tbuckley/cabot-search huggingface dataset:
Bioequivalence of twice-daily oral tacrolimus in transplant recipients: More evidence for consensus?
Authors: Simon Ball
Journal: PLoS Medicine (2017)

In many healthcare systems, the high cost of long-term immunosuppression is borne by the transplant recipient.Even in the world's wealthiest economies the annual cost of an individual's immunosuppression is a significant proportion of median income.This can contribute to nonadherence with the prescribed immunosuppressive regime and therefore economically driven health inequality, even in the most highly developed healthcare systems [1].In developing countries, access to immunosuppression not only affects outcome but also the very opportunity to undergo transplantation [2].The careful use of cheaper, generic formulations of immunosuppression therefore has the potential to significantly benefit healthcare systems by reducing the long-term cost of immunosuppression and improve patient-level outcomes by promoting long-term adherence and access to transplantation.In this issue of PLOS Medicine, Alloway and colleagues have addressed an important question regarding the bioequivalence of different formulations of tacrolimus in transplant recipients.Bioequivalence is a prerequisite for the extrapolation of clinical outcome study results using the originator's formulation to the use of generic formulations [3].The calcineurin inhibitor tacrolimus was approved by the United States Food and Drug Administration (FDA) for immunosuppression of liver transplant recipients in 1994 and kidney transplant recipients in 1997.By 2007, it was administered to more than 80% of kidney transplant recipients in the US Renal Data System.In that year the ELiTE-SYMPHONY study was published comparing 4 different immunosuppressive regimes in kidney transplantation [4].Its findings contributed to FDA approval in 2009 for the combined use of mycophenolate mofetil and tacrolimus, which has become the standard of therapy for kidney transplantation in many healthcare systems.In that year, the first generic formulation of tacrolimus became available, and there are currently 6 products approved by the FDA.Tacrolimus has a narrow therapeutic index and is subject to routine therapeutic drug monitoring and dose adjustment.High peripheral blood concentrations of tacrolimus are associated with the nonspecific consequences of over-immunosuppression and specific effects of calcineurin inhibition, notably nephrotoxicity, neurotoxicity, and thrombotic microangiopathy.Low peripheral blood concentrations of tacrolimus are associated with acute rejection.In kidney transplant recipients, there is also evidence that high within-patient variability in trough tacrolimus concentration is associated with adverse outcomes, including acute rejection, chronic antibody mediated rejection, and ultimately allograft failure [5].This association may in part be consequent upon nonadherence with the prescribed immunosuppression regime, but other contributory factors are also likely to be important [6].
Long-Term Structural Integrity and Durability of the Medtronic CoreValve System After Transcatheter Aortic Valve Replacement
Authors: Nahid El Faquir, Ben Ren, Marguerite Faure, Marjo de Ronde, Patrick Geeve, Anne-Marie Maugenest, Isabella Kardys, Marcel L. Geleijnse, Peter P. de Jaegere, Ricardo P.J. Budde, Nicolas M. Van Mieghem
Journal: JACC. Cardiovascular imaging (2017)
Simulation Models of Therapy Intensification in Lipid-Lowering Medicine—Reply
Authors: Christopher Cannon, Irfan Khan, Robert Sanchez
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is Independent of BRCA Status in Triple-Negative Breast Cancer
Authors: Jason. P.W. Carey, Cansu Karakas, Tuyen Bui, Xian Chen, Smruthi Vijayaraghavan, Yang Zhao, Jing Wang, Keith Mikule, Jennifer K. Litton, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2017)

Abstract PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several of those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are associated with worse overall survival. Combining MYC blockade with PARPi yielded synthetic lethality in MYC-driven TNBC cells. Using the cyclin-dependent kinase inhibitor dinaciclib, which downregulates MYC expression, we found that combination with the PARPi niraparib increased DNA damage and downregulated homologous recombination, leading to subsequent downregulation of the epithelial–mesenchymal transition and cancer stem-like cell phenotypes. Notably, dinaciclib resensitized TBNC cells, which had acquired resistance to niraparib. We found that the synthetic lethal strategy employing dinaciclib and niraparib was also highly efficacious in ovarian, prostate, pancreatic, colon, and lung cancer cells. Taken together, our results show how blunting MYC oncogene addiction can leverage cancer cell sensitivity to PARPi, facilitating the clinical use of c-myc as a predictive biomarker for this treatment. Significance: Dual targeting of MYC-regulated homologous recombination and PARP-mediated DNA repair yields potent synthetic lethality in triple-negative breast tumors and other aggressive tumors characterized by MYC overexpression. Cancer Res; 78(3); 742–57. ©2017 AACR.
Topical Tacalcitol for Family Occurrence of Follicular Keratosis of the Chin
Authors: Aline Aniela Buechner, Martin Theiler, Barbara Krayenbuehl, Lisa Weibel
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
PTBP3-Mediated Regulation of ZEB1 mRNA Stability Promotes Epithelial–Mesenchymal Transition in Breast Cancer
Authors: Pingfu Hou, Lin Li, Fang Chen, Yansu Chen, Hui Liu, Jingjing Li, Jin Bai, Junnian Zheng
Journal: Cancer Research (2017)

The RNA polypyrimidine tract-binding protein PTBP3 is a little studied paralog of PTBP1, which has oncogenic properties. In this study, we demonstrate that PTBP3 induces epithelial-mesenchymal transition (EMT) in breast tumor cells and promotes their invasive growth and metastasis. Elevated expression of PTBP3 associated significantly with lymph node metastasis, advanced histology grade, TNM stage, and poor 5-year overall survival of patients. In human mammary epithelial cells, PTBP3 overexpression was sufficient to induce EMT and to enhance cell migration, invasion, and cancer stem-like cell properties. PTBP3 regulated expression of the EMT regulatory transcription factor ZEB1 by binding the 3'UTR of its mRNA, thereby preventing its degradation. Conversely, ZEB1 ablation blocked the ability of PTBP3 to induce EMT. Overall, our findings define PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they establish an oncogenic function of PTBP3, suggesting its candidacy as a theranostic target.Significance: These findings define PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they establish an oncogenic function of PTBP3, suggesting its candidacy as a theranostic target. Cancer Res; 78(2); 387-98. ©2017 AACR.
The Impact of the CD9 Tetraspanin on Lentivirus Infectivity and Exosome Secretion
Authors: Kai O. Böker, Nicolas Lemus-Diaz, Rafael Rinaldi Ferreira, Lara Schiller, Stefan Schneider, Jens Gruber
Journal: Molecular Therapy (2017)

Efficient transduction tools are a hallmark for both research and therapy development. Here, we introduce new insights into the generation of lentiviral vectors with improved performance by utilizing producer cells with increased production rates of extracellular vesicles through CD9 overexpression. Most human cells secrete small vesicles from their surface (microvesicles) or intraluminal endosome-derived membranes (exosomes). In particular, enhanced levels of the tetraspanin CD9 result in significantly increased numbers of extracellular vesicles with exosome-like features that were secreted from four different human cell lines. Intriguingly, exosomes and their biogenesis route display similarities to lentivirus and we examined the impact of CD9 expression on release and infectivity of recombinant lentiviral vectors. Although the titers of released viral particles were not increased upon production in high CD9 cells, we observed improved performance in terms of both speed and efficiency of lentiviral gene delivery into numerous human cell lines, including HEK293, HeLa, SH-SY5Y, as well as B and T lymphocytes. Here, we demonstrate that enhanced CD9 enables lentiviral transduction in the absence of any pseudotyping viral glycoprotein or fusogenic molecule. Our findings indicate an important role of CD9 for lentiviral vector and exosome biogenesis and point out a remarkable function of this tetraspanin in membrane fusion, viral infectivity, and exosome-mediated horizontal information transfer.
P2.07-025 Increased Antitumor Response to Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non-Small Cell Lung Cancer
Authors: S.E. Park, Y. Kim, H.K. Kim, H. Lee, J.H. Cho, S.W. Lim, S. Lee, J.S. Ahn, K. Park, M. Ahn, J. Sun
Journal: Journal of Thoracic Oncology (2017)
Enhanced Bordetella pertussis acquisition rate in adolescents during the 2012 epidemic in the Netherlands and evidence for prolonged antibody persistence after infection
Authors: Saskia van der Lee, Susanne P. Stoof, Mariette B. van Ravenhorst, Pieter G.M. van Gageldonk, Nicoline A.T. van der Maas, Elisabeth A.M. Sanders, Anne-Marie Buisman, Guy A.M. Berbers
Journal: Eurosurveillance (2017)

IntroductionIn 2012 a large epidemic of pertussis occurred in the Netherlands. We assessed pertussis toxin (PT) antibody levels in longitudinal serum samples from Dutch 10-18 year-olds, encompassing the epidemic, to investigate pertussis infection incidence. Methods: Blood was sampled in October 2011 (n = 239 adolescents), then 1 year (2012; n = 228) and 3 years (2014; n = 167) later. PT-IgG concentrations were measured by immunoassay and concentrations ≥50 IU/mL (seropositive) assumed indicative of an infection within the preceding year. Results: During the 2012 epidemic, 10% of participants became seropositive, while this was just 3% after the epidemic. The pertussis acquisition rate proved to be sixfold higher during the epidemic (97 per 1,000 person-years) compared with 2012-2014 (16 per 1,000 person-years). In 2012, pertussis notifications among adolescents nationwide were 228/100,000 (0.23%), which is at least 40 times lower than the seropositivity percentage. Remarkably, 17 of the 22 seropositive participants in 2011, were still seropositive in 2012 and nine remained seropositive for at least 3 years. Discussion: Longitudinal studies allow a better estimation of pertussis infections in the population. A PT-IgG concentration ≥50 IU/mL as indication of recent infection may overestimate these numbers in cross-sectional serosurveillance and should be used carefully.
P2.06-009 Trace Elements Affect Lung Cancer Subtypes
Authors: R. Chiba, N. Morikawa, K. Sera, S. Moriguchi, H. Saito, W. Shigeeda, H. Deguchi, M. Tomoyasu, T. Tanita, K. Ishida, T. Sugai, K. Yamauchi, M. Maemondo
Journal: Journal of Thoracic Oncology (2017)
C末端エンドセリン1前駆体断片(CT-proET-1)は心血管疾患の血液透析患者において心機能不全を反映する
Authors: Yoshihara Fumiki, Ernst Andrea, G Morgenthaler Nils, Horio Takeshi, Nakamura Satoko, Bergmann Andreas, Kangawa Kenji, Kawano Yuhei
Journal: Circulation (2009)
Outcomes of an innovative six-week standardized residential training course for physicians and nurses to provide primary palliative care in India.
Authors: Suresh Reddy, Nandini Vallath, Mona Gupta, Manoj Gujela, Sarath Mohan, Navami Naik, Sriram Yennu, Eduardo Bruera, M.R Rajagopal
Journal: Journal of Clinical Oncology (2017)

160 Background: The National Program on Palliative Care (NPPC) by the Government of India has emphasized the need for training clinicians in providing palliative care (PC) with minimum of 6 weeks of residential training. However, there are limited studies on feasibility of such standardized training in PC offered to palliative care providers interested in transition to palliative care. Aim: To evaluate the feasibility, and change in the self-reported perception of knowledge in palliative care following a 6 weeks standardized residential training course (SRTC) for physicians and nurses to provide primary PC in India. Methods: A 6 week standardized residential type educational program which combined didactics, and bedside hands on palliative care training by PC specialists in five preselected centers in India. To be eligible licensed physicians and nurses should, (a) qualify in focused interview aimed to evaluate both interest and commitment to provide primary palliative care following the training, (b) Agree to complete all the required surveys. Results: 46/53 (86%) completed the pre and post surveys. 50/53 (94%) participants completed the course and passed the certification exam. Median age (IQR) was 31 (27, 41). 53% were female and 53% were physicians. Median reported knowledge (1-5) for pain, fatigue, delirium, medical ethics were 4,3,2,2.5 before training Vs 5 (P=0.001), 5 (P=0.001), 5 (P=0.001), 5 (P=0.001) after training respectively. All other core areas improved significantly. All participants noted satisfaction with faculty as high (5/5). Conclusions: Conducting a six weeks standardized residential training course in PC for physicians and nurses in India is feasible. There was a significant improvement in self-reported knowledge of all components of palliative care curriculum. Long term impact studies are needed.
Decompression surgery fails to relieve shoulder impingement in trial
Authors: Susan Mayor
Journal: BMJ (2017)

Decompression surgery does not significantly reduce symptoms in patients with subacromial shoulder pain, show the results of a randomised trial to assess this common surgical procedure.1

“Our findings call into question the value of shoulder decompression surgery for this group of patients and should be communicated to patients and doctors considering this type of surgery,” said David Beard, co-chief investigator of the trial, from the University of Oxford. “In light of our results, other ways to treat shoulder impingement could be considered, such as painkillers, physiotherapy, and steroid injections.”

Shoulder pain accounts for more than 2% of …
Abstract 19850: Elevated Exercise Blood Pressure in Middle Aged Women Identifies Features of Stage A Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Satyam Sarma, Justin Lawley, Erin J Howden, William K Cornwell, Mitchel Samels, Braden Everding, Sheryl Livingston, Dean Palmer, Jarett Berry, Benjamin D Levine
Journal: Circulation (2015)

Introduction: Elevated systolic blood pressure (SBP) during exercise is associated with abnormal vascular function and left ventricular (LV) hypertrophy. While women have lower exercise BP compared to men, few studies have explored the underlying sex differences associated with exercise BP response. We hypothesized women who generated higher exercise SBP would be more likely than men to have abnormal measures of cardiac and vascular stiffness as well as lower aerobic fitness, features associated with stage A HFpEF. Methods: We studied 85 (45% male) healthy normotensive middle aged subjects (53 ± 5 yrs). VO2 (Douglas bags) and BP (ECG gated electrosphygmomanometry) were measured at rest and maximal exercise. Resting cardiac function was assessed using echo (2D, 3D) and invasive measurement (right heart catheterization) of LV filling pressure under varying preloads. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve. Aortic pulse wave velocity (PWV) and central aortic pressure were measured by arterial tonometry. Two factor ANCOVA was used to determine interaction between men and women using SBP as the independent variable. Results: In men, low fitness (peak VO2) was the best predictor of elevated exercise SBP. (R2 0.24) Similarly for women, fitness was predictive of exercise SBP in addition to vascular stiffness (PWV). (R2 0.55) When compared to men, women with elevated exercise SBP were distinctly more likely to have higher LV and vascular stiffness, impaired LV relaxation (IVRT; isovolumic relaxation time) as well as higher body fat percentage. (Table) Conclusions: In otherwise healthy middle aged women, elevated exercise BP was associated with increased LV and vascular stiffness, impaired LV relaxation and higher body fat, pre-clinical features consistent with stage A HFpEF. These relationships were not seen in men. Elevated exercise SBP in middle aged women may help identify a vulnerable population at risk for future HFpEF.
Abstract 13597: Gender Difference in Left Atrial Electroanatomical Remodeling and Hemodynamic Association With Left Atrial Pulse Pressure in Patients With Paroxysmal Atrial Fibrillation
Authors: Junbeom Park, Tae-Hoon Kim, Ki-Woon Kang, Jin-Kyu Park, Nam Kyun Kim, Jae-Sun Uhm, Chi Young Shim, Jong-Young Kim, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2013)

Background:  We previously reported that female patients with atrial fibrillation (AF) have more advanced electroanatomical remodeling of left atrium (LA) and elevated left ventricular (LV) filling pressure (E/Em). Stiff LA physiology has been known to be proportional to LA pulse pressure (LApp). We hypothesized that gender difference in LA remodeling has hemodynamic linkage to stiff LA physiology in patients with AF.   Methods:  We included 180 women (60±10 years, 68% paroxysmal AF [PAF]) and 180 age-AF type matched men who underwent radiofrequency catheter ablation (RFCA). LApp was measured at the beginning of procedure in sinus rhythm, and defined as LA peak pressure (v-wave) minus LA nadir pressure (y-descent). We compared LApp with clinical findings, clinical outcome, and characteristics of electroanatomical remodeling (Echo, CT, NavX) depending on gender.   Results:  1. In patients with PAF, female had greater E/Em (11.7±4.9 vs. 9.3±3.1, p 2 , p 2  vs. 72.2±20.8ml/m 2 , p   Conclusion:  Stiff LA physiology, represented by elevated LApp, is more significant in female patients with PAF. However, this gender difference in LA remodeling disappeared in PeAF.
Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation
Authors: Antonio Galleu, Yanira Riffo-Vasquez, Cristina Trento, Cara Lomas, Luigi Dolcetti, Tik Shing Cheung, Malte von Bonin, Laura Barbieri, Krishma Halai, Sophie Ward, Ling Weng, Ronjon Chakraverty, Giovanna Lombardi, Fiona M. Watt, Kim Orchard, David I. Marks, Jane Apperley, Martin Bornhauser, Henning Walczak, Clare Bennett, Francesco Dazzi
Journal: Science Translational Medicine (2017)

The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression. When examining patients with GvHD who received MSCs, we found a striking parallel, whereby only those with high cytotoxic activity against MSCs responded to MSC infusion, whereas those with low activity did not. The need for recipient cytotoxic cell activity could be replaced by the infusion of apoptotic MSCs generated ex vivo. After infusion, recipient phagocytes engulf apoptotic MSCs and produce indoleamine 2,3-dioxygenase, which is ultimately necessary for effecting immunosuppression. Therefore, we propose the innovative concept that patients should be stratified for MSC treatment according to their ability to kill MSCs or that all patients could be treated with ex vivo apoptotic MSCs.
Carne picada de vacuno y salmonelosis en el hombre: resumen de las investigaciones de tres brotes ocurridos en Francia
Authors: S Haeghebaert, L Duché, C Gilles, B Masini, M Dubreuil, J C Minet, P Bouvet, F Grimont, E Delarocque Astagneau, V Vaillant
Journal: Eurosurveillance (2001)

La sintesis de las investigaciones de tres brotes de salmonelosis ocurridos en Francia entre 1998 y 2000 confirma la implicacion del consumo de carne picada de vacuno, y subraya la importancia de las medidas de prevencion.