tbuckley/cabot-search huggingface dataset:
The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma
Authors: E. Giné, S. Montoto, F. Bosch, L. Arenillas, S. Mercadal, N. Villamor, A. Martínez, L. Colomo, E. Campo, E. Montserrat, A. López-Guillermo
Journal: Annals of Oncology (2006)
Effects of ADHD, Conduct Disorder, and Gender on Substance Use and Abuse in Adolescence
Authors: Elizabeth R. Disney, Irene J. Elkins, Matt McGue, William G. Iacono
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The relationships of attention deficit hyperactivity disorder (ADHD), conduct disorder, and gender to substance abuse were studied in a large population-based sample of adolescent twins. METHOD: Structured interviews were administered to 626 pairs of 17-year-old twins (674 girls and 578 boys) and their mothers to generate lifetime psychiatric diagnoses, and computerized measures of current substance use were obtained. Hierarchical logit analyses were performed to assess the independent effects of ADHD, conduct disorder, and gender on current substance use, frequency of substance use, and DSM-III-R diagnoses of substance use disorders. RESULTS: Conduct disorder was found to increase the risk of substance use and abuse in adolescents regardless of gender. In contrast, independent of its association with conduct disorder, an ADHD diagnosis did not significantly increase the risk of substance use problems. CONCLUSIONS: This study found no significant gender differences in the effects of ADHD and conduct disorder on substance use and abuse, although there was some suggestion that girls with ADHD might be at slightly higher risk than boys for substance abuse. In addition, increased risk of substance abuse among adolescents with conduct disorder may be primarily confined to those with persistent conduct disorder.
Carotid Pulses and Peripheral Plethysmograms at Rest
Authors: A. S. DONTAS, ERNST SIMONSON
Journal: Circulation Research (1961)

In 75 healthy men and 47 men with previous coronary occlusion (mean age for both groups 60.0 years), the right carotid pulses and an impedance plethysmogram of the forehead were recorded. There were no significant differences between the major items of the carotid pulse in the two groups, but the absolute and relative peak times of the forehead plethysmograms of the coronary group were shorter than those of the normal group of the same age, and more similar to the pulse contours in healthy younger population. The correlation between the carotid pulse and the forehead impedance plethysmograms was highly significant for most items in the healthy group, whereas in the coronary group only the ratio of initial anacrotic break height to maximal pulse height was significantly correlated in the two pulses. The results suggest a compensatory reaction of peripheral circulation in patients with previous coronary occlusion, and the possible mechanism is discussed.
Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence
Authors: Yonggang Ma, Ying Ann Chiao, Ryan Clark, Elizabeth R. Flynn, Andriy Yabluchanskiy, Omid Ghasemi, Fouad Zouein, Merry L. Lindsey, Yu-Fang Jin
Journal: Cardiovascular Research (2015)

Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6–9 months), middle-aged (12–15 months), old (18–24 months), and senescent (26–34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction.
Effects of maternal diabetes on fetal rat lung ion transport. Contribution of alveolar and bronchiolar epithelial cells to Na+,K(+)-ATPase expression.
Authors: E Pinter, J A Peyman, K Snow, J D Jamieson, J B Warshaw
Journal: Journal of Clinical Investigation (1991)

Fetuses of streptozotocin-induced diabetic rats exhibited delayed lung maturation and a 40% reduction in the steady-state level of lung Na+,K(+)-ATPase alpha 1 subunit mRNA and Na+,K(+)-ATPase activity at 21 d of gestation. In in situ hybridization experiments the signal specific for Na(+)-pump alpha 1 subunit message was strongest above columnar epithelial cells of air-conducting structures. Strong labeling was also present above cuboidal cells lining the forming alveoli, but not above mesenchymal cells. Immunocytochemical localization of the protein paralleled the distribution of the mRNA. Mesenchymal cells were more abundant in fetal lungs of diabetic mothers, and thus the decreased overall levels of Na+,K(+)-ATPase may result from the observed morphological pulmonary immaturity. One day after birth there was no apparent difference in lung morphology at the light microscopic level, in the localization or the steady-state level of Na+,K(+)-ATPase alpha 1 isoform mRNA, or in enzyme activity. Na+,K(+)-ATPase has a likely role in the active phase of fluid absorption in the airways of newborns before the onset of breathing. Decreased fluid clearance and lack of thinning of the lung's connective tissue may contribute to the increased risk for respiratory distress in infants of diabetic mothers.
Toward an Evolutionary Theory of Dreaming
Authors: FREDERICK SNYDER
Journal: American Journal of Psychiatry (1966)

The basic mystery of the biological condition associated with human dreaming, the REM State, is how the purposes of survival are served by such intervals of remarkable nervous excitation which punctuate the sleep of all mammals. The author postulates that while extended sleep achieves conservation of energy, the REM State serves a "sentinel" function, bringing about brief but periodic awakenings after preparing the organism for immediate fight or flight. Such a built-in physiological mechanism presumably would provide maximal security from external danger compatible with minimal disturbance to the continuity of sleep. These may have been unique and critical survival advantages in the early mammalian predicament.
Advanced Cardiac Life Support in Out-of-Hospital Cardiac Arrest
Authors: Ian G. Stiell, George A. Wells, Brian Field, Daniel W. Spaite, Lisa P. Nesbitt, Valerie J. De Maio, Graham Nichol, Donna Cousineau, Josée Blackburn, Doug Munkley, Lorraine Luinstra-Toohey, Tony Campeau, Eugene Dagnone, Marion Lyver
Journal: New England Journal of Medicine (2004)

The Ontario Prehospital Advanced Life Support (OPALS) Study tested the incremental effect on the rate of survival after out-of-hospital cardiac arrest of adding a program of advanced life support to a program of rapid defibrillation.This multicenter, controlled clinical trial was conducted in 17 cities before and after advanced-life-support programs were instituted and enrolled 5638 patients who had had cardiac arrest outside the hospital. Of those patients, 1391 were enrolled during the rapid-defibrillation phase and 4247 during the subsequent advanced-life-support phase. Paramedics were trained in standard advanced life support, which includes endotracheal intubation and the administration of intravenous drugs.From the rapid-defibrillation phase to the advanced-life-support phase, the rate of admission to a hospital increased significantly (10.9 percent vs. 14.6 percent, P<0.001), but the rate of survival to hospital discharge did not (5.0 percent vs. 5.1 percent, P=0.83). The multivariate odds ratio for survival after advanced life support was 1.1 (95 percent confidence interval, 0.8 to 1.5); after an arrest witnessed by a bystander, 4.4 (95 percent confidence interval, 3.1 to 6.4); after cardiopulmonary resuscitation administered by a bystander, 3.7 (95 percent confidence interval, 2.5 to 5.4); and after rapid defibrillation, 3.4 (95 percent confidence interval, 1.4 to 8.4). There was no improvement in the rate of survival with the use of advanced life support in any subgroup.The addition of advanced-life-support interventions did not improve the rate of survival after out-of-hospital cardiac arrest in a previously optimized emergency-medical-services system of rapid defibrillation. In order to save lives, health care planners should make cardiopulmonary resuscitation by citizens and rapid-defibrillation responses a priority for the resources of emergency-medical-services systems.
Tumor Gene Expression and Prognosis in Breast Cancer Patients with 10 or More Positive Lymph Nodes
Authors: Melody A. Cobleigh, Bita Tabesh, Pincas Bitterman, Joffre Baker, Maureen Cronin, Mei-Lan Liu, Russell Borchik, Juan-Miguel Mosquera, Michael G. Walker, Steven Shak
Journal: Clinical Cancer Research (2005)

Abstract Purpose: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)–positive, node-negative breast cancer patients. Experimental Design: Patients with ≥10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Results: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. Conclusion: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.
Public support for hybrid embryos rises with knowledge, poll shows
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

The Human Fertilisation and Embryology Authority, the United Kingdom's fertility watchdog, will decide this week whether to approve in principle the use of hybrid animal-human embryos for research.

Results of a public consultation on the matter, which were released before the authority's decisive meeting that was due to be held on Wednesday 5 September, indicate a widespread lack of understanding among the public on the need and worth of creating hybrid embryos. This is undermining public support for the matter. However, support for hybrid research increases as people appreciate the science involved and its possible applications. 

Scientists …
Inferring the kinetics of stochastic gene expression from single-cell RNA-sequencing data
Authors: Jong Kyoung Kim, John C Marioni
Journal: Genome biology (2013)

Genetically identical populations of cells grown in the same environmental condition show substantial variability in gene expression profiles. Although single-cell RNA-seq provides an opportunity to explore this phenomenon, statistical methods need to be developed to interpret the variability of gene expression counts.We develop a statistical framework for studying the kinetics of stochastic gene expression from single-cell RNA-seq data. By applying our model to a single-cell RNA-seq dataset generated by profiling mouse embryonic stem cells, we find that the inferred kinetic parameters are consistent with RNA polymerase II binding and chromatin modifications. Our results suggest that histone modifications affect transcriptional bursting by modulating both burst size and frequency. Furthermore, we show that our model can be used to identify genes with slow promoter kinetics, which are important for probabilistic differentiation of embryonic stem cells.We conclude that the proposed statistical model provides a flexible and efficient way to investigate the kinetics of transcription.
Influence of Syrosingopine on the Cardiovascular Response to Acute Hypoxemia and Exercise
Authors: CHARLES A. CHIDSEY, ROBERT L. FRYE, RICHARD L. KAHLER, EUGENE BRAUNWALD
Journal: Circulation Research (1961)

Large parenteral doses of a rauwolfia alkaloid, syrosiiigopine, administered to normal volunteers, although inducing a consistent reduction in pulse rate, did not interfere with the increase in cardiac output resulting from acute hypoxemia and exercise. The physiological and pharmacological implications of these observations are discussed.
Polymorphisms in the <i>Interleukin-4 Receptor</i> Gene are Associated with Better Survival in Patients with Glioblastoma
Authors: Michael E. Scheurer, E. Amirian, Yumei Cao, Mark R. Gilbert, Kenneth D. Aldape, David G. Kornguth, Randa El-Zein, Melissa L. Bondy
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Previous literature provides some evidence that atopic diseases, IgE levels, and inflammatory gene polymorphisms may be associated with risk of glioblastoma. The purpose of this study was to investigate the effects of certain inflammatory gene single nucleotide polymorphisms (SNP) on patient survival. Malignant gliomas are the most common type of primary brain tumor in adults, however, few prognostic factors have been identified. Experimental Design: Using 694 incident adult glioma cases identified between 2001 and 2006 in Harris County, TX, we examined seven SNPs in the interleukin (IL)-4, IL-13, and IL-4 receptor (IL4R) genes. Cox proportional hazards regression was used to examine the association between the SNPs and overall and long-term survival, controlling for age at diagnosis, time between diagnosis and registration, extent of surgical resection, radiation therapy, and chemotherapy. Results: We found that among high-grade glioma cases, IL4R rs1805016 (TT versus GT/GG) was significantly protective against mortality over time [hazard ratios (HR), 0.59; 95% confidence intervals (CI), 0.40-0.88]. The IL4R rs1805016 and rs1805015 TT genotypes were both found to be significantly associated with survival beyond 1 year among patients with high-grade glioma (HR, 0.44; 95% CI, 0.27-0.73 and HR, 0.63; 95% CI, 0.44-0.91, respectively). Furthermore, the IL4R haplotype analysis showed that SNPs in the IL4R gene may be interacting to affect long-term survival among high-grade glioma cases. Conclusions: These findings indicate that polymorphisms in inflammation pathway genes may play an important role in glioma survival. Further research on the effects of these polymorphisms on glioma prognosis is warranted.
Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks
Authors: Andrey Morgun, Amiran Dzutsev, Xiaoxi Dong, Renee L Greer, D Joseph Sexton, Jacques Ravel, Martin Schuster, William Hsiao, Polly Matzinger, Natalia Shulzhenko
Journal: Gut (2015)

Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited.Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network.We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments.In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.
UK may allow creation of “cybrids” for stem cell research
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Lester Crawford, former commissioner of the US Food and Drug Administration, was last week fined $89 377 (£45 800; €67 000), sentenced to three years of supervised probation, and required to do 50 hours of community service by Judge Deborah Robinson of the US District Court for the District of Columbia.Last October Dr Crawford (below) pleaded (below) pleaded pleaded guilty to two charges: failing to report that he and his wife owned shares in companies regulated by the agency and filing false
Nutlin-3 Downregulates the Expression of the Oncogene <i>TCL1</i> in Primary B Chronic Lymphocytic Leukemic Cells
Authors: Rebecca Voltan, Maria Grazia di Iasio, Raffaella Bosco, Nicola Valeri, Yuri Pekarski, Mario Tiribelli, Paola Secchiero, Giorgio Zauli
Journal: Clinical Cancer Research (2011)

The oncogene TCL1 plays a key role in the development of B chronic lymphocytic leukemia (B-CLL), but it is not known whether TCL1 could be modulated by therapeutic approaches.B-CLL patient samples (n = 35) and B leukemic cell lines (EHEB, JVM2, JVM3, MEC1, MEC2, and BJAB) with different p53 status were exposed to Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction. Modulations of the steady-state mRNA levels of TCL1 were analyzed by quantitative real-time PCR and Western blotting in both primary B-CLL samples and leukemic cell lines. In addition, transfection experiments with either p53 siRNA or with a TCL1 expression plasmid were carried out in the EHEB B-CLL cell line.Upon ex vivo treatment with Nutlin-3, TCL1 was significantly (P < 0.05) decreased in 23 of 28 B-CLL p53(wild-type). The functionality of the p53 pathway in the same leukemic cell samples was underscored by the concomitant ability of Nutlin-3 to significantly (P < 0.05) upregulate the p53 target gene MDM2 in the p53(wild-type) leukemic cells. The dependence of TCL1 downregulation by a functional p53 pathway was confirmed in a panel of B lymphoblastoid cell lines and by p53 knockdown experiments with p53 siRNA. The importance of TCL1 in promoting leukemic cell survival was underscored in transfection experiments, in which TCL1 overexpression significantly counteracted the Nutlin-3-mediated induction of apoptosis in EHEB.Our data indicate that the Nutlin-3 downregulates TCL1 mRNA and protein, which likely represents an important molecular determinant in the proapoptotic activity of Nutlin-3.
Moving Radioimmunotherapy Forward for Follicular Lymphoma
Authors: Thomas E. Witzig
Journal: Journal of Clinical Oncology (2012)

The treatment of follicular non-Hodgkin lymphoma (NHL), which is the second most common NHL in Western countries, continues to evolve. In this issue of Journal of Clinical Oncology, two important reports deal with the upfront use of radioimmunotherapy (RIT) in follicular lymphoma (FL). Both of these studies enrolled FL patients who were considered to be in need of therapy. The report by Scholz et al 1 used RIT as a single-agent without any chemotherapy, whereas the second study by Press et al 2 was a phase III randomized trial of the standard six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) versus six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with RIT as consolidation (Southwest Oncology Group [SWOG] S0016). The results of these studies have implications for current care and the design of future studies but, as is typical for FL studies, leave us with nagging unanswered questions. RIT is a unique therapeutic modality that uses an antibody carrier to target high-energy, short–path-length radionuclides to tumor sites with little effect on other solid organs. If pretherapy guidelines are followed, the only toxicity is reversible myelosuppression. The known sensitivity of FL to conventional radiation therapy and the usual widespread nature of FL make this type of NHL an attractive target for RIT. Indeed, early randomized studies of unlabeled antibody versus the radiolabeled version of essentially the same antibody in relapsed indolent NHL demonstrated the advantage of the radioimmunoconjugate (RIC) with respect to the overall response rate (ORR) and complete response (CR) rates. 3,4
Giving homoeopathy on the NHS is unethical and unreliable, MPs are told
Authors: A. O'Dowd
Journal: BMJ (2009)

Experts have described the practice of prescribing homoeopathic medicines on the NHS as unethical, unreliable, and pointless.

Several witnesses giving evidence to MPs on the parliamentary science and technology committee on 25 November questioned the wisdom of giving such remedies to patients in an NHS setting.

The committee was holding a one-off evidence session on homoeopathy as part of an investigation of the scientific evidence that underpins the government’s existing policies.

MPs asked about the ethical dimension and James Thallon, medical director of NHS West Kent, giving evidence, said: “I’m not saying that it does not happen, but in principle if you prescribe with that which you know to have no clinical efficacy on …