tbuckley/cabot-search huggingface dataset:
Genome-wide analysis of genomic imbalances in intracranial ependymomas
Authors: Piergiorgio Modena, Joris Weltman, Elena Lualdi, Federica Facchinetti, Irene Janssen, Lisenka Wissers, Felice Giangaspero, Marco Forni, Gaetano Finocchiaro, Riccardo Riccardi, Franca Fossati Bellani, Maura Massimino, Eric Schoenmakers, Gabriella Sozzi
Journal: Cancer Research (2004)

1671  Ependymoma is a rare glial neoplasm that accounts for approximately 10% of brain tumors in childhood. This tumor is frequent in young children, and half of the cases occur before age 5. In contrast to adult ependymomas, that are located mostly in the spinal cord and display frequent NF2 mutations, pediatric ependymomas are 90% intracranial and do not display NF2 mutations. The most frequently rearranged chromosomal regions identified by either cytogenetic or molecular approaches are 1q, 6q, 16, 17p, 22q. The chromosomal region 22q is the most frequently lost in intracranial cases, but the involvement of known tumor suppressors located in 22q has been already investigated and excluded. So far, few molecular studies have analyzed the genetic alterations of intracranial ependymomas, and were unable to refine sufficiently the chromosomal regions rearranged in order to identify the genes involved. Diagnosis and treatment of the Italian patients follows uniform criteria established by a national protocol, providing a homogeneous sample of patients informative for correlation between genetic alterations and clinical parameters. Our aim is to analyse retrospectically and prospectically the Italian cases by microarray-based Comparative Genomic Hybridization (array-CGH), and preliminary results obtained so far will be presented. We analysed 22 paediatric intracranial ependymoma cases by array-CGH at 1 Mb resolution. This technique allows the detection of genomic imbalances at higher resolution compared to traditional CGH by substituting chromosome preparations with well-defined genomic DNA fragments arrayed on glass slides, as hybridization targets. We detected frequent regions of loss on chromosomes 6q, 9, 16q, 17p, 22 and regions of gain on chromosomes 1q, 11q, 7 and 20. We confirmed array-CGH results by either loss of heterozigosity or interphase-FISH analyses. Several tumors showed evidence of genetic heterogeneity by array-CGH analysis, and this phenomenon was clearly confirmed by FISH experiments, demonstrating the high sensitivity of array-CGH procedure. Investigation of the minimally involved chromosomal regions and of association between genetic profiles and clinical parameters will be presented.
Clinical competence in elective direct current (DC) cardioversion
Authors: Peter M. Yurchak, None Task Force Member, Sankey V. Williams, James L. Achord, William A. Reynolds, Charles Fisch, Gottlieb C. Friesinger, Francis J. Klocke, Masood Akhtar, Thomas J. Ryan, Robert C. Schlant
Journal: Journal of the American College of Cardiology (1993)
Government abandons plans to allow trusts to use “safe spaces” to investigate safety breaches
Authors: Clare Dyer
Journal: BMJ (2018)

The UK government has dropped controversial plans to accredit NHS trusts in England to conduct their own safety investigations under rules which prohibit sharing information with patients who have experienced harm or their families.

The Department of Health and Social Care revealed the change of plan in its response to the report of the joint committee of parliamentarians …
P050 Long-Term Survival of Stage IIIA-N2 NSCLC Patients with Interstitial Lung Diseases
Authors: J. Watanabe, H. Horinouchi, Y. Shinno, S. Murakami, Y. Goto, S. Kanda, Y. Fujiwara, N. Yamamoto, Y. Nakamura, S. Watanabe, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
T cell therapy with EBV-specific cytotoxic T-lymphocytes for patients with nasopharyngeal carcinoma
Authors: P. Pedrazzoli, P. Comoli, S. Secondino, A. Gurrado, A. Pagani, M. Zecca
Journal: Annals of Oncology (2018)

Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related, highly chemo-radiosensitive malignancy. However, one-third of patients are considered to be incurable because of metastatic or recurrence disease. Expression of antigenic viral proteins by malignant cells constitutes a good target for immunotherapeutic strategies. Although the majority of clinical data have been obtained in the setting of EBV-related posttransplant lymphoproliferative disorders, this therapeutic approach has been more recently applied to solid tumors. Methods: We and others have implemented T-cell therapy programs for patients with NPC failing conventional treatment. The feasibility of expanding EBV-targeted cytotoxic T lymphocytes (CTL) by stimulation with EBV-transformed lymphoblastoid cell lines (LCLs) has been demonstrated, and clinical trials were conducted, based on administration of 2 or more doses of EBV-CTLs (4-40 x 107/dose), supported by in vivo rhIL-2 infusion and, in some cases, pre-treatment with lymphodepleting chemo or immunotherapy. Results: So far, more than 60 patients were treated in different centers for refractory/relapsed advanced NPC, and about 20% objective responses, including some complete responses, were observed, with no or limited adverse events. These results are encouraging, although further improvements to the laboratory and clinical protocols are clearly necessary to increase anti-cancer activity. One approach that our center has lately pursued is to test the efficacy of CTL therapy in earlier stages of disease, in particular immediately after first line chemotherapy for relapsed disease. The clinical results of this attempt seem to improve overall survival as compared with conventional therapies, and justify a prospective trial in this specific setting. Conclusions: EBV-specific CTL therapy is safe and associated with clinical benefit in patients with refractory or metastatic NPC. Sequential combination of CTL therapy with other agents, such as checkpoint inhibitors, could yield optimal results. Legal entity responsible for the study: Paolo Pedrazzoli. Funding: Fondazione IRCCS Policlinico San Matteo. Disclosure: All authors have declared no conflicts of interest.
OA13 High-dose Icotinib in Advanced NSCLC with EGFR 21 L858R Mutation: A Randomized, Open-Label Phase II Study
Authors: X. Li, L. Zhang, D. Jiang, Y. Wang, A. Zang, C. Ding, M. Zhao, W. Su, Y. Zhang, D. Zhong, J. Wu, G. An, C. Zhang, X. Hu, G. Cheng, H. Wang, Z. Han, X. He, J. Liu, L. Liang, S. Zhang
Journal: Journal of Thoracic Oncology (2018)
Abstract 18056: Novel Stem Cell Therapy for Heart Failure Using 3D Printed Cardiac Tissue
Authors: Chin Siang Ong, Takuma Fukunishi, Adriana Blazeski, Huaitao Zhang, Andrew R Nashed, Luca Vricella, John Conte, Leslie Tung, Gordon F Tomaselli, Narutoshi Hibino
Journal: Circulation (2016)

Introduction: Alternative treatments for heart failure such as stem cell therapy and tissue engineering approaches have been developed recently. However attempts to demonstrate significant myocardi...
Correction: Effective Targeting of the Survivin Dimerization Interface with Small-Molecule Inhibitors
Authors: Jing Qi, Zizheng Dong, Jianguo Liu, Robert C. Peery, Shaobo Zhang, Jing-Yuan Liu, Jian-Ting Zhang
Journal: Cancer Research (2018)

In the original version of [this article][1] ([1][2]), the Western blot image in Fig. 4F was inadvertently taken from the results of a different experiment. The authors provided the Western blot image from the correct experiment and the error has been corrected in the latest online HTML and PDF
Abstract 17778: Combination of Soluble Guanylate Cyclase Stimulation and Mineralocorticoid Receptor Antagonism as New Treatment Option for Heart Failure With Preserved Ejection Fraction (hfpef): Results From A Preclinical Study With Vericiguat and Finerenone
Authors: Ilka Mathar, Axel Kretschmer, Elke Hartmann, Peter Kolkhof, Peter Sandner
Journal: Circulation (2017)

Introduction: There is a substantial unmet medical need for new and efficacious treatment options for HFpEF. Combination of pharmacological approaches could address different pathophysiological key...
Myocardial Revascularization Trials
Authors: Marc Ruel, Volkmar Falk, Michael E. Farkouh, Nick Freemantle, Mario F. Gaudino, David Glineur, Duke E. Cameron, David P. Taggart
Journal: Circulation (2018)

This article reviews the context and evidence of recent myocardial revascularization trials that compared percutaneous coronary intervention with coronary artery bypass grafting for the treatment of left main and multivessel coronary artery disease. We develop the rationale that some of the knowledge synthesis resulting from these trials, particularly with regard to the claimed noninferiority of percutaneous coronary intervention beyond nondiabetic patients with low anatomic complexity, may have been affected by trial design, patient selection based on suitability for percutaneous coronary intervention, and end point optimization favoring percutaneous coronary intervention over coronary artery bypass grafting. We provide recommendations that include holding a circumspect interpretation of the currently available evidence, as well as suggestions for the collaborative design and conduct of future clinical trials in this and other fields.
Abstract 9727: High Serum Level of Tenascin-c is Related to Coronary Plaque Rupture in Patients With Acute Coronary Syndrome
Authors: Nobuo Sakamoto, Tomofumi Misaka, Hiroyuki Mizukami, Satoshi Suzuki, Koichi Sugimoto, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2012)

Purpose: Tenascin-C is a multifunctional protein and increases the expression of matrix metalloproteinases which lead to atherosclerotic plaque instability. Destabilization of coronary plaque is relevant to plaque rupture resulting in acute coronary syndrome (ACS). We hypothesized that serum tenascin-C level is higher in patients with ACS than in those with stable effort angina (SAP), and high serum level of tenascin-C is associated with plaque rupture in patients with ACS. Methods: Consecutive 52 ACS patients who underwent emergent percutaneous coronary intervention (PCI) and consecutive 66 patients with SAP who underwent elective PCI were enrolled in this study. Blood samples were obtained from ascending aorta just prior to the PCI procedures, and circulating serum level of tenascin-C was measured using there samples. After coronary guidewire crossing, intravascular ultrasound (IVUS) was performed for assessment of plaque characterization including coronary plaque rupture. ACS patients were assigned to two groups according to whether there was ruptured plaque (ACS-ruptured group) or not (ACS-non-ruptured group). Results: There were 23 patients in ACS-ruptured group and 29 patients in ACS-non-ruptured group. Clinical characteristics and IVUS findings of the lesion did not differ among SAP, ACS-ruptured and ACS-non-ruptured groups. Serum tenascin-C level in ACS-ruptured group was significantly higher than SAP patients, whereas there was no significant difference between ACS-non-ruptured group and SAP group. Importantly, in ACS-ruptured group, serum tenascin-C level was significantly higher than ACS non-ruptured group. Conclusions: Our data demonstrate that serum tenascin-C level is related to the pathological condition of ACS, especially the ruptured plaque estimated by IVUS observation. These results suggest that serum tenascin-C level is a novel biomarker for coronary plaque rupture in patients with ACS.
Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation
Authors: Zhiyang Chen, Elias Moris Amro, Friedrich Becker, Martin Hölzer, Seyed Mohammad Mahdi Rasa, Sospeter Ngoci Njeru, Bing Han, Simone Di Sanzo, Yulin Chen, Duozhuang Tang, Si Tao, Ronny Haenold, Marco Groth, Vasily S. Romanov, Joanna M. Kirkpatrick, Johann M. Kraus, Hans A. Kestler, Manja Marz, Alessandro Ori, Francesco Neri, Yohei Morita, K. Lenhard Rudolph
Journal: The Journal of Experimental Medicine (2018)

Organism aging is characterized by increased inflammation and decreased stem cell function, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells (HSPCs) exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signaling, which increases chromatin accessibility in the vicinity of NF-κB target genes in response to inflammation. Rad21 is required for normal differentiation, but limits self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB–dependent manner. HSCs from aged mice fail to down-regulate Rad21/cohesin and inflammation/differentiation signals in the resolution phase of inflammation. Inhibition of cohesin/NF-κB reverts hypersensitivity of aged HSPCs to inflammation-induced differentiation and myeloid-biased HSCs with disrupted/reduced expression of Rad21/cohesin are increasingly selected during aging. Together, Rad21/cohesin-mediated NF-κB signaling limits HSPC function during aging and selects for cohesin-deficient HSCs with myeloid-skewed differentiation.
Club Cell Secretory Protein Deficiency Leads to Altered Lung Function
Authors: Jing Zhai, Michael Insel, Kenneth J. Addison, Debra A. Stern, William Pederson, Alane Dy, Joselyn Rojas-Quintero, Caroline A. Owen, Duane L. Sherrill, Wayne Morgan, Anne L. Wright, Marilyn Halonen, Fernando D. Martinez, Monica Kraft, Stefano Guerra, Julie G. Ledford
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases.Objectives: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions.Methods: Using human data from the birth cohort of the Tucson Children's Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC16−/− mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway.Measurements and Main Results: We observed that Tucson Children's Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC16−/− mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC16−/− mice had significantly elevated gene expression of procollagen type I, procollagen type III, and α-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness.Conclusions: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.
His Resynchronization Versus Biventricular Pacing in Patients With Heart Failure and Left Bundle Branch Block
Authors: Ahran D. Arnold, Matthew J. Shun-Shin, Daniel Keene, James P. Howard, S.M. Afzal Sohaib, Ian J. Wright, Graham D. Cole, Norman A. Qureshi, David C. Lefroy, Michael Koa-Wing, Nick W.F. Linton, Phang Boon Lim, Nicholas S. Peters, D. Wyn Davies, Amal Muthumala, Mark Tanner, Kenneth A. Ellenbogen, Prapa Kanagaratnam, Darrel P. Francis, Zachary I. Whinnett
Journal: Journal of the American College of Cardiology (2018)

His bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT). The authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function. Patients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation. In 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (−18.6 ms; 95% confidence interval [CI]: −31.6 to −5.7 ms; p = 0.007), left ventricular activation time (−26 ms; 95% CI: −41 to −21 ms; p = 0.002), and left ventricular dyssynchrony index (−11.2 ms; 95% CI: −16.8 to −5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04). His resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.
Total mesorectal excision with or without preoperative chemoradiotherapy for resectable mid/low rectal cancer: a long‐term analysis of a prospective, single‐center, randomized trial
Authors: Fulong Wang, Wenhua Fan, Jianhong Peng, Zhenhai Lu, Zhizhong Pan, Liren Li, Yuanhong Gao, Hui Li, Gong Chen, Xiaojun Wu, Peirong Ding, Zhifan Zeng, Desen Wan
Journal: Cancer Communications (2018)

Abstract Background The preliminary results of our phase II randomized trial reported comparable functional sphincter preservation rates and short‐term survival outcomes between patients undergoing total mesorectal excision (TME) with or without preoperative concurrent chemoradiotherapy (CCRT). We now report the long‐term results after a median follow‐up of 71 months. Methods Between March 23, 2008 and August 2, 2012, 192 patients with T3‐T4 or node‐positive, resectable, mid/low rectal adenocarcinoma were randomly assigned to receive TME with or without preoperative CCRT. The following endpoints were assessed: cumulative rates of local recurrence and distant metastasis, disease‐free survival (DFS), and overall survival (OS). Results The data of 184 eligible patients were analyzed: 94 patients in the TME group and 90 patients in the CCRT + TME group. In the whole cohort, the 5‐year DFS and OS rates were 84.8% and 85.1%, respectively. The 5‐year DFS rates were 85.2% in the CCRT + TME group and 84.3% in the TME group ( P = 0.969), and the 5‐year OS rates were 83.5% in the CCRT + TME group and 86.5% in the TME group ( P = 0.719). The 5‐year cumulative rates of local recurrence were 6.3% and 5.0% ( P = 0.681), and the 5‐year cumulative rates of distant metastasis were 15.0% and 15.7% ( P = 0.881) in the CCRT + TME and TME groups, respectively. No significant improvements in 5‐year DFS and OS were observed with CCRT by subgroup analyses. Conclusions Both treatment strategies yielded similar long‐term outcomes. A selective policy towards preoperative CCRT is thus recommended for rectal cancer patients if high‐quality TME surgery and enhanced chemotherapy can be performed. Trial registration ChiCTR‐TRC‐08000122. Registered 16 July 2008
Interim Analysis of Phase II Study of Venetoclax with 10-Day Decitabine (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Abhishek Maiti, Courtney D. DiNardo, Jorge E. Cortes, Gautam Borthakur, Naveen Pemmaraju, Christopher B. Benton, Tapan M. Kadia, Koichi Takahashi, Kiran Naqvi, Farhad Ravandi, Yesid Alvarado, Nicholas J Short, Naval G. Daver, Koji Sasaki, Maro N. Ohanian, Guillermo Garcia-Manero, Philip A. Thompson, Steven M. Kornblau, Lucia Masarova, Nitin Jain, Elias J. Jabbour, Michael Andreeff, Rita Maduike, Julio A Guerrero, Qi Zhang, Antonio Cavazos, Helen Ma, Caitlin R. Rausch, Carol A. Bivins, Kenneth Vaughan, Sherry A. Pierce, Jing Ning, Wei Qiao, John S. Welch, Hagop M. Kantarjian, Marina Y. Konopleva
Journal: Blood (2018)
Potential Harms of HIPAA—Reply
Authors: Donald Berwick, Martha E. Gaines
Journal: JAMA (2018)

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<i>Phf6</i> Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL
Authors: Agnieszka A. Wendorff, S. Aidan Quinn, Marissa Rashkovan, Chioma J. Madubata, Alberto Ambesi-Impiombato, Mark R. Litzow, Martin S. Tallman, Elisabeth Paietta, Maddalena Paganin, Giuseppe Basso, Julie M. Gastier-Foster, Mignon L. Loh, Raul Rabadan, Pieter Van Vlierberghe, Adolfo A. Ferrando
Journal: Cancer Discovery (2018)

Abstract The plant homeodomain 6 gene (PHF6) is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL); however, its specific functional role in leukemia development remains to be established. Here, we show that loss of PHF6 is an early mutational event in leukemia transformation. Mechanistically, genetic inactivation of Phf6 in the hematopoietic system enhances hematopoietic stem cell (HSC) long-term self-renewal and hematopoietic recovery after chemotherapy by rendering Phf6 knockout HSCs more quiescent and less prone to stress-induced activation. Consistent with a leukemia-initiating tumor suppressor role, inactivation of Phf6 in hematopoietic progenitors lowers the threshold for the development of NOTCH1-induced T-ALL. Moreover, loss of Phf6 in leukemia lymphoblasts activates a leukemia stem cell transcriptional program and drives enhanced T-ALL leukemia-initiating cell activity. These results implicate Phf6 in the control of HSC homeostasis and long-term self-renewal and support a role for PHF6 loss as a driver of leukemia-initiating cell activity in T-ALL. Significance: Phf6 controls HSC homeostasis, leukemia initiation, and T-ALL leukemia-initiating cell self-renewal. These results substantiate a role for PHF6 mutations as early events and drivers of leukemia stem cell activity in the pathogenesis of T-ALL. This article is highlighted in the In This Issue feature, p. 305