tbuckley/cabot-search huggingface dataset:
Contraception: drive to increase use by women in poorest countries is stalling, report finds
Authors: Sophie Cousins
Journal: BMJ (2018)

A global push to boost the number of women and girls using modern contraception by 2020 in some of the world’s poorest countries is failing, a report has concluded.1

Published by the global partnership Family Planning 2020, the report found that the number of women in 69 of the world’s lowest income countries using modern contraception rose by 46 million in the past six years to reach 317 million. However, to attain the goal of an additional 120 million users by 2020, another 74 million women would have to be reached in the next two years.

“Looking at projected trends, the hill is simply too steep to climb in the two short years remaining in this initiative,” the report …
PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients
Authors: Aung Naing, Jeffrey R. Infante, Kyriakos P. Papadopoulos, Ivan H. Chan, Cong Shen, Navneet P. Ratti, Bianca Rojo, Karen A. Autio, Deborah J. Wong, Manish R. Patel, Patrick A. Ott, Gerald S. Falchook, Shubham Pant, Annie Hung, Kara L. Pekarek, Victoria Wu, Matthew Adamow, Scott McCauley, John B. Mumm, Phillip Wong, Peter Van Vlasselaer, Joseph Leveque, Nizar M. Tannir, Martin Oft
Journal: Cancer Cell (2018)
The role of erythropoietin (EPO) in angiogenesis and tumorigenesis
Authors: Kenneth R. Lamontagne, Jeannene Butler, Ze’ev Gechtman, Jennifer Tullai, Mary Ryan, Linda Jolliffe, Francis Farrell
Journal: Cancer Research (2005)

4670  Angiogenesis is one of the key events deciding on tumour feature and consequently also an important process for anticancer drug development. Despite general validity of environmentally driven angiogenesis model, they are some avascular tissues present in human body, such as cartilage or cornea. These tissues are obviously able to overcome hypoxia and acidosis based proangiogenic stimulation. To prove antiangiogenic features of cartilage we have used the medium conditioned by human primary chondrocytes. We have showed in vitro, that chondrocytes secrete anti-angiogenic compounds able to inhibit proliferation and sprouting of HUVEC cells activated by VEGF or EGF respectively Proliferation activity of HUVEC cells treated with 100 μl cartilage conditioned medium was 80% decreased in comparison with control. This effect is not caused due to dilution of HUVEC medium by “used” cartilage medium, because obvious HUVEC proliferation inhibition was observed also when only 10% of conditioned medium was used. MTT assay showed minimal detrimental effect even using 100% conditional cartilage medium on smooth muscle cells proliferation activity, meaning that medium does not contain general antiproliferation compounds, but antiangiogenic substances specifically inhibiting HUVEC proliferation. The primary chondrocytes in culture quickly loose their phenotype due to dedifferentiation during passaging. Antiangiogenic activity of chondrocytes from third passage is lower that one from first passage. This might indicate, that antiangiogenic effect is specific to chondrocyte phenotype. Anti-angiogenic effect of chondrocyte-conditioned medium, is comparable with effect of anti-angiogenic drug Rapamycin used in its optimal concentration. Antiangiogenic activity of chondrocyte-conditioned medium was demonstrated more directly by inhibition of activated HUVEC spheroid sprouting in collagen matrix after treatment with cartilage conditional medium. Sprouting activated by 25 ng VEGF or 50 ng EGF was clearly inhibited due to treatment with 100 μl of chondrocyte-conditioned medium. Interestingly, medium conditioned by chondrosarcoma cell line SW1363 has contrary proangiogenic effect demonstrated by activation of HUVEC proliferation and sprouting. We have assayed by ELISA, that VEGF content of all chondrocyte conditioned media is very high reaching value 3 ng/ml. Obvious anti-angiogenic effect of chondrocyte conditioned medium is strongly pronounced despite high content of proangiogenic VEGF, what indicates, that chondrocyte antiangiogenic effect is based on active mechanism overcoming strong VEGF based proangiogenic activation. Our experiments clearly show strong antiangiogenic activity of compounds produced specifically by primary chondrocytes missing by chondrosarcoma cells. Corresponding genes will be indentified.
Effect of second-line ramucirumab in east Asian patients with refractory and aggressive disease: Subgroup analysis from REVEL and JVCG trials in non-small cell lung cancer
Authors: K. Yoh, K. Nakagawa, G.-C. Chang, Y. Hosomi, T.-C. Hsia, T. Tamura, R. Cheng, R. Varea, S. Enatsu, A. Hayden Zimmermann, J.-Y. Shih
Journal: Annals of Oncology (2018)
Effects of a Chitosan Oligomer on proliferation and morphology of SKOV-3 cells
Authors: Theresa A. Okeyo-Owuor, Gloria Regisford, Ayana Young, Laura Carson
Journal: Cancer Research (2006)

4947  Chitosan is a derivative of chitin and is known to have immuno-enhancing effects, antitumor activities and increased protective effects against infection caused by certain pathogens. It is a polymer consisting of repeating units with a molecular weight of 348. Chitosan is known to be biodegradeable and non-toxic and is therefore tissue compatible. The objective of this study was to determine the effects of enzymatically degraded chitosan on SK-OV-3 cells, a highly aggressive epithelial ovarian cancer cell line. We hypothesized that the chitosan oligomer will decrease proliferation rate and cause changes in cell morphology. SKOV-3 cells (10,000/ml) were cultured in 25 cm3 flasks, allowed to attach for 24 hours and then treated over a period of four days with 0, 100, 250 and 500 μg/ml of chitosan oligomer(n=3 per treatment). Changes in proliferation and morphology were observed using hematoxin staining and MTT cell proliferation assay at the end of treatment. A significant decrease in proliferation was observed in all the chitosan oligomer treated cells. The decreased rate of proliferation was dose-dependent, with the 500 μg/ml treatment having the greatest decrease in growth relative to control. Differences in morphology were also observed in chitosan-treated cells compared to control. The chitosan treated SKOV-3 cells tended to be lean in shape compared to control. Some cells in the chitosan treatment also lost their adherent qualities and viability. In summary, chitosan treatment decreases SK-OV-3 cell proliferation and causes morphological changes in this cell line and may therefore be a natural alternative treatment for ovarian cancer.
Multicenter validation of the flow measurement of classical monocyte fraction for chronic myelomonocytic leukemia diagnosis
Authors: Sihem Tarfi, Véronique Harrivel, Florent Dumezy, Julien Guy, Mikael Roussel, Aguirre Mimoun, Pierre Fenaux, Nicolas Chapuis, Eric Solary, Dorothée Selimoglu-Buet, Orianne Wagner-Ballon
Journal: Blood Cancer Journal (2018)

Abstract Peripheral blood monocytes include three subsets defined by CD14 and CD16 surface markers. An increase in the CD14 ++ CD16 − classical monocyte fraction ≥ 94% of the total monocytes was proposed to rapidly and efficiently distinguish chronic myelomonocytic leukemia from reactive monocytosis. The robustness of this assay required a multicenter validation. The flow cytometry assay designed to quantify peripheral blood monocyte subsets was implemented by multiple diagnosis laboratories in France. A nationwide survey was performed to evaluate its performance. All the 48 French laboratories answered the questionnaire, revealing that 63% use this assay routinely. Central blind reanalysis of 329 cytometry files collected from five laboratories demonstrated an excellent correlation in classical monocyte fraction measurement (r = 0.93; p &lt; 0.0001). The cutoff value of 94% classical monocytes being the critical readout for diagnosis, we then compared 115 patients with classical monocytes ≥ 94% and 214 patients with a fraction &lt; 94% between initial analysis and reanalysis. An agreement was obtained in 311 files. Finally, an overt diagnosis, available for 86 files, confirmed a good sensitivity (93.6%) and specificity (89.7%). This survey demonstrates the robustness of the flow assay with limited variability of classical monocyte percentage between centers, validates the 94% cutoff value, and confirms its sensitivity and specificity.
Abstract 12836: Low-Intensity Pulsed Ultrasound Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia -Potential Involvement of Mechanotransduction
Authors: Tomohiko Shindo, Kenta Ito, Kenichiro Hanawa, Kentaro Aizawa, Takashi Shiroto, Tsuyoshi Ogata, Kensuke Nishimiya, Yuhi Hasebe, Ryuji Tsuburaya, Satoshi Miyata, Hideyuki Hasegawa, Satoshi Yasuda, Hiroshi Kanai, Hiroaki Shimokawa
Journal: Circulation (2014)

Purpose: Despite recent progress in the management of ischemic heart disease (IHD), the number of patients with severe IHD is increasing. In this study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD and to elucidate the underlying molecular mechanisms for the LIPUS-induced angiogenesis. Methods and Results: We first confirmed that the LIPUS up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle in cultured human vascular endothelial cells (HUVECs). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n=28). The heart was treated with either sham or LIPUS (32-cycle, 20 min) at 3 different short axis levels (n=14 each). Four weeks after the therapy, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P&lt;0.05), whereas it remained unchanged in the control group. Capillary density and regional myocardial blood flow in the ischemic region were also increased in the LIPUS group but not in the control group. The protein expressions of VEGF, eNOS and bFGF in the ischemic area were enhanced in the LIPUS group compared with the control group. To further examine the signaling pathways responsible for the LIPUS-induced angiogenesis, HUVECs were transfected with siRNA or scrambled siRNA of either β1 integrin or caveolin-1. Knockdown of either β1 integrin or caveolin-1 with siRNA suppressed the LIPUS-induced up-regulation of VEGF. siRNA-mediated suppression of either focal adhesion kinase (FAK) or Fyn also inhibited the LIPUS-induced up-regulation of VEGF. Knockdown of these molecules with siRNA was confirmed with real-time PCR. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD and that β1 integrin and caveolin-1 may be involved in underlying molecular mechanisms for the beneficial effects of the LIPUS.
Molecular mechanism of decitabine -induced degradation of DNA methyltransferase 1 (DNMT1) in cancer cells
Authors: Kalpana Ghoshal, Jharna Datta, Sarmila Majumder, Huban Kutay, Samson T. Jacob
Journal: Cancer Research (2004)

1594  Decitabine (5-dAzaC) alone or in combination with inhibitors of histone deacetylases is used as a chemotherapeutic agent against leukemia. It is a well-known irreversible inhibitor of DNA methyltransferases. Once incorporated into the DNA it forms a covalent complex with a serine residue at the active site of DNA methyltransferase resulting in its inactivation. Recently we have shown that treatment of mouse lymphosarcoma cells with 5-dAzaC resulted in the decline of Dnmt1 steady state level (Ghoshal et al. Mol. Cell. Biol. 2002, 22:8302-8319). Later on, studies with different types of cancer cells of human, mouse and rat origin have demonstrated that treatment of cells with decitabine not only inactivates DNMT1 but also facilitates its rapid degradation. This nucleoside analog-induced degradation of DNMT1 occurs in a time and concentration dependent manner. Among different protease inhibitors tested, only MG132 and lactacystin blocked 5-dAzaC-induced degradation of DNMT1, implicating its degradation by the proteasomal pathway. To further confirm this phenomenon, we used a cell line (ts20), a Balbc 3T3-derived cell line harboring a temperature-sensitive mutant of ubiquitin-activating enzyme (E1), the first enzyme of proteasomal pathway. E1 in these cells is active when grown at 31°C but is inactivated when growth temperature is shifted at 39°C. DNMT1 was degraded in a time-dependent manner when cells were treated with decitabine at 31°C. In contrast, the inhibitor-induced degradation was significantly impeded in cells preincubated for 24 hr at 39°C. These results further reinforce the notion that the nucleoside analog facilitates ubiquitination and proteasomal degradation of DNMT1. Analysis of the primary structure of DNMT1 revealed existence of a conserved KEN box, a targeting signal for ubiquitination and subsequent proteasomal degradation. Currently we are exploring the role of KEN box, if any, in 5-AzaC-mediated degradation of DNMT1. (supported, in part, by grants, ES 10874, CA 81024)
Use of Renin Angiotensin System Blockers After Acute Kidney Injury
Authors: Robert J. Alpern, Aldo J. Peixoto
Journal: JAMA Internal Medicine (2018)

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Clinical Outcomes of MDS Patients Who Were Allogeneic Hematopoietic Stem Cell Transplant Candidates but Did Not Proceed with Transplantation
Authors: Rohan Gupta, Ibrahim Aldoss, Dongyun Yang, Sally Mokhtari, Samer K. Khaled, Monzr Al Malki, Amandeep Salhotra, Haris Ali, Ahmed Aribi, Thai Cao, Joycelynne Palmer, Margaret O'Donnell, Auayporn P. Nademanee, Pablo Parker, Stephen J Forman, David S Snyder, Vinod A. Pullarkat, Ketevan Gendzekhadze, Anthony S. Stein, Guido Marcucci, Ryotaro Nakamura
Journal: Blood (2018)
P16INK4a is a tumor autoantigen in HR-HPV induced cancers
Authors: Nicolas A. Wentzensen, Andreas Kaufmann, Miriam Reuschenbach, Michael Linnebacher, Magnus Von Knebel Doeberitz
Journal: Cancer Research (2005)

5140  The cellular tumor suppressor gene p16INK4a is over-expressed in a large number of high-risk human papilloma virus (HR-HPV) induced tumors, especially in cervical cancers. The massive over-expression results from a disrupted feed back mechanism of the Rb/E2F pathway induced by the HPV oncoprotein E7. In contrast, p16INK4a is expressed only in few normal cells, mainly terminally differentiated cells with low antigen presenting capacity. We could show previously, that T-cells from healthy donors can be stimulated to react against p16INK4a peptides presented by HLA-A2 positive cells. To further analyze if p16INK4a acts as a tumor autoantigen in cervical cancer, humoral and cellular immune responses against p16INK4a were monitored in cervical cancer patients. To measure humoral immune responses, sera derived from 70 cervical cancer patients were analyzed by western blotting. Using recombinant p16INK4a protein blotted on nylon membranes, five patients showed clear p16INK4a specific signals that could be blocked by serum pre-incubation with recombinant p16INK4a. For the analysis of cellular immune responses, infiltrating T-cells (TILs) were isolated from ten freshly resected cervical cancers or highly dysplastic lesions (CIN3) and tested for their reactivity against p16INK4a peptides. In two patients, TILs with a significant reactivity against the identical p16INK4a peptide that showed strong stimulation of the healthy donor T-cells were isolated from the respective lesions. These findings indicate that cervical carcinoma patients can develop humoral and cellular immune responses against the cellular tumor suppressor protein p16INK4a. P16INK4a can therefore be added to the group of over-expressed tumor autoantigens (like HER2/neu, hTERT, MUC1) and might be used as a novel target in immunotherapy of HR-HPV induced cancer.
Development of Inhibitors of PIP4K2 As a Treatment for Patients with Hematologic Malignancies
Authors: David L McElligott, Edward Kesicki, Kannan Karukarichi, Hyeseok Shim, Rui Wang, Albert S. Yu, Parisa Zolfaghari, Johan Linstrom, Lars Persson, Andreas Hoglund, Ulrika Ericsson, Lionel Trésaugues, Madeleine Livendahl, Ellen Santangelo, Jenny Viklund, Mariell Pettersson, Horst Wähling, Rickard Forsblom, Fredrik Karlsson, Tobias Ginman, Tiago Braga, Aine Brigette Henley, Antoine Talagas, Fredrik Rahm, Tommy Johansson, Jessica Martinsson, Martin Andersson, Lewis Cantley
Journal: Blood (2018)
Firearms and Dementia
Authors: Alan R. Ertle
Journal: Annals of Internal Medicine (2018)

Letters20 November 2018Firearms and DementiaAlan R. Ertle, MD, MPH, MBAAlan R. Ertle, MD, MPH, MBAEmeritus Enterprises, Bend, Oregon (A.R.E.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0522 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was disappointed that Betz and colleagues (1) did not clarify the actual size of the problem of suicide by firearm in patients with dementia. The authors provide only a theoretical context in stating that the number of patients with dementia is increasing, some of these patients will commit suicide by firearm, and many households have firearms. In 2011, Seyfried and associates (2) described a retrospective analysis of data from the U.S. Department of Veterans Affairs between 2001 and 2005 on 294 952 patients with dementia, 97.2% of whom were male. They found that 241 patients committed suicide, ...References1. Betz ME, McCourt AD, Vernick JS, Ranney ML, Maust DT, Wintemute GJ. Firearms and dementia: clinical considerations. Ann Intern Med. 2018;169:47-9. [PMID: 29801058]. doi:10.7326/M18-0140 LinkGoogle Scholar2. Seyfried LS, Kales HC, Ignacio RV, Conwell Y, Valenstein M. Predictors of suicide in patients with dementia. Alzheimers Dement. 2011;7:567-73. [PMID: 22055973] doi:10.1016/j.jalz.2011.01.006 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Emeritus Enterprises, Bend, Oregon (A.R.E.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0522. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFirearms and Dementia: Clinical Considerations Marian E. Betz , Alexander D. McCourt , Jon S. Vernick , Megan L. Ranney , Donovan T. Maust , and Garen J. Wintemute Firearms and Dementia Marian E. Betz , Alexander D. McCourt , Jon S. Vernick , Megan L. Ranney , and Garen J. Wintemute Metrics 20 November 2018Volume 169, Issue 10Page: 739-740KeywordsAntidepressantsConflicts of interestDementiaDisclosureFirearm injuriesInpatientsRacial and ethnic issuesSuicide ePublished: 20 November 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 17684: A Novel System for the Rapid and Automated Detection of Atrial Fibrillation
Authors: Grant Kruger, Rakesh Latchamsetty, Nicholas B Langhals, Miki Yokokawa, Aman Chugh, Fred Morady, Hakan Oral, Omer Berenfeld
Journal: Circulation (2015)

Introduction: Home telemetry monitoring with accurate automated rhythm classification can have important clinical benefits in the timely diagnosis and appropriate management of patients with atrial fibrillation (AF). We clinically validated a novel personal e-Health device and algorithm developed to distinguish AF from sinus rhythm (SR). Methods: A handheld electrocardiogram (ECG) recording system (Maestro) and signal processing platform were developed. The Maestro provides an LCD interface that continuously shows an ECG, heart rate, and heart rhythm status. Twenty second ECG signals analogous to Lead I were acquired from 66 patients presenting to the arrhythmia clinic at the University of Michigan Hospital either in SR or AF. Electrograms were segmented into non-overlapping 6-second samples and one random segment per patient was selected for analysis by the Maestro system. Simultaneous 5 or 12 lead ECGs were obtained from these patients and 3 expert physicians blinded to the Maestro analysis identified the rhythm as SR or AF. The Maestro system applied several signal conditioning algorithms to each ECG sample. The dimensionless temporal R-R interval variability (VRR) index and spectral frequency dispersion metric (FDM) were computed. Results: The 2-dimensional scatter-gram of the samples demonstrated 2 distinct clusters of VRR and FDM for patients with SR and AF. The VRR index clusters for SR and AF patients were 0.018 ± 0.013 and 0.187 ± 0.073 (mean±std), respectively (p &lt; 0.001). The FDM clusters for SR and AF patients occurred at 10.5 ± 5.916 and 15.892 ± 3.337, respectively (p &lt; 0.001). We developed a Gaussian Mixed Model (GMM) classifier to distinguish between the AF and SR clusters. Only after the GMM classifier was obtained were the Maestro classifications compared to the physicians’ readings. The algorithm correctly categorized AF (N = 46) and SR (N = 20) for all Maestro segments analyzed with 100% specificity and sensitivity. Conclusion: The Maestro handheld telemetry unit utilizes a novel classification algorithm and was demonstrated to acquire and automatically analyze 6-second electrograms for rapid and accurate classification of patients in SR or AF in this initial clinical validation trial.
A powerful sybr® green one-step rt-pcr master mix tool: Power sybr green RNA-to-CTtm 1-step kit
Authors: Tom Xu, Claire Marjoribanks, Chris Trinh, Julie Nguyen
Journal: Cancer Research (2008)

5144   Real-time PCR as a powerful and versatile tool has been widely used in R&D and other practical fields. One-step RT-PCR combines reverse transcription of RNA to cDNA with PCR amplification into a single step operation, and it offers fast turn-around time of results to researchers. Using dsDNA binding dye SYBR Green I as a reporter, with no FRET probe required, SYBR Green PCR has become one of the main chemistries in real-time PCR because it is easy to use, flexible, and inexpensive. However, PCR not only can amplify wanted DNA target but also can amplify non-targeted DNA or generate primer-dimers under certain conditions. Because of this, sometimes the results become ambiguous, especially for SYBR 1-step RT-PCR since SYBR Green can detect any double strand DNA. To overcome this problem, we have developed a new SYBR one-step RT-PCR master mix kit: Power SYBR Green RNA-To-C T  TM  1-Step Kit. This pre-formulated kit contains all of the reagents necessary for performing SYBR Green one-step RT-PCR, including our new high purity hot-start AmpliTaq Gold ®  DNA Polymerase UP (Ultra Pure) and robust reverse transcriptase, ArrayScript. Extensive testing has shown that this kit can deliver highly sensitive and specific quantitation over a wide range of RNA template concentration, detecting as low as a single copy of target gene.