tbuckley/cabot-search huggingface dataset:
Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer
Authors: Laurie L. Brunette, Shahram Bonyadlou, Lingyun Ji, Susan Groshen, Dena Shuster, Arjun Mehta, Richard Sposto, Koji Matsuo, Yvonne G. Lin, Lynda D. Roman
Journal: Clinical Nuclear Medicine (2018)

Purpose The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUV max (nSUV max ). Materials and Methods A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUV max measurements were normalized to the SUV of the pelvic blood pool. Patient, tumor, and PET/CT data were correlated to extracervical recurrence-free survival (ecRFS) and lymph node pathology. Results Of 113 patients, there were 23 (20%) extracervical recurrences. On univariate analysis, stage, histology, nSUV max , and radiographic size of the primary tumor, and nSUV max of the most hypermetabolic lymph node were significantly associated with ecRFS. On multivariable analysis, nSUV max and radiographic size of the primary tumor remained associated with ecRFS (both P &lt; 0.001). Sixty-six patients underwent pelvic, common iliac, and/or para-aortic nodal sampling. The sensitivity, specificity, false-negative, and false-positive rates of PET/CT for lymph node metastases were 53%, 75%, 6%, and 82%, respectively. On univariate analysis, nSUV max , and radiographic size of the primary tumor, and nSUV max of the most hypermetabolic lymph node, and radiographic size of the largest lymph node, were associated with the presence of at least one pathologically positive lymph node. On multivariable analysis, only the radiographic size of the largest lymph node remained significantly associated with lymph node metastases ( P &lt; 0.001). Conclusions The size and nSUV max of the primary tumor were associated with ecRFS. PET/CT has a low false-negative rate but high false-positive rate for lymph node metastases.
Abstract 12519: Age Impacts the Interpretation of Myocardial Blood Flow Values in Cardiac PET/CT
Authors: Hannah E Raasch, Raymond O McCubrey, Jon-David Ethington, Steve Mason, Viet T Le, Ritesh Dhar, Kent G Meredith, Jeffrey L Anderson
Journal: Circulation (2015)

Introduction: Quantitative myocardial blood flow (MBF) obtained via Rb82 PET/CT using regadenoson provides the ability to assess ischemia through analysis of stress MBF and coronary flow reserve (CFR), the augmentation of flow expressed as a stress/rest ratio. It is unknown to what extent, if any, age-related changes in arteries (i.e. arterial stiffening, atherosclerosis) impact MBF and, thus, the interpretation of ischemia. Hypothesis: MBF values change as a function of age and impact PET interpretation. Methods: Patients who underwent PET/CT from May 2013 to April 2015 with normal perfusion images and no history of PCI or CABG were included (n=3329, 1720 women, 1498 men). Rest MBF, stress MBF, and CFR) (mL/min/g) were recorded in all vessels separated by gender and by age &lt;60 or ≥60. Analysis was conducted on individual vessels and global estimates were calculated averaging all vessels. Estimated average median differences between age &lt;60 and ≥60 were adjusted for traditional cardiovascular risk factors (BMI, smoking, diabetes, hypertension, hyperlipidemia, family history). Results: Effects of Age on Global MBF Adjusted for Traditional Risk Factors Conclusions: In patients ≥60 years of age with normal perfusion imaging, rest MBF increases, stress MBF decreases, and the resultant CFR is decreased, all statistically significant. This may reflect a higher fixed level of vasodilation in older vessels at rest and a more limited ability to vasodilate with stress independent of other CV risk factors. Given the increasing use of PET/CT for ischemia assessment, it is important to recognize expected MBF changes with age to decrease false positive studies and unwarranted invasive testing.
Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study
Authors: Joseph Mikhael, Judith Manola, Amylou C. Dueck, Suzanne Hayman, Kurt Oettel, Abraham S. Kanate, Sagar Lonial, S. Vincent Rajkumar
Journal: Blood Cancer Journal (2018)

Abstract Renal insufficiency is common in patients with relapsed multiple myeloma and can often limit choice of therapy. Lenalidomide, a critical agent in the treatment of relapsed multiple myeloma, is renally cleared., This phase I/II trial evaluated the efficacy and safety of lenalidomide with dexamethasone in patients with relapsed multiple myeloma and renal insufficiency. Three groups were treated, with creatinine clearance 30–60 cc/hr (group A), CrCl &lt; 30 not on dialysis (group B), and patients on dialysis (group C) at escalating doses of lenalidomide. A total of 63 patients were treated and no DLTs were observed in phase I. All three groups were able to escalate to full dose lenalidomide 25 mg daily 21/28 days, although due to reduced accrual the phase II component was not entirely completed for groups B and C. Adverse events were as expected, including anemia, diarrhea and fatigue. Ten patients experienced grade 3–4 pneumonia. Overall response rate was 54% across all groups. PFS was 7.5 months and OS was 19.7 months. Lenalidomide can be given at full dose 25 mg daily 21/28 in patients with a CrCl &gt; 30, and can be given daily to those with CrCl &lt; 30, even when on dialysis, at doses of at least 15 mg daily.
MERIT: Systematic Analysis and Characterization of Mutational Effect on RNA Interactome Topology
Authors: Yongsheng Li, Daniel J. McGrail, Juan Xu, Junyi Li, Ning‐Ning Liu, Ming Sun, Richard Lin, Rita Pancsa, Jiwei Zhang, Ju‐Seog Lee, Hui Wang, Gordon B. Mills, Xia Li, Song Yi, Nidhi Sahni
Journal: Hepatology (2018)

The interaction between RNA‐binding proteins (RBPs) and RNA plays an important role in regulating cellular function. However, decoding genome‐wide protein–RNA regulatory networks as well as how cancer‐related mutations impair RNA regulatory activities in hepatocellular carcinoma (HCC) remains mostly undetermined. We explored the genetic alteration patterns of RBPs and found that deleterious mutations are likely to occur on the surface of RBPs. We then constructed protein–RNA interactome networks by integration of target binding screens and expression profiles. Network analysis highlights regulatory principles among interacting RBPs. In addition, somatic mutations selectively target functionally important genes (cancer genes, core fitness genes, or conserved genes) and perturb the RBP–gene regulatory networks in cancer. These regulatory patterns were further validated using independent data. A computational method (Mutational Effect on RNA Interactome Topology) and a web‐based, user‐friendly resource were further proposed to analyze the RBP–gene regulatory networks across cancer types. Pan‐cancer analysis also suggests that cancer cells selectively target “vulnerability” genes to perturb protein–RNA interactome that is involved in cancer hallmark–related functions. Specifically, we experimentally validated four pairs of RBP–gene interactions perturbed by mutations in HCC, which play critical roles in cell proliferation. Based on the expression of perturbed RBP and target genes, we identified three subtypes of HCC with different survival rates. Conclusion: Our results provide a valuable resource for characterizing somatic mutation‐perturbed protein–RNA regulatory networks in HCC, yielding valuable insights into the genotype–phenotype relationships underlying human cancer, and potential biomarkers for precision medicine.
Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals
Authors: Álvaro Hernáez, Olga Castañer, Roberto Elosua, Xavier Pintó, Ramón Estruch, Jordi Salas-Salvadó, Dolores Corella, Fernando Arós, Lluis Serra-Majem, Miquel Fiol, Manuel Ortega-Calvo, Emilio Ros, Miguel Ángel Martínez-González, Rafael de la Torre, M. Carmen López-Sabater, Montserrat Fitó
Journal: Circulation (2017)

Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). Results: Both TMDs increased cholesterol efflux capacity relative to baseline ( P =0.018 and P =0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P =0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P =0.039, P =0.012, and P =0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P &lt;0.001). Conclusions: The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans. Clinical Trial Registration: URL: http://www.controlled-trials.com . Unique identifier: ISRCTN35739639.
Abstract 16162: Left Atrial Deformation at Rest Predicts Peak Exercise Pulmonary Artery Wedge Pressure and Mean Pulmonary Artery Pressure
Authors: Tor Biering-Sørensen, Mário Santos, Jose Rivero, Erin West, Alexander R Opotowsky, Aaron B Waxman, David M Systrom, Amil M Shah
Journal: Circulation (2016)

Introduction: Impaired left atrial (LA) function may contribute to exertional limitation. LA strain (LAS), is a novel echocardiographic measure of LA function, but its relationship to the hemodynam...
Adaptive optics imaging of the human retina
Authors: Stephen A. Burns, Ann E. Elsner, Kaitlyn A. Sapoznik, Raymond L. Warner, Thomas J. Gast
Journal: Progress in Retinal and Eye Research (2018)

Adaptive Optics (AO) retinal imaging has provided revolutionary tools to scientists and clinicians for studying retinal structure and function in the living eye. From animal models to clinical patients, AO imaging is changing the way scientists are approaching the study of the retina. By providing cellular and subcellular details without the need for histology, it is now possible to perform large scale studies as well as to understand how an individual retina changes over time. Because AO retinal imaging is non-invasive and when performed with near-IR wavelengths both safe and easily tolerated by patients, it holds promise for being incorporated into clinical trials providing cell specific approaches to monitoring diseases and therapeutic interventions. AO is being used to enhance the ability of OCT, fluorescence imaging, and reflectance imaging. By incorporating imaging that is sensitive to differences in the scattering properties of retinal tissue, it is especially sensitive to disease, which can drastically impact retinal tissue properties. This review examines human AO retinal imaging with a concentration on the use of the Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO). It first covers the background and the overall approaches to human AO retinal imaging, and the technology involved, and then concentrates on using AO retinal imaging to study the structure and function of the retina.
Protective Role of Hepatocyte Cyclooxygenase‐2 Expression Against Liver Ischemia–Reperfusion Injury in Mice
Authors: Omar Motiño, Daniel E. Francés, Natalia Casanova, Marina Fuertes‐Agudo, Carme Cucarella, Juana M. Flores, María Teresa Vallejo‐Cremades, Luis Olmedilla, José Pérez Peña, Rafael Bañares, Lisardo Boscá, Marta Casado, Paloma Martín‐Sanz
Journal: Hepatology (2018)

Liver ischemia and reperfusion injury (IRI) remains a serious clinical problem affecting liver transplantation outcomes. IRI causes up to 10% of early organ failure and predisposes to chronic rejection. Cyclooxygenase‐2 (COX‐2) is involved in different liver diseases, but the significance of COX‐2 in IRI is a matter of controversy. This study was designed to elucidate the role of COX‐2 induction in hepatocytes against liver IRI. In the present work, hepatocyte‐specific COX‐2 transgenic mice (hCOX‐2‐Tg) and their wild‐type (Wt) littermates were subjected to IRI. hCOX‐2‐Tg mice exhibited lower grades of necrosis and inflammation than Wt mice, in part by reduced hepatic recruitment and infiltration of neutrophils, with a concomitant decrease in serum levels of proinflammatory cytokines. Moreover, hCOX‐2‐Tg mice showed a significant attenuation of the IRI‐induced increase in oxidative stress and hepatic apoptosis, an increase in autophagic flux, and a decrease in endoplasmic reticulum stress compared to Wt mice. Interestingly, ischemic preconditioning of Wt mice resembles the beneficial effects observed in hCOX‐2‐Tg mice against IRI due to a preconditioning‐derived increase in endogenous COX‐2, which is mainly localized in hepatocytes. Furthermore, measurement of prostaglandin E 2 (PGE 2 ) levels in plasma from patients who underwent liver transplantation revealed a significantly positive correlation of PGE 2 levels and graft function and an inverse correlation with the time of ischemia. Conclusion: These data support the view of a protective effect of hepatic COX‐2 induction and the consequent rise of derived prostaglandins against IRI.
Abstract 18631: Ulk1-dependent Alternative Mitochondrial Autophagy Plays a Protective Role in Response to Pressure Overload
Authors: Jihoon Nah, Akihiro Shirakabe, Peiyong Zhai, Wataru Mizushima, Junichi Sadoshima
Journal: Circulation (2017)

Introduction: Well-controlled mitochondrial homeostasis, including mitochondrial autophagy, is essential to maintaining cardiac function. Recent studies revealed that mitochondrial autophagy (herea...
Economic complexities and cognitive hurdles: Accounting for specific economic misconceptions without an ultimate cause
Authors: David Leiser, Yhonatan Shemesh
Journal: Behavioral and Brain Sciences (2018)

Abstract Do folk-economic beliefs have an ultimate cause? We argue that, in many cases, the answer is negative. Cognition is constrained in both scope (via long-term memory [LTM]) and depth (via working memory [WM]). Consequently, laypeople are challenged by concepts essential for understanding complex systems, economics included: aggregation, indirect causation, and equilibrium. We discuss several economic misconceptions arising from this acute mismatch.
Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis
Authors: Rajiv Chowdhury, Anna Ramond, Linda M O’Keeffe, Sara Shahzad, Setor K Kunutsor, Taulant Muka, John Gregson, Peter Willeit, Samantha Warnakula, Hassan Khan, Susmita Chowdhury, Reeta Gobin, Oscar H Franco, Emanuele Di Angelantonio
Journal: BMJ (2018)

<h3>ABSTRACT</h3> <h3>Objective</h3> To conduct a systematic review and meta-analysis of epidemiological studies investigating the association of arsenic, lead, cadmium, mercury, and copper with cardiovascular disease. <h3>Design</h3> Systematic review and meta-analysis. <h3>Data sources</h3> PubMed, Embase, and Web of Science searched up to December 2017. <h3>Review methods</h3> Studies reporting risk estimates for total cardiovascular disease, coronary heart disease, and stroke for levels of arsenic, lead, cadmium, mercury, or copper were included. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks were standardised to a common scale and pooled across studies for each marker using random effects meta-analyses. <h3>Results</h3> The review identified 37 unique studies comprising 348 259 non-overlapping participants, with 13 033 coronary heart disease, 4205 stroke, and 15 274 cardiovascular disease outcomes in aggregate. Comparing top versus bottom thirds of baseline levels, pooled relative risks for arsenic and lead were 1.30 (95% confidence interval 1.04 to 1.63) and 1.43 (1.16 to 1.76) for cardiovascular disease, 1.23 (1.04 to 1.45) and 1.85 (1.27 to 2.69) for coronary heart disease, and 1.15 (0.92 to 1.43) and 1.63 (1.14 to 2.34) for stroke. Relative risks for cadmium and copper were 1.33 (1.09 to 1.64) and 1.81 (1.05 to 3.11) for cardiovascular disease, 1.29 (0.98 to 1.71) and 2.22 (1.31 to 3.74) for coronary heart disease, and 1.72 (1.29 to 2.28) and 1.29 (0.77 to 2.17) for stroke. Mercury had no distinctive association with cardiovascular outcomes. There was a linear dose-response relation for arsenic, lead, and cadmium with cardiovascular disease outcomes. <h3>Conclusion</h3> Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease. Mercury is not associated with cardiovascular risk. These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.
Abstract 17214: Autologous CD34+ Cell Therapy Reduces Mortality and Improves Exercise Capacity in Patients With Refractory Angina
Authors: Thomas J Povsic, Timothy D Henry, E M Jolicoeur, Jay H Traverse, Richard A Schatz, Andrea S Hunt, Douglas W Losordo
Journal: Circulation (2016)

Introduction: Phase I, II and prematurely terminated phase III trials of autologous CD34+ cell therapy provide consistent evidence for improving exercise time, angina and trends towards reductions ...
Abstract A33: Histone demethylase KDM3A in rhabdomyosarcoma
Authors: Lays M. Sobral, Paul Jedlicka
Journal: Clinical Cancer Research (2018)

Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, adolescents, and young adults, presenting a myogenic phenotype. RMS can be divided into two major histopathologic subtypes: driver oncofusion (PAX3/7-FOXO1) positive, alveolar (ARMS), and oncofusion-negative embryonal (ERMS). Histone methylation is a key element of chromatin-based modifications that regulates a number of cellular processes, including DNA replication, DNA repair, and gene transcription. Histone demethylase gene family members (HDMs) regulate gene expression by removing methyl marks on histone tails to activate or repress transcription. KDM3A (lysine-specific demethylase 3A or JMJD1A) is a histone demethylase belonging to the Jumonji C-terminal domain (JmjC)-containing histone demethylases that selectively removes mono- and dimethyl groups from H3K9. It has been demonstrated that KDM3A is overexpressed in many kinds of cancer, such as bladder, lung, and breast cancer, and, previously shown by our laboratory, in Ewing sarcoma, contributing to carcinogenesis. We and others have identified KDM3A as overexpressed in RMS, but the functional consequences of this overexpression have not been examined. The aim of this study was to analyze the influence of KDM3A on RMS biology. Two different RMS cells lines were used, RH30 (ARMS) and RD (ERMS), to perform stable shRNA-mediated KDM3A knockdown. The protein and RNA levels were analyzed by Western blotting and RT-qPCR, respectively. The phenotypic effects of KDM3A knockdown were analyzed by proliferation assays (MTT and clonogenic assay) and cell migration (transwell migration assay). KDM3A knockdown was able to inhibit the proliferation, colony formation, and migration of RMS cell lines, demonstrating an important role in RMS biology. Citation Format: Lays M. Sobral, Paul Jedlicka. Histone demethylase KDM3A in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A33.
Partnership to Develop Over-the-Counter Flu Tests
Authors: Rita Rubin
Journal: JAMA (2018)

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Abstract 16559: Implantable Cardioverter Defibrillator Recipient’s Perceptions of Healthcare Provider’s Discussions Related to Device Therapy
Authors: Martha J Biddle, JungHee Kang, Jennifer L MIller, Muna Hammash, Jan Cameron, Misook L Chung, Debra K Moser
Journal: Circulation (2016)

Introduction: Healthcare providers are challenged to have in-depth discussions related to deactivation and illness trajectory with ICD recipients. However, these discussions may be perceived differ...
Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis
Authors: Robert J. Fox, Christopher S. Coffey, Robin Conwit, Merit E. Cudkowicz, Trevis Gleason, Andrew Goodman, Eric C. Klawiter, Kazuko Matsuda, Michelle McGovern, Robert T. Naismith, Akshata Ashokkumar, Janel Barnes, Dixie Ecklund, Elizabeth Klingner, Maxine Koepp, Jeffrey D. Long, Sneha Natarajan, Brenda Thornell, Jon Yankey, Robert A. Bermel, Josef P. Debbins, Xuemei Huang, Patricia Jagodnik, Mark J. Lowe, Kunio Nakamura, Sridar Narayanan, Ken E. Sakaie, Bhaskar Thoomukuntla, Xiaopeng Zhou, Stephen Krieger, Enrique Alvarez, Michelle Apperson, Khurram Bashir, Bruce A. Cohen, Patricia K. Coyle, Silvia Delgado, L. Dana Dewitt, Angela Flores, Barbara S. Giesser, Myla D. Goldman, Burk Jubelt, Neil Lava, Sharon G. Lynch, Harold Moses, Daniel Ontaneda, Jai S. Perumal, Michael Racke, Pavle Repovic, Claire S. Riley, Christopher Severson, Shlomo Shinnar, Valerie Suski, Bianca Weinstock-Guttman, Vijayshree Yadav, Aram Zabeti
Journal: New England Journal of Medicine (2018)

There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.