tbuckley/cabot-search huggingface dataset:
Response to: ‘Monocyte type I interferon signature in antiphospholipid syndrome is related to pro-inflammatory monocyte subsets, hydroxychloroquine and statin use’ by van den Hoogen<i>et al</i>
Authors: Srilakshmi Yalavarthi, Robert C Grenn, Jason S Knight
Journal: Annals of the Rheumatic Diseases (2016)

Primary antiphospholipid syndrome (APS) is an autoimmune disorder of unknown cause, characterised by not only thrombotic events and pregnancy morbidity but also accelerated atherosclerosis. We reviewed with great interest the letter by van den Hoogen et al ,1 which comments on our recent paper.2 In our study, we discovered a defect in endothelial progenitor function in patients with primary APS—such defects have been described as predecessors to atherosclerosis. We subsequently revealed a type I interferon (IFN) signature in peripheral blood mononuclear cells of the same patients. Importantly, inhibition of the type I IFN receptor restored normal differentiation of endothelial progenitors into endothelial cells in vitro. Further, we detected the IFN signature not only in our local primary APS cohort but also in a cohort of patients from Mexico.

van den Hoogen et al 1 have now detected a type I IFN signature in a third cohort of patients with primary APS, this one recruited in the Netherlands. Going further, they reanalysed …
Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management
Authors: Frank Bridoux, Vincent Javaugue, Sébastien Bender, Fannie Leroy, Pierre Aucouturier, Céline Debiais-Delpech, Jean-Michel Goujon, Nathalie Quellard, Amélie Bonaud, Marie Clavel, Patrick Trouillas, Florent Di Meo, Jean-Marc Gombert, Jean-Paul Fermand, Arnaud Jaccard, Michel Cogné, Guy Touchard, Christophe Sirac
Journal: Kidney International (2016)
Chemokines in Leukemic Infiltration of the Central Nervous System in Childhood Acute Lymphoblastic Leukemia.
Authors: Manuel Ramirez, Ana M Gomez, Carolina Martinez, Alvaro Lassaletta, Jose L Fuster, Carlos Esquembre, Mercedes Guibelalde, Gomez Pedro, Carlota Calvo, Javier Molina, Jose L Vivanco, Jose Sanchez de Toledo, Encarna Bureo, Luis Madero
Journal: Blood (2009)
Prospective pharmacogenetic analysis in advanced colorectal cancer (CRC) patients receiving first-line cetuximab-UFT-irinotecan therapy: Importance of gene polymorphisms related to antibody-dependent cellular cytotoxicity (ADCC)
Authors: M. Etienne-Grimaldi, J. Bennouna, J. Formento, J. Douillard, M. Francoual, E. François, R. Faroux, C. El Hannani, J. Jacob, G. Milano
Journal: Journal of Clinical Oncology (2009)

4069 Background: Our purpose was to test the predictive value of germinal gene polymorphisms potentially linked to cetuximab, fluoropyrimidine and irinotecan pharmacodynamics on toxicity, clinical response, time to progression (TTP) and overall survival (OS). Methods: 52 patients with advanced CRC were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial (33 men, 19 women, mean age 63, range 36–84, PS 0–1). Treatment consisted in cetuximab (day 1-day 8-day 15, 250 mg/m 2 /week following a 400 mg/m 2 loading dose) associated with irinotecan (day 1, 250 mg/m 2 ) and UFT-folinic acid (day 1 to day 14, 250 mg/m 2 /day UFT, 90 mg/day folinic acid). Median number of administered cycles was 7 (range 1–8). The following gene polymorphisms were analyzed on blood genomic DNA: EGFR (CA repeats in intron 1, - 216G&gt;T, -191C&gt;A), EGF (61A&gt;G), FCGR2A (131Arg&gt;His), FCGR3A (158Phe&gt;Val), UGT1A1 (TA repeats), TYMS (28 bp repeats including the G&gt;C mutation on the 3R allele, 6 bp deletion in 3’ UTR), MTHFR (677C&gt;T, 1298A&gt;C). Results: Grade 3–4 toxicity was recorded in 59.6 % of patients. The toxicity score (sum of maximum grade for each toxicity pattern) was significantly linked to the FCGR2A genotype (median score 9, 9.5 and 13 in Arg/Arg, Arg/His and His/His patients, respectively, p = 0.035) and to the EGFR -191 genotype (median score 11 in CC patients versus 8.5 in CA patients, p = 0.040). Response rate was 49% (3 CR and 21 PR over 49 assessable patients) and was significantly higher in patients bearing the FCGR3A Val allele (62.1 % in Val/Val or Val/Phe versus 26.3 % in Phe/Phe, p = 0.020) or the TYMS 3RG allele (65.0 % versus 28.6 % in patients with no 3RG allele, p = 0.029). Gene polymorphisms did not influence TTP. A multivariate Cox analysis including gene polymorphisms and PS showed that overall survival was improved in patients bearing the FCGR3A Val allele (relative risk of death was 2.25 in Phe/Phe patients relative to Val-containing genotypes, 95% CI 1.03–4.91, p = 0.041). Conclusions: Present data suggest the importance of ADCC in cetuximab pharmacodynamics, as outlined by the role of FCGR gene polymorphisms on toxicity, responsiveness and survival. No significant financial relationships to disclose.
Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells
Authors: Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Journal: Nature Immunology (2016)
Effect of Demethylating Agents (5-Azacytidine/5-AzaC) On the Immune Response
Authors: Silvia Gutiérrez Cosío, Esteban Ballestar, Carlos Santamaría, Belén Blanco, Luis Ignacio Sánchez Abarca, Teresa Caballero Velázquez, Carmen Herrero Sánchez, Soraya Carrancio, Laura Ciudad, Consuelo Cañizo, Jesus F San Miguel, Jose Antonio Pérez Simón
Journal: Blood (2010)
Allergy in severe asthma
Authors: S. R. Del Giacco, A. Bakirtas, E. Bel, A. Custovic, Z. Diamant, E. Hamelmann, E. Heffler, Ö. Kalayci, S. Saglani, S. Sergejeva, S. Seys, A. Simpson, L. Bjermer
Journal: Allergy (2016)

It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4–5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma.
Multi-Trial Safety Evaluation of the Fully Antagonistic Human Anti-CD40 Monoclonal Antibody Lucatumumab (HCD122) in Patients with Relapsed or Refractory B-Cell Malignancies,
Authors: Michelle Fanale, William I Bensinger, John C. Byrd, Brett Ewald, Daniel Carreon, Johan Baeck, Arnold S. Freedman
Journal: Blood (2011)
The potential impact of media reporting in syndromic surveillance: an example using a possible Cryptosporidium exposure in North West England, August to September 2015
Authors: Alex J Elliot, Helen E Hughes, John Astbury, Grainne Nixon, Kate Brierley, Roberto Vivancos, Thomas Inns, Valerie Decraene, Katherine Platt, Iain Lake, Sarah J O’Brien, Gillian E Smith
Journal: Eurosurveillance (2016)

During August 2015, a boil water notice (BWN) was issued across parts of North West England following the detection of Cryptosporidium oocysts in the public water supply. Using prospective syndromic surveillance, we detected statistically significant increases in the presentation of cases of gastroenteritis and diarrhoea to general practitioner services and related calls to the national health telephone advice service in those areas affected by the BWN. In the affected areas, average in-hours general practitioner consultations for gastroenteritis increased by 24.8% (from 13.49 to 16.84) during the BWN period; average diarrhoea consultations increased by 28.5% (from 8.33 to 10.71). Local public health investigations revealed no laboratory reported cases confirmed as being associated with the water supply. These findings suggest that the increases reported by syndromic surveillance of cases of gastroenteritis and diarrhoea likely resulted from changes in healthcare seeking behaviour driven by the intense local and national media coverage of the potential health risks during the event. This study has further highlighted the potential for media-driven bias in syndromic surveillance, and the challenges in disentangling true increases in community infection from those driven by media reporting.
MNGO-21GENOTYPING OF MENINGIOMA BY TARGETED AMPLICON SEQUENCING USING MiSeq
Authors: Sayaka Yuzawa, Hiroshi Nishihara, Hiromi Mouri, Lei Wang, Taichi Kimura, Masumi Tsuda, Mishie Tanino, Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Norihiro Sato, Shinya Tanaka
Journal: Neuro-Oncology (2015)

BACKGROUND: Meningiomas are the most common primary brain tumors, accounting for about 27% of all intracranial tumors.Loss of Neurofibromin 2 (NF2) is found in about half of sporadic meningiomas, and recently, mutations in TRAF7, KLF4, AKT1, and SMO are reported in non-NF2 meningioma.To establish practical genotyping methods, we performed targeted amplicon sequencing with 45 meningioma specimens and evaluated the association with clinicopathological features.METHODS: Frozen samples of 45 meningiomas were fixed with PAXgene Tissue System (QIAGEN) and embedded in paraffin (PFPE).Amplicon sequencing panel targeted NF2, TRAF7, KLF4, AKT1 and SMO were designed by GeneRead Mix-n-Match panel and Custom panel (QIAGEN).Genomic DNA was extracted from PFPE tissues and libraries were prepared using GeneRead DNAseq Targeted Panels V2 (QIAGEN).The libraries were sequenced by the MiSeq (Illumina).The raw read data obtained from amplicon sequencing were processed by GeneRead Panel Variant Calling service for analysis of mutations and copy number alterations (CNA).RESULTS: Thirty three cases (73%) harbored NF2 loss, in which 20 cases (61%) simultaneously carried NF2 mutation.Mutations in TRAF7, KLF4, AKT1, and SMO were observed in 6 (13 %), 4 (9 %), 2 (4 %) and 0 (0%) cases, respectively.Altogether, 40 of 45 case (89 %) carried at least one or more gene alteration including mutations in 5 genes listed above and NF2 loss.Result of genotyping was correlated with histological subtypes as follows.All of nine fibrous meningiomas carried NF2 loss, while all of 4 meningiomas with secretory component carried both TRAF7 and KLF4 mutations.A case of chordoid meningioma harbored only AKT1-E17K mutation.CONCLUSIONS: Here we established the clinical sequence system for meningioma by targeted amplicon sequencing with desktop sequencer in which we demonstrated favorable results for CNAs as well as mutations.Overall survival
GW26-e1464 PHA665752, Hepatocyte Growth Factor/c-Met Inhibitor, Reduces the Ventricular Fibrillation Threshold in Myocardial Infarction Rats Treated with Cardiac Stem Cells Transplantation.
Authors: Shaoxin Zheng, Fei Wang, Huibao Long, Jingying Hou, Tong Wang
Journal: Journal of the American College of Cardiology (2015)
Various Abnormalities at Chromosome 7 Carry Distinct Biologic and Prognostic Implications In Myelodysplastic/Myeloproliferative Syndromes and Related Marrow Failures
Authors: Aaron D Viny, Bartlomiej Przychodzen, Christine L. O'Keefe, Hideki Makishima, Yuka Sugimoto, Sanjay R. Mohan, Marcin W. Wlodarski, Seiji Kojima, Mikkael A. Sekeres, Jaroslaw P Maciejewski
Journal: Blood (2010)
Birth complications are more common within two years of bariatric surgery, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Birth complications are more common within two years of bariatric surgery, study finds Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Abstract B39: Identifying molecular signatures of tumor dormancy as a basis for the rational design of precision nanomedicines
Authors: Galia Tiram, Shiran Ferber, Ronit Satchi-Fainaro
Journal: Cancer Research (2016)

Abstract Tumor progression is dependent on a number of sequential steps, including initial tumor-vascular interactions and recruitment of blood vessels (i.e., the “angiogenic switch”), as well as an established interaction of tumor cells with their surrounding microenvironment and its different immune, endothelial and connective cellular and extra-cellular components. Failure of a microscopic tumor, either primary, recurrent or metastatic, to complete one or more of these early stages may lead to delayed clinical manifestation of the cancer (i.e., tumor dormancy). Micrometastasis, dormant tumors, and residual tumor cells - referred to as minimal residual disease, contribute to the occurrence of relapse, and constitute fundamental clinical manifestations of tumor dormancy that together are responsible for the vast majority of cancer deaths. However, although the tumor dormancy phenomenon has critical implications for early detection and treatment of cancer, it is one of the most neglected areas in cancer research and the associated biological mechanisms are still mostly unknown. We have created several models of patient-derived xenografts mimicking pairs of dormant vs fast-growing, primary vs metastatic and drug-sensitive vs resistant cancers. We investigated the molecular and cellular changes in tumor-host interactions that govern tumor progression. Those led to the discovery of novel targets and provided important tools for cancer theranostics (therapy and diagnostics). Based on the acquired knowledge, we designed a new strategy to improve treatment outcomes of patients with bone neoplasms, glioblastoma, brain metastases, melanoma, breast and prostate cancers. We have identified molecular signatures which following their selective delivery into target cells, can potentially induce a dormant-like phenotype. This goal was achieved by utilizing polymeric nanomedicines and guidance by high resolution, intravital non-invasive imaging techniques. A better understanding of tumor dormancy and the availability of relevant markers will most likely change the way we diagnose and treat the disease using novel combined theranostic nanomedicines. Citation Format: Galia Tiram, Shiran Ferber, Ronit Satchi-Fainaro. Identifying molecular signatures of tumor dormancy as a basis for the rational design of precision nanomedicines. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B39.
GW26-e4570 Assessment of MESP1 in White Blood Cells May be Useful for Brugada Syndrome Diagnosis
Authors: Anyu Zhou, Ning Jiang, Lakir Patel, Marco Denegri, Guangbin Shi, An Xie, Hong Liu, Man Liu, Euy-Myong Jeong, Carlo Napolitano, Silvia G. Priori, Samuel C. Dudley
Journal: Journal of the American College of Cardiology (2015)
GW26-e4379 Left Atrial Pressure Predicts Atrial Fibrillation Recurrence after Catheter Ablation
Authors: Xiaobo Liao, Yanzong Yang, Lianjun Gao, Yunlong Xia, Dong Chang, Xiaomeng Yin, Yingxue Dong, Xiaohong Yu, Xianjie Xiao, Shulong Zhang
Journal: Journal of the American College of Cardiology (2015)
Final Analysis of a Randomized, Phase III, Trial Using Etoposide and G-CSF with or without Rituximab (R) for Peripheral Stem Cell Mobilization (PSC) in B-Cell Non-Hodgkin Lymphoma (B-NHL).
Authors: Brad Pohlman, Lisa Rybicki, Elizabeth Kuczkowski, Stacey Brown, Matt Kalaycio, Ronald Sobecks, Steven Andresen, Brian J. Bolwell
Journal: Blood (2005)
Evaluation of computed tomography in patients with atypical angina or chest pain clinically referred for invasive coronary angiography: randomised controlled trial
Authors: Marc Dewey, Matthias Rief, Peter Martus, Benjamin Kendziora, Sarah Feger, Henryk Dreger, Sascha Priem, Fabian Knebel, Marko Böhm, Peter Schlattmann, Bernd Hamm, Eva Schönenberger, Michael Laule, Elke Zimmermann
Journal: BMJ (2016)

<b>Objective</b> To evaluate whether invasive coronary angiography or computed tomography (CT) should be performed in patients clinically referred for coronary angiography with an intermediate probability of coronary artery disease. <b>Design</b> Prospective randomised single centre trial. <b>Setting</b> University hospital in Germany. <b>Participants</b> 340 patients with suspected coronary artery disease and a clinical indication for coronary angiography on the basis of atypical angina or chest pain. <b>Interventions</b> 168 patients were randomised to CT and 172 to coronary angiography. After randomisation one patient declined CT and 10 patients declined coronary angiography, leaving 167 patients (88 women) and 162 patients (78 women) for analysis. Allocation could not be blinded, but blinded independent investigators assessed outcomes. <b>Main outcome measure</b> The primary outcome measure was major procedural complications within 48 hours of the last procedure related to CT or angiography. <b>Results</b> Cardiac CT reduced the need for coronary angiography from 100% to 14% (95% confidence interval 9% to 20%, P&lt;0.001) and was associated with a significantly greater diagnostic yield from coronary angiography: 75% (53% to 90%) <i>v</i> 15% (10% to 22%), P&lt;0.001. Major procedural complications were uncommon (0.3%) and similar across groups. Minor procedural complications were less common in the CT group than in the coronary angiography group: 3.6% (1% to 8%) <i>v</i> 10.5% (6% to 16%), P=0.014. CT shortened the median length of stay in the angiography group from 52.9 hours (interquartile range 49.5-76.4 hours) to 30.0 hours (3.5-77.3 hours, P&lt;0.001). Overall median exposure to radiation was similar between the CT and angiography groups: 5.0 mSv (interquartile range 4.2-8.7 mSv) <i>v</i> 6.4 mSv (3.4-10.7 mSv), P=0.45. After a median follow-up of 3.3 years, major adverse cardiovascular events had occurred in seven of 167 patients in the CT group (4.2%) and six of 162 (3.7%) in the coronary angiography group (adjusted hazard ratio 0.90, 95% confidence interval 0.30 to 2.69, P=0.86). 79% of patients stated that they would prefer CT for subsequent testing. The study was conducted at a University hospital in Germany and thus the performance of CT may be different in routine clinical practice. The prevalence was lower than expected, resulting in an underpowered study for the predefined primary outcome. <b>Conclusions</b> CT increased the diagnostic yield and was a safe gatekeeper for coronary angiography with no increase in long term events. The length of stay was shortened by 22.9 hours with CT, and patients preferred non-invasive testing. <b>Trial registration</b> ClinicalTrials.gov NCT00844220.
Phase I trial of EC90 (keyhole-limpet hemocyanin fluorescein isothiocyanate conjugate) with GPI-0100 followed by EC 17 (folate- fluorescein isothiocyanate conjugate) in combination with interferon-alpha (ifnα) and interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (MRCC)
Authors: T. Mohammad, R. J. Amato, J. Hernandez-McClain, R. Messman, D. Morgenstern, P. Low, S. Bevers
Journal: Journal of Clinical Oncology (2008)

3081 Background: FolateImmune is a folate-receptor (FR)-targeted immunotherapy that induces an immune response against tumor cells by marking tumor cells with a folate-hapten conjugate targeted to over expressed FR in RCC. It is comprised of a vaccine containing EC90, an adjuvant (GP-0100), and folate-hapten conjugate (Folate-FITC). Patients (pts) receive a series of subcutaneous (SQ) injections of EC90 vaccine to stimulate production of antibodies to fluorescein-hapten. Followed by SQ injections of EC17, forming a molecular bridge between tumor cell and the endogenous circulating anti-fluorescein IgG antibody. This may initiate an Fc-mediated immune response leading to antibody-dependent cellular cytotoxicity in phagocyotosis. Phase I study to optimize the dose and schedule of EC90 vaccine and EC17 folate-targeted therapy was previously reported at ASCO, 2004. IFN-α and IL-2 were administered. The objective of this phase I study was to optimize doses of IFN-α and IL-2 to further boost the immune system. Methods: Eligibility included: any prior therapy, measurable disease and no active CNS involvement, adequate organ/marrow function. Results: 11 pts were enrolled with the following pathologic classification: 9-clear cell, 2- papillary. Grade 1–2 toxicity: rash, puritus, fatigue, and flu-like symptoms. All pts, were evaluable for safety; 10 evaluable for response. No partial responses were seen. Stable disease (SD) for ≥3 months was seen in 5 (50%) patients. Median progression-free survival was 3.2+ months (1.6 - 11.3+), median overall survival was 8.2 +months (0.5–12.4+). Conclusions: Folate immune targeted therapy combined with IFN- α and IL-2 was well tolerated with reversible toxicities. Antitumor activity was seen in 50% (SD) which was encouraging in a group of previously treated MRCC pts. EC90/GPI-0100 1.2/3.0mg Day 1 EC17 3.0mg/kg Days 1–5 C1, W1–4 C1, W2–5 C2, W1–2 C2+, W1–4 C3+, W1 IFN 3.0MIU Days 1, 3, 5 *Cohort 1 C1, W3–5 IL-2 7.0MIU Days 1, 3, 5 C2+, W1–4 C1, W3–5; C2+, W1–4 *Cohort 2 IL-2 12MIU C1, W3–4 IL-2 3.0MIU C1, W5; C2+, W1–4 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Endocyte Endocyte
Induction of Autophagic Cell Death Circumvents Azacitidine-Resistance In Myelodysplastic Syndrome-Derived Cell Lines
Authors: Thomas Cluzeau, Guillaume Robert, Jean-Michel Karsenti, Frederic Luciano, Alexandre Puissant, S. Dominique Raynaud, Lionel Mannone, Jill-Patrice Cassuto, Nicolas Mounier, Patrick Auberger
Journal: Blood (2010)