tbuckley/cabot-search huggingface dataset:
LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription
Authors: Bingqiu Xiu, Yayun Chi, Lei Liu, Weiru Chi, Qi Zhang, Jiajian Chen, Rong Guo, Jing Si, Lun Li, Jingyan Xue, Zhi-Ming Shao, Zhao-Hui Wu, Shenglin Huang, Jiong Wu
Journal: Molecular Cancer (2019)

The majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.lncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.We identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.Our findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.
Quality of Life and Glucose Control After 1 Year of Nationwide Reimbursement of Intermittently Scanned Continuous Glucose Monitoring in Adults Living With Type 1 Diabetes (FUTURE): A Prospective Observational Real-World Cohort Study
Authors: Sara Charleer, Christophe De Block, Liesbeth Van Huffel, Ben Broos, Steffen Fieuws, Frank Nobels, Chantal Mathieu, Pieter Gillard
Journal: Diabetes Care (2019)

OBJECTIVE In 2016, nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) for people living with type 1 diabetes treated in specialist diabetes centers was introduced in Belgium. We undertook a 12-month prospective observational multicenter real-world study to investigate impact of isCGM on quality of life and glycemic control. RESEARCH DESIGN AND METHODS Between July 2016 and July 2018, 1,913 adults with type 1 diabetes were consecutively recruited in three specialist diabetes centers. Demographic, metabolic, and quality of life data were collected at baseline, 6 months, and 12 months of standardized clinical follow-up. The primary end point was evolution of quality of life from baseline to 12 months. Secondary outcome measures were, among others, change in HbA1c, time spent in different glycemic ranges, occurrence of acute diabetes complications, and work absenteeism. RESULTS General and diabetes-specific quality of life was high at baseline and remained stable, whereas treatment satisfaction improved (P &amp;lt; 0.0001). Admissions for severe hypoglycemia and/or ketoacidosis were rare in the year before study (n = 63 out of 1,913; 3.3%), but decreased further to 2.2% (n = 37 out of 1,711; P = 0.031). During the study, fewer people reported severe hypoglycemic events (n = 280 out of 1,913 [14.6%] vs. n = 134 out of 1,711 [7.8%]; P &amp;lt; 0.0001) or hypoglycemic comas (n = 52 out of 1,913 [2.7%] vs. n = 18 out of 1,711 [1.1%]; P = 0.001) while maintaining HbA1c levels. Fewer people were absent from work (n = 111 out of 1,913 [5.8%] vs. n = 49 out of 1,711 [2.9%]; P &amp;lt; 0.0001). Time spent in hypoglycemia significantly decreased in parallel with less time in range and more time in hyperglycemia. Eleven percent (n = 210) of participants experienced skin reactions, leading to stopping of isCGM in 22 participants (1%). CONCLUSIONS Nationwide unrestricted reimbursement of isCGM in people with type 1 diabetes treated in specialist diabetes centers results in higher treatment satisfaction, less severe hypoglycemia, and less work absenteeism, while maintaining quality of life and HbA1c.
Neuroimaging of US Government Personnel Exposed to Directional Phenomena—Reply
Authors: Ragini Verma, Randel L. Swanson, Douglas H. Smith
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Association between body surface area and prescribed doses of guideline‐directed medications among international patients with heart failure and reduced ejection fraction
Authors: Tiew‐Hwa Katherine Teng, Lauren Cooper, Wan Ting Tay, Nancy Luo, Abhinav Sharma, David Whellan, Inder Anand, Ileana L. Pina, Jasper Tromp, A. Mark Richards, William E. Kraus, Christopher M. O' Connor, Robert J. Mentz, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2019)
Haploidentical transplantation might have superior graft-versus-leukemia effect than HLA-matched sibling transplantation for high-risk acute myeloid leukemia in first complete remission: a prospective multicentre cohort study
Authors: Sijian Yu, Fen Huang, Yu Wang, Yajing Xu, Ting Yang, Zhiping Fan, Ren Lin, Na Xu, Li Xuan, Jieyu Ye, Wenjing Yu, Jing Sun, Xiaojun Huang, Qifa Liu
Journal: Leukemia (2019)
Generalisability of results from UK Biobank: comparison against a pooling of 18 prospective cohort studies with conventional response rates
Authors: GD Batty, CR Gale, M Kivimäki, IJ Deary, Steven Bell
Journal: BMJ (2019)

GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01; 1R01AG052519-01A1); MK by the UK Medical Research Council (MR/R024227), US National Institute on Aging (NIH), US (R01AG056477), NordForsk, and Academy of Finland (311492); CRG by the UK Medical Research Council (MRC_MC_UU_12011/2 and MRC_MC_UP_A620_1015); and SB by the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194), and NIHR Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust.  There was no direct financial or material support for the work reported in the manuscript.
John Anthony Lynn
Authors: Paul David Lewis
Journal: BMJ (2019)

The endocrine surgeon John Anthony Lynn was born in Caversham, Berkshire, on 28 July 1941, the son of a pharmacist. He was educated at the Thomas Hardye School in Dorchester and trained as a doctor at King’s College Hospital Medical School, London, graduating in 1964. After mandatory house jobs he worked in general practice for a year, during which he began studying for a surgical career. …
Klf5 is a transcriptional regulator of cardiac Med13 and affects high fat diet-induced obesity
Authors: Konstantinos Drosatos, Nina M. Pollak, Michael John Jurczak, Panagiotis Ntziachristos, Chad M. Trent, Yunying Hu, Iannis Aifantis, Gerald I. Shulman, Ira J. Goldberg
Journal: Circulation (2014)
Review: In patients with cancer, prophylactic anticoagulants reduce VTE and do not increase major bleeding
Authors: Julio Hajdenberg
Journal: Annals of Internal Medicine (2019)

Source Citation Barbarawi M, Zayed Y, Kheiri B, et al. The role of anticoagulation in venous thromboembolism primary prophylaxis in patients with malignancy: a systematic review and meta-analysis o...
Abstract B23: Bioadhesive nanoparticles as a delivery vehicle in pancreatic cancer epithelial cells and pancreatic fibroblasts
Authors: Nesrin M. Hasan, Hee Won Suh, Mark Saltzman, Nita Ahuja
Journal: Cancer Research (2019)

Abstract Pancreatic cancer, referred to as pancreatic ductal adenocarcinoma (PDAC), is characterized by high lethality and limited treatment options. PDAC is generally diagnosed at a later stage and is resistant to chemotherapy and radiation therapy. Therefore, there is an urgent unmet need for novel treatment options to improve the survival of patients. PDAC is characterized by dense solid tumors that hinder drug penetration, and novel treatment technologies should be utilized to improve drug access to cancer cells. Nanoparticle-based compounds have been shown to improve site specific targeting, intracellular penetration, and circulation time and therefore can be used for therapeutic delivery to solid tumors. In our study, we performed in vitro characterization studies of non-bioadhesive nanoparticles (NNPs) and bioadhesive nanoparticles (BNPs) in pancreatic cancer epithelial cells and pancreatic fibroblasts. NNPs are polylactic acid-hyperbranched polyglycerol (PLA-HPG) nanoparticles and BNPs are obtained through conversion of HPG to an aldehyde-rich corona, which increases the bioadhesive property through formation of linkages with proteins. The aim of our study was to characterize the internalization of nanoparticles in vitro in different pancreatic cell lines. We incubated pancreatic cancer epithelial cells (PANC-1 and MIA PaCa-2) and pancreatic fibroblasts with fluorescent DiO-loaded NNPs and BNPs to assess internalization. Both DiO-NNPs and DiO-BNPs were internalized by PANC-1, MIA PaCa-2, and pancreatic fibroblasts as determined by both flow cytometry and fluorescence microscopy. The nanoparticles were internalized in a dose- and treatment time-dependent manner. Although both nanoparticles were internalized, due to their increased bioadhesive properties BNPs had 1.7-fold higher internalization compared to NNPs. Viability of the cells following DiO-NNPs and DiO-BNPs treatment was assessed through both acridine orange staining and flow cytometry analysis. DiO-NNPs and DiO-BNPs treatments did not affect the viability of the cells. Similar results were obtained with DiI-loaded nanoparticles. In summary, our study shows that nanoparticles can be internalized by pancreatic cancer epithelial cells and pancreatic fibroblasts and do not cause any loss of viability. Our results demonstrate the potential applicability of nanoparticles, especially bioadhesive nanoparticles, for synergistic therapeutic targeting of different cell types in pancreatic cancer to improve treatment outcomes. Citation Format: Nesrin M. Hasan, Hee Won Suh, Mark Saltzman, Nita Ahuja. Bioadhesive nanoparticles as a delivery vehicle in pancreatic cancer epithelial cells and pancreatic fibroblasts [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B23.
Abstract C13: A “mouse hospital” for preclinical testing of diagnostic and treatment modalities in pancreatic ductal adenocarcinoma (PDA)
Authors: Cynthia Clendenin, Rina Sor, Deirdre McMenamin, Ben Z. Stanger, Gregory Beatty, Robert H. Vonderheide
Journal: Cancer Research (2019)

Abstract A major challenge for cancer drug development is deciding which compounds to bring forward to clinical trials. Mouse models provide a helpful prescreening tool, but xenograft and subcutaneous models can be poorly predictive of a treatment’s efficacy against a naturally occurring tumor. Preclinical models that more accurately reproduce all the features of a tumor, including its microenvironment, may provide a more accurate readout for response to therapy. Genetically engineered mouse (GEM) models of pancreatic ductal adenocarcinoma (PDA) have been developed that exploit the fact that virtually all PDAs exhibit activating mutations in Kras (exon 12) and that over 75% have mutations in p53. These models use a pancreas-specific Cre recombinase to create mutations in Kras and p53 in the pancreatic epithelium. Tumors in these “KPC” mice recapitulate the salient clinical, histopathologic, and molecular features of the human disease. Importantly, the tumor arises in an immune-competent host. A variant of the KPC model, known as KPCY, also has a fluorescent lineage label on pancreatic epithelial cells, permitting the evaluation of a treatment’s effects on metastatic incidence or growth. Our KPC and KPCY mice are on the C57 BL/6 strain background. Alternatively, syngeneic models provide a less labor-intensive tool for evaluating the efficacy of cancer therapies in the presence of a functional immune system. The mouse hospital employs both laparotomy and a relatively new technique of ultrasound-guided injection for orthotopic implantation of a murine PDA cell line in C57 BL/6 mice. This technique is faster, less invasive, and requires less recovery time than a traditional laparotomy. The mission of the Pancreatic Cancer Mouse Hospital of the Abramson Cancer Center is to evaluate novel PDA therapies on behalf of investigators who are at the University of Pennsylvania or are collaborating with Penn investigators. Our mouse studies are designed to mimic human clinical trials, including the use of eligibility criteria and randomized treatment assignment. Ultrasound is used for screening and to measure changes in tumor in response to therapy; serial studies permit measurement of time to diagnosis and rate of tumor progression. Additional endpoints include overall survival, serum chemistries, histology, tissue collection for pharmacodynamics studies, and immune subtyping as would be performed in a human clinical trial. Citation Format: Cynthia Clendenin, Rina Sor, Deirdre McMenamin, Ben Z. Stanger, Gregory Beatty, Robert H. Vonderheide. A “mouse hospital” for preclinical testing of diagnostic and treatment modalities in pancreatic ductal adenocarcinoma (PDA) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C13.
Gout Is Associated With Increased Coronary Artery Calcification and Adverse Cardiovascular Outcomes
Authors: Jared L. Christensen, Wenzheng Yu, Sydney Tan, Alice Chu, Fabian Vargas, Maen Assali, Nishant R. Shah, Anthony M. Reginato, Wen-Chih Wu, Gaurav Choudhary, Alan R. Morrison
Journal: JACC. Cardiovascular imaging (2019)
Organic Solute Transporter Alpha Deficiency: A Disorder With Cholestasis, Liver Fibrosis, and Congenital Diarrhea
Authors: Emily Gao, Huma Cheema, Nadia Waheed, Iqra Mushtaq, Nihan Erden, Carol Nelson‐Williams, Dhanpat Jain, Carol J. Soroka, James L. Boyer, Youssef Khalil, Peter T. Clayton, Pramod K. Mistry, Richard P. Lifton, Sílvia Vilarinho
Journal: Hepatology (2019)

Gao, Emily; Cheema, Huma; Waheed, Nadia; Mushtaq, Iqra; Erden, Nihan; Nelson‐Williams, Carol; Jain, Dhanpat; Soroka, Carol J.; Boyer, James L.; Khalil, Youssef; Clayton, Peter T.; Mistry, Pramod K.; Lifton, Richard P.; Vilarinho, Sílvia Author Information
TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product
Authors: Trudy Straetemans, Anke Janssen, Koen Jansen, Ruud Doorn, Tineke Aarts, Anna D.D. van Muyden, Marieke Simonis, Judith Bergboer, Moniek de Witte, Zsolt Sebestyen, Jurgen Kuball
Journal: Molecular Therapy (2019)

Despite extensive usage of gene therapy medicinal products (GTMPs) in clinical studies and recent approval of chimeric antigen receptor (CAR) T cell therapy, little information has been made available on the precise molecular characterization and possible variations in terms of insert integrity and vector copy numbers of different GTMPs during the complete production chain. Within this context, we characterize αβT cells engineered to express a defined γδT cell engineered to express a defined γδT receptor (TEG) currently used in a first-in-human clinical study (NTR6541). Utilizing targeted locus amplification in combination with next generation sequencing for the vector producer clone and TEG001 products, we report on five single-nucleotide variants and nine intact vector copies integrated in the producer clone. The vector copy number in TEG001 cells was on average a factor 0.72 (SD 0.11) below that of the producer cell clone. All nucleotide variants were transferred to TEG001 without having an effect on cellular proliferation during extensive in vitro culture. Based on an environmental risk assessment of the five nucleotide variants present in the non-coding viral region of the TEG001 insert, there was no altered environmental impact of TEG001 cells. We conclude that TEG001 cells do not have an increased risk for malignant transformation in vivo. Despite extensive usage of gene therapy medicinal products (GTMPs) in clinical studies and recent approval of chimeric antigen receptor (CAR) T cell therapy, little information has been made available on the precise molecular characterization and possible variations in terms of insert integrity and vector copy numbers of different GTMPs during the complete production chain. Within this context, we characterize αβT cells engineered to express a defined γδT cell engineered to express a defined γδT receptor (TEG) currently used in a first-in-human clinical study (NTR6541). Utilizing targeted locus amplification in combination with next generation sequencing for the vector producer clone and TEG001 products, we report on five single-nucleotide variants and nine intact vector copies integrated in the producer clone. The vector copy number in TEG001 cells was on average a factor 0.72 (SD 0.11) below that of the producer cell clone. All nucleotide variants were transferred to TEG001 without having an effect on cellular proliferation during extensive in vitro culture. Based on an environmental risk assessment of the five nucleotide variants present in the non-coding viral region of the TEG001 insert, there was no altered environmental impact of TEG001 cells. We conclude that TEG001 cells do not have an increased risk for malignant transformation in vivo.
Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study
Authors: Hiddo J L Heerspink, Avraham Karasik, Marcus Thuresson, Cheli Melzer-Cohen, Gabriel Chodick, Kamlesh Khunti, John P H Wilding, Luis Alberto Garcia Rodriguez, Lucia Cea-Soriano, Shun Kohsaka, Antonio Nicolucci, Giuseppe Lucisano, Fang-Ju Lin, Chih-Yuan Wang, Eric Wittbrodt, Peter Fenici, Mikhail Kosiborod
Journal: The Lancet Diabetes & Endocrinology (2019)
Mgta-456, an Aryl Hydrocarbon Receptor (AHR) Antagonist Based Expansion of CD34+ Hematopoietic Stem Cells (HSC), Permits Selection of Better HLA Matched Cord Blood Units (CBUs) and Promotes Faster Neutrophil Recovery and Uniform Engraftment with Potentially Less Acute Graft-Vs-Host Disease (GVHD)
Authors: Heather Stefanski, Claudio G Brunstein, David H. McKenna, Darin Sumstad, Jeffrey S. Miller, Bruce R. Blazar, Todd E. DeFor, Anthony E. Boitano, Michael P. Cooke, Glen D. Raffel, John C. Davis, John E. Wagner
Journal: Blood (2019)
A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells
Authors: L. Bertrand, M. Balteau, A. Timmermans, B. Viollet, K. Sakamoto, O. Feron, S. Horman, J. L. Vanoverschelde, C. Beauloye, C. De Meester
Journal: Cardiovascular Research (2012)
Effectiveness and Cost-Effectiveness of Human Papillomavirus Vaccination Through Age 45 Years in the United States
Authors: Jean-François Laprise, Harrell W. Chesson, Lauri E. Markowitz, Mélanie Drolet, Dave Martin, Élodie Bénard, Marc Brisson
Journal: Annals of Internal Medicine (2019)

Background: In the United States, the routine age for human papillomavirus (HPV) vaccination is 11 to 12 years, with catch-up vaccination through age 26 years for women and 21 years for men. U.S. vaccination policy on use of the 9-valent HPV vaccine in adult women and men is being reviewed. Objective: To evaluate the added population-level effectiveness and cost-effectiveness of extending the current U.S. HPV vaccination program to women aged 27 to 45 years and men aged 22 to 45 years. Design: The analysis used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), an individual-based transmission dynamic model of HPV infection and associated diseases, calibrated to age-specific U.S. data. Data Sources: Published data. Target Population: Women aged 27 to 45 years and men aged 22 to 45 years in the United States. Time Horizon: 100 years. Perspective: Health care sector. Intervention: 9-valent HPV vaccination. Outcome Measures: HPV-associated outcomes prevented and cost-effectiveness ratios. Results of Base-Case Analysis: The model predicts that the current U.S. HPV vaccination program will reduce the number of diagnoses of anogenital warts and cervical intraepithelial neoplasia of grade 2 or 3 and cases of cervical cancer and noncervical HPV-associated cancer by 82%, 80%, 59%, and 39%, respectively, over 100 years and is cost saving (vs. no vaccination). In contrast, extending vaccination to women and men aged 45 years is predicted to reduce these outcomes by an additional 0.4, 0.4, 0.2, and 0.2 percentage points, respectively. Vaccinating women and men up to age 30, 40, and 45 years is predicted to cost $830 000, $1 843 000, and $1 471 000, respectively, per quality-adjusted life-year gained (vs. current vaccination). Results of Sensitivity Analysis: Results were most sensitive to assumptions about natural immunity and progression rates after infection, historical vaccination coverage, and vaccine efficacy. Limitation: Uncertainty about the proportion of HPV-associated disease due to infections after age 26 years and about the level of herd effects from the current HPV vaccination program. Conclusion: The current HPV vaccination program is predicted to be cost saving. Extending vaccination to older ages is predicted to produce small additional health benefits and result in substantially higher incremental cost-effectiveness ratios than the current recommendation. Primary Funding Source: Centers for Disease Control and Prevention.