tbuckley/cabot-search huggingface dataset:
Value of endoscopic ultrasonographic features in predicting the malignancy of pancreatic mucinous cystic neoplasms and intraductal papillary mucinous neoplasms
Authors: X.-B. Zhan, B. Xie, D. Ma, Z.-S. Li
Journal: Gut (2011)

<h3>Introduction</h3> Pancreatic mucinous neoplasms, which mainly include mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), possess a potentially malignant tendency. It remains difficult to adopt reliable methods in predicting the malignancy progression of the conditions.1 Endoscopic ultrasonography (EUS) can present relatively high diagnostic value in respect of sensitivity and specificity.2 However, its value in predicting their malignancy is unclear yet. <h3>Methods</h3> The data of EUS features of 21 patients with pancreatic mucinous neoplasms (18 males and 3 females) were reviewed. All the patients were admitted in Changhai hospital between January 1998 and December 2007. Surgical resection were completed and confirmed by subsequent surgical pathology in all the patients. Of them, 11 were IPMNs (5 benign, 2 borderline, 4 malignant) and 10 were MCNs (2 benign, 8 malignant). With the SPSS10.0 statistical software, independent sampler t test was performed on the norm variables in mean±SD form, while enumeration data in fourfold table was verified by χ<sup>2</sup> test with Fisher exact probabilistic method. Area under the receiver operating characteristic curve (ROC) for all data was calculated and the optimal cut-off values were determined by Youden Index. A p value of less than 0.05 was considered to be statistically significant. <h3>Results</h3> It was found that the main pancreatic duct with a diameter of ≥11.0 mm can predict the malignancy of IPMNs with a sensitivity of 75% and specificity of 100%, and the mural nodule with a height of ≥4.3 mm can predict the malignancy of IPMNs with a sensitivity of 100% and specificity of 100%. Cystic wall with a thickness of ≥2.4 mm can predict the malignancy of MCNs with a sensitivity of 100% and specificity of 100%, and mural nodule with a height of ≥8.9 mm can predict the malignancy of MCNs with a sensitivity of 87.5% and specificity of 100%. <h3>Conclusion</h3> EUS features are of high value in predicting the malignancy of MCNs and IPMNs.
Dissecting the expression landscape of RNA-binding proteins in human cancers
Authors: Bobak Kechavarzi, Sarath Chandra Janga
Journal: Genome biology (2014)

Abstract Background RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level. Results We explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact. Conclusions Overall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.
Micro- and Nanomechanics of the Cochlear Outer Hair Cell
Authors: W. E. Brownell, A. A. Spector, R. M. Raphael, A. S. Popel
Journal: Annual Review of Biomedical Engineering (2001)

▪ Abstract Outer hair cell electromotility is crucial for the amplification, sharp frequency selectivity, and nonlinearities of the mammalian cochlea. Current modeling efforts based on morphological, physiological, and biophysical observations reveal transmembrane potential gradients and membrane tension as key independent variables controlling the passive and active mechanics of the cell. The cell's mechanics has been modeled on the microscale using a continuum approach formulated in terms of effective (cellular level) mechanical and electric properties. Another modeling approach is nanostructural and is based on the molecular organization of the cell's membranes and cytoskeleton. It considers interactions between the components of the composite cell wall and the molecular elements within each of its components. The methods and techniques utilized to increase our understanding of the central role outer hair cell mechanics plays in hearing are also relevant to broader research questions in cell mechanics, cell motility, and cell transduction.
Towards an integrated proteomic and glycomic approach to finding cancer biomarkers
Authors: Allen D Taylor, William S Hancock, Marina Hincapie, Naoyuki Taniguchi, Samir M Hanash
Journal: Genome Medicine (2009)

Advances in mass spectrometry have had a great impact on the field of proteomics. A major challenge of proteomic analysis has been the elucidation of glycan modifications of proteins in complex proteomes. Glycosylation is the most structurally elaborate and diverse type of protein post-translational modification and, because of this, proteomics and glycomics have largely developed independently. However, given that such a large proportion of proteins contain glycan modifications, and that these may be important for their function or may produce biologically relevant protein variation, a convergence of the fields of glycomics and proteomics would be highly desirable. Here we review the current status of glycoproteomic efforts, focusing on the identification of glycoproteins as cancer biomarkers.
Expiratory muscle training in patients recovering open thoracic and cardiac surgery
Authors: Ernesto Crisafulli, Massimo Cerulli, Elena Venturelli, Fabio Florini, Nicoletta Kidonias, Assunta De Biase, Vittoria Furino, Enrico M. Clini
Journal: European Respiratory Journal (2012)

Respiratory muscle training has been so far demonstrated to be effective as a rehabilitation technique in COPD patients. However, it is still not clear whether it may similarly be useful when used in patients recovering open thoracic and cardiac surgery.

We have therefore undertaken a randomised 14-day trial in these patients to evaluate changes in maximal expiratory (MEP, as the primary outcome) and inspiratory (MIP) pressures, lung volumes (FEV1, FCV, CV, CI, VR), oxygenation index (PaO2/FiO2), perceived symptoms (VAS), and generic quality of life (SF36) following an early intervention including lung expansion + expiratory muscle training (Active) or lung expansion + sham training (Control). Training has been set with incremental resistive load over the study period.

At present, 39 patients (out of the 54 programmed) completed the study, 19 and 20 in Active and Control respectively, with one patient dropped in each group. Anthropometrics and general characteristics, type of surgery, and functional variables at baseline were similar. Pre-to-post change of MEP showed a greater (p<0.043) change in Active (+17.5±25.7 cmH2O) than in Control (+14.4±26.2 cmH2O), whereas FVC, VC, TLC, and SF36 (mental and physical components) trended to better improve in the Active population. Daily recording of VAS dyspnea, discomfort and pain scores similarly decreased in the two groups.

This study confirms that specific and early expiratory muscle training is feasible and effective in patients recovering open thoracic and cardiac surgery.

(Unrestricted research grant by Medinet-Italia).
Overexpression of Histone Deacetylase 1 Confers Resistance to Sodium Butyrate–Mediated Apoptosis in Melanoma Cells through a p53-Mediated Pathway
Authors: Debdutta Bandyopadhyay, Anupam Mishra, Estela E. Medrano
Journal: Cancer Research (2004)

Melanoma cells typically express wild-type p53, yet they are notoriously resistant to DNA-damaging agents. Here, we show that sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor, induced apoptosis in human melanoma cells in a dose- and time-dependent manner. Apoptosis was associated with HDAC1-dependent induction of Bax and acetylation of p53. Down-regulation of HDAC1 by an antisense vector sensitized the cells to NaB-induced apoptosis, whereas its overexpression conferred resistance to this agent. Increased HDAC1 levels and activity impaired NaB-mediated activation of Bax promoter and Bax protein levels. Finally, using p53-null melanoma cell line and RNA interference in cells expressing wild-type p53 protein, we show that Bax induction and NaB-mediated apoptosis is p53 dependent.
Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: A Randomized Controlled Trial
Authors: Antonio Palumbo, Sara Bringhen, Davide Rossi, Maide Cavalli, Alessandra Larocca, Roberto Ria, Massimo Offidani, Francesca Patriarca, Chiara Nozzoli, Tommasina Guglielmelli, Giulia Benevolo, Vincenzo Callea, Luca Baldini, Fortunato Morabito, Mariella Grasso, Giovanna Leonardi, Manuela Rizzo, Antonietta Pia Falcone, Daniela Gottardi, Vittorio Montefusco, Pellegrino Musto, Maria Teresa Petrucci, Giovannino Ciccone, Mario Boccadoro
Journal: Journal of Clinical Oncology (2010)

Purpose The combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation. Patients and Methods A total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival. Results The 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio [HR], 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P &lt; .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP. Conclusion VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.
Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer
Authors: P. Schöffski, B. Thate, G. Beutel, O. Bolte, D. Otto, M. Hofmann, A. Ganser, A. Jenner, P. Cheverton, J. Wanders, T. Oguma, R. Atsumi, M. Satomi
Journal: Annals of Oncology (2004)
Pseudomonas infection risk in bronchiectasis: A retrospective cohort analysis of longitudinal microbiology in 174 patients
Authors: Hannah Jary, Jim MacFarlane, Katy Hester, Paul McAlinden, Therese Small, John Perry, Kathy Walton, Anthony De Soyza
Journal: European Respiratory Journal (2012)

Background: Pseudomonas aeruginosa (PA) is a key pathogen in bronchiectasis, a disease characterised by recurrent infections. However, little is known of the infection risk in bronchiectasis stratified by levels of airflow impairment.  Aims: To explore the relationship between longitudinal airway microbiology in bronchiectasis and clinical markers of disease severity.  Methods: A retrospective database review of consecutive adult patients attending a UK bronchiectasis clinic from 2007 and 2010. We stratified patients by lung function (FEV1 % predicted: severe ≤40%; moderate 41-79%; mild ≥ 80%).  Results: 174 patients were identified with mean microbiological data for 6 years. Mean exacerbation frequency in 152 patients was 4.17/year; 70% reported 3+ exacerbations per year. Patients had a mean FEV1 % predicted of 65.7 (±30.1), with minimal, moderate and severe airflow limitation found in 27.0%, 50.0% 21.8% of patients respectively (2 patients had missing data). Aetiology of bronchiectasis was found to be idiopathic or post-infectious in 58.8% and COPD in 9.2%. Isolation of Haemophilus influenzae (HI) was more common than of PA (52.9% vs 47.1%), but persistent colonisation was more common with PA. Of patients with minimal airflow limitation, 31.9% isolated PA compared to 71.1% of those with severe airflow limitation. Hospital admissions but not self reported exacerbations were more common in the PA infected group.  Conclusions: PA is associated with greater persistence rates and more hospital admissions than HI. PA infection occurs across all strata of lung function impairment. Careful microbiology follow up is required even in those with preserved lung function.
Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer
Authors: Georgios Giamas, Aleksandra Filipović, Jimmy Jacob, Walter Messier, Hua Zhang, Dongyun Yang, Wu Zhang, Belul Assefa Shifa, Andrew Photiou, Cathy Tralau-Stewart, Leandro Castellano, Andrew R Green, R Charles Coombes, Ian O Ellis, Simak Ali, Heinz-Josef Lenz, Justin Stebbing
Journal: Nature Medicine (2011)
What monkeys can tell us about metacognition and mindreading
Authors: Nate Kornell, Bennett L. Schwartz, Lisa K. Son
Journal: Behavioral and Brain Sciences (2009)

Abstract Thinkers in related fields such as philosophy, psychology, and education define metacognition in a variety of different ways. Based on an emerging standard definition in psychology, we present evidence for metacognition in animals, and argue that mindreading and metacognition are largely orthogonal.
High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas
Authors: Begoña Diosdado, Tineke E. Buffart, Russell Watkins, Beatriz Carvalho, Bauke Ylstra, Marianne Tijssen, Anne S. Bolijn, Fraser Lewis, Karen Maude, Caroline Verbeke, Iris D. Nagtegaal, Heike Grabsch, Chris J.J. Mulder, Phil Quirke, Peter Howdle, Gerrit A. Meijer
Journal: Clinical Cancer Research (2010)

The molecular pathogenesis of small intestinal adenocarcinomas is not well understood. Understanding the molecular characteristics of small bowel adenocarcinoma may lead to more effective patient treatment.Forty-eight small bowel adenocarcinomas (33 non-celiac disease related and 15 celiac disease related) were characterized for chromosomal aberrations by high-resolution array comparative hybridization, microsatellite instability, and APC promoter methylation and mutation status. Findings were compared with clinicopathologic and survival data. Furthermore, molecular alterations were compared between celiac disease-related and non-celiac disease-related small bowel adenocarcinomas.DNA copy number changes were observed in 77% small bowel adenocarcinomas. The most frequent DNA copy number changes found were gains on 5p15.33-5p12, 7p22.3-7q11.21, 7q21.2-7q21.3, 7q22.1-7q34, 7q36.1, 7q36.3, 8q11.21-8q24.3, 9q34.11-9q34.3, 13q11-13q34, 16p13.3, 16p11.2, 19q13.2, and 20p13-20q13.33, and losses on 4p13-4q35.2, 5q15-5q21.1, and 21p11.2-21q22.11. Seven highly amplified regions were identified on 6p21.1, 7q21.1, 8p23.1, 11p13, 16p11.2, 17q12-q21.1, and 19q13.2. Celiac disease-related and non-celiac disease-related small bowel adenocarcinomas displayed similar chromosomal aberrations. Promoter hypermethylation of the APC gene was found in 48% non-celiac disease-related and 73% celiac disease-related small bowel adenocarcinomas. No nonsense mutations were found. Thirty-three percent of non-celiac disease-related small bowel adenocarcinomas showed microsatellite instability, whereas 67% of celiac disease-related small bowel adenocarcinomas were microsatellite unstable.Our study characterized chromosomal aberrations and amplifications involved in small bowel adenocarcinoma. At the chromosomal level, celiac disease-related and non-celiac disease-related small bowel adenocarcinomas did not differ. A defect in the mismatch repair pathways seems to be more common in celiac disease-related than in non-celiac disease-related small bowel adenocarcinomas. In contrast to colon and gastric cancers, no APC nonsense mutations were found in small bowel adenocarcinoma. However, APC promoter methylation seems to be a common event in celiac disease-related small bowel adenocarcinoma. Clin Cancer Res; 16(5); 1391-401.
Oxidative stress modulates vascular smooth muscle cell phenotype via CTGF in thoracic aortic aneurysm
Authors: E. Branchetti, P. Poggio, R. Sainger, E. Shang, J. B. Grau, B. M. Jackson, E. K. Lai, M. S. Parmacek, R. C. Gorman, J. H. Gorman, J. E. Bavaria, G. Ferrari
Journal: Cardiovascular Research (2013)

Dissection and rupture of the ascending aorta are life-threatening conditions resulting in 80% mortality. Ascending aortic replacement in patients presenting with thoracic aortic aneurysm (TAA) is determined by metric measurement. However, a significant number of dissections occur outside of the parameters suggested by the current guidelines. We investigate the correlation among altered haemodynamic condition, oxidative stress, and vascular smooth muscle cell (VSMC) phenotype in controlling tissue homoeostasis.We demonstrate using finite element analysis (FEA) based on computed tomography geometries that TAA patients have higher wall stress in the ascending aorta than non-dilated patients. We also show that altered haemodynamic conditions are associated with increased levels of reactive oxygen species (ROS), direct regulators of the VSMC phenotype in the microregional area of the ascending aorta. Using in vitro and ex vivo studies on human tissues, we show that ROS accumulation correlates with media layer degeneration and increased connective tissue growth factor (CTGF) expression, which modulate the synthetic VSMC phenotype. Results were validated by a murine model of TAA (C57BL/6J) based on Angiotensin II infusion showing that medial thickening and luminal expansion of the proximal aorta is associated with the VSMC synthetic phenotype as seen in human specimens.Increased peak wall stress correlates with change in VSMC towards a synthetic phenotype mediated by ROS accumulation via CTGF. Understanding the molecular mechanisms that regulate VSMC towards a synthetic phenotype could unveil new regulatory pathways of aortic homoeostasis and impact the risk-stratification tool for patients at risk of aortic dissection and rupture.
MicroRNA-218 Inhibits Glioma Invasion, Migration, Proliferation, and Cancer Stem-like Cell Self-Renewal by Targeting the Polycomb Group Gene <i>Bmi1</i>
Authors: Yanyang Tu, Xingchun Gao, Gang Li, Hualin Fu, Daxiang Cui, Hui Liu, Weilin Jin, Yongsheng Zhang
Journal: Cancer Research (2013)

Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically reduces the migration, invasion, and proliferation of glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that expression of the stem cell-promoting oncogene Bmi1 was decreased after overexpression of miR-218 in glioma cells. Mechanistic investigations defined Bmi1 as a functional downstream target of miR-218 through which miR-218 ablated cell migration and proliferation. We documented that miR-218 also blocked the self-renewal of glioma stem-like cells, consistent with the suggested role of Bmi1 in stem cell growth. Finally, we showed that miR-218 regulated a broad range of genes involved in glioma cell development, including Wnt pathways that suppress glioma cell stem-like qualities. Taken together, our findings reveal miR-218 as a tumor suppressor that prevents migration, invasion, proliferation, and stem-like qualities in glioma cells.
End-Stage Renal Disease Measures of Quality
Authors: Jonathan Himmelfarb, Alan S. Kliger
Journal: Annual Review of Medicine (2007)

During the past 35 years, there has been a geometric expansion of the population of patients receiving chronic dialysis therapy in the United States. As the size and associated costs of the dialysis population have grown, there has been a consistent and evolving emphasis on measuring and improving the quality of dialysis care. These efforts, aided by robust data collection vehicles, have translated into defined clinical performance measures; nevertheless, morbidity and mortality rates remain high for the dialysis population. Recently, attention has focused on whether improved outcomes could be obtained by paying physicians and dialysis providers on the basis of quality metrics. The feasibility, value, pitfalls, and appropriate quality metrics in a "payment-for-quality" program for dialysis care are currently under vigorous discussion.
Identification of Novel Interactions Between Domains of Myosin Binding Protein-C That Are Modulated by Hypertrophic Cardiomyopathy Missense Mutations
Authors: Johanna Moolman-Smook, Emily Flashman, Willem de Lange, Zhili Li, Valerie Corfield, Charles Redwood, Hugh Watkins
Journal: Circulation Research (2002)

Cardiac myosin binding protein-C (cMyBPC) is a modular protein consisting of 11 domains whose precise function and sarcomeric arrangement are incompletely understood. Identification of hypertrophic cardiomyopathy (HCM)–causing missense mutations in cMyBPC has highlighted the significance of certain domains. Of particular interest is domain C5, an immunoglobulin-like domain with a cardiac-specific insert, which is of unknown function yet is the site of two HCM-causing missense mutations. To identify interactors with this region, a human cardiac cDNA library was screened in a yeast two-hybrid (Y2H) assay using the C5 sequence as bait. Screening &gt;7×10 6 clones surprisingly revealed that domain C5 preferentially bound to clones encoding C-terminal fragments of cMyBPC; the interacting region was narrowed to domain C8 by deletion mapping. A surface plasmon resonance assay using purified recombinant cMyBPC domains was used to measure the affinity of C5 and C8 in vitro (K a =1×10 5 mol/L −1 ). This affinity was decreased about 2-fold by the HCM mutation R654H, and by at least 10-fold by the mutation N755K. Further Y2H assays also demonstrated specific binding between domains C7 and C10 of cMyBPC. Based on these novel interactions, and previous biochemical and structural data, we propose that cMyBPC molecules trimerize into a collar around the thick filament, with overlaps of domains C5-C7 of one cMyBPC with C8-C10 of another. We speculate that this interaction may be dynamically formed and released, thereby restricting or favoring cross-bridge formation, respectively. We suggest that the HCM mutations act by altering the cMyBPC collar, indicating its importance in thick filament structure and regulation.