tbuckley/cabot-search huggingface dataset:
Lamin B1 regulates somatic mutations and progression of B-cell malignancies
Authors: T Klymenko, J Bloehdorn, J Bahlo, S Robrecht, G Akylzhanova, K Cox, S Estenfelder, J Wang, J Edelmann, J C Strefford, T K Wojdacz, K Fischer, M Hallek, S Stilgenbauer, M Cragg, J Gribben, A Braun
Journal: Leukemia (2017)

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.
Cancer Self-Defense: An Immune Stealth
Authors: Kosei Nakajima, Pratima Nangia-Makker, Victor Hogan, Avraham Raz
Journal: Cancer Research (2017)

The hurdles in realizing successful cancer immunotherapy stem from the fact that cancer patients are either refractory to immune response and/or develop resistance. Here, we propose that these phenomena are due, in part, to the deployment/secretion of a "decoy flare," for example, anomalous cancer-associated antigens by the tumor cells. The cancer secretome, which resembles the parent cell make-up, is composed of soluble macromolecules (proteins, glycans, lipids, DNAs, RNAs, etc.) and insoluble vesicles (exosomes), thus hindering cancer detection/recognition by immunotherapeutic agents, resulting in a "cancer-stealth" effect. Immunotherapy, or any treatment that relies on antigens' expression/function, could be improved by the understanding of the properties of the cancer secretome, as its clinical evaluation may change the therapeutic landscape. Cancer Res; 77(20); 5441-4. ©2017 AACR.
B cell OX40L supports T follicular helper cell development and contributes to SLE pathogenesis
Authors: Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunninghame Graham, Marina Botto, Timothy James Vyse
Journal: Annals of the Rheumatic Diseases (2017)

TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus.We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity.Physiologically, OX40L on both B and T cells contributed to the humoral immune response, but B cell OX40L supported the secondary humoral response and antibody affinity maturation. Our data also indicated that loss of B cell OX40L impeded the generation of splenic T follicular helper cells. We further show that in two models of SLE-a spontaneous congenic model and the H2-IAbm12 graft-versus-host-induced model-loss of B cell OX40L ameliorates the autoimmune phenotype. This improvement was, in each case, accompanied by a decline in T follicular helper cell numbers. Importantly, the germline knockout did not exhibit a markedly different phenotype from the B cell knockout in these models.These findings contribute to a model in which genetically determined increased OX40L expression promotes human SLE by several mechanisms, contingent on its cellular expression. The improvement in pathology in two models of systemic autoimmunity indicates that OX40L is an excellent therapeutic target in SLE.
Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants
Authors: R Hehlmann, M Lauseker, S Saußele, M Pfirrmann, S Krause, H J Kolb, A Neubauer, D K Hossfeld, C Nerl, A Gratwohl, G M Baerlocher, D Heim, T H Brümmendorf, A Fabarius, C Haferlach, B Schlegelberger, M C Müller, S Jeromin, U Proetel, K Kohlbrenner, A Voskanyan, S Rinaldetti, W Seifarth, B Spieß, L Balleisen, M C Goebeler, M Hänel, A Ho, J Dengler, C Falge, L Kanz, S Kremers, A Burchert, M Kneba, F Stegelmann, C A Köhne, H W Lindemann, C F Waller, M Pfreundschuh, K Spiekermann, W E Berdel, L Müller, M Edinger, J Mayer, D W Beelen, M Bentz, H Link, B Hertenstein, R Fuchs, M Wernli, F Schlegel, R Schlag, M de Wit, L Trümper, H Hebart, M Hahn, J Thomalla, C Scheid, P Schafhausen, W Verbeek, M J Eckart, W Gassmann, A Pezzutto, M Schenk, P Brossart, T Geer, S Bildat, E Schäfer, A Hochhaus, J Hasford
Journal: Leukemia (2017)

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.
Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth
Authors: Marta Canel, Adam Byron, Andrew H. Sims, Jessy Cartier, Hitesh Patel, Margaret C. Frame, Valerie G. Brunton, Bryan Serrels, Alan Serrels
Journal: Cancer Research (2017)

Abstract Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell-cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1-regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through posttranslational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription. Cancer Res; 77(19); 5301–12. ©2017 AACR.
Updated Cost-effectiveness Analysis of PCSK9 Inhibitors Based on the Results of the FOURIER Trial
Authors: Dhruv S. Kazi, Joanne Penko, Pamela G. Coxson, Andrew E. Moran, Daniel A. Ollendorf, Jeffrey A. Tice, Kirsten Bibbins-Domingo
Journal: JAMA (2017)

This study uses the results of the FOURIER trial to assess the current cost-effectiveness of PCSK9 inhibitors over the lifetime analytic horizon for patients with atherosclerotic cardiovascular disease in the United States.
How prostacyclin therapy improves right ventricular function in pulmonary arterial hypertension
Authors: Rebecca R. Vanderpool, Ankit A. Desai, Shannon M. Knapp, Marc A. Simon, Aiden Abidov, Jason X.-J. Yuan, Joe G.N. Garcia, Lillian M. Hansen, Steven R. Knoper, Robert Naeije, Franz P. Rischard
Journal: European Respiratory Journal (2017)

Within recent years, right ventricular (RV) function has been recognised as a major determinant of outcome in pulmonary arterial hypertension (PAH) [1, 2]. Clinical [3] and in vitro experimental [4, 5] data suggest that prostacyclins, the treatment of choice for most severely ill PAH patients [6], might have a positive inotropic effect on RV function, and reduce pulmonary vascular resistance (PVR). Nevertheless, inotropic effects are difficult to demonstrate in vivo , as ventricular contractility adjusts to afterload to preserve ventricular-arterial coupling [7]. In fact, the ratio of ventricular end-systolic elastance (Ees), a measure of in vivo contractility, to pulmonary arterial elastance (Ea) or the "coupling ratio" (Ees/Ea), was restored by epoprostenol in a model of load-induced acute RV failure; however, this was explained by a reduction in afterload [8]. Prostacyclin reduces right ventricular contractility, but improves ejection fraction and exercise capacity in PAH <http://ow.ly/m5S830dpcZv>
血管新生ペプチドナノファイバーを用いた後肢虚血の治療【Powered by NICT】
Authors: A Kumar Vivek, Liu Qi, C Wickremasinghe Navindee, Shi Siyu, T Cornwright Toya, Deng Yuxiao, Azares Alon, N Moore Amanda, M Acevedo-Jake Amanda, R Agudo Noel, Pan Su, G Woodside Darren, Vanderslice Peter, T Willerson James, A Dixon Richard, D Hartgerink Jeffrey
Journal: Biomaterials (2016)
Prenatal stress exposure is associated with increased dyspnoea perception in adulthood
Authors: Andreas von Leupoldt, Eline Mangelschots, Nils Georg Niederstrasser, Marijke Braeken, Thibo Billiet, Bea R.H. Van den Bergh
Journal: European Respiratory Journal (2017)

Dyspnoea is the aversive cardinal symptom in various prevalent conditions such as respiratory, cardiovascular and neuromuscular diseases and is associated with great individual and socioeconomic burden [1]. Over the past years, several physiological and also psychological factors have been demonstrated to affect the perception of dyspnoea [1, 2]. For example, high levels of anxiety in adulthood were associated with increased dyspnoea perception in patients with asthma or chronic obstructive pulmonary disease (COPD), but also in healthy controls [2]. Moreover, adverse, separation-related experiences in childhood were linked to the subsequent development of increased anxiety and dyspnoea [3]. However, the effects of adverse experiences in early, prenatal life on dyspnoea perception remain widely unknown, although prenatal exposure to maternal stress and anxiety has convincingly been related to the development of other health and behavioural problems later in life, including impairments of the respiratory control system and high anxiety levels [4–9]. Therefore, this study investigated the relationship between prenatal exposure to maternal stress and the perception of dyspnoea in adulthood 28 years later. Prenatal exposure to maternal stress is associated with increased perception of dyspnoea in adulthood 28 years later <http://ow.ly/M6EH30d1NEQ>
Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia
Authors: Oliver M. Dovey, Jonathan L. Cooper, Annalisa Mupo, Carolyn S. Grove, Claire Lynn, Nathalie Conte, Robert M. Andrews, Suruchi Pacharne, Konstantinos Tzelepis, M. S. Vijayabaskar, Paul Green, Roland Rad, Mark Arends, Penny Wright, Kosuke Yusa, Allan Bradley, Ignacio Varela, George S. Vassiliou
Journal: Blood (2017)
Peripheral Neuropathy (PN) with Immunomodulatory Drugs in Patients with Multiple Myeloma (MM)
Authors: Melinda Mezo, Carmen Castaneda, Lilia Weiss, Neil Minton, Damien Hirsch, Christine Renz, Uma Arunagiri, Benton Brown, Dominique Gambini, Michael Peng, Zhinuan Yu, Xin Yu, John Freeman
Journal: Blood (2016)
Balancing the Need for Access With the Imperative for Empirical Evidence of Benefit and Risk
Authors: Robert M. Califf
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
Supercritical Fluids: Supercritical Fluid Technology: An Emphasis on Drug Delivery and Related Biomedical Applications (Adv. Healthcare Mater. 16/2017)
Authors: Ranjith Kumar Kankala, Yu Shrike Zhang, Shi‐Bin Wang, Chia‐Hung Lee, Ai‐Zheng Chen
Journal: Advanced Healthcare Materials (2017)

The supercritical fluid technology produces polymeric carriers in various forms in a non-toxic, cost-effective, and environmental-friendly manner. In article number 1700433, Yu Shrike Zhang, Ai-Zheng Chen, and co-workers provide an overview of the history, principle, and preparation methods involving this versatile technology and its use in fabrication of polymeric carriers for applications in biomedicine with a focus on drug delivery.
Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up
Authors: André van der Merwe, Frank Graewe, Alexander Zühlke, Nicola W Barsdorf, Amir D Zarrabi, Jeremy T Viljoen, Hilgard Ackermann, Pieter V Spies, Dedan Opondo, Talal Al-Qaoud, Karla Bezuidenhout, Johan D Nel, Bertha Bailey, M Rafique Moosa
Journal: The Lancet (2017)
PMO-249 Quantitative proteomic analysis of intermediate filament profile in ulcerative colitis reveals increased levels of keratins 8, 18 and 19 in patients with longstanding pan colitis which are reduced with development of dysplasia: Abstract PMO-249 Figure 1
Authors: D Majumdar, B M Corfe, C Evans, A J Lobo
Journal: Gut (2012)

<h3>Introduction</h3> Intermediate filaments (IF), principally keratins (K), are key components of epithelial cytoskeleton. K8, 18 and 19 are expressed in intestinal epithelial cells and play a role in cell-death signalling pathways, in particular apoptosis mediated by tumour necrosis factor-α. Reduced K8 and K20 expression is linked to epithelial-to-mesenchymal transition indicative of increased tumour aggressiveness. We investigated the change in levels of insoluble IF proteins in well-characterised groups of patients at differing risk of UC-associated cancer. <h3>Methods</h3> Rectal biopsies were obtained from patients with inactive UC with: (1) Long-standing (20–40 years) pancolitis (LSPC) (n=10); (2) Recent onset (&lt;5 years) UC (ROUC) (n=8); (3) UC with primary sclerosing cholangitis (PSC) (n=7); (4) pancolitis with dysplasia (n=4) and 10 controls, with additional biopsies from dysplastic/neoplastic lesions and snap frozen. An iTRAQ (isobaric tagging for relative and absolute quantification)-compatible extraction and solubilisation protocol for IF proteins was developed. Labelled peptides from pooled patients were analysed by SCX-LC-MS/MS (strong cation exchange-reverse phase HPLC tandem mass spectrometry) and data reconstituted in GeneBio Phenyx. Inter-group comparisons were made using in-house algorithms based on t-testing with multiple test correction. <h3>Results</h3> Tandem mass spectrometry (MS/MS) identified 52 proteins; 32 (61.5%) were matched by two or more peptides. Abstract PMO-249 figure 1A shows the log fold change in IF levels compared to control, with significant increase in levels of K8, K19 and vimentin in those with LSPC, but marked reduction in IF levels in areas of dysplasia (DT) and rectal mucosa distant from this (DR). Marked increase in levels of keratins was noted in patients with LSPC compared to those with ROUC (Abstract PMO-249 figure 1B), suggesting an effect of disease duration on IF levels. <h3>Conclusion</h3> This is the first study using a quantitative proteomic approach with an iTRAQ based proteomic workflow to analyse changes in IF levels in patients with UC with differing colon cancer risk. LSPC is associated with enhanced mucosal levels of keratins, spectrin and xin, which is reduced in dysplasia and in distant rectal mucosa of those with dysplasia—suggesting a field change. These changes need further characterisation including of post-translational modifications, which may help better understanding of the pathogenesis of colitis associated cancer. <h3>Competing interests</h3> None declared.
Association Between Purpose in Life and Objective Measures of Physical Function in Older Adults
Authors: Eric S. Kim, Ichiro Kawachi, Ying Chen, Laura D. Kubzansky
Journal: JAMA Psychiatry (2017)

Higher purpose in life is hypothesized to reduce the likelihood of developing weak grip strength and slow walking speed because purpose has been linked with a range of positive health behaviors and biological processes that are potentially protective against declining physical function. However, the association between purpose in life and objective physical function has not been examined.To assess whether higher purpose in life among adequately functioning older adults is associated with lower risk of developing weak grip strength and slow walking speed over time.Data for a longitudinal cohort study were collected in 2006 and again in 2010 from the Health and Retirement Study, a nationally representative study of US adults older than 50 years. Data analysis was conducted from November 23, 2016, to June 2, 2017.The risk of developing weak grip strength (assessed as a binary yes or no outcome) or slow walking speed (yes or no) during the 4-year follow-up period. Grip strength was assessed using Smedley spring-type hand dynamometers, and walking speed was assessed by asking respondents to walk 2.5 m at their normal walking pace.In this study, 4486 adults had grip scores at baseline indicating adequate function (2665 women and 1821 men; mean [SD] age, 63.0 [8.2] years) and 1461 adults had walking scores at baseline indicating adequate function (801 women and 660 men; mean [SD] age, 70.8 [6.5] years). After controlling for sociodemographic factors, each 1-SD increase in purpose was associated with a 13% decreased risk (95% CI, 1%-23%) of developing weak grip strength and a 14% decreased risk (95% CI, 8%-20%) of developing slow walking speed. Associations with walking speed were maintained in all covariate models (fully adjusted model: risk ratio, 0.89; 95% CI, 0.83-0.95), but associations with grip strength did not reach conventional levels of statistical significance after additionally adjusting for relevant baseline health factors, depressive symptoms, and health behaviors (fully adjusted model: risk ratio, 0.91; 95% CI, 0.80-1.04).Purpose in life was prospectively associated with a decreased risk of developing weak grip strength and slow walking speed, although the findings were more robust for walking speed than for grip strength. These findings suggest that a sense of purpose in life, a modifiable factor, may play an important role in maintaining physical function among older adults.
Doctor who plagiarised two papers is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2017)

A doctor who tried to submit for publication two research papers written by others has been suspended for 12 months by a medical practitioners tribunal.

Mohammed Shali, who qualified in Mysore (now Mysuru), India, in 1998, sent an email in February 2013 to the editor of the International Journal of Clinical Skills attaching two papers. He named himself as first author of “An Unusual Cause of Dyspnoea—Mural Thrombus” and as coauthor of “An Unusual Cause of Dyspnoea—Atrial Myxoma.”

The first paper had already been published elsewhere under a different title, and Shali had no role in its authorship. He falsely …
心臓弁組織工学におけるマイクロおよびナノ技術【Powered by NICT】
Authors: Hasan Anwarul, Saliba John, Pezeshgi Modarres Hassan, Bakhaty Ahmed, Nasajpour Amir, R K Mofrad Mohammad, Sanati-Nezhad Amir
Journal: Biomaterials (2016)
プラズマ化学酸化されたチタン合金のゲンタマイシン被覆はラットにおけるインプラント関連骨髄炎を予防する【Powered by NICT】
Authors: M Diefenbeck, C Schrader, F Gras, T Mueckley, J Schmidt, S Zankovych, J Bossert, K D Jandt, A Volpel, B W Sigusch, H Schubert, S Bischoff, W Pfister, B Edel, M Faucon, U Finger
Journal: Biomaterials (2016)
Levels of Nrf2 and Keap1 Are Associated with Poor Prognostic Features In Myelodysplastic Syndromes (MDS)
Authors: Francesco Paolo Tambaro, Carlos Vigil, Yumin Hu, Hui Yang, Zhihong Fang, Jack Yu Jia, Hong Zheng, Yue Wei, Hagop Kantarjian, Lucia Altucci, Felicetto Ferrara, Guillermo Garcia-Manero
Journal: Blood (2010)
Pulmonary delivery of liposomal dry powder inhaler formulation for effective treatment of idiopathic pulmonary fibrosis
Authors: S. Chennakesavulu, A. Mishra, A. Sudheer, C. Sowmya, C. Suryaprakash Reddy, E. Bhargav
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide (BUD) and Colchicine (COL) liposomes were prepared by thin layer film hydration method (TFH) using 1,2-Dipalmitoyl-sn-glycero-3- phosphoglycerol sodium (DPPG), Hydrogenated Soyaphosphotidylcholine (HSPC), Soyaphosphatidylcholine (SPC), cholesterol (CHOL) and drug in different weight ratios. The optimum lipid composition for BUD (74.22 ± 0.97%) was DPPG: HSPC: CHOL (4:5:1) and for COL (50.94 ± 2.04%) was DPPG: SPC: CHOL (3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency (97.89 - 98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler (DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2 (86.53 ± 1.9%), Colchicine DPI Formulation C2 (90.54 ± 2.3 %) and BUD and COL DPI Combination M2 (89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal dry powder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at (25 °C ± 2 °C, 60% ± 5% RH) and refrigerated conditions (2 - 8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.