tbuckley/cabot-search huggingface dataset:
Multimodality Imaging of Angiogenesis in a Rabbit Atherosclerotic Model by GEBP11 Peptide Targeted Nanoparticles
Authors: Tao Su, Ya-Bin Wang, Dong Han, Jing Wang, Shun Qi, Lei Gao, Ya-Hui Shao, Hong-Yu Qiao, Jiang-Wei Chen, Shu-Hui Liang, Yong-Zhan Nie, Jia-Yi Li, Feng Cao
Journal: Theranostics (2017)

Background and Aims: Angiogenesis is an important pathological process during progression of plaque formation, which can result in plaque hemorrhage and vulnerability. This study aims to explore non-invasive imaging of angiogenesis in atherosclerotic plaque through magnetic resonance imaging (MRI) and positron emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis were performed to detect the effects of NGD-MNPs on cell proliferation, cell cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo MRI and PET imaging of atherosclerotic plaque were carried out at different time points after intravenous injection of nanoparticles. Results: The NGD-MNPs with hydrodynamic diameter of 130.8 nm ± 7.1 nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co-localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a promising MR and PET dual imaging probe for visualizing the vulnerable plaques.
A novel single domain antibody (sdAb) SBT-100 targeting intracellular STAT3 to inhibit major subtypes of human breast cancer.
Authors: Sunanda Singh, Genoveva Murillo, Rajendra Mehta, Dong Chen, Avani Singh, Samara Singh, Anjali Singh, Ashutosh S Parihar
Journal: Journal of Clinical Oncology (2016)

e14000 Background: The primary role of ER+/PR+ and HER2+ in breast cancers is well known. It has been well established that antiestrogens and Herceptin are very efficacious for ER+/PR+ and HER2+ cancers respectively. However the management of triple negative breast cancer (TNBC) has been challenging. In literature there is strong evidence for the role of activated STAT3 in the pathogenesis of TNBC. What is less understood is whether activated STAT3 plays a significant role in the malignant phenotype of ER+/PR+ and HER2+ breast cancers. Therefore we evaluated effects of SBT-100, a novel single domain antibody, on ER+/PR+, HER2+, and TNBC subtypes of breast cancers. Methods: Human breast cancers cells MCF-7 (ER+/PR+), BT474 (HER2+), and MDA-MB-231 (TNBC) were grown in culture. The breast cancers cells were treated at varying doses of SBT-100, that specifically binds to human STAT3, ranging from 0ug/ml to 200ug/ml. MTT assays were performed after 3 days of treatment with SBT-100 and the growth inhibition was calculated. Immunoprecipitation (IP) and western blot analyses were carried out to confirm the binding of STAT3 to SBT-100. Results: Compared to controls, which received only vehicle, all evaluated cell lines, MCF-7, BT474 and MDA-MB-231 (TNBC) cells, demonstrated > 90% inhibition of cell proliferation (p < 0.001) at 100ug/ml. The IC50's of SBT-100 for MCF-7 is 986nM, BT474 is 1.68uM, and MDA-MB-231 is 666nM. Immunoprecipitation and western blot analyses showed that SBT-100 binds to both the unphosphorylated and phosphorylated STAT3. Conclusions: These results indicated that the novel single domain antibody, SBT-100, binds to human STAT3 resulting in statistically significant growth suppression in ER+/PR+, HER2+, and TNBC breast cancers. SBT-100 is being further evaluated in depth for possible management of breast cancers.
Effect of Financial Incentives on Glucose Monitoring Adherence and Glycemic Control Among Adolescents and Young Adults With Type 1 Diabetes
Authors: Charlene A. Wong, Victoria A. Miller, Kathryn Murphy, Dylan Small, Carol A. Ford, Steven M. Willi, Jordyn Feingold, Alexander Morris, Yoonhee P. Ha, Jingsan Zhu, Wenli Wang, Mitesh S. Patel
Journal: JAMA Pediatrics (2017)

Glycemic control often deteriorates during adolescence and the transition to young adulthood for patients with type 1 diabetes. The inability to manage type 1 diabetes effectively during these years is associated with poor glycemic control and complications from diabetes in adult life.To determine the effect of daily financial incentives on glucose monitoring adherence and glycemic control in adolescents and young adults with type 1 diabetes.The Behavioral Economic Incentives to Improve Glycemic Control Among Adolescents and Young Adults With Type 1 Diabetes (BE IN CONTROL) study was an investigator-blinded, 6-month, 2-arm randomized clinical trial conducted between January 22 and November 2, 2016, with 3-month intervention and follow-up periods. Ninety participants (aged 14-20) with suboptimally controlled type 1 diabetes (hemoglobin A1c [HbA1c] >8.0%) were recruited from the Diabetes Center for Children at the Children's Hospital of Philadelphia.All participants were given daily blood glucose monitoring goals of 4 or more checks per day with 1 or more level within the goal range (70-180 mg/dL) collected with a wireless glucometer. The 3-month intervention consisted of a $60 monthly incentive in a virtual account, from which $2 was subtracted for every day of nonadherence to the monitoring goals. During a 3-month follow-up period, the intervention was discontinued.The primary outcome was change in HbA1c levels at 3 months. Secondary outcomes included adherence to glucose monitoring and change in HbA1c levels at 6 months. All analyses were by intention to treat.Of the 181 participants screened, 90 (52 [57.8%] girls) were randomized to the intervention (n = 45) or control (n = 45) arms. The mean (SD) age was 16.3 (1.9) years. The intervention group had significantly greater adherence to glucose monitoring goals in the incentive period (50.0% vs 18.9%; adjusted difference, 27.2%; 95% CI, 9.5% to 45.0%; P = .003) but not in the follow-up period (15.3% vs 8.7%; adjusted difference, 3.9%; 95% CI, -2.0% to 9.9%; P = .20). The change in HbA1c levels from baseline did not differ significantly between groups at 3 months (adjusted difference, -0.08%; 95% CI, -0.69% to 0.54%; P = .80) or 6 months (adjusted difference, 0.03%; 95% CI, -0.55% to 0.60%; P = .93).Among adolescents and young adults with type 1 diabetes, daily financial incentives improved glucose monitoring adherence during the incentive period but did not significantly improve glycemic control.clinicaltrials.gov Identifier: NCT02568501.
Abstract P132: Diabetes-Induced Cardiac Dysfunction Is Rescued by Endothelial Cationic Amino Acid Transporter 1 Overexpression in Mice
Authors: Rebecca H Ritchie, Makhala M Khammy, Marissa A Bowden, Jennifer Irvine, Karen Andrews, Karina Huynh, Helen Kiriazis, David Kaye, Kylie Venardos
Journal: Circulation Research (2011)

Nitric oxide (NO) bioavailability is markedly impaired in diabetes, contributing to endothelial and myocardial dysfunction. Our aim was to determine if endothelial-specific overexpression of Cationic Amino Acid Transporter 1 (CAT-1, to enhance L-arginine uptake and NO generation) prevents diabetes-induced endothelial and cardiac dysfunction in diabetic mice. Male CAT-1 transgenic and non-transgenic (Ntg) 6 week old mice were administered streptozotocin (STZ, 55mg/kg ip daily for 5 days). Sham mice received citrate buffer vehicle. Myocardial function was assessed in anaesthetised mice in vivo 12 weeks later, via echocardiography. Vascular reactivity was then assessed in vitro. Compared to their non-diabetic littermates (n=6), Ntg STZ mice (n=6) exhibited reduced early-to-late blood flow velocity ratios (E/A, 1.7±0.2 vs 2.4±0.1, p&lt;0.01) and prolonged deceleration time (DT, 40±1 vs 31±2msec, p&lt;0.002), indicative of diastolic dysfunction. Decreased E-wave velocity (109±4 vs 76±12msec, p&lt;0.01) and increased A-wave velocity (45±3 vs 55±4msec, p&lt;0.05) were also observed. Systolic dysfunction was observed in Ntg STZ mice compared to shams, on reduced fractional shortening (FS, 30±1 vs 39±1%, p&lt;0.002). In CAT-1 mice, diabetes did not impair E/A ratio (2.1±0.2), FS (40±3%) or DT (33±1msec, n=8). Thoracic aortic responses to the endothelium-dependent vasodilator acetylcholine (ACh) were unchanged by diabetes in Ntg and CAT-1 Tg mice compared to sham Ntg mice (pEC50 7.0±0.1 vs 7.2±0.1 and 7.1±0.1). There was a non-significant trend for sham CAT-1 Tg mice to show greater sensitivity to ACh than sham Ntg mice (pEC50 7.5±0.1 vs 7.1±0.1). Responses to the endothelium-independent vasodilator sodium nitroprusside and the vasoconstrictor noradrenaline were unaffected by diabetes and/or genotype. In conclusion, our results suggest that endothelial-specific CAT-1 overexpression protects against cardiac dysfunction via a mechanism independent of the systemic vasculature. The involvement of the coronary vasculature remains to be determined. Endothelial CAT-1 up-regulation as a potential therapeutic target for diabetic cardiomyopathy is an exciting prospect.
Abstract #1737: Structural and functional analysis of Nucleophosmin I (NPM1) in human malignant gliomas.
Authors: Gamil Antoun, Francis Ali-Osman
Journal: Cancer Research (2009)

Nucleophosmin I (NPM1), a member of the NPM family, is an abundant phosphoprotein that contains a nuclear localization signal and thus shuttles between the nuclear and cytoplasmic cellular compartments, particularly, during cell cycle progression. A multifunctional protein, NPM1 is involved in a variety of cellular functions, including, transcriptional regulation, cellular proliferation, apoptosis, differentiation and motility, as well as, in the chaperoning of pre-ribosomal particles and ribosome biogenesis, stress response, the maintenance of genomic stability and DNA repair. More recent studies have suggested NPM1 to be a marker of malignancy in gliomas and to regulate the activity of tumor suppressors and cytoskeletal dynamics in astrocytes. In other malignancies, notably, acute myeloid leukemia, mutations at exon 12 of NPM1 have been associated with the relocalization of NPM1 from the nucleolus to the cytoplasm and with differential prognosis. These NPM1 mutant proteins are characterized by, at least one tryptophan residue affecting codon 289 and/or 291 residues within the nucleolar localization signal domain at the C-terminus of the protein. Against this background, we examined a panel of malignant glioma cell lines and primary specimens, including, glioblastomas, anaplastic astrocytomas and normal astrocytomas for the expression and mutational status of NPM1. NPM1 mutations were examined by amplifying a DNA fragment containing the mutational hotspot in exon 12, the PCR product purified and directly sequenced. Transcriptional expression was determined by either immunohistochemistry and/or quantitative RT-PCR. The results showed no detectable mutations in exon 12 of the NPM1 gene in any of the specimens and cell lines, regardless of histology. In contrast, we observed a significant heterogeneity in expression of NPM1 gene transcripts, with the highest level in glioblastomas. Flow cytometry indicated a relationship between the level of NPM1 gene transcripts and/or protein expression and an increased fraction of S-phase cells. These results suggest that in malignant gliomas, the NPM1 gene is not regulated by structural alterations, i.e. mutations, but rather by transcriptional regulation. The findings suggest a direct role of NPM1 in the biology of gliomas. Ongoing studies are directed at determining the mechanistic basis of the differential NPM1 expression in gliomas and its effect on therapeutic response.  Supported by NIH grants RO1 CA127872, RO1 CA 112519, P50CA108786 and  P30-CA14236.    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1737.
Encuesta EUVAC-NET: sistemas nacionales de vigilancia del sarampión en la UE, Suiza, Noruega e Islandia
Authors: S Glismann, T Ronne, J E Schmidt
Journal: Eurosurveillance (2001)

La red EUVAC-NET llevo a cabo un estudio por cuestionario sobre los sistemas de vigilancia de sarampion en los paises miembros de la UE, Suiza, Noruega and Islandia. Se cumplimentaron todos los cuestionarios. De los 18 paises, 16 cuentan con sistemas de vigilancia de sarampion. Casi todos ellos disponen de datos de casos y, en todos los paises, la tendencia es el paso hacia esta vigilancia de casos individualizados, aunque existen diferencias en lo que atane a las definiciones y clasificaciones de casos. En todos los paises de EUVAC-NET existe un programa de vacunacion de dos dosis de SPR, pero los metodos utilizados para evaluar la cobertura vacunal son variados.
Modulation of Bcl-2 expression in androgen independent human prostate carcinoma LNCaP-LN3 cells leads to increased apoptosis and decreased growth
Authors: Renduo Song, Curtis A. Pettaway
Journal: Cancer Research (2005)

2729   Bcl-2 is an outer mitochondrial membrane protein with potent anti-apoptotic properties. Our previous studies demonstrated that highly metastatic androgen independent human prostate carcinoma LNCaP-LN3 cells express higher  bcl-2 , higher PSA (prostate specific antigen) (Clin Cancer Res 2:1627, 1996, Cancer Res 56:5594, 1996), and lower androgen receptor levels with relative resistance to apoptosis in androgen depleted charcoal stripped serum (CSS). The purpose of the present studies was to determine the phenotypic consequences of modulating Bcl-2 expression in metastatic androgen independent cells. LNCaP-LN3 cells were transfected with an siRNA-Bcl-2 oligonucleotide (small interference RNA), and a Western blot was performed to confirm down-modulation of Bcl-2 expression. Cell growth and apoptosis were evaluated using BrDU incorporation and TUNEL studies. The results indicated that after down regulation of Bcl-2 expression (41%), LNCaP-LN3 cells exhibited 30-36% growth inhibition in CSS culture media in comparison with cells transfected with non-specific siRNA. Cell proliferation was decreased 53% ± 4 and apoptosis increased 77% ± 16. These data suggest that in LNCaP-LN3 cells resistance to androgen ablation  in vitro  is mediated in part via Bcl-2 protein. cDNA microarray analysis is in progress to determine which genes affecting apoptosis and proliferation were modulated subsequent to altering Bcl-2 protein levels.
P2.03b-083 Soluble Angiogenic Factors as Predictive Biomarkers of Response to Docetaxel plus Nintedanib as Second Line Therapy in NSCLC
Authors: Denisse Lee-Cervantes, Graciela Cruz-Rico, David Michel-Tello, Laura-Alejandra Ramírez-Tirado, Eduardo Amieva-Rivera, Omar Macedo-Pérez, Diana Flores-Estrada, Andrés Cardona, Oscar Arrieta
Journal: Journal of Thoracic Oncology (2017)
Implementación del Reglamento Sanitario Internacional (2005) en Europa
Authors: G Rodier, M Hardiman, B Plotkin, B Ganter
Journal: Eurosurveillance (2006)

La adopcion del Reglamento Sanitario Internacional (2005) (tambien conocido como RSI (2005) o Reglamento revisado) proporciona una nueva y relevante herramienta legal para la proteccion de la salud publica internacional. Entrara en vigor el 15 de Junio de 2007, y el Articulo 2 (« Objeto y alcance ») define el objetivo global de los esfuerzos de los Estados Partes (y de la Organizacion Mundial de la Salud) en el marco del Reglamento revisado que sera la prevencion, el control y la lucha contra la difusion internacional de las enfermedades, a traves de medidas proporcionales a los riesgos de salud publica, sin contrarrestar inutilmente el trafico internacional. Las medidas sanitarias tomadas en el marco del Reglamento revisado se llevaran a cabo respetando los derechos humanos de los viajeros, lo que necesita nuevas obligaciones especificas en este area. 
Segun el RSI (2005), los Estados Partes (estados miembros de la OMS que estaran ligados por el RSI (2005) deberan tener recursos de salud publica dedicados a la vigilancia y al control de las enfermedades, como tambien recursos suplementarios para los puertos, aeropuertos y fronteras internacionales designados. Este compromiso colectivo unico necesitara una colaboracion estrecha entre la OMS y los Estados Partes, y una colaboracion intersectorial en cada Estado, incluyendo una cooperacion entre los distintos niveles administrativos o gubernamentales – un objetivo delicado para los estados federales – y una cooperacion transversal entre ministerios y disciplinas. La cooperacion entre los estados partes es un aspecto clave del Reglamento revisado, sea entre paises vecinos, entre paises que tienen relaciones comerciales o simplemente con otros miembros de la comunidad internacional. Esta colaboracion es particularmente relevante para los Estados Miembros de la Union Europea.
Aparición de Salmonella typhimurium DT 104 resistente a múltiples fármacos en la República Checa
Authors: R Karpíšková, D Benes, D Dedicova
Journal: Eurosurveillance (1999)

La Republica Checa es un pais situado en la zona central de Europa, cuya poblacion asciende a unos 10 millones de habitantes. La salmonelosis es la infeccion intestinal que se declara con mayor frecuencia. Hasta 1989, se declaraban unos 10.000 casos por ano, aislandose un numero similar de Salmonella enteritidis y S. typhimurium. Desde 1989, los casos de salmonelosis humana han aumentado rapidamente. Entre 1993 y 1997, el numero de casos anuales notificado cada ano fluctuo de 39.862 a 54.554, lo que supone una incidencia de 386 a 518 casos por 100.000 habitantes, y alcanzo su punto maximo en 1995. La S. enteritidis represento el 95% de los casos declarados y S. typhimurium, el 3%.
Brief Report: Association of Natural Killer Cell Ligand Polymorphism HLA-C Asn80Lys With the Development of Anti-SSA/Ro-Associated Congenital Heart Block
Authors: Hannah C. Ainsworth, Miranda C. Marion, Tiziana Bertero, Antonio Brucato, Rolando Cimaz, Nathalie Costedoat‐Chalumeau, Micaela Fredi, Patrick Gaffney, Jennifer Kelly, Kateri Levesque, Alice Maltret, Nathalie Morel, Veronique Ramoni, Amelia Ruffatti, Carl D. Langefeld, Jill P. Buyon, Robert M. Clancy
Journal: Arthritis & Rheumatology (2017)

Objective Fetal exposure to maternal anti‐ SSA /Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block ( CHB ), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA –C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin‐like receptor ( KIR ) and thus renders natural killer ( NK ) cells incapable of restricting inflammation, contributes to the development of CHB . Methods Members of 192 pedigrees in the US and Europe (194 cases of CHB , 91 unaffected siblings, 152 fathers, 167 mothers) and 1,073 out‐of‐study controls were genotyped on the Immunochip single‐nucleotide polymorphism microarray. Imputation was used to identify associations at HLA –C Asn80Lys (Asn, C1; Lys, C2) and KIR . Tests for association were performed using logistic regression. McNemar's test and the pedigree disequilibrium test ( PDT ) were used for matched analyses between affected and unaffected children. Results Compared with out‐of‐study controls of the same sex, the C2 allele was less frequent in the mothers (odds ratio [ OR ] 0.63, P = 0.0014) and more frequent in the fathers ( OR 1.40, P = 0.0123), yielding a significant sex‐by‐C2 interaction ( P = 0.0002). The C2 allele was more frequent in affected siblings than in unaffected siblings ( OR 3.67, P = 0.0025), which was consistent with the PDT results ( P = 0.016); these results were observed in both sexes and across the US and European cohorts. There was no difference in the frequency of the inhibitory KIR genotype ( KIR AA ) between affected and unaffected children ( P = 0.55). Conclusion These data establish C2 as a novel genetic risk factor associated with CHB . This observation supports a model in which fetuses with C2 ligand expression and maternal anti‐ SSA /Ro positivity may have impaired NK cell surveillance, resulting in unchecked cardiac inflammation and scarring.
TCT-185 Impact of liver cirrhosis on early- and mid-term result after transcatheter aortic valve replacement for sever aortic stenosis
Authors: Yuki Nakamura, Toru Kuratani, Kei Torikai, Kazuo Shimamura, Koichi Maeda, Isamu Mizote, Yasuhiro Ichibori, Toshinari Onishi, Yasushi Sakata, Yoshiki Sawa
Journal: Journal of the American College of Cardiology (2017)
JAM-A as a prognostic factor and new therapeutic target in multiple myeloma
Authors: A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Journal: Leukemia (2017)

Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.