tbuckley/cabot-search huggingface dataset:
Genetic Background of Idiopathic Bone Marrow Failure Syndromes in Children
Authors: Atsushi Narita, Yusuke Okuno, Hideki Muramatsu, Kenichi Yoshida, Yuichi Shiraishi, Yuko Sekiya, Kenichi Chiba, Hiroko Tanaka, Xinan Wang, Nozomu Kawashima, Nobuhiro Nishio, Sayoko Doisaki, Asahito Hama, Yoshiyuki Takahashi, Hirotoshi Sakaguchi, Nao Yoshida, Koji Kato, Satoru Miyano, Masafumi Ito, Seishi Ogawa, Seiji Kojima
Journal: Blood (2015)
SOX11 Directly Represses Wnt/β-Catenin Signaling and Identifies a Subgroup of Mantle Cell Lymphoma Patients with Improved Survival with Intensive Treatment
Authors: Pei-Yu Kuo, Violetta V. Leshchenko, Melissa J Fazzari, Tobias A. Gellen, Javeed Iqbal, Stefanie Baumgartner-Wennerholm, Lina Nygren, K. Stephen Suh, Andre Goy, David T. Yang, Wing-Chung Chan, Brad S Kahl, Amit Verma, Randy D. Gascoyne, Eva Kimby, Birgitta Sander, B. Hilda Ye, Ari Melnick, Samir Parekh
Journal: Blood (2012)
Evaluation of Peroxiredoxins (PRDX1, PRDX2 and PRDX6) Expression in Patients with Chronic Myeloid Leukemia (CML) Treated with Imatinib in First Line
Authors: Cintia Mascarenhas, Lara Woldmar, Maria Helena Almeida, Rosangela Vieira Andrade, Anderson Ferreira Cunha, Carmino A De Souza
Journal: Blood (2014)
NTCT-03CEREBRAL MICROBLEEDS AFTER WHOLE BRAIN RADIATION THERAPY IN MEDULLOBLASTOMA PATIENTS
Authors: Duangnapa Roongpiboonsopit, Lily L. Alstein, Hugo J. Kuijf, Andreas Charidimou, Li Xiong, Anastasia Vashkevich, Sergi Martinez-Ramirez, Helen Shih, Anand Viswanathan, Jorg Dietrich
Journal: Neuro-Oncology (2015)

BACKGROUND: Radiation therapy is part of the standard treatment for medulloblastoma patients. The pattern and incidence of neurovascular toxicities, such as cerebral microbleeds (CMBs) following whole brain radiation therapy (WBRT) is poorly characterized in long-term survivors. The aim of this study is to determine the temporal and spatial pattern of CMBs after WBRT in medulloblastoma patients. METHODS: We retrospectively identified medulloblastoma patients treated with WBRT at the Massachusetts General Hospital between 1999 and 2014. Longitudinal magnetic resonance imaging data was reviewed, and the incidence, prevalence and spatial pattern of CMBs were characterized over time. RESULTS: We identified 27 patients previously treated with WBRT for medulloblastoma and who had complete longitudinal imaging datasets available for review, including GRE, T1 and T2 imaging sequences. CMBs were found in >65% (18/27) of patients when followed for a median time of at least 4 years. Incidence of CMBs was increasing with each year from time of WBRT, and was more likely in patients treated at age of <20 years (100% incidence). CMBs were mostly found in lobar distribution and predominately in occipital and temporal lobes. Antithrombotic use and hypertension were associated with a significantly higher incidence of CMBs (p = 0.041). CONSLUSIONS: Our data demonstrate a surprisingly high prevalence of CMBs following WBRT, increasing with each year from time of WBRT. Strikingly, the spatial distribution of CMBs was similar to a pattern seen in patients with cerebral amyloid angiopathy. Use of antithrombotic therapy appears to accelerate the rate of CMBs and may represent an independent risk factor for long-term neurovascular injury.
Proteomic Analysis of Chronic Lymphocytic Leukemia Cells Identifies Vimentin as a Novel Prognostic Factor for Aggressive Disease.
Authors: Grzegorz S. Nowakowski, Yean K. Lee, Nancy D. Bone, William G. Morice, David Barnidge, Diane F. Jelinek, Renee Tschumper, Tait D. Shanafelt, Clive S. Zent, Laura Z. Rassenti, Thomas J. Kipps, Neil E. Kay
Journal: Blood (2005)
SP0078 When and How To Manage Primary Raynaud's Phenomenon
Authors: J.-L. Cracowski
Journal: Annals of the Rheumatic Diseases (2016)

Primary Raynaud9s phenomenon (PRP) is a common condition characterized by transient ischemia in the extremities in response to cold or emotions, which does not progress to digital ulcerations. The pathophysiology of PRP is multifactorial and complex, and while PRP is considered as a benign condition, it can be associated with significant disability during the cold season. The objective of this talk is to further clarify how a diagnosis of PRP can be performed, and to review the different pharmacological and non pharmacological treatments currently used in the management of RP, from their mechanism of action to the available evidence regarding their efficacy. We will also address the issue of drug-induced RP. <h3>Disclosure of Interest</h3> J.-L. Cracowski Grant/research support from: Pfizer; Bioprojet
Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes
Authors: David G. Kugler, Francis A. Flomerfelt, Diego L. Costa, Karen Laky, Olena Kamenyeva, Paul R. Mittelstadt, Ronald E. Gress, Stephan P. Rosshart, Barbara Rehermann, Jonathan D. Ashwell, Alan Sher, Dragana Jankovic
Journal: The Journal of Experimental Medicine (2016)

Because antigen-stimulated naive T cells either die as effectors or enter the activated/memory pool, continuous egress of new T lymphocytes from thymus is essential for maintenance of peripheral immune homeostasis. Unexpectedly, we found that systemic infection with the protozoan Toxoplasma gondii triggers not only a transient increase in activated CD4 + Th1 cells but also a persistent decrease in the size of the naive CD4 + T lymphocyte pool. This immune defect is associated with decreased thymic output and parasite-induced destruction of the thymic epithelium, as well as disruption of the overall architecture of that primary lymphoid organ. Importantly, the resulting quantitative and qualitative deficiency in naive CD4 + T cells leads to an immunocompromised state that both promotes chronic toxoplasma infection and leads to decreased resistance to challenge with an unrelated pathogen. These findings reveal that systemic infectious agents, such as T. gondii , can induce long-term immune alterations associated with impaired thymic function. When accumulated during the lifetime of the host, such events, even when occurring at low magnitude, could be a contributing factor in immunological senescence.
Downregulation of Ribosomal Proteins Is Seen in Non 5q- MDS
Authors: Davendra P. Sohal, Andrea Pellagati, Li Zhou, Yongkai Mo, Joanna B. Opalinska, Christina Alencar, Christoph Heuck, Amittha Wickrema, Ellen Friedman, John Greally, Benjamin L. Ebert, Jonathan Warner, Jacqueline Boultwood, Amit Verma
Journal: Blood (2008)
Effect of early supervised physiotherapy on recovery from acute ankle sprain: randomised controlled trial
Authors: Robert J Brison, Andrew G Day, Lucie Pelland, William Pickett, Ana P Johnson, Alice Aiken, David R Pichora, Brenda Brouwer
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess the efficacy of a programme of supervised physiotherapy on the recovery of simple grade 1 and 2 ankle sprains. <b>Design</b>&nbsp;A randomised controlled trial of 503 participants followed for six months. <b>Setting</b>&nbsp;Participants were recruited from two tertiary acute care settings in Kingston, ON, Canada. <b>Participants</b>&nbsp;The broad inclusion criteria were patients aged ≥16 presenting for acute medical assessment and treatment of a simple grade 1 or 2 ankle sprain. Exclusions were patients with multiple injuries, other conditions limiting mobility, and ankle injuries that required immobilisation and those unable to accommodate the time intensive study protocol. <b>Intervention</b>&nbsp;Participants received either usual care, consisting of written instructions regarding protection, rest, cryotherapy, compression, elevation, and graduated weight bearing activities, or usual care enhanced with a supervised programme of physiotherapy. <b>Main outcome measures</b>&nbsp;The primary outcome of efficacy was the proportion of participants reporting excellent recovery assessed with the foot and ankle outcome score (FAOS). Excellent recovery was defined as a score ≥450/500 at three months. A difference of at least 15% increase in the absolute proportion of participants with excellent recovery was deemed clinically important. Secondary analyses included the assessment of excellent recovery at one and six months; change from baseline using continuous scores at one, three, and six months; and clinical and biomechanical measures of ankle function, assessed at one, three, and six months. <b>Results</b>&nbsp;The absolute proportion of patients achieving excellent recovery at three months was not significantly different between the physiotherapy (98/229, 43%) and usual care (79/214, 37%) arms (absolute difference 6%, 95% confidence interval −3% to 15%). The observed trend towards benefit with physiotherapy did not increase in the per protocol analysis and was in the opposite direction by six months. These trends remained similar and were never statistically or clinically important when the FAOS was analysed as a continuous change score. <b>Conclusions</b>&nbsp;In a general population of patients seeking hospital based acute care for simple ankle sprains, there is no evidence to support a clinically important improvement in outcome with the addition of supervised physiotherapy to usual care, as provided in this protocol. <b>Trial registration</b>&nbsp;ISRCTN 74033088 (www.isrctn.com/ISRCTN74033088)
Biochemical Characterization of a Recombinant FIX Drug Candidate for Treatment of Hemophilia B
Authors: Peter Turecek, Susanne Vejda, Katalin Varadi, Hanspeter Rottensteiner, Ernst Boehm, Manfred Reiter, Martin Kaliwoda, Wolfgang Mundt, Hartmut J. Ehrlich, Friedrich Scheiflinger
Journal: Blood (2010)
Coadministration of the Hexavalent Combination Vaccine Infanrix hexa™ and the Pneumoccoccal Conjugate Vaccine Prevenar™ Provides Early and Comprehensive Vaccination Coverage in Children after Related and Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Roland Meisel, Lisa Kuypers, Bernd Gruhn, Gabi Strauss, Brigitte Strahm, Karoline Ehlert, Karin Beutel, Wolfgang Holter, Renate Bluetters-Sawatzki, Tobias Feuchtinger, Hans-Peter Gruettner, Ralf Schubert, Sabine Diedrich, Marion Riffelmann, Hans-Juergen Laws, Dagmar Dilloo
Journal: Blood (2007)
Farnesoid X receptor ablation sensitizes mice to hepatitis b virus X protein–induced hepatocarcinogenesis
Authors: Yongdong Niu, Meishu Xu, Betty L. Slagle, Haihua Huang, Song Li, Grace L. Guo, Ganggang Shi, Wenxin Qin, Wen Xie
Journal: Hepatology (2016)

Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) is a hepatitis B virus protein that has multiple cellular functions, but its role in HCC pathogenesis has been controversial. Farnesoid X receptor (FXR) is a nuclear receptor with activities in anti-inflammation and inhibition of hepatocarcinogenesis. However, whether or how FXR can impact hepatitis B virus/HBx-induced hepatocarcinogenesis remains unclear. In this study, we showed that HBx can interact with FXR and function as a coactivator of FXR. Expression of HBx in vivo enhanced FXR-responsive gene regulation. HBx also increased the transcriptional activity of FXR in a luciferase reporter gene assay. The HBx-FXR interaction was confirmed by coimmunoprecipitation and glutathione S-transferase pull-down assays, and the FXR activation function 1 domain was mapped to bind to the third α helix in the C terminus of HBx. We also found that the C-terminally truncated variants of HBx, which were found in clinical HCC, were not effective at transactivating FXR. Interestingly, recruitment of the full-length HBx, but not the C-terminally truncated HBx, enhanced the binding of FXR to its response element. In vivo, FXR ablation markedly sensitized mice to HBx-induced hepatocarcinogenesis.We propose that transactivation of FXR by full-length HBx may represent a protective mechanism to inhibit HCC and that this inhibition may be compromised upon the appearance of C-terminally truncated HBx or when the expression and/or activity of FXR is decreased. (Hepatology 2017;65:893-906).
Simultaneous Targeting of Bcl-2/Bcl-Xl and MEK/ERK Results in Highly Synergistic Induction of Apoptosis in Human AML, Both in Vitro and In Vivo.
Authors: Marina Konopleva, Michele Milella, Julie C Watts, Maria Rosaria Ricciardi, Borys Korchin, Twee Tsao, Paola Bergamo, Duncan H. Mak, Samantha Decandia, James McCubrey, Agostino Tafuri, Michael Andreeff
Journal: Blood (2009)
PVAG (Prednisone, Vinblastine, Doxorubicin and Gemcitabine) In Elderly Patients with Intermediate or Advanced Stage Hodgkin Lymphoma: Final Results of a Phase II Study of the German Hodgkin Study Group (GHSG).
Authors: Boris Böll, Teresa Halbsguth, Helen Görgen, Henning Bredenfeld, Hans Eich, Michael Fuchs, Peter Borchmann, Andreas Engert
Journal: Blood (2010)
SP0185 Reflex Dystrophy: Diagnosis and Treatment
Authors: A. Giusti
Journal: Annals of the Rheumatic Diseases (2016)

Complex Regional Pain Syndrome type I (CRPS-I), in the past called reflex dystrophy, is a disabling disorder affecting a peripheral limb, usually developing after a trauma to an extremity. Several different diagnostic criteria have been proposed, and recently updated "Budapest Criteria" have been widely accepted, to diagnose CRPS-I. The diagnosis is made using clinical criteria and is based on the sole clinical history and examination. CRPS-I is characterized by the presence of spontaneous or stimulus-induced pain, disproportionate to the inciting event, allodynia and hyperalgesia. These symptoms are associated to a wide variety of autonomic and motor disturbances, or trophic abnormalities. There are no specific laboratory or radiological diagnostic procedures for CRPS-I, but a variety of tests may be useful to exclude other clinical conditions. These include x-rays, three-phase bone scintigraphy and MRI. At present, several pharmacological treatments (e.g., analgesics, anesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, bisphosphonates, and calcium channel blockers) have been proposed to reduce pain and pain sensitization, and to improve functional status in patients presenting with CRPS-I. While most of these medications demonstrated poor or partial efficacy on the short-term, bisphosphonates (BPs) showed better long-term beneficial effects on pain reduction and functional recovery. BPs are potent inhibitors of osteoclastic activity widely used for the management of osteoporosis and other metabolic bone diseases. Their primary pharmacological action is the reduction of bone turnover. An enhanced osteoclastic activity has never been clearly demonstrated in CRPS-I. Therefore, it is likely that the positive effects of BPs in this condition are not related to their anti-resorptive properties, but to a more complex interaction between these pharmacological agents and the pathophysiological mechanisms underlying CRPS-I. Results of several clinical trials have suggested the potential beneficial effects of BPs in CRPS-I. In five randomized-controlled trials, oral and intravenous alendronate, and intravenous clodronate, pamidronate and neridronate demonstrated to be effective in reducing pain and improving physical function in patients presenting with CRPS-I, with a good profile of safety and tolerability. Although these trials have a number of limitations, including the small samples enrolled, there is sufficient evidence to support the use of BPs as agents of choice in the management of CRPS-I. <h3>Disclosure of Interest</h3> A. Giusti Consultant for: Chiesi, Dynamicom, Eli Lilly, Abiogen, Speakers bureau: Merck &amp; Co., AMGEN, Eli Lilly, Chiesi, Abiogen
Acquisition of Mutations in the PSMB5 Gene during Chronic Exposure of Human Acute Lymphoblastic Leukemia CCRF-CEM Cells to the Proteasome Inhibitor Bortezomib
Authors: Niels E Franke, Ruud Oerlemans, Ina van Zantwijk, Katarina Vojtekova, Gertjan L Kaspers, Gerrit Jansen, Jacqueline Cloos
Journal: Blood (2008)
The Expanding Role of the BCL6 Oncoprotein as a Cancer Therapeutic Target
Authors: Mariano G. Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D. MacKerell, Ari M. Melnick
Journal: Clinical Cancer Research (2016)

BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes and then repressing these genes by recruiting several different chromatin-modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly, a number of compounds have been designed to bind to BCL6 and block corepressor recruitment. These compounds, based on peptide or small-molecule scaffolds, can potently block BCL6 repression of target genes and kill lymphoma cells. In the case of diffuse large B-cell lymphomas (DLBCL), BCL6 inhibitors are equally effective in suppressing both the germinal center B-cell (GCB)- and the more aggressive activated B-cell (ABC)-DLBCL subtypes, both of which require BCL6 to maintain their survival. In addition, BCL6 is implicated in an expanding scope of hematologic and solid tumors. These include, but are not limited to, B-acute lymphoblastic leukemia, chronic myeloid leukemia, breast cancer, and non-small cell lung cancer. BCL6 inhibitors have been shown to exert potent effects against these tumor types. Moreover, mechanism-based combinations of BCL6 inhibitors with other agents have yielded synergistic and often quite dramatic activity. Hence, there is a compelling case to accelerate the development of BCL6-targeted therapies for translation to the clinical setting. Clin Cancer Res; 23(4); 885-93. ©2016 AACR.
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Authors: Claudio Vernieri, Stefano Casola, Marco Foiani, Filippo Pietrantonio, Filippo de Braud, Valter Longo
Journal: Cancer Discovery (2016)

Abstract Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics. Significance: To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315–33. ©2016 AACR.
PTH-028 How About Resurrecting The Research of Mechanically Actuated Robotic Capsule Endoscopy by Designing Novel Pressure Crystallised Self-Powering Composite Structures?
Authors: P Tian, C Xu, H Huang, X Chen, L Zhao, J Lyu
Journal: Gut (2016)

<h3>Introduction</h3> Mechanically actuated robotic capsule endoscopes for active locomotion have demonstrated considerable clinical potential for conducting biopsies or therapeutic intervention in human gastrointestinal (GI) tract.<sup>1</sup> Nevertheless, the research began to slow down owing to on-board power limitations and mechanical complexity in miniaturising electronic elements incorporated in the capsule body.<sup>2</sup> Ideally, such swallowable capsules should be self-powered in vivo by converting the numerous GI-providing energy, such as the energy from the peristalsis near gastroesophageal junction and the high shear intestinal fluid flow.<sup>3</sup> <h3>Methods</h3> Graphene nanoplatelet (GNP), consisting of stacked layers of graphene to enable the delivery of a broad range of therapeutics, was pre-mixed and then melt blended with poly (vinylidene fluoride) (PVDF). The as fabricated binary composites were crystallised at pressure with a piston-cylinder apparatus. <h3>Results</h3> Controllable rapid growth of unique self-powering 3 D hybrid nanoarchitectures, assembled from 1 D PVDF micro/nanowires on GNPs, was achieved by the pressure crystallisation of GNP/PVDF composites (Figure 1 a-c). By controlling the crystallisation conditions, the PVDF nanowires, with piezoelectric crystalline beta phase, were obtained respectively with folded- and extended-chain lamellae as their substructures. The GNPs may play the role as a catalyst in the composite system, due to their size effect, which catalysed the self-assembly of the PVDF molecules into nanowires and then resulted in the radial nanowire clusters. Although the original surfaces of GNP/PVDF composites were high hydrophobic, they were successfully converted into hydrophilic surfaces through the pressure treatment followed by appropriate etching process (Figure 1 d and e). <h3>Conclusion</h3> The pressure crystallised GNP/PVDF composites may permit niche applications in the fabrication of a new-generation of self-powering robotic capsule endoscopes to meet the environmental conditions of each section of GI tract for energy scavenging. This study was funded by the National Natural Science Foundation of China (51373139). <h3>References</h3> 1 Munoz F, Alici G, Li WH. <i>Adv Drug Deliver Rev</i> 2014;<b>71</b>:77–85. 2 Slawinski PR, Obstein KL, Valdastri P. <i>World J Gastroentero</i> 2015;<b>21</b>:10528–41. 3 Wang ZL, Song J. <i>Science</i> 2006;<b>312</b>:242–6. <h3>Disclosure of Interest</h3> None Declared
Current Psychosomatic Practice
Authors: Giovanni A. Fava, Fiammetta Cosci, Nicoletta Sonino
Journal: Psychotherapy and Psychosomatics (2016)

Psychosomatic research has advanced over the past decades in dealing with complex biopsychosocial phenomena and may provide new effective modalities of patient care. Among psychosocial variables affecting individual vulnerability, course, and outcome of any medical disease, the role of chronic stress (allostatic load/overload) has emerged as a crucial factor. Assessment strategies include the Diagnostic Criteria for Psychosomatic Research. They are presented here in an updated version based on insights derived from studies carried out so far and encompass allostatic overload, type A behavior, alexithymia, the spectrum of maladaptive illness behavior, demoralization, irritable mood, and somatic symptoms secondary to a psychiatric disorder. Macroanalysis is a helpful tool for identifying the relationships between biological and psychosocial variables and the individual targets for medical intervention. The personalized and holistic approach to the patient includes integration of medical and psychological therapies in all phases of illness. In this respect, the development of a new psychotherapeutic modality, Well-Being Therapy, seems to be promising. The growth of subspecialties, such as psychooncology and psychodermatology, drives towards the multidisciplinary organization of health care to overcome artificial boundaries. There have been major transformations in health care needs in the past decades. From psychosomatic medicine, a land of innovative hypotheses and trends, many indications for changes in the current practice of medicine are now at hand. The aim of this critical review is to outline current and potential clinical applications of psychosomatic methods.