tbuckley/cabot-search huggingface dataset:
Assessment of HER2 status in resected gastric cancer in European population
Authors: Nieves Martinez Lago, Ihab Abdulkader Nallib, Dora Insua Santamaria, Patricia Viaño Nuñez, Jose Carrera Juan, Ramón Antunez Lopez Jose, Elena Padin Iruegas Maria, Rafael Lopez
Journal: Annals of Oncology (2017)
Excellent outcome of non-myeloablative stem cell transplant (NMSCT) for good risk myeloma: The EBMT experience
Authors: M Lalancette, K Rezvani, R Szydlo, S Mackinnon, Gunnar Juliusson, M Michallet, S Slavin, F Frassoni, D Niederwieser, G Gahrton, J Apperley
Journal: Blood (2000)
Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma
Authors: Loren K. Mell, Kevin T. Brumund, Gregory A. Daniels, Sunil J. Advani, Kaveh Zakeri, Mary E. Wright, Sara-Jane Onyeama, Robert A. Weisman, Parag R. Sanghvi, Peter J. Martin, Aladar A. Szalay
Journal: Clinical Cancer Research (2017)

Purpose: Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer.Experimental Design: Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials.Results: Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1-2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively.Conclusions: Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. Clin Cancer Res; 23(19); 5696-702. ©2017 AACR.
Abstract P011: Endothelial Differentiation and Lineage Tracing in Adipocyte-Derived Multipotent Cells
Authors: Medet Jumabay, Raushan Abdmaulen, Yucheng Yao, Kristina Bostrom
Journal: Circulation Research (2011)

We previously showed that so-called de-differentiated fat (DFAT) cells, which are derived from mature white adipocytes, spontaneously differentiate into beating cardiomyocytes. Our aim in this study was to investigate if DFAT cells also differentiate into endothelial cells (ECs) in vitro, and to further examine the cellular origin of DFAT cells as well as adipose stromal cells (ASCs) using lineage tracing. First, we examined DFAT and ASCs prepared from aP2-Cre+/+;LacZ ROSA(R26R)+/+ double transgenic mice, which express LacZ under the aP2 promoter. The results revealed that 99.9% of DFAT cells and 45% of the ASCs stained positive for LacZ, supporting that the DFAT cells and part of the ASCs are of adipocytic origin. Second, we allowed newly isolated DFAT cells to spontaneously undergo EC differentiation, which was monitored by expression of EC lineage markers as determined by real-time PCR, immunofluorescence, and FACS. Expression of the EC markers CD31 and VE-cadherin increased progressively during 2 weeks in culture, the percentage of CD31(+) cells increased from 0.0% to 8.3%, and the cells formed multi-cellular tube structures when placed in Matrigel™/Collagen gels. The data supported that a fraction of the DFAT cells differentiate into ECs. Furthermore, the EC differentiation could be enhanced in DFAT cells by treatment with bone morphogenetic protein (BMP)-4 and BMP-9. In addition to EC differentiation, the DFAT cells also expressed markers of other cardiovascular lineages including smooth muscle cells and pericytes. The multipotency of DFAT cells suggests that cellular de-differentiation might be a way for differentiated cells to regain stem cell-like properties. Thus, white mature adipocytes maybe a new stem cell source for cardiovascular regeneration.
Laparoscopic Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis for Ulcerative Colitis: A Quantum Shift in Surgical Care?
Authors: E Nzewi, S Hussain, P Neary
Journal: Endoscopy (2006)

Aims: Restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis traditionally involves a large surgical incision, significant morbidity and prolonged inpatient stay (17.37 days, DOH 2003). We present a video demonstration of this surgery performed laparoscopically in a tertiary referral specialised colorectal unit.
Abstract 18536: Nanoparticle-mediated Simultaneous Targeting to Mitochondria and Inflammatory Monocytes Confers Additive Cardioprotection Against Myocardial Ischemia-reperfusion Injury
Authors: Gentaro Ikeda, Tetsuya Matoba, Kensuke Egashira
Journal: Circulation (2015)

Introduction: Mitochondrial injury and inflammation play temporally and spatially different roles in myocardial ischemia-reperfusion (IR) injury, which demand novel strategy to target these 2 mediators specifically. Previously, we have engineered poly (lactic-co-glycolic acid) nanoparticle containing cyclosporine A (CsA-NP) or pitavastatin (Pit-NP), and reported that the former inhibits the opening of mitochondrial permeability transition pore (mPTP) and the latter reduces monocyte-mediated inflammation in IR hearts. Hypothesis: Nanoparticle-mediated simultaneous targeting to mPTP and monocytes confer additive cardioprotection against IR injury. Methods and Results: We produced mice lacking both cyclophilin D (CypD, a key molecule for mPTP opening) and CCR2 (a receptor for monocyte chemoattractant protein-1), and found that the double KO mice displayed dramatic reduction in myocardial IR injury model (Fig. A). Fluorescence reflectance image (FRI) revealed that CypD deficiency reduced Annexin-positive infarct area in the center of ischemic area, compared with WT mice at 10 min after reperfusion (Fig. B). Although infarct areas were equivalent between WT and CCR2 KO mice at 10 min after reperfusion, CCR2 deficiency inhibited the expansion of the infarct area during 24 hours. Flow cytometric analysis and fluorescence molecular tomography showed that inflammation was markedly inhibited in CCR2 KO and double KO mice, but not in CypD KO mice at 24 hours after reperfusion (Fig. C). In CypD KO mice, Pit-NP reduced recruitment of Ly6Chigh inflammatory monocytes and infarct size, whereas CsA-NP reduced infarct size in CCR2 KO mice. Simultaneous treatment with CsA-NP and Pit-NP at the time of reperfusion reduced infarct size by an additive manner (Fig. D). Conclusions: Nanoparticle-mediated simultaneous targeting to mitochondria and inflammatory monocytes can be developed as a novel therapeutic strategy for myocardial IR injury.
PTH-019 Bleeding during endoscopic resection: a novel extracellular scaffold matrix is a safe and effective haemostatic agent
Authors: S Subramaniam, K Kandiah, S Thayalasekaran, G Longcroft-Wheaton, P Bhandari
Journal: Endoscopy (2017)

<h3>Introduction</h3> Bleeding is a well recognised complication of endoscopic resection (ER), particularly in endoscopic submucosal dissection (ESD). Electrocautery can be used to control bleeding but does increase the risk of perforation. A novel extracellular scaffold matrix (Purastat) has recently been approved for gastrointestinal haemostasis. This self-assembling peptide forms a transparent gel that can be applied via a catheter through the scope over the bleeding area. We conducted a feasibility study in a high bleeding risk cohort to assess its applicability, safety and efficacy. We also aimed to ascertain the mean volume of Purastat required to cover the resection base prophylactically. <h3>Method</h3> This was a prospective observational cohort study of patients undergoing complex ER in a tertiary referral centre from December 2015–2016. Purastat was used for prophylaxis over the resection base in high bleeding risk procedures or for primary haemostasis in active bleeding. Data was collected on patient and lesion characteristics including surface area, technical feasibility of gel application, haemostasis and delayed bleeding rate. <h3>Results</h3> Purastat was used in 74 patients (average age 69 years, male to female ratio of 2:1). All lesions were &gt;2 cm and 33.8% (25/74) had cardiac co-morbidities with anticoagulant or antiplatelet usage reflecting a high bleeding risk. 60 (81.1%) had ESD and 14 (18.9%) had endoscopic mucosal resection. Table 1 shows the distribution of lesions according to location and size. Abstract PTH-019 Table 1 Abstract PTH-019 Table 2 <h3>Purastat on its own was effective in stopping bleeding in 35/48 (72.9%) cases (see Table 2). It was successfully applied in all patients with no interference in visibility or catheter blockage</h3> The mean surface area of the resection base was 16.2cm<sup>2</sup> requiring a mean Purastat<sup>®</sup> volume of 2.7mls, or 0.2mls/cm<sup>2</sup>. On follow up in 1 month, delayed bleeding was noted in 3/74 (4%) patients. All were managed with endoscopic intervention and no transfusion was required. <h3>Conclusion</h3> Purastat was effective in controlling bleeding in almost ¾ of the cases where it was used for primary haemostasis. It is safe, easy to use and does not hamper ongoing ER. Only a small amount is needed to effectively cover the resection base for prophylaxis. Our data has demonstrated its potential as a novel haemostatic agent that can minimise bleeding during ER. <h3>Disclosure of Interest</h3> S. Subramaniam: None Declared, K Kandiah: None Declared, S Thayalasekaran: None Declared, G Longcroft-Wheaton: None Declared, P Bhandari Conflict with: Receives educational grants from Fujifilm, Olympus and Pentax
Treating Perioperative Complications
Authors: Jason C. Pradarelli, Hari Nathan
Journal: JAMA Surgery (2017)

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Concordance of results of blood and tissue cultures from patients with pyogenic spondylitis: a retrospective cohort study
Authors: J.Y. Bae, C.-J. Kim, U.J. Kim, K.-H. Song, E.S. Kim, S.J. Kang, M.-d. Oh, K.-H. Park, N.J. Kim
Journal: Clinical Microbiology and Infection (2017)
Excellent Results of Biliary Sphincterotomy for Sphincter of Oddi Dysfunction (Modified Criteria)
Authors: AR Aftab, G Cullen, F Zeb, G Courtney
Journal: Endoscopy (2006)

Aims: Sphincter of Oddi Dysfunction (SOD) is classed as Types 1, 2 or 3 based on the Hogan-Geenen classification. We aimed to assess the outcomes for patients with suspected SOD who were diagnosed without biliary manometry or drainage time estimation.
How Many Newly Diagnosed HbsAg Positive Individuals Will Require Antiviral Treatment?
Authors: PB Allen, WP Murphy, PV Coyle, C McCaughey, NI McDougall, ME Callender
Journal: Endoscopy (2006)

Aims: To determine how many newly-detected HBsAg-positive individuals are likely to require anti-viral drug treatment and the proportion who attend Clinics where treatment is available.
Long-Term Outcome of Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Waldenstrom Macroglobulinemia (WM)-a Retrospective Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Charalampia Kyriakou, Ariane Boumendil, Herve Finel, Norbert Schmitz, Henrik Sengeloev, Stephen Mackinnon, Didier Blaise, Patrice Chevallier, Paul Browne, Charles Craddock, Dietger W. Niederwieser, Johannes Schetelig, Stig Lenhoff, Nathalie Fegueux, Silvia Montoto, Peter Dreger
Journal: Blood (2016)
Enhancing P300-BCI performance using latency estimation
Authors: Md Rakibul Mowla, Jane E. Huggins, David E. Thompson
Journal: Brain-Computer Interfaces (2017)

Brain Computer Interfaces (BCIs) offer restoration of communication to those with the most severe movement impairments, but performance is not yet ideal. Previous work has demonstrated that latency jitter, the variation in timing of the brain responses, plays a critical role in determining BCI performance. In this study, we used Classifier-Based Latency Estimation (CBLE) and a wavelet transform to provide information about latency jitter to a second-level classifier. Three second-level classifiers were tested: least squares (LS), step-wise linear discriminant analysis (SWLDA), and support vector machine (SVM). Of these three, LS and SWLDA performed better than the original online classifier. The resulting combination demonstrated improved detection of brain responses for many participants, resulting in better BCI performance. Interestingly, the performance gain was greatest for those individuals for whom the BCI did not work well online, indicating that this method may be most suitable for improving performance of otherwise marginal participants.
Radiosensitization of Adenoid Cystic Carcinoma with MDM2 Inhibition
Authors: Prashanth J. Prabakaran, Amal M. Javaid, Adam D. Swick, Lauryn R. Werner, Kwangok P. Nickel, Emmanuel Sampene, Rong Hu, Irene M. Ong, Justine Y. Bruce, Gregory K. Hartig, Aaron M. Wieland, Jude Canon, Paul M. Harari, Randall J. Kimple
Journal: Clinical Cancer Research (2017)

Purpose: Adenoid cystic carcinoma (ACC) is a rare cancer arising from the major or minor salivary gland tissues of the head and neck. There are currently no approved systemic agents or known radiosensitizers for ACC. Unlike the more common head and neck squamous cell carcinomas that frequently harbor TP53 mutations, ACCs contain TP53 mutations at a rate of <5%, rendering them an attractive target for MDM2 inhibition.Experimental Design: We report the successful establishment and detailed characterization of a TP53-WT ACC patient-derived xenograft (PDX), which retained the histologic features of the original patient tumor. We evaluated this model for response to the MDM2 inhibitor AMG 232 as monotherapy and in combination with radiotherapy.Results: AMG 232 monotherapy induced modest tumor growth inhibition, and radiation monotherapy induced a transient tumor growth delay in a dose-dependent fashion. Strikingly, combination treatment of AMG 232 with radiotherapy (including low-dose radiotherapy of 2 Gy/fraction) induced dramatic tumor response and high local tumor control rates 3 months following treatment. Posttreatment analysis revealed that although both AMG 232 and radiotherapy alone induced TP53 tumor-suppressive activities, combination therapy amplified this response with potent induction of apoptosis after combination treatment.Conclusions: These data identify that MDM2 inhibition can provide potent radiosensitization in TP53-WT ACC. In light of the absence of effective systemic agents for ACC, the powerful response profile observed here suggests that clinical trial evaluation of this drug/radiotherapy combination may be warranted to improve local control in this challenging malignancy. Clin Cancer Res; 23(20); 6044-53. ©2017 AACR.
A video analysis of head injuries satisfying the criteria for a head injury assessment in professional Rugby Union: a prospective cohort study
Authors: Ross Tucker, Martin Raftery, Gordon Ward Fuller, Ben Hester, Simon Kemp, Matthew J Cross
Journal: British Journal of Sports Medicine (2017)

Concussion is the most common match injury in professional Rugby Union, accounting for 25% of match injuries. The primary prevention of head injuries requires that the injury mechanism be known so that interventions can be targeted to specifically overall incidence by focusing on characteristics with the greatest propensity to cause a head injury.611 head injury assessment (HIA) events in professional Rugby Union over a 3-year period were analysed, with specific reference to match events, position, time and nature of head contact.464 (76%) of HIA events occur during tackles, with the tackler experiencing a significantly greater propensity for an HIA than the ball carrier (1.40 HIAs/1000 tackles for the tackler vs 0.54 HIAs/1000 tackles for the ball carrier, incidence rate ratio (IRR) 2.59). Propensity was significantly greater for backline players than forwards (IRR 1.54, 95% CI 1.28 to 1.84), but did not increase over the course of the match. Head to head contact accounted for the most tackler HIAs, with the greatest propensity.By virtue of its high propensity and frequency, the tackle should be the focus for interventions that may include law change and technique education. A specific investigation of the characteristics of the tackle is warranted to refine the approach to preventative strategies.
A Reappraisal of Testosterone’s Binding in Circulation: Physiological and Clinical Implications
Authors: Anna L Goldman, Shalender Bhasin, Frederick C W Wu, Meenakshi Krishna, Alvin M Matsumoto, Ravi Jasuja
Journal: Endocrine Reviews (2017)

In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.
Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience
Authors: H. Beköz, N. Karadurmuş, S. Paydaş, A. Türker, T. Toptaş, T. Fıratlı Tuğlular, M. Sönmez, Z. Gülbaş, E. Tekgündüz, A.H. Kaya, M. Özbalak, N. Taştemir, L. Kaynar, R. Yıldırım, I. Karadoğan, M. Arat, F. Pepedil Tanrıkulu, V. Özkocaman, H. Abalı, M. Turgut, M. Kurt Yüksel, M. Özcan, M.H. Doğu, S. Kabukçu Hacıoğlu, I. Barışta, M. Demirkaya, F.D. Köseoğlu, S.K. Toprak, M. Yılmaz, H.C. Demirkürek, O. Demirkol, B. Ferhanoğlu
Journal: Annals of Oncology (2017)
CAN WE LIMIT TRAINING DAYS LOST DUE TO OSGOOD SCHLATTERS DISEASE IN JUNIOR SQUASH ATHLETES?
Authors: Cosmin Horobeanu, Thomas Jones, Amanda Johnson
Journal: British Journal of Sports Medicine (2017)

Background High-intensity sports like Squash expose immature athletes to the risk of developing Osgood-Schlatter's (OSD) disease during critical periods of growth. Acute OSD episodes have been associated with changes in training load and recognized as a common cause of lost training days. Objective To investigate the influence of periodic OSD monitoring and any subsequent alterations in training load on the number of training days lost. Design Prospective data analysis over 2 seasons (80 weeks), repeated measures. Setting Elite youth sports academy. Patients (or Participants) Highly-trained adolescent Squash athletes (n=9) who were identified as being “at risk” based on; previous episodes of OSD, chronological age (12–15 years) and maturity status. Interventions (or Assessment of Risk Factors) On a weekly basis a physiotherapist graded each athlete on a scale of 5 (“free of OSD symptoms”) to 1 (“unable to train”). The grading was based on clinical assessments including; pain level over the tibial tuberosity during palpation, functional movements, and strength assessments of the Quadriceps and Hamstrings. When an athlete was rated ≤3 coaching staff were advised to reduce the training load for the subsequent week. Training load was quantified using Edwards Training Impulse calculated from heart rate data. Main Outcome Measurements The number of training days lost due to OSD. Any alterations in training load following a rating of ≤3. Results Over the intervention period there were 24 ratings of ≤3. Weekly training load following a rating of ≤3 was significantly lower than the average weekly load (245.4±231.2 Vs. 658.5±154.7 arbitrary units, P&lt;0.001). Five training days lost due to OSD were recorded during the intervention period. Conclusions Periodic monitoring of OSD symptoms, with basic clinical tests, appear to alert the medical staff about potential acute onsets. Subsequent recommendations to reduce training load resulted in low training days lost due to OSD.
Relative contribution of baseline variables in a nomogram to predict survival in patients treated with nab-paclitaxel plus gemcitabine or gemcitabine alone for metastatic pancreatic cancer
Authors: David Goldstein, Daniel Von Hoff, E. Chiorean, Michele Reni, Josep Tabernero, Ramesh Ramanathan, Julia Wilkerson, Marc Botteman, Abdalla Aly, Sandra Margunato-Debay, Brian Lu, Chrystal Louis, Markus Renschler, Desmond McGovern, Chee Lee
Journal: Annals of Oncology (2017)
An Ongoing Open-Label Phase 1/2 Study of INCB050465, a Selective PI3Kδ Inhibitor, in Patients with Previously Treated B-Cell Malignancies
Authors: Tycel Phillips, Rod Ramchandren, Michael S Wertheim, Martin E Gutierrez, William J Edenfield, Fitzroy Dawkins, Doug J DeMarini, Li Zhou, Swamy Yeleswaram, Robert C Newton, Xuejun Chen, Andres Forero-Torres
Journal: Blood (2016)