tbuckley/cabot-search huggingface dataset:
Abstract P5-14-05: α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro
Authors: K-W Tam, C-H Lee
Journal: Cancer Research (2018)

Abstract Background: The cancer preventive activity of vitamin E (α-tocopherol, α-TP) has been suggested by many epidemiologic studies. Our previous study showed that Tocopherol-Associated Protein (TAP), a major tocopherol–binding protein, is preferentially detected in normal breast tissues than in tumor regions among 93 clinical breast cancer patients, which postulate its tumor suppressive role in breast cells. Pterostilbene (3,5-dimethoxi-49-hydroxystilbene, PS) is a natural dimethylated analogue of Resveratrol found in different plants. Previous studies have shown that PS has the ability to induce apoptosis in a range of cancer cell lines. The purpose of our study was to assess the effect of TAP and Pterostilbene in tumor suppression of breast cancer cell. Methods: Cell growth, proliferation, and viability were determined using the MTT assay. TAP protein expression was ablated in MDA-MB-231 breast cancer cell with nine independent siRNA sequences. MDA-MB-231 cells were transfected with pcDNA5 plasmids expressing the firefly luciferase gene. TAP protein expressions for each plasmid transfection were measured by western-blot analysis. Synergic effects of tumor growth and metastasis inhibitions in MDA-MB-231 xenograft animal model by PS and α-tocopherol treatment were evaluated. Results: TAP served as a key molecular in responding to α-tocopheryl succinate (α-TOS) induced cell cycle regulation. PS has demonstrated the synergic decrease on breast cancer cell growth effects by the combination of α-TOS exposure. In animal model, treatment of PS and high level vitamin E diet not only induced breast tumor growth inhibition, but also suppressed tumor cell invasion by measuring circulation tumor cells in mouse blood. Conclusions: Upon the evidences showed in this study, we suggest taking vitamin E and PS as supplements may provide both breast tumor preventative and therapeutic benefits in clinic. Citation Format: Tam K-W, Lee C-H. α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-14-05.
LONG-TERM PROGNOSIS OF PATIENTS WITH IRREGULAR PROTRUSION AFTER SECOND-GENERATION DRUG-ELUTING STENT IMPLANTATION: OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Yoshinori Sanuki, Shinjo Sonoda, Toshiya Miura, Akiyoshi Shimizu, Hironori Takami, Reo Anai, Yoshitaka Muraoka, Yuki Tsuda, Masaru Araki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2018)
Abstract 18074: Fast and Accurate View Classification of Cardiac Echocardiograms Using Deep Learning
Authors: Ali Madani, Ramy Arnaout, Mohammad Mofrad, Rima Arnaout
Journal: Circulation (2017)

Background: Echocardiography is essential to modern cardiology. However, human interpretation limits accurate and standardized high-throughput analysis, limiting echocardiography from reaching its ...
Analysis of dendritic cells and ischemia-reperfusion changes in postimplantation renal allograft biopsies may serve as predictors of subsequent rejection episodes
Authors: Ibrahim Batal, Sumit Mohan, Sacha A. De Serres, Elena-Rodica Vasilescu, Demetra Tsapepas, Russel J. Crew, Shefali S. Patel, Geo Serban, Kasi McCune, Syed A. Husain, Jae-Hyung Chang, Jan M. Herter, Govind Bhagat, Glen S. Markowitz, Vivette D. D’Agati, Mark A. Hardy, Lloyd Ratner, Anil Chandraker
Journal: Kidney International (2018)
Beyond foundation programmes
Authors: Rhona MacDonald
Journal: BMJ (2004)

Pathology, “is the fundamental basis of medicine and surgery,” according to the vice president of the Royal College of Pathologists, a specialist registrar in forensic pathology, and a research fellow in transfusion medicine (p 187). But before you dismiss this bold statement as being understandably biased, consider the fact that UK pathologists are involved in about 70% of all diagnoses. Despite this, fewer medical …
TOXIC MYOCARDITIS FROM COMBINED CANNABIS AND BUTANE INHALATION
Authors: Venkat Lakshmi, Kishan Vuddanda, Naga Sai, Shravan Turaga, Mohammad-Ali Jazayeri, Bhavya Yarlagadda, Mohit Turagam, Yeruva Madhu Reddy, Seth Sheldon, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2018)
CLINICAL OUTCOMES TO 4 YEARS IN PATIENTS IMPLANTED WITH BIOABSORBABLE POLYMER SYNERGY VERSUS PERMANENT POLYMER EVEROLIMUS-ELUTING STENTS: THE EVOLVE II RANDOMIZED TRIAL
Authors: Robert Jobe, Stephan Windecker, Akil Loli, David Mego, Kenji Ando, Toshiya Muramatsu, Francis Stammen, Michael Curtis, Steffen Helqvist, Thomas Christen, Dominic Allocco, Ian Meredith, Dean Kereiakes
Journal: Journal of the American College of Cardiology (2018)
Functional outcome and quality of life in patients undergoing salvage radical prostatectomy (SRPE).
Authors: David Pfister, Jasmin Pullankavumkal, Friederike Haidl, Vahudin Zugor, Tobias Kohl, Daniel Porres-Knoblauch, Axel Heidenreich
Journal: Journal of Clinical Oncology (2018)

212 Background: Salvage radical prostatectomy is one option for patients with locally recurrent disease with proven long term oncologic control. There are concerns about worse functional results due to fibrotic tissue after radiotherapy and patients are treated with palliative systemic androgendreptivation. We retrospectively analyzed continence and quality of life in patients undergoing SRPE. Methods: After biopsy proven local recurrent prostate cancer 138 patients were offered SRPE and extended lymphadenectomy. Continence and quality of life had been collected before 6 and 12 months after surgery. Validated questionaires with ICIQ and EORTC qlq 30 had been used. Results: Präoperatively at 6 monts and 12 months the feed back was available in 93, 84 and 82 patients respectively. Präoperatively there was no or mild incontinence in 38(40.8%), moderate in 33 (35.5%) and strong incontinence in 22 (23.7%) of the patients. There is a significant decrease in the rate of continence after 6 and 12 months to no or mild in 19 (23.1%), moderate in 19 (23.2%) and strong incontinence in 44 (53.7%) of the patients. In 5 patients an artifitial sphinkter was implanted. Quality of life did not change significantly before and 12 months after surgery. Median value of Question 30 was 6 and five respectively. Conclusions: Patients need to be informed about a worse functional outcome and the potential need for further surgical interventions as artificial sphinkter implantion compared to primary radical prostatectomy. Quality of life seems to be affected only moderatly. Nevertheless there is already a rather high rate of any incontinence before surgery that needs to be taken into account.
O018 CCR6+ T helper cells drive antigen-induced arthritis via the IL-23R pathway
Authors: W Razawy, PS Asmawidjaja, A-M Mus, N Salioska, M Van Meurs, I Haspels-Brouwers, N Kops, E Lubberts
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The IL-23/IL-17A immune pathway is important for the progression of T cell-mediated arthritis. However, it is not known where IL-23R<sup>+</sup> T cells locate at different stages of arthritis and which IL-23R<sup>+</sup> cells are drivers of joint inflammation. <h3>Objectives</h3> We aimed to identify IL-23R<sup>+</sup> T cells in the secondary lymphoid organs and synovium during the development and progression of antigen-induced arthritis (AIA). Furthermore, we studied which IL-23R<sup>+</sup> cells drive full-blown AIA. <h3>Methods</h3> To induce AIA, IL-23R<sup>+/+</sup> (wild type), heterozygous IL-23R<sup>+/GFP</sup> (IL-23R-GFP.KI reporter), and IL-23R<sup>GFP/GFP</sup> (IL-23RKO) mice were immunised with methylated bovine serum albumin (mBSA) in Complete Freund’s Adjuvant. After 7 days mice were injected in the knee joints with mBSA. Mice were macroscopically scored and knees were used for histological analysis of inflammation and bone erosion. The spleen, inguinal and popliteal lymph nodes, and the synovium were collected and assessed for expression of GFP/IL-23R<sup>+</sup> cells. Adoptive transfer of CCR6<sup>+</sup> T helper cells and γδ T cells from heterozygous mice into IL-23RKO mice was performed via i.v. injection prior to AIA induction. <h3>Results</h3> AIA disease progression was mainly driven by the IL-23R pathway as IL-23RKO mice had significantly lower arthritis scores and less bone damage. Heterozygous mice had similar disease scores to WT mice, indicating that half of the receptor expression is sufficient to drive disease. Flow cytometric analysis of GFP/IL-23R expression revealed that among the T cells, CCR6<sup>+</sup> T helper and γδ T cells but not CD8<sup>+</sup> T cells expressed the IL-23R in the lymphoid tissues. During the progressive phase of arthritis, lymphoid tissue cell numbers were lower in IL-23RKO mice. On the other hand, the overall percentage of T cells was higher in the IL-23RKO lymphoid tissues, suggesting that these cells develop but remain in the lymphoid tissues. CD4<sup>+</sup> and γδ T cells but not CD8<sup>+</sup> T cells were abundantly present in the WT joints during arthritis, but decreased in IL-23RKO joints. Adoptive transfer of CCR6<sup>+</sup> T helper and γδ T cells into IL-23RKO mice revealed that CCR6<sup>+</sup> T helper cells are the main drivers of AIA. <h3>Conclusions</h3> AIA progression is driven by IL-23R signalling and CCR6 +T helper cells can rescue arthritis in IL-23R deficient mice. Among the T cells, only CCR6<sup>+</sup> T helper and γδ T cells express the IL-23R in the lymphoid tissues. IL23R signalling might be involved in T cell proliferation and/or migration, since CD4<sup>+</sup> and γδ T cell infiltration is decreased in the IL-23RKO synovium. <h3>Disclosure of interest</h3> None declared
Circulating microbiome in blood of different circulatory compartments
Authors: Robert Schierwagen, Camila Alvarez-Silva, Mette Simone Aae Madsen, Carl Christian Kolbe, Carsten Meyer, Daniel Thomas, Frank Erhard Uschner, Fernando Magdaleno, Christian Jansen, Alessandra Pohlmann, Michael Praktiknjo, Gunnar T Hischebeth, Ernst Molitor, Eicke Latz, Benjamin Lelouvier, Jonel Trebicka, Manimozhiyan Arumugam
Journal: Gut (2018)

We read with interest the recent review by Tilg et al ,1 which summarised the role of microbiota in liver diseases and pointed out that a causal link with systemic inflammation has still not been established. This letter fills in this gap and provides an analysis of the circulating microbiota in portal vein as the link between gut and liver. The access to portal circulation is possible during the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Therefore, we characterised the circulating microbiome in portal vein (first venous outflow in gut–liver axis), liver outflow, central venous blood and peripheral venous blood from seven patients with decompensated liver cirrhosis receiving TIPS for either variceal bleeding (n=3) or refractory ascites (n=4) (mean Model for End-stage Liver Disease (MELD) 8.4 (range 6–13), Child-Pugh-Score (CHILD) A: n=4, CHILD B: n=3) (figure 1A). We performed 16S ribosomal RNA (rRNA) gene sequencing of buffy coat samples and identified 65 genera belonging to four phyla (predominantly Proteobacteria) in this cohort (online supplementary figure 1 and figure 1B). Blood microbiome phylum compositions identified in our …
CORRELATION OF AORTIC VALVE ANNULAR PLANE ASSESSMENT BY PRE-PROCEDURAL COMPUTED TOMOGRAPHY VERSUS ON-TABLE 3-DIMENSIONAL ROTATIONAL ANGIOGRAPHY
Authors: Ivan P. Casserly, Sean Murphy, Ciara Malone, Richard Tanner, Ronan Margey, Catherine McGorrian, Declan Sugrue, Andrew Roy
Journal: Journal of the American College of Cardiology (2018)
Temozolomide chemotherapy in newly-diagnosed adult glioblastoma: a systematic review using a computational evidence aggregation technique
Authors: Redwan Farooq, Olivia Lucas, Anthony Hunter, Matthew Williams
Journal: Neuro-Oncology (2018)

Standard treatment for newly-diagnosed glioblastoma in adults consists of maximal surgical resection, followed by radiotherapy with concurrent and adjuvant temozolomide. Many trials have attempted to improve on this regimen. Conventional methods of meta-analysis are limited by problems with lack of transparency and interactivity. We conducted a systematic review using a novel computational method to synthesise and explore the robustness of evidence for new treatment options. We identified all randomised controlled trials in newly-diagnosed adult glioblastoma which included temozolomide in at least one treatment arm. We excluded trials conducted exclusively in the elderly. We extracted data on treatment, overall survival, progression-free survival and toxicities, and assessed the quality of evidence using GRADE criteria. We used a computational evidence aggregation technique to summarise the results in a graphical treatment network. This shows which treatments are superior, the evidence supporting that assessment, and the effect of applying different subjective preference criteria regarding the relative importance of various outcome measures in defining superiority. We analysed data from 24 trials (4756 patients). There is robust evidence supporting the use of standard chemoradiotherapy (7 trials). We identify four additional treatment regimens which may confer a survival advantage: 1) addition of tumour-treating fields, 2) addition of bevacizumab, 3) addition of induction temozolomide, and 4) addition of dendritic cell vaccine. However, the evidence for three of these has significant weaknesses. Our computational evidence aggregation technique shows patterns of hierarchical superiority in temozolomide chemotherapy regimens for newly-diagnosed glioblastoma in adults. We identify several treatment regimens which may be superior to standard chemoradiotherapy. The best supported option is the addition of tumour-treating fields. In addition, we provide a novel graphical method for reviewing the evidence base. This allows clear visualisation of the available evidence, both for understanding the current evidence and planning future trials.
PRE-TRANSPLANT USE OF AMIODARONE IN PRE-TRANSPLANT CARDIOMYOPATHY PATIENTS IS ASSOCIATED WITH INCREASED CARDIOVASCULAR RISK: A META-ANALYSIS
Authors: Jai Parekh, Gaurav Aggarwal, Abhishek Thandra, Rohit Arora, Venkata Alla
Journal: Journal of the American College of Cardiology (2018)
NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018
Authors: Richard T. Hoppe, Ranjana H. Advani, Weiyun Z. Ai, Richard F. Ambinder, Patricia Aoun, Philippe Armand, Celeste M. Bello, Cecil M. Benitez, Philip J. Bierman, Robert Chen, Bouthaina Dabaja, Robert Dean, Andres Forero, Leo I. Gordon, Francisco J. Hernandez-Ilizaliturri, Ephraim P. Hochberg, Jiayi Huang, Patrick B. Johnston, Mark S. Kaminski, Vaishalee P. Kenkre, Nadia Khan, Kami Maddocks, David G. Maloney, Monika Metzger, Joseph O. Moore, David Morgan, Craig H. Moskowitz, Carolyn Mulroney, Rachel Rabinovitch, Stuart Seropian, Randa Tao, Jane N. Winter, Joachim Yahalom, Jennifer L. Burns, Ndiya Ogba
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.
A Multicomponent, Preschool to Third Grade Preventive Intervention and Educational Attainment at 35 Years of Age
Authors: Arthur J. Reynolds, Suh-Ruu Ou, Judy A. Temple
Journal: JAMA Pediatrics (2018)

Educational attainment is the leading social determinant of health, but few studies of prevention programs have examined whether the programs are associated with educational attainment outcomes after the mid-20s, especially for large-scale programs that provide a longer duration of services.To examine the association between a preschool to third grade intervention and educational attainment at midlife and differences by program duration, sex, and parental educational level.This matched-group, alternative intervention study assessed 1539 low-income minority children born in 1979 or 1980 who grew up in high-poverty neighborhoods in Chicago, Illinois. The comparison group included 550 children primarily from randomly selected schools participating in the usual early intervention. A total of 989 children who entered preschool in 1983 or 1984 and completed kindergarten in 1986 were included in the Chicago Longitudinal Study and were followed up for 27 to 30 years after the end of a multicomponent intervention. A total of 1398 participants (90.8%) in the original sample had educational attainment records at 35 years of age. The study was performed from January 1, 2002, through May 31, 2015.The Child-Parent Center Program provides school-based educational enrichment and comprehensive family services from preschool to third grade (ages 3-9 years).Educational outcomes from administrative records and self-report included school dropout, 4-year high school graduation, years of education, postsecondary credential, and earned degrees from associate's to master's or higher.A total of 1539 participants (mean [SD] age, 35.1 [0.32] years; 1423 [92.9%] black and 108 [7.1%] Hispanic) were included in the study. After weighting on 2 propensity scores, preschool participants had higher rates of postsecondary degree completion, including associate's degree or higher (15.7% vs 10.7%; difference, 5.0%; 95% CI, 1.0%-9.0%), master's degree (4.2% vs 1.5%; difference, 2.7%; 95% CI, 1.3%-4.1%), and years of education (12.81 vs 12.32; difference, 0.49; 95% CI, 0.20-0.77). Duration of participation showed a consistent linear association with outcomes. Compared with fewer years, preschool to second or third grade participation led to higher rates of associate's degree or higher (18.5% vs 12.5%; difference, 6.0%; 95% CI, 1.0%-11.0%), bachelor's degree (14.3% vs 8.2%; difference, 6.1%; 95% CI, 1.3%-10.9%), and master's degree or higher (5.9% vs 2.3%; difference, 3.6%; 95% CI, 1.4%-5.9%). The pattern of benefits was robust and favored male participants for high school graduation, female participants for college attainment, and those from lower-educated households.This study indicates that an established early and continuing intervention is associated with higher midlife postsecondary attainment. Replication and extension of findings to other locations and populations should further strengthen confidence in the health benefits of large-scale preventive interventions.
Reduction of T-Box 15 gene expression in tumor tissue as a prognostic biomarker for patients with hepatocellular carcinoma.
Authors: Yuji Morine, Tohru Utsunomiya, Satoru Imura, Tetsuya Ikemoto, Shuichi Iwahashi, Yu Saito, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2018)

341 Background: Genome-wide analysis is widely applied to detect molecular alterations in tumor and non-tumor tissue during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), which was is the third-highest cause of cancer-related deaths worldwide, and investigated the clinical role of most heyper-methylated gene, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. Methods: We used an Illumina Infinium HumanMethylation450 BeadChip Kit to conduct a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC. Methylation scores for CpG sites were assigned a Beta-value. Another validation set, which comprised 58 patients with HCC who underwent radical resection, was analyzed to investigate the relationships between tumor phenotype, prognosis, and TBX15 mRNA expression. Results: TBX15 was the most hyper-methylated gene (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue), and TBX15 mRNA levels in tumor tissues were significantly lower compared with those of non-tumor tissues (p &lt; 0.0001). When we assigned a cutoff value = 0.5-fold to define differential expression of TBX15 mRNA, low TBX15 expression significantly correlated with higher serum DCP levels, and the overall survival 5-year survival rates of the low-expression group (n = 17) were significantly shorter compared with those of the high-expression group (n = 41) (43.3% vs. 86.2%, p = 0.001). Multivariate analysis identified low TBX15 expression as an independent prognostic factor for overall and disease-free survival. Conclusions: Genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of TBX15 in tumor tissue represents a potential biomarker for predicting tumor progression and poor survival of patients with HCC.
HIGH WALL SHEAR STRESS IN THE PROXIMAL SEGMENTS OF HEMODYNAMICALLY SIGNIFICANT CORONARY LESIONS IS INDEPENDENTLY PREDICTIVE OF SUBSEQUENT MYOCARDIAL INFARCTION: A MECHANISTIC SUB-STUDY OF THE FAME II TRIAL
Authors: Arnav Kumar, Elizabeth Thompson, Emily Davis, David Molony, Nikita Chand, Hee S. Lee, Adrien Lefieux, Bill Gogas, Jon Suh, Yi-An Ko, Daniel Molloy, Stephane Fournier, Anastasios Milkas, Alessandro Veneziani, Don Giddens, Bernard D. Bruyne, Habib Samady
Journal: Journal of the American College of Cardiology (2018)
Epidermal Growth Factor Receptor activity is elevated in glioma cancer stem cells and is required to maintain chemotherapy and radiation resistance
Authors: Lisa Pang, David Argyle
Journal: Neuro-Oncology (2018)

Glioblastoma remains among the most aggressive of all human and canine malignancies, displaying high mortality rates and limited treatment options. We propose that given the similarities between canine and human gliomas, such as incidence of occurrence, histopathology, molecular characteristics, and response to therapy, that canine gliomas are a natural model of the human disease. A range of human and canine tumours have been shown to harbor specific subpopulations of cells with stem cell-like properties that initiate and maintain neoplasticity while resisting conventional therapies. Here, we show that both canine and human glioma cell lines contain a small population of cancer stem cells (CSCs), and by molecular profiling highlight the important role of the epidermal growth factor receptor (EGFR) pathway in canine CSCs. EGFR signaling is crucial in the regulation of cancer cell proliferation, migration and survival. To date EGFR-targeted interventions alone have been largely ineffective. Our findings confirm that specifically inhibiting EGFR signaling alone has no significant effect on the viability of CSCs. However inhibition of EGFR did enhance the chemo- and radio-sensitivity of both canine and human glioma CSCs, enabling this resistant, tumourigenic population of cells to be effectively targeted by conventional therapies.
Wales is “ill prepared” for crisis in GP recruitment, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2014)

The NHS is currently facing a GP recruitment crisis “for which Wales is ill prepared,” the BMA has said. It warned that many GPs in Wales were considering early retirement, that there were problems in recruiting for both daytime and out of hours services, and that too few GPs were in training in Wales.

BMA Wales’s General Practitioners Committee (GPCW) has issued a report that sets out the issues affecting GPs in Wales.1 The report said, “The whole time equivalent for GPs is said to have increased by 11%, but the methodology for calculating this appears to be flawed. GPCW believes that the whole time equivalent number has remained broadly static.”

It said that 23% of GPs in Wales were aged 55 or over and that, to meet the demands of rising workload in general practice, at least 1.6 whole time equivalent GPs were needed to replace each retiring GP in Wales. In addition to an …