tbuckley/cabot-search huggingface dataset:
Mitochondrial Oxidative Stress Reduces the Immunopotency of Mesenchymal Stromal Cells in Adults With Coronary Artery Disease
Authors: Ozge Kizilay Mancini, Maximilien Lora, Alexanne Cuillerier, Dominique Shum-Tim, Reggie Hamdy, Yan Burelle, Marc J. Servant, Ursula Stochaj, Inés Colmegna
Journal: Circulation Research (2017)

Rationale: Mesenchymal stromal cells (MSCs) are promising therapeutic strategies for coronary artery disease; however, donor-related variability in cell quality is a main cause of discrepancies in preclinical studies. In vitro, MSCs from individuals with coronary artery disease have reduced ability to suppress activated T-cells. The mechanisms underlying the altered immunomodulatory capacity of MSCs in the context of atherosclerosis remain elusive. Objective: The aim of this study was to assess the role of mitochondrial dysfunction in the impaired immunomodulatory properties of MSCs from patients with atherosclerosis. Methods and Results: Adipose tissue–derived MSCs were isolated from atherosclerotic (n=38) and nonatherosclerotic (n=42) donors. MSCs:CD4 + T-cell suppression was assessed in allogeneic coculture systems. Compared with nonatherosclerotic-MSCs, atherosclerotic-MSCs displayed higher levels of both intracellular ( P =0.006) and mitochondrial ( P =0.03) reactive oxygen species reflecting altered mitochondrial function. The increased mitochondrial reactive oxygen species levels of atherosclerotic-MSCs promoted a phenotypic switch characterized by enhanced glycolysis and an altered cytokine secretion (interleukin-6 P &lt;0.0001, interleukin-8/C-X-C motif chemokine ligand 8 P =0.04, and monocyte chemoattractant protein-1/chemokine ligand 2 P =0.01). Furthermore, treatment of atherosclerotic-MSCs with the reactive oxygen species scavenger N-acetyl- l -cysteine reduced the levels of interleukin-6, interleukin-8/C-X-C motif chemokine ligand 8, and monocyte chemoattractant protein-1/chemokine ligand 2 in the MSC secretome and improved MSCs immunosuppressive capacity ( P =0.03). Conclusions: An impaired mitochondrial function of atherosclerotic-MSCs underlies their altered secretome and reduced immunopotency. Interventions aimed at restoring the mitochondrial function of atherosclerotic-MSCs improve their in vitro immunosuppressive ability and may translate into enhanced therapeutic efficiency.
Metronomic chemotherapy (mCHT) in HER2-ve advanced breast cancer (ABC) patients (pts): old drugs, new results. The multicenter VICTOR-6 study
Authors: M. Cazzaniga, L. Orlando, E. Melegari, V. Arcangeli, A. Butera, G. Pinotti, I. Vallini, C. Mocerino, F. Giovanardi, E. Cretella, A. Gambaro, M. Pistelli, S. Donati, L. Pizzuti, A. Spagnuolo, C. Putzu, V. Leonardi, C. De Angelis, S. Pedroli, V. Torri
Journal: Annals of Oncology (2017)
OA 08.03 Effect of TOP2A and ERCC1 Genes Polymorphism on the Efficacy and Toxicity of Cisplatin and Etoposide Therapy in SCLC Patients
Authors: M. Nicoś, P. Krawczyk, A. Rolska-Kopińska, A. Grenda, A. Bożyk, M. Szczyrek, J. Milanowski
Journal: Journal of Thoracic Oncology (2017)
Planes contra la pandemia de gripe en Europa
Authors: J F Aguilera, W J Paget
Journal: Eurosurveillance (2001)

La Organizacion Mundial de la Salud recomienda energicamente a todos los paises que preparen con antelacion planes multidisciplinares de prevencion y control contra la proxima pandemia de gripe. Hemos realizado una encuesta sobre los metodos de vigilancia de la gripe entre los miembros de la red europea de vigilancia de la gripe (European Influenza Surveillance Scheme; EISS), icluyendo una serie de preguntas sobre la planificacion de la lucha contra la pandemia. Todos los paises salvo uno disponen de planes anti-pandemicos o estan desarrollando uno. La coordinacion de los distintos planes nacionales en el ambito europeo probablemente contribuya a mejorar su impacto y eficacia.
Scientific Trials—In the Laboratories, Not the Courts
Authors: Nicolas Bagley, Aaron E. Carroll, Pieter A. Cohen
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
P3.03-015 ROS-1 Rearranged Non-Small Cell Lung Cancer and Crizotinib: An Indian Experience
Authors: V. Talreja, V. Patil, A. Joshi, V. Noronha, C. Mv, R. Kaushal, A. Mahajan, A. Janu, K. Prabhash
Journal: Journal of Thoracic Oncology (2017)
Integrating programmed cell death ligand 1 (PD-L1) and neutrophil to lymphocyte ratio (NLR) as predictive panel of response to nivolumab in non-small cell lung cancer (NSCLC)
Authors: C. Bennati, V. Mazza, M. D'Arcangelo, G. Minuti, S. Vecchiarelli, L. Attilia, A. Gili, M. Montanari, L. Landi, F. Cappuzzo
Journal: Annals of Oncology (2017)
Abstract 13577: Increased Iron Accumulation in Human Abdominal Aortic Aneurysm
Authors: Hisashi Sawada, Yoshiro Naito, Hiroyuki Hao, Makiko Oboshi, Toshihiro Iwasaku, Yoshitaka Okuhara, Daisuke Morisawa, Akiyo Eguchi, Shinichi Hirotani, Seiichi Hirota, Yuji Miyamaoto, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Circulation (2013)

Background:  Iron is an essential element in the body, while excess iron leads to tissue damages causing by oxidative stress and inflammation. Although inflammation and oxidative stress play critical roles in the pathophysiological mechanism of abdominal aortic aneurysm (AAA), it has not been investigated whether iron play a role in the pathophysiological mechanism of AAA. The aim of this study is to examine iron accumulation in human AAA tissue.   Methods:  Aortic tissue samples were collected from 53 patients undergoing cardiovascular surgery (AAA: n=19, Control: n=34). Non aneurysmal control aortic tissue were obtained from patients undergoing aortic valve replacement for aortic valve stenosis or aortic valve regurgitation and extracted from ascending aortas at the time of establishment of cardiopulmonary bypass. Aortic iron content was assessed by atomic absorption spectrometry and berlin blue staining. In addition, immunohistochemical analyses for CD68 and 8-Hydroxydeoxyguanosine (8-OHdG) were performed to evaluate inflammation and oxidative stress in aortic tissue.   Results:  The percentage of male patients was higher in AAA than Control (84 vs 38%, p p  p    Conclusion:  Iron was markedly accumulated in human AAA tissue and localized with CD68 and 8-OHdG positive area. These results indicate that iron may be involved in the pathophysiology of AAA.
CMET-01. EFFICACY AND OUTCOME OF ANTI-PD1 THERAPY IN PATIENTS WITH LUNG CANCER BRAIN METASTASIS
Authors: Bicky Thapa, Bhavan Shah, Adam Lauko, Manmeet Ahluwalia
Journal: Neuro-Oncology (2017)

There is very limited data on the benefit of checkpoint blockade in the lung cancer brain metastasis (LCBM). The only prospective data available is the study consisting of 18 patients with LCBM treated with pembrolizumab. We report our experience of 100 patients having LCBM treated with nivolumab and pembrolizumab. After IRB approval, LCBM patients treated with whole-brain radiation therapy (WBRT), surgery, or stereotactic radio-surgery (SRS) and or Anti-PD1 at a single tertiary care institution from 2014–2017 were reviewed. Kaplan-Meier survival analysis with survival plot was used to assess the overall survival (OS). 100 patients with LCBM treated with anti-PD1 therapy were identified. Forty five percent were males, 13% harbored EGFR mutation and 18% had KRAS mutation. Median KPS was 90 (50–100) and the median age of the patient was 61 years (30–81). The median follow up was 6 months, 55% of the patients died. Fifty patients were treated with nivolumab or pembrolizumab at diagnosis of LCBM. The OS of 8.9 months (CI 6.6, 11.2) was observed in that cohort of patients in contrast with the OS of 14.9 months (CI 12.1, 17.6) was observed in 49 patients who received nivolumab or pembrolizumab after the progression of LCBM following the initial treatment with surgery, WBRT, SRS and/or medical therapy. OS for the entire cohort was 12.288 (CI 10.280, 14.297). Further efficacy analysis including response criteria are ongoing and will be presented at the meeting. Nivolumab or Pemrolizumab are safe and effective in the treatment of LCBM and prospective trials are needed.
TMIC-36. CROSSTALK OF GLIOMA STEM CELLS WITH VASCULAR ENDOTHELIAL CELLS PERSISTS THEIR PRONEURAL PHENOTYPE AND THERAPY RESISTANCE VIA ENDOCAN-CD11A INTERACTION
Authors: Soniya Bastola, Marat Pavlyukov, Yasmin Ghochani, Hai Yu, Suojun Zhang, Shinobu Yamaguchi, Mutsuko Minata, Giovanni Coppola, Kyung-Don Kang, Heba Allah Alsheikh, Riki Kawaguchi, Jun Wang, Svetlana Komarova, Sooryanarayana Varambally, Darshan Shimoga Chandrashekar, Harley Kornblum, Ichiro Nakano
Journal: Neuro-Oncology (2017)

GBM cells tend to invade into adjacent normal brain tissues and cannot be completely resected surgically. These remaining tumor cells are the “seeds” to escape post-surgical therapies, hence contributing to tumor recurrence. The exact mechanisms by which these seeds confer to therapy resistance remains elusive. Several studies have shown the functional contribution of tumor microenvironment to glioma stemness and highlighted the importance of vascular endothelial(VE) cells in tumor initiation and progression. Here, we aim to determine the role of crosstalk of VE cells with glioma stem cells (GSCs) to develop GBM recurrence. We first assessed the effect of VE conditioned media (VE-CM) on patient-derived GBM neurospheres in vitro and in vivo. Culturing GBM neurospheres with VE-CM or their coculturing with VE cells promoted growth and migration of GBM neurospheres. Mice coinjected with VE cells and GBM neurospheres resulted in an increase of tumor growth compared to the injection of GBM neurospheres alone. To understand the mechanism of action, we performed RNA sequencing with CD31+ VE cells and A2B5+ GSCs directly isolated from patients with therapy-refractory epilepsy or GBM to identify factors secreted by these cells. We identified that Endocan is upregulated in VE cells, whereas CD11a – a receptor for Endocan, is upregulated in GSCs. Preferential expression of CD11a in perivascular region of GBM tissues was observed by immunohistochemistry. Irradiating VE cells substantially increased ESM1, by which VE cells provide extrinsic signals for elevated malignancy of GSCs after radiation therapy. Functionally, adding VE-CM or recombinant ESM1 protected GBM neurospheres from undergoing irradiation induced apoptosis and mesenchymal transition. We are currently investigating exact mechanism by which Endocan secretion from VE cells promotes GSC malignancy after radiation. Taking these data together, targeting ESM1 in VE cells or CD11a in GBM cells may provide a novel and effective strategy for preventing GBM recurrence.
Malaria aeroportuale: una malattia rara ancora poco compresa
Authors: J Mouchet
Journal: Eurosurveillance (2000)

L'articolo di Daniel Lusina e colleghi, in questo numero di Eurosurveillance (1), giunge tempestivamente a ricordarci quelli che sono i pericoli della malaria aeroportuale. Dal 1977, quando la malattia e stata documentata per la prima volta, ad oggi, sono stati osservati in Europa occidentale 75 casi di malaria aeroportuale, di cui 28 si sono verificati in Francia. I pazienti si sono infettati in Europa, senza che mai avessero soggiornato in aree endemiche, fatto che solleva il problema di una malattia rara che non viene ricercata in maniera sistematica con gli esami di laboratorio.
PATH-13. SNCA, A NOVEL MARKER FOR GROUP 4 MEDULLOBLASTOMAS
Authors: Yong-Xiao Li, Zhen-Wei Yu, Qing Chang
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The current consensus is that MB is a heterogeneous group of tumors containing at least four clinically, transcriptionally, and genetically distinct molecular subgroups. Among them, Group 4 is the largest subgroup, but its underlying biology is the least understood. The aim of this study is to explore potential therapeutic as well as diagnostic markers within each subgroup of MB, in particular within Group 4, to facilitate diagnosis together with precision gene therapy. For this purpose, total 33 genes were used for evaluation of MB samples with the Nanostring assay. Besides 22 well-characterized group specific genes, ten of eleven tumor related genes were shown to have high subgroup sensitivity and specificity based on classic gene panel assignment. Some of these genes have been identified as therapeutic targets in various tumors, such as PDGFRA, FGFR1, ALK and CCND1 etc. Expression of α-synuclein （SNCA）has high correlation with SNCAIP in MBs and both of them are associated with Group 4. In addition, promoter hypermethylation was involved in regulation of transcriptional expression of the SNCA gene in MB cells, and was correlated with lower expression of α-synuclein on the protein level in primary tumors. Knock down and overexpression assay of SNCA demonstrated the ability of this gene on inhibiting tumor invasion. In conclusion, for the first time, we identify SNCA as a novel sensitive and specific biomarker for Group 4 medulloblastoma, and its expression may be regulated by DNA hypermethylation. Moreover, some subtype-specific signature genes evaluated here also shed light on clinical usage of molecular subtyping as well as gene therapy of MB patients.
Why not consider a sex factor within the ISO 11088 ski binding setting standard?
Authors: Gerhard Ruedl, Martin Burtscher
Journal: British Journal of Sports Medicine (2017)

In recreational alpine skiing, about one-third of all injuries are related to the knee joint.1 However, female recreational skiers have twice the knee injury incidence of male skiers and the ACL injury risk is even three times higher in female skiers.1 A total of 60%–80% of knee injuries after a self-inflicted fall seem to be associated with a failure of binding release and again with decisive sex differences.1 Female skiers reported about 20% more often failure of binding release than men.1 In an epidemiological study including more than 1300 injured recreational skiers, self-reported failure of binding release was significantly higher in women when compared with men (51% vs 32%), irrespective of the injured body part.2 Noteworthy, among uninjured skiers, three times more women were unable to release their ski bindings during a self-release test even though their bindings were currently adjusted according to the official ski standards (International Organization for Standardization (ISO) 11088) for binding setting values.3 

Strong thigh muscles seem to be a prerequisite for the ability to self-release the ski binding especially when set at a high level. …
P3.16-047 Salvage Surgery for Locoregional Recurrence or Persistent Residual Tumor After Definitive Chemoradiation Therapy
Authors: J. Osawa, H. Ito, M. Nito, K. Inafuku, J. Samejima, T. Nagashima, H. Nakayama, K. Yamada, T. Yokose
Journal: Journal of Thoracic Oncology (2017)
Association between lipoprotein (a) and proprotein convertase substilisin/kexin type 9 in patients with heterozygous familial hypercholesterolemia: A case‐control study
Authors: Di Sun, Sha Li, Xi Zhao, Na-Qiong Wu, Cheng-Gang Zhu, Yuan-Lin Guo, Ying Gao, Ping Qing, Chuan-Jue Cui, Geng Liu, Jing Sun, Qian Dong, Jian-Jun Li
Journal: Metabolism (2017)
MA 05.13 Scavenger Receptor MARCO Defines a Targetable Tumor-Associated Macrophage Subset in Lung Cancer
Authors: L. La Fleur, V. Boura, A. Berglund, J. Mattsson, D. Djureinovic, J. Persson, H. Brunnström, J. Isaksson, E. Branden, H. Koyi, P. Micke, M. Karlsson, J. Botling
Journal: Journal of Thoracic Oncology (2017)
EXTH-07. MUTANT ISOCITRATE DEHYDROGENASE 1 (IDH1) INHIBITOR SYC-435 SYNERGISTICALLY PROLONGS ANIMAL SURVIVAL WITH STANDARD THERAPIES IN PATIENT-DERIVED IDH1 MUTANT GLIOMA XENOGRAFT MOUSE MODELS
Authors: Mari Kogiso, Lin Qi, Huiyuan Zhang, Frank Braun, Yuchen Du, Yulun Huang, Holly Lindsay, Sibo Zhao, Sarah Injac, Zhen Liu, Patricia Baxter, Jack Su, Laszlo Perlaky, D Will Parsons, Murali Chintagumpala, Adekunle Adesina, Jialiang Wang, Yongcheng Song, Xiao-Nan Li
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common primary brain tumor with a median survival of 14.5 months, despite maximal therapy consisting of surgical resection, radiation and temozolomide (TMZ).Genetic profiling has shown an average of three driver mutations localized to the p53, Rb and receptor tyrosine kinase networks, to be responsible for selective growth advantage of GBM.However, single cells from the same tumor often have different combinations of these driver mutations.This intra-tumoral heterogeneity is a major cause of treatment failure and disease recurrence.microRNA-34a (miR-34a) modulates the expression of multiple genes in all three deregulated GBM networks and therefore has the potential to counteract intra-tumor heterogeneity, thereby optimizing treatment.Transfection of miR-34a as monotherapy significantly reduced proliferation in multiple established GBM cell lines (A172, LN229, T98G and U251) and three primary patient-derived cell cultures (GBM6, GBM118 and GBM 126).The latter cultures were respectively characterized as classical, mesenchymal and proneural, based on mRNA expression analysis.In our in vitro experiments and the literature, T98G and U251 cell lines are resistant to TMZ, while A172 and LN229 are sensitive.miR-34a sensitized TMZ resistant, TMZ sensitive and primary cell cultures to TMZ.As an in vitro model of TMZ resistance, we cultured cells in TMZ for two weeks and created two stable TMZ resistant lines from A172 and LN229 which could be sensitized to TMZ after miR-34a treatment.Mechanistic studies indicate that miR-34a synergizes with TMZ due, in part, to direct inhibition of Bcl2 protein expression by miR-34a.Efforts also are ongoing to deliver miR-34a to orthotopic tumors using different types of nanoparticles.In conclusion, miR-34a is a promising novel therapeutic that inhibits proliferation and synergizes with TMZ in multiple GBM established cell lines and primary cultures.
Infertility in an adult cohort with primary ciliary dyskinesia: phenotype–gene association
Authors: Gert Jan Vanaken, Laurence Bassinet, Mieke Boon, Rahma Mani, Isabelle Honoré, Jean-Francois Papon, Harry Cuppens, Martine Jaspers, Natalie Lorent, André Coste, Estelle Escudier, Serge Amselem, Bernard Maitre, Marie Legendre, Sophie Christin-Maitre
Journal: European Respiratory Journal (2017)

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder (prevalence 1:10 000 to 1:40 000 births) characterised by impaired mucociliary clearance because of abnormal motile ciliary function [1, 2]. Five main ultrastructural PCD phenotypes have been described. Most result from a lack of dynein arms (DAs): no outer and inner DAs (2DAs), outer DAs alone (ODA) or inner DAs with microtubular disorganisation (IDA/MTD); or defects yielding an abnormal central complex (CC). Some patients with genetically confirmed PCD have apparently normal ciliary structure on electron microscopy (nEM). More than 30 genes encoding proteins involved in the structure or assembly of the axoneme, the ciliary internal cytoskeleton, are implicated in PCD [3]; their analysis enables identification of bi-allelic disease-causing mutations in 50–75% of patients. Approximately half of PCD cases are associated with situs inversus , thereby defining Kartagener's syndrome. Moreover, because motile cilia and sperm flagella share common axonemal structures, most PCD-affected males are thought to be infertile [4]. According to the literature, male infertility is caused by severe or total asthenozoospermia and is currently treated by recourse to in vitro fertilisation or intracytoplasmic sperm injection [5, 6]. However, spontaneous fatherhood of PCD patients has been reported. Infertility, observed in 75% of male and 61% of female PCD patients, is dependent on ultrastructural and gene defects <http://ow.ly/P4K030fPnPp> We thank all the individuals and their families for their cooperation, as well as all the referring physicians. The researchers participate in the network of COST Action BEAT-PCD (Better Evidence to Advance Therapeutic Options for PCD; no. BM 1407). L. Bassinet, I. Honoré, J.-.F Papon, A. Coste, E. Escudier, S. Amselem, B. Maitre, M. Legendre and S. Christin-Maitre are members of the RadiCONetwork (Inserm, France).
Preparación y respuesta frente al bioterrorismo en los institutos de salud europeos
Authors: B Coignard
Journal: Eurosurveillance (2001)

Los ataques terroristas del 11 de septiembre de 2001 y la emision intencionada de esporas de B. anthracis en los Estados Unidos tuvieron repercusiones sanitarias no solo en ese pais, sino tambien en Europa. Los sistemas sanitarios europeos se vieron obligados a gestionar un gran numero de materiales postales posiblemente contaminados con esporas de B. anthracis . Nuestra encuesta, con la participacion de 18 institutos de salud publica europeos de 16 paises, tenia como proposito documentar la respuesta de los institutos a los recientes eventos bioterroristas para identificar las posibles lagunas a corregir. Las amenazas bioterroristas en Europa fueron solo una falsa alarma, y deberian considerarse como un ejercicio de preparacion del que pueden extraerse tres lecciones. En primer lugar, debido a los planes inadecuados de preparacion, planificacion y financiacion, Europa no estaba preparada en octubre de 2001 para hacer frente al bioterrorismo. En segundo lugar, a pesar de que los institutos de salud hayan reaccionado rapidamente, adaptando sus prioridades a un nuevo tipo de amenaza, necesitaran recibir el apoyo adecuado y permanente de los gobiernos de cada pais para mantener su capacidad global. En tercer lugar, la crisis reciente puso de manifiesto la necesidad de una inversion mayor en programas de formacion epidemiologica y en la creacion de una unidad de coordinacion tecnica para la vigilancia y respuesta internacional a los brotes en la Union Europea.