tbuckley/cabot-search huggingface dataset:
Baseline-derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) to predict the benefit of immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) patients.
Authors: Laura Mezquita, Edouard Auclin, Roberto Ferrara, Clarisse Audigier-Valette, Laurent Tessonnier, Melinda Charrier, Marie Eve Boucher, Jihene Lahmar, Caroline Caramella, Jordi Remon, David Planchard, Julien Adam, Anas Gazzah, Nathalie Chaput, Jean-Charles Soria, Benjamin Besse
Journal: Journal of Clinical Oncology (2017)

9089 Background: dNRL (Neutrophils/Leucocytes-Neutrophils) and LDH were recently correlated to ICI benefit in melanoma. We tested if dNLR and LDH could have the same role in NSCLC patients. Methods: Baseline dNLR and LDH were collected in 234 patients treated with PD1/PDL1 inhibitors from Nov. 2013 to Dec. 2016, in a discovery (D) cohort (N = 161) from Gustave Roussy and an independent validation (V) cohort (N = 73) from 2 centers. ICI benefit was analyzed according to overall survival (OS), progression free survival (PFS) and response rate (RR) by RECIST 1.1. Kaplan-Meier and Cox regression were performed. Results: In the D cohort, 100 patients (62%) were males, 136 (85%) smokers and PS ≤1, with median age 61.5; 133 patients (81%) stage IV; 100 (62%) had adenocarcinoma and 46 (29%) squamous cells carcinoma; 35 (22%) were KRASmut, 13 (8%) EGFRmut and 3 (2%) ALKpositive. PDL1 expression was positive in 43 (75%), negative in 14 (25%) and unknown in 78. 132 (82%) patients received PD1 inhibitors; the median of prior lines was 1 (1-11). dNLR &gt; 3 and LDH &gt; upper normal limit (UNL) were independent factors for poor OS (HR 4,67, p = 0.011 and HR 2,65, p = 0.002, respectively) and poor PFS (HR 4,71, p = 0.001 and HR 1,68, p = 0.042 respectively). The median follow-up (FU) was 12 months (m) [95% CI 11-14], the median PFS 3m [2-4] and the median OS 10m [8-13]. In the V cohort, with a median FU of 11m [8-14], dNLR &gt; 3 and LDH &gt; UNL were significantly associated with poor OS (both p = 0.001), with a trend toward association with PFS (p = 0.06, p = 0.08, respectively). A Lung Immune Predictive Index (LIPI) was tested considering dNLR &gt; 3 and LDH &gt; UNL, with three groups. In D cohort, the median OS for good (no factor), intermediate (one factor) and poor (two factors) was 34m [17-NR], 10m [8-NR], 3m [1-NR], respectively (p = 0.0001), and PFS was similarly correlated (p = 0.001). Same results were demonstrated in the V cohort. Conclusions: Baseline dNLR &gt; 3 and LDH &gt; UNL can predict the benefit of ICI in advanced NSCLC patients. The LIPI at baseline is an easy tool to identify the candidates to immunotherapy. Confirmation cohorts are ongoing to validate the predictive role of the LIPI.
<i>EGFR</i> -Mutant Non–Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline <i>EGFR</i> T790M Testing
Authors: Ammar Sukari, Misako Nagasaka, Erin Wakeling
Journal: Journal of the National Comprehensive Cancer Network (2017)

With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non–small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself. Germline T790M mutation should be suspected and tested for when multiple biopsies show de novo T790M mutations or when de novo T790M is found in patients with a family history of lung cancer. This case report presents a 60-year-old woman with bilateral NSCLC with 3 different distinct histologic diagnoses. Evaluating the molecular profile using NGS completely changed the diagnosis, prognosis, and management of this rare presentation of NSCLC.
Phase I study of apalutamide (ARN) plus abiraterone acetate (AA), docetaxel (D) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC)
Authors: A.M. Molina, P.J. Christos, Y. Whang, L. Nordquist, A.L. Hackett, H. Beltran, B. Faltas, D. Nanus, P. Giannakakou, S.T. Tagawa
Journal: Annals of Oncology (2017)
GW28-e0524 Magnetocardiographic polar map image reveal regional wall motion abnormalities: comparison study with stress-echocardiography
Authors: Illya Chaikovsky, Mykhail Primin, Igor Nedayvoda, Andrey Verba, Georg Mjasnikov, Anatoly Kazmirchyk, Wenmig Ji, X. Fan, X. Tan, M. Lei, Z. Fan
Journal: Journal of the American College of Cardiology (2017)
Prise en charge des patients en Allemagne avec suspicion de fièvre hémorragique virale et autres infections contagieuses potentiellement mortelles
Authors: A Wirtz, M Niedrig, R Fock
Journal: Eurosurveillance (2002)

Les patients presentant une fievre hemorragique virale (FHV), doivent faire l’objet d’une prise en charge particuliere. Le diagnostic clinique est difficile car les premiers symptomes ne sont pas specifiques. L’Allemagne dispose de deux centres munis d’in
Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of programmed cell death 1 ligand 2–positive dendritic cells in allergic asthma
Authors: Minkyoung Cho, Jeong-Eun Lee, Hoyong Lim, Hyun-Woo Shin, Roza Khalmuratova, Garam Choi, Hyuk Soon Kim, Wahn Soo Choi, Young-Jun Park, Inbo Shim, Byung-Seok Kim, Chang-Yuil Kang, Jae-Ouk Kim, Shinya Tanaka, Masato Kubo, Hui-Ying Tung, Cameron T. Landers, David B. Corry, Farrah Kheradmand, Yeonseok Chung
Journal: Journal of Allergy and Clinical Immunology (2017)
Abstract 13179: Bare Metal vs Drug Eluting Stent Choice: The Impact of Atrial Fibrillation and Setting of Care Among Medicare Beneficiaries
Authors: Gregory A Dadekian, Jeremy Smith, Nancy E Morden, Aaron V Kaplan
Journal: Circulation (2015)

Background: In treating coronary artery disease, many factors influence the choice of bare metal (BMS) or drug eluting stents (DES), including bleeding risk and suitability for prolonged dual anti-platelet therapy (DAPT). Atrial fibrillation (AF) further complicates this choice. We examined stent selection among Medicare beneficiaries by AF status to explore how cardiologists are managing this complex choice overall and how this choice varies across academic medical centers (AMC). Methods: Using a 100% Medicare denominator file and associated inpatient claims (2008-2012), we identified patients over age 65 receiving inpatient coronary artery stents. We measured BMS and DES use in AF and non-AF patients overall and assessed variation in stent choice across 50 high volume AMCs. Results: Overall, 1,269,239 stent procedures were studied. BMS, as a percent of total inpatient stents, declined from 2008 to 2012 in AF (41% to 34%) and non-AF (30% to 21%) patients. Across high volume AMCs in 2012, the proportion of stent patients receiving BMS (5th to 95th percentile) ranged from 15% to 63% in AF patients and from 8% to 37% in non-AF patients. In 2012, the AMC-level difference in BMS stent use by AF status (proportion of BMS among AF patients minus proportion BMS in non-AF patients) ranged from 4% to 35% (5th to 95th percentile). Conclusions: Among stent recipients, AF patients are more likely to receive BMS than non-AF patients but treatment varies widely across AMCs, suggesting a lack of consensus. Studies of stent choice and outcomes among AF patients are needed to guide care decisions and optimize outcomes.
Clinical impact of atypical phenotypes in adult t cell lymphoma/leukemia among HTLV carriers
Authors: D. Enriquez Vera, G. De la Cruz Ku, J. Haro Varas, P. Rioja, Z. Morante Cruz, N.I. Valdiviezo Lama, R. Luque, E. Eyzaguirre, M. Lujan, A. Saavedra, M. Mayuri Monsefu, G. Ferreyros, M. Retamozo Alvarado, J. Vidal Ayllón, S. Neciosup Delgado, L.A. Mas Lopez
Journal: Annals of Oncology (2017)
Alternative Polyadenylation: Methods, Findings, and Impacts
Authors: Wei Chen, Qi Jia, Yifan Song, Haihui Fu, Gang Wei, Ting Ni
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Alternative polyadenylation (APA), a phenomenon that RNA molecules with different 3′ ends originate from distinct polyadenylation sites of a single gene, is emerging as a mechanism widely used to regulate gene expression. In the present review, we first summarized various methods prevalently adopted in APA study, mainly focused on the next-generation sequencing (NGS)-based techniques specially designed for APA identification, the related bioinformatics methods, and the strategies for APA study in single cells. Then we summarized the main findings and advances so far based on these methods, including the preferences of alternative polyA (pA) site, the biological processes involved, and the corresponding consequences. We especially categorized the APA changes discovered so far and discussed their potential functions under given conditions, along with the possible underlying molecular mechanisms. With more in-depth studies on extensive samples, more signatures and functions of APA will be revealed, and its diverse roles will gradually heave in sight.
Abstract #1247: In vitro and in vivo efficacy of Lpathomab\#8482;, a monoclonal antibody directed against lysophosphatidic acid (LPA), in ovarian cancer models.
Authors: Barbara Visentin, Angela Gentile, Rosalia Matteo, Victoria Tripple, Katherine Nguyen, Kelli Moreno, Masao Hiraiwa, Roger Sabbadini
Journal: Cancer Research (2009)

Ovarian cancer is associated with a poor overall survival due to the advanced stage of the disease at the time of diagnosis and the high incidence of acquired resistance to standard treatments. Identification of the major determinants of ovarian cancer progression and the development of more efficacious treatments still remain challenging. Lysophosphatidic acid (LPA) has been associated with multiple aspects of ovarian cancer biology (Lee et al, 2006; Fang et al., 2002) such as VEGF over-expression, activation of metalloproteinases, and production of both pro-angiogenic and pro-metastatic cytokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). LPA not only modulates tumor cell responses but also influences cellular and molecular cross-talk among cancer cells, stroma, vascular and extracellular matrix components in the tumor microenvironment. LPA has also been found elevated in sera and ascites fluid of patients with early and late stage disease (Sutphen et al, 2004). Based on this evidence, LPA and its signaling network represent attractive molecular and cellular targets for rational drug discovery in the treatment of ovarian cancer. LpathomabTMis a high-affinity monoclonal antibody directed against LPA and acts as a molecular sponge to absorb extracellular LPA, neutralizing the biological activities of the lipid produced by tumor cells or other components of tumor microenvironment. We report here experimental data supporting Lpathomab efficacy tested in a panel of relevant in vitro assays using the ovarian cell line SKOV3. Lpathomab significantly reduced IL-8 and IL-6 cytokine release in SKOV3 conditioned media, and blocked tumor cell migration triggered by LPA. More importantly, Lpathomab retarded the progression of SKOV3 tumor cells when injected into the peritoneal cavity of nude mice. Furthermore, Lpathomab reduced levels of relevant pro-angiogenic and pro-metastatic cytokines in sera and ascites fluid of these animals. In addition, we demonstrated that Lpathomab reduces neovascularization in two classical angiogenic models (Matrigel plug and CNV models) and shows preliminary anti-metastatic activity when tested in the B16-F10 metastasis model. In view of these promising preclinical results, we hypothesize that the anti-LPA antibody-based neutralization of LPA may offer the potential to augment the efficacy of current ovarian cancer therapy by blocking the growth-promoting, angiogenic and metastatic effects of LPA generated either by ovarian cancer cells or the tumor microenvironment.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1247.
A <i>katG</i> 315 mutation alone should not lead to exclusion of isoniazid in treatment of multidrug-resistant tuberculosis
Authors: Einar Heldal
Journal: European Respiratory Journal (2017)

We thank D. Chesov and co-workers for sharing data on isoniazid-resistant strains in Moldova as a comment on our paper on shorter regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) [1]. In strains from MDR-TB patients, a high proportion (88%) had a mutation in the katG gene at position 315, results which " …strongly suggest that high-dose isoniazid should not be part of a standardised treatment regimen for patients with MDR-TB… ", based on the " …general consensus that high-level isoniazid resistance due to a mutation in the katG gene at position 315 cannot be overcome by high-dose isoniazid treatment… ". They refer to a recent TBNET/RESIST-TB consensus statement [2] which says that molecular testing for isoniazid resistance should be done since " …it offers the possibility to add INH to a second-line drug regimen in the absence of a katG 315 mutation… ". A katG 315 mutation alone should not lead to exclusion of isoniazid in treatment of multidrug-resistant tuberculosis <http://ow.ly/18cd30fiJfs>
GW28-e1206 C-Reactive Protein Causes ERK1/2 Activation and Aggravates Myocardial Ischemia Reperfusion Injury in Primary Culture of Cardiomyocytes
Authors: Weina Pei, Fan Liu, Haijuan Hu, Bing Xiao, Wei Cui
Journal: Journal of the American College of Cardiology (2017)
First-line treatment patterns by age for patients (pts) with HER2+ metastatic breast cancer (MBC) in the SystHERs registry
Authors: M. Jahanzeb, D. Tripathy, S.A. Hurvitz, J. O'Shaughnessy, G. Mason, D.A. Yardley, A. Brufsky, H.S. Rugo, M. Cobleigh, S.M. Swain, L. Chu, V. Antao, B. Yoo, P.A. Kaufman
Journal: Annals of Oncology (2017)
CWP232291, a Wnt/β-catenin inhibitor, to suppress the growth and development of gastrointestinal cancers.
Authors: Jun Won Park, Hyejin Um, Hanna Yang, Joo Young Cha, Kyoung-June Lee, Hark K. Kim
Journal: Journal of Clinical Oncology (2017)

e15534 Background: CWP232291 (JW Pharmaceutical Corp, Seoul, Korea) is a potent β-catenin inhibitor currently tested in phase I trials for AML and MM. We evaluated the preclinical efficacy of CWP232291 for gastrointestinal cancers using xenograft and genetically-engineered mouse (GEM) models. Methods: For xenograft experiments, we intraperitoneally administered 150 mg/kg of CWP232291 twice a week to 14 heterotopic and 2 orthotopic xenografts of human gastric cancer cell lines formed in NOD/SCID mice. For GEM experiments, we intraperitoneally administered 100 mg/kg of CWP232291 (n = 19) or vehicle (n = 27) twice a week for 17 weeks to 3-week-old Villin-Cre;Smad4 F/F ;Trp53 F/F GEM mice that spontaneously form intestinal tumors with the β-catenin signaling activation. Results: CWP232291 exhibited in vivo activity in human gastric cancer xenografts. Activity of CWP232291 was more prominent in human gastric cancer cell lines harboring mutations in the β-catenin signaling pathway, such as APC, and in the 5-FU-resistant derivative of SNU-620, than in the other xenografts (P = 0.028, t-test). In the MKN-45 orthotopic xenograft, we noted a decrease in luciferase signal intensity after 4 weeks of CWP232291 treatment. CWP232291 demonstrated synergistic activity with paclitaxel and irinotecan in the SNU-484 heterotopic xenograft. In GEM experiments, CWP232291 treatment significantly suppressed the spontaneous development of intestinal tumors (56.3% vs. 91.3% with vehicle) in Villin-Cre;Smad4 F/F ;Trp53 F/F mice. Furthermore, CWP232291 treatment significantly reduced the number of mice that develop intestinal adenocarcinomas (37.5% vs. 78.3% with vehicle). Immunohistochemistry revealed CD8 T cell activation within the mouse intestinal tumors. Conclusions: CWP232291 demonstrated significant preclinical efficacy in gastrointestinal tumors, especially in cancers with the β-catenin signaling activation.
Evaluation épidémiologique et virologique de l’activité grippale en Europe, hiver 2004-2005
Authors: A Meijer, W J Paget, T J Meerhoff, C S Brown, L. E. Meuwissen, J Van Der Velden
Journal: Eurosurveillance (2006)

La saison grippale 2004-2005 a debute vers la fin decembre 2004 et s’est d’abord manifestee au Sud et a l’Ouest de l’Europe (Espagne, Royaume-Uni et Irlande). L’activite grippale s’est ensuite progressivement deplacee vers l’est a travers l’Europe en janvier et au debut de fevrier 2005, puis essentiellement du sud vers le nord entre fin fevrier et fin mars. Dans dix pays sur 23, l’activite grippale a ete plus intense que lors de la saison 2003-2004, et d’intensite egale ou inferieure dans les 13 autres. Les taux de consultations les plus eleves etaient generalement observes chez les enfants de 0 a 14 ans. Les pics de consultations pour des syndromes grippaux ou des infections respiratoires aigues n’ont pas connu de hausse particuliere, compares aux donnees historiques. La souche virale A (83% des detections totales), avec un sous-type H3 (85% des virus A sous-types H) etait la souche predominante, suivie par la souche B (17% des detections) ou A(H1) (15% des virus A sous-types H). La grande majorite des virus A(H3) etaient analogues aux souches de reference A/Wellington/1/2004 (H3N2) et de ce fait aux souches A/California/7/2004 (H3N2) variants tres proches de la souche A/Fujian/411/2002 (H3N2) du vaccin prototype. Les virus B et A ont co-circule pendant toute la saison grippale dans 11 des 24 pays. 
Sept d’entre eux sont situes dans le nord-est de l’Europe, et la proportion de virus B y etait plus elevee (31 a 60%) que dans le reste de l’Europe (6 a 26%). Dans 13 pays sur 24, les virus B ont circule relativement tard dans la saison. Environ 43% de tous les virus B dont l’antigene est caracterise etaient des B/Hong Kong/330/2001-like (lignee des B/Victoria/2/87), une souche differente de la souche vaccinale anti-influenza B, a savoir un virus de type B/Yamagata/16/88. Sur la base des virus detectes dans le monde jusqu’a fevrier 2005, l’Organisation Mondiale de la Sante a modifie la composition du vaccin anti-grippal 2005-2006, en ajoutant au vaccin de la saison 2004-2005 un nouveau composant : une souche analogue au virus A/California/7/2004 (H3N2).
Abstract 1362: The Rho Guanine Exchange Factor ECT2 is Upregulated in a Stretch-Dependent Manner in Arteries of Hypertensive Rats and Contributes to Cell Proliferation
Authors: David Ferland-McCollough, Crystelle Cario-Toumaniantz, Gilles Toumaniantz, Stephanie Lehoux, Pierre Pacaud, Gervaise Loirand
Journal: Circulation (2008)
GW28-e0634 Effect of Walkway Length and Shape on Six-Minute Walk Distance among 20-30 Years Old Healthy Adults: An Observational Study
Authors: Yu Gao, Yafei Wang, Qi Liang, Beibei Feng, Haixia Xie, Yuling Wang, Junsheng Peng
Journal: Journal of the American College of Cardiology (2017)
Vigilancia de las infecciones por neumococos en Europa
Authors: R G Pebody, W Hellenbrand, F D'Ancona, P Ruutu
Journal: Eurosurveillance (2006)

Las infecciones por neumococos son responsables de las infecciones invasivas por neumococos – principalmente meningitis y septicemia – y son un problema de salud publica importante en Europa. Tras la comercializacion de una vacuna conjugada eficaz (PCV) en Europa, varios paises europeos, incluyendo Francia, Alemania, los Paises Bajos, Noruega, Espana y Reino-Unido, implementaron, o estan a punto de hacerlo, un programa de vacunacion universal infantil contra las infecciones por neumococos. Bajo el programa Pnc-EURO sobre infecciones por neumococos financiado por la Union Europea, se envio un cuestionario a finales de 2003 a los 25 Estados miembros actuales de la Union Europea, mas Noruega y Suiza, para conocer mejor la vigilancia nacional de las infecciones invasivas por neumococos (IIN) en Europa. En 2006, se contacto de nuevo con todos los respondientes para actualizar sus datos. 
De los 27 paises, 22 respondieron al cuestionario, de los cuales cuatro no incluyeron las IIN en las enfermedades de declaracion obligatoria. Diez y ocho paises declararon 27 sistemas nacionales de vigilancia. Las definiciones de caso variaban segun los sistemas. Catorce paises de los 18 envian las cepas de IIN a un solo laboratorio de referencia para el serotipado y 12 paises las envian a un solo laboratorio para los analisis de sensibilidad. Se recogen generalmente los datos sobre edad y sexo, pero solamente 11 sistemas de los 27 recogen informacion sobre el estatus vacunal por la vacuna polisacarida y cinco sobre el estatus vacunal por la vacuna conjugada. La incidencia de los IIN en los 18 paises varia entre 0,4 y 20/100.000 en la poblacion general, con un total de 23.470 casos declarados en un periodo de 12 meses. 
La vigilancia de las IIN en Europa es muy heterogenea. Varios paises no tienen ningun sistema de vigilancia. Si la vigilancia de las IIN en Europa se reforzara, los paises podrian tomar decisiones documentadas sobre la introduccion de nuevas vacunas contra las infecciones por neumococos y tambien controlar y comparar el impacto y la eficacia de nuevos programas
Nucleos(t)ide analogue interruption: Alternative approach to intrahepatic set point for spontaneous control of HBV replication?
Authors: Yiqi Yu, Jing Wang, Guojun Li, Chuan Shen, Shaolong Chen, Jun Huang, Xinyu Wang, Caiyan Zhao, Yuxian Huang, Bin Wang, Xuanyi Wang, Jiming Zhang, Chao Qiu, Wenhong Zhang
Journal: Journal of Hepatology (2017)
Current procedural terminology (CPT)
Journal: JAMA (1970)

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Real-world use of docetaxel for metastatic castration-resistant prostate cancer in China: Results from a large observational study
Authors: D. He, Z. Sun, J. Guo, Z. Zhang, Y. Shan, L. Ma, H. Li, J. Jin, Y. Huang, J. Xiao, Q. Wei, D. Ye
Journal: Annals of Oncology (2017)