Shahram Yazdani, Deepak L. Bhatt, Jeroen Bax, Samir Kapadia, Howard C. Herrmann, Michael Mack, Martin B. Leon
Journal: Journal of the American College of Cardiology (2020)

Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction. The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes. The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low–surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory. The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04). Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.
AB0267 BODY COMPOSITION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: N. Toroptsova, O. Dobrovolskaya, N. Demin, L. Shornikova
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a complex inflammatory disease that modifies body composition. Using the dual-energy x-ray absorptiometry (DXA) in RA patients could be a method for body composition changes detection. Objectives: To study the body composition using DXA in patients with RA. Methods: The study involved 79 women with RA, median age 60 [55; 65] years. The bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry using «Discovery A» (Hologic, USA). Assessment of body composition was carried out, using the program «Whole body». Sarcopenia (SP) was diagnosed as a decrease in appendicular mass index (AMI) &lt;6.0 kg/m 2 . Osteoporosis (OP) was diagnosed as a decrease in T-score &lt;-2.5 SD. Osteosarcopenia was determined when T-score was &lt;-1.0 SD, AMI was &lt;6.0 kg/m 2 , osteosarcopenic obesity - T-score was &lt;-1.0 SD, AMI was &lt;6.0 kg/m 2 and total fat was &gt;35%. Results: The mean duration of RA was 9 [3; 11] years. The mean body mass index (BMI) was 27.6±4.8 kg/m 2 . Disease activity score in 28 joints-erythrocyte sedimentation rate was 4.5±1.3 points for the group. 39 (49.3%) patients used oral glucocorticoids continuously. Appendicular muscle mass and AMI were on average 17.8±3.0 kg and 6.8±1.0 kg/m 2 , respectively. AMI &lt;6 kg/m 2 was detected in 20 (25.3%) patients. 56 (70.9%) women with RA had total fat &gt; 35%, while only 22 (27.8%) of women with RA had obesity according to BMI (BMI &gt;30 kg/m 2 ). Isolated OP was found in 13 (16.5%), osteosarcopenia in 7 (8.9%) and osteosarcopenic obesity in 13 (16.5%) patients RA. No cases with isolated sarcopenia or sarcopenic obesity were detected. Only 3 (3.8%) patients did not have appendicular muscle mass, AMI and BMD decrease and overfat or obesity. Conclusion: About 97% women with RA had abnormal body composition phenotype: 16,5% - OP, 8.9% -osteosarcopenia, 16,5% - osteosarcopenic obesity and 54,4% - overfat. Disclosure of Interests: None declared
Covid-19: the medical students responding to the pandemic
Authors: Florence Kinder, Anna Harvey
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: the medical students responding to the pandemic Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
コロネン・イオン・スパッター源を使用したコデイン負荷ポリ(L-乳酸)フィルムの定量的XPS深度プロファイリング
Authors: Rafati Ali, C Davies Martyn, G Shard Alexander, Hutton Simon, Mishra Gautam, R Alexander Morgan
Journal: Journal of Controlled Release (2009)
Cumulative Incidence of Child Protection Services Involvement Before Age 5 Years in 153 670 Australian Children
Authors: Kathleen Falster, Mark Hanly, Rhiannon Pilkington, Sandra Eades, Jessica Stewart, Louisa Jorm, John Lynch
Journal: JAMA Pediatrics (2020)

This study examines the incidence of notifications to and investigations, substantiations, and out-of-home care placements by child protection services for children aged 0 to 5 years in New South Wales, Australia.
Abstract A11: STAT1 mediates resistance to experimental oral cancer that is associated with enhanced antitumor T-cell responses
Authors: Nathan Ryan, Kelvin Anderson, Greta Volpedo, Omar Hamza, Sanjay Varikuti, Abhay Satoskar, Steve Oghumu
Journal: Clinical Cancer Research (2020)

Abstract Cancers of the oral cavity and pharynx remain among the 10 most prevalent cancers in the United States. Signal Transducer and Activation of Transcription 1 (STAT1) is a transcription factor primarily involved in mediating responses to IFNs, as well as interleukin (IL) 21, 27, and 35. STAT1 has been shown to promote or suppress tumors in different cancer types, but its role in oral cavity cancers has not been examined. We examined the role of STAT1 in oral cancer using orthotopic models in wild-type (WT) and STAT1-deficient BALB/c mice. Metastatic (LY2) or nonmetastatic (B4B8) HNSCC cell lines were injected into the oral cavity and tumor development was monitored over a period of three or six weeks, respectively. At terminal sacrifice, tumors, spleens, draining lymph nodes, and bone marrow tissues were analyzed for tumor growth, metastasis, and immunologic responses. Tumors from STAT1-deficient mice injected with B4B8 cells were twice as large as tumors from WT mice. Interestingly, LY2-injected STAT1-deficient mice possessed tumors that were five times as large as tumors from LY2-injected WT mice. The increased tumor burdens in metastatic tumors were associated with a decrease in CD4+ and CD8+ T-cell infiltration into the draining lymph nodes of tumor-bearing STAT1-deficient mice compared to WT mice. Further, lymph node and splenic CD4+ and CD8+ T cells in tumor-bearing STAT1-deficient mice produced significantly lower TNF-alpha compared to WT mice. Finally, tumor-bearing STAT1-deficient mice displayed a significant accumulation of CD11b+ Ly6G+ myeloid cells in the spleens and bone marrow compared to WT counterparts in both metastatic and nonmetastatic HNSCC models. Our results demonstrate that STAT1 mediates resistance to oral tumor development that is associated with enhanced T-cell migration, TNF-alpha mediated antitumor T-cell responses, and diminished accumulation of tumor-promoting CD11b+ Ly6G+ myeloid cells. Citation Format: Nathan Ryan, Kelvin Anderson, Greta Volpedo, Omar Hamza, Sanjay Varikuti, Abhay Satoskar, Steve Oghumu. STAT1 mediates resistance to experimental oral cancer that is associated with enhanced antitumor T-cell responses [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A11.
Response to: ‘Off-label use of tofacitinib: a potential treatment option for SAPHO syndrome’ by Xie et al
Authors: Yueting Li, Yihan Cao, Chen Li, Wen Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Response to: 'Off-label use of tofacitinib: a potential treatment option for SAPHO syndrome' by Xie et alWe would like to thank Xie et al 1 for their interest in our paper 2 and for their insights into the possible mechanism of action of tofacitinib in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and the trend of stratified medicine.As Xie et al highlighted, tofacitinib presented clinical and radiological efficacy in patients with SAPHO syndrome who had an inadequate response to tumour necrosis factor (TNF) inhibitors or bisphophonates.Similarly, a clinical trial proved that tofacitinib was effective in patients with TNF inhibitor-resistant psoriatic arthritis (PsA). 3][6][7][8][9][10] We speculated that the multipathway inhibitory effect of tofacitinib might contribute to its efficacy in refractory SAPHO syndrome.The heterogeneity of treatment response also raises the issue of stratified treatment approach in SAPHO syndrome.Clinical and genetic markers have been identified using machine learning to enable prediction of treatment responses to anti-TNF agents in rheumatoid arthritis. 11Furthermore, Miyagawa et al proved that strategic treatment based on immunological phenotypes of the individual patient yielded a significant decrease in disease activity compared with routine treatment in PsA. 12 Given the high heterogeneity of SAPHO syndrome, we believe that further efforts in precision medicine may facilitate the understanding and management of the disease.As mentioned by Xie et al, our retrospective study had a limited sample size and follow-up time.It was the first step to demonstrate a new potential treatment for SAPHO syndrome.Future controlled perspective study with a larger sample size and longer follow-up duration is required to establish the efficacy and safety of tofacitinib in SAPHO syndrome.
B55α/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling
Authors: Manuel Ehling, Ward Celus, Rosa Martín-Pérez, Roser Alba-Rovira, Sander Willox, Donatella Ponti, Maria C. Cid, Elizabeth A.V. Jones, Giusy Di Conza, Massimiliano Mazzone
Journal: Circulation Research (2020)

Rationale: How endothelial cells (ECs) migrate and form an immature vascular plexus has been extensively studied. Yet, mechanisms underlying vascular remodeling remain poorly established. A better understanding of these processes may lead to the design of novel therapeutic strategies complementary to current angiogenesis inhibitors. Objective: Starting from our previous observations that PP2A (protein phosphatase 2) regulates the HIF (hypoxia-inducible factor)/PHD-2 (prolyl hydroxylase 2)-constituted oxygen machinery, we hypothesized that this axis could play an important role during blood vessel formation, tissue perfusion, and oxygen restoration. Methods and Results: We show that the PP2A regulatory subunit B55α is at the crossroad between vessel pruning and vessel maturation. Blood vessels with high B55α counter cell stress conditions and thrive for stabilization and maturation. When B55α is inhibited, ECs cannot cope with cell stress and undergo apoptosis, leading to massive pruning of nascent blood vessels. Mechanistically, we found that the B55α/PP2A complex restrains PHD-2 activity, promoting EC survival in a HIF-dependent manner, and furthermore dephosphorylates p38, altogether protecting ECs against cell stress occurring, for example, during the onset of blood flow. In tumors, EC-specific B55α deficiency induces pruning of immature-like tumor blood vessels resulting in delayed tumor growth and metastasis, without affecting nonpathological vessels. Consistently, systemic administration of a pan-PP2A inhibitor disrupts vascular network formation and tumor progression in vivo without additional effects on B55α-deficient vessels. Conclusions: Our data underline a unique role of the B55α/PP2A phosphatase complex in vessel remodeling and suggest the use of PP2A-inhibitors as potent antiangiogenic drugs targeting specifically nascent blood vessels with a mode-of-action complementary to VEGF-R (vascular endothelial growth factor receptor)-targeted therapies. Graphical Abstract: A graphical abstract is available for this article.
Aortic Root Dilatation as a Cause of Isolated, Severe Aortic Regurgitation
Authors: Mary J. Roman, Richard B. Devereux, Nathaniel W. Niles, Clare Hochreiter, Paul Kligfield, Nina Sato, Mariane C. Spitzer, Jeffrey S. Borer
Journal: Annals of Internal Medicine (2020)

Abstract To evaluate the relation of aortic root dilatation to aortic regurgitation, we examined clinical, echocardiographic, and radionuclide cineangiographic findings in 102 patients with severe ...
COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study
Authors: Marina Chiara Garassino, Jennifer G Whisenant, Li-Ching Huang, Annalisa Trama, Valter Torri, Francesco Agustoni, Javier Baena, Giuseppe Banna, Rossana Berardi, Anna Cecilia Bettini, Emilio Bria, Matteo Brighenti, Jacques Cadranel, Alessandro De Toma, Claudio Chini, Alessio Cortellini, Enriqueta Felip, Giovanna Finocchiaro, Pilar Garrido, Carlo Genova, Raffaele Giusti, Vanesa Gregorc, Francesco Grossi, Federica Grosso, Salvatore Intagliata, Nicla La Verde, Stephen V Liu, Julien Mazieres, Edoardo Mercadante, Olivier Michielin, Gabriele Minuti, Denis Moro-Sibilot, Giulia Pasello, Antonio Passaro, Vieri Scotti, Piergiorgio Solli, Elisa Stroppa, Marcello Tiseo, Giuseppe Viscardi, Luca Voltolini, Yi-Long Wu, Silvia Zai, Vera Pancaldi, Anne-Marie Dingemans, Jan Van Meerbeeck, Fabrice Barlesi, Heather Wakelee, Solange Peters, Leora Horn
Journal: The Lancet Oncology (2020)
An age-independent gene signature for monitoring acute rejection in kidney transplantation
Authors: Brian I Shaw, Daniel K. Cheng, Chaitanya R. Acharya, Robert B Ettenger, Herbert Kim Lyerly, Qing Cheng, Allan D Kirk, Eileen T Chambers
Journal: Theranostics (2020)

Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods.
Gendered effects of school closures during the COVID-19 pandemic
Authors: Katarzyna Burzynska, Gabriela Contreras
Journal: The Lancet (2020)

between girls and boys.We call for a gendered perspective in developing policy responses by tackling the sexual and reproductive health and socioeconomic issues addressed here to bring girls back to school after the measures to contain the COVID-19 pandemic end.We also ask governments to collect data specifically on non-paid housework and childcare respon sibilities frequently ignored when investigating the consequences of child labour.Addressing the health and socioeconomic issues girls might face during this pandemic, as well as collecting data to quantify their effects, are important in honouring the commitment to the Sustainable Development Goals.We declare no competing interests.
Melanocortin-4 receptor antagonist TCMCB07 ameliorates cancer- and chronic kidney disease–associated cachexia
Authors: Xinxia Zhu, Michael F. Callahan, Kenneth A. Gruber, Marek Szumowski, Daniel L. Marks
Journal: Journal of Clinical Investigation (2020)

Cachexia, a devastating wasting syndrome characterized by severe weight loss with specific losses of muscle and adipose tissue, is driven by reduced food intake, increased energy expenditure, excess catabolism, and inflammation. Cachexia is associated with poor prognosis and high mortality and frequently occurs in patients with cancer, chronic kidney disease, infection, and many other illnesses. There is no effective treatment for this condition. Hypothalamic melanocortins have a potent and long-lasting inhibitory effect on feeding and anabolism, and pathophysiological processes increase melanocortin signaling tone, leading to anorexia, metabolic changes, and eventual cachexia. We used 3 rat models of anorexia and cachexia (LPS, methylcholanthrene sarcoma, and 5/6 subtotal nephrectomy) to evaluate efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor. Our data show that peripheral treatment using TCMCB07 with intraperitoneal, subcutaneous, and oral administration increased food intake and body weight and preserved fat mass and lean mass during cachexia and LPS-induced anorexia. Furthermore, administration of TCMCB07 diminished hypothalamic inflammatory gene expression in cancer cachexia. These results suggest that peripheral TCMCB07 treatment effectively inhibits central melanocortin signaling and therefore stimulates appetite and enhances anabolism, indicating that TCMCB07 is a promising drug candidate for treating cachexia.
Defining Very Preterm Populations for Systematic Reviews With Meta-analyses
Authors: Mariane Sentenac, Isabelle Boutron, Elizabeth S. Draper, Eero Kajantie, Rolf F. Maier, Dieter Wolke, Jennifer Zeitlin
Journal: JAMA Pediatrics (2020)

This review compares the selection criteria, findings, and heterogeneity of systematic reviews with meta-analyses of cognitive outcomes among children considered very preterm at birth.
Computed Tomographic Angiography Assessment of Epicardial Coronary Vasoreactivity for Early Detection of Doxorubicin-Induced Cardiotoxicity
Authors: Attila Feher, Nabil E. Boutagy, John C. Stendahl, Christi Hawley, Nicole Guerrera, Carmen J. Booth, Eva Romito, Steven Wilson, Chi Liu, Albert J. Sinusas
Journal: JACC CardioOncology (2020)

The vascular endothelium is a novel target for the detection, management, and prevention of doxorubicin (DOX)-induced cardiotoxicity.The study aimed to: 1) develop a methodology by computed tomography angiography (CTA) to evaluate stress-induced changes in epicardial coronary diameter; and 2) apply this to a chronic canine model of DOX-induced cardiotoxicity to assess vascular toxicity.To develop and validate quantitative methods, sequential retrospectively gated coronary CTAs were performed in 16 canines. Coronary diameters were measured at prespecified distances during rest, adenosine (ADE) (280 μg/kg/min), rest 30 min post-ADE, and dobutamine (DOB) (5 μg/kg/min). A subgroup of 8 canines received weekly intravenous DOX (1 mg/kg) for 12 to 15 weeks, followed by rest-stress CTA at cumulative doses of ∼4-mg/kg (3 to 5 mg/kg), ∼8-mg/kg (7 to 9 mg/kg), and ∼12-mg/kg (12 to 15 mg/kg) of DOX. Echocardiograms were performed at these timepoints to assess left ventricular ejection fraction and global longitudinal strain.Under normal conditions, epicardial coronary arteries reproducibly dilated in response to ADE (left anterior descending coronary artery [LAD]: 12 ± 2%, left circumflex coronary artery [LCx]: 13 ± 2%, right coronary artery [RCA]: 14 ± 2%) and DOB (LAD: 17 ± 3%, LCx: 18 ± 2%, RCA: 15 ± 3%). With DOX, ADE vasodilator responses were impaired after ∼4-mg/kg (LAD: -3 ± 1%, LCx: 0 ± 2%, RCA: -5 ± 2%) and ∼8-mg/kg (LAD: -3 ± 1%, LCx: 0 ± 1%, RCA: -2 ± 2%). The DOB dilation response was preserved at ∼4-mg/kg of DOX (LAD: 18 ± 4%, LCx: 11 ± 3%, RCA: 11 ± 2%) but tended to decrease at ∼8-mg/kg of DOX (LAD: 4 ± 2%, LCx: 8 ± 3%, RCA: 3 ± 2%). A significant left ventricular ejection fraction reduction was observed only at 12 to 15 mg/kg DOX (baseline: 63 ± 2%, 12-mg/kg: 45 ± 3%). Global longitudinal strain was abnormal at ∼4-mg/kg of DOX (p = 0.011).CTA can reliably assess epicardial coronary diameter in response to pharmacological stressors, providing a noninvasive functional index of coronary vasoreactivity. Impaired epicardial vasodilation occurs early in DOX-induced cardiotoxicity.