tbuckley/cabot-search huggingface dataset:
Clinical Implications of Phosphorylated STAT3 Expression in <i>De Novo</i> Diffuse Large B-cell Lymphoma
Authors: Chi Young Ok, Jiayu Chen, Zijun Y. Xu-Monette, Alexandar Tzankov, Ganiraju C. Manyam, Ling Li, Carlo Visco, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han van Krieken, Jooryung Huh, Xiaoying Zhao, Maurilio Ponzoni, Andrés J.M. Ferreri, Francesco Bertoni, John P. Farnen, Michael B. Møller, Miguel A. Piris, Jane N. Winter, L. Jeffrey Medeiros, Ken H. Young
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of phosphorylated STAT3 (pSTAT3) on prognosis are limited. Experimental Design: We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma biomarkers, and genetic translocations. Results: pSTAT3 expression was observed in 16% of DLBCL and was associated with advanced stage, multiple extranodal sites of involvement, activated B-cell–like (ABC) subtype, MYC expression, and MYC/BCL2 expression. Expression of pSTAT3 predicted inferior overall survival (OS) and progression-free survival (PFS) in patients with de novo DLBCL. When DLBCL cases were stratified according to COO or MYC expression, pSTAT3 expression did not predict inferior outcome, respectively. Multivariate analysis showed that the prognostic predictability of pSTAT3 expression was due to its association with the ABC subtype, MYC expression, and adverse clinical features. GEP demonstrated upregulation of genes, which can potentiate function of STAT3. GSEA showed the JAK–STAT pathway to be enriched in pSTAT3+ DLBCL. Conclusions: The results of this study provide a rationale for the ongoing successful clinical trials targeting the JAK–STAT pathway in DLBCL. Clin Cancer Res; 20(19); 5113–23. ©2014 AACR.
Lung cancer patterns of care in south western Sydney, Australia
Authors: S K Vinod, G P Delaney, A E Bauman, M B Barton
Journal: Thorax (2003)

Lung cancer is the leading cause of cancer deaths in New South Wales (NSW). There is a significantly higher incidence of lung cancer in the South Western Sydney Area Health Service (SWSAHS) than the NSW average. The aim of this study was to document patterns of lung cancer care for SWSAHS residents.SWSAHS residents diagnosed with lung cancer in 1993 and 1996 were identified from the NSW Central Cancer Registry and their medical records reviewed.The study population comprised 527 patients of median age 68 years. 12% did not see a lung cancer specialist, 9% did not have a pathological diagnosis, and 28% did not receive any active treatment throughout the course of their illness. The median survival was 6.7 months and the 5 year overall survival was 8% (95% CI 6 to 10). The rates of pathological diagnosis, specialist referral, and treatment decreased with older age and poorer performance status.The management of lung cancer patients in SWSAHS is suboptimal. A significant proportion of patients are not receiving treatment. To improve patient care and outcomes, all lung cancer patients should be referred to a specialist for management, ideally in a multidisciplinary setting. Both consumers and general practitioners need to be educated about options available for the management of lung cancers and ageist and nihilistic attitudes need to be overcome.
Transcriptome-wide signatures of tumor stage in kidney renal clear cell carcinoma: connecting copy number variation, methylation and transcription factor activity
Authors: Qi Liu, Pei-Fang Su, Shilin Zhao, Yu Shyr
Journal: Genome Medicine (2014)

Comparative analysis of expression profiles between early and late stage cancers can help to understand cancer progression and metastasis mechanisms and to predict the clinical aggressiveness of cancer. The observed stage-dependent expression changes can be explained by genetic and epigenetic alterations as well as transcription dysregulation. Unlike genetic and epigenetic alterations, however, activity changes of transcription factors, generally occurring at the post-transcriptional or post-translational level, are hard to detect and quantify.Here we developed a statistical framework to infer the activity changes of transcription factors by simultaneously taking into account the contributions of genetic and epigenetic alterations to mRNA expression variations.Applied to kidney renal clear cell carcinoma (KIRC), the model underscored the role of methylation as a significant contributor to stage-dependent expression alterations and identified key transcription factors as potential drivers of cancer progression.Integrating copy number, methylation, and transcription factor activity signatures to explain stage-dependent expression alterations presented a precise and comprehensive view on the underlying mechanisms during KIRC progression.
Characteristics of Single Aortic and Right Subclavian Baroreceptor Fiber Activity in Rabbits with Chronic Renal Hypertension
Authors: JENNIFER E. ANGELL-JAMES
Journal: Circulation Research (1973)

Experimental renal hypertension was induced in rabbits by wrapping polyethylene around one kidney and removing the other. The impulse activity in single baroreceptor fibers of the aortic nerves to the aortic arch and the right subclavian areas was studied 7-19 weeks postoperatively during nonpulsatile perfusion of an isolated aortic arch preparation. The results were compared with those obtained in normal rabbits. Curves relating the impulse frequency to the aortic arch pressure were constructed. In rabbits with hypertension, the threshold pressure of the aortic baroreceptor fibers was increased from a normal value of 52.5 ± 5.5 to 106.5 ± 5.8 mm Hg, and the point of inflection was increased from 112.4 ± 6.2 to 163.4 ± 5.1 mm Hg. The sensitivity of the baroreceptors to changes in pressure was reduced from 1.19 ± 0.14 to 0.64 ± 0.06 impulses/sec mm Hg -1 . Similar results were obtained for the right subclavian area. Hysteresis, as indicated by the separation of the curves produced by first increasing and then reducing the aortic pressure, was more evident in rabbits with hypertension than in normal rabbits. The changes in baroreceptor activity in rabbits with hypertension were associated with alterations in the mechanical properties of the arterial walls, which were demonstrated by the pressure-volume curves. Also, there were demonstrable histological lesions of the arterial walls and the receptors in rabbits with hypertension.
Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML
Authors: Jessica A. Pollard, Todd A. Alonzo, Robert B. Gerbing, Phoenix A. Ho, Rong Zeng, Yaddanapudi Ravindranath, Gary Dahl, Norman J. Lacayo, David Becton, Myron Chang, Howard J. Weinstein, Betsy Hirsch, Susana C. Raimondi, Nyla A. Heerema, William G. Woods, Beverly J. Lange, Craig Hurwitz, Robert J. Arceci, Jerald P. Radich, Irwin D. Bernstein, Michael C. Heinrich, Soheil Meshinchi
Journal: Blood (2010)
Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Bart Van Overmeire, Karel Allegaert, Alexandra Casaer, Christian Debauche, Wim Decaluwé, Ann Jespers, Joost Weyler, Inge Harrewijn, Jean-Paul Langhendries
Journal: The Lancet (2004)
Attachment and life history strategy
Authors: Aurelio José Figueredo, Jon A. Sefcek, Sally G. Olderbak
Journal: Behavioral and Brain Sciences (2009)

Abstract Del Giudice addresses a complex and pertinent theoretical issue: the evolutionary adaptiveness of sex differences in attachment styles in relation to life history strategy. Although we applaud Del Giudice for calling attention to the problem, we regret that he does not sufficiently specify how attachment styles serve as an integral part of a coordinate life history strategy for either sex.
Quality of life of idiopathic pulmonary fibrosis patients
Authors: J. De Vries, B.L.J. Kessels, M. Drent
Journal: European Respiratory Journal (2001)

Little attention has been paid to quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to address this issue and study the relationship between QOL, depressive symptoms, and breathlessness in these patients. Forty-one IPF patients and 41 healthy persons matched for age and sex completed the World Health Organization Quality of Life assessment instrument-100. The IPF patients also completed the Beck Depression Inventory, the Bath Breathlessness Scale, a social support questionnaire and a question concerning perceived seriousness of illness. Compared to the control group, QOL in IPF patients was mainly impaired in the domains “physical health” and “level of independence”. A number of relationships were found between pulmonary function tests and QOL. The QOL facet “negative feelings” was highly associated with scores on depression. Subjective breathlessness was related to depressive symptoms and QOL. Moreover, sex and effective/emotional breathlessness predicted overall QOL. In conclusion, the impairment of the quality of life areas “physical health” and “level of independence” are important issues in idiopathic pulmonary fibrosis. Subjective breathlessness, especially the effective/emotional scale, seems related to quality of life and depressive symptoms. Rehabilitation programmes are needed that are aimed at physiological aspects and psychosocial aspects of idiopathic pulmonary fibrosis in order to enhance the quality of life of these patients.
Iron metabolism in the lower respiratory tract
Authors: F. Mateos, J. H Brock, J. L. Perez-Arellano
Journal: Thorax (1998)

Iron metabolism is of crucial importance in the biology and pathophysiology of the lower respiratory tract. As with many other factors involved in inflammation, it is very important that an appropriate iron balance is maintained. Local deficiency could impair growth and proliferation of cells responsible for the inflammatory response and tissue repair (lymphocytes and fibroblasts) and the synthesis of mediators (for example, arachidonic acid derivatives).1 In contrast, excessive accumulation of iron, especially in free form—that is, not bound to one of the specific iron-binding proteins—facilitates the generation of potentially toxic hydroxyl radicals2 and increases the ability of intracellular bacteria such as mycobacteria to grow.3-5 

Research into iron metabolism in the lower respiratory tract has taken advantage of bronchoalveolar lavage, a technique by which it is possible to obtain the cells and fluid lining the alveoli. Determination of iron content in the alveolo-interstitial region shows that 80% is present in the cells and 20% in the epithelial lining fluid of the lung.6 Since alveolar macrophages constitute the major cell population in this region, and because the iron content of lymphocytes, neutrophils, and monocytes is very low in comparison with alveolar macrophages,6 7 these cells are of special interest.

In this paper we review current knowledge of iron and iron-binding proteins in bronchoalveolar lavage fluid, and the special features of iron metabolism in alveolar macrophages.

Iron is principally required for haemoglobin synthesis, and its uptake, utilisation and storage are carefully regulated to ensure an adequate supply without excessive accumulation which could lead to toxicity. Intestinal iron absorption is related to erythropoietic requirements, although the regulatory mechanism(s) remain unknown. The usual source of iron in the lung is serum iron which is derived from catabolised erythrocytes and absorbed iron. However, in pathological states, iron can enter the lung …
Wartime migration and the incidence of tuberculosis in the Zagreb region, Croatia
Authors: M Pavlovic, D Simic, M Krstic-Buric, N Corovic, D Zivkovic, A Rozman, T Peros-Golubicic
Journal: European Respiratory Journal (1998)

The objective of the present study was to investigate the rate of decline in the incidence of tuberculosis (TB) in residents (1985-1994) and in refugees and displaced persons (1992-1994) during prewar and war periods (1985-1994) in the region of Zagreb, Croatia, and to examine a possible change in the trend of decline in the resident population. Data on the incidence of TB were obtained from the Epidemiology Department, Institute for Lung Diseases, Zagreb, Croatia. The sample comprised two groups of subjects: residents (800,000-1,000,000 inhabitants) and all refugees and displaced persons temporarily residing in the Zagreb region (78,000-95,000 persons). Data were analysed by stepwise logistic regression. The most significant predictors of the TB incidence rate were the square of the year and residence status. The rate of TB incidence in nonresidents was significantly higher than in residents. The decline in incidence in residents was significantly slower than in the nonresident group. The results did not indicate a potential change in the natural decline of the incidence of tuberculosis in the resident population during the study periods. The difference between the regression trends of the incidence of tuberculosis in residents and nonresidents was the result of various concomitant factors, including artefacts of the war.
Phase I Trial and Pharmacokinetic Study of Bevacizumab in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study
Authors: Julia L. Glade Bender, Peter C. Adamson, Joel M. Reid, Lu Xu, Sylvain Baruchel, Yuval Shaked, Robert S. Kerbel, Erin M. Cooney-Qualter, Diana Stempak, Helen X. Chen, Marvin D. Nelson, Mark D. Krailo, Ashish M. Ingle, Susan M. Blaney, Jessica J. Kandel, Darrell J. Yamashiro
Journal: Journal of Clinical Oncology (2008)

Purpose We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)–neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer. Patients and Methods BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors. Results Twenty-one patients enrolled, 20 (median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered (median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg (range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data. Conclusion BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned.
Health Research Authority outlines plans to improve transparency of UK clinical research
Authors: A. O'Dowd
Journal: BMJ (2013)

The body that represents the interests of UK patients in health research is working on ways to ensure that the results of clinical studies see the light of day.

Plans to improve NHS research were detailed in the Health Research Authority’s official response to MPs on the House of Commons Science and Technology Committee. The authority also said that it would be looking at ways to speed up how quickly proposed research studies could …
Early descriptions of Adamantiades-Behcet's disease
Authors: C C Zouboulis
Journal: Annals of the Rheumatic Diseases (2003)

A fter the publication of an article on “Behcet’s disease and thrombophilia” by Leiba et al ,1 Ehrlich2 and Leiba et al 3 discussed descriptions of the disease before Behcet. They agreed that Behcet was the first modern author to group the various ophthalmic, dermatological, and orogenital lesions together as a syndrome.

However, during the annual meeting of the Medical Society of Athens on 15 November 1930, Benediktos Adamantiades (1875–1962),4–6 Greek ophthalmologist from Prussa, Asia minor (nowadays Bursa, Turkey), presented a lecture entitled “A case of relapsing iritis with hypopyon”, describing a 20 year old male patient with …
Introduction of a Xenogeneic Gene via Hematopoietic Stem Cells Leads to Specific Tolerance in a Rhesus Monkey Model
Authors: Dominik A. Heim, Yutaka Hanazono, Neelam Giri, Tong Wu, Richard Childs, Stephanie E. Sellers, Linda Muul, Brian A. Agricola, Mark E. Metzger, Robert E. Donahue, John F. Tisdale, Cynthia E. Dunbar
Journal: Molecular Therapy (2000)

Host immune responses against foreign transgenes may be a major obstacle to successful gene therapy. To clarify the impact of an immune response to foreign transgene products on the survival of genetically modified cells, we studied the in vivo persistence of cells transduced with a vector expressing a foreign transgene compared to cells transduced with a nonexpressing vector in the clinically predictive rhesus macaque model. We constructed retroviral vectors containing the neomycin phosphotransferase gene (neo) sequences modified to prevent protein expression (nonexpressing vectors). Rhesus monkey lymphocytes or hematopoietic stem cells (HSCs) were transduced with nonexpressing and neo-expressing vectors followed by reinfusion, and their in vivo persistence was studied. While lymphocytes transduced with a nonexpressing vector could be detected for more than 1 year, lymphocytes transduced with a neo-expressing vector were no longer detectable within several weeks of infusion. However, five of six animals transplanted with HSCs transduced with nonexpression or neo-expression vectors, and progeny lymphocytes marked with either vector persisted for more than 2 years. Furthermore, in recipients of transduced HSCs, infusion of mature lymphocytes transduced with a second neo-expressing vector did not result in elimination of the transduced lymphocytes. Our data show that introduction of a xenogeneic gene via HSCs induces tolerance to the foreign gene products. HSC gene therapy is therefore suitable for clinical applications where long-term expression of a therapeutic or foreign gene is required.
Spatial Distribution of Selection Pressure on a Protein Based on the Hierarchical Bayesian Model
Authors: Teruaki Watabe, Hirohisa Kishino
Journal: Molecular Biology and Evolution (2013)

Proteins adapt to novel environments and/or gain function by substitution in amino acid sequences. Therefore, mutations in protein-coding genes are subject to selection pressure. The strength and character of selection pressure may vary among the regions of the protein. Thus, the spatial distribution of selection pressure provides information on the adaptive evolution of the protein. We developed a hierarchical Bayesian model that detects the spatial distribution of selection pressure on a protein. We expressed selection pressure by the substitution rate ratio of nonsynonymous to synonymous substitutions in the DNA sequence. The Potts model describes the prior distribution of spatial aggregation of selection pressure. The hyperparameters that define the strength and range of spatial clustering are estimated by maximizing the marginal likelihood. Because our prior distribution is un-normalized, we calculated the log marginal likelihood by "thermodynamic integration." We applied the method to historical data on the influenza hemagglutinin protein, comparing the estimated spatial distribution of the substitution rate ratio with that of antigenic sites A-E. The amino acid residues with higher substitution rate ratios, representing diversifying selection pressure, overlapped the antigenic sites.
A Functional Magnetic Resonance Imaging Study of Auditory Mismatch in Schizophrenia
Authors: Cynthia G. Wible, Marek Kubicki, Seung-Schik Yoo, Daniel F. Kacher, Dean F. Salisbury, Mark C. Anderson, Martha E. Shenton, Yoshio Hirayasu, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing. METHOD: Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly. RESULTS: The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition. CONCLUSIONS: This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.