tbuckley/cabot-search huggingface dataset:
Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques
Authors: Sarah R. Langley, Karin Willeit, Athanasios Didangelos, Ljubica Perisic Matic, Philipp Skroblin, Javier Barallobre-Barreiro, Mariette Lengquist, Gregor Rungger, Alexander Kapustin, Ludmilla Kedenko, Chris Molenaar, Ruifang Lu, Temo Barwari, Gonca Suna, Xiaoke Yin, Bernhard Iglseder, Bernhard Paulweber, Peter Willeit, Joseph Shalhoub, Gerard Pasterkamp, Alun H. Davies, Claudia Monaco, Ulf Hedin, Catherine M. Shanahan, Johann Willeit, Stefan Kiechl, Manuel Mayr
Journal: Journal of Clinical Investigation (2017)

The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms.We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies.Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study.The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery.UK: British Heart Foundation (BHF); King's BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy's and St Thomas' NHS Foundation Trust and King's College London in partnership with King's College Hospital. Austria: Federal Ministry for Transport, Innovation and Technology (BMVIT); Federal Ministry of Science, Research and Economy (BMWFW); Wirtschaftsagentur Wien; and Standortagentur Tirol.
Concurrent chemotherapy practice patterns for head and neck cancer: What is standard of care?
Authors: S. J. Wong, Z. Agha, S. Milligan
Journal: Journal of Clinical Oncology (2006)

5542 Background: The superiority of concurrent high dose cisplatin and radiation (RT) compared to RT alone for pts with locally advanced squamous cell cancer of the head and neck (SCCHN) has been demonstrated in large prospective phase III clinical trials. However, little is known regarding general prescribing patterns for chemotherapy (CT) utilization in combined modality treatment (CMT) for SCCHN. We conducted the present study to gain insight as to whether results from pivotal phase III trials affect utilization of concurrent CT in academic and community centers. Methods: We analyzed individual data from 326 SCCHN pts treated with concurrent CT and RT between 03/2003 and 12/2004 from 53 centers (43 community-based, 7 academic, and 3 VA or military) using electronically captured data from IntelliDose, a chemotherapy order software program. Results: Of 326 total pts, 123 pts (38%) received single agent cisplatin. From this group, 71 (58%) received low dose cisplatin (&lt;74 mg/m 2 , mean initial dose 67 mg), while 52 patients (42%) received high dose cisplatin (≥ 74 mg/m 2 , mean initial dose 189 mg). 72 pts (22%) received carboplatin/paclitaxel, 60 pts (18%) received cisplatin /5FU, 18 pts (5.5%) received single agent carboplatin, while 6 pts (1.8%) received cetuximab either alone or in combination with cisplatin. Other infrequently used regimens (each &lt; 5%) cumulatively accounted for 14% of pts treated. Comparison of chemotherapy utilization between academic and community-based practice centers showed no statistical difference with respect to use of high dose cisplatin versus low dose cisplatin, or single agent cisplatin versus non-cisplatin regimens. Conclusions: Despite evidence from phase III studies that concurrent high dose cisplatin is the standard of care for CMT of locally advanced SCCHN, utilization of other regimens, such as weekly low dose cisplatin, are commonly utilized. [Table: see text]
Persistent pain following breast cancer surgery: Why does it hurt more for some survivors than others?
Authors: Amy Lowery, Dana H. Bovbjerg, Ellen Ingalls Beckjord, Adam Brufsky, Carol Marie Greco, Carissa A. Low, Jodi Martin, Donna M. Posluszny, John E. Schmidt, John R. Shaffer, Inna Belfer
Journal: Journal of Clinical Oncology (2014)

e20634 Background: Persistent pain after breast cancer surgery (PP) is common, can last years, and is difficult to treat pharmacologically. Among survivors with PP, however, there is considerable variability in pain severity. The factors responsible for this variability are not known, but studies suggest it may be related to psychosocial factors, not medical or treatment-related factors. Based on evidence that sleep disturbance (SD) is associated with increased pain, we hypothesize that survivors with SD will have more severe PP and may suffer disproportionally from effects of known psychological predictors of pain, such as anxiety and depression, as well as pain catastrophizing. Methods: Self-report data collected with validated questionnaires were used to analyze responses from 282 females reporting some level of PP (age: M=59.3 years, SD=11.0; years since surgery M=3.0, SD=2.9). Data analysis included chi-square tests, independent samples t-tests and Pearson’s correlations. Results: SD was found in 29.4% (n=83) of the sample. Good sleepers did not differ by age, education, race, marital status, work status, income, alcohol use, exercise, body mass index, postmenopausal status, history of radiotherapy, chemotherapy or hormone therapy, or time since surgery (ps>.05). Those with SD reported significantly more pain (t[280]=-2.33) and analgesic use (χ2=13.94). They also reported significantly more depression (t[280]=-3.57) and anxiety (t[280]=-4.52), as well as pain catastrophizing (t[280]=-4.52). Depression (r=.36) and anxiety (r=.25) were the strongest correlates of pain severity in good sleepers. In contrast, pain catastrophizing (r=.49) (rumination, magnification, helplessness [rs=.42-.48) were the strongest correlates of pain severity in those with SD. Conclusions: This supports our hypothesis that SD is related to more severe PP following breast cancer surgery, and suggests that the well-known strong relationship of pain catastrophizing and pain severity may in part be due to concurrent SD. Future research should explore the possible beneficial effects of behavioral interventions that concurrently address SD and pain catastrophizing among women with PP following breast cancer surgery.
LONG-TERM RISK OF RECURRENT ARRHYTHMIA IN PATIENTS WITH TYPICAL ATRIAL FLUTTER UNDERGOING PULMONARY VEIN ANTRUM ISOLATION OR CAVO-TRICUSPID ISTHMUS ABLATION WITH PERMANENT ISOLATION
Authors: Sanghamitra Mohanty, Luigi Di Biase, Chintan Trivedi, Carola Gianni, John Burkhardt, Javier Sanchez, Amin Al-Ahmad, Rodney Horton, Gemma Pelargonio, Giovanni Forleo, Sakis Themistoclakis, Michela Casella, Antonio Dello Russo, Claudio Tondo, Andrea Natale
Journal: Journal of the American College of Cardiology (2017)
Probing the Evolutionary History of Human Bitter Taste Receptor Pseudogenes by Restoring Their Function
Authors: Davide Risso, Maik Behrens, Eduardo Sainz, Wolfgang Meyerhof, Dennis Drayna
Journal: Molecular Biology and Evolution (2017)

Lineage-specific gene losses can be driven by selection or environmental adaptations. However, a lack of studies on the original function of species-specific pseudogenes leaves a gap in our understanding of their role in evolutionary histories. Pseudogenes are of particular relevance for taste perception genes, which encode for receptors that confer the ability to both identify nutritionally valuable substances and avoid potentially harmful substances. To explore the role of bitter taste pseudogenization events in human origins, we restored the open reading frames of the three human-specific pseudogenes and synthesized the reconstructed functional hTAS2R2, hTAS2R62 and hTAS2R64 receptors. We have identified ligands that differentially activate the human and chimpanzee forms of these receptors and several other human functional TAS2Rs. We show that these receptors are narrowly tuned, suggesting that bitter-taste sensitivities evolved independently in different species, and that these pseudogenization events occurred because of functional redundancy. The restoration of function of lineage-specific pseudogenes can aid in the reconstruction of their evolutionary history, and in understanding the forces that led to their pseudogenization.
FAMILIAL COMBINED HYPERLIPIDEMIA IS CHARACTERIZED BY HIGHER ARTERIAL AND HEPATIC FLUORODEOXYGLUCOSE UPTAKE COMPARED TO HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
Authors: Koutagiar Peter Iosif, Konstantinos Toutouzas, Georgios Benetos, Nikoletta Pianou, Ioannis Skoumas, Alexandros Georgakopoulos, Spyridon Galanakos, Pavlos Kafouris, Angeliki Rigatou, Andreas Synetos, George Spyrou, Eleftherios Tsiamis, Michael Peters, Constantinos Anagnostopoulos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2017)
ATHEROGENIC LIPOPROTEIN VARIABILITY CORRELATES WITH CORONARY ATHEROMA PROGRESSION: INSIGHTS FROM SERIAL INTRAVASCULAR ULTRASONOGRAPHY
Authors: Donald Clark, Stephen Nicholls, Julie St. John, Mohamed Elshazly, Samir Kapadia, Murat Tuzcu, Steven Nissen, Rishi Puri
Journal: Journal of the American College of Cardiology (2017)
Outcomes of conservatively managed localized prostate cancer
Authors: G. Lu-Yao, P. C. Albertsen, D. F. Moore, Y. Lin, W. Shih, M. J. Barry, A. Zietman, M. O’Leary, E. Walker-Corkery, R. S. DiPaola, S. Yao
Journal: Journal of Clinical Oncology (2009)

5010 Background: The natural history of screen-detected prostate cancer has not been well described. Methods: Cancer-specific and overall mortality, assessed through competing risk analyses, were determined for 14,516 men aged 65 years or older diagnosed between 1992–2002 and did not receive surgery or radiation within 6 months of cancer diagnosis. The population-based cohort was identified from US cancer registries, which had 98% completeness in case ascertainment. Results: Compared to earlier era studies, survival has improved considerably for conservatively managed patients diagnosed in the contemporary prostate specific antigen (PSA) era ( Table ). Conclusions: Men diagnosed with prostate cancer in the PSA era have survival outcomes significantly better than those in the past. Patients and healthcare providers may need to reassess some treatment options in light of these data. [Table: see text] No significant financial relationships to disclose.
DOES BALLOON PREDILATATION INFLUENCE OUTCOME WITH THE LOTUS VALVE: 30-DAY RESULTS FROM THE RESPOND STUDY
Authors: Nicolas M. Van Mieghem, Jochen Woehrle, David Hildick-Smith, Sabine Bleiziffer, Daniel J. Blackman, Mohamed Abdel-Wahab, Ulrich Gerckens, Axel Linke, Hueseyin Ince, Peter M. Wenaweser, Dominic Allocco, Keith Dawkins, Volkmar Falk
Journal: Journal of the American College of Cardiology (2017)
R497K of EGFR and BIM deletion polymorphisms as predictive biomarkers to EGFR TKIs in NSCLCs harboring wild-type EGFR.
Authors: Jin Hyoung Kang, Jung-Young Shin, Jeong-Oh Kim, Ji-Eun Oh, Eun Kyoung Jeon, Sook Hee Hong, Sang Hoon Chun
Journal: Journal of Clinical Oncology (2013)

1540 Background: Activating EGFR mutations are strongly predictive of EGFR tyrosine kinase inhibitor (TKI) activity in NSCLCs, however, some patients having wild type EGFRdo not infrequently show clinically favorable outcome to EGFR TKIs. The key proapoptotic proteins have been reported to be involved in TKI-induced cell death. The up-regulation of BIM, a pro-apoptotic protein of BCL2 family, is required for TKIs to induce apoptosis in cancers. Methods: For 150 advanced or metastatic NSCLC pts. receiving gefitinib or erlotinib, we assayed mutation status of EGFR in paraffin embedded tumor tissue using PNA clamping (PANAGENE, Korea) and direct sequencing. Six different genetic variants of EGFR (-191C&gt;A, -216 G&gt;T, CA repeat number, R497K, 2607G&gt;A, and D994D) and BIMdeletion in genomic DNA extracted from peripheral blood were analyzed. Results: M:F ratio was 72:78 and median age was 63 (35~82). Histological subtypes are as follows: 131 adenocarcinoma (87.3%), 16 squamous cell ca. (10.7%) and 3 large cell ca. (1.3%). Objective tumor response (CR+PR) was observed in 60 pts. (40.0%) and SD in 44 pts. (29.3%). Median PFS and OS were 4.3 (0.4~67.4) and 18.6 (0.9~78.1) months, respectively. Of 129 pts. in whom EGFR mutation could be analyzed, 41 pts. (31.8%) had activating EGFR mutation. In univariate analysis, only gender was associated with objective response to EGFR TKI in activating EGFR mutant group (P=0.048). In wild type EGFR group (n=88), R497K (P=0.04) and BIM (P=0.04) as well as gender (P=0.05) were significantly correlated with objective response. In addition, multivariate analysis demonstrated that gender, R497K and BIM were associated with objective response to EGFR TKIs in wild type EGFR group with statistical significance (P=0.023, 0.027 and 0.018, repectively). Neither six EGFR polymorphisms nor BIM was correlated with PFS and OS in activating EGFR mutant group. Meanwhile, in wild type EGFR group, R497K was significantly associated with OS (P=0.028). Conclusions: Taken together, our data suggest that R497K of EGFR and BIM deletion polymorphisms are useful pharmacogenetic biomarkers to predict objective tumor response for EGFR TKIs in advanced NSCLC pts. harboing wild type EGFR.
ASCENDING AORTIC DIMENSIONS IN FORMER NATIONAL FOOTBALL LEAGUE ATHLETES
Authors: James L. Gentry, David Carruthers, Christopher Maroules, Parag Joshi, Colby Ayers, Philip Aagaard, Rory Hachamovitch, Reginald Dunn, Andrew Lincoln, Andrew Tucker, Kezia Alexander, Dermot Phelan
Journal: Journal of the American College of Cardiology (2017)
To ProtecT Our Patients With Prostate Cancer
Authors: Daniel E. Spratt
Journal: JAMA Oncology (2017)

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Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells
Authors: Ran Ma, Govindasamy-Muralidharan Karthik, John Lövrot, Felix Haglund, Gustaf Rosin, Anne Katchy, Xiaonan Zhang, Lisa Viberg, Jan Frisell, Cecilia Williams, Stig Linder, Irma Fredriksson, Johan Hartman
Journal: JNCI Journal of the National Cancer Institute (2017)

Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer. Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ERβ-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis. Results: We identified an absence of ERα but upregulation of ERβ in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ERβ caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate < 0.001) upregulated in ERβ-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ERβ (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts. Conclusion: We identify ERβ as a mediator of estrogen action in BSCs and a novel target for endocrine therapy.
PREDICTORS AND CLINICAL OUTCOMES OF NEXT-DAY DISCHARGE AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Norihiko Kamioka, John Wells, Stamatios Lerakis, Frank Corrigan, Jose Condado Contreras, Hope Caughron, Andy Dong, Patricia Keegan, Amy Simone, Jose Binongo, Bradley Leshnower, Chandan M. Devireddy, Kreton Mavromatis, Robert Guyton, Vinod Thourani, Peter Block, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2017)
PERSISTENCE WITH THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION: THE GLORIA-AF REGISTRY
Authors: Miney Paquette, Menno Huisman, Gregory Lip, Hans-Christoph Diener, Sergio Dubner, Jonathan Halperin, Changsheng Ma, Kenneth Rothman, Christine Teutsch, Shihai Lu, Lionel Riou França, Kristina Zint, Dorothee B. Bartels, Robby Nieuwlaat
Journal: Journal of the American College of Cardiology (2017)
Assessment of Patients Fitness at Diagnosis in Elderly Acute Myeloid Leukemia
Authors: Semra Aydin, Ernesta Audisio, Stefano D'Ardia, Bernardino Allione, Barbara Nicolino, Alessandro Busca, Chiara Dellacasa, Giorgia Iovino, Andrea Evangelista, Giovannino Ciccone, Umberto Vitolo
Journal: Blood (2016)
HEART FAILURE WITH REDUCED EJECTION FRACTION CARE PATTERNS IN THE OUTPATIENT PRACTICE SETTING: INITIAL FINDINGS FROM CHAMP-HF
Authors: Gregg C. Fonarow, Nancy Albert, Javed Butler, J. Herb Patterson, John Spertus, Fredonia Williams, Stuart Turner, Wing Chan, Carol Duffy, Adam DeVore, Xiaojuan Mi, Laine Thomas, Adrian Hernandez
Journal: Journal of the American College of Cardiology (2017)
SEGMENTAL CIRCUMFERENTIAL STRAIN DERIVED FROM DENSE PREDICTS IMPROVEMENT OF LEFT VENTRICULAR FUNCTION POST ST ELEVATION MYOCARDIAL INFARCTION: THE BHF MR-MI STUDY
Authors: Kenneth Mangion, Guillaume Clerfond, Christopher Rush, David Carrick, Christie McComb, Hao Gao, Xiaoyu Luo, Hany Eteiba, Martin Lindsay, Margaret McEntegart, Stuart Hood, Mark Petrie, Keith Oldroyd, Stuart Watkins, Andrew Davie, Xiaodong Zhong, Caroline Haig, Colin Berry
Journal: Journal of the American College of Cardiology (2017)
Clinical Characterization of a Novel Oral Thrombopoietin Mimetic LGD-4665 in Healthy Volunteers Demonstrate Safe and Sustained Increases in Platelet Counts with Flexible Dosing Choices for Phase II Trials.
Authors: Zofia E. Dziewanowska, Ram P. Kapil, J. K. Zhang, Jolene K. Berg, Victor J. Stevens, Richard M. Matsumoto, Lisa Greenberg, Maryanna Y. Morris
Journal: Blood (2008)
INFLAMMATORY RESPONSE AND INFARCTION SIZE ARE DECREASED WITH TICAGRELOR COMPARED TO CLOPIDOGREL IN PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Slobodan Dusan Obradovic, Boris Dzudovic, Nemanja Djenic, Radoslav Romanovic, Zoran Jovic, Marijan Spasic
Journal: Journal of the American College of Cardiology (2017)
CAROTID PLAQUE IS PREDICTIVE OF CARDIO VASCULAR EVENTS IN ASYMPTOMATIC DIABETES: A PROSPECTIVE STUDY
Authors: Anand Jeevarethinam, Shreenidhi Venuraju, Alain Dumo, Sherezade Ruano, Miranda Rosenthal, Devaki Nair, Daniel Darko, Mark Cohen, Avijit Lahiri, Roby Rakhit
Journal: Journal of the American College of Cardiology (2017)
Clinical observation of external compound Chinese herbal extract LC09 with capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer.
Authors: Yanni Lou, Liqun Jia, Yuan Li, Liya Li, Shijie Zhu, Huangying Tan, Donggui Wan, Zhiqiang Cheng, Meng Liu, Bo Deng
Journal: Journal of Clinical Oncology (2015)

e12006 Background: Capecitabine(Cape) maintenance therapy after response to Cape-based combination chemotherapy(chemo) is one of the standard regimens recommended by NCCN for metastatic breast cancer(MBC) treatment. Hand-foot syndrome (HFS) induced by Cape may lead to dose modification or treatment interruption, even when the therapy may prove beneficial. The earlier-phase data of external compound Chinese herbal extract LC09 (Herba Geranii, etc.) has shown significant effective on treating HFS. This study aimed to evaluate the efficacy of LC09 with Cape maintenance therapy in MBC. Methods: MBC patients (pts) who responded to the first-line Cape-based combination chemo (docetaxel/navelbine/gemcitabine and cape, 6 cycles) were assigned to Cape maintenance therapy until disease progression or intolerable toxicity. Pts were randomly to receive LC09 and Cape (LC09 Group) versus single Cape (Control Group). Cape 1,000 mg/m2, PO, twice daily, d1-14, every 21 days. LC09 granules 10g was dissolved in 1,000ml of warm water (keep 34°C-37°C in a footbath), pts soaked their feet and hands in this lotion for 20 minutes, twice daily. The primary endpoint was progression-free survival (PFS) and secondary endpoints included HFS incidence rate, HFS NCI Grade as well as safety. Results: A total of 32 pts have been enrolled, all of them are Asian and female. The median age was 45.5yrs (range 27-70). The cycles of Cape maintenance chemo were 113 in LC09 group, 80 in control group. The LC09 group decreased the HFS incidence rate than control group (18.75% vs. 43.75%; p<0.01), and achieved longer median PFS (8.4 months vs. 7.35 months; p<0.05). NCI Grade for HFS as 1/2/3, Grade 2/1/0 in LC09 group (3/16), and 2/3/2 in control group (7/16). The cape withdrawal rate induced by HFS was 0 in LC09 group, 6.25% (1/16) in control group. Conclusions: Compound external Chinese herbal extract LC09 plus Cape maintenance therapy, could decrease the HFS incidence rate and cape withdrawal rate, and thus has shown the tendency to improve the PFS. Further research and overall survival (OS) should be observed. (Funded by No.2015BAI04B07)
SEX DIFFERENCES IN THE RISK FACTORS FOR ENDOTHELIAL AND MICROVASCULAR DYSFUNCTION IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Vedant Pargaonkar, Yuhei Kobayashi, Takumi Kimura, David Lee, Marcia Stefanick, William Fearon, Alan Yeung, Jennifer Tremmel
Journal: Journal of the American College of Cardiology (2017)