tbuckley/cabot-search huggingface dataset:
Isolation of lymphatic endothelium from human tonsil
Authors: Giulio Alessandri, Emirena Garrafa, Arnaldo Caruso, Eugenio Parati
Journal: Cancer Research (2004)

4949  The lymphatic microvasculature is important for the continuous removal of interstitial fluid and proteins and is an important entry point for leukocytes, tumor cells and pathogen microrganisms. Attempts to isolate and grow human lymphatic endothelial cells (LECs) have prevalently been made from human dermal endothelial cell cultures allowing their preliminary phenotypic characterization. Palatine tonsils are specialized lymphatic organs within the orphaning, and display a richness in lymphatic venules as compared to blood vessels. By using monoclonal antibodies against Vascular Endothelial Grow Factor Receptor-3, a marker highly expressed on LECs, we isolated LECs from human tonsils (Td-LEC) and studied their phenotypic and functional properties. Td-LECs cultured on collagen-fibronectin coated flasks in the presence of Endothelial Grow Medium (EGM) showed a good proliferation rate (doubling time of about 72h hours), and were maintained in culture for up to 8-10 passages. The presence of a functional VEGFR-3 molecule on cultured Td-LECs was confirmed by their sensitivity to VEGF-C activity. Addition of VEGF-C to Td-LEC cultures determined a 3-4 fold increase of LEC proliferation rate (doubling time of 18-24h) as compared to control cells, and also increased the expression of the proliferation related markers ki67 and CD105. Cultured Td-LECs also retained the phenotypic properties of tonsil lymphatic endothelium. In fact, they were positive for the expression of endothelial cell markers such as UEA-1 (Ulex europaeus agglutinin 1), PIH12/CD146, CD31, von Willebrand factor (vWf) and Ve-cadherins but completely negative for CD34 and KDR. We conclude that tonsils are a sufficiently easy source for isolation and in vitro expansion of human microvascular LECs. Td-LECs can be cultured without losing their differentiated properties and functional activity, and may represent a new model for investigating the function and biochemical properties of this particular lymphatic endothelium.
Risks of Statins for Lower-Risk Individuals—Reply
Authors: Harlan M. Krumholz
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 02: Does Pokemon Go Help Players be More Active? An Evaluation of Pokemon Go and Physical Activity
Authors: Hanzhang Xu, Ying Xian, Haolin Xu, Li Liang, Adrian F Hernandez, Tracy Y Wang, Eric D Peterson
Journal: Circulation (2017)

Objective: Pokémon Go is a location-based augmented reality game for mobile devices. Leveraging GPS and camera on the smartphone, Pokémon Go requires the player to travel around an area capturing animated creatures. This study aimed to evaluate physical activity associated with Pokémon Go. Methods: We recruited 167 iPhone users who had played Pokémon Go in July 2016. Study participants provided screenshots of their daily “steps” reported on their iPhone Health app between June 15, 2016 and Jul 31, 2016. The primary outcome measures were average daily “steps” and % of days &gt; 10,000 steps/day before and after playing Pokémon Go. Results: Of 167 volunteers, the mean age were 26±6 years. The average daily steps was 5678±2833 (median 5718 [IQR 3675-7279]) before the participants played Pokémon Go and this number increased to 7654± 3616 (median 7232 IQR [5041-9744]) after they started playing the game. On average, we observed an increase of 1976 (95% CI 1494-2458, p&lt;0.001) in daily steps ( Figure ). Additionally, participants were more likely to achieve 10,000 steps/day goal after playing Pokémon Go (15.3% before vs. 27.5% after; OR 2.06, 95% CI 1.70-2.50). Results from subgroup analyses also showed significant increased level of physical activity after Pokémon Go. Participants who spent more time playing (2-2.5 hours/day 2861 more steps, 95% CI 1884-3837; &gt;2.5 hours/day 2238 more steps, 95% CI 1008-3467), overweight/obese (3031 more steps, 95% CI 2132-3929), or with a lower baseline physical activity level (lowest quartile, 2,899 more steps, 95% CI 2030-3767) had the largest increase after the initiation of the game. Conclusion: We observed a significant increase in physical activity associated with Pokémon Go. Games like Pokémon Go may provide an alternative way to encourage exercise, especially among young adults with low baseline physical activity levels and/or overweight/obesity.
The Sustainability of Evidence-Based Interventions and Practices in Public Health and Health Care
Authors: Rachel C. Shelton, Brittany Rhoades Cooper, Shannon Wiltsey Stirman
Journal: Annual Review of Public Health (2018)

There is strong interest in implementation science to address the gap between research and practice in public health. Research on the sustainability of evidence-based interventions has been growing rapidly. Sustainability has been defined as the continued use of program components at sufficient intensity for the sustained achievement of desirable program goals and population outcomes. This understudied area has been identified as one of the most significant translational research problems. Adding to this challenge is uncertainty regarding the extent to which intervention adaptation and evolution are necessary to address the needs of populations that differ from those in which interventions were originally tested or implemented. This review critically examines and discusses conceptual and methodological issues in studying sustainability, summarizes the multilevel factors that have been found to influence the sustainability of interventions in a range of public health and health care settings, and highlights key areas for future research.
Targeting IRF3 as a YAP agonist therapy against gastric cancer
Authors: Shi Jiao, Jingmin Guan, Min Chen, Wenjia Wang, Chuanchuan Li, Yugong Wang, Yunfeng Cheng, Zhaocai Zhou
Journal: The Journal of Experimental Medicine (2018)

The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The transcription factor IRF3 is essential for innate antiviral immunity. In this study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The expression of IRF3 is positively correlated with that of YAP and its target genes in gastric cancer; the expression of both IRF3 and YAP is up-regulated and prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the nucleus to enhance their interaction, promoting nuclear translocation and activation of YAP. IRF3 and YAP–TEAD4 are associated genome-wide to cobind and coregulate many target genes of the Hippo pathway. Overexpression of active IRF3 increased, but depletion of IRF3 reduced, the occupancy of YAP on the target genes. Knockdown or pharmacological targeting of IRF3 by Amlexanox, a drug used clinically for antiinflammatory treatment, inhibits gastric tumor growth in a YAP-dependent manner. Collectively, our study identifies IRF3 as a positive regulator for YAP, highlighting a new therapeutic target against YAP-driven cancers.
Abstract 19135: Small, Dense LDL Has Protective Association for Long-Term Mortality After Myocardial Infarction Compared With Large, Buoyant LDL Particles: Insights From the TRIUMPH Study
Authors: Bhaskar Bhardwaj, Yashashwi Pokharel, Yuanyuan Tang, Arooge Towheed, Mohammed Qintar, Krishnaji Kulkarni, Seth Martin, Salim Virani, John Spertus
Journal: Circulation (2016)

Introduction: Small dense LDL particles are associated with stronger risk for incident coronary heart disease (CHD) than large buoyant LDL particles. Whether small dense LDL particles are associate...
The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic competing endogenous RNA network
Authors: Xiaochao Tan, Priyam Banerjee, Xin Liu, Jiang Yu, Don L. Gibbons, Ping Wu, Kenneth L. Scott, Lixia Diao, Xiaofeng Zheng, Jing Wang, Ali Jalali, Milind Suraokar, Junya Fujimoto, Carmen Behrens, Xiuping Liu, Chang-gong Liu, Chad J. Creighton, Ignacio I. Wistuba, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2018)

Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT-activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1-driven were enriched in miR-181b targets. ZEB1 relieved a strong basal repression of α1 integrin (ITGA1) mRNA, which in turn upregulated adenylyl cyclase 9 mRNA (ADCY9) by sponging miR181b. Ectopic expression of the ITGA1 3'-untranslated region reversed miR-181b-mediated metastasis suppression and increased the levels of adenylyl cyclase 9 protein (AC9), which promoted tumor cell migration and metastasis. In human lung adenocarcinomas, ITGA1 and ADCY9 levels were positively correlated, and an AC9-activated transcriptomic signature had poor-prognostic value. Thus, ZEB1 initiates a miR-181b-regulated ceRNA network to drive metastasis.
Temporal changes in the incidence of treated psychiatric and neurodevelopmental disorders during adolescence: an analysis of two national Finnish birth cohorts
Authors: David Gyllenberg, Mikko Marttila, Reijo Sund, Elina Jokiranta-Olkoniemi, André Sourander, Mika Gissler, Tiina Ristikari
Journal: The Lancet Psychiatry (2018)
Hepatic Gi signaling regulates whole-body glucose homeostasis
Authors: Mario Rossi, Lu Zhu, Sara M. McMillin, Sai Prasad Pydi, Shanu Jain, Lei Wang, Yinghong Cui, Regina J. Lee, Amanda H. Cohen, Hideaki Kaneto, Morris J. Birnbaum, Yanling Ma, Yaron Rotman, Jie Liu, Travis J. Cyphert, Toren Finkel, Owen P. McGuinness, Jürgen Wess
Journal: Journal of Clinical Investigation (2018)

An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis. Moreover, increased Gi signaling stimulated glucose release in human hepatocytes. A lack of functional Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. Additionally, we delineated a signaling cascade that links hepatic Gi signaling to ROS production, JNK activation, and a subsequent increase in HGP. Taken together, our data support the concept that drugs able to block hepatic Gi-coupled GPCRs may prove beneficial as antidiabetic drugs.
A new murine model for colon cancer using non-operative trans-anal rectal injection
Authors: Laurie Norcross, Melissa Donigan, John Aversa, Rafael Madero-Visbal, Jimmie Colon, Joshua Smith, Renee Mueller, Paul Williamson, Samuel DeJesus, Andrea Ferrara, Joseph Gallagher, Cheryl Baker
Journal: Cancer Research (2008)

2941    Background:  Currently, the most accurate orthotopic representation of human colon cancer is a cecal injection. However this requires a surgical incision and therefore limits the ability to accurately measure immune responses to any subsequent colon resections. Therefore, in order to study the immunological response following large bowel resection on mice with colon cancer, the traditional cecal injection model must be modified. In this study we designed an alternative orthotopic model for primary colon cancer by using a trans-anal approach.   Methods:  Anesthetized Balb/c mice were injected with 25,000 murine colon cancer CT26 cells using a 30-gauge syringe, submucosally into the distal, posterior rectum. Care was taken not to pass transmurally into the pelvic cavity. Seven mice were injected using operating loupes with 10x magnification and sacrificed on post-injection day 17. An additional 10 mice were injected using 100 x magnifications and sacrificed on day 20. The rectum, rectal wall and lungs were photographed, measured, and processed for histology and reviewed by a pathologist.   Results:  Three of seven mice in the initial study had notable, large tumor originating from the rectal wall, all showing poorly differentiated adenocarcinoma. In the second group, eight out of ten mice had gross tumor originating from the rectal wall. Four of these mice had abnormal lung tissue, suggesting metastasis. Slides from the second group of mice are under review. A 10x magnification resulted in a 43% tumor growth. In contrast and an 80% tumor growth rate was observed with 100x magnification. The overall success rate of tumor growth was 65% using the trans-anal, submucosal tumor injection model. Conclusion:  Trans-anal injection of colon cancer cells offers an alternative non-operative orthotopic murine model for colon cancer. By using an orthotopic model that does not require abdominal surgery for implantation, more aspects of inflammation and immune response can be evaluated without the influence of a previous abdominal surgery.
New-Onset Cardiovascular Morbidity in Older Adults With Stage I to III Colorectal Cancer
Authors: Kelly M. Kenzik, Courtney Balentine, Joshua Richman, Meredith Kilgore, Smita Bhatia, Grant R. Williams
Journal: Journal of Clinical Oncology (2018)

Purpose We sought to determine the long-term risk of cardiovascular disease (CVD)-stroke and myocardial infarction-and congestive heart failure (CHF) in older patients with colorectal cancer, as well as to understand the roles that preexisting comorbidities and cancer therapy play in increasing this risk. Patients and Methods We evaluated individuals from the SEER-Medicare database with incident stage I to III colorectal cancer at age older than 65 years between January 1, 2000, and December 31, 2011 (n = 72,408) and compared these patients with a matched cohort of Medicare patients without cancer (n = 72,408). Results Median age at diagnosis of colorectal cancer was 78 years (range, 66 years to 106 years), and median follow-up was 8 years since diagnosis. The 10-year cumulative incidence of new-onset CVD and CHF were 57.4% and 54.5% compared with 22% and 18% for control, respectively ( P < .001). The interaction between hypertension and chemotherapy was significant ( P < .001) for CVD, and that between diabetes and chemotherapy was significant ( P < .001) for CHF. Within the first 2 years since diagnosis, exposure to capecitabine alone increased CHF hazard (hazard ratio [HR], 3.6; 95% CI, 12.76 to 4.38) compared with exposure to fluorouracil alone. Conversely, patients who were treated with fluorouracil alone had a higher CVD hazard at < 2 years and > 2 years since diagnosis compared with patients who received capecitabine alone (< 2 years HR, 0.63; 95% CI, 0.53 to 0.75; > 2 years HR, 0.72; 95% CI, 0.62 to 0.84). Conclusion Older patients with colorectal cancer are at increased risk of developing CVD and CHF. Diabetes and hypertension interact with chemotherapy to increase the risk of cardiovascular morbidity. Future studies should assess the potential for personalized therapeutic options for those with preexisting morbidities and for structured monitoring for patients with a history of exposure to chemotherapy regimens, as well as explore the management of preexisting comorbidities to address long-term cardiovascular morbidity.
GW572016, a dual tyrosine kinase inhibitor, blocks activation of ErbB1 and ErbB2 in a bladder cancer cell line
Authors: Lynsey A. McHugh, Thomas R. Griffiths, Alexandra J. Colquhoun, Marina Kriajevska, J. Kilian Mellon
Journal: Cancer Research (2004)

4398  Introduction: Approximately 50% of bladder tumors exhibit strong immunohistochemical staining for ErbB1 (epidermal growth factor receptor, EGFR) and approximately 45% express ErbB2, both of which are associated with poor prognosis. Activation of these receptors leads to stimulation of downstream signaling pathways such as the mitogen-activated protein kinase (MAPK) and the anti-apoptotic kinase AKT pathways. They are also implicated in activation of STAT1, a signal transducer and transcription activator. Ultimately, activation of these pathways results in increased cell survival and proliferation. Thus, inhibition of ErbB1 and ErbB2 function may be methods of improving outcome for patients with bladder cancer. Methods: RT112 (a muscle invasive bladder cancer cell line) cells were treated with either EGF (100ng/ml), GW572016 (using IC50 dose of 1.1μM, previously determined), or GW572016 followed by EGF. Expression and activation (phosphorylation) of ErbB1 and ErbB2, and the downstream markers p42/44 MAPK, AKT and STAT1, were determined using Western analyses. Results: EGF stimulation resulted in significant phosphorylation of ErbB1, ErbB2, p42/44 MAPK and AKT. Treatment with GW572016 markedly reduced the activation of these proteins. When EGF was added after treatment with GW572016, EGF-induced phosphorylation was also reduced. These effects were most marked in the AKT pathway. EGF did not activate STAT1, nor was its baseline phosphorylation reduced by GW572016. Conclusions: In a bladder cancer cell line, dual inhibition of ErbB1 and ErbB2 by GW572016 leads to decreased activation of downstream pathways implicated in cell survival and proliferation, even in the presence of a known ligand of ErbB1. Constitutive activation of AKT has previously been linked to chemoresistance. Consequently, GW572016 is an attractive novel therapy for the treatment of bladder cancer, and may represent an effective method of chemosensitisation in advanced disease. GW572016 is a product of GlaxoSmithKline.
Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board
Authors: S.P. Somashekhar, M.-J. Sepúlveda, S. Puglielli, A.D. Norden, E.H. Shortliffe, C. Rohit Kumar, A. Rauthan, N. Arun Kumar, P. Patil, K. Rhee, Y. Ramya
Journal: Annals of Oncology (2017)
Somatic mutations precede acute myeloid leukemia years before diagnosis
Authors: Pinkal Desai, Nuria Mencia-Trinchant, Oleksandr Savenkov, Michael S. Simon, Gloria Cheang, Sangmin Lee, Michael Samuel, Ellen K. Ritchie, Monica L. Guzman, Karla V. Ballman, Gail J. Roboz, Duane C. Hassane
Journal: Nature Medicine (2018)
The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex Test Potential
Authors: Peter Ström, Tobias Nordström, Markus Aly, Lars Egevad, Henrik Grönberg, Martin Eklund
Journal: European Urology (2018)

It has been shown that the Stockholm-3 model (S3M) outperforms prostate-specific antigen (PSA) as a screening tool for prostate cancer. To update the S3M, to give a detailed account of the value of each predictor in the S3M, and to evaluate the S3M as a reflex test for men with PSA ≥3 ng/ml. During 2012–2015, the Stockholm-3 study evaluated the S3M relative to PSA as tests for Gleason score ≥7 prostate cancers among men aged 50–69 yr. The participants (n = 59 159) underwent both tests, and biopsy was recommended if at least one was positive. A total of 5073 men had a biopsy because of elevated PSA (≥3 ng/ml). Logistic regression was used to update the S3M: intact PSA was removed, HOXB13 was included, and the model was fitted to data from the Stockholm-3 training and validation cohorts. To compare S3M with PSA, we fixed the sensitivity for detection of high-grade cancer and evaluated the performance as the number of biopsies needed to achieve that sensitivity for each test. The updated S3M slightly improved the area under the receiver operating characteristic curve compared to previously published results (0.75 vs 0.74). When used as a reflex test for men with PSA ≥3 ng/ml, S3M reduced the number of biopsies needed by 34% compared to the use of PSA alone, with equal sensitivity. A limitation is the ethnically homogeneous population. A major problem with PSA screening—too many unnecessary biopsies—can be mitigated if S3M is used as a reflex test. To find aggressive prostate cancer with the minimum number of negative biopsies and detection of clinically insignificant cancers, we evaluated the use of a personalized diagnostic prediction model as a second test for men with a positive prostate-specific antigen (PSA) test. We found that this two-step approach could reduce prostate biopsies by a third compared to using PSA alone.
Human Lung DNA Methylation Quantitative Trait Loci Colocalize with Chronic Obstructive Pulmonary Disease Genome-Wide Association Loci
Authors: Jarrett D. Morrow, Kimberly Glass, Michael H. Cho, Craig P. Hersh, Victor Pinto-Plata, Bartolome Celli, Nathaniel Marchetti, Gerard Criner, Raphael Bueno, George Washko, Augustine M. K. Choi, John Quackenbush, Edwin K. Silverman, Dawn L. DeMeo
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

As the third leading cause of death in the United States, the impact of chronic obstructive pulmonary disease (COPD) makes identification of its molecular mechanisms of great importance. Genome-wide association studies (GWASs) have identified multiple genomic regions associated with COPD. However, genetic variation only explains a small fraction of the susceptibility to COPD, and sub-genome-wide significant loci may play a role in pathogenesis.
Emerging souvenirs—clinical presentation of the returning traveller with imported arbovirus infections in Europe
Authors: I. Eckerle, V.T. Briciu, Ö. Ergönül, M. Lupşe, A. Papa, A. Radulescu, S. Tsiodras, C. Tsitou, C. Drosten, V.R. Nussenblatt, C.B. Reusken, L.A. Sigfrid, N.J. Beeching
Journal: Clinical Microbiology and Infection (2018)
Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms
Authors: B.-H. Ryu, J.Y. Kim, T. Kim, M.-C. Kim, M.J. Kim, Y.-P. Chong, S.-O. Lee, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-H. Kim
Journal: Clinical Microbiology and Infection (2018)