tbuckley/cabot-search huggingface dataset:
Stratification markers for the risk of recurrence after curative resection of stage II or III gastric cancer and potential clinical applications.
Authors: Takashi Oshima, Kentaro Sakamaki, Yohei Miyagi, Takaki Yoshikawa, Manabu Shiozawa, Haruhiko Cho, Yasushi Rino, Chikara Kunisaki, Akira Tsuburaya, Toshio Imada, Munetaka Masuda
Journal: Journal of Clinical Oncology (2015)

11040 Background: Standard treatment for stage II or III gastric cancer is curative resection followed by adjuvant chemotherapy. Treatment outcomes are expected to be further improved by individualized therapy based on biomarker analysis. We extracted mRNA from frozen specimens of gastric cancer to establish a cDNA bank and then analyzed markers for stratifying the risk of recurrence after curative resection of stage II or III gastric cancer. We report our currently available findings. Methods: The study group comprised 255 patients with stage II or III gastric cancer who underwent curative resection and were followed up for ≥ 5 years after surgery. The patients were divided into 2 groups: a training set consisting of 145 patients and a validation set consisting of 110 patients. A total of 104 genes were selected as candidate biomarkers on the basis of comprehensive screening by DNA microarray, extraction by SAGE library analysis, and the identification of target molecules and related families, including the results of preclinical studies. The relative expression levels of target genes in gastric cancer tissue were measured by quantitative polymerase chain reaction. Genes identified be independent predictors of poor outcomes in the training set were verified in the validation set by Cox proportional-hazards analysis. Results: In the training set of stage II or III gastric cancer, 38 genes were evaluated to be independent predictors of poor outcomes. Verification analysis was then performed using the validation set, and the following 12 genes were selected as candidate markers for recurrence risk stratification (P < 0.2): SPARC, INHBA, HRBB2, VSNL1, CXCR4, EZH2, CCR7, PDGFRB, P53, MMP11, MRP1, and CEACAM7. Good reproducibility was obtained for 5 of these genes: SPARC, INHBA, HRBB2, VSNL1, and CXCR4 (P < 0.05). Conclusions: Promising candidate markers for stratification of recurrence risk after curative resection of stage II or III gastric cancer were identified. These candidate markers are now being analyzed at the protein level by tissue microarray, using specimens from about 500 patients each at two high-volume centers, with the goal of developing clinical applications.
FRI-167-Effectiveness and safety with tenofovir alafenamide (TAF) for hepatitis B in US clinical practice
Authors: Michael Curry, Ho Bae, Douglas Dieterich, Victor Ankoma-Sey, Rajender Reddy, Calvin Pan, Hie-Won Hann, Myron Tong, W. Ray Kim, Paul Kwo, Lynn Frazier, Scott Milligan, Keith Spitz, Nezam Afdhal
Journal: Journal of Hepatology (2019)
Advanced Intrahepatic Cholangiocarcinoma: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials
Authors: Angela Lamarca, Paul Ross, Harpreet S Wasan, Richard A Hubner, Mairéad G McNamara, Andre Lopes, Prakash Manoharan, Daniel Palmer, John Bridgewater, Juan W Valle
Journal: JNCI Journal of the National Cancer Institute (2019)

The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care). Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided. Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval [CI] = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16). Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design.
When van Mechelen's sequence of injury prevention model requires pragmatic and accelerated action: the case of para alpine skiing in Pyeong Chang 2018
Authors: Cheri Blauwet, Nick Webborn, James Kissick, Jan Lexell, Jaap Stomphorst, Peter van de Vliet, Dimitrije Lazarovski, Wayne Derman
Journal: British Journal of Sports Medicine (2019)

Results of the Paralympic Injury and Illness Surveillance Study noted an unusually high injury incidence rate (IR) in the sport of Para alpine skiing at the 2014 Sochi Paralympic Games (IR 48.3, a sixfold increase in acute injuries in comparison to the Vancouver 2010 Paralympic Games).1–3 There were likely several associated factors. Some were clearly modifiable such as the course design, number of training runs permitted on the course and the command and control structure between the technical and medical staff. Additionally, Paralympic officials recognised that careful monitoring of weather data and timely management of snow production, taking advantage of modern technology, had the potential to reduce injury risk. Thus, for the 2018 PyeongChang Paralympic Winter Games (the Games), the International Paralympic Committee (IPC) Medical Committee, in collaboration with the World Para Alpine Skiing (WPAS) sport technical staff, implemented a series of changes following Professor Willem van Mechelen’s ‘Sequence of (Injury) Prevention’ model4:

The Paralympic Injury and Illness Surveillance Study carried out at the Sochi 2014 Paralympic Games demonstrated a dramatic …
The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing
Authors: Jun Ishihara, Ako Ishihara, Richard D. Starke, Claire R. Peghaire, Koval E. Smith, Thomas A. J. McKinnon, Yoji Tabata, Koichi Sasaki, Michael J. V. White, Kazuto Fukunaga, Mike A. Laffan, Matthias P. Lutolf, Anna M. Randi, Jeffrey A. Hubbell
Journal: Blood (2019)
Reversion of cardiac dysfunction by a novel orally available calcium/calmodulin-dependent protein kinase II inhibitor, RA306, in a genetic model of dilated cardiomyopathy
Authors: Philippe Beauverger, Marie-Laure Ozoux, Guillaume Bégis, Valérie Glénat, Véronique Briand, Marie-Claire Philippo, Cyril Daveu, Georges Tavares, Sébastien Roy, Alain Corbier, Pascale Briand, Olivier Dorchies, Anne-Laure Bauchet, Eric Nicolai, Olivier Duclos, Dorothée Tamarelle, Marie-Pierre Pruniaux, Anthony J Muslin, Philip Janiak
Journal: Cardiovascular Research (2019)

Despite improvements in patient identification and management, heart failure (HF) remains a major public health burden and an important clinical challenge. A variety of animal and human studies have provided evidence suggesting a central role of calcium/calmodulin-dependent protein kinase II (CaMKII) in the development of pathological cardiac remodelling and HF. Here, we describe a new potent, selective, and orally available CaMKII inhibitor.Chemical optimization led to the identification of RA306 as a selective CaMKII inhibitor. This compound was found potent on the cardiac CaMKII isoforms delta and gamma (IC50 in the 10 nM range), with pharmacokinetic properties allowing oral administration in animal models of HF. RA306 was administered to diseased mice carrying a mutation in alpha-actin that is responsible for dilated cardiomyopathy (DCM) in humans. In two separate studies, RA306 was orally administered at 30 mg/kg either for 2 weeks (twice a day) or for 2 months (once a day). Echocardiography monitoring showed that RA306 significantly improved cardiac function (ejection fraction and cardiac output) as compared to vehicle. These disease modifying effects of RA306 were associated with inhibition of cardiac phosphorylation of phospholamban (PLN) at threonine-17, indicating reduced cardiac CaMKII activity.This work supports the feasibility of identifying potent orally available CaMKII inhibitors suitable for clinical use to treat heart disease.
SAT-189-GCAC1809-1812TTCT a novel viral quadruple mutation is strongly associated with basal core promotor double mutation and viral load in Hepatitis B e antigen negative chronic hepatitis B virus infected patients
Authors: Kai-Henrik Peiffer, Lisa Kuhnhenn, Catrina Spengler, Bingfu Jiang, Michael Basic, Johannes Vermehren, Viola Knop, Stefan Zeuzem, Christoph Sarrazin, Eberhard Hildt
Journal: Journal of Hepatology (2019)
Randomized pilot study comparing high-dose (HD) influenza vaccine to standard-dose (SD) influenza vaccine in adult oncology patients younger than 65 receiving chemotherapy.
Authors: Saad Jamshed, Ann R Falsey, Lynda J Dimitroff, Jeanine S Santelli, Edward E Walsh
Journal: Journal of Clinical Oncology (2015)

9614 Background: Pts on chemotherapy often fail to develop a robust response to influenza vaccine. Compared to SD influenza vaccine, HD vaccine has shown improved immunogenicity & protection against influenza illness in adults ≥65 yrs. This study compared the immunogenicity & tolerability of HD to SD vaccine in pts <65 yrs receiving chemotherapy. Methods: 105 pts were randomized to receive either SD or HD (51 vs 54) vaccine on day1 of chemotherapy during 2012-2013 & 2013-2014 seasons. HAI titers were measured prior to & 4-wks after vaccination. HAI were summarized as GMT, seroconversion & seroprotection rates. Sample size calculation was based on 30-50% effect size on GMTs. Equal numbers were expected in each group & assumed 80% power. GMTs for each strain were transformed to log 2, t-test was performed on log-transformed HAI titer. χ2 was used for seroconversion rate. A p-value > 0.05 was considered significant. Results: 5 pts were excluded, 1 received the vaccine twice. 4 pts who enrolled both yrs, were included only once (yr 1). Mean age (52.9 vs 53.9 yrs) and baseline HAI titers were equivalent; 90% in both arms had solid tumors & 58 vs 50% were receiving curative therapy in SD vs HD arms, respectively. Both vaccines were well tolerated with no SAEs. Seroprotection was excellent for all antigens in both arms. Seroconversion rate for all 3 influenza antigens & post vaccination GMTs for H3N2 & B strains were significantly improved with HD vaccine (Table). Conclusions: Trivalent HD influenza vaccine can be safely administered to chemotherapy pts with improved immunogenicity over SD vaccine. A larger study is needed to show clinical benefits with HD vaccine. Clinical trial information: NCT01666782. Vaccine Antigen SD (n = 50) Post HAI GMT (95% CI) HD (n = 50) Post HAI GMT (95% CI) (t-test) H1N1 979.1 (609.1-1349.0) 1350.1 (819.8-1880.4) p = 0.106 H3N2 811.2 (401.2-1221.3) 1143.4 (739.6-1547.3) p = 0.005 B 228.0 (129.9-326.2) 351.6 (215.6-487.7) p = 0.02 Seroconversion Rate (%) (≥ 4 fold change) (χ2) H1N1 46.0 72.0 p = 0.014 H3N2 58.0 80.0 p = 0.029 B 44.0 80.0 p = 0.0004
Just 11 years to avert disaster
Authors: Alex Armitage
Journal: BMJ (2019)

PA

Radical environmentalists took to the streets of London on 15 April to launch a new approach to saving the world. Extinction Rebellion activists aimed to bring the city centre to a standstill to spark a radical change of direction in the national conversation: away from Brexit and towards a much more pressing issue—ecological breakdown.

As a paediatrician …
Abstract 10620: Giant Coronary Artery Aneurysm Presenting as Diffuse ST Elevation
Authors: Anu Salwan, Assad Mohammedzein, Nethuja Salagundla, Masoud Alzeerah, Manish Patel
Journal: Circulation (2018)

Introduction: Giant coronary artery aneurysm (GCAA) measuring > 5 cm are extremely rare. We describe a 9 x 8.3 x 10 cm GCAA in a 38-year-old male, that was initially thought to be cardiac mass of p...
Extensive Immunosuppression in the Acute Myeloid Leukemia (AML) Bone Marrow and Discovery of NK Cells As Biomarker of Superior Survival
Authors: Oscar Brück, Sami Blom, Olli Dufva, Riku Turkki, Antonio Ribeiro, Sanna Siitonen, Panu Kovanen, Olli Kallioniemi, Kimmo Porkka, Teijo Pellinen, Satu Mustjoki
Journal: Blood (2017)
Abstract 19212: Quantitative Relationship of End-Tidal Carbon Dioxide With Ventilation Characteristics During CPR
Authors: Abhishek Bhardwaj, Magda Wernovsky, Audrey L Blewer, Eric Mutter, Benjamin S Abella, Marion Leary
Journal: Circulation (2017)

Background: End Tidal CO2 (ETCO2) has been used as a surrogate for systemic blood flow during CPR. Resuscitation guidelines suggest the use of ETCO2 for assessing chest compression effectiveness. While previous studies have found a relationship between deeper chest compression depth and higher ETCO2, there is paucity of clinical research examining the effect of ventilation parameters on ETCO2 during CPR. Objective: To quantify the relationship of ETCO2 independently with respiratory rate (RR), minute ventilation (MV) and tidal volume (TV) during clinical CPR. Methods: We performed an observational study which captured time synchronized respiratory data from adult cardiac arrest events at 2 sites between 02/2015-04/2016 using a respiratory profile monitor (Philips Respironics NM3, Andover, MA). ETCO2, RR, MV and TV were averaged over each minute and analyzed using mixed effects regression modeling to account for patient as a cluster. Results: 11 subjects had a total of 129 average breaths per min of respir...
PS-036-Optimization and validation of a novel three-dimensional co-culture system in decellularized human liver scaffold for the study of liver fibrosis and cancer
Authors: Kessarin Thanapirom, Luca Frenguelli, Walid Al-Akkad, ZhenZhen Zhang, Massimo Pinzani, Giuseppe Mazza, Krista Rombouts
Journal: Journal of Hepatology (2019)
Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition
Authors: Victoria A. Jennings, Gina B. Scott, Ailsa M.S. Rose, Karen J. Scott, Gemma Migneco, Brian Keller, Katrina Reilly, Oliver Donnelly, Howard Peach, Donald Dewar, Kevin J. Harrington, Hardev Pandha, Adel Samson, Richard G. Vile, Alan A. Melcher, Fiona Errington-Mais
Journal: Molecular Therapy (2019)

A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data are available regarding the mechanisms of human anti-tumor immune priming, an improved understanding of which could inform the development of future combination strategies with improved efficacy. This study addressed direct oncolysis and innate and adaptive human immune-mediated effects of a closely related HSV encoding GM-CSF (HSVGM-CSF) alone and in combination with histone deacetylase inhibition. We found that HSVGM-CSF supported activation of anti-melanoma immunity via monocyte-mediated type I interferon production, which activates NK cells, and viral maturation of immature dendritic cells (iDCs) into potent antigen-presenting cells for cytotoxic T lymphocyte (CTL) priming. Addition of the histone deacetylase inhibitor valproic acid (VPA) to HSVGM-CSF treatment of tumor cells increased viral replication, viral GM-CSF production, and oncolysis and augmented the development of anti-tumor immunity. Mechanistically, VPA increased expression of activating ligands for NK cell recognition and induced expression of tumor-associated antigens, supporting innate NK cell killing and CTL priming. These data support the clinical combination of talimogene laherparepvec with histone deacetylase inhibition to enhance oncolysis and anti-tumor immunity.
Subjects’ views on compensation for donating biospecimens.
Authors: Rebecca D. Pentz, Travis Ryan Deal, Taylor White, Margie Dixon, Kristopher A Hendershot
Journal: Journal of Clinical Oncology (2015)

11015 Background: Biobanking for research is an increasingly common practice. Ethical concerns regarding ownership of tissue and compensation for donation have arisen as the prevalence of biobanks has increased. Methods: Patients eligible for surgical removal of tumors or other tissues at the Winship Cancer Institute were asked to donate tissue by physicians during a surgical oncology clinic as well as by tissue donation staff carrying out a national, multisite NCI biobanking study. We surveyed 101 of these patients, regardless of whether they donated tissue, about informed consent issues surrounding broad future research use of donated tissues. One question queried participants on their preferences regarding compensation for biospecimen donation. Once consented, participants had the option of completing the interview on-site or over the phone. We did not collect any Protected Health Information, other than contact information, which was destroyed upon completion of the interview. Results: Of the 140 patient approached, 101 (72%) participated, with 94 (93%) completing the interview over the phone. 19 (14%) patients refused to participate and 20 (14%) were lost to follow up. 52 (51%) were male, 74 (73%) white, and the median age was 62 years. 50 (50%) had a college degree, and the average income bracket was $60,000 - $80,000. Seventy-five (74%) did not think they should be paid for donating tissue. When probed as to their reasons for not wanting payment, most subjects [46 (61%)} provided altruistic reasons. Five noted that biobank participants were not subjected to any additional burden, and three mentioned that the tissue would be destroyed if they had not participated. Seven of the 75 said payment would be appreciated though not expected. Nine (9%) said donors should be paid, with five citing ownership of the tissues. 14 (14%) believed they should only be paid under certain conditions, most commonly referring to tissue use by for-profit companies. Three (3%) had no opinion. Conclusions: The majority of subjects did not feel that they should be compensated for tissues provided, viewing it as an opportunity to help others. A small minority believed compensation was due, especially in the case of tissue use by private researchers in for-profit companies.
Obstructive Sleep Apnea in Adults
Authors: Sigrid C. Veasey, Ilene M. Rosen
Journal: New England Journal of Medicine (2019)

Obstructive sleep apnea is common and is associated with daytime sleepiness and increased risks of motor vehicle accidents and cardiovascular disease. CPAP is considered first-line therapy for symptomatic or moderate-to-severe obstructive sleep apnea; mandibular-advancement devices and various surgical options are other approaches.
Circulating tumor cell (CTC) EMT and stem cell biomarker expression predict overall survival (OS) in mCRC by a combined immunomagnetic qRT-PCR approach.
Authors: Yan Ning, Wu Zhang, Diana L. Hanna, Angela Mendez, Dongyun Yang, Yu Sunakawa, Stefan Stremitzer, Satoshi Matsusaka, Satoshi Okazaki, Anish Parekh, Rita Elie El-Khoueiry, Becky Flores, Siegfried Hauch, Afsaneh Barzi, Anthony B. El-Khoueiry, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

11018 Background: CTCs harboring epithelial, mesenchymal and stem cells direct the metastatic process. CTC enumeration and biomarker expression have been associated with clinical outcomes in mCRC patients (pts). We developed and validated a combined immunomagnetic qRT-PCR protocol for colorectal CTC characterization based on epithelial, EMT, and stem cell biomarkers with sufficient sensitivity, specificity, and efficiency. The goal of this study was to test whether molecular characterization of CTCs will more effectively predict OS. Methods: CTCs were obtained from 94 pts with mCRC [Median age: 56.5 years, Median follow up: 17.3 (1.3, 39.5) mos and OS: 11.4 (9.0, 21.1) mos]. All pts were refractory to standard treatments and were enrolled in clinical trials at USC from 2009 to 2014. Prior to treatment initiation, peripheral blood was collected for CTC isolation. Immunomagnetic qRT-PCR was used for CTC detection based on the presence of CK20 and survivin gene expression. We then selected, based on functional roles and reliability of detection in CTCs, and quantified markers of EMT (PI3Kα, Akt-2) and stem cell (ALDH1) pathway activation in CTC-positive mCRC pts with AdnaGen primer mixture. Cut-off values were determined by Receiver-operating characteristic (ROC) curves. Results: 74 of 94 (79%) pts with CTCs based on CK20 and/or survivin gene expression (CTC-positive group) had a significantly worse OS (10 mos v. not yet reached;) compared with the CTC-negative group (21%) in both univariate (HR:3.383 [ 1.04, 11.01], P = 0.001) and multivariate analyses (HR : 4.557 [1.097, 18.926], P = 0.037). All CTC-positive pts, which had PI3Kα(57%), Akt-2(56%) and ALDH1(80%) mRNA expression, independently predicted OS based on cut-off values of each marker. Higher gene expression associated with significantly worse OS compared to those with lower gene expression: PI3Kα: 6.4 v. 10.4 mos; Akt-2: 8.6 v. 23.6 mos; ALDH1: 7.8 v. 10.3 mos (P < 0.001 for all comparisons). Conclusions: Our study is the first to demonstrate the prognostic and predictive significance of this CTC EMT and stem cell gene signature in mCRC pts. This technology may allow real time molecular monitoring of drug efficacy.
High-Fiber Diet Might Protect Against Range of Conditions
Authors: Rita Rubin
Journal: JAMA (2019)

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