tbuckley/cabot-search huggingface dataset:
Hybrid treatment of tandem, common carotid/innominate artery and ipsilateral carotid bifurcation stenoses by simultaneous, retrograde proximal stenting and eversion carotid endarterectomy: Preliminary results of a case series
Authors: Giulio Illuminati, Giulia Pizzardi, Rocco Pasqua, Francesca Frezzotti, Piergaspare Palumbo, Francesco Macrina, Francesco Calio'
Journal: International Journal of Surgery (2018)
AB0228 Increase in global dna methylation at 3 months of methotrexate use is not associated to response in early ra patients
Authors: H.R. Gosselt, M.C. de Rotte, J.M. Hazes, R. de Jonge, S.G. Heil
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Methotrexate (MTX) is a first-line therapy in early Rheumatoid Arthritis (eRA). Still, up to 40% of treated patients do not adequately respond to MTX. MTX interferes with the folate cycle, where it indirectly inhibits the global DNA methylation donor S-adenosylmethionine (SAM). Thus, we hypothesised that global DNA methylation changes during MTX use are associated with treatment response. <h3>Objectives</h3> To examine whether there is a change in global DNA methylation (Δ%Meth) upon MTX use and if this change is associated to MTX response (ΔDAS28) in eRA patients. <h3>Methods</h3> DNA was isolated from whole blood (n=120) and Peripheral Blood Mononuclear Cells (PBMCs, n=83) of eRA patients, before and 3 months after MTX use. Samples were collected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH), a multicenter, stratified single-blind clinical trial of eRA patients. Selected patients received triple (MTX +SSZ + HCQ) or monotherapy (MTX) combined with corticosteroids. 7 CpG sites within Long-Interspersed Nuclear Elements (LINE-1), a proxy for global DNA methylation, were quantified by Sequenom Epityper. Paired t-tests or Wilcoxon Signed Rank tests were conducted to assess a change in methylation. ΔDAS28 score over 3 months was used as a measure for response. Associations between ΔDAS28 and Δ%Meth were corrected for baseline DAS28 in a linear regression model. <h3>Results</h3> In leukocytes,%Meth did not significantly change over time. However, in PBMCs%Meth in CpG1 (ΔMeth=2.61%, p=0.008), CpG2 (ΔMeth=0.73%, p=0.039) and CpG11.12 (ΔMeth=0.56%, p=0.016) significantly increased over 3 months of MTX use after Bonferroni correction. Δ%Meth in CpG8.9 was significantly associated to the ΔDAS28 (B=0.29, p=0.039), yet this was no longer significant after Bonferroni correction. Δ%Meth was not significantly associated to ΔDAS28 in any of the other LINE1 CpG sites tested. <h3>Conclusions</h3> PBMC global DNA methylation in LINE-1 CpG sites increased upon 3 months of MTX use. However, this change in methylation is not associated to MTX response. Further research is needed to investigate the role of global DNA methylation in these patients. <h3>Disclosure of Interest</h3> None declared
Chest Reconstruction and Chest Dysphoria in Transmasculine Minors and Young Adults
Authors: Johanna Olson-Kennedy, Jonathan Warus, Vivian Okonta, Marvin Belzer, Leslie F. Clark
Journal: JAMA Pediatrics (2018)

Transmasculine youth, who are assigned female at birth but have a gender identity along the masculine spectrum, often report considerable distress after breast development (chest dysphoria). Professional guidelines lack clarity regarding referring minors (defined as people younger than 18 years) for chest surgery because there are no data documenting the effect of chest surgery on minors.
THE PROGNOSTIC VALUE OF COMPUTED TOMOGRAPHY FRAILTY MEASURES FOR PROLONGED HOSPITAL STAY AFTER TAVR IN 429 PATIENTS
Authors: Eva Maret, Martin Willemink, Kegan Moneghetti, Juyong Kim, Francois Haddad, Yukari Kobayashi, Craig Miller, Alan Yeung, Michael Fishbein, William Fearon, Dominik Fleischmann
Journal: Journal of the American College of Cardiology (2018)
OBESITY DOES NOT PROLONG LENGTH OF STAY IN HEART FAILURE ADMISSIONS: A CO-MORBIDITY MATCHED ANALYSES FROM A UNITED STATES NATIONAL DATABASE
Authors: Olatunde Oladipupo Ola, Odunayo Olorunfemi, Oladimeji Akinboro, Amole Ojo, Rebecca Ojo, Gbolahan Ogunbayo
Journal: Journal of the American College of Cardiology (2018)
Association of PD-L1 mRNA levels in plasma-derived exosomes with response to nivolumab and pembrolizumab in melanoma and NSCLC.
Authors: Marzia Del Re, Riccardo Marconcini, Giulia Pasquini, Eleonora Rofi, Caterina Vivaldi, Francesco Bloise, Giuliana Restante, Elena Arrigoni, Mariagrazia Bianco, Chiara Caparello, Stefania Crucitta, Iacopo Petrini, Enrico Vasile, Riccardo Morganti, Alfredo Falcone, Romano Danesi
Journal: Journal of Clinical Oncology (2018)

210 Background: The anti-PD-1 monoclonal antibodies (moAb) nivolumab and pembrolizumab have improved the survival of melanoma and non-small cell lung cancer (NSCLC) patients. However, treatment selection is based on tumor PD-L1 expression by immuno-histochemistry and no specific approaches are available to monitor treatment response. The aim of this study was to investigate the association between PD-L1 mRNA levels in plasma-derived exosomes and response to nivolumab and pembrolizumab in patients affected by melanoma (n = 18) and NSCLC (n = 8). Methods: Blood (6 ml) was obtained at 1) baseline (before initiation of anti-PD1 moAb or at the time of last available radiological evaluation of disease response) and 2) after two months of treatment (at the time of first response evaluation or disease re-assessment). Exosomes were extracted from plasma and PD-L1 mRNA expression was measured by digital PCR and expressed as copies/ml. Results: Overall, the number of copies of mRNA PD-L1/ml plasma varied according to tumor response; in particular, an increase was found in patients with PD and a decrease was observed in patients who achieved a CR/PR. The mean±SEM values of PD-L1 in patients responding to treatment (CR+PR) were 830.4±231.3 and 242.5±82.5 copies/ml (baseline vs. 2 months, p = 0.016), respectively. In patients with stable disease the mean±SEM values were as expected 298.8±97.2 vs. 247.5±29.8 copies/ml (p = 0.586), while in progressive disease PD-L1 expression levels were 204.0±68.8 vs. 416.0±87.8 copies/ml (p = 0.001), respectively. Conclusions: In the present study, we demonstrate for the first time that changes in exosomal PD-L1 expression occur in melanoma and NSCLC patients treated with nivolumab or pembrolizumab and may correlate with the radiological tumor response. This proof-of-concept study demonstrates the feasibility of detecting PD-L1 in plasma and its relationship with response to treatment.
Topography imaging of herpesvirus in native condition using atomic force microscopy
Authors: M. Delguste, M. Koehler, L. Gillet, D. Alsteens
Journal: Clinical Microbiology and Infection (2018)

Currently two principal techniques are used to visualize virus structure: X-ray diffraction and electron microscopy. However, those techniques require virus fixation or drying steps. In addition, they are averaging methods that do not reveal the characteristics of individual particles.
Extended and Continuous Decline in Effective Population Size Results in Low Genomic Diversity in the World’s Rarest Hyena Species, the Brown Hyena
Authors: Michael V Westbury, Stefanie Hartmann, Axel Barlow, Ingrid Wiesel, Viyanna Leo, Rebecca Welch, Daniel M Parker, Florian Sicks, Arne Ludwig, Love Dalén, Michael Hofreiter
Journal: Molecular Biology and Evolution (2018)

Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of <10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low-coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa. We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started ∼1 Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species.
Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma
Authors: Hirokazu Sadahiro, Kyung-Don Kang, Justin T. Gibson, Mutsuko Minata, Hai Yu, Junfeng Shi, Rishi Chhipa, Zhihong Chen, Songjian Lu, Yannick Simoni, Takuya Furuta, Hemragul Sabit, Suojun Zhang, Soniya Bastola, Shinobu Yamaguchi, Hebaallah Alsheikh, Svetlana Komarova, Jun Wang, Sung-Hak Kim, Dolores Hambardzumyan, Xinghua Lu, Evan W. Newell, Biplab DasGupta, Mitsutoshi Nakada, L. James Lee, Burt Nabors, Lyse A. Norian, Ichiro Nakano
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM and showed that knockdown of AXL induced apoptosis of mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report that BGB324, a novel small molecule inhibitor of AXL, prolongs the survival of immunocompromised mice bearing GSC-derived mesenchymal GBM-like tumors. We show that protein S (PROS1), a known ligand of other TAM receptors, was secreted by tumor-associated macrophages/microglia and subsequently physically associated with and activated AXL in mesenchymal GSC. PROS1-driven phosphorylation of AXL (pAXL) induced NFκB activation in mesenchymal GSC, which was inhibited by BGB324 treatment. We also found that treatment of GSC-derived mouse GBM tumors with nivolumab, a blocking antibody against the immune checkpoint protein PD-1, increased intratumoral macrophages/microglia and activation of AXL. Combinatorial therapy with nivolumab plus BGB324 effectively prolonged the survival of mice bearing GBM tumors. Clinically, expression of AXL or PROS1 was associated with poor prognosis for patients with GBM. Our results suggest that the PROS1–AXL pathway regulates intrinsic mesenchymal signaling and the extrinsic immune microenvironment, contributing to the growth of aggressive GBM tumors. Significance: These findings suggest that development of combination treatments of AXL and immune checkpoint inhibitors may provide benefit to patients with GBM. Cancer Res; 78(11); 3002–13. ©2018 AACR.
COMPARING THE IMPACT OF CONCOMITANT SIGNIFICANT MITRAL REGURGITATION ON THE ECHOCARDIOGRAPHIC PROFILE OF PATIENTS WITH LOW-FLOW VERSUS NORMAL-FLOW SEVERE AORTIC STENOSIS AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: Nicholas Ngiam, Nicholas Chew, Rebecca Teng, Jonathan D. Kochav, Stephanie Kochav, Edgar Tay, Tiong Cheng Yeo, Kian Keong Poh
Journal: Journal of the American College of Cardiology (2018)
EFFECT OF INTRAVENOUS FENTANYL ADMINISTRATION ON MYOCARDIAL INJURY IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: A SUB-ANALYSIS OF THE PACIFY RANDOMIZED CLINICAL TRIAL
Authors: Rohan Shah, Khalil Ibrahim, Rakesh Goli, Thomas S. Kickler, William A. Clarke, Steven Schulman, John McEvoy
Journal: Journal of the American College of Cardiology (2018)
BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions
Authors: Xiangyou Hu, Brati Das, Hailong Hou, Wanxia He, Riqiang Yan
Journal: The Journal of Experimental Medicine (2018)

BACE1 initiates the generation of the β-amyloid peptide, which likely causes Alzheimer’s disease (AD) when accumulated abnormally. BACE1 inhibitory drugs are currently being developed to treat AD patients. To mimic BACE1 inhibition in adults, we generated BACE1 conditional knockout (BACE1fl/fl) mice and bred BACE1fl/fl mice with ubiquitin-CreER mice to induce deletion of BACE1 after passing early developmental stages. Strikingly, sequential and increased deletion of BACE1 in an adult AD mouse model (5xFAD) was capable of completely reversing amyloid deposition. This reversal in amyloid deposition also resulted in significant improvement in gliosis and neuritic dystrophy. Moreover, synaptic functions, as determined by long-term potentiation and contextual fear conditioning experiments, were significantly improved, correlating with the reversal of amyloid plaques. Our results demonstrate that sustained and increasing BACE1 inhibition in adults can reverse amyloid deposition in an AD mouse model, and this observation will help to provide guidance for the proper use of BACE1 inhibitors in human patients.
Alveolar ridge preservation in the esthetic zone
Authors: Ronald E. Jung, Alexis Ioannidis, Christoph H. F. Hämmerle, Daniel S. Thoma
Journal: Periodontology 2000 (2018)

Abstract In the esthetic zone, in the case of tooth extraction, the clinician is often confronted with a challenge regarding the optimal decision‐making process for providing a solution using dental implants. This is because, after tooth extraction, alveolar bone loss and structural and compositional changes of the covering soft tissues, as well as morphological alterations, can be expected. Ideally, the therapeutic plan starts before tooth extraction and it offers three options: spontaneous healing of the extraction socket; immediate implant placement; and techniques for preserving the alveolar ridge at the site of tooth removal. The decision‐making process mainly depends on: (i) the chosen time‐point for implant placement and the ability to place a dental implant; (ii) the quality and quantity of soft tissue in the region of the extraction socket; (iii) the remaining height of the buccal bone plate; and (iv) the expected rates of implant survival and success. Based on scientific evidence, three time‐periods for alveolar ridge preservation are described in the literature: (i) soft‐tissue preservation with 6–8 weeks of healing after tooth extraction (for optimization of the soft tissues); (ii) hard‐ and soft‐tissue preservation with 4–6 months of healing after tooth extraction (for optimization of the hard and soft tissues); and (iii) hard‐tissue preservation with &gt; 6 months of healing after tooth extraction (for optimization of the hard tissues).
ROTATIONAL ATHERECTOMY VERSUS STANDARD PCI IN PATIENTS WITH CALCIFIED CORONARY LESIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Mohan Babu Palla, Alexandros Briasoulis, Arshad Ali Javed, Sagar Mallikethi-Reddy, Luis Afonso, Theodore Schreiber, Cindy Grines
Journal: Journal of the American College of Cardiology (2018)
THE EFFECT OF CANGRELOR VERSUS TICAGRELOR ON PLATELET ACTIVITY, CORONARY MICRO-CIRCULAR FUNCTION AND INFARCT SIZE IN PATIENTS SUFFERING ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION: A RANDOMIZED CONTROLLED TRIAL
Authors: Salahaddin Ubaid, Tom Ford, Colin Berry, Saib Khogali, Benjamin Wrigley, Shahzad Munir, Joe Martins, Rumi Jaumdally, Vincent Amoah, Nazish Khan, Townend Jon, Elisa McAlindon, James Cotton
Journal: Journal of the American College of Cardiology (2018)
Overtreatment of Asymptomatic Hypertension—Urgency Is Not an Emergency
Authors: Jeong Yun Yang, Sophia Chiu, Mona Krouss
Journal: JAMA Internal Medicine (2018)

This Teachable Moment differentiates between hypertensive emergency and hypertensive urgency and examines the case of a woman who was incorrectly treated for hypertensive emergency when treatment for hypertensive urgency would have been more appropriate.
Stent trial researchers are accused of changing endpoints to suit results
Authors: Jacqui Wise
Journal: BMJ (2018)

The organisers of a major clinical trial have been accused of moving the goalposts by quietly changing the study’s primary endpoints shortly before reporting its results.

The change to include softer endpoints to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial has caused controversy and a row on Twitter.

The $84m (£60m; €68m) trial, funded by the US National Institutes of Health, was designed to provide a clear answer as to whether stents provided more than symptomatic relief to patients who have stable angina.

The investigators changed the primary endpoints of the trial to add admission to hospital for unstable angina or heart failure to the hard endpoints of cardiovascular death and myocardial infarction. There was no public announcement of the change, but in January the trial’s description was updated on the ClinicalTrial.Gov website (https://clinicaltrials.gov/ct2/show/NCT01471522). …
INTERLEUKIN-1 BLOCKADE IMPROVES LEFT VENTRICULAR PERFORMANCE IN DECOMPENSATED HEART FAILURE WITHOUT INCREASING MYOCARDIAL WORK
Authors: Leo F. Buckley, Salvatore Carbone, Cory Trankle, Justin Canada, Michele M. Viscusi, Jessica Regan, Dinesh Kadariya, Hayley Billingsley, Ross Arena, Antonio Abbate, Benjamin Van Tassell
Journal: Journal of the American College of Cardiology (2018)
Royal college raises alarm over shortage of paediatric consultants out of hours
Authors: Helen Jaques
Journal: BMJ (2013)

Most paediatric units do not have enough consultants available to review acute admissions at night and at weekends, the Royal College of Paediatrics and Child Health has warned.

It said that fewer children are reviewed by a senior doctor within four hours of admission at weekends and at night than on weekdays. Its audit of acute paediatric units in the UK also reported a shortage of consultants at peak times, defined as between 5 pm and 10 pm.

Hilary Cass, the royal college’s president, said that the …
Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma
Authors: Mi Na Kim, Jung Yeon Hong, Doo Hee Shim, In Suk Sol, Yun Seon Kim, Ji Hyun Lee, Kyung Won Kim, Jae Myun Lee, Myung Hyun Sohn
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation.In this study, we investigated the role of ALCAM in the development of inflammation in allergic asthma.An ovalbumin (OVA)-induced allergic asthma model was established in wild-type (WT) and ALCAM-deficient (ALCAM-/-) mice. T-cell proliferation was evaluated in cocultures with dendritic cells (DCs). Bone marrow-derived dendritic cells (BMDCs) from WT and ALCAM-/- mice were cultured and adoptively transferred to OT-II mice for either OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM concentrations in the sputum and serum of children with asthma were quantified by ELISA.Inflammatory responses were lower in ALCAM-/- mice than in WT mice, and T cells cocultured with DCs from ALCAM-/- mice showed reduced proliferation relative to those cocultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM-/- mice as compared with that observed after transfer of BMDCs from WT mice. In addition, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM concentrations were higher in children with asthma than in control subjects.ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.
I am interested in pursuing a career in a non-governmental organisation or the United Nations in a medical capacity. How do I go about this?
Authors: Mark Wilson
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
EVALUATION OF NOVEL RISK SCORE FOR REFINING STROKE RISK IN “LOW-RISK” ATRIAL FIBRILLATION PATIENTS WITH CHA2DS2-VASC SCORE OF 0 AND 1
Authors: Yoav Arnson, Moshe Hoshen, Adi Berliner Senderey, Orna Reges, Ran Balicer, Morton Leibowitz, Meytal Avgil Tsadok, Moti Haim
Journal: Journal of the American College of Cardiology (2018)
Abstract PD1-01: Triple negative breast cancer predisposition genes
Authors: FJ Couch, H Shimelis, H LaDuca, C Hu, SN Hart, EC Polley, T Pesaran, B Tippin-Davis, DE Goldgar, JS Dolinsky
Journal: Cancer Research (2018)

Abstract Background: Germline cancer testing panels provide an effective method for identifying individuals at increased risk for breast cancer. However, estimates of risk for triple negative breast cancer (TNBC) (estrogen receptor-negative, progesterone receptor-negative, HER2-negative) associated with pathogenic mutations in panel genes have not been established. We sought to define the genes that contribute to TNBC. Methods:Germline hereditary cancer multigene panel testing results were obtained for 8,753 TNBCs evaluated by a clinical testing laboratory. Associations between pathogenic mutations in individual genes and TNBC were assessed by comparing mutation frequencies in TNBCs and in the Exome Aggregation Consortium, non-Finn European, non-Cancer Genome Atlas reference controls. Results: Inactivating mutations in 21 known cancer predisposition genes were identified in 14.6% of TNBCs. BRCA1, BRCA2, PALB2, BARD1, and RAD51D alterations were associated with high risks (odds ratio(OR)&amp;gt;5.0) of TNBC and variants in BRIP1, RAD51C, MSH6, and TP53 were associated with moderate risks (OR&amp;gt;2). In contrast, ATM, CHEK2, NBN, and RAD50 yielded no clinically relevant risks of TNBC. Pathogenic mutations in these established non-BRCA1/2 TNBC susceptibility genes were detected in 6.3% of TNBCs. Similar trends were observed among African American TNBCs. Overall, 5.5% of TNBCs with pathogenic mutations did not meet NCCN clinical testing criteria for BRCA1/2 due to a lack of significant family history and diagnosis over the age of 60. Conclusions: The identification of genes associated with elevated risk of TNBC will improve understanding of the etiology of this aggressive form of breast cancer and inform risk management of individuals receiving panel testing. The high frequency of pathogenic variants suggests that all patients with TNBC, regardless of age of diagnosis or family history of cancer, should be considered for multigene panel testing. Citation Format: Couch FJ, Shimelis H, LaDuca H, Hu C, Hart SN, Polley EC, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS. Triple negative breast cancer predisposition genes [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 PD1-01.