tbuckley/cabot-search huggingface dataset:
In vitro evidence for the role of hepsin in metastatic prostate cancer
Authors: Rebecca Foster, David Smart, Lucy Elliott, Jessica Meyer, Sally Hampton, Doreen Ashworth, Robert Haigh, Chris Yea, Marc Princivalle
Journal: Cancer Research (2007)

466  Hepsin is a type II transmembrane serine protease documented to be up regulated in prostate cancer (1), and implicated in other cancers such as renal cell carcinoma and ovarian cancer. Hepsin expression has additionally been correlated with progression of prostate cancer and poor prognosis (2). An in vivo model has demonstrated a role for hepsin in basement membrane degradation and prostate cancer metastasis (3) but exactly how hepsin promotes metastasis is not clear. One known substrate for hepsin is Hepatocyte Growth Factor (HGF) (4). Expression of HGF and its receptor c-Met, are associated with tumor progression in prostate cancer, as well as other cancer types. HGF and c-Met have also been associated with the progression of prostate tumors to an androgen-independent state (5).  In order to better understand how hepsin contributes to prostate tumor development and the metastatic process, we have investigated the phenotypic effects of stably over-expressing human Hepsin in PNT2 cells, a human prostate epithelial cell line. Hepsin expressed by the stable cell line was demonstrated to be active in a protease assay.  Using colony formation assays to assess cell survival and proliferation, we have demonstrated that over expression of hepsin does not affect cell survival but instead leads to a decrease in the rate of cell proliferation as determined by colony area (p  To more accurately mimic an in vivo setting, we have cultured control or hepsin expressing PNT2 cells as 3D spheroids. These were co-cultured with osteoblast cells, since osteoblasts are reported to produce pro-HGF and prostate cancer commonly metastasizes to the bone. Hepsin expression altered the morphology and growth of the spheroids, with Hepsin expression leading to increased proliferation and invasive properties of the cells.  In conclusion, expression of Hepsin in prostate epithelial cells leads to increased cell motility and migration, altered cell morphology and promotes growth in the presence of essential factors provided by osteoblasts. We believe that in prostate cancer, these changes contribute to the metastatic process and aid tumor growth at metastatic sites. We are currently using a number of in vivo models in order to confirm these observations.  (1) Magee et al (2001) Cancer Res. 61: 5692-5696  (2) Xuan et al (2006) Cancer Res. 66: 3611-3619  (3) Klezovitch et al (2004) Cancer Cell 6: 185-195  (4) Herter et al (2005) Biochem J. 390: 125-136  (5) Maeda et al (2006) BBRC. 347: 1158-1165
Coding Error in Study of Rotavirus Vaccination and Type 1 Diabetes in Children
Authors: Kirsten P. Perrett, Kim Jachno, Terry M. Nolan, Leonard C. Harrison
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Working With Patients Who Self-injure
Authors: John G. Gunderson, Lois W. Choi-Kain
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Association of Biologic Prescribing for Inflammatory Bowel Disease With Industry Payments to Physicians
Authors: Rishad Khan, Cameron M. Nugent, Michael A. Scaffidi, Nikko Gimpaya, Samir C. Grover
Journal: JAMA Internal Medicine (2019)

This economic evaluation examines whether pharmaceutical industry payments to gastroenterologists are associated with how often they prescribe the pharmaceuticals’ drugs for inflammatory bowel disease.
Workplace Secondhand Tobacco Smoke Exposure Among U.S. Nonsmoking Workers, 2015
Authors: Chia-ping Su, Girija Syamlal, Sara Tamers, Jia Li, Sara E. Luckhaupt
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Secondhand tobacco smoke (SHS) exposure contributes to ill health and disease, including heart disease, lung cancer, and stroke (1). Although cigarette smoking has declined among U.S. workers, workplace exposure to SHS remains high, particularly among workers in certain industries, such as construction (2,3). Implementation of smoke-free laws has proven to be beneficial in reducing SHS exposure in general (1). CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement to assess the prevalence of self-reported workplace SHS exposure among nonsmoking workers by smoke-free policy status in the workers' states of residence and in detailed industry categories and subcategories. In 2015, 19.9% of nonsmoking workers reported any exposure to SHS at work during the 12 months preceding the interview, and 10.1% reported frequent exposure (twice a week or more). Nonsmoking workers who resided in states with comprehensive smoke-free laws in all three categories of venues (private worksites, bars, and restaurants) were least likely to report frequent exposure to workplace SHS. Nonsmoking workers employed in the commercial and industrial machinery and equipment repair and maintenance industry reported the highest prevalences of any workplace SHS exposure (65.1%), whereas the construction industry had the highest reported number of exposed workers (2.9 million); these industry categories/subcategories include outdoor workplaces and other settings that are unlikely to be protected by smoke-free laws. Identifying specific at-risk workplaces and implementing targeted intervention strategies could help reduce SHS exposure at work and protect workers' health.
Sensitisation to staphylococcal enterotoxins and asthma severity: a longitudinal study in the EGEA cohort
Authors: Ina Sintobin, Valerie Siroux, Gabriële Holtappels, Christophe Pison, Rachel Nadif, Jean Bousquet, Claus Bachert
Journal: European Respiratory Journal (2019)

Introduction Evidence is accumulating that Staphylococcus aureus plays an important role as disease modifier in upper and lower airway diseases. Sensitisation to S. aureus enterotoxins (SEs) was associated with an increased risk of severe asthma in previous cross-sectional studies, but evidence from longitudinal studies is lacking. We aimed to assess associations between SE-sensitisation and the subsequent risk for asthma severity and exacerbations. Methods This is a nested case–control study from the 20-year Epidemiological Study of the Genetics and Environment of Asthma (EGEA) cohort, including 225 adults (75 without asthma, 76 with mild asthma and 74 with severe asthma) in EGEA2 (2003–2007). For 173 of these individuals, SE-sensitisation was measured on samples collected 11 years earlier (EGEA1). Cross-sectional associations were conducted for EGEA1 and EGEA2. Longitudinal analyses estimated the association between SE-sensitisation in EGEA1 and the risk of severe asthma and asthma exacerbations assessed in the follow-up. Models were adjusted for sex, age, smoking, parental asthma/allergy and skin-prick test to house dust mite. Results SE-sensitisation varied between 39% in controls to 58% and 76% in mild and severe asthma, respectively, in EGEA1. An adjusted cross-sectional association showed that SE-sensitisation was associated with an increased risk of severe, but not for mild asthma. SE-sensitisation in EGEA1 was associated with severe asthma (adjusted OR 2.69, 95% CI 1.18–6.15) and asthma exacerbations (adjusted OR 4.59, 95% CI 1.40–15.07) assessed 10–20 years later. Conclusion For the first time, this study shows that being sensitised to SEs is associated with an increased subsequent risk of severe asthma and asthma exacerbations.
Generation of Quiescent Cardiac Fibroblasts From Human Induced Pluripotent Stem Cells for In Vitro Modeling of Cardiac Fibrosis
Authors: Hao Zhang, Lei Tian, Mengcheng Shen, Chengyi Tu, Haodi Wu, Mingxia Gu, David T. Paik, Joseph C. Wu
Journal: Circulation Research (2019)

Activated fibroblasts are the major cell type that secretes excessive extracellular matrix in response to injury, contributing to pathological fibrosis and leading to organ failure. Effective anti-fibrotic therapeutic solutions, however, are not available due to the poorly defined characteristics and unavailability of tissue-specific fibroblasts. Recent advances in single-cell RNA-sequencing fill such gaps of knowledge by enabling delineation of the developmental trajectories and identification of regulatory pathways of tissue-specific fibroblasts among different organs.This study aims to define the transcriptome profiles of tissue-specific fibroblasts using recently reported mouse single-cell RNA-sequencing atlas and to develop a robust chemically defined protocol to derive cardiac fibroblasts (CFs) from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis and drug screening.By analyzing the single-cell transcriptome profiles of fibroblasts from 10 selected mouse tissues, we identified distinct tissue-specific signature genes, including transcription factors that define the identities of fibroblasts in the heart, lungs, trachea, and bladder. We also determined that CFs in large are of the epicardial lineage. We thus developed a robust chemically defined protocol that generates CFs from human induced pluripotent stem cells. Functional studies confirmed that iPSC-derived CFs preserved a quiescent phenotype and highly resembled primary CFs at the transcriptional, cellular, and functional levels. We demonstrated that this cell-based platform is sensitive to both pro- and anti-fibrosis drugs. Finally, we showed that crosstalk between human induced pluripotent stem cell-derived cardiomyocytes and CFs via the atrial/brain natriuretic peptide-natriuretic peptide receptor-1 pathway is implicated in suppressing fibrogenesis.This study uncovers unique gene signatures that define tissue-specific identities of fibroblasts. The bona fide quiescent CFs derived from human induced pluripotent stem cells can serve as a faithful in vitro platform to better understand the underlying mechanisms of cardiac fibrosis and to screen anti-fibrotic drugs.
Prediction of Lymph Node Metastasis in Early Gastric Cancer by Collagen Signature—Endoscopists’ Viewpoint
Authors: Li Min, Yu Zhao, Shutian Zhang
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
A variant erythroferrone disrupts iron homeostasis in <i>SF3B1</i> -mutated myelodysplastic syndrome
Authors: Sabrina Bondu, Anne-Sophie Alary, Carine Lefèvre, Alexandre Houy, Grace Jung, Thibaud Lefebvre, David Rombaut, Ismael Boussaid, Abderrahmane Bousta, François Guillonneau, Prunelle Perrier, Samar Alsafadi, Michel Wassef, Raphaël Margueron, Alice Rousseau, Nathalie Droin, Nicolas Cagnard, Sophie Kaltenbach, Susann Winter, Anne-Sophie Kubasch, Didier Bouscary, Valeria Santini, Andrea Toma, Mathilde Hunault, Aspasia Stamatoullas, Emmanuel Gyan, Thomas Cluzeau, Uwe Platzbecker, Lionel Adès, Hervé Puy, Marc-Henri Stern, Zoubida Karim, Patrick Mayeux, Elizabeta Nemeth, Sophie Park, Tomas Ganz, Léon Kautz, Olivier Kosmider, Michaëla Fontenay
Journal: Science Translational Medicine (2019)

A variant erythroferrone contributes to hepcidin modulation and systemic iron accumulation in patients with SF3B1 -mutated myelodysplastic syndrome.
Oral Systemic Bioavailability of Bisphenol A and Bisphenol S in Pigs
Authors: Véronique Gayrard, Marlène Z. Lacroix, Flore C. Grandin, Séverine H. Collet, Hanna Mila, Catherine Viguié, Clémence A. Gély, Blandine Rabozzi, Michèle Bouchard, Roger Léandri, Pierre-Louis Toutain, Nicole Picard-Hagen
Journal: Environmental Health Perspectives (2019)

Background: Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral availability and systemic persistency, were higher than those of BPA. Objectives: The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK. Methods: Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds. Results: The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds. Conclusion: Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599
Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis
Authors: J. Rodríguez-Baño, M.A. Pérez-Moreno, G. Peñalva, J. Garnacho-Montero, C. Pinto, I. Salcedo, R. Fernández-Urrusuno, O. Neth, M.V. Gil-Navarro, A. Pérez-Milena, R. Sierra, Á. Estella, C. Lupión, A. Irastorza, J.L. Márquez, Á. Pascual, M.D. Rojo-Martín, M.J. Pérez-Lozano, R. Valencia-Martín, J.M. Cisneros
Journal: Clinical Microbiology and Infection (2019)
Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients
Authors: Alessandro Loglio, Peter Ferenci, Sara Colonia Uceda Renteria, Christine Y.L. Tham, Florian van Bömmel, Marta Borghi, Heidemarie Holzmann, Riccardo Perbellini, Elena Trombetta, Silvia Giovanelli, Letizia Greco, Laura Porretti, Daniele Prati, Ferruccio Ceriotti, Giovanna Lunghi, Antonio Bertoletti, Pietro Lampertico
Journal: Journal of Hepatology (2019)
Prognostic factors and therapeutic options for epithelioid hemangioendothelioma (EHE): A multicenter analysis of a series of fifty-seven cases.
Authors: Aurore Vozy, Audrey Simonaggio, Philippe Terrier, Valerie Paradis, Nicolas Penel, Olivier Mir, Charles Honoré, Sarah Naomie Dumont, Jean-Philippe Spano, Axel Le Cesne
Journal: Journal of Clinical Oncology (2019)

11062 Background: EHE is a rare vascular mesenchymal tumor for which there is currently no standard for treatment particularly for metastatic disease. EHE often present metastatic evolution but metastases are not a poor prognostic factor. The aim of this study was to improve knowledge of outcome of EHE patients and see the impact of active surveillance on outcome for metastatic EHE patients. Methods: Patients with EHE treated at three centers in France were included in this retrospective cohort. Univariate analysis of prognostic factors was performed using the Cox model. Survival was estimated using the Kaplan-Meier method and long rank analysis. Results: Fifty-seven patients with EHE were collected in this analysis: 27 (47%) women and 30 (53%) men, with a median age at diagnosis of 39 years (range, 12-83). At diagnosis, 17 (29.8%) patients had a localized tumor, while 40 (70.2%) patients had synchronous metastases. The most commonly affected organs were liver (29.8%), bones (14.0%), skin, lungs and soft tissues (10.5% each). For the 17 patients with localized EHE, the median distant recurrence-free survival after resection of primary was 64.6 months, 95% CI [29.4, NA], (median follow-up of 62.7 months, range, 12.5-234.8). For the 40 patients with metastatic EHE, the median progression-free survival (PFS) was 59.0 months, 95% CI [21.3, NA], (median follow-up of 121.1 months, range, 1.0-202.0). No prognostic factor was identified for localized EHE. For metastatic EHE, age was associated with progression (p = 0.019), and presence of pleural/ascites/pericarditis effusion adversely affected overall survival (OS) (p = 0.002). An initial “wait and see” attitude was proposed to 23 patients (57.5%) while 17 patients (42.5%) were treated at diagnosis with local or systemic treatment (monotherapy or combination of chemotherapy with anthracyclin, taxane, cyclophosphamide). OS were similar in both groups of patients, 174months and 121months for chemotherapy treated patients and active surveillance patients respectively (p = 0.56). Conclusions: Presence of effusion was a significant poor prognostic factor in metastatic EHE patients. Active surveillance could be proposed for asymptomatic patients without effusion but this strategy need to be confirmed in largest or prospective randomized trials.
Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies
Authors: Nikolas G. Balanis, Katherine M. Sheu, Favour N. Esedebe, Saahil J. Patel, Bryan A. Smith, Jung Wook Park, Salwan Alhani, Brigitte N. Gomperts, Jiaoti Huang, Owen N. Witte, Thomas G. Graeber
Journal: Cancer Cell (2019)
The gut-bone axis: how bacterial metabolites bridge the distance
Authors: Mario M. Zaiss, Rheinallt M. Jones, Georg Schett, Roberto Pacifici
Journal: Journal of Clinical Investigation (2019)

The gut microbiome is a key regulator of bone health that affects postnatal skeletal development and skeletal involution. Alterations in microbiota composition and host responses to the microbiota contribute to pathological bone loss, while changes in microbiota composition that prevent, or reverse, bone loss may be achieved by nutritional supplements with prebiotics and probiotics. One mechanism whereby microbes influence organs of the body is through the production of metabolites that diffuse from the gut into the systemic circulation. Recently, short-chain fatty acids (SCFAs), which are generated by fermentation of complex carbohydrates, have emerged as key regulatory metabolites produced by the gut microbiota. This Review will focus on the effects of SCFAs on the musculoskeletal system and discuss the mechanisms whereby SCFAs regulate bone cells.
Differences in immune tumor microenvironment between primary and metastatic castration-resistant prostate cancer.
Authors: Yuanquan Yang, Yali Zhang, Jianmin Wang, John Krolewski, Ellis Glenn Levine, James Mohler, Gurkamal S. Chatta, Pawel Kalinski
Journal: Journal of Clinical Oncology (2019)

58 Background: Androgen deprivation therapy (ADT)-induced immunosuppression has been described in animal models as contributing to castration-resistant prostate cancer (CRPC) development, but the clinical relevance of these observations has not been established. In this study, we compared the immune tumor microenvironment (iTME) of primary prostate cancer (PPC) versus metastatic CRPC (mCRPC). Methods: Genomic and clinically annotated data were obtained of PPC and mCRPC from the TCGA provisional and SU2C/PCF databases. Patients without RNA-seq data were excluded. 22 iTME cell subsets were estimated using CIBERSORT LM22 algorithm. Relative cell proportions and gene expression in log-transformed FPKM were compared using Wilcoxon tests. Results: 499 PPC and 118 mCRPC were studied. Compared to PPC, mCRPC had higher percentage of M2 macrophages (24.6% vs. 10.2%, p&lt;0.0001). High M2 in mCRPC was associated with 2.5-, 6- and 19.5-fold increases in IL-10, VEGFA and ARG1 mRNA levels, respectively (p&lt;0.0001). T- cell exhaustion markers, LAG3 and CD160, were upregulated in mCRPC by 43.2% and 266.7% (p&lt;0.0001). Although CD8 T-cells were higher in mCRPC, the CD8/M2 ratio was lower (1.1 vs. 1.5, p=0.002). Prior use of abiraterone or enzalutamide in the mCRPC cohort (n=54) did not alter iTME cell fractions compared to AR antagonist naïve mCRPC. The detailed iTME comparisons were listed in Table. Conclusions: Our data indicate the development of tumor-favoring iTME in the course of progression to mCRPC while on ADT. The iTME is characterized by increased M2 macrophage infiltration that may provide a novel and important therapeutic target. [Table: see text]