tbuckley/cabot-search huggingface dataset:
P138/O10 Investigating gene expression patterns and function of tolerogenic dendritic cells
Authors: L Nwosu, K Smith, C Hilkens, J Isaacs
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Dendritic cells (DCs) are professional antigen-presenting cells and play a major role in immune system responses and function. They express a repertoire of toll-like receptors (TLRs) that recognise pathogens. Tolerogenic dendritic cell (tolDC) therapy is a promising cellular therapy that aims to restore tolerance in autoimmune disease. Exposure to dexamethasone leads to the expression of TLR2; however, expression of this marker is not homogeneous. Some tolDCs have low TLR2 expression while some others have high TLR2 expression. Despite these differences in TLR2 expression, we hypothesised that tolDCs are homogenous in terms of their gene expression and function. <h3>Objectives</h3> The study aimed to investigate the gene expression and function of tolDCs to determine if expression patterns and function seen in low TLR2 expressing tolDCs are similar to those of high TLR2 expressing tolDCs. <h3>Methods</h3> Peripheral blood CD14<sup>+</sup> monocytes, obtained from healthy individuals (n=8) were differentiated for 7 days into tolDCs using IL-4, granulocyte-macrophage colony–stimulating factor (GM-CSF), dexamethasone and Vitamin D3. As a control, mature DCs were differentiated using IL-4, GM-CSF and IFN-γ. TolDCs were stained for TLR2 and fluorescence activated cell sorted (FACS) as the 20% lowest TLR2 expressing tolDCs and the 20% highest TLR2 expressing tolDCs. TolDC phenotype was explored using flow cytometry, gene expression of pro-inflammatory, anti-inflammatory and migratory genes by quantitative PCR and CD40-Ligand re-stimulation and mixed lymphocyte reaction assay to investigate function. <h3>Results</h3> Phenotypic marker expression was different between tolDCs and mature DCs, with tolDCs expressing low levels of CD83 and CD86 and high levels of HLA-DR, latency-associated peptide (LAP) and TLR2. In general, TLR2Low and TLR2High tolDCs showed similar phenotypic properties, gene expression patterns and tolerogenic functions. TLR2High tolDCs had increased LAP and HLA-DR expression. TLR2Low tolDCs had higher gene expression for CCR7 and TNF-α. Cytokine (IL-6 and IL-10) production for both TLR2Low and TLR2High tolDCs was not significantly different upon re-stimulation with CD40-ligand and both populations had similar immunosuppressive capacity for CD4+ T cells compared to mature DCs. <h3>Conclusions</h3> Both populations of tolDCs displayed similar gene expression profiles and phenotypic properties for the majority of characteristics investigated. The minor differences observed may be attributable to stochastic differences in dendritic cell exposure to, or uptake of dexamethasone. Despite these differences, all tolDCs function similarly, which is the most important factor when considering tolDCs as a therapy. <h3>Disclosure of Interest</h3> None declared.
Novel Antibodies Against Glycoprotein Ibα Inhibit Pulmonary Metastasis By Affecting Vwf-Gpibα Interaction
Authors: Qi Yingxue, Wenchun Chen, Ke Xu, Fengying Wu, Xuemei Fan, Shengxiang Ren, Junling Liu, Wei Deng, Jun Zhang, Renhao Li, Jianwen Liu, Xin Liang
Journal: Blood (2018)
Response to Letters Regarding Article, “Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi–Seropositive Former Blood Donors” [Carta]
Authors: Ester C. Sabino, Antonio L. Ribeiro, Vera M. C. Salemi, Barbara M. Ianni, Luciano Nastari, Fabio Fernandes, Claudia Di Lorenzo Oliveira, Andre P. Antunes, Marcia M. Menezes, Giuseppina M. Patavino, Ligia Capuani, Cesar de Almeida-Neto, Vandana Sachdev, Danielle M. Carrick, David Wright, Katherine Kavounis, Thelma T. Gonzalez, Brian Custer, Michael P. Busch, Edward L. Murphy, Anna-Barbara Carneiro-Proietti
Journal: Circulation (2013)
Magnetic beads-assisted endoscopic submucosal dissection of duodenal heterotopic gastric mucosa with fibrosis
Authors: Lin Jie Guo, Liansong Ye, Zhi Ying Huang, Xiaoxue Yin, Bing Hu
Journal: Endoscopy (2019)

A 53-year-old man was referred to our hospital for full evaluation of the nature of a lesion in the descending duodenum. Upper endoscopy showed a wide-based laterally spreading tumor-like mass (about 15 × 20 mm) with a depression at the top of the lesion ([Fig. 1]). Endoscopic ultrasound (EUS) revealed a medium-echo lesion in the mucosal layer ([Fig. 2]). The biopsy result was inconclusive. Diagnostic endoscopic submucosal dissection (ESD) was attempted. However, despite repeated injections, lifting of the lesion was not satisfactory and the submucosal layer could not be exposed clearly, because of fibrosis ([Fig. 3 a]). Magnetic beads were used to apply traction by gravity. An endoclip was used to attach the thread of a magnetic bead to the edge of the mucosa. When two magnetic beads had been attached, the cutting line was clearly exposed and the lesion was smoothly dissected en bloc ([Fig. 3 b – d], [Video 1]).
Interval From Initiation of Prasugrel to Coronary Angiography in Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Johanne Silvain, Tomasz Rakowski, Benoit Lattuca, Zhenyu Liu, Leonardo Bolognese, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jur ten Berg, Petr Widimsky, Debra Miller, Jean-Jacques Portal, Jean-Philippe Collet, Eric Vicaut, Gilles Montalescot, Dariusz Dudek
Journal: Journal of the American College of Cardiology (2019)
Mitophagy Is Essential for Maintaining Cardiac Function During High Fat Diet-Induced Diabetic Cardiomyopathy
Authors: Mingming Tong, Toshiro Saito, Peiyong Zhai, Shin-ichi Oka, Wataru Mizushima, Michinari Nakamura, Shohei Ikeda, Akihiro Shirakabe, Junichi Sadoshima
Journal: Circulation Research (2019)

Rationale: Diabetic patients develop cardiomyopathy characterized by hypertrophy, diastolic dysfunction, and intracellular lipid accumulation, termed lipotoxicity. Diabetic hearts utilize fatty acids as a major energy source, which produces high levels of oxidative stress, thereby inducing mitochondrial dysfunction. Objective: To elucidate how mitochondrial function is regulated in diabetic cardiomyopathy. Methods and Results: Mice were fed either a normal diet or high-fat diet (HFD, 60 kcal % fat). Although autophagic flux was activated by HFD consumption, peaking at 6 weeks ( P &lt;0.05), it was attenuated thereafter. Mitophagy, evaluated with Mito-Keima, was increased after 3 weeks of HFD feeding (mitophagy area: 8.3% per cell with normal diet and 12.4% with HFD) and continued to increase even after 2 months ( P &lt;0.05). By isolating adult cardiomyocytes from GFP-LC3 mice fed HFD, we confirmed that mitochondria were sequestrated by LC3-positive autophagosomes during mitophagy. In wild-type mice, cardiac hypertrophy, diastolic dysfunction (end diastolic pressure-volume relationship =0.051±0.009 in normal diet and 0.11±0.004 in HFD) and lipid accumulation occurred within 2 months of HFD feeding ( P &lt;0.05). Deletion of atg7 impaired mitophagy, increased lipid accumulation, exacerbated diastolic dysfunction (end diastolic pressure-volume relationship =0.11±0.004 in wild type and 0.152±0.019 in atg7 cKO; P &lt;0.05) and induced systolic dysfunction (end systolic pressure-volume relationship =24.86±2.46 in wild type and 15.93±1.76 in atg7 cKO; P &lt;0.05) during HFD feeding. Deletion of Parkin partially inhibited mitophagy, increased lipid accumulation and exacerbated diastolic dysfunction (end diastolic pressure-volume relationship =0.124±0.005 in wild type and 0.176±0.018 in Parkin KO, P &lt;0.05) in response to HFD feeding. Injection of TB1 (Tat-Beclin1) activated mitophagy, attenuated mitochondrial dysfunction, decreased lipid accumulation, and protected against cardiac diastolic dysfunction (end diastolic pressure-volume relationship =0.110±0.009 in Control peptide and 0.078±0.015 in TB1, P &lt;0.05) during HFD feeding. Conclusions: Mitophagy serves as an essential quality control mechanism for mitochondria in the heart during HFD consumption. Impairment of mitophagy induces mitochondrial dysfunction and lipid accumulation, thereby exacerbating diabetic cardiomyopathy. Conversely, activation of mitophagy protects against HFD-induced diabetic cardiomyopathy.
Multifocal Small Bowel Carcinoid
Authors: Michael Clark, Mark Nathan, Stephen M. Broski
Journal: Clinical Nuclear Medicine (2019)

Carcinoid is a subtype of neuroendocrine tumor, a rare group of tumors that are known to express somatostatin receptor 2. Ga-DOTATATE is a somatostatin analog that is specific for somatostatin receptor 2 and therefore allows visualization of neuroendocrine tumors. We present 2 cases of primary multifocal small bowel carcinoid evaluated using Ga-DOTATATE PET/CT, along with contrast-enhanced CT corollary findings. Given the increased sensitivity of Ga-DOTATATE PET/CT compared with CT and In-octreotide scintigraphy, we expect multifocal carcinoid to become increasingly recognized.
HOUT-32. SIGNIFICANCE OF COMORBIDITY INDEX IN ELDERLY PATIENTS WITH GLIOBLASTOMA
Authors: Masaki Okada, Daisuke Ogawa, Keisuke Miyake, Takashi Tamiya
Journal: Neuro-Oncology (2018)

Comorbidity is a common problem in the treatment of elderly patients, but there is no standard method of the evaluation in glioblastoma patients. Gagne comorbidity index (GCI) has been proposed to be an integrated prognostic index of the Charlson comorbidity index and Elixhauser index, associating with the short-term survival of various diseases. We examined the relationship between GCI and prognosis of elderly patients with glioblastoma. 31 patients over 70 years treated at our hospital from Dec.2006 to Aug.2017. 16 males and 15 females. Mean age 76.8 years (70–86 years old). Relationship to overall survival (OS) was examined focusing on the age, GCI at hospitalization(low:≤1, intermediate:2–4, high:≥5), Karnofsky Performance Status (KPS), surgery, radiotherapy (standard and hypofractionated), and temozolomide-based chemotherapy. RESULT: Median OS of entire cohort was 13.0 months. There was no significant correlation between age and GCI, but a negative correlation between KPS and GCI (r=-0.427). Median OS was longer in the resection group (resection; 13.5m vs non-resection; 8.6m), and in chemo-radiotherapy (standard radiotherapy+TMZ: 13.5m and hypofractionated radiotherapy+TMZ: 10.1m), though, GCI has no relationship to such treatment option. Nevertheless, high GCI indicated poor prognosis with a median OS in the group of low GCI:13.0m, intermediate GCI:14.5m and high GCI:5.3m (p=0.002). DISCUSSION: The presence of comorbidities is one of the factors related to prognosis, and glioblastoma affecting the brain is in a disadvantageous condition due to cognitive dysfunction and paralysis. Since surgical excision and radiation chemotherapy lead to improvement in prognosis even in the elderly, it is important to complete the treatment paying maximum attention to the management of comorbidities. GCI would be useful to evaluate comorbidities. Further examination is needed in large cohort.
Abstract 1318: Establishment of patient primary colorectal tumor xenograft models for test of anticancer agents
Authors: Changnian Liu, Hani Alsanabani, Wen Zhou, Rong Liu, Fang He, Wenwei Li, Chunpin Xu
Journal: Cancer Research (2012)

Abstract BACKGROUND Human xenograft tumor models established by transplantation of human tumor cell lines into immunodifficient mice have been routinely used for preclinical test of anticancer agents. But tumor cell lines have a relatively low transplantability, which resulted a limited number of tumor models available for test of novel anticancer agents. Recently, we have developed a large number of patients’ primary colorectal tumor xenograft models by transplanting human fresh colorectal tumor tissues into nude mice, which have been employed for preclinical test of standard clinically used drugs and novel anticancer agents for their chemosensitivity screening. METHODS The fresh colorectal tumor samples were collected from local hospitals. The tumor fragments of 2-3 mm were subcutaneously implanted in the flanks of nude mice by trocar needle. Sixteen tumor fragments were grafted into four mice from one patient tumor tissue (passage 1). The clinically used drugs included 5-FU, irinotecan, oxaliplatin, and avastin. The histology and gene sequensing of the established primary tumor models were analyzed and compared with patients’ original tumors. RESULTS A total of 120 patients’ colorectal tumor samples were implanted into nude mice; and 65 primary tumor models have been established with a tumor taking rates of 54% for the first passage. The tumor taking rates were higher in the later passages ranged from approximately 80-100%. The test anticancer drugs’ therapeutic efficacy was consistent with their clinical findings. The patients’ primary colorectal tumor xenografts from 5 passages retained a similarity in architecture, histopathological morphology, and genomic mutation status to their patients’ original tumors. CONCLUSIONS The patient primary tumor model system can provide a larger number of models for selection of right models for preclinically testing novel agents based on their anticancer mechanism. The primary tumor models retain a similarity in histology and genomic mutation status to their patients’ original tumors. They may predict more relevant clinical response rate and higher correlation with clinical findings than use of traditional xenograft models established from long-term cultured cancer cell lines. Especially, they have advantages for test of target-oriented therapeutics in new drugs development programs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1318. doi:1538-7445.AM2012-1318
PIM1 inhibition effectively enhances plerixafor-induced HSC mobilization by counteracting CXCR4 upregulation and blocking CXCL12 secretion
Authors: Tony Andreas Müller, Sandra Pennisi, Anabel Zwick, Sarah Decker, Claudius Klein, Benjamin Rister, Alina Rudorf, Sandra Kissel, Marie Follo, Ralph Wäsch, Anna Lena Illert, Dietmar Pfeifer, Robert Oostendorp, Claudia Waskow, Christine Dierks, Justus Duyster
Journal: Leukemia (2019)
Ropeginterferon Alfa-2b Induces High Rates of Clinical, Hematological and Molecular Responses in Polycythemia Vera: Two-Year Results from the First Prospective Randomized Controlled Trial
Authors: Heinz Gisslinger, Christoph Klade, Pencho Georgiev, Dorota Krochmalczyk, Liana Gercheva, Miklos Egyed, Viktor Rossiev, Petr Dulicek, Árpád Illés, Halyna Pylypenko, Lylia Sicheva, Jiri Mayer, Vera Yablokova, Kurt Krejcy, Barbara Grohmann-Izay, Hans Carl Hasselbalch, Robert Kralovics, Jean-Jacques Kiladjian
Journal: Blood (2017)
Measuring Breast Milk Nutrients to Support Optimal Infant Growth
Authors: Rebecca Voelker
Journal: JAMA (2019)

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(14) Lichen myxoedematosus
Authors: R.W. Gange, R.H. Marten
Journal: British Journal of Dermatology (1974)

Journal Article (14) Lichen myxoedematosus Get access R.W. Gange, R.W. Gange Kings College Hospital, London Search for other works by this author on: Oxford Academic Google Scholar R.H. Marten R.H. Marten Kings College Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 59–60, https://doi.org/10.1111/j.1365-2133.1974.tb12517.x Published: 01 July 1974
Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats
Authors: Susanne Bäck, Julie Necarsulmer, Leslie R. Whitaker, Lamarque M. Coke, Pyry Koivula, Emily J. Heathward, Lowella V. Fortuno, Yajun Zhang, C. Grace Yeh, Heather A. Baldwin, Morgan D. Spencer, Carlos A. Mejias-Aponte, James Pickel, Alexander F. Hoffman, Charles E. Spivak, Carl R. Lupica, Suzanne M. Underhill, Susan G. Amara, Andrii Domanskyi, Jenni E. Anttila, Mikko Airavaara, Bruce T. Hope, F. Kent Hamra, Christopher T. Richie, Brandon K. Harvey
Journal: Neuron (2019)
US patients live longer in areas with more primary care doctors, study finds
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

US patients who live in areas with more primary care doctors have a 51.5 day higher life expectancy, a study has found. However, the number of primary care doctors per 100 000 population has decreased over a 10 year period.1

A major issue in healthcare is whether to invest in increasing the number of primary care physicians and whether this leads to better health outcomes and lower mortality. In the US doctors are drawn toward specialties that offer higher incomes than primary care.

A study by Sanjay Basu and colleagues from Stanford University, California, looked for associations between the supply of primary care doctors and mortality throughout the US. Primary care doctors were …
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Authors: Piotr S. Kowalski, Arnab Rudra, Lei Miao, Daniel G. Anderson
Journal: Molecular Therapy (2019)

mRNA has broad potential as a therapeutic. Current clinical efforts are focused on vaccination, protein replacement therapies, and treatment of genetic diseases. The clinical translation of mRNA therapeutics has been made possible through advances in the design of mRNA manufacturing and intracellular delivery methods. However, broad application of mRNA is still limited by the need for improved delivery systems. In this review, we discuss the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in biomaterials and delivery strategies, and we present an overview of the applications of mRNA-based delivery for protein therapy, gene editing, and vaccination.
Abstract PR07: Functional analysis of diverse oncogenic driver mutations using an isogenic cell line library identifies novel drug responses and alterations in metabolism
Authors: Maria M. Martins, Alicia Y. Zhou, Alexandra Corella, Dai Horiuchi, Christina Yau, Taha Rakshandehroo, John D. Gordan, Rebecca S. Levin, Jeff Johnson, John Jascur, Mike Shales, Antonio Sorrentino, Jaime Cheah, Paul A. Clemons, Alykhan Shamji, Stuart Schreiber, Stuart Schreiber, Nevan J. Krogan, Kevan M. Shokat, Kevan M. Shokat, Frank McCormick, Daniel Nomura, Sourav Bandyopadhyay, Andrei Goga
Journal: Cancer Research (2015)

Abstract There is an urgent need in oncology to link molecular aberrations in tumors with altered cellular behaviors, such as metabolic derangements, and to identify novel therapeutics for cancer treatment. We have sought to identify synthetic-lethal genetic interactions that cancer cells acquire in the presence of specific mutations. Using engineered isogenic cells, we generated an unbiased and quantitative chemical-genetic interaction map that measures the influence of 51 aberrant cancer genes on 90 drug responses. The dataset strongly predicts drug responses found in cancer cell line collections, indicating that isogenic cells can model more complex cellular contexts. Applied to triple-negative breast cancer, we report clinically actionable interactions with the MYC oncogene including resistance to PI3K/AKT pathway inhibitors and an unexpected sensitivity to dasatinib through LYN inhibition in a synthetic-lethal manner. These studies provide new drug and biomarker pairs for clinical investigation. We have also performed global metabolomics analysis in a subset of the isogenic cell lines demonstrating alterations in metabolic pathways that are shared across multiple oncogenes, as well as those that are distinct to specific oncogenic drivers. This scalable approach enables the prediction of drug responses from patient data and can be used to accelerate the development of new genotype-directed therapies. This abstract is also presented as a poster at the Translation of the Cancer Genome conference. Citation Format: Maria M. Martins, Alicia Y. Zhou, Alexandra Corella, Dai Horiuchi, Christina Yau, Taha Rakshandehroo, John D. Gordan, Rebecca S. Levin, Jeff Johnson, John Jascur, Mike Shales, Antonio Sorrentino, Jaime Cheah, Paul A. Clemons, Alykhan Shamji, Stuart Schreiber, Stuart Schreiber, Nevan J. Krogan, Kevan M. Shokat, Kevan M. Shokat, Frank McCormick, Daniel Nomura, Sourav Bandyopadhyay, Andrei Goga. Functional analysis of diverse oncogenic driver mutations using an isogenic cell line library identifies novel drug responses and alterations in metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr PR07.
Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches
Authors: Madelene W. Dahlgren, Stephen W. Jones, Kelly M. Cautivo, Alexandra Dubinin, Jorge F. Ortiz-Carpena, Sepideh Farhat, Kevin S. Yu, Katharine Lee, Chaoqun Wang, Anna V. Molofsky, Aaron D. Tward, Matthew F. Krummel, Tien Peng, Ari B. Molofsky
Journal: Immunity (2019)