tbuckley/cabot-search huggingface dataset:
<i>BMPR2</i>mutation status influences bronchial vascular changes in pulmonary arterial hypertension
Authors: Maria-Rosa Ghigna, Christophe Guignabert, David Montani, Barbara Girerd, Xavier Jaïs, Laurent Savale, Philippe Hervé, Vincent Thomas de Montpréville, Olaf Mercier, Olivier Sitbon, Florent Soubrier, Elie Fadel, Gérald Simonneau, Marc Humbert, Peter Dorfmüller
Journal: European Respiratory Journal (2016)

The impact of bone morphogenetic protein receptor 2 (BMPR2) gene mutations on vascular remodelling in pulmonary arterial hypertension (PAH) is unknown. We sought to identify a histological profile of BMPR2 mutation carriers.Clinical data and lung histology from 44 PAH patients were subjected to systematic analysis and morphometry.Bronchial artery hypertrophy/dilatation and bronchial angiogenesis, as well as muscular remodelling of septal veins were significantly increased in PAH lungs carrying BMPR2 mutations. We found that patients displaying increased bronchial artery remodelling and bronchial microvessel density, irrespective of the mutation status, were more likely to suffer from severe haemoptysis. History of substantial haemoptysis (>50 mL) was significantly more frequent in BMPR2 mutation carriers. 43.5% of BMPR2 mutation carriers, as opposed to 9.5% of noncarriers, displayed singular large fibrovascular lesions, which appear to be closely related to the systemic lung vasculature.Our analysis provides evidence for the involvement of the pulmonary systemic circulation in BMPR2 mutation-related PAH. We show that BMPR2 mutation carriers are more prone to haemoptysis and that haemoptysis is closely correlated to bronchial arterial remodelling and angiogenesis; in turn, pronounced changes in the systemic vasculature correlate with increased pulmonary venous remodelling, creating a distinctive profile in PAH patients harbouring a BMPR2 mutation.
A Constitutivly Active NFkB Non Canonical Pathway Is Maintained by RelB Repression of TRAF2 to Prevent Autophagy-Mediated Cell Death in Hodgkin Lymphomas
Authors: Stella M. Ranuncolo, Wenming Xiao, George Wright, Mones S Abu-Asab, Stefania Pittaluga, Elaine S. Jaffe, Brian A Lewis
Journal: Blood (2011)
Protection of the Intestinal Epithelium from Conditioning with R-spondin1 Ameliorates Graft-Versus-Host Disease
Authors: Shuichiro Takashima, Kazutoshi Aoyama, Motoko Koyama, Daigo Hashimoto, Takeshi Oshima, Kazuma Tomizuka, Koichi Akashi, Takanori Teshima
Journal: Blood (2008)
Multiple Myeloma (MM) in Young Patients (pts): Clinical Features and Outcome in 259 Patients Younger Than 40 Years in Comparison to 8,296 pts Aged ≥ 40 Years.
Authors: Heinz Ludwig, B. Durie, V. Bolejack, A. Hoering, M. Dimopoulos, R. Kyle, R. Fonseca, M. Beksac, J. San Miguel, J. Crowley, J. Blade, M. Boccadoro, H. Avet Loiseau, G. Morgan, K. Shimizu, C. Shustik, P. Sonneveld, P. Tosi, I. Turesson, J. Westin
Journal: Blood (2005)
Safety and Pharmacokinetics of Ruxolitinib (INC424) in Healthy Japanese Volunteers: Placebo-Controlled, Double-Blind, Dose-Escalation Phase 1 Study
Authors: Yoichiro Ogama, Tomoko Mineyame, Asuka Yamamoto, Naomi Shimada, Taro Amagasaki, Kazuto Natsume
Journal: Blood (2011)
ACE-536, a Modified Type II Activin Receptor Increases Red Blood Cells In Vivo by Promoting Maturation of Late Stage Erythroblasts
Authors: Rajasekhar NVS Suragani, Samuel M. Cadena, Dianne Mitchell, Dianne Sako, Monique Davies, Kathleen Tomkinson, Mathew Devine, Jeff Ucran, Asya Grinberg, Kathryn Underwood, R. Scott Pearsall, Jasbir Seehra, Ravindra Kumar
Journal: Blood (2010)
A Measured Approach to Vena Cava Filter Use—Respect Rather Than Regret
Authors: Michael R. Jaff, John Kaufman
Journal: JAMA Cardiology (2016)

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Preliminary Results of Southwest Oncology Group Study S0106: An International Intergroup Phase 3 Randomized Trial Comparing the Addition of Gemtuzumab Ozogamicin to Standard Induction Therapy Versus Standard Induction Therapy Followed by a Second Randomization to Post-Consolidation Gemtuzumab Ozogamicin Versus No Additional Therapy for Previously Untreated Acute Myeloid Leukemia.
Authors: Stephen Petersdorf, Kenneth Kopecky, Robert K Stuart, Richard A. Larson, Thomas J. Nevill, Leif Stenke, Marilyn L. Slovak, Martin S. Tallman, Cheryl L. Willman, Harry Erba, Frederick R Appelbaum
Journal: Blood (2009)
PTPS-03EPIGENETIC SILENCING OF β-ARRESTIN1 AND ITS INTRAGENIC miR-326 CONTROLS MEDULLOBLASTOMA GROWTH
Authors: Evelina Miele, Angela Mastronuzzi, Francesca del Bufalo, A. Po, S. Valente, Andrea Carai, I Screpanti, Felice Giangaspero, M. Levrero, Franco Locatelli, Elisabetta Ferretti
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB) is the most common malignant brain tumor. It is classified into four subgroups characterized by distinct mutations, deregulation of specific signaling pathways and different clinical outcomes. A series of pathways and epigenetic mechanisms are deregulated across multiple subtypes, thus representing a window of opportunity for the identification of common targets. A common feature is the presence of stem-like cells (SLCs), a fraction of the tumor bulk which retains the ability to sustain tumor growth and may represent the progenitor giving rise to MB. Recent studies have highlighted the crucial role of microRNAs tumor signaling pathway deregulation. We have previously identified microRNAs deregulated MB and showed that miR-326 is strongly downregulated and represses Hedgehog/Gli signaling. Human and murine MB SLCs were derived and cultured as oncospheres. We investigated the expression levels of miR-326 and its host gene β-arrestin1 in MB specimens and in SLC, the role of the two molecules in MB and the regulation of miR-326/ β-arrestin1 transcriptional unit in SLC. A pharmacological approach was utilized to modulate the expression of miR-326/ β-arrestin1 in MB both in vitro and in vivo. We found that miR-326 cooperates with its host gene β-arrestin1 as tumor suppressor, and is lost in both MB and SLC. Such unit suppresses Hedgehog signaling at multiple levels: β-arrestin1 modulates Gli1-K518 acetylation while miR-326 controls Gli2 and Smo, activatory molecules of the pathway. The analysis of the potential mechanisms involved in the downregulation of this transcriptional unit showed that β-arrestin1/miR-326 are silenced through epigenetic mechanisms at histone levels. Indeed, epigenetic drugs are able to reactivate the miR-326/β- arrestin1 expression and suppress MB and SLC growth in vitro and in vivo. Our study reveals a new microRNA/host gene network in MB and proposes miR-326/β-arrestin1 as tumor suppressors for medulloblastoma patients, susceptible to be re-expressed by epigenetic treatments.
TAP- and Proteasome-Dependent Endogenous Antigen Loading of HLA Class II in Leukemic Blasts Introduces a Promising New Target for Generating Leukemia-Specific CD4+ T Cells
Authors: Marvin M. van Luijn, Maaike E. Ressing, Emmanuel J.H.J. Wiertz, Adri Zevenbergen, Martine E.D. Chamuleau, Yuri Souwer, Suzanne Ostrand-Rosenberg, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht, S. Marieke van Ham
Journal: Blood (2008)
Post-Approval U.S. Experience With Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation
Authors: Vivek Y. Reddy, Douglas N. Gibson, Saibal Kar, William O’Neill, Shephal K. Doshi, Rodney P. Horton, Maurice Buchbinder, Nicole T. Gordon, David R. Holmes
Journal: Journal of the American College of Cardiology (2016)

Left atrial appendage closure (LAAC) was approved by the U.S. Food and Drug Administration (FDA) as a stroke prevention alternative to warfarin for patients with nonvalvular atrial fibrillation. However, clinical decision-making is confounded by the fact that although LAAC attenuates the anticoagulant-related lifetime risk of bleeding, implantation is associated with upfront complications. Thus, enthusiasm for LAAC as a treatment option has been appropriately tempered, particularly as the therapy is introduced beyond the clinical trial sites into general clinical practice. This study evaluated the acute procedural performance and complication rates for all cases performed in the United States since FDA approval. In the absence of a formal national clinical registry since regulatory approval in March 2015, we obtained procedural data on implantation procedures. Every LAAC procedure requires the presence of a manufacturer clinical specialist and for procedural parameter and periprocedural complication data to be collected using a standardized process and forms. In 3,822 consecutive cases, implantation was successful in 3,653 (95.6%), with a median procedure time of 50 min (range 10 to 210 min). Implanting physicians performing these procedures (n = 382) included 71% new, nonclinical trial implanters, who performed 50% of the procedures. Procedural complication rates included 39 pericardial tamponades (1.02%) (24 treated percutaneously, 12 surgically, and 3 fatal); 3 procedure-related strokes (0.078%); 9 device embolizations (0.24%) (6 requiring surgical removal); and 3 procedure-related deaths (0.078%). Despite a large fraction of previously inexperienced operators, in the real-world post-FDA approval experience of LAAC, procedural success was high and complication rates were low.
P0684 : Modulation of hepatitis C virus infection through KHSRP-dependent regulation of MIRNA-122 maturation and intracellular RNA degradation
Authors: P. Bruscella, H. Danso, C. Baudesson, T. Durand, H. Colman, M. Ventura, M. Trabucchi, J.-M. Pawlotsky, C. Féray
Journal: Journal of Hepatology (2015)
Eph Receptor Tyrosine Kinases in Tumor Immunity
Authors: Eileen Shiuan, Jin Chen
Journal: Cancer Research (2016)

Abstract The family of Eph receptor tyrosine kinases and their ephrin ligands regulate a diverse array of physiologic processes, such as axonal guidance, bone remodeling, and immune cell development and trafficking. Eph/ephrin interactions have also been implicated in various pathologic processes, including inflammation, cancer, and tumor angiogenesis. Because Eph receptors play prominent roles in both the immune system and cancer, they likely impact the tumor immune microenvironment, an area in which Eph receptors remain understudied. Here, we provide the first comprehensive review of Eph receptors in the context of tumor immunity. With the recent rise of cancer immunotherapies as promising therapeutic interventions, further elucidation of the roles of Eph receptors in the tumor immune microenvironment will be critical for understanding and developing novel targets against tumor immune evasion. Cancer Res; 76(22); 6452–7. ©2016 AACR.
Chronic Graft Vs Host Disease Is The Strongest Predictor Of Outcome After Reduced Intensity Conditioning Stem Cell Transplantation In Chronic Lymphocytic Leukemia and Is Associated With Pretransplant B Cell Characteristics
Authors: Saad Sirop Kenderian, Ruchi G. Sharma, Mrinal M Patnaik, Timothy G. Call, Shahrukh K Hashmi, Neil E. Kay, Wei Ding, Mark R. Litzow, Kari G. Rabe, William Hogan, Tait D. Shanafelt
Journal: Blood (2013)
SPECT/CT’s Advantage for Preoperative Localization of Small Parathyroid Adenomas in Primary Hyperparathyroidism
Authors: Patricia Sandqvist, Inga-Lena Nilsson, Per Grybäck, Alejandro Sanchez-Crespo, Anders Sundin
Journal: Clinical Nuclear Medicine (2016)

The aims of this study were to assess the performance of Tc-sestamibi SPECT/CT, with diagnostic CT quality, compared with SPECT alone for preoperative localization of parathyroid adenomas and to assess the influence of adenoma weight on the correct adenoma lateralization with SPECT/CT and with SPECT alone.Two hundred forty-nine consecutive patients, biochemically diagnosed with primary hyperparathyroidism, were examined with a combined SPECT/CT scanner. Subsequently, 200 patients with confirmed histopathology and biochemical cure after parathyroidectomy were included in this study (16 with multiglandular disease). For each patient, the SPECT-alone data were analyzed first. Thereafter, the CT information was added, and a new evaluation was performed with the combined data. In addition, for each patient, the diagnostic confidence with each method was graded on a scale based on the presence of different image features. The preoperative diagnostic findings were then compared with the surgical and histopathologic reports.The distribution of adenoma weights showed a peak at 210 mg, with a median at 338 mg. The sensitivity and specificity (multiglandular disease included) for correct classification of adenomas were significantly higher for SPECT/CT, 83% and 96%, respectively, than for SPECT alone, 80% and 93% (P < 0.01). Below 210 mg, the differences between SPECT/CT and SPECT alone in accurate adenoma lateralization were more prominent. Sixty-seven percent of all adenomas were graded with the highest confidence score with SPECT/CT compared with 53% with SPECT.SPECT/CT yields fewer false-positive findings than SPECT alone. The advantage of SPECT/CT over SPECT alone was most apparent for correct lateralization of small adenomas (<210 mg).
Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes: A Center for International Blood and Marrow Transplant Registry (CIBMTR®) Study
Authors: Aaron T. Gerds, Matt E. Kalaycio, Kwang Woo Ahn, Zhen-Huan Hu, Edwin P. Alyea, Uday R. Popat, Ronald M. Sobecks, Wael Saber
Journal: Blood (2015)
Survival after T-Cell Replete Haploidentical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor (MUD) Transplant for Lymphoid Malignancies
Authors: Alberto Mussetti, Abraham Sebastian Kanate, Mohamed A Kharfan-Dabaja, Kwang Woo Ahn, Alyssa DiGilio, Stefan O Ciurea, Philippe Armand, Rachel B. Salit, Timothy S. Fenske, Sonali M. Smith, Anna Sureda, Javier Bolanos-Meade, Mehdi Hamadani
Journal: Blood (2015)
Displaced Niche Location and Decreased Quiescence Maintenance of Hematopoietic Stem Cells Due to Dysregulation of Notch Adhesive Interaction with Stromal Environment in Mice with Notch O-Fucosylation Deficiency
Authors: Weihuan Wang, Xiaoran Huang, Jay Myers, Yiwei Wang, Wei Xin, Alex Y Huang, Lan Zhou
Journal: Blood (2012)
Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials
Authors: Giuseppe Gargiulo, Stephan Windecker, Bruno R da Costa, Fausto Feres, Myeong-Ki Hong, Martine Gilard, Hyo-Soo Kim, Antonio Colombo, Deepak L Bhatt, Byeong-Keuk Kim, Marie-Claude Morice, Kyung Woo Park, Alaide Chieffo, Tullio Palmerini, Gregg W Stone, Marco Valgimigli
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes. <b>Design</b>&nbsp;Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes. <b>Data source</b>&nbsp;Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials. <b>Primary outcome</b>&nbsp;Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat. <b>Results</b>&nbsp;Six trials including 11 473 randomised patients were pooled. Of these patients, 3681 (32.1%) had diabetes and 7708 (67.2%) did not (mean age 63.7 (SD 9.9) and 62.8 (SD 10.1), respectively), and in 84 (0.7%) the information was missing. Diabetes was an independent predictor of MACE (hazard ratio 2.30, 95% confidence interval 1.01 to 5.27; P=0.048 At one year follow-up, long term DAPT was not associated with a decreased risk of MACE compared with short term DAPT in patients with (1.05, 0.62 to 1.76; P=0.86) or without (0.97, 0.67 to 1.39; P=0.85) diabetes (P=0.33 for interaction). The risk of myocardial infarction did not differ between the two DAPT regimens (0.95, 0.58 to 1.54; P=0.82; for those with diabetes and 1.15, 0.68 to 1.94; P=0.60; for those without diabetes (P=0.84 for interaction). There was a lower risk of definite/probable stent thrombosis with long term DAPT among patients with (0.26, 0.09 to 0.80; P=0.02) than without (1.42, 0.68 to 2.98; P=0.35) diabetes, with positive interaction testing (P=0.04 for interaction), although the landmark analysis showed a trend towards benefit in both groups. Long term DAPT was associated with higher rates of major or minor bleeding, irrespective of diabetes (P=0.37 for interaction). <b>Conclusions</b>&nbsp;Although the presence of diabetes emerged as an independent predictor of MACE after implantation of a drug eluting stent, compared with short term DAPT, long term DAPT did not reduce the risk of MACE but increased the risk of bleeding among patients with stents with and without diabetes.
Prescription of Prophylactic Antiemetic Drugs for Patients Receiving Chemotherapy With Minimal and Low Emetic Risk
Authors: Ayako Okuyama, Fumiaki Nakamura, Takahiro Higashi
Journal: JAMA Oncology (2016)

The use of antiemetic drugs for patients receiving chemotherapy with low or minimal emetic risk has been recognized as a growing concern for health care costs and patients' welfare. Relatively few studies have examined antiemetic prophylaxis or treatment of emesis associated with chemotherapy with lower emetic risk.To describe the pattern in Japan of overprescribing prophylactic antiemetic drugs to patients who have received intravenous chemotherapy with minimal or low emetic risk.This secondary analysis of a health insurance claims database linked with the hospital-based cancer registry of 122 designated cancer care hospitals covered the period from September 1, 2010, to December 31, 2012. Data were included from patients who (1) were diagnosed with breast, lung, colorectal, stomach, cervical, or prostate cancer; (2) were 20 years or older at the time of the diagnosis; and (3) received intravenous chemotherapy with minimal or low emetic risk. The data from patients with advanced stage cancer (stage IV) were excluded. Data were analyzed from March 20, 2014, to June 30, 2016.The percentage of chemotherapy administration involving patients prescribed prophylactic antiemetic drugs, namely, a neurokinin 1 receptor antagonist, serotonin receptor antagonist, and/or dexamethasone, was calculated. The costs of potentially unnecessary antiemetic drugs were estimated using the National Health Insurance drug price list for 2011.A total of 8545 patients (5886 women [68.9%] and 2659 men [31.1%]; mean [SD] age, 61.9 [12.8] years) undergoing 73 577 administrations of chemotherapy with minimal emetic risk (2464 patients; 22 619 administrations) or low emetic risk (6081 patients; 50 958 administrations) were identified. Of these, patients who received 24 373 administrations of chemotherapy with a low emetic risk (47.8%) and 633 administrations of chemotherapy with a minimal emetic risk (2.8%) were prescribed serotonin receptor antagonists and dexamethasone. Outpatients in the low emetic risk group underwent more frequent administration of chemotherapy that included prescription of both drugs (53.1% of the chemotherapy; 95% CI, 51.6%-54.7%) compared with inpatients (33.7% of the chemotherapy; 95% CI, 31.7%-35.9%). Consequently, approximately ¥170 million (US $1.6 million) was unnecessarily spent on prophylactic antiemetic drugs for these patients.A substantial number of patients receiving chemotherapy with minimal and low emetic risk were prescribed potentially unnecessary prophylactic antiemetic drugs. The judicious use of these drugs could spare the burden of extra costs and the potential risk for adverse effects for patients.
Insulin-Like Growth Factor 1 Receptor-Dependent Pathway Drives Epicardial Adipose Tissue Formation After Myocardial Injury
Authors: Lior Zangi, Marcela S. Oliveira, Lillian Y. Ye, Qing Ma, Nishat Sultana, Yoav Hadas, Elena Chepurko, Daniela Später, Bin Zhou, Wei Leong Chew, Wataru Ebina, Maryline Abrial, Qing-Dong Wang, William T. Pu, Kenneth R. Chien
Journal: Circulation (2016)

Epicardial adipose tissue volume and coronary artery disease are strongly associated, even after accounting for overall body mass. Despite its pathophysiological significance, the origin and paracrine signaling pathways that regulate epicardial adipose tissue's formation and expansion are unclear.We used a novel modified mRNA-based screening approach to probe the effect of individual paracrine factors on epicardial progenitors in the adult heart.Using 2 independent lineage-tracing strategies in murine models, we show that cells originating from the Wt1+ mesothelial lineage, which includes epicardial cells, differentiate into epicardial adipose tissue after myocardial infarction. This differentiation process required Wt1 expression in this lineage and was stimulated by insulin-like growth factor 1 receptor (IGF1R) activation. IGF1R inhibition within this lineage significantly reduced its adipogenic differentiation in the context of exogenous, IGF1-modified mRNA stimulation. Moreover, IGF1R inhibition significantly reduced Wt1 lineage cell differentiation into adipocytes after myocardial infarction.Our results establish IGF1R signaling as a key pathway that governs epicardial adipose tissue formation in the context of myocardial injury by redirecting the fate of Wt1+ lineage cells. Our study also demonstrates the power of modified mRNA -based paracrine factor library screening to dissect signaling pathways that govern progenitor cell activity in homeostasis and disease.
Transferrin-inspired vehicles based on pH-responsive coordination bond to combat multidrug-resistant breast cancer
Authors: Yu-Jing He, Lei Xing, Peng-Fei Cui, Jia-Liang Zhang, Yong Zhu, Jian-Bin Qiao, Jin-Yuan Lyu, Mei Zhang, Cheng-Qiong Luo, Yu-Xin Zhou, Na Lu, Hu-Lin Jiang
Journal: Biomaterials (2016)
Michael Sweet-Escott
Authors: Karen Escott
Journal: BMJ (2016)

Michael Sweet-Escott, the eldest of the three sons of Will and Olive, was born in Lyme Regis, Dorset. He was educated at Westminster School, where he was a scholar, specialising in classics at school and winning a scholarship to Christ Church College, Oxford, in 1941, where he gained a first in part 1 of a degree in classics.

He joined the Royal Air Force in August 1942, and trained in Canada as a pilot, qualifying in 1943. He then did further training as a specialist navigator and taught navigation for 18 months. In early 1945 he was posted to an operational training unit on mosquitoes in eastern Canada, narrowly surviving a dramatic episode in which he crash landed with an engine on fire and had to be cut …