tbuckley/cabot-search huggingface dataset:
Liver X receptors and copper metabolism: New frontiers for the oxysterol receptors
Authors: Chiara Gabbi, Marco Bertolotti
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article by Hamilton et al.1 showing that treatment with the liver X receptor (LXR) agonist, T0901317, ameliorates disease manifestation in a mouse model of Wilson disease (WD), but only with a partial effect in inducing the predicted LXR target genes. It should be noted that T0901317 is a synthetic LXR ligand that has a weak LXR specificity given that it can also bind to and activate other nuclear receptors, such as farnesoid X receptor (FXR) and pregnane X receptor.2 Interestingly, the activity of the bile acid receptor, FXR, has recently been shown to be down‐regulated in both patients and an animal model of WD, exhibiting elevated serum bile acids and bilirubin levels.4 Therefore, the beneficial effects of T0901317 may be attributed to a simultaneous activation of both FXR and LXR in livers affected by WD. Nevertheless, what is the link between a selective LXR activation and copper homeostasis? First, copper may bind with high affinity to the DNA‐binding domain of several nuclear receptors, including LXRs, inducing a conformational change that prevents DNA binding and, in turn, their transcriptional activity.4 Second, and most interestingly, microarray studies in wild‐type mice treated with the more selective LXR agonist, GW3965, showed an up‐regulation of a cluster of genes involved in copper homeostasis, such as metallothionein 1 and 2, the copper transport protein, Atcx1, and ceruloplasmin.5 Taken together, all those studies open new perspective for the oxysterol receptors, LXRs, involved not only in controlling lipid metabolism, inflammation, water transport, and cell proliferation, but also in regulating copper homeostasis.
Quantitative mass spectrometry-based proteomics identifies FRalpha and GARFT as predictive biomarkers in tissues of non-squamous NSCLC patients treated with pemetrexed
Authors: Alshehri Abdulrahman, Eunkiung An, Fabiola Cecchi, Adele Blackler, Shankar Sellappan, Matt Smolkin, Todd Hembrough, Manish Monga
Journal: Journal of Thoracic Oncology (2016)
Adriamycin Damage: In Vivo Repair by Lymphoma Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M Potmesil, M Levin, A Goldfeder, R Silber
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Adriamycin Damage: In Vivo Repair by Lymphoma Cells Get access Milan Potmesil, Milan Potmesil Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark Levin, Mark Levin Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna Goldfeder, Anna Goldfeder Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Silber Robert Silber Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 6, December 1981, Pages 1259–1263, https://doi.org/10.1093/jnci/67.6.1259 Published: 01 December 1981 Article history Received: 12 December 1980 Revision received: 09 June 1981 Accepted: 13 July 1981 Published: 01 December 1981
Vena Caval Filter Utilization and Outcomes in Pulmonary Embolism
Authors: Behnood Bikdeli, Yun Wang, Karl E. Minges, Nihar R. Desai, Nancy Kim, Mayur M. Desai, John A. Spertus, Frederick A. Masoudi, Brahmajee K. Nallamothu, Samuel Z. Goldhaber, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2016)
Work in non-insulin diabetes corroborates study's findings
Authors: R Davison, P West, H Tindall
Journal: BMJ (1996)

get treatment of the highest surgical and ethical standard: the interests of parents and patients may, we fear, be suffering as a result.In the past two months both the Cleft Lip and Palate Association and the charity Changing Faces have received calls from anxious and confused parents and patients who have been told categorically that one course of surgery is preferable or, worse, that their surgery to date has been poor and needs revision.In our view, this is an unacceptable and unprofessional way for patients to be treated.Our response to such distressing calls is to emphasise the importance of a multidisciplinary approach to the management of cleft lip and palate so that specialists, including psychologists, speech therapists, and paediatricians, together agree the priorities and objectives for surgery and therefore the most appropriate procedures in consultation with fully informed parents and patients.This is almost impossible at present because plastic sur- geons and oral surgeons do not seem to be collaborating in clinical practice; rather, they seem to be in open competition.As lay people we are unable to judge the strength of the arguments on both sides, and more research over 10-20 years may well be called for.Meanwhile, patients should not be pawns in a profes- sional (unprofessional) feud.The Royal College of Surgeons or some other powerful agency urgently needs to organise discussion in camera before more distress is caused.
The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women
Authors: Sung Jin Huh, Hannah Oh, Michael A. Peterson, Vanessa Almendro, Rong Hu, Michaela Bowden, Rosina L. Lis, Maura B. Cotter, Massimo Loda, William T. Barry, Kornelia Polyak, Rulla M. Tamimi
Journal: Cancer Research (2016)

The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.
Photolytic Protein Aggregates: Versatile Materials for Controlled Release of Active Proteins
Authors: Akira Ishiwatari, Satoshi Yamaguchi, Satoshi Takamori, Shinya Yamahira, Kosuke Minamihata, Teruyuki Nagamune
Journal: Advanced Healthcare Materials (2016)

Photolytic protein aggregates are developed as a facile and versatile platform for light-induced release of active proteins. The proteins modified with biotin through a photo-cleavable linker rapidly form aggregates with streptavidin and biotinylated functional molecules simply by mixing. Light irradiation releases active proteins from the aggregates in high yields, and light-induced uptake of drug-modified transferrin into living cells is successfully demonstrated. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers
Authors: Peter Tomassen, Griet Vandeplas, Thibaut Van Zele, Lars-Olaf Cardell, Julia Arebro, Heidi Olze, Ulrike Förster-Ruhrmann, Marek L. Kowalski, Agnieszka Olszewska-Ziąber, Gabriele Holtappels, Natalie De Ruyck, Xiangdong Wang, Cornelis Van Drunen, Joaquim Mullol, Peter Hellings, Valerie Hox, Elina Toskala, Glenis Scadding, Valerie Lund, Luo Zhang, Wytske Fokkens, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2016)
Secondary Malignancies After Autologous Stem Cell Transplantation In Patients With Relapsed / Refractory Hodgkin´s Lymphoma. A Retrospective Analysis On Behalf Of The Lymphoma Working Party Of The European Society For Blood and Marrow Transplantation (EBMT)
Authors: Anna Sureda, Ariane Boumendil, Michal Sieniawski, Kirsty Thomson, Martin Gramatzki, Didier Blaise, Catherine Thieblemond, Charles Crawley, Marc Renaud, Patrice Chevalier, Jian Jian Luan, Kim H. Orchard, Paneesha Shankara, Urs Schanz, Norbert Schmitz, Peter Dreger
Journal: Blood (2013)
Four-year assessment of a day hospital-inn program as an alternative to inpatient hospitalization
Authors: J E Gudeman, B Dickey, A Evans, M F Shore
Journal: American Journal of Psychiatry (1985)

The authors report on a new system of care in which all patients who require psychiatric hospitalization are admitted to a day hospital with an inn and an intensive care unit. Data on use of services, length of stay, recidivism, security, medical emergencies, staff accidents, and seclusion and restraint over a 4-year period suggest that the new delivery system provides care which is at least as effective as the previous system of care. Evidence is presented that the new system offers certain advantages, including less seclusion and restraint, fewer episodes of escape, and substantial cost savings.
EPCR Limits Nitric Oxide Levels, Mediating Human and Murine Stem Cell Adhesion and Retention In The Bone Marrow, By Conjugating PAR1 and CXCR4 Signaling
Authors: Shiri Gur Cohen, Tomer Itkin, Aya Ludin, Sagarika Chakrabarty, Orit Kollet, Karin Golan, Alexander Kalinkovich, Eitan Wong, Ayelet Erez, Irit Sagi, Charles T Esmon, Wolfram Ruf, Tsvee Lapidot
Journal: Blood (2013)
Real-Time Identification of Lung Adenocarcinoma Tumor Lesions Likely to Respond to Vintafolide Treatment By Using Etarfolatide
Authors: E.B. Garon, W.A. Harb, P. Bonomi, S. Yao, B. Nguyen, R. Mogg, M.J. Edelman
Journal: Annals of Oncology (2014)
Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population
Authors: Jalpa A. Doshi, Junko Takeshita, Lionel Pinto, Penxiang Li, Xinyan Yu, Preethi Rao, Hema N. Viswanathan, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2016)
Abstract 18340: Practice Patterns and Trends in the Use of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention
Authors: Pallav Garg, Lingsong Yun, Harindra C Wijeysundera, Warren Cantor, Dennis T Ko
Journal: Circulation (2013)

Background: Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). It is unknown to what degree medical therapy is applied before Percutaneous Coronary Intervention (PCI) in practice. We evaluated the practice patterns in the use of medical therapy in stable CAD patients undergoing PCI, and whether the COURAGE study changed medication practice patterns. Methods: We evaluated medication prescription rates in 23,680 patients over 65 years of age with stable CAD undergoing PCI in Ontario between December 2003 and March 2010. Medication use before and after PCI was compared, including after stratification on comorbidities and Canadian Cardiovascular Society (CCS) angina class, and in the periods before and after the publication of the COURAGE trial (March 2007). Optimal medical therapy (OMT) was defined as prescription for beta-blocker, statin and either ACE-inhibitor or ARB in the 90 days prior to PCI and the same medications along with a thienopyridine in the 90 days following PCI and suboptimal as having been prescribed at least one of the above medications. Results: Compared to before PCI, more patients were on optimal medical therapy after PCI [11,149 (47.1%) vs. 8023 (33.9%), p&lt;0.001]. Patients who were receiving OMT were more likely to have comorbidities, cardiovascular disease and had a prior stress test. Patients with angina at higher CCS class were less likely to be on OMT prior to PCI as compared with post-PCI (29.5% vs. 51.1%, p&lt;0.001). 11,984 (50.6%) patients underwent PCI in the period before publication of the COURAGE trial. Before PCI, OMT rate was lower in the period after the COURAGE trial compared with before the trial (32.8% vs. 34.9%, p&lt;0.001). The rate of OMT following PCI was lower in the period after the COURAGE trial compared with before the trial (47.3% vs. 46.9%, p&lt;0.001). Conclusion: Among patients with stable CAD undergoing PCI, only a third of patients were prescribed OMT in the 90 days prior to their procedure, and less than half were receiving optimal medical therapy in the 90 days following PCI. There was no substantial change in medical therapy practice pattern over the study period, including following the publication of the COURAGE trial.
Molecular identification of emergent GII.P17-GII.17 norovirus genotype, Romania, 2015
Authors: Sorin Dinu, Mariana Nagy, Dana Gabriela Negru, Emilian Damian Popovici, Lavinia Zota, Gabriela Oprișan
Journal: Eurosurveillance (2016)

The novel GII.P17-GII.17 norovirus genotype has been reported as cause of gastroenteritis outbreaks in China and Japan since the winter season 2014/15, replacing the pandemic strain GII.4 Sydney 2012. These emergent strains have also been sporadically reported on other continents than Asia. GII.P17-GII.17 isolates, similar to Kawasaki308 2015, were identified in three patients during a large outbreak of acute gastroenteritis affecting 328 people in Romania, in neighbouring localities, in 2015.
Homologous Transfer of Rous Sarcoma by Cells&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Jan Pontén
Journal: JNCI Journal of the National Cancer Institute (1962)

Primary Rous sarcomas induced by virus were transplanted homologously in solid or ascites form. A sex chromosome marker was used to distinguish transplanted cells from tumor cells induced in the recipient by Rous virus infection. The events after transfer of Rous cells bore a superficial resemblance to transplantation, but virus infection and induction of Rous cells were found to be the quantitatively dominating process. Only in the early stages of tumor development were any numbers of dividing transplanted cells identified. In old ascites or solid tumors almost all metaphases were derived from host elements. When graded amounts of Rous cells were inoculated, doses larger than 4 × 105 cells had to be used to get any detectable metaphases derived from the original Rous cells. In a second transplant generation, less than 0.5 percent of the metaphases were of the same sex as the original Rous cells.
A crucial juncture
Authors: Gordon Moore
Journal: BMJ (2008)

The NHS is at a crucial juncture, as Salisbury points out.1 At issue is whether the British public is better served by owner operated independent small GP businesses or by corporate practices, in which the autonomy of GPs is reduced. Corporatisation could result in practices being privately funded and designed, with the doctor retaining autonomy and responsibility for “business” or it could move towards doctors being hired hands.

My first …
Reduced oxygen saturation is not linked to repeat hospital visits in infant bronchiolitis
Authors: Susan Mayor
Journal: BMJ (2016)

Infants with bronchiolitis who have reduced oxygen saturation after discharge from emergency departments show comparable rates of repeat hospital visits to infants with higher oxygen saturation, in a prospective study that questions the value of monitoring desaturation in this situation.1

Pulse oximetry is sometimes used as a proxy for illness severity in bronchiolitis despite poor correlation between these parameters. Experts have been concerned that rising rates of hospital admissions among infants with bronchiolitis may be due to …
Abstract 104: The Utility of Cerebral Oximetry (rSO2%) During In-Hospital Cardiac Arrest as a Marker for the Prediction of Return of Spontaneous Circulation (ROSC)
Authors: Sam Parnia, Loren Inigo Santiago, Anna Ahn, Charles Deakin, Kim Golder, Pauline Bartlett, David Pogson, Sarah Cooke, Christopher Walker, Ken Spearpoint, Stephen Brett, David Kitson, Gavin Perkins, Teresa Melody, Mehboob Chilwan, Jerry Nolan, Jie Yang, Jiawen Zhu
Journal: Circulation (2013)

Background: Real time recognition of the quality of brain oxygen delivery is critical during resuscitation. Although end tidal CO2 monitoring (ETCO2) has been proposed as a marker of organ perfusio...
Characterization of Virus-Free Guinea Pig Tumors Induced by Kirsten Sarcoma Virus 2
Authors: J. S. Rhim, H. Y. Cho, J. M. Kim, I. Green
Journal: JNCI Journal of the National Cancer Institute (1976)

Tumors were induced by Kirsten sarcoma virus (KiSV) in an inbred guinea pig, strain 13. The tumor cells were established in culture and characterized. The KiSV-induced sarcoma cells were virus-free and nonproducing; however, they contained resuable sarcoma genome. A type B guinea pig retravirus was readily activated from the tumor cells after induction with 5-bromodeoxyuridine (BUDR). BUDR induction of guinea pig retravirus was further enhanced by treatment with dexamethasone, a synthetic glucocorticoid hormone.
P0942 : Immune reactions in steatohepatitis initiation and progression to fibrosis: Critical role of Th17 and Th22 lymphocytes
Authors: E. Alchera, S. Rolla, C. Imarisio, V. Bardi, G. Valente, A. Follenzi, B. Revanna Chandrashekar, F. Novelli, R. Carini
Journal: Journal of Hepatology (2015)
Platelet‐Derived S100A8/A9 and Cardiovascular Disease in Systemic Lupus Erythematosus
Authors: Christian Lood, Helena Tydén, Birgitta Gullstrand, Andreas Jönsen, Eva Källberg, Matthias Mörgelin, Robin Kahn, Iva Gunnarsson, Tomas Leanderson, Fredrik Ivars, Elisabet Svenungsson, Anders A. Bengtsson
Journal: Arthritis & Rheumatology (2016)

Objective Levels of S100A8/A9, a proinflammatory and prothrombotic protein complex, are increased in several diseases, and high levels predispose to cardiovascular disease (CVD). Recently, platelet S100A8/A9 synthesis was described in mice and humans in relation to CVD. The aim of this study was to investigate the role of platelet S100A8/A9 in systemic lupus erythematosus (SLE), a disease with markedly increased cardiovascular morbidity, as well as the exact platelet distribution of the S100A8/A9 proteins. Methods The occurrence and distribution of platelet S100A8/A9 protein were detected by enzyme‐linked immunosorbent assay, electron microscopy, Western blotting, and flow cytometry in healthy controls (n = 79) and in 2 individual cohorts of SLE patients (n = 148 and n = 318, respectively) and related to cardiovascular morbidity. Results We observed that human platelets expressed S100A8/A9 proteins, and that these were localized in close proximity to intracellular membranes and granules as well as on the cell surface upon activation with physiologic and pathophysiologic stimuli. Interestingly, S100A8/A9 was enriched at sites of membrane interactions, indicating a role of S100A8/A9 in cell–cell communication. S100A8/A9 levels were highly regulated by interferon‐α, both in vivo and in vitro. Patients with SLE had increased platelet S100A8/A9 content compared with healthy individuals. Increased levels of platelet S100A8/A9 were associated with CVD, particularly myocardial infarction (odds ratio 4.8, 95% confidence interval 1.5–14.9, P = 0.032 [adjusted for age, sex, and smoking]). Conclusion Platelets contain S100A8/A9 in membrane‐enclosed vesicles, enabling rapid cell surface deposition upon activation. Furthermore, platelet S100A8/A9 protein levels were increased in SLE patients, particularly in those with CVD, and may be a future therapeutic target.
Blunted Cortisol Stress Response and Depression-Induced Hypocortisolism Is Related to Inflammation in Patients With CAD
Authors: Christiane Waller, Johann Bauersachs, Uta Hoppmann, Julia Höch, Sabrina Krause, Franziska Szabo, Harald Engler, Edit Rottler, Christoph Herrmann-Lingen, Harald Gündel
Journal: Journal of the American College of Cardiology (2016)
Abstract 176: β-Adrenergic Receptor--Mediated Regulation of Cardiac Gene Expression Is Gefitinib Sensitive
Authors: Douglas G Tilley, Jennifer A Talarico, Laurel A Grisanti, Rhonda L Carter
Journal: Circulation Research (2012)

BetaAR-mediated transactivation of epidermal growth factor receptor (EGFR) has been shown to promote cardioprotection in a mouse model of heart failure, however the mechanism(s) responsible for this pro-survival response are not known. We hypothesized that this transactivation event could impact a number of processes in the heart, including survival, via regulation of gene expression. To test the capacity of BetaAR-mediated EGFR transactivation to regulate this process, acute changes in cardiac gene expression were assessed via RNA sequencing in the hearts of C57BL/6 mice given i.p. injections of the BetaAR agonist isoproterenol (ISO, 1mg/kg) in the presence or absence of the EGFR antagonist gefitinib (Gef, 5mg/kg) for 1 hour. The total RNA from 4 hearts per treatment group (Control, ISO, Gef, Gef/ISO) were combined and underwent DNA library generation and SOLiD sequencing analysis, which revealed a substantial number of genes and isoforms regulated by each of the treatments. Interestingly, Gef alone significantly altered the expression of 270 genes compared to control suggesting potential Gef-dependent alterations in the heart during clinical use. ISO alone and Gef/ISO significantly altered 401 and 723 distinct genes compared to control, respectively. Further statistical analysis was performed between the ISO and Gef/ISO groups to assess true Gef sensitivity of ISO-regulated genes in the heart, confirming 173 genes significantly altered between the groups. Classification of these genes revealed 4 categories: ISO-dependent gene upregulation (1) or downregulation (2) antagonized by Gef, and ISO-dependent gene upregulation (3) or downregulation (4) promoted in presence of Gef. Identified within these categories were several genes known to be involved in the regulation of cardiac hypertrophy, apoptosis, sarcomeric structure and Ca2+-handling, which were selected for validation via qPCR. In conclusion, BetaAR-mediated EGFR transactivation induces rapid modulation of cardiac gene expression in response to catecholamine stimulation in vivo, with potential functional impacts on a number of cellular processes, while simultaneously acting to antagonize gene expression changes mediated via distinct BetaAR-mediated signaling pathways.
Clinical skills still provoke debate
Authors: T. Woodcock
Journal: BMJ (1995)

EDITOR,--J Goodwin's editorial on the importance of clinical skills fails to offer any worthwhile evidence for the hypotheses proposed.1 The author opines that only the “clinically inexperienced” depend on the Swan-Ganz catheter for measuring intracardiac pressures in critically ill patients, yet the author offers no evidence to support this “good example” of undue reliance on technology and ignores objective …