tbuckley/cabot-search huggingface dataset:
Rituximab maintenance for patients with diffuse large B-cell lymphoma in first complete remission: Results from a randomized HOVON-Nordic Lymphoma Group phase III study.
Authors: Elly J. Lugtenburg, Peter Brown, Bronno van der Holt, Francesco D'Amore, Harry R Koene, Eva de Jongh, Rob Fijnheer, Olaf Loosveld, Lara H Böhmer, Hans Pruijt, Gregor Verhoef, Mels Hoogendoorn, Yavuz Bilgin, Marcel Nijland, King H Lam, Bart de Keizer, Daphne de Jong, Josee M Zijlstra
Journal: Journal of Clinical Oncology (2019)

7507 Background: This randomized phase III trial assessed whether intensification of rituximab (R) during the first 4 cycles of R-CHOP can improve outcome of diffuse large B-cell lymphoma (DLBCL) patients compared with standard R-CHOP. Patients in complete remission (CR) after induction treatment were randomized between rituximab maintenance and observation. Intensification of rituximab was not more effective than standard R-CHOP, showing same CR-rates and progression free survival after induction (ASCO 2016 # 7504). Here, we report the results of the second randomization for rituximab maintenance therapy. Methods: Patients in CR after R-CHOP were randomized between 24 months of rituximab maintenance 375 mg/m 2 intravenous every 8 weeks (n = 199 ) or observation (n = 199). CT scans were performed at 6, 12, 18 and 24 months in both arms. The primary endpoint was disease free survival (DFS) from maintenance randomization. Secondary endpoints were overall survival (OS) and adverse events (AEs). ( www.trialregister.nl NTR1014). Results: Median age was 65 years (range 31-80), 48% were 66 years or older and 49% were male. The majority of patients (54%) had a high-intermediate or high aa-IPI score. After a median follow-up of 79.9 months (maximum 125.7 months), the 5-year DFS rate was 79% for rituximab maintenance versus 74% for observation. This difference was not statistically significant, with a hazard ratio of 0.83 (95% confidence interval 0.57-1.19, p= 0.31, adjusted for age and aa-IPI). The secondary endpoint OS was also not significantly different (85% versus 83% at 5 years). No clinical subgroup benefited from rituximab maintenance. Toxicity was mild. Among patients who received rituximab maintenance CTCAE grade 3 and 4 AEs were reported in 17% and 6% of patients, respectively. Infection was the most frequent AE, a grade 3 infection occurred in 6% of patients. Neutropenia was seen in 1% (grade 3) and 3% (grade 4) of patients. Conclusions: Rituximab maintenance therapy provides no additional benefit for DLBCL patients in first CR after R-CHOP. Clinical trial information: www.trialregister.nl NTR1014.
Application of Ti<sub>3</sub>C<sub>2</sub> MXene Quantum Dots for Immunomodulation and Regenerative Medicine
Authors: Alireza Rafieerad, Weiang Yan, Glen Lester Sequiera, Niketa Sareen, Ejlal Abu‐El‐Rub, Meenal Moudgil, Sanjiv Dhingra
Journal: Advanced Healthcare Materials (2019)

Abstract Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next‐generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti 3 C 2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material‐based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4 + IFN‐γ + T‐lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4 + CD25 + FoxP3 + regulatory T‐cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow‐derived mesenchymal stem cells and induced pluripotent stem cell‐derived fibroblasts. Finally, Ti 3 C 2 MQDs are incorporated into a chitosan‐based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell‐based therapies for tissue repair and treatment of inflammatory and degenerative diseases.
Abstract P376: Improving Cardiovascular Health Among African-Americans Through a Community-based Mobile Health Lifestyle Intervention: The FAITH! (Fostering African-American Improvement in Total Health) App! Pilot Study
Authors: LaPrincess C Brewer, Sarah Jenkins, Kandace Lackore, Jacqueline Johnson, Clarence Jones, Lisa A Cooper, Carmen Radecki Breitkopf, Sharonne N Hayes, Christi Patten
Journal: Circulation (2018)

Introduction: Compared to Whites, African-Americans (AAs) have 82% lower odds of meeting ideal levels for five or more cardiovascular (CV) health components that comprise the American Heart Association’s Life’s Simple 7, an evidenced-based metric of seven health promoting behaviors and biological factors that improve CV outcomes. Given expanding mobile technology use among AAs, mobile health (mHealth) interventions are promising avenues to promote CV health within this population. Hypothesis: An evidence-based, theory-informed, culturally relevant, community-based mHealth lifestyle intervention would improve CV health among AAs adults. Methods: Five predominately AA churches collaborated in a community-based participatory research approach to develop a 10-week CV health and wellness digital application-based program ( FAITH! App ). We enrolled AA adults [N=50, mean age 49.6 (SD 12.7), 70% women (35/50)] into a single group, 10-week intervention centered on the FAITH! App with adjunct in-person sessions. The FAITH! App included ten core video education modules from health professionals on CV health, interactive diet/physical activity self-monitoring and a sharing board. The primary outcome was change in individual CV health behaviors (body mass index, physical activity, diet, cigarette smoking) and biological factors (blood pressure (BP), total cholesterol, fasting glucose) from baseline to post-intervention at 28 weeks. Results: Participants were overall high CV risk at baseline (hypertensive [40% (20/50)] with poor/intermediate physical activity [79% (37/47)] and diet [72% (36/50)]). At 28 weeks, there were substantial improvements in CV health factors (systolic and diastolic BPs), CV health behaviors (diet, physical activity) and psychological/psychosocial variables to promote behavior change ( Table 1 ). Conclusions: This study supports the benefits of a culturally relevant, community-based mHealth lifestyle intervention to promote CV health among AAs with high cardiometabolic risk.
Abstract 5197: Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression
Authors: Zong-long Hu, Ya-fang Wang, Yi Su, Yan-yan Shen, Yan-fen Fang, Jian Ding, Yi Chen
Journal: Cancer Research (2019)

Abstract The approved pan-histone deacetylase (HDAC) inhibitors have brought impressive therapeutic benefits for patients with a few subtypes of hematologic malignancies. Favorable outcomes in breast cancer have not been observed, although multiple HDAC inhibitors have been therapeutically validated in preclinical breast cancer models. Here, we report that pan-HDAC inhibitors provoke breast cancer metastasis in vitro and in vivo, which will severely impede their clinical benefits. Given the role of HDAC inhibitors in the epigenetic control of transcription, we utilized RNA sequencing (RNA-seq) analysis to analyze global gene-expression changes following LBH589 treatment of MCF-7 cells. Pathway enrichment analysis of the 1591 identified genes based on GO analysis showed that 146 GO were significantly altered. Interestingly, most of the changes were related to cytoskeletal, cell junction, and biological adhesion pathways. Genes in the above mentioned GO were intersected to obtain seven genes by Venn analysis. NEDD9 was among the most significantly upregulated transcripts by LBH589, for which was suggested as a metastasis marker in the last decade. We substantiated this result by detecting the mRNA and protein levels of NEDD9 in HDAC inhibitors treated cells. As with the RNA-seq results, a notable upregulation of NEDD9 mRNA and protein were induced by HDAC inhibitors in breast cancer in vitro and in vivo. Mechanistically, pan-HDAC inhibitors enhance acetylation of H3K9 at the NEDD9 gene promoter to upregulate NEDD9 expression via inhibition of HDAC4, and activate FAK phosphorylation. Notably, we demonstrated that FAK inhibitor can reverse pan-HDAC inhibitor-induced breast cancer metastasis, which may improve HDAC inhibitors efficacy for breast cancer. In summary, we demonstrated an NEDD9-FAK signaling pathway, which was induced by pan-HDAC inhibitors, leading to breast cancer metastasis, and thereby caused limitation of the clinical benefits of HDAC inhibitors on breast cancer. We propose that HDAC4 has an upstream regulatory role in NEDD9 expression, leading to FAK phosphorylation and subsequent stimulation of breast cancer metastasis through epigenetic regulation. Our results suggest a need for increased isoform selective HDAC inhibitor research and development. Citation Format: Zong-long Hu, Ya-fang Wang, Yi Su, Yan-yan Shen, Yan-fen Fang, Jian Ding, Yi Chen. Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5197.
National and State Estimates of Lost Earnings From Cancer Deaths in the United States
Authors: Farhad Islami, Kimberly D. Miller, Rebecca L. Siegel, Zhiyuan Zheng, Jingxuan Zhao, Xuesong Han, Jiemin Ma, Ahmedin Jemal, K. Robin Yabroff
Journal: JAMA Oncology (2019)

Information on the economic burden of cancer mortality can serve as a tool in setting policies and prioritizing resources for cancer prevention and control. However, contemporary data are lacking for the United States nationally and by state.To estimate lost earnings due to death from cancer overall and for the major cancers in the United States nationally and by state.Person-years of life lost (PYLL) were calculated using numbers of cancer deaths and life expectancy data in individuals aged 16 to 84 years who died from cancer in the United States in 2015. The annual median earnings in the United States were used to assign a monetary value for each PYLL by age and sex. Cancer mortality and life expectancy data were obtained from the National Center for Health Statistics and annual median earnings from the US Census Bureau's 2016 Current Population Survey's March Annual Social and Economic Supplement. Data analysis was performed from October 22, 2018, to February 25, 2019.Lost earnings due to cancer death, represented as estimated future wages in the absence of premature death.A total of 8 739 939 person-years of life were lost to cancer death in persons aged 16 to 84 years in the United States in 2015, translating to lost earnings of $94.4 billion (95% CI, $91.7 billion-$97.3 billion). For individual cancer sites, lost earnings were highest for lung cancer ($21.3 billion), followed by colorectal ($9.4 billion), female breast ($6.2 billion), and pancreatic ($6.1 billion) cancer. Age-standardized lost earning rates per 100 000 were lowest in the West and highest in the South, ranging from $19.6 million (95% CI, $19.1 million-$20.2 million) in Utah to $35.3 million ($34.4 million-$36.3 million) in Kentucky. Approximately 2.4 million PYLL and $27.7 billion (95% CI, $26.9 billion-$28.5 billion) in lost earnings (29.3% of total that occurred in 2015) would have been avoided in 2015 if all states had the same age-specific PYLL or lost earning rates as Utah.Our findings indicate large state variation in the economic burden of cancer and suggest the potential for substantial financial benefit through delivery of effective cancer prevention, screening, and treatment to minimize premature cancer mortality in all states.
Abstract 14146: Brain-derived Neurotrophic Factor Plays an Important Role of Exercise Capacity and Mitochondrial Function in the Skeletal Muscle in Mice With Post-infarct Heart Failure
Authors: Takayuki Nakajima, Shintaro Kinugawa, Junichi Matsumoto, Shingo Takada, Takaaki Furihata, Masaya Tsuda, Takashi Katayama, Hideo Nanbu, Ryosuke Shirakawa, Satoshi Maekawa, Naoya Kakutani, Wataru Mizushima, Takashi Yokota, Koichi Okita, Hiroyuki Tsutsui
Journal: Circulation (2016)

Background: Exercise intolerance is an independent prognostic factor in patients with heart failure (HF), which is involved in the dysfunction of skeletal muscle. We previously reported that serum ...
REPORT OF COMMITTEE ON GRADING LESIONS, COUNCIL ON ARTERIOSCLEROSIS, AMERICAN HEART ASSOCIATION
Authors: HENRY C. MCGILL, B. W. BROWN, IRA GORE, GARDNER C. MCMILLAN, JAMES C. PATERSON, O. J. POLLAK, JAMES C. ROBERTS, ROBERT W. WISSLER
Journal: Circulation (1968)

The American Heart Association's Committee on Grading Lesions of the Council on Arteriosclerosis has devised a method of grading the severity of atherosclerosis in human coronary arteries and aortas. The method uses two series of color photographs of arteries arranged in increasing severity of atherosclerosis. The Committee tested the method for inter-observer reproducibility by exhibiting the panel at two national scientific conventions and inviting visitors to grade a set of arteries with the panel. The test demonstrated a reasonable degree of inter-observer reproducibility despite a wide range of experience and disciplinary background. Inter-observer variability decreases with increasing experience in working with atherosclerotic lesions. Training graders who participate in a study may reduce inter-observer bias. For populations with predominantly less or predominantly more atherosclerosis, the investigator should construct special panels with different ranges of severity. The Committee revised the panel in the light of the results of the two exhibits and the comments of users in a field trial. The revised panel provides seven possible scores for each coronary artery and for each aorta. This panel provides a relatively simple and speedy quantitative method of comparing autopsy data on atherosclerosis among many kinds of studies and has the added advantages of facilitating comparisons between different geographic locations and different times.
Abstract 14624: Clinical Status at Age 16 Years is a Powerful Predictor of Survival in the Fontan Adult
Authors: Mark Dennis, Diana Zannino, Karin du Plessis, Yves D’Udekem, David Celermajer, Rachael Cordina
Journal: Circulation (2018)

Background: A high risk of morbidity and mortality is well-documented in adults living with a Fontan circulation. The impact of being well without significant morbidity at transition to adult care ...
Abstract 3055: Genome-wide CRISPR/Cas9 screen for the identification of novel YAP1/TAZ modulators
Authors: Jan Naujoks, Lisette Potze, Anna Anurin, Julia Kuehnlenz, Ralf Lesche, Atanas Kamburov, Ekaterina Nevedomskaya, Andreas Steffen, Martin Lange, Barbara Nicke
Journal: Cancer Research (2019)

Abstract Aberrant activation of the Hippo pathway effectors YAP1/TAZ promotes cell proliferation and tumorigenesis. To identify novel regulators of YAP1/TAZ as a possible means to treat cancer, we established a novel, FACS-based screening system monitoring YAP1/TAZ activity in MDA-MB-231 breast cancer cells. Using these cells, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. We identified approximately 50 genes potentially activating YAP1/TAZ with functions in the Actin Cytoskeleton signaling, p53 signaling, cell polarity or ER stress, amongst others. Moreover, we identified about 30 potential targets which when knocked out induce activity of YAP1/TAZ. The list of hits included genes known to affect the YAP1/TAZ activity such as AJUBA, LATS2 and TEAD, demonstrating the validity of the screen. Functional validation of the novel potential YAP1/TAZ modulators will aid to the further understanding of YAP1/TAZ biology and may open the door to new therapeutic avenues for targeting YAP1/TAZ in cancer. Citation Format: Jan Naujoks, Lisette Potze, Anna Anurin, Julia Kuehnlenz, Ralf Lesche, Atanas Kamburov, Ekaterina Nevedomskaya, Andreas Steffen, Martin Lange, Barbara Nicke. Genome-wide CRISPR/Cas9 screen for the identification of novel YAP1/TAZ modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3055.
Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes
Authors: Leslee J. Shaw, Ron Blankstein, David L. Brown, Sanket S. Dhruva, Pamela S. Douglas, Tessa S.S. Genders, Raymond J. Gibbons, John P. Greenwood, Raymond Kwong, Jonathon Leipsic, John J. Mahmarian, David Maron, Eike Nagel, Ed Nicol, Koen Nieman, Patricia A. Pellikka, Rita F. Redberg, Jonathan Weir-McCall, Michelle C. Williams, Y. Chandrasekhar
Journal: JACC. Cardiovascular imaging (2019)
Abstract 14229: Accurate Infarct Identification by Combined Electromechanical Mapping and Magnetic Resonance Imaging to Improve the Targeting of Intramyocardial Injections in a Porcine Model of Chronic Myocardial Infarction
Authors: René van Es, Frebus J van Slochteren, Mariann Gyöngyösi, Tycho I van der Spoel, Stefan Koudstaal, Tim Leiner, Pieter A Doevendans, Steven A Chamuleau
Journal: Circulation (2015)

Introduction: For optimal success of cardiac regenerative therapy intramyocardial catheter guided stem cell transplantations are performed in infarct border zone areas i.e. the closest region of viable myocardium in the vicinity of the infarct area. To optimize the therapeutic effect this area should be accurately identified. The gold standard technique to determine the infarct size and location is late gadolinium enhanced (LGE) MRI. Nevertheless, the NOGA®XP electromechanical mapping (EMM) system is used to guide injections to the infarct border zone. Since EMM is expensive, time consuming and has a low spatial resolution, we have developed a practical and accurate technique to fuse the NOGA®XP electromechanical maps with LGE-MRI to guide injections based on high resolution MRI data. Methods: LGE-MRI and EMM were obtained in 17 pigs with chronic myocardial infarction. MRI and EMM datasets were registered using our in-house developed 3D CartBox image registration software toolbox. Comparisons between MRI and EMM were performed to assess: 1) feasibility of the 3D CartBox fusion technique, 2) the EMM values measured in the areas with a distinct infarct transmurality (IT). Results: Registration was successful in all datasets, and resulted in a mean error of 3.01±1.94mm between the MRI mesh and EMM points (Fig 1A). The highest sensitivity and specificity to identify infarct border zone of 50% IT was found for bipolar voltage between 1.2 and 1.7mV (Fig 1B). Conclusions: Our new 3D CartBox image registration toolbox enables real time registration of the EMM on MRI during the injection procedure. The optimal spatial resolution and the instant visualization of the MRI images enables users to easily guide injections to the most optimal injection location for cardiac regenerative therapy based on the gold standard infarct imaging technique. This technique allows physicians to harness the full therapeutic effect of the therapy.
Abstract 18752: An Ultra-short Cognitive Screening Test to Detect Significant Post-stroke Vascular Cognitive Impairment
Authors: Catherine Dong, Kenny Xu, Christopher Chen
Journal: Circulation (2015)

Objective: The National Institute of Neurological Disease and Stroke – Canadian Stroke Network (NINDS-CSN) harmonization battery recommended a 5-minute bedside cognitive screening test drawn from the Montreal Cognitive Assessment (MoCA). However this 5-minute cognitive screening test consisted of (5 word registration, recall, recognition, orientation, animal fluency) was based on expert opinion and not empirical evidence. We therefore aimed to establish an ultra-short cognitive screening test for the detection of post-stroke vascular cognitive impairment (VCI). Method: Patients with ischemic stroke/ Transient Ischemic Attack received MoCA within 14 days after stroke and at 3-6 months later. Cognitive outcomes was defined by formal neuropsychological evaluation at month 3-6 and classified as either ‘none-mild VCI (impairment ≤2 domains)’ or ‘moderate-severe VCI (impairment &gt;2 domains)’. Results: There were 327 out of 400 patients completed neuropsychological assessments 3-6 months after stroke onset. Of these, 250 (76.5%) had no-mild VCI and 77 (23.5%) had moderate-severe VCI. Most patients were Chinese (70.3%) and males (69.8%) with age of 59.8 ± 11.6 years and education of 7.7 ± 4.3 years. Random forest analysis showed 5 most sensitive items of MoCA for the ultra-short test (5-Min MoCA) at baseline and 3 months to detect significant VCI at 3-6 months. These 5 items were the clock, serial 7s, animal fluency, recall and orientation. Receiver operating characteristic curve analysis showed that MoCA at 3 months had the largest area under curve (AUC) (0.90), followed by 5-Min MoCA at 3-6 months (0.89), baseline MoCA (0.86) and baseline 5-min MoCA (0.83). At 3-6 months, 5-Min MoCA was equivalent to the MoCA and superior to 5-Min MoCA at baseline (p=0.17 and p=0.04, respectively). The cutoff points for 5-Min MoCA at 3-6 months and baseline was the same (cutoff: 12/13 vs 12/13, sensitivity: 0.70 vs 0.74; specificity: 0.87 vs 0.74; classification accuracy: 0.83 vs 0.74, respectively). Conclusion: The empirically derived 5-min MoCA differs from the NINDS-CSN 5-min test. The established 5-min MoCA at 3-6 months after stroke is equivalent to the MoCA and superior to the 5-min MoCA at baseline, therefore should be used for routine practice.
Abstract 16171: A Simple Risk Score to Predict Mortality for Patients With Heart Failure With Preserved Ejection Fraction -A Report From the CHART-2 Study-
Authors: Shintaro Kasahara, Yasuhiko Sakata, Kotaro Nochioka, Ruri Abe, Takuya Oikawa, Masayuki Sato, Hajime Aoyanagi, Takashi Shiroto, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Although several prediction models for patients with heart failure (HF) are available, they require complicated calculation with various variables. Moreover, few risk models are availab...