tbuckley/cabot-search huggingface dataset:
Abstract P358: Relation of Microvascular Endothelial Function and Cognitive Performance in the ELSA-Brasil Study
Authors: Luisa C Brant, Daniel Bos, Larissa F Araujo, Arfan Ikram, Antonio L Ribeiro, Sandhi M Barreto
Journal: Circulation (2018)

Introduction: Microvascular endothelial dysfunction may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Hypothesis: More impaired endothelial function (EF) is related to worse cognitive performance in adults. Methods: In the ELSA-Brasil baseline examination, 1,521 non-demented participants underwent peripheral arterial tonometry (PAT) to quantify microvascular EF [PAT-ratio and mean baseline pulse amplitude (BPA)] and cognitive tests covering the domains of memory, semantic and phonemic fluency, and executive function. Linear regression and generalized linear models were used to assess the association between EF, global and specific cognitive performance. Adjustments were made for sex, age, level of education, alcohol intake, BMI, systolic blood pressure, antihypertensive use, diabetes mellitus, total/HDL cholesterol, smoking, prevalent cardiovascular disease, and use of neuroleptics. Results: In unadjusted analyses, more impaired PAT measures was associated with worse global cognitive performance [difference per unit increase, BPA: -0.07 (95%CI: -0.11; -0.03), PAT-ratio: 0.11 (95%CI: 0.01; 0.20)]. Specifically, BPA and PAT-ratio were related to worse learning memory [difference per unit increase, BPA: -0.54 (95%CI: -0.78; -0.31), PAT-ratio: 0.96 (95%CI: 0.43; 1.48)], delayed memory [difference per unit increase, BPA: -0.26 (95%CI:-0.37; -0.14), PAT-ratio: 0.51 (95%CI: 0.25; 0.77)], and semantic fluency [difference per unit increase, BPA: -0.46 (95%CI:-0.77; -0.14), PAT-ratio: 0.72 (95%CI: 0.01; 1.43)]. However, adjustments for age, sex and level of education rendered the associations statistically non-significant. Conclusions: The association between microvascular EF and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may therefore be of limited value with regard to preclinical cognitive deficits.
BARIATRIC SURGERY IN MORBIDLY OBESE ADVANCED HEART FAILURE PATIENTS
Authors: Candace A. Becker, Maggie D. Mendenhall, Susan George, Tonia Jacob, Angela Patrick, Melissa Duke, Megan Corder, Neela Chelikani, Douglas Horstmanshof, Hamilton Le, James Long
Journal: Journal of the American College of Cardiology (2018)
Predictive biomarker of response to anti-PD-1 treatment in non-small cell lung cancer patients.
Authors: Xuan Zheng, Yi Hu, Junxun Ma, Fan Zhang, Danyang Sun, Lingling Li
Journal: Journal of Clinical Oncology (2018)

148 Background: PD-1 inhibitors have shown significant clinical activity in different cancer types. However, responses in pts with NSCLC are variable, and insights are needed to identify a predictive biomarker of response with greater diagnostic accuracy. Here we tested the hypothesis tha tserum TNF-a level is predictive of response to anti-PD-1 treatment. Methods: NSCLC patients treated with nivolumab or pembrolizumab were studied. Pts received nivolumab (3mg/kg, q2w) or pembrolizumab ( 2mg/kg, q3w). Pts on anti-PD1 were classified as either responders (R) deriving clinical benefit (with SD, PR, CR) or non-responders (NR) not deriving clinical benefit (PD) based on RECIST criteria.Serum was collected at baseline; at 2-3 weeks after the first dose (early stage); and at the time of response evaluation. Serum TNF-a levels were determined by Luminex kit. Changes in serum TNF-a levels and their strength of association with response were compared with Non-parametric Analysis. Results: Evaluable plasma samples were collected from twenty-one NSCLC patients treated with nivolumab or pembrolizumab. There was no significant difference in baseline serum TNF-a levels in responders (n = 15) vs non-responders (n = 6). Between baseline and early stage ,serum TNF-a levels significantly increased in responders (P = 0.010), while in non-responders, no significant change was found. High early change rate of serum TNF-a levels ( &gt; 50%) was observed only in responders(n = 7).At early stage, responders had significantly higher serum TNF-a levels than non-responders(P = 0.008). We found no significant difference in serum TNF-a levels at the time of response evaluation. Conclusions: Early changes in serum TNF-a levels and high serum TNF-a levels at early stage in non-small cell lung cancer patients correlate to response to anti-PD-1 treatment.
Metastasis to the Sellar/Suprasellar Region in a Patient With Endometrial Carcinoma Detected by 18F-FDG PET/CT
Authors: Barbara Salvatore, Domenico D’Amico, Rosa Fonti
Journal: Clinical Nuclear Medicine (2018)

Metastases to pituitary gland, suprasellar region or skull base from endometrial carcinoma are an extremely rare occurrence. We report the case of a 77-year-old woman with metastasis to the sellar/suprasellar region from endometrial carcinoma revealed by F-FDG PET/CT and confirmed by subsequent CT and MRI of the brain. This case highlights the usefulness of a whole-body imaging methodology such as F-FDG PET/CT in the detection of distant and/or atypical sites of metastasis therefore being of help in guiding towards the correct diagnosis.
Comprehensive genomic profiling to identify recurrent kinase fusions in pancreatic ductal adenocarcinoma.
Authors: Aatur D. Singhi, Joel R. Greenbowe, Jon Chung, Andrew Eugene Hendifar, Nathan Bahary, Alexa Betzig Schrock, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Siraj Mahamed Ali, Ben George
Journal: Journal of Clinical Oncology (2018)

292 Background: Kinases activated by gene fusions represent an important class of oncogenes that have been detected in hematologic and solid malignancies. These fusion genes have been well-described in non-small cell lung cancer, and such patients often benefit from matched kinase inhibitors. Recent work in pancreatic ductal adenocarcinoma (PDAC) has also identified recurrent ALK and BRAF rearrangements. Further, patients harboring the former have benefited from ALK inhibitors, as previously reported. We present a survey of kinase fusion genes identified in a large, consecutive series of PDACs. Methods: In the context of clinical care, hybrid-capture based CGP was performed prospectively on 3,426 PDACs for up to 315 cancer-related genes and intronic regions of up to 28 genes that are commonly rearranged in cancer. Results: Overall, kinase fusion genes were identified in 32 (1%) patients with PDAC. The patients consisted of 8 females and 23 males, and ranged in age between 31 and 83 years (median, 58 years). PDACs harboring kinase fusions were predominantly KRAS-wildtype (97%). In fact, the prevalence of kinase fusion genes among KRAS-wildtype PDACs was 8%. Gene fusions involved BRAF (n = 22), ALK (n = 5), NTRK (n = 3) and MET (n = 2). Concurrent genomic alterations included CDKN2A/B (41%), TP53 (28%), GNAS (19%), SMAD4 (16%), MCL1 (16%), ARID1A (13%) and MYC (13%). Updated clinical history will be presented on patients, who previously benefitted from ALK inhibitors. Conclusions: Recurrent gene fusions involving BRAF, ALK, NTRK and MET occur in a subset of PDACs. Although rare, these kinase fusions potentially represent actionable targets and screening should be considered, especially in KRAS-wildtype PDACs.
Beulah Bewley: public health doctor and advocate for women in medicine
Authors: Anne Gulland
Journal: BMJ (2018)

For the first 15 years of her working life, Beulah Bewley had what she described as a “zig zag career.”1 She did some paediatrics, some psychiatry, and some family planning, as, like so many professional women of her time, her career was subordinate to that of her husband and the bringing up of her five children.

However, in 1969, after seeing an advertisement in The BMJ for a new MSc in social medicine and epidemiology at the London School of Hygiene and Tropical Medicine (LSHTM), she decided to go back into education. Bewley was 40 and the only woman among 11 younger men, with whom, at the beginning, she felt she had to “catch up.”

In her second year Bewley studied smoking among primary school children in Lambeth, and this, after she graduated, led to a five year study looking at smoking rates among secondary school children in Derbyshire and Kent. Children and their parents would fill in questionnaires about their smoking with space to write comments: one mother said it was impossible to stop her child smoking because she ran a pub.



Bewley and her fellow researchers found that …
Women Not Receiving Optimal Preventive Medications
Authors: Bridget M. Kuehn
Journal: Circulation (2018)

Women continue to be suboptimally treated with medications to prevent cardiac events, according to data presented at the American Heart Association's Scientific Sessions and the European Society of Cardiology Congress.Women have long suffered higher rates of death resulting from cardiovascular causes than men, explained Annabelle Volgman, MD, medical director of the Rush University Heart Center for Women in Chicago.But a renewed emphasis on women's cardiology research and improving the care of women with heart disease since 2000 has helped physicians close the survival gap between women and men."Since we started paying attention, the mortality has plummeted so that in the last data from 2014, we're seeing less mortality in women from cardiovascular disease than in men," said Volgman.The new studies show there is room for further improvement, particularly in the use of preventive medication for women.
PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma
Authors: Matthew W. Rosenbaum, Benjamin J. Gigliotti, Sara I. Pai, Sareh Parangi, Heather Wachtel, Mari Mino-Kenudson, Viswanath Gunda, William C. Faquin
Journal: Endocrine Pathology (2018)
FEASIBILITY AND VALIDITY OF MEASURING PATIENT-REPORTED HEALTH STATUS AT TIME OF PCI: RESULTS FROM A SINGLE-CENTER QUALITY IMPROVEMENT INITIATIVE
Authors: Usman Baber, Serdar Farhan, Nitin Barman, Joseph Sweeny, Jason Kovacic, George Dangas, Roxana Mehran, Annapoorna Subhash Kini, Samin K. Sharma
Journal: Journal of the American College of Cardiology (2018)
EXERCISE AND PHARMACOLOGIC STRESS-INDUCED T-WAVE HETEROGENEITY FOR DETECTION OF CLINICALLY SIGNIFICANT CORONARY ARTERY STENOSIS
Authors: Anderson Carlos Silva, Victor Zandona De Antonio, Jakub Sroubek, Ernest Gervino, Kalon Ho, Fernando G. Stocco, Bruce D. Nearing, Richard L. Verrier
Journal: Journal of the American College of Cardiology (2018)
Resistant to Targeted Therapy - Aim for Metabolic Liabilities
Authors: André Lima Queiroz, Helin Vakifahmetoglu-Norberg, Erik Norberg
Journal: Theranostics (2018)

The advent of targeted therapies generated much optimism when discovered. Targeted therapies, are however associated with rapid acquisition of resistance. In a recent study by Dong et al. (Theranostics 2018; 8(7):1808-1823. doi:10.7150/thno.23177) it was shown that lung tumors resistant to the EGFR-inhibitor (Erlotinib), reprogram their metabolism and acquire a pro-survival dependency on Phosphoglycerate Dehydrogenase (PHGDH) that can be targeted to eliminate resistant tumors.
Professor Sir John Lilleyman
Authors: Leyla Sanai
Journal: BMJ (2006)

Professor Sir John Lilleyman is a paediatric haematologist. He has been president of the Royal College of Pathologists, vice chairman of the Academy of Medical Royal Colleges, and vice chairman of the Joint Consultants Committee. In April 2004 he became medical director of the National Patient Safety Agency (NPSA), and in July 2004 he became president of the Royal Society of Medicine.
Self-reported quality of life as a predictor of survival in renal cell carcinoma.
Authors: Ridwan Alam, Hiten Patel, Phillip M. Pierorazio
Journal: Journal of Clinical Oncology (2018)

595 Background: Quality of life (QOL) in cancer patients has gained increasing attention and may provide prognostic value above and beyond traditional demographic and disease parameters. We evaluate the utility of self-reported QOL to predict mortality in patients with renal cell carcinoma (RCC). Methods: The Medicare Health Outcomes Survey was linked to SEER data to identify patients who completed a QOL questionnaire after the diagnosis of RCC from 1998-2014. Mental component summary (MCS) and physical component summary (PCS) scores were classified as high (≥50) or low ( &lt; 50) based on a population mean score of 50 points. Patients were classified into four groups: 1) high MCS, high PCS; 2) high MCS, low PCS; 3) low MCS, high PCS; and 4) low MCS, low PCS. Multivariable Cox proportional hazards regression evaluated associations between QOL and all-cause mortality (ACM). The Harrell’s concordance statistic (C-index) estimated predictive accuracy. Fine and Gray competing risks models adjusted for stage, demographics, and comorbidities evaluated RCC-specific and non-RCC-specific mortality. Results: A total of 1494 patients with a median age of 73.4 years (IQR 68.8-79.3) at survey completion were included. Median follow-up was 5.6 years (IQR 4.0-8.3). There were 747 deaths, of which 139 were due to RCC. Models showed that each additional MCS and PCS point reduced the hazard of ACM by 1.3% (95% CI 0.981-0.993, P&lt; 0.001) and 2.2% (95% CI 0.972-0.985, P&lt; 0.001), respectively. The C-index was 72.1%. In the competing risks model, the subdistribution hazard ratio (SHR) of RCC mortality in Groups 2, 3, and 4 were 2.71 (95% CI 1.18-6.22, P= 0.02), 4.55 (95% CI 1.57-13.18, P= 0.005), and 3.11 (95% CI 1.35-7.16, P= 0.008), respectively, compared to Group 1. The SHR for non-RCC mortality were 1.50 (95% CI 1.16-1.94, P= 0.002), 1.03 (95% CI 0.59-1.78, P= 0.9), and 1.83 (95% CI 1.41-2.38, P&lt; 0.001), respectively, relative to Group 1. Conclusions: Self-reported QOL metrics can be used to predict ACM in RCC patients with good accuracy; lower PCS and MCS scores led to higher rates of ACM, even after accounting for differences in disease, demographics, and comorbidity. Furthermore, non-RCC mortality was associated more with low physical health rather than low mental health.
MicroRNA-17-92 is required for T-cell and B-cell pathogenicity in chronic graft-versus-host disease in mice
Authors: Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P. Flynn, David Bastian, M. Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R. Blazar, Xue-Zhong Yu
Journal: Blood (2018)
Bucindolol Evaluation in Acute Myocardial Infarction Trial Group: Congestive heart failure with preserved left ventricular systolic function in acute myocardial infarction: clinical and prognostic implications
Authors: B. Brenderup, M. Ottesen, L. Kober, Kenneth Egstrup, S.H. Poulsen, C. Torp-Pedersen
Journal: European Journal of Heart Failure (2003)
Abstract ES2-3: Managing increased breast cancer risk based on high and moderate penetrance gene mutations
Authors: JE Garber
Journal: Cancer Research (2018)

Abstract Genetic testing in the modern era increasingly examines multiple genes using next generation technologies. Most assays include the high penetrance genes, which confer lifetime breast cancer risk greater than 5-fold, include BRCA1/2, TP53, CDH1 and PALB2. Moderate penetrance genes are associated with lifetime breast cancer risk in the range of 2-3 fold, and include ATM, NF1, CHEK2 (mutation-specific) and NBN, with BARD1 and others potentially joining the group. Substantial data has emerged from studies of women with BRCA1/2 mutations, evaluating the performance of screening technologies, such as mammogram, breast MRI and ultrasound, and the efficacy of risk-reducing breast and ovarian/fallopian tube surgical procedures. Guidelines exist in the NCCN (US) and ESMO guidelines in Europe, among others, trying to provide recommendations for the age at which to initiate screening or undergo risk-reducing salpingo-oophorectomies, for example. Data are increasing on the moderate penetrance genes but there is still much reliance on extrapolation from the high-penetrance genes, which should be done thoughtfully. One approach is to estimate the age at which lifetime breast cancer risk equals the risk from a high penetrance gene when screening is to begin and initiate imaging surveillance at that time. For example, initiation of annual breast imaging would be at age 40 for ATM (RR 2.8) instead of age 25 as is done for BRCA1/2 or age 20 as for TP53. However, there are no data that this is the correct age at which to initiate screening, so this practical suggestion must meet criteria for reasonableness as well as effectiveness. Other source of data may include more precise gene-specific risk estimates from focused genetic epidemiology studies, and ongoing data from studies of prospectively identified mutation carriers. Further understanding of the mechanisms of carcinogenicity for mutation carriers may also help to provide insights that can guide therapeutic and preventive approaches. For example, the work on RANK ligand by Lindeman et al has led to the development of a definitive breast cancer prevention trial examining the RANK-Ligand inhibitor Denosumab in BRCA1 mutation carriers, entitled BRCA-P, being led by C. Singer of the ABCSG and Dr. Lindeman, and to be conducted in sites around the world. Other approaches are in development and will be discussed. Citation Format: Garber JE. Managing increased breast cancer risk based on high and moderate penetrance gene mutations [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 ES2-3.
HIS BUNDLE PACING RESULTS IN A NARROWER PACED QRS COMPARED TO BI-VENTRICULAR PACING FOR CARDIAC RESYNCHRONIZATION THERAPY
Authors: Nicholas J. Serafini, Nidhi Madan, Estefania Oliveros, Henry Huang, Richard Trohman, Parikshit Sharma
Journal: Journal of the American College of Cardiology (2018)
Microbiome and Esophageal Adenocarcinoma—Letter
Authors: Nadeem O. Kaakoush
Journal: Cancer Research (2018)

The article by Peters and colleagues ([1][1]) published in Cancer Research presents exciting new evidence on the association between the oral microbiome and the two main esophageal cancers, adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The authors examined 368 samples consisting of cases
CLINICAL OUTCOMES BY SEX AND ETHNICITY AFTER PERCUTANEOUS CORONARY INTERVENTION
Authors: Asha Mahajan, Jaya Chandrasekhar, Samantha Sartori, Usman Baber, George Dangas, Jason Kovacic, Prakash Krishnan, Pedro Moreno, Joseph Sweeny, Nitin Barman, Pooja Vijay, Annapoorna Subhash Kini, Roxana Mehran, Samin K. Sharma
Journal: Journal of the American College of Cardiology (2018)
Platelet-activating factor and its receptor mediate melanoma progression by regulating expression of MMP-2, MT1-MMP and MCAM/MUC18
Authors: Vladislava Melnikova, Alexandra Zeidan, Maya Zigler, Hua Wang, Dina Lev, Menashe Bar-Eli
Journal: Cancer Research (2007)

2461   Enzymatic and oxidative degradation of cellular and lipoprotein-associated phosphatidylcholine produces key initial components of an inflammatory response - platelet-activating factor (PAF) and PAF mimetics. These short-lived biologically active phospholipid autocoids act through the specific GPCR-type PAF receptor to activate platelets, inflammatory and endothelial cells. Nevertheless, the functions of PAF/PAFR in tumor cells are largely unknown. We have found that PAF receptor antagonist PCA4248 inhibits growth of experimental A375SM human melanoma lung metastasis in nude mice.  In vitro  analysis of a panel of melanoma cells demonstrated that all melanoma cell lines express PAF receptor and that stimulation of metastatic melanoma cells with exogenous PAF results in the expression and activation of matrix metalloproteinases MMP-2 and MT1-MMP. This effect was mediated by PAF-induced phosphorylation and activation of transcription factors CREB and ATF-1, which occurred through a PAFR-mediated mechanism that utilized Gα q  proteins, adenylate cyclase, p38 MAP kinase and protein kinase A. These results suggest that CREB and ATF-1 may act as molecular sensors to PAF-mediated stimulation. Consequently, the inflammatory tumor microenvironment may control specific transcriptional responses associated with overexpression of CREB and ATF-1, which is known to take place during the acquisition of the metastatic phenotype by melanoma cells. Our further studies indicate that PAF is also involved in constitutive gene expression in melanoma cells. First, we found that several structurally independent PAFR antagonists inhibit the  in vitro  growth of A375SM melanoma cells, most probably by downregulating their constitutive Cyclin D1 expression. Targeting PAFR expression in A375SM cells with small interfering RNA oligonucleotides confirmed that downregulation of Cyclin D1 expression was mediated via PAFR signaling. Second, PAFR knockdown with siRNA revealed that PAFR mediates constitutive expression of the melanoma cell adhesion protein MCAM/MUC18, a marker of metastatic melanoma as well as melanoma cancer stem cells. Conversely, inhibition of MCAM/MUC18 expression in A375SM cells  by means of siRNA or shRNA led to an increase in PAFR expression, suggesting the existence of a feedback loop regulation between PAFR and MCAM/MUC18 expression. Overall, our results demonstrate that PAF acts as a promoter of melanoma metastasis by mediating gene expression in melanoma cells.
Postgraduate diploma in adolescent addiction studies
Authors: Jayne Reed
Journal: BMJ (2006)

This is a part time course aimed at a wide range of healthcare professionals, researchers, educators, and policy makers working in the field of addiction, adolescent addiction, and adolescent mental health; it is also for other teams and organisations such as social services and youth offender teams. Applicants should have a degree in a relevant subject or an equivalent professional qualification. Consideration will be given to other applicants with the appropriate experience.

I did the course from September 2004 to May 2006. The postgraduate diploma course run by Keele University Medical School (with teaching based at the academic psychiatry unit, Harplands Hospital, Stoke on Trent) takes two academic years.

Although adolescent addiction is a growing specialty, working in the field can be isolated and available training is limited. My background is adolescent mental health, and I learnt most about my current position from psychiatrists in the adult addiction field. I wanted to learn more about research and the practicalities and good practice guidelines …
LOOP-DIURETIC USE PRIOR TO TRANSCATHETER AORTIC VALVE REPLACEMENT IS ASSOCIATED WITH INCREASED MORTALITY
Authors: Eric Cantey, John Blair, Lillian R. Benck, Quentin Youmans, Abdulrahman Abutaleb, Chetan Huded, Joseph Feinglass, Ranya Sweis, Duc Pham, Andrei Churyla, Mark Ricciardi, S. Chris Malaisrie, Charles Davidson, James Flaherty
Journal: Journal of the American College of Cardiology (2018)
CONDUCTION DISTURBANCES IN TRANSCATHETER AORTIC VALVE REPLACEMENT: THE COST OF LESS PARAVALVULAR LEAK?
Authors: Giorgio Medranda, Kunal Brahmbhatt, Anjili Srivastava, Paul Sapia, Richard Schwartz, Kevin Marzo, Stephen Green, Ramesh Daggubati
Journal: Journal of the American College of Cardiology (2018)
I am keen to pursue a surgical career, but with the proposed changes in surgical training and the reduced availability and length of SHO training programmes, I am unsure which direction to take. Which posts should I be applying for?
Authors: Faisal Hanif
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>