tbuckley/cabot-search huggingface dataset:
FRI-134-Comparative analysis of intrahepatic and peripheral chemokine responses in chronic hepatitis B, C and D in vivo
Authors: Jan-Hendrik Bockmann, Matin Kohsar, Lena Allweiss, Tassilo Volz, Janine Kah, Marc Luetgehmann, Ansgar W. Lohse, Julian Schulze zurWiesch, Maura Dandri
Journal: Journal of Hepatology (2019)
Abstract 17907: Clinical Outcomes and Mortality Impact of Hyperbaric Oxygen Therapy in Patients With Carbon Monoxide Poisoning
Authors: Jason J Rose, Seyed M Nouraie, Marc C Gauthier, Anthony F Pizon, Melissa I Saul, Michael P Donahoe, Mark T Gladwin
Journal: Circulation (2017)

Introduction: Carbon Monoxide (CO) poisoning affects 50,000 per year in the United States alone. Mortality is approximately 3% and up to 40% of survivors suffer from permanent neurocognitive and af...
Activators of tissue and urokinase types plasminogen in basal cell skin cancer.
Authors: Yury Valentinovich Przhedetsky, Elena Mikhaylovna Frantsiyants, Ekaterina Komarova, Ekaterina Sharay
Journal: Journal of Clinical Oncology (2015)

e22220 Background: Researches have demonstrated the role of plasminogen activators in processes of progression in various neoplasms. However, the contemporary authors give little coverage to this issue for basal cell skin cancer. Methods: The content and activity of urokinase type plasminogen activator (uPA) and tissue type one (tPA) were determined in 10% cytosolic fractions of basal cell skin cancer tumor tissue of solid (n = 15), ulcerous infiltrative (n = 10) and superficial (n = 8) variants, as well as in the tissue of recurrent cases (n = 20), by ELISA. Healthy skin obtained in surgical treatment of patients having no oncopathology (n = 15) was used as control. Results: The content of tPA in tumor tissue of all groups under study was higher: 1,8 times in the solid variant, 2,8 times in the ulcerous infiltrative one, 1,9 times in the superficial one, and in the recurrent cases tissue – 1,7 times higher than in the control samples. The activity of tPA was also elevated – on average, 2,4 times higher than that in the control tissues. The content of uPA was 3,9 and 2,9 times higher in the tissues of solid and superficial variants of basal cell skin cancer, respectively, while it was 4,9 and 5,6 times as high in the ones of ulcerous infiltrative variant and in the recurrent cancer tissues. In all variants of cancer, the activity of uPA in the tumor tissue increased 1,6 times, while in the recurrent cancer one, it was almost 2 times as high. The proportion of content and activity of tPA in the tumor tissue did not validly differ from that in the healthy skin. By contrast, the balance of the content and activity of uPA was significantly higher in all tumor tissues: 2,4 times -in the solid variant, 3 times – in the ulcerous infiltrative one, 1,8 times – in the superficial one, and 2,8 times as high in the recurrent tumor against the control values. Conclusions: Increased synthesis and activity of both tissue type and urokinase type plasminogen activators has been found in the tumor tissue of basal cell skin cancer, irrespective of the cancer variant, as well as in the tissue of recurrent tumors. However, the analysis of balance of the level and activity of the activators allows supposing that it is urokinase which prevails in activation of plasminogen in basal cell skin cancer.
Prognostic value of CD8-positive tumor stroma-infiltrating lymphocytes and PD-L1 positive tumor cells at initial biopsy in patients with locally advanced NSCLC treated with chemoradiotherapy
Authors: K. Gennen, L. Käsmann, C. Eze, M. Dantes, O. Roengvoraphoj, J. Taugner, J. Neumann, A. Tufman, M. Orth, S. Reu, C. Belka, F. Manapov
Journal: Annals of Oncology (2019)

Background: According to results of PACIFIC trial, immune checkpoint inhibitors (CPIs) are an integral part of the multimodal treatment approach for inoperable locally-advanced non-small cell lung cancer (LA-NSCLC). The purpose of this single-center study was to investigate a prognostic value of CD8-positive tumor stroma-infiltrating lymphocytes (TILs) and PD-L1 positive tumor cells at initial biopsy in patients treated with definitive chemoradiotherapy (CRT). Methods: We collected initial tumor tissue samples and reviewed the clinical characteristics of 36 LA-NSCLC patients treated at our center with definitive CRT between 2000 and 2004. The analyzed tumor tissue was taken before start of multimodal treatment. An experienced pathologist performed the immunohistochemistry analysis and interpretation. Tumor cells and CD8-positive tumor stroma-infiltrating lymphocytes were analyzed separately. Based on PD-L1 expression on tumor cells, patients were divided into three subgroups (0%, 1-5%, >5%). Two patient subgroups were defined according to CD8 expression in the tumor-surrounding stroma (low and high density: 0-40% vs. 41-100%). Results: Thirty-six patients with LA-NSCLC were treated with definitive CRT (stage II, III and IV: 2, 30 and 4 patients). 18 (50%) patients had squamosa cell carcinoma, 14 patients (39%) adenocarcinoma and 4 patients (11%) NOS. Patients with high density of CD8 positive tumor stroma-infiltrating lymphocytes (TILS) showed a significantly reduced overall survival than patients with low density (13 vs. 19 months, one-year survival 56.5 vs. 69.2% p = 0.047); Patients without (0%) and low expression (1-5%) of PD-L1 on tumor cells showed a significantly improved overall survival compared to patients with a PD-L1 expression on tumor cells over 5% (median survival: 13.8 vs. 6.6 months, 1-year survival rate: 67.7 vs. 33.3%; p = 0.039). Conclusions: High density of CD8-positive tumor stroma-infiltrating lymphocytes and PDL1 expression on tumor cells over 5% at initial biopsy correlates significantly with reduced overall survival in patients with LA-NSCLC treated with CRT. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Bioresorbable Electronic Implants: History, Materials, Fabrication, Devices, and Clinical Applications
Authors: Gi Doo Cha, Dayoung Kang, Jongha Lee, Dae‐Hyeong Kim
Journal: Advanced Healthcare Materials (2019)

Medical implants, either passive implants for structural support or implantable devices with active electronics, have been widely used for the diagnosis and treatment of various diseases and clinical issues. These implants offer various functions, including mechanical support of biological structures in orthopedic and dental applications, continuous electrophysiological monitoring and feedback of electrical stimulation in neuronal and cardiac applications, and controlled drug delivery while maintaining arterial structure in drug-eluting stents. Although these implants exhibit long-term biocompatibility, surgery for their retrieval is often required, which imposes physical, biological, and economical burdens on the patients. Therefore, as an alternative to such secondary surgeries, bioresorbable implants that disappear after a certain period of time inside the body, including bioresorbable active electronics, have been highlighted recently. This review first discusses the historical background of medical implants and briefly define related terminology. Representative examples of non-degradable medical implants for passive structural support and/or for diagnosis and therapy with active electronics are also provided. Then, recent progress in bioresorbable active implants composed of biosignal sensors, actuators for therapeutics, wireless power supply components, and their integrated systems are reviewed. Finally, clinical applications of these bioresorbable electronic implants are exemplified with brief conclusion and future outlook.
FRI-194-The novel antiviral agent inarigivir inhibits both nucleos (t)ide analogue and capsid assembly inhibitor resistant HBV in vitro
Authors: Danni Colledge, Kathy Jackson, Vitina Sozzi, XIn Li, Michael Beard, Nicholas Eyre, JunJie Zhang, Haitao Guo, Nezam Afdhal, Radhakrishnan Iyer, Stephen Locarnini
Journal: Journal of Hepatology (2019)
Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species
Authors: Rapolas Zilionis, Camilla Engblom, Christina Pfirschke, Virginia Savova, David Zemmour, Hatice D. Saatcioglu, Indira Krishnan, Giorgia Maroni, Claire V. Meyerovitz, Clara M. Kerwin, Sun Choi, William G. Richards, Assunta De Rienzo, Daniel G. Tenen, Raphael Bueno, Elena Levantini, Mikael J. Pittet, Allon M. Klein
Journal: Immunity (2019)
Sitting Time, Physical Activity, and Risk of Mortality in Adults
Authors: Emmanuel Stamatakis, Joanne Gale, Adrian Bauman, Ulf Ekelund, Mark Hamer, Ding Ding
Journal: Journal of the American College of Cardiology (2019)

It is unclear what level of moderate to vigorous intensity physical activity (MVPA) offsets the health risks of sitting. The purpose of this study was to examine the joint and stratified associations of sitting and MVPA with all-cause and cardiovascular disease (CVD) mortality, and to estimate the theoretical effect of replacing sitting time with physical activity, standing, and sleep. A longitudinal analysis of the 45 and Up Study calculated the multivariable-adjusted hazard ratios (HRs) of sitting for each sitting-MVPA combination group and within MVPA strata. Isotemporal substitution modeling estimated the per-hour HR effects of replacing sitting. A total of 8,689 deaths (1,644 due to CVD) occurred among 149,077 participants over an 8.9-year (median) follow-up. There was a statistically significant interaction between sitting and MVPA only for all-cause mortality. Sitting time was associated with both mortality outcomes in a nearly dose-response manner in the least active groups reporting <150 MVPA min/week. For example, among those reporting no MVPA, the all-cause mortality HR comparing the most sedentary (>8 h/day) to the least sedentary (<4 h/day) groups was 1.52 (95% confidence interval: 1.13 to 2.03). There was inconsistent and weak evidence for elevated CVD and all-cause mortality risks with more sitting among those meeting the lower (150 to 299 MVPA min/week) or upper (≥300 MVPA min/week) limits of the MVPA recommendation. Replacing sitting with walking and MVPA showed stronger associations among high sitters (>6 sitting h/day) where, for example, the per-hour CVD mortality HR for sitting replaced with vigorous activity was 0.36 (95% confidence interval: 0.17 to 0.74). Sitting is associated with all-cause and CVD mortality risk among the least physically active adults; moderate-to-vigorous physical activity doses equivalent to meeting the current recommendations attenuate or effectively eliminate such associations.
Pre-Phase Chemotherapy Followed By Ofatumumab (OFA) and Reduced Dose CHOP (OFA-mini-CHOP) for Patients over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – a Lymphoma Study Association (LYSA) Prospective Phase II Study (LNH09-7B)
Authors: Frédéric Peyrade, Bologna Serge, Vincent Delwail, Jean François Emile, Christian Rose, Christophe Fermé, Jean-Marc Schiano, Bertrand Coiffier, Bernadette Corront, Hassan Farhat, Christophe Fruchart, Herve Ghesquieres, Margaret Macro, Hervé Tilly, Bachra Choufi, Richard Delarue, Olivier Fitoussi, Jean Gabarre, Corinne Haioun, Fabrice Jardin
Journal: Blood (2014)
GS-12-Ascending dose cohort study of inarigivir - A novel RIG I agonist in chronic HBV patients: Final results of the ACHIEVE trial
Authors: Man-Fung Yuen, Chi-Yi Chen, Chun-Jen Liu, RachelWen-Juei Jeng, Magdy Elkhashab, Carla Coffin, Won Kim, Susan Greenbloom, Alnoor Ramji, Young-Suk Lim, Yoon Jun Kim, Scott Fung, Dong Joon Kim, JeongWon Jang, Kwan Sik Lee, Nezam Afdhal, Radhakrishnan Iyer, Chelsea Macfarlane, Kathy Jackson, Stephen Locarnini, Henry Chan
Journal: Journal of Hepatology (2019)
The Association Of Corticosteroid Therapy And The Outcome Of Critically Ill Patients With The Middle East Respiratory Syndrome
Authors: Y M Arabi, Y Mandourah, F Al-Hameed, A Al Omari, A Sindi, B Alraddadi, S Shalhoub, A Al Motairi, K Al Khatib, A A Mommin, I A Qushmaq, A Mady, O Solaiman, A Al Aithan, H H Balkhy, R Al-Raddadi, A Rajab, G A Al Mekhlafi, A Al Harthy, A Kharaba, A Al-Jabbary, R Pinto, M Sadat, H Al Mutairi, E Al Qasim, J Jose, A M Deeb, L Merson, F G Hayden, R Fowler, A S Aldawood
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
PS-034-MCJ: A therapeutic target in hepatic ischemia and reperfusion injury
Authors: Naroa Goikoetxea, David Fernández Ramos, Marina Serrano-Macia, Maria Eugenia Cornide, Mónica Jiménez-Castro, Bennedetta Alfano, Diego Saenz de Urturi, Francisco Gonzalez-Romero, Virginia Gutiérrez de Juan, Begoña Rodriguez Iruretagoyena, Teresa Cardoso Delgado, Fernando Lopitz Otsoa, Lucía Barbier Torres, Pablo Fernández Tussy, Jorge Simón, Paloma Martín, Juan Anguita, Marina Perez Redondo, Eduardo Miñambres, Shelly C. Lu, José M. Mato, Guadalupe Sabio, Carmen Peralta, Patricia Aspichueta, Marta Casado, Cesar Martin, Marta Varela-Rey, María Luz Martínez-Chantar
Journal: Journal of Hepatology (2019)
Development of a new patient‐reported outcome measure to evaluate treatments for acne and acne scarring: the <scp>ACNE</scp> ‐Q
Authors: A.F. Klassen, S. Lipner, M. O'Malley, N.M. Longmire, S.J. Cano, T. Breitkopf, C. Rae, Y.L. Zhang, A.L. Pusic
Journal: British Journal of Dermatology (2019)

Psychosocial concerns represent important outcomes in studies of treatments for acne and acne scarring. Also important, but largely overlooked, is the concept of appearance.To design an acne-specific patient-reported outcome measure for acne and acne scarring.We used a mixed-methods approach. Phase I involved 21 patient interviews that were audio-recorded, transcribed and coded. Concepts were identified and developed into scales that were refined through 10 cognitive interviews and input from 16 clinical experts. Phase II involved data collection at hospital and community-based dermatology clinics in Canada and the U.S.A. Eligible participants were aged 12 years and older with acne and/or acne scars on the face, chest and/or back. Rasch Measurement Theory (RMT) analyses were performed to examine psychometric properties.Phase I led to the development of seven scales that measure appearance of facial skin, acne (face, chest and back) and acne scars, acne-specific symptoms and appearance-related distress. In phase II, 256 patients completed the ACNE-Q. RMT analysis provided evidence that the items of each scale worked together conceptually and statistically. Most participants scored within the range of measurement for each scale (81·9-93·1%). Reliability was high, with person separation index values and Cronbach alpha values > 0·90 for the appearance scales, ≥ 0·87 for appearance-related distress and ≥ 0·75 for symptoms. Worse scores on appearance scales correlated with worse symptom scores and more appearance-related distress.The ACNE-Q is a rigorously developed instrument that can be used to measure appearance and other patient-centred concerns. What's already known about this topic? Acne is a common dermatological condition that can have an important impact on psychosocial function. Current patient-reported outcome measures specific to acne focus mostly on measuring psychological and social impact. What does this study add? The ACNE-Q provides a set of independently functioning scales that measure appearance of facial, back and chest acne, acne scarring and facial skin. Additional scales measure appearance-related distress and acne symptoms. What are the clinical implications of this work? ACNE-Q provides the dermatology community with a rigorously developed patient-reported measure for acne that can be applied in clinical trials, research and patient care. The measurement of appearance by ACNE-Q scales is more comprehensive than in other instruments providing important information on appearance of their acne and/or acne scars from the patient perspective.
Real‐world treatment patterns of sacubitril/valsartan: a longitudinal cohort study in Germany
Authors: Rolf Wachter, Ana F. Fonseca, Bogdan Balas, Elisabeth Kap, Johanna Engelhard, Raymond Schlienger, Sven Klebs, Sara Bruce Wirta, Karel Kostev
Journal: European Journal of Heart Failure (2019)

Aims To analyse real‐world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany. Methods and results A retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre‐ and post‐index and compliance and persistence during 12 months post‐index. Two‐thirds of patients were prescribed the lowest sac/val dose of 50 mg twice daily (b.i.d.) at index and up‐titration during the first 6 months was attempted in 41% of these patients. Ten percent of patients prescribed 200 mg b.i.d. at index had to be stably down‐titrated; among patients prescribed 50 or 100 mg b.i.d. at index that were up‐titrated, &gt; 80% remained on the higher dose. Overall, the mean daily diuretic dose decreased by 25% after initiation of sac/val. High compliance and persistence rates were observed across sac/val doses, increasing with higher sac/val dose at index. Prior dose of angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker had only minor impact on first sac/val dose, compliance and persistence. Conclusions Most patients prescribed sac/val are not initiated on the recommended dose nor up‐titrated as recommended by the EU Summary of Product Characteristics. Initiation of sac/val was associated with high persistence and compliance and a dose reduction of diuretics. Barriers to up‐titration must be explored.
Proximity ligation assay (PLA) to identify HER2-negative breast carcinomas responding in HER-3 targeting agents.
Authors: Michalis Karamouzis, Georgia Dalagiorgou, Urania Georgopoulou, Michalis Kontos, Athanasios G. Papavassiliou
Journal: Journal of Clinical Oncology (2015)

e22184 Background: Many BC patients present resistance to anti-HER2 directed therapies. Growing evidence support the participation of HER3 and heregulin (Hg) on activation of HER2, regardless of its expression. Our goal was to evaluate the dimerization pattern of EGFR, HER2/3/4 in human tissues with various HER2 expression and the same with or without the addition of Hg and HER3 targeting agents in cell cultures. Methods: MCF7 and SKBR3 cell lines and15 human paraffin-embedded tissues (PFETs) were used. Dimerization was studied using PLA and immunofluorescence, where proximal proteins can be visualized combining immunocytochemistry with rolling circle amplification. The protocol was based on manufacturer’s instructions. Reagents: HRG1-β1 (R&D Systems), Pertuzumab (P) (Genetech), U3 (U) inhibitor (U3 Pharma). After blocking, cells were incubated with combination of primary antibodies (antiHER2/HER3, antiHER2/HER4, antiEGFR/HER3, anti-EGFR/HER4, antiEGFR/EGFR). Cells were then incubated with PLA probes (1:5) in antibody diluent (Olink Bioscience). Fluorescence images acquired using Zeiss Axiovert microscope. Data analysis was done with Duolink Image Tool Software. Results: In MCF7 cells (PLA signals scale 0-12), Hg addition increased EGFR/HER3 (8,07 vs 3,36) and less HER2/HER3 (4,12 vs 3,35). The addition of Hg and P resulted in EGFR/HER3 2,46, HER2/HER3 3,0 while Hg and U resulted in EGFR/HER3 0,6, HER2/HER3 0,6. In SKBR3 cells (PLA signals scale 0-60), Hg addition increased HER2/HER3 (26,93 vs 15,92) and less EGFR/HER3 (16 vs 10,6). The addition of Hg and P resulted in HER2/HER3 19,9, EGFR/HER3 12,5 while Hg and U resulted in HER2/HER3 0,7, EGFR/HER3 0,7. The dimmers in PFETs are shown in the Table. All images, data analysis and clinical data will be presented in full detail. Conclusions: PLA is a reliable method fordetecting EGFR member dimerization patterns in culture and human BC cells. Using PLA in PFETs can identify HER2 negative patients who may benefit by HER3 targeting agents. PLA scale 0-45 HER2/HER3 EGFR/HER3 HER2/HER4 EGFR/HER4 EGFR/EGFR HER2 0 2,30 2,30 3,10 2,10 1,60 HER2 1/2+ (FISH-) 6,15 13,64 3,30 2,00 2,10 HER3+ 30,62 40,65 15,76 30,46 13,67
Accurate prediction of optimal cancer drug therapies from molecular profiles by a machine-learning algorithm.
Authors: John F. McDonald, Roman Mezencev, Tran Q. Long, Benedict Benigno, Ioana Bonta, Giuseppe Del Priore
Journal: Journal of Clinical Oncology (2015)

e22182 Background: A major goal of cancer genomic medicine is the accurate prediction of optimal personalized therapies from the molecular profiles of individual patient tumors. With notable exceptions, this goal has yet to be realized across a broad spectrum of cancers due to the complexity of the disease and our limited understanding of the causal mechanisms involved. Methods: We have developed a robust machine learning method (SVM) to accurately link individual genomic profiles to drug responsiveness. Results: The algorithm predicts the responsiveness of a diversity of human cancer cell lines to individual and combination treatments of eight cancer drugs (carboplatin, cisplatin, docetaxel, paclitaxel, doxorubicin, erlotinib, gemcitabine and topotecan) with 80-100% accuracy. Gene expression data were found to be generally more informative than DNA sequence data in the generation of optimally accurate predictions. The results of preliminary studies using the algorithm to retrospectively and prospectively predict the responsiveness of ovarian cancer patients to first line cancer therapies will be presented. Conclusions: Machine learning is an objective, data-driven approach to the prediction of optimal cancer drug therapies from the genomic profiles of individual patient samples. The high predictive accuracy of the method is independent of underlying causal mechanisms and, thus, of current clinical potential.