tbuckley/cabot-search huggingface dataset:
P16.05 Percutaneous vertebral body stenting to restore stability of the anterior column in extreme spinal osteolysis
Authors: A. Cianfoni, D. Distefano, V. Espeli, G. Bonaldi, P. Scarone, G. Pesce
Journal: Neuro-Oncology (2017)

Introduction: Extreme neoplastic osteolysis of the vertebral body (VB) determines risk of collapse and instability. The current treatment of extensive VB lesions aims to restore stability with instrumentation generally performed with a combined, anterior and posterior, surgical approach. The anterior part of this operation carries significant morbidity related to its invasiveness, long hospitalization and high complication rate. Percutaneous vertebral augmentation is a palliative treatment of painful or at-risk of- collapse lytic VB lesions, but osteolysis with wide cortical involvement has higher risk of cement leakage, possibly limiting the amount of cement injected, resulting in insufficient stabilization. Vertebral body stent (VBS) is a barrel-shaped semi-rigid implant with large support surface, that can be inserted with a percutaneous image-guided minimally invasive technique, and allows primary stabilization of anterior column and cement containment. The aim of our work was to assess technical and clinical results and complications of a procedure of kyphoplasty with VBS for pain palliation and spinal stabilization in selected patients with extreme lytic VB lesions. Materials and Methods: retrospective review of a prospectively maintained database of 29 consecutive patients with extensive neoplastic osteolysis (>2/3 of the VB with erosion of the cortical boundaries) in one or more VB, from T1 to S1, for a total of 42 spinal levels, treated with kyphoplasty and VBS between March 2013 and September 2016. All target lesions presented morphological criteria of instability based on SINS and/or Taneichi criteria. Post-procedural CT images were reviewed in consensus by two neuroradiologists and one neurosurgeon to assess the correct placement of the devices and the cement filling of the lytic cavities, to evaluate the results in terms of restoration of VB height, stabilization of the target level, and to detect technical complication. Clinical and radiological follow-up was performed at 30 days and patients were followed up clinically and radiologically as per oncology clinical practice. Follow-up ranges between 1 and 24 months. Results: The procedure was deemed technically successful in providing structural stability in 40/42 cases. Epidural or foraminal leaks of cement occurred in 5/42 levels without clinical consequences. In 1 case there was an anterior mobilization of the stents with onset of dysphagia, at 30 days, that gradually resolved, with no further implant mobilization at 3 months. Pain reduction was attributable to the procedure itself in 19 cases, in combination with radiation and/or chemotherapy in 6, while 4 patients reported no significant pain amelioration. Conclusions: Our preliminary results support the use of kyphoplasty with VBS as an effective and safe procedure to restore stability and reduce pain in selected patients with extreme spinal osteolysis.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the
Authors: Sharon Ann Hunt, William T. Abraham, Marshall H. Chin, Arthur M. Feldman, Gary S. Francis, Theodore G. Ganiats, Mariell Jessup, Marvin A. Konstam, Donna M. Mancini, Keith Michl, John A. Oates, Peter S. Rahko, Marc A. Silver, Lynne Warner Stevenson, Clyde W. Yancy, Elliott M. Antman, Sidney C. Smith, Cynthia D. Adams, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Jonathan L. Halperin, Loren F. Hiratzka, Alice K. Jacobs, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel
Journal: Circulation (2005)
P01.33 Upregulated expression of the Aryl hydrocarbon receptor pathway in brain metastases from malignant melanoma
Authors: M. Timmer, N. von Spreckelsen
Journal: Neuro-Oncology (2017)

Objective: The Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor initially linked to exogenic carcinogenic agents such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). In 2011, the tryptophan (TRP) catabolite kynurenine (KYN) was identified as the first endogenous ligand activating the AHR pathway. AHR has been shown to be involved in several biochemical pathways and cellular processes such as cell cycle, cell migration, tumorigenesis, cell migration and immune function. AHR is expressed in cells of the central nervours system and dysregulation of AHR, its nuclear translocator (ARNT), its Repressor AHRR and the KYN building Enzyme TRP-2,3-dioxygenase 2 (TDO) has been linked to poor survival in patients with Glioblastoma. In this study we aimed to evaluate a potential role of the AHR pathway in brain metastases. Methods: Using quantitative RT-PCR, gene expression was analyzed in 19 brain-metastases of melanoma patients, 10 control tissues from peritumoral brain areas histopathologically classified as tumorfree and 10 glioblastoma (GBM) samples. Differences in the expression of AHR, ARNT, AHRR, TDO as well as the AHR/AHRR ratio between tumor tissue and control were analyzed using the Mann-Whitney-U test. Results are depicted in mean values with standard deviation (SD) and in Arbitrary Units (AU). A Value of p<.05 was considered significant. Results: Both, AHR and ARNT were massively overexpressed in metastatic tissues (p<.01) (6- and 4.5-fold) compared to normal brain (AHR: 3.64 ± 2.32 vs. .58 ±.50; p<0.01 and ARNT: 3.81 ± 2.25 vs. .83 ±.48, p<.01). AHRR and TDO where not significantly upregulated (.73 ±.88 vs. .41 ±.35; p=.31 and .37 ±.61 vs. .14 ±.09; p=.46). However, when comparing the ratio of the transcription factor AHR and its Repressor AHRR (AHRR/AHR) in metastatic and control tissue, the imbalance between the severely upregulated AHR in tumortissue and AHRR was distinctly significant. (.55 ± 1.09 vs. .18 ± 1.60 p<.01) Comparing AHR expression between malignant melanoma metastasis and GBM exhibt the following values: 3.64 ± 2.32 vs. 1.27 ± 1.89; p=.055. Moreover, ARNT was significantly elevated in metastasis compared to GBM: 3.81 ± 2.25 vs. 1.7 ±.1.15, p<.01. Conclusion: Our data reveal a significant upregulation of key components of the AHR pathway in melanoma brain metastases in comparison to peritumoral brain and partly even glioblastoma. This could indicate a major pathophysiological role of this pathway not only in glioblastomas like shown before, but also in the progression of brain metastasis. While the AHR-pathway can play a dual role in tumorigenesis, i.e. it can be either tumor-suppressive or tumor-promoting, its role in brain metastases of melanomas has to be further elucidated based on these findings.
Small Molecules Targeting Rad51 Recombinase Synergize with Imatinib and Overcome Imatinib-Resistance in CML.
Authors: Longen Zhou, Jiewen Zhu, Heiko Konig, Xiaoqin Lin, Ravi Bhatia, A. Richard Chamberlin, Phang-Lang Chen, Wen-Hwa Lee
Journal: Blood (2007)
Cardiac Resynchronization Therapy With Wireless Left Ventricular Endocardial Pacing
Authors: Vivek Y. Reddy, Marc A. Miller, Petr Neuzil, Peter Søgaard, Christian Butter, Martin Seifert, Peter Paul Delnoy, Lieselot van Erven, Martin Schalji, Lucas V.A. Boersma, Sam Riahi
Journal: Journal of the American College of Cardiology (2017)
Abstract P200: Transcriptional Regulation of <i>tcap</i> Conveys an Inhibitory Mechanotransductive Response to Modulate Cardiomyocyte Size
Authors: Jingchun Yang, Yonghe Ding, Xiaojing Sun, Xiaolei Xu
Journal: Circulation Research (2011)

To sense and to respond to mechanical stimuli is a fundamental process of cardiomyocytes during both heart development and diseases. However, how mechanical stimuli control cardiomyocyte size remains elusive. Here, we report a novel inhibitory mechanotransductive response suggested by loss-of-functions studies of α-Actinin2 (Actn2), a predominant sarcomeric Z-disc protein. During zebrafish cardiogenesis, depletion of Actn2 results in a defective Z-disc, while other sarcomeric substructures remain normal. As a consequence, ventricle chamber size is severely reduced. Interestingly, this chamber size reduction can be rescued by the cessation of heart contraction, suggesting the involvement of an inhibitory mechanotransductive reponse. At the molecular level, both tcapa and tcapb, two zebrafish tcap homologues that are transcriptionally responsive to stretch, are transcriptionally activated in actn2 knockdown embryos while activation of these gene results in smaller cardiomyocytes. Depletion of either gene rescues the reduced cardiomyocyte size in actn2 knockdown embryos. Consistent to embryonic studies, tcaps are transcriptionally activated during pathogenesis of anemia-induced cardiomyopathy, while over expression of tcapa via transgenics exerts a cardioprotective effect. Together, we conclude that transcriptional regulation of tcaps conveys a novel inhibitory mechanotransductive response that modulates cardiomyocyte size during both zebrafish cardiogenesis and adult cardiac remodeling.
Antipsychotic drugs: Comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection (Pharmacological Reviews (2002) 60, (358-403))
Authors: J. A. Lieberman, F. P. Bymaster, H. Y. Meltzer, A. Y. Deutch, G. E. Duncan, C. E. Marx, J. R. Aprille, D. S. Dwyer, X. M. Li, S. P. Mahadik, R. S. Duman, J. H. Porter, J. S. Modica-Napolitano, S. S. Newton, J. G. Csernansky
Journal: Pharmacological Reviews (2008)
Predictors of brain relapse in HER-2 positive metastatic breast cancer (MBC) patients (pts)
Authors: R. Duchnowska, B. Czartoryska-Arlukowicz, B. Radecka, B. Szostakiewicz, K. Sosinska, A. Karpinska, R. Dziadziuszko, T. Kubiatowski, E. Staroslawska, C. Szczylik
Journal: Journal of Clinical Oncology (2006)

10508 Background: Brain relapse is a common occurrence in HER2-positive breast cancer pts. We assessed factors determining the risk of this event in a large unselected series of HER2-positive MBC pts. Methods: Study group included 233 consecutive HER2-positive (IH 3+ or FISH+) MBC pts (median age 53 years); 49% premenopausal, 49% postmenopausal and 2% with unknown menopausal status. Dominant site of disease included viscera (78%), soft tissue (11%) and bones (10%). Of the 206 pts (88%) with known steroid receptor status, ER+/PgR+, ER+/PgR-, ER-/PgR+, ER-/PgR- phenotypes included 58%, 15%, 5% and 21% of pts, respectively. Prior (neo)adjuvant chemotherapy, endocrine therapy or a combination thereof was administered in 40%, 6% and 35% of pts, respectively. Disease-free interval to the development of MBC ranged between 0 and 142 months (median 16 months). 184 pts (79%) received trastuzumab for MBC, usually in combination with chemotherapy. Statistical analysis included contingency tables, chi-square test, Kaplan-Meier survival analysis and Cox proportional hazard model. Results: Median follow-up from the development of MBC was 25 months (range 0.5–130 months). 54 pts (23%) developed brain metastases after a median of 13 months (range, 0 to 81 months). Cumulative risk of brain relapse was 11% (95% CI: 7–16%) and 24% (95% CI: 17–32%) at one and two years, respectively. Trastuzumab treatment was associated with insignificantly reduced risk of brain metastases (HR 0.63, 95% CI 0.29–1.39, p = 0.25). In the univariate analysis, premenopausal status was the only significant factor associated with increased risk of brain relapse (HR 2.56, 95% CI 1.28–5.00, p = 0.008). Conclusion: HER-2 positive MBC pts carry high risk of brain relapse, in particular prior to menopause. Protective role of trastuzumab warrants further research. [Table: see text]
Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease
Authors: Stefan Uderhardt, Jochen A. Ackermann, Tobias Fillep, Victoria J. Hammond, Johann Willeit, Peter Santer, Manuel Mayr, Markus Biburger, Meike Miller, Katie R. Zellner, Konstantin Stark, Alexander Zarbock, Jan Rossaint, Irene Schubert, Dirk Mielenz, Barbara Dietel, Dorette Raaz-Schrauder, Cihan Ay, Thomas Gremmel, Johannes Thaler, Christian Heim, Martin Herrmann, Peter W. Collins, Gernot Schabbauer, Nigel Mackman, David Voehringer, Jerry L. Nadler, James J. Lee, Steffen Massberg, Manfred Rauh, Stefan Kiechl, Georg Schett, Valerie B. O’Donnell, Gerhard Krönke
Journal: The Journal of Experimental Medicine (2017)

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase-derived hydroxyeicosatetraenoic acid-phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease.
Estimating the Prevalence of Sexual Minority Adolescents
Authors: Mitchell R. Lunn, Juno Obedin-Maliver, Kirsten Bibbins-Domingo
Journal: JAMA (2017)

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
Low-Intensity Weight-Maintenance Program Keeps Pounds Off
Authors: Anita Slomski
Journal: JAMA (2017)

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 P208: Depletion of Dapper-1 Acts Antihypertrophic on Cardiomyocytes and Inhibits Wnt3a- and Wnt5a-Mediated Activation of the Wnt Signaling Pathway
Authors: Marco Hagenmueller, Hugo A Katus, Stefan E Hardt
Journal: Circulation Research (2011)

Background: Cardiac development is regulated by the evolutionary conserved Wnt signaling pathway. While Wnt activity is silenced in the adult heart under normal conditions this pathway is activated during myocardial remodeling following pathological injury such as myocardial infarction. Among other members of this pathway Dapper-1 was suggested to antagonize Wnt activation but its role in Wnt signaling is poorly understood. In a murine myocardial infarction model as well as in a cardiomyocyte hypoxia model we found a robust over-expression of Dapper-1. To elucidate its function in cardiomyocytes we performed Dapper-1 specific siRNA mediated knockdown experiments. Results: Depletion of Dapper-1 leads to reduction of cardiomyocyte surface area (-10% ± 4%, p&lt;0.001 vs. control), attenuation of global protein content (-20% ± 3%, p&lt;0.02 vs. control) and diminishes global protein synthesis (-27% ± 10%, p&lt;0.02 vs. control). Augmentation of protein synthesis by β-adrenic Isoproterenol stimulation is widely inhibited. Wnt3a induced stimulation of protein synthesis and enlargement of cardiomyocyte surface area is blocked in Dapper-1 knockdown cardiomyocytes. Furthermore, we observed reduced total- and active-β-catenin protein levels. Moreover, Dapper-1 knockdown inhibits β-catenin from translocation to the nucleus following Wnt3a stimulation. TCF/LEF reporter activity was reduced in Dapper-1-diminished -and elevated in Dapper-1-overexpressed cardiomyocytes after Wnt3a treatment. Robust Ser9 -and weak Tyr216 phosphorylation of GSK3β suggested a GSK3β independent inhibition of canonical Wnt signaling. In addition, activation of non-canonical Wnt/JNK pathway by Wnt5a conditioned medium was completely inhibited in Dapper-1 knockdown cells. Summary: Dapper1 is an essential modulator for global protein synthesis. Furthermore, Dapper-1 is required to activate canonical and noncanonical Wnt signaling pathways in cardiomyocytes.
P08.41 The metabolic effect of bevacizumab in mutant IDH1 glioma cells assessed by NMR spectroscopy
Authors: T. Mesti, N. Bouchemal, C. Banissi, M. Triba, C. Marbeuf-Gueye, L. Le Moyec, J. Ocvirk, P. Savarin, A. Carpentier
Journal: Neuro-Oncology (2017)

Introduction: Malignant gliomas are rapidly growing and invasive tumours that secrete vascular endothelial growth factor (VEGF) to stimulate tumour angiogenesis. Bevacizumab by neutralizing the biological activity of VEGF normalizes tumour vasculature, and inhibits further angiogenesis, thereby inhibiting tumour growth. However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Our study was performed to assess the effects of bevacizumab on the metabolism of glioma cells carrying the IDH1 mutation [a mutation associated with better prognosis and treatment outcome]. Material and Methods: The effect of different time exposures (from 24h to 72h) and bevacizumab concentrations (0.1 mg/mL to 1 mg/mL) was assessed with the MTT Assay. VEGF secretion was assessed by immunoassay. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS). Results: mIDH1-U87 cells secrete VEGF (13 ng/mL). Regardless, Bevacizumab had no cytotoxic effect, even after a 72 h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (PUFA, glycerophosphocholine, and phosphocholine). Conclusions: We have identified changes in glutamine group metabolites and lipids as metabolic markers of bevacizumab treatment on mIDH1-U87. Our data support the possibility of a functional tricarboxylic acid cycle in these cells that uses glutamine as an alternative nutrient input (anaplerosis).
Abstract P308: Detection of Transient Regional Myocardial Ischemia with 80-Electrode Body Surface Delta Map and Its Comparison with Myocardial Perfusion Imaging and 12-Lead ECG
Authors: Mehmood Zeb, Florence Garty, Wendy Banister, Nirmala Nagaraj, Nick Curzen
Journal: Circulation Research (2011)

Background The diagnosis of transient regional myocardial ischaemia (TRMI) in patients presenting to the Chest Pain Clinics is a challenge. Traditionally EET has been most commonly employed test for diagnosing TRMI, however due to the limitations of 12-Lead ECG this is no longer recommended. Thus the clinicians have to rely on more expensive and time consuming test including Myocardial Perfusion Imaging (MPI) and Cardiac MRI. Delta Map was described by this group and is an intuitive colour display of digitally subtracted ST segment shift derived from two 80-electrode BSM recordings, one at baseline and one at peak stress. Objectives The purpose of this pilot study was to asses the diagnostic ability of Delta-Map &amp; 12-Lead ECG in detection of TRMI, and to compare the results with MPI. Method Forty consecutive patients who were referred by two consultant cardiologist for MPI with a history of angina-like symptoms were consented and recruited in to this study. The Delta Map was derived from two 80-electrode PRIME BSM carried out simultaneously with MPI at rest and peak stress, using dobutamine.12-Lead ECGs were also recorded at the same time. Results The mean age was 68±7.1, 50% (20/20) were female, 70% (28/40) hyperlipidaemic, 64% (25/40) had history of hypertension and 60% (24/40) were smoker, 27% (11/40) patients had previous PCI. Using MPI as the reference, PRIME Delta Map was more sensitive for the detection of TRMI than the 12-Lead ECG 77% vs. 15%, p 0.0001 and was also more specific for TRMI 96% vs. 84%, p 0.0001. The PPV &amp; NPV for Delta Map was 91% &amp; 89% respectively, where as 33.3% &amp; 66.7% for 12-Lead ECG. Conclusion The PRIME ECG Delta map is a near patient, rapid, accurate, objective and intuitive method for detecting TRMI and is superior to the 12-Lead ECG. The Delta Map could potentially facilitate more rapid identification and appropriate treatment in patients with coronary artery disease. A larger clinical study is now required.