tbuckley/cabot-search huggingface dataset:
Abstract 4048: Histological image profiling identifies aggressive glioblastoma phenotype with poorer survival
Authors: Yuexin Liu, Ilya Shmulevich, Gregory Fuller, Wei Zhang
Journal: Cancer Research (2011)

Abstract The stratification of glioblastoma (GBM) patients into clinically relevant subtypes is an essential step in the direction of personalized genomic medicine. In contrast to currently employed time- and cost-intensive genomic methodologies, we describe here a novel cost-effective approach capable of detecting predictors of invasive disease in GBM based on profiling of histological images. Unsupervised statistical analysis of imaging feature data first distinguishes two major clusters with strikingly different phenotypes. The subsequent Kaplan-Meier survival analysis of these two clusters shows that patients who had tumors in cluster 2 (which we refer to as aggressive subtype for the purpose of clarity) had poorer overall survival. Among the differentially varied features, the aspect ratio parameter, which is a strong indicator of cell movement, exhibits larger values in the aggressive subtype, suggesting greater invasiveness of this subset. Based on the initial dataset, a predictive model comprised of informative features was constructed using a weighted voting algorithm. Cross-validation of this sample set revealed a predictive accuracy of over 90% in correctly classifying these two groups, with specificity of ∼94% and sensitivity of ∼90% as determined by the receiver operating characteristic curves method. In a manner similar to gene biomarkers, some of imaging features can be used as diagnostic and prognostic factors in GBM. To identify the molecular events underlying the identified phenotypes, we performed genome-wide expression data analysis of the same sample set. Among the marker genes identified as overexpressed in the aggressive subtype were CHI3L1, CD44 and TNFRSF1A, which have been previously associated with poorer survival in GBM. In addition, pathway analysis of differentially-expressed genes indicates significant activation of the glioma invasiveness signaling and NF-κB signaling pathways; most of the altered genes in both pathways are more highly expressed in the aggressive GBM subtype and are thus potentially linked to the poorer survival of this group. Our novel approach has the potential to unify the imaging and genomic dimensions of GBM for clinical stratification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4048. doi:10.1158/1538-7445.AM2011-4048
Abstract 3330: Nanog, cancer stem cells, and resistance to chemotherapy
Authors: Man-Tzu Wang, Daotai Nie
Journal: Cancer Research (2010)

Abstract It has been increasingly appreciated that cancer stem cells are responsible for initiating tumor formation as well as resistance to chemoradiotherapy, but the mechanisms involved remain unknown. Nanog is a transcription factor essential for self-renewal of embryonic stem cells. The expression of Nanog has been reported in some cancer cells but its role in tumor initiation and resistance to chemotherapy has not been convincingly demonstrated. Herein, we report that Nanog is expressed in tumorigenic prostate cancer cells and further it plays an essential role of Nanog in tumor formation and resistance to chemotherapy. Enrichment for Nanog-expressing tumor cells led to an increase in the number of cells positive for stem/progenitor markers, increased clonogenic growth, and increased ability to form prostaspheres. When injected into mice, enriched Nanog-expressing cells formed tumors earlier and formed larger tumors than the vector control cells did. Knockdown of Nanog in tumorigenic cancer cells, via small hairpin RNAs, reduced clonogenic growth, stimulated epithelial differentiation, and significantly compromised their tumor initiating ability. Prospective enrichment of tumor cells with endogenous Nanog expression also led to enrichment of tumor cells resistant to Taxol, vinblastine, and doxorubicin, but not camptothecin (CPT). The increased resistance in Nanog expressing cells was attenuated, but not abolished, by inhibitors of p-glycoprotein, the ATP-bind cassette efflux transporter B1 (ABCB1), or by knockdown of ABCB1 via small hairpin RNAs (shRNAs). Expression of ABCB1 was increased in tumor cells enriched with endogenous Nanog expression while knockdown of Nanog reduced the expression of ABCB1 and sensitized tumor cells toward chemotherapeutics. Taken together, the data from gain-of-function and loss-of-function studies suggest an essential role of Nanog for prostate cancer cells to self-renew or propagate, to initiate tumor formation, and to resist chemotherapy via regulating the expression of ABC transporters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3330.
SP0199 Chair of Health Professionals Standing Committee: Who I Am and What I Will Do to Represent the Vision for H PS Within Eular
Authors: S.M. Oliver
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> This session will provide the audience with a short overview of my expertise and interests within the field of rheumatology and histroical interaction with Eular over the last ten years. The main focus of this session will be to explain the role of the Chair of the Health Professionals Standing Committee and outline what, as incoming Chair, I hope to achieve during my term of office in the context of Eular Strategic Objectives and Vision for 2020. The aim also is to encourage attendees to voice their specific questions and needs. Further Interaction and open discussion will be encouraged as part of the overall session. <h3>Disclosure of Interest</h3> None Declared
Accountability and Feedback, Part IV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2013)

There are times that feedback is destructive rather than helpful to the employee and the organization. Occasionally, this is deliberate, such as when a boss does not like someone for reasons that have nothing to do with his/her performance as an employee, or his/her character. More often, it is inadvertent. This could be due to erroneous information from others or the leader's failure to take the time to adequately observe or supervise others. It could also be due to a lack of understanding of the individual's communication style, or failure to take into account age, cultural, religious, or sex differences. This article addresses some of these issues and what to do about it.
Proliferation of Multiple Cell Types in the Skeletal Muscle Tissue Elicited by Acute p21 Suppression
Authors: Maria Grazia Biferi, Carmine Nicoletti, Germana Falcone, Eleonora M R Puggioni, Nunzia Passaro, Alessia Mazzola, Deborah Pajalunga, Germana Zaccagnini, Emanuele Rizzuto, Alberto Auricchio, Lorena Zentilin, Gabriele De Luca, Mauro Giacca, Fabio Martelli, Antonio Musio, Antonio Musarò, Marco Crescenzi
Journal: Molecular Therapy (2015)

Although in the last decades the molecular underpinnings of the cell cycle have been unraveled, the acquired knowledge has been rarely translated into practical applications. Here, we investigate the feasibility and safety of triggering proliferation in vivo by temporary suppression of the cyclin-dependent kinase inhibitor, p21. Adeno-associated virus (AAV)-mediated, acute knockdown of p21 in intact skeletal muscles elicited proliferation of multiple, otherwise quiescent cell types, notably including satellite cells. Compared with controls, p21-suppressed muscles exhibited a striking two- to threefold expansion in cellularity and increased fiber numbers by 10 days post-transduction, with no detectable inflammation. These changes partially persisted for at least 60 days, indicating that the muscles had undergone lasting modifications. Furthermore, morphological hyperplasia was accompanied by 20% increases in maximum strength and resistance to fatigue. To assess the safety of transiently suppressing p21, cells subjected to p21 knockdown in vitro were analyzed for γ-H2AX accumulation, DNA fragmentation, cytogenetic abnormalities, ploidy, and mutations. Moreover, the differentiation competence of p21-suppressed myoblasts was investigated. These assays confirmed that transient suppression of p21 causes no genetic damage and does not impair differentiation. Our results establish the basis for further exploring the manipulation of the cell cycle as a strategy in regenerative medicine.
Corticosteroids as Adjunctive Therapy for Severe<i>Pneumocystis carinii</i>Pneumonia in the Acquired Immunodeficiency Syndrome
Authors: Suzanne Gagnon, Ahmad M. Boota, Margaret A. Fischl, Horst Baier, Otis W. Kirksey, Lawrence La Voie
Journal: New England Journal of Medicine (1990)

Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy.
Antinuclear Antibodies in Families of Patients with Systemic Lupus Erythematosus
Authors: Victor E. Pollak
Journal: New England Journal of Medicine (1964)

IN the last decade systemic lupus erythematosus has been reported in 2 or more members of over 20 families.1 , 2 Systematic studies of families of patients have demonstrated an increased incidence of biologic false-positive reactions for syphilis,3 4 5 6 of rheumatoid factor3 , 5 , 7 and of positive Coombs tests5 in healthy relatives. These observations suggest that hereditary factors are important in the pathogenesis.Of the many immunologic abnormalities that occur in the disease L.E. cells and antinuclear antibodies are the most characteristic. In a preliminary communication antinuclear antibodies were reported in the serum of 24 of 50 relatives of patients with systemic lupus erythematosus.8 Other . . .
AB0584 Tocilizumab increases hemoglobin production in patient with juvenile idiopatic arthritis and beta thalassemic trait:
Authors: V. Bruner, A. Spanò, G. Tramontano, N. Bertolini, M. Raimondo, S. Padula, L. Nappi, R. Scarpa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is classified as an acquired autoinflammatory disease. The interleukin-1 and interleukin-6 play an pivotal role in pathogenesis of this disease (1). The systemic manifestations as well as arthritis in sJIA are related to IL-6 action. Il-6 appears to be responsible for the anemia seen in sJIA, mainly inducing the production of hepcidin. Hepcidin prevents the release of iron from the macrophages, hepatocytes, and enterocytes to the plasma, causing a decrease in serum iron levels (2). Thus, the effective blockade of IL-6R signaling is expected to decrease hepcidin levels and increase iron availability for hemoglobin production (3), but in a beta thalassemic trait subject it may be unexpected. <h3>Objectives</h3> Our objective is to evaluate the efficacy of tocilizumab therapy in a JIA patient with beta thalassemic trait. <h3>Methods</h3> A.M. is a 25 yrs. caucasian male, affected by JIA since ten years and beta thalassemic trait (mother and brother too). The patient received over the time different traditional and biologic DMARDs, with an inadeguate control on arthritis' flares, inflammatory values and anemia. He was treated with MTX in monotherapy (2001-2002); Etanercept in association with MTX first, then Cyclosporine and at last Leflunomide (2002 – 2005); Anakinra (2005 – 2007); Adalimumab (2007 – 2008); Etanercept again (2008 – 2009); Abatacept (2009 – 2010). In 2009 he started Abatacept therapy with DAS28CRP value of 5,27 (TJC: 6, SJC: 2, CRP 75 mg/dL, PGA 70 mm) and hemoglobin was 8,8 g/dL. Because of recurrent arthritis' flares, on April 2010 he started Tocilizumab monotherapy (8 mg/kg monthly i.v.) after two months wash out. <h3>Results</h3> At the baseline of Tocilizumab treatment DAS28CRP and HAQ were respectively 4,17 (TJC: 4, SJC: 2, CRP 6,84 md/dL, PGA 71 mm), and 1 and hemoglobin was 8,6 g/dL. At 18th month was present a remission since about six months and the hemoglobin was 11,6 g/dL, as reported in Table 1. <h3>Conclusions</h3> Although in JIA patients there is an anemia due to chronic inflammation, the patient of this report has also a beta thalassemic trait as confounding factor. After Tocilizumab therapy, we obtained a low disease activity after three months and a complete remission after one year, otherwise previous biologic therapies. In addition to this result, the increased of hemoglobin concentration (3 g/dL respect basal value) suggest that Tocilizumab therapy is able to reset low hemoglobin levels due to chronic inflammation. <h3>References</h3> Berent Prakken et al. Juvenile idiopathic arthritis. The Lancet, 2011: 377; 9783:2138 - 2149 Gurion R.et al. Systemic arthritis in children: a review of clinical presentation and treatment. Int. J Infl. 2012;2012:271569 M. C. Genovese et al. Arthritis&amp;Rheum 2008:58(10);2968–2980. <h3>Disclosure of Interest</h3> None Declared
Additional Prone 18F-FDG PET/CT Acquisition to Improve the Visualization of the Primary Tumor and Regional Lymph Node Metastases in Stage II/III Breast Cancer
Authors: Suzana Cipriano Teixeira, Bas B. Koolen, Wouter V. Vogel, Jelle Wesseling, Marcel P. M. Stokkel, Marie-Jeanne T. F. D. Vrancken Peeters, Vincent van der Noort, Emiel J. Th. Rutgers, Renato A. Valdés Olmos
Journal: Clinical Nuclear Medicine (2015)

To prospectively compare prone and supine acquired 18F-FDG PET/CT for visualization of primary tumors and regional lymph nodes in stage II/III breast cancer patients.One hundred ninety-eight patients were included consecutively from August 2010 to April 2012. One hour after administration of 180-240 MBq 18F-FDG, PET/CT images of the thorax were firstly acquired in prone position. Subsequently, a standard PET/CT in supine position from skull base to thighs was made. Both sets of images were tested in a univariate and a multivariate analysis for the number of lesions per breast or lymph node (LN) region and anatomical mismatch between PET and CT images.Images in prone position showed less compression of breast tissue, more primary tumor (PT) multifocality (P < 0.001) and more avid axillary LNs (P < 0.001) compared with supine position. Anatomical mismatch of the axillary LN metastases was found more often on supine PET/CT images compared with prone (P = 0.004). Prone images showed a smaller PT functional volume compared with supine position (P < 0.001).Prone position PET/CT improved the visualization of PT multifocality and the number of detected axillary lymph nodes. Therefore, it is a valuable addition to standard supine PET/CT in the protocol for locoregional assessment in stage II/III breast cancer patients.
1311 HIGH SERUM ENDOCAN IS A MARKER OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND CORONARY ARTERY DISEASE (CAD)
Authors: E. Elsheikh, Z. Younoszai, M. Otgonsuren, S. Hunt, B. Raybuck, Z.M. Younossi
Journal: Journal of Hepatology (2013)
Abstract LB-260: Sensitivity of breast cancer stem cells to TRA-8 anti-DR5 monoclonal antibody
Authors: Angelina I. Londoño Joshi, Patsy G. Oliver, Andres Forero, Albert F. LoBuglio, Donald J. Buchsbaum
Journal: Cancer Research (2010)

Abstract Breast cancer stem cells (BrCSC) are reported to be responsible for self-replication, treatment resistance, and metastases. Doubly enriched populations of BrCSC have been isolated using combined stem cell markers for CD44+/CD24- and increased levels of ALDEFLUOR® positivity based on aldehyde dehydrogenase enzyme activity. We have examined the sensitivity of doubly enriched populations of BrCSC isolated from basal-like breast cancer cell lines as regards anti-DR5 agonistic monoclonal antibody (TRA-8) mediated cytotoxicity. Methods: BrCSC were isolated and characterized from basal breast cancer cell lines (SUM159, SUM149, HCC38 and 2LMP) based on the intracellular accumulation of ALDEFLUOR® reagent and CD44+/CD24- surface expression by flow cytometry. DR5 expression on the BrCSC subpopulation, in vitro cytotoxicity after 24 h exposure to TRA-8, and caspase activation after TRA-8 exposure were evaluated. The effects of TRA-8 on secondary tumorosphere formation were also investigated. Results: Unsorted basal-like cell lines were highly sensitive to TRA-8 mediated cytotoxicity with IC50 values of 0.7-3.0 ng/ml. Doubly enriched CD44+/CD24−/ALDEFLUOR+ BrCSC from these cell lines exhibited comparable DR5 expression and were similarly highly sensitive to TRA-8 induced cytotoxicity with rapid induction of caspase 3 and 8 cleavage. Secondary tumorosphere formation was greater than 90% inhibited by TRA-8 exposure. An agonistic anti-DR4 monoclonal antibody (2E12) had no effect, and TRAIL was only partially inhibitory to secondary tumorosphere formation at equimolar concentrations. TRA-8 effect on BrCSC tumorigenicity will be presented. These studies suggest that TRA-8 may be an effective targeted therapy directed at BrCSC in basal-like breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-260.
Plenty of Nothing — A Report from the Medicare Commission
Authors: B C Vladeck
Journal: New England Journal of Medicine (1999)

The National Bipartisan Commission on the Future of Medicare, which began its work to great fanfare just over a year ago, held its last meeting on March 16. The commission, established by the Balanced Budget Act of 1997, had 17 members. The act required 11 affirmative votes for the adoption of any recommendations, a provision interpreted by the commission's cochairs, Senator John Breaux (D-La.) and Representative Bill Thomas (R-Calif.), as requiring 11 votes for any action, even issuing a report. Thus, when on March 16 a package of proposals assembled by the chairs commanded only 10 “yeas,” the commission concluded . . .
AB0040 Il17 and IFN gamma are important in the severity of kidney disease in SLE
Authors: M. Uysal-Yazıcı, D. Orhan, B. Gülhan, N. Beşbaş, G. Kale, S. Özen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Kidney involvement, especially class IV nephritis, has a large impact on the morbidity and mortality of lupus patients. <h3>Objectives</h3> We aimed to understand the role of Th17 and Th1 cells in the pathogenesis and severity of lupus nephritis. <h3>Methods</h3> We retrospectively studied the renal biopsies of systemic lupus erythematosus (SLE) patients with nephritis class II, III and IV; who were admitted to our university hospital and biopsied in the last 20 years. The glomeruler and tubuler frequency and intensity of IFN-gama and IL-17 were determined by immunohistochemical analyses of kidney sections. Patient files were analysed for clinical and laboratory data and SLE Disease Activity Index (SLEDAI) scores. <h3>Results</h3> Out of 39 patients, 6 (15,38%) were males. 14 of the patients had class II and III lupus nephritis and 25 had class IV. The mean age of diagnosis was 12,5±2,7 years (range 6-17). The SLEDAI score and the level of anti-ds DNA before treatment were higher among the patients with Class IV nephritis compared to classes II and III (p=0,033 and p=0,014, respectively). The glomerular and tubular immunohistochemical frequency and intensity of IL-17 and IFN gamma were statistically significant higher in class 4 nephritis when compared with class 2-3 nephritis group (p=0,00). There were negative correlations between the GFR of the subjects and the extent of both IL17 and IFN gamma. The intensity of the glomerular IL17 staining correlated with the IFN staining. There were also significant correlations between SLEDAI and the extent of the IL17 staining whereas there was a negative correlation between the extent of IFN and the complement 3 levels. <h3>Conclusions</h3> The difference in the staining intensity between patients with class IV nephritis and those with milder involvement and the correlations with certain disease activity indices suggest that a Th17 and Th1 dominance may play a role in the progression of the kidney disease. <h3>References</h3> Shin MS, Lee N, Kang I. Effector T-cell subsets in systemic lupus erythematosus: update focusing on Th17 cells. Curr Opin Rheumatol 2011; 23: 444-448. Perry D, Peck AB, Carcamo WC, Morel L, Nguyen CQ. The current concept of Th 17 cells and their expanding role in systemic lupus erythematosus. Arthritis 2011; 810649: Epub Mar 22. <h3>Disclosure of Interest</h3> None Declared
Effect of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor on Chemotherapy-Induced Myelosuppression
Authors: Karen S. Antman, James D. Griffin, Anthony Elias, Mark A. Socinski, Louise Ryan, Stephen A. Cannistra, Dagmar Oette, Mary Whitley, Emil Frei, Lowell E. Schnipper
Journal: New England Journal of Medicine (1988)

An increase in the dose of chemotherapy enhances the response of many experimental and clinical cancers, but the extent of dose escalation is often limited by myelosuppression. In preliminary trials, recombinant human granulocytemacrophage colony-stimulating factor (rhGM-CSF) has augmented leukocyte numbers and function, but the optimal dose is not established. We treated 16 adults who had inoperable or metastatic sarcomas with escalating doses of rhGM-CSF before and immediately after a first cycle of chemotherapy (cycle 1) to assess hematologic response and toxicity. A second cycle of chemotherapy (cycle 2) was given without rhGM-CSF. RhGM-CSF was tolerated well at doses of 4 to 32 μg per kilogram of body weight per day. At 64 μg per kilogram per day, edema and thrombi around a central venous catheter developed in two of four patients. Leukocyte and granulocyte counts increased significantly during the rhGM-CSF infusion. Neutropenia after cycle 1 was significantly less severe and shorter in duration than after cycle 2 (P<0.01). Mean total leukocyte and platelet nadirs were 1.0 and 101x109 per liter for cycle 1 and 0.45 and 44x109 per liter for cycle 2 (P<0.01), and the median intervals from day 1 of chemotherapy to neutrophil recovery (>0.500x109 per liter) were 15 and 19 days, respectively (P<0.01). The duration of neutropenia was 3.5 days with cycle 1 and 7.4 days with cycle 2 (P<0.01).
Appearance of a Hepatic Hemangioma on Prostate Immunoscintigraphy
Authors: BORYS R. KRYNYCKYI, ANDREW GANELES, LEONARD M. FREEMAN, LIONEL S. ZUCKIER
Journal: Clinical Nuclear Medicine (1996)

In this case, the authors describe the appearance of hemangioma, the most common benign tumor of the liver, on early and delayed In-111 CP antibody images. The early immunoscintigraphic images show intense blood pool activity comparable in appearance to labeled RBC imaging, the current procedure of choice for confirming the diagnosis of hemangioma. In combination with disappearance of blood pool activity on the late scintigraphic images, these findings are pathognomonic for hemangioma and sufficiently distinct from the appearance of hepatic metastases on In-111 labeled antibody images to obviate the need for further confirmatory diagnostic studies.
Polymorphism of the Collagen Type Iα1 Gene and Ethnic Differences in Hip-Fracture Rates
Authors: Sian Beavan, Ann Prentice, Bakary Dibba, Liya Yan, Cyrus Cooper, Stuart H. Ralston
Journal: New England Journal of Medicine (1998)

To the Editor: The susceptibility to osteoporotic fracture varies markedly among ethnic groups, and the differences are partly independent of differences in bone mass. For example, hip fractures ar...
Age-sex–specific ranges of platelet count and all-cause mortality: prospective findings from the MOLI-SANI study
Authors: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia De Curtis, Maria Benedetta Donati, Chiara Cerletti, Giovanni de Gaetano, Licia Iacoviello
Journal: Blood (2016)