tbuckley/cabot-search huggingface dataset:
Isochromosome 17q Is a Negative Prognostic Factor in Poor-Risk Childhood Medulloblastoma Patients
Authors: Edward Pan, Malgorzata Pellarin, Emi Holmes, Ivan Smirnov, Anjan Misra, Charles G. Eberhart, Peter C. Burger, Jaclyn A. Biegel, Burt G. Feuerstein
Journal: Clinical Cancer Research (2005)

Abstract Background: Medulloblastomas are the most common primary malignant childhood intracranial neoplasms. Patients are currently sorted into three risk groups based on clinical criteria: standard, poor, and infant (&amp;lt;18 months old). We hypothesized that genetic copy number aberrations (CNA) predict prognosis and would provide improved criteria for predicting outcome. Methods: DNA from 35 medulloblastoma patients from four Children's Cancer Group trials was analyzed by comparative genomic hybridization to determine CNAs. The genetic alterations were evaluated using statistical and cluster analyses. Results: The most frequent CNAs were gains on 17q, 7, 1q, and 7q and losses on 17p, 10q, X, 16q, and 11q. Amplification at 5p15.1-p15.3 was also detected. Isochromosome 17q (i(17)(q10)) was associated with poor overall survival (P = 0.03) and event-free survival (P = 0.04) independent of poor risk group classification. Age &amp;lt;3 tended to be associated with &amp;lt;3 CNAs (P = 0.06). Unsupervised cluster analysis sorted the study patients into four subgroups based on CNAs. Supervised analysis using the program Significance Analysis of Microarrays (SAM) quantitatively validated those CNAs identified by unsupervised clustering that significantly distinguished among the four subgroups. Conclusions: Medulloblastomas are genetically heterogeneous and can be categorized into separate genetic subgroups by their CNAs using unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent negative prognostic factor. Infant medulloblastomas may be a distinct genetic subset from those of older patients.
Hypothyroidism Is a Risk Factor for New-Onset Diabetes: A Cohort Study
Authors: Naomi Gronich, Spyros N. Deftereos, Idit Lavi, Andreas S. Persidis, Darrell R. Abernethy, Gad Rennert
Journal: Diabetes Care (2015)

To identify risk factors for the development of statin-associated diabetes mellitus (DM).The study was conducted in two phases. Phase one involved high-throughput in silico processing of a large amount of biomedical data to identify risk factors for the development of statin-associated DM. In phase two, the most prominent risk factor identified was confirmed in an observational cohort study at Clalit, the largest health care organization in Israel. Time-dependent Poisson regression multivariable models were performed to assess rate ratios (RRs) with 95% CIs for DM occurrence.A total of 39,263 statin nonusers were matched by propensity score to 20,334 highly compliant statin initiators in 2004-2005 and followed until the end of 2010. Within 59,597 statin users and nonusers in a multivariable model, hypothyroidism and subclinical hypothyroidism carried an increased risk for DM (RR 1.53 [95% CI 1.31-1.79] and 1.75 [1.40-2.18], respectively). Hypothyroidism increased DM risk irrespective of statin treatment (RR 2.06 [1.42-2.99] and 1.66 [1.05-2.64] in statin users and nonusers, respectively). Subclinical hypothyroidism risk for DM was prominent only upon statin use (RR 1.94 [1.13-3.34] and 1.20 [0.52-2.75] in statin users and nonusers, respectively). Patients with hypothyroidism treated with thyroid hormone replacement therapy were not at increased risk for DM.Hypothyroidism is a risk factor for DM. Subclinical hypothyroidism-associated risk for DM is prominent only upon statin use. Identifying and treating hypothyroidism and subclinical hypothyroidism might reduce DM risk. Future clinical studies are needed to confirm the findings.
740 HBSAG KINETICS IN PATIENTS WITH CHRONIC HEPATITIS B (CHB) TREATED WITH TENOFOVIR DISOPROXIL FUMARATE (TDF) FOR UP TO 4 YEARS
Authors: P. Marcellin, E.J. Heathcote, M. Buti, Z. Krastev, I. Jacobson, R.A. de Man, G. Dusheiko, S. Zeuzem, C. Barnes, C. Ng, L. Lou
Journal: Journal of Hepatology (2011)
Secretion of plasminogen activator by bone marrow-derived mononuclear phagocytes and its enhancement by colony-stimulating factor
Authors: H-S Lin, S Gordon
Journal: The Journal of Experimental Medicine (1978)

We have studied the production of plasminogen activator (PA) by mononuclear phagocytes derived from mouse bone marrow precursor cells (CFU-C) in culture. Bone marrow-derived macrophages (BMDM) obtained after 6-8-d cultivation in a liquid medium containing L-cell-conditioned medium (LCM), a source of colony stimulating factor (CSF), showed a high level of fibrinolytic activity comparable to that of thioglycollate medium-induced peritoneal macrophages (TPM) and at least 20-fold higher than that of resident peritoneal macrophages (RPM). Fibrinolysis was a result of active secretion of PA into the culture medium and plaques of caseinolysis could be detected by an overlay assay over all macrophage colonies formed after cloning of bone marrow cells in culture. When the fibrinolytic activity of BMDM harvested at different times was investigated, it was found that the level of PA activity of a given BMDM population correlated well with the incidence of cells (5-15 percent) able to proliferate and form colonies in agar after 7-14 d, somewhat more slowly than CFU-C. This correlation between the level of PA secretion and the incidence of agar colony-forming cells was also found with other mononuclear phagocyte populations. Active fibrinolysis and slow growing colony-forming cells were observed at the same time as adherent macrophages appeared, 2-3 d after the start of bone marrow culture, they persisted for 10 d before declining. Some of the factors which influenced PA production by BMDM were examined. Fibrinolysis could be enhanced two- to fourfold by exposing the cells for 4 h to concanavalin A (Con A), to medium conditioned by Con A-stimulated spleen cells and to LCM, but not by phagocytosis of latex particles. The substance in LCM that stimulated PA production appeared to be identical to CSF. Mononuclear phagocyte targets differed in their response to LCM, which stimulated fibrinolysis readily in BMDM, to a lesser extent in TPM and not at all in RPM. We conclude that CSF stimulates both proliferation and fibrinolytic activity in BMDM and that the level of macrophage activation, as defined by PA production, can be further enhanced by lymphokines. Induction of PA in BMDM provides a rapid and sensitive assay for measuring the activity of CSF and defining its role in macrophage activation.
Reutilization of &lt;sup&gt;131&lt;/sup&gt;I-5-Iodo-2′-Deoxyuridine as Compared to &lt;sup&gt;3&lt;/sup&gt;H-Thymidine in Mouse Duodenum and Mammary Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dethlefsen, Lyle A.
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Reutilization of 131I-5-Iodo-2′-Deoxyuridine as Compared to 3H-Thymidine in Mouse Duodenum and Mammary Tumor Get access Lyle A. Dethlefsen Lyle A. Dethlefsen Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 44, Issue 4, April 1970, Pages 827–840, https://doi.org/10.1093/jnci/44.4.827 Published: 01 April 1970 Article history Received: 10 October 1969 Accepted: 30 December 1969 Published: 01 April 1970
Extensions of Errorless Learning for Social Problem-Solving Deficits in Schizophrenia
Authors: Robert S Kern, Michael F Green, Sharon Mitchell, Alex Kopelowicz, Jim Mintz, Robert P Liberman
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: There is a clear need to develop psychosocial rehabilitation methods that compensate for neurocognitive deficits common to persons with severe and persistent mental illness. Errorless learning, a compensatory training intervention, has been successful in teaching entry-level job tasks. However, errorless learning's applicability to broader, more complex functions is unknown. The present study tested the extension of errorless learning for deficits in social problem-solving skills in patients with schizophrenia. METHOD: Sixty clinically stable outpatients with schizophrenia or schizoaffective disorder were stratified by gender and level of memory impairment before being randomly assigned to one of two training programs: errorless learning or symptom management. Groups were matched for training time, format and structure of training, and types of teaching aids used. Social problem-solving ability, measured by the Assessment of Interpersonal Problem-Solving Skills, was assessed at baseline, within 2 days of training completion, and after 3 months. Dependent measures were the scores for the receiving, processing, and sending skills areas from the Assessment of Interpersonal Problem-Solving Skills. RESULTS: A repeated-measures analysis of covariance was conducted for each dependent measure with baseline Assessment of Interpersonal Problem-Solving Skills score entered as a covariate. For all three skills, there was a significant training group effect favoring errorless learning. Durability of errorless learning training effects extended to the 3-month follow-up assessment for processing and sending skills but not receiving skills. CONCLUSIONS: Results support the extension of errorless learning to complex functions such as social problem-solving skills in the rehabilitation of persons with schizophrenia.
The Complete Mitochondrial Genome of Tupaia belangeri and the Phylogenetic Affiliation of Scandentia to Other Eutherian Orders
Authors: J Schmitz, M Ohme, H Zischler
Journal: Molecular Biology and Evolution (2000)

The complete mitochondrial genome of Tupaia belangeri, a representative of the eutherian order Scandentia, was determined and compared with full-length mitochondrial sequences of other eutherian orders described to date. The complete mitochondrial genome is 16, 754 nt in length, with no obvious deviation from the general organization of the mammalian mitochondrial genome. Thus, features such as start codon usage, incomplete stop codons, and overlapping coding regions, as well as the presence of tandem repeats in the control region, are within the range of mammalian mitochondrial (mt) DNA variation. To address the question of a possible close phylogenetic relationship between primates and Tupaia, the evolutionary affinities among primates, Tupaia and bats as representatives of the Archonta superorder, ferungulates, guinea pigs, armadillos, rats, mice, and hedgehogs were examined on the basis of the complete mitochondrial DNA sequences. The opossum sequence was used as an outgroup. The trees, estimated from 12 concatenated genes encoded on the mitochondrial H-strand, add further molecular evidence against an Archonta monophyly. With the new data described in this paper, most of both the mitochondrial and the nuclear data point away from Scandentia as the closest extant relatives to primates. Instead, the complete mitochondrial data support a clustering of Scandentia with Lagomorpha connecting to the branch leading to ferungulates. This closer phylogenetic relationship of Tupaia to rabbits than to primates first received support from several analyses of nuclear and partial mitochondrial DNA data sets. Given that short sequences are of limited use in determining deep mammalian relationships, the partial mitochondrial data available to date support this hypothesis only tentatively. Our complete mitochondrial genome data therefore add considerably more evidence in support of this hypothesis.
Interfacing Kidney Stroma with Dendritic Cells
Authors: Zae Kim, Peter J. Nelson
Journal: Journal of the American Society of Nephrology (2009)

The vast majority of ongoing clinical trials using multipotent, mesenchymal stromal cells (MSCs) seek to harness their immunomodulatory properties,[1][1] attesting to the regulatory interface that exists between MSCs and their stromal cell lineage and immunocytes. Specifically regarding
Ranked prediction of p53 targets using hidden variable dynamic modeling.
Authors: Martino Barenco, Daniela Tomescu, Daniel Brewer, Robin Callard, Jaroslav Stark, Michael Hubank
Journal: Genome biology (2006)

Abstract Full exploitation of microarray data requires hidden information that cannot be extracted using current analysis methodologies. We present a new approach, hidden variable dynamic modeling (HVDM), which derives the hidden profile of a transcription factor from time series microarray data, and generates a ranked list of predicted targets. We applied HVDM to the p53 network, validating predictions experimentally using small interfering RNA. HVDM can be applied in many systems biology contexts to predict regulation of gene activity quantitatively.
Early Evidence on the Effects of Regulators’ Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents
Authors: Robert D. Gibbons, C. Hendricks Brown, Kwan Hur, Sue M. Marcus, Dulal K. Bhaumik, Joëlle A. Erkens, Ron M.C. Herings, J. John Mann
Journal: American Journal of Psychiatry (2007)

Objective: In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. Method: The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. Results: SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. Conclusions: In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.
RESPONSE OF CULTURED MACROPHAGES TO <i>MYCOBACTERIUM TUBERCULOSIS</i>, WITH OBSERVATIONS ON FUSION OF LYSOSOMES WITH PHAGOSOMES
Authors: J. A. Armstrong, P. D'Arcy Hart
Journal: The Journal of Experimental Medicine (1971)

The cytological response to the ingestion of tubercle bacilli by cultured mouse peritoneal macrophages has been studied by electron microscopy. Methods included a quantitative assessment based on systematic surveying of cell profiles, and of phagosomes and their contained bacteria, encountered in thin sections; classification of the sectioned bacteria into visibly damaged and apparently intact categories; prelabeling of dense granules (secondary lysosomes) with ferritin as an aid to identifying the occurrence and frequency of phagosome-lysosome fusion; and monitoring of bacterial growth and viability by light microscopy and cultural counts. The situations studied were as follows: progressive infection with the multiplying virulent strain H37Rv; ingestion of the same strain previously inactivated by gamma radiation; infection with an attenuated strain (BCG); and a stabilized virulent infection induced by the surfactant Macrocyclon. In the bacterial suspensions used routinely for inoculation, about half the bacilli were viable, matching closely the proportions of intact and damaged organisms identified with the electron microscope. In the inoculated macrophages, some phagosomes containing intact bacilli and others containing damaged bacilli were always to be found; but the proportion of organisms scored as damaged increased, and that of intact organisms decreased, in situations where the population as a whole had been rendered nonviable before inoculation, or where they became so intracellularly as in the late stages of a BCG infection. Evidence of fusion of ferritin-marked lysosomes with some bacterium-containing phagosomes was obtained in all experiments, but a significant difference was regularly observed according to whether the bacilli were damaged or intact. Virtually all phagosomes containing damaged bacilli showed signs of fusion; but when many phagosomes were present containing apparently intact organisms (as with actively multiplying strain H37Rv or with this strain held at a steady level of viability by Macrocyclon, and also with strain BCG at an early stage of that infection), signs of fusion of lysosomes with these phagosomes were infrequent. From these findings it is inferred that intracellular survival of M. tuberculosis in cultured macrophages is associated with a tendency to nonfusion of dense granules with the phagosome, thus avoiding direct exposure of the bacilli to the contents of these organelles. It is suggested, further, that fusion of dense granules with the phagosome, leading to digestion, is determined by recognition of the bacillus as nonviable. The possibility is discussed that the cytological response to different mycobacterial infections may reflect differences of a basic nature between facultative and obligate intracellular parasitism.
Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis
Authors: X. Mariette, M. Matucci-Cerinic, K. Pavelka, P. Taylor, R. van Vollenhoven, R. Heatley, C. Walsh, R. Lawson, A. Reynolds, P. Emery
Journal: Annals of the Rheumatic Diseases (2011)

This project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational studies.The authors undertook comprehensive searches of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and American College of Rheumatology, European League against Rheumatism and British Society for Rheumatology conference abstracts according to a prespecified protocol.The searches identified 2039 full-text papers and 1979 conference abstracts, of which 21 full texts and eight abstracts met the inclusion criteria. The pooled estimate for the risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05). Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy. In patients with previous malignancies there was a higher risk of a new/recurring malignancy. This risk was not increased further by exposure to TNFi, although CI were wide. Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI 0.70 to 1.51).This systematic review and meta-analysis shows that TNFi treatments do not increase the risk of malignancy, particularly lymphoma. However, they do appear to increase the risk of skin cancer, including melanoma.
Athletes and doping: effects of drugs on the respiratory system
Authors: P N R Dekhuijzen, H A Machiels, L M A Heunks, H F M van der Heijden, R H H van Balkom
Journal: Thorax (1999)

Doping is an area of ongoing public, legal, and medical debate and in recent years it has been reported to be connected with many sports including athletics, cycling, body building, soccer, and swimming. Ethical issues related to doping include the honesty of the sports competition and the safety of drugs and other methods applied to improve the physical performance. These issues are of increasing interest and importance since drugs on the prohibited list are easily accessible by medically uncontrolled means such as the Internet.

According to the International Olympic Committee (IOC)1doping consists of (1) the administration of substances belonging to prohibited classes of pharmacological agents and/or (2) the use of various prohibited methods. There are five prohibited classes of substances: stimulants, narcotics, anabolic agents, diuretics, and peptide and glycoprotein hormones and their analogues (table 1). Prohibited methods include blood doping and pharmacological, chemical and physical manipulation.

View this table:

Table 1 
Prohibited classes of substances and prohibited methods (shortened and adapted from IOC1)



Several respiratory drugs are included in the list of prohibited substances unless they are administered by inhalation. This paper reviews the current literature concerning the effects of respiratory and some other drugs on the respiratory system in the broadest sense—that is, from the respiratory controllers to the respiratory muscles and the lungs themselves. We will focus on the effects in athletes and healthy trained and untrained subjects but, where appropriate, we will also refer to studies in patients, to animal studies, and to studies in peripheral skeletal muscles.

In general, the respiratory system does not limit maximal oxygen consumption (V˙o 2max) in healthy subjects.2 3 Only in highly trained endurance athletes may blood oxygen saturation fall during heavy exercise.4 5 

The maximal sustainable ventilation decreases with time, and the level that can be sustained …