tbuckley/cabot-search huggingface dataset:
B-MIND: MOR208 plus bendamustine (BEN) versus rituximab (RTX) plus BEN in patients with relapsed or refractory (R-R) diffuse large B-cell lymphoma (DLBCL): An open-label, randomized phase II/III trial.
Authors: Grzegorz S. Nowakowski, David Belada, Lysianne Molina, Katerina Kopeckova, Kamel Laribi, Raquel del Campo Garcia, Bertrand Coiffier, Wojciech Jurczak, Mathias J. Rummel, Georg Hess, Andreas Rosenwald, Mark Winderlich, Roman Korolkiewicz, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2017)

TPS7571 Background: Patients ineligible for stem cell transplantation (SCT) or who relapse after SCT, and those who fail to respond to second-line or salvage chemotherapy, represent an unmet medical need for which new therapeutic strategies are required. MOR208 is a novel Fc-enhanced, humanized, monoclonal antibody directed against CD19. Significant single-agent activity of MOR208 in patients with R-R DLBCL (Jurczak et al., J Clin Oncol 34, 2016 [suppl; abstr 7545]) and enhancement of MOR208-mediated cytotoxicity by BEN in preclinical studies, provide a strong rationale to study MOR208 + BEN in patients with R-R DLBCL. Methods: B-MIND is a randomized (1:1), two-arm, multicenter, open-label, adaptive design, phase II/III study of MOR208 + BEN vs RTX + BEN in adult patients with histologically confirmed DLBCL who have relapsed after or are refractory to 1 to 3 prior lines of therapy and who are not candidates for high-dose chemotherapy and autologous SCT. At least 1 prior therapy line must have included a CD20-targeted therapy. Other key inclusion criteria: age ≥18 years; measurable disease; availability of tumor tissue for central pathology review; ECOG 0–2, and adequate major organ systems function. Key exclusion criteria: primary refractory DLBCL; central nervous system involvement, and known double/triple hit DLBCL genetics. The safety of the combination will be assessed in an initial phase II evaluation. Treatment will comprise 6 cycles of MOR208 (12 mg/kg IV) + BEN (90 mg/m 2 IV) or RTX 375 mg/m 2 IV + BEN. Patients achieving a response after cycle 6 will continue to receive antibody treatment for up to 18 additional cycles. Primary endpoint: progression-free survival (PFS); secondary endpoints include: best overall response, overall survival, safety, quality of life, immunogenicity and pharmacokinetics. Enrollment of 330 patients is anticipated in Europe, US and Asia-Pacific countries. Fourteen patients have been randomized to date. Clinical trial information: NCT02763319.
Real life experience with nivolumab in patients (pts) with advanced non-squamous NSCLC (nSq-NSCLC) exhibiting KRAS mutations: The Italian Expanded Access Program (EAP)
Authors: F. Cappuzzo, P. Bidoli, R. Chiari, A. Chirco, D. Turci, A. Ardizzoni, A. Santoro, C. Natoli, G. Francini, M. Giordano, G. Borra, C. Defferrari, L. Livi, A. Berruti, M. Minelli, E. Ricevuto, A. Illiano, G. Puppo, A. Delmonte, A. Misino
Journal: Annals of Oncology (2017)
Mass immunisation campaign in a Roma settled community created an opportunity to estimate its size and measles vaccination uptake, Poland, 2009
Authors: P Stefanoff, H Orlikova, J Rogalska, E Kazanowska-Zielinska, J Slodzinski
Journal: Eurosurveillance (2010)

During a mass immunisation campaign following an outbreak of measles in a Roma community settled in the town of Pulawy, Poland, we performed an estimation of the size of this Roma population and an assessment of its vaccination uptake. We obtained a list of Roma residing in Pulawy from the local municipality and estimated using a simple capture-recapture formula that Pulawy had 377 Roma residents (43% under 20 years old), which was 27% more than the 295 registered at the municipality. During the vaccination campaign, demographic information was recorded that could be linked to information from the municipality list as well as to prior immunisation status. Among the people whose data were recorded during the vaccination campaign, 14% were not registered at the primary healthcare centres, and were therefore deprived of access to healthcare. Among 102 screened subjects under the age of 20 years, 51% were vaccinated according to schedule. Vaccine uptake for the first dose of measles-containing vaccine was 56% (54/96) and for the second dose 37% (18/49). The present study indicates the need to get a better demographic overview of Roma communities living in Poland and to understand the barriers limiting their access to healthcare and social services. Organisation of catch-up immunisations of this vulnerable population is necessary.
Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling
Authors: Min Zhang, Heloise Mongue-Din, Daniel Martin, Norman Catibog, Ioannis Smyrnias, Xiaohong Zhang, Bin Yu, Minshu Wang, Ralf P Brandes, Katrin Schröder, Ajay M Shah
Journal: Cardiovascular Research (2017)

NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4.Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization.Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density.
A large prospective cohort study of the clinical features of advanced lung cancer harboring HER2 aberrations (HER2-CS STUDY)
Authors: T. Tanaka, H. Yoshioka, A. Bessho, N. Ishikawa, M. Yamasaki, T. Shibayama, K. Aoe, T. Kozuki, N. Fujimoto, K. Genba, Y. Ueda, M. Inoue, T. Murakami, S. Kuyama, H. Kawai, K. Fujitaka, K. Inoue, M. Takata, H. Yanai, K. Kiura
Journal: Annals of Oncology (2017)
Curing Hepatitis C Virus Infection: Best Practices From the U.S. Department of Veterans Affairs
Authors: Pamela S. Belperio, Maggie Chartier, David B. Ross, Poonam Alaigh, David Shulkin
Journal: Annals of Internal Medicine (2017)

The U.S. Department of Veterans Affairs (VA) is the nation's largest care provider for hepatitis C virus (HCV)–infected patients and is uniquely suited to inform national efforts to eliminate HCV. An extensive array of delivery of services, policy guidance, outreach efforts, and funding has broadened the reach and capacity of the VA to deliver direct-acting antiviral (DAA) HCV therapy, supported by an infrastructure to effectively implement change and informed by extensive population health data analysis. The VA has treated more than 92 000 HCV-infected veterans since all-oral DAAs became available in January 2014, with cure rates exceeding 90%; only 51 000 veterans in VA care are known to remain potentially eligible for treatment. Key actions advancing the VA's aggressive treatment of HCV infection that are germane to non-VA settings include expansion of treatment capacity through the use of nonphysician providers, video telehealth, and electronic technologies; expansion of integrated care to address psychiatric and substance use comorbidities; and electronic data tools for patient tracking and outreach. A critical component of effective implementation has been building infrastructure through the creation of regional multidisciplinary HCV Innovation Teams, whose system redesign efforts have produced innovative HCV practice models addressing gaps in care while providing more efficient and effective HCV management for the populations they serve. Financing for HCV treatment and infrastructure resources coupled with reduced drug prices has been paramount to the VA's success in curing HCV infection. The VA is poised to share and extend best practices to other health care organizations and providers delivering HCV care, contributing to a concerted effort to reduce the overall burden of HCV infection.
CA-170, a first in class oral small molecule dual inhibitor of immune checkpoints PD-L1 and VISTA, demonstrates tumor growth inhibition in pre-clinical models and promotes T cell activation in Phase 1 study
Authors: J. Powderly, M.R. Patel, J.J. Lee, J. Brody, F. Meric-Bernstam, E. Hamilton, S. Ponce Aix, J. Garcia-Corbacho, Y-J. Bang, M-J. Ahn, S.Y. Rha, K-P. Kim, M. Gil Martin, H. Wang, A. Lazorchak, T. Wyant, A. Ma, S. Agarwal, D. Tuck, A. Daud
Journal: Annals of Oncology (2017)
Chronic but not intermittent infection with<i>Pseudomonas aeruginosa</i>is associated with global changes of the lung microbiome in cystic fibrosis
Authors: Sébastien Boutin, Simon Y. Graeber, Mirjam Stahl, A. Susanne Dittrich, Marcus A. Mall, Alexander H. Dalpke
Journal: European Respiratory Journal (2017)

Chronic pulmonary infection with Pseudomonas aeruginosa that triggers chronic airway inflammation and structural lung damage remains a key risk factor for morbidity and mortality in patients with cystic fibrosis (CF) [1]. Previously, culture-based diagnostics considered airway infections in CF patients as mono-pathogenic, but recent approaches using culture-independent methods showed that bacterial infection of the CF lung involves a polymicrobial community [2–4]. Chronic infection with typical CF pathogens like P. aeruginosa is associated with a decline in lung function and correlates with a decrease of diversity in the lung microbiota. However, the interactions between pathogens and the microbiota remains poorly understood, and it has been hypothesised that dysbiosis of the microbiota may pre-exist and facilitate growth of pathogens such as P. aeruginosa in the CF lung. The aim of the current study was to evaluate the influence of P. aeruginosa infection on the dysbiosis of the microbiota in the CF lung. Chronic but not intermittent P. aeruginosa infection results in dysbiosis of lung microbiota in cystic fibrosis <http://ow.ly/cDKO30eOnx5> We acknowledge the excellent technical support by Jessica Panitz, Selina Hassel, David Ibbersson and the technical team from Bioquant. We are also grateful to Iris Kühbandner for patient recruitment and sample collection. Author contributions: Conception and design of the study: S. Boutin, S.Y. Graeber, M. Stahl, A.S. Dittrich, M.A. Mall, A.H. Dalpke; acquisition, analysis and interpretation of the data: S. Boutin, S.Y. Graeber, M. Stahl, A.S. Dittrich, M.A. Mall, A.H. Dalpke; drafting the article or revising it critically for important intellectual content: S. Boutin, S.Y. Graeber, M. Stahl, A.S. Dittrich, M.A. Mall, A.H. Dalpke.
PD-L1 expression and prognosis significance in advanced ovarian cancer
Authors: E. Høgdall, C. Høgdall, T.T. Vo, W. Zhou, M. Busch-Sørensen, S.M. Soerensen, D. Chappell, J. Georgsen, E. Mejlgaard, L. Nedergaard, T. Steiniche
Journal: Annals of Oncology (2017)
A randomized phase 2 study of pomalidomide/dexamethasone with or without elotuzumab in patients with relapsed/refractory multiple myeloma.
Authors: Jesus San Miguel, Marc S. Raab, Hartmut Goldschmidt, Sagar Lonial, Paul G. Richardson, Suresh Shelat, Eric W. Bleickardt, Antonio Palumbo
Journal: Journal of Clinical Oncology (2016)

TPS8066 Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulatory monoclonal antibody targeting SLAMF7, is FDA approved in combination with lenalidomide and dexamethasone in patients with MM who have received 1 to 3 prior therapies; approval was based on the results of the Phase 3 ELOQUENT-2 trial.1 Clinical trials have shown minimal added toxicity when elotuzumab is combined with the immunomodulatory drugs lenalidomide and thalidomide.1,2 Preclinical results of the OPM-2 xenograft model in ICR-SCID mice (previously used to show synergy of lenalidomide and elotuzumab) demonstrated that the combination of elotuzumab and pomalidomide synergize to kill tumor cells in vivo. Methods: This Phase 2, open-label, randomized study (NCT02654132) will evaluate the efficacy of elotuzumab in combination with pomalidomide and dexamethasone vs pomalidomide and dexamethasone alone. Patients with relapsed/refractory MM who have received ≥ 2 prior lines of therapy that included ≥ 2 consecutive cycles of lenalidomide and a proteasome inhibitor alone or in combination are eligible for inclusion. Patients are randomized to receive either pomalidomide/dexamethasone or the investigational combination pomalidomide/dexamethasone/elotuzumab in 28-day cycles. The dosing schedule consists of elotuzumab 10 mg/kg IV on Days 1, 8, 15, and 22 of Cycles 1 and 2 and elotuzumab 20 mg/kg IV on Day 1 of Cycles 3 and thereafter; pomalidomide 4 mg PO on Days 1–21 of each cycle; dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle (except on elotuzumab dosing weeks when dosing is 28 mg PO and 8 mg IV; if > 75 years old, dexamethasone dosing is 20 mg or, on elotuzumab dosing weeks, 8 mg PO and 8 mg IV). The primary endpointis progression-free survival; secondary endpointsareobjective response rate and overall survival. Study start is scheduled for February 2016; 114 patients are planned for enrollment. References: 1. Lonial S et al. N Engl J Med 2015;373:621–31. 2. Mateos M et al. Haematologica 2014;99:364–65. Clinical trial information: NCT02654132.
Genetic factors in nickel allergy evaluated in a population based female twin sample
Authors: L.E. Bryld, C. Hindsberger, Kirsten Ohm Kyvik, T. Agner, T. Menné
Journal: British Journal of Dermatology (2004)

Environmental exposures are important for development of allergic contact dermatitis, but genetic factors have been proposed to be of additional importance for contact sensitization. Recently genetic factors were shown to be of significance for hand eczema. In this study, a sample of twins recruited on the basis of hand eczema has been evaluated with respect to influence of genetic factors on development of nickel sensitization. A total of 1076 individual twins were patch tested and underwent clinical examination, and in the final genetic statistical analysis 630 females were available, of which 146 had a positive patch test to nickel. The aggregation of nickel allergy among twin pairs was measured by the casewise concordance and the twin odds ratio. The twin odds ratio were adjusted for effects of risk factors known to be associated with nickel allergy, namely, wet work, atopic dermatitis, and self-reported hand eczema. There was a small tendency for larger odds ratio among monozygotic twins than among dizygotic twins, which was not statistically significant. As a result of the statistical analysis, it is concluded that allergic nickel contact dermatitis is mainly caused by environmental and only to a lesser degree genetic factors. The selection of twins on the basis of hand eczema may theoretically influence the prevalence of nickel allergy and concordance estimates, which should be considered before extrapolating the data to a random population-based twin sample.
Complete kinetic follow‐up of symptoms and complement parameters during a hereditary angioedema attack
Authors: N. Veszeli, K. V. Kőhalmi, E. Kajdácsi, D. Gulyás, G. Temesszentandrási, L. Cervenak, H. Farkas, L. Varga
Journal: Allergy (2017)

Abstract We studied the kinetics of C1‐inhibitor (C1‐ INH ) and other complement parameters in a self‐limited edematous attack ( EA ) in a patient with hereditary angioedema due to C1‐ INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EA s. C1‐ INH concentration and functional activity (C1‐ INH c+f ), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC 5b‐9 levels were measured in blood samples obtained during the 96‐hour observation period. The highest C1‐ INH c+f , C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase, and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1‐ INH did not increase after resolution of the attack suggesting that factors other than C1‐ INH may be important in this process. C4a may be a useful biomarker for the prediction of EA s.
Association of Mitochondrial DNA Copy Number With Cardiovascular Disease
Authors: Foram N. Ashar, Yiyi Zhang, Ryan J. Longchamps, John Lane, Anna Moes, Megan L. Grove, Josyf C. Mychaleckyj, Kent D. Taylor, Josef Coresh, Jerome I. Rotter, Eric Boerwinkle, Nathan Pankratz, Eliseo Guallar, Dan E. Arking
Journal: JAMA Cardiology (2017)

Mitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function.To determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD.Prospective, population-based cohort analysis including 21 870 participants (20 163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11 153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the data was conducted from March 10, 2014, to January 29, 2017.Mitochondrial DNA-CN measured from buffy coat/circulating leukocytes.Incident CVD, which combines coronary heart disease, defined as the first incident myocardial infarction or death owing to coronary heart disease, and stroke, defined as the first nonfatal stroke or death owing to stroke.Of the 21 870 participants, the mean age was 62.4 years (ARIC, 57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants were women. The hazard ratios for incident coronary heart disease, stroke, and CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33), 1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN to the 2013 American College of Cardiology/American Heart Association Pooled Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was associated with improved risk classification (continuous net reclassification index, 0.194; 95% CI, 0.130-0.258; P < .001). Mitochondrial DNA-CN further improved sensitivity and specificity for the 2013 American College of Cardiology/American Heart Association recommendations on initiating statin therapy for primary prevention of ASCVD (net 221 individuals appropriately downclassified and net 15 individuals appropriately upclassified).Mitochondrial DNA-CN was independently associated with incident CVD in 3 large prospective studies and may have potential clinical utility in improving CVD risk classification.
Durable complete response in HER2-positive breast cancer: A multicenter retrospective analysis
Authors: A. Shimomura, N. Niikura, Y. Fukatsu, M. Sawaki, R. Ogiya, H. Yasojima, T. Fujisawa, M. Yamamoto, M. Tsuneizumi, A. Kitani, J. Watanabe, A. Matsui, Y. Takahashi, S. Takashima, T. Shien, K. Tamura, S. Saji, N. Masuda, Y. Tokuda, H. Iwata
Journal: Annals of Oncology (2017)
Phase I expansion cohort of TAS-115, a novel oral MET/VEGFR/FMS inhibitor, for castration-resistant prostate cancer patients (CRPC pts) with bone metastases
Authors: N. Matsubara, Y. Naito, M. Sasaki, N. Yamamoto, S. Takahashi, H. Uemura, T. Doi
Journal: Annals of Oncology (2017)
Nutritional recovery after open and laparoscopic distal gastrectomy for early gastric cancer: A prospective multicenter comparative trial (CCOG1204)
Authors: C. Tanaka, M. Kanda, K. Misawa, S. Ito, Y. Ito, Y. Mochizuki, K. Ishigure, T. Yaguchi, J. Teramoto, H. Nakayama, Y. Kawase, M. Fujiwara, Y. Kodera
Journal: Annals of Oncology (2017)
Phase II study of Ccr-based dose-control of S-1 in the first-line chemotherapy of S-1/oxaliplatin (SOX) + bevacizumab regimen for advanced colorectal cancer
Authors: D. Manaka, R. Nishitai, S. Konishi, T. Ohta, T. Hattori, H. Ann, K. Kawaguchi, Y. Nishikawa, R. Kudo, S. Hamasu
Journal: Annals of Oncology (2017)
NEUTRON ACTIVATION ANALYSIS OF TRACE ELEMENTS IN SKIN.
Authors: MOHAMED M. MOLOKHIA, BENJAMIN PORTNOY
Journal: British Journal of Dermatology (1970)

SUMMARY. Levels of the trace metals copper, manganese and zinc in skin were found to vary in the same individual from one region of the body to another. The lowest concentrations were found in plantar epidermis while the highest levels were found in the epidermis of the foreskin. It is possible that these variations are related to dendritic cell populations in these areas.
PD-L1 expression in primary tumours and paired lymph node metastases in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma: Relationship with MSI status and prognosis
Authors: M. Svensson, D. Borg, C. Hedner, J. Eberhard, B. Nodin, K. Leandersson, K. Jirström
Journal: Annals of Oncology (2017)