tbuckley/cabot-search huggingface dataset:
Survival-Related Profile, Pathways, and Transcription Factors in Ovarian Cancer
Authors: Anne P. G Crijns, Rudolf S. N Fehrmann, Steven de Jong, Frans Gerbens, Gert Jan Meersma, Harry G Klip, Harry Hollema, Robert M. W Hofstra, Gerard J. te Meerman, Elisabeth G. E de Vries, Ate G. J van der Zee
Journal: PLoS Medicine (2009)

Ovarian cancer has a poor prognosis due to advanced stage at presentation and either intrinsic or acquired resistance to classic cytotoxic drugs such as platinum and taxoids. Recent large clinical trials with different combinations and sequences of classic cytotoxic drugs indicate that further significant improvement in prognosis by this type of drugs is not to be expected. Currently a large number of drugs, targeting dysregulated molecular pathways in cancer cells have been developed and are introduced in the clinic. A major challenge is to identify those patients who will benefit from drugs targeting these specific dysregulated pathways.The aims of our study were (1) to develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, (2) to assess the association of pathways and transcription factors with overall survival, and (3) to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers.According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using approximately 35,000 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available dataset of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent dataset to assess the similarities with results from our own dataset. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19 versus 41 mo, respectively; permutation p-value of log-rank statistic = 0.015) and maintained its independent prognostic value in multivariate analysis. Genes that composed the overall survival profile were also able to discriminate between the two risk groups in the independent dataset. In our dataset 17/167 pathways and 13/111 transcription factors were associated with overall survival, of which 16 and 12, respectively, were confirmed in the independent dataset.Our study provides new clues to genes, pathways, and transcription factors that contribute to the clinical outcome of serous ovarian cancer and might be exploited in designing new treatment strategies.
voom: precision weights unlock linear model analysis tools for RNA-seq read counts
Authors: Charity W Law, Yunshun Chen, Wei Shi, Gordon K Smyth
Journal: Genome biology (2014)

Abstract New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments. The voom method estimates the mean-variance relationship of the log-counts, generates a precision weight for each observation and enters these into the limma empirical Bayes analysis pipeline. This opens access for RNA-seq analysts to a large body of methodology developed for microarrays. Simulation studies show that voom performs as well or better than count-based RNA-seq methods even when the data are generated according to the assumptions of the earlier methods. Two case studies illustrate the use of linear modeling and gene set testing methods.
Nutritional Factors in Hemodynamics
Authors: RICHARD E. LEE, SACHIKO TANAKA, ELIZABETH A. HOLZE
Journal: Circulation (1952)

Albino rats treated with pteroylglutamic acid (PGA) developed a significant increase in blood pressure, as compared with litter mate controls of the same sex. The hypertension was associated with wedge-shaped fibroblastic renal cortical lesions. Factors possibly important etiologically in the elevation of blood pressure are discussed in relation to certain of the metabolic roles of pteroylglutamic acid.
A 62-Year-Old Man With Fluctuating Neurological Deficits and Skin Lesions
Authors: John J. Konikkara, Osvaldo H. Perurena, Steven Warach, Steven C. Bauserman
Journal: JAMA Neurology (2013)

A 62-year-old man with no significant medical history experienced fatigue, night sweats, hoarseness of voice, and dry cough, which were followed by vision disturbances in his left eye. He lost about 4.5 kg (10 lb) in just over a month. Three weeks later, he had difficulty recollecting his e-mail password and trouble with word finding. The next day, he experienced numbness in his left arm. He also developed a maculopapular and erythematous rash in the groin, genitalia, and buttocks. The results of an initial neurological examination were normal, including his higher mental functions. An initial blood workup revealed normocytic normochromic anemia. The results of cerebrospinal fluid studies were unremarkable. Magnetic resonance imaging of his brain at hospital admission revealed multifocal increased T2 signals in the subcortical white matter. A conventional cerebral angiogram was unremarkable. A biopsy specimen from the right frontal lobe revealed demyelination and perivascular lymphocytic infiltration. A provisional diagnosis of acute disseminated encephalomyelitis was made. In spite of steroid treatment and plasmapheresis, his clinical status deteriorated rapidly. The approach to the diagnosis of a rapidly progressive multifocal brain disorder is discussed.
Belief in evolved belief systems: Artifact of a limited evolutionary model?
Authors: Tyler J. Wereha, Timothy P. Racine
Journal: Behavioral and Brain Sciences (2009)

Abstract Belief in evolved belief systems stems from using a population-genetic model of evolution that misconstrues the developmental relationship between genes and behaviour, confuses notions of “adapted” and “adaptive,” and ignores the fundamental role of language in the development of human beliefs. We suggest that theories about the evolution of belief would be better grounded in a developmental model of evolution.
EVIDENCE SUPPORTING A TWO-GENE MODEL FOR THE H-2 HISTOCOMPATIBILITY SYSTEM OF THE MOUSE
Authors: Jan Klein, Donald C. Shreffler
Journal: The Journal of Experimental Medicine (1972)

The genetic structure of the H-2 system has been traditionally interpreted as consisting of multiple regions controlling histocompatibility antigens. Recently however, many difficulties have been encountered in attempts to construct a single, consistent linear H-2 map on this basis. We have shown that the genetic, serological, and biochemical findings on the H-2 system can be more readily explained by the assumption that there are only two histocompatibility regions (loci) in the H-2 system, H-2D and H-2K, which are separated by loci controlling serum proteins (Ss-Slp), immune response (Ir-1), and perhaps others. Evidence supporting such an interpretation of the H-2 system was obtained by a transplantation analysis of the 14 well-defined H-2 crossovers. F(1) hybrids between different H-2 crossovers were produced and challenged with skin grafts from third party strains. The donor-recipient relationships in these combinations were such that in at least 10 cases the skin grafts should have been rejected if the multiple-region H-2 map is correct but should survive permanently if the two-region model is correct. In all instances, the skin grafts survived permanently, providing further evidence for the two-region map of the H-2 complex.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition – Colonoscopic surveillance following adenoma removal
Authors: W. Atkin, R. Valori, E. Kuipers, G. Hoff, C. Senore, N. Segnan, R. Jover, W. Schmiegel, R. Lambert, C. Pox
Journal: Endoscopy (2012)

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.
PARP1 is required for adhesion molecule expression in atherogenesis
Authors: Tobias von Lukowicz, Paul O. Hassa, Christine Lohmann, Jan Borén, Vincent Braunersreuther, François Mach, Bernhard Odermatt, Monika Gersbach, Giovanni G. Camici, Barbara E. Stähli, Felix C. Tanner, Michael O. Hottiger, Thomas F. Lüscher, Christian M. Matter
Journal: Cardiovascular Research (2007)

Atherosclerosis is the leading cause of death in Western societies and a chronic inflammatory disease. However, the key mediators linking recruitment of inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme, which plays a role in acute inflammatory diseases.In order to test the role of PARP in atherogenesis, we applied chronic pharmacological PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and measured plaque formation, adhesion molecules, and features of plaque vulnerability. After 12 weeks of high-cholesterol diet, plaque formation in male apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic PARP activity or genetic deletion of PARP1 by 46 or 51%, respectively (P < 0.05, n >or= 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished expression of inducible nitric oxide synthase, vascular cell adhesion molecule-1, and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness, and decreased necrotic core size and cell death (P < 0.05, n >or= 6).Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosis.
Do Physical Activity and Aerobic Fitness Moderate the Association Between Birth Weight and Metabolic Risk in Youth?
Authors: Charlotte L. Ridgway, Soren Brage, Sigmund A. Anderssen, Luis B. Sardinha, Lars Bo Andersen, Ulf Ekelund
Journal: Diabetes Care (2010)

OBJECTIVE Lower birth weight has been associated with a greater risk of metabolic diseases. The aim of this study was examine whether physical activity and aerobic fitness may modify associations between birth weigh and metabolic risk. RESEARCH DESIGN AND METHODS The European Youth Heart Study is a population-based study of 9 and 15 year olds (n = 1,254). Birth weight was maternally reported. Skin fold measures were used to calculate body fat and fat mass index (FMI = fat mass [kilograms]/height2). Insulin was measured using fasting blood samples. Physical activity was measured using a hip-worn accelerometer (MTI Actigraph) for &amp;gt;600 min/day for ≥3 days and is expressed as “average activity” (counts per minute) and time spent in above moderate intensity activity (&amp;gt;2000 cpm). Aerobic fitness was assessed using a maximal cycle ergometry test (watts per kilogram fat-free mass). RESULTS Higher birth weight was associated with higher FMI (β = 0.49 [95% CI 0.21–0.80]; P = 0.001) and greater waist circumference (0.90 [0.32–1.47]; P &amp;lt; 0.001), adjusted for sex, age-group, sexual maturity, height, and socioeconomic status. Lower birth weight was associated with higher fasting insulin only after further adjustment for adolescent waist circumference and height (−0.059 [−0.107 to −0.011]; P = 0.016). There was no evidence for any modification of the associations after adjustment for physical activity or aerobic fitness. CONCLUSIONS The present study did not find any evidence that physical activity or aerobic fitness can moderate the associations among higher birth weight and increased fat mass and greater waist circumference or between lower birth weight and insulin resistance in healthy children and adolescents.
Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis
Authors: J P Kaltwasser, E Werner, K Schalk, C Hansen, R Gottschalk, C Seidl
Journal: Gut (1998)

Background —Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. Aims —To investigate this effect in patients with genetic haemochromatosis, and, more importantly, the effect of regular tea drinking on the accumulation of storage iron in these patients over one year. Patients —Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, they were separated into a group instructed to drink a particularly tannin rich tea regularly with meals and a control group. Methods —Intestinal iron absorption from a test meal was measured using whole body counting. Body iron stores were evaluated quantitatively by exhaustive phlebotomy, using haemoglobin, saturation of serum iron binding capacity, and serum ferritin for the assessment of body iron status. Results —A significant reduction in iron absorption was observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one third compared with that of the control group. Conclusions —Regular tea drinking with meals reduces the frequency of phlebotomies required in the management of patients with haemochromatosis.
How Strong Is the Mutagenicity of Recombination in Mammals?
Authors: Shiao-Wei Huang, Robert Friedman, Ning Yu, Alex Yu, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2004)

It is commonly believed that a high recombination rate such as that in a pseudoautosomal region (PAR) greatly increases the mutation rate because a 170-fold increase was estimated for the mouse PAR region. However, sequencing PAR and non-PAR introns of the Fxy gene in four Mus taxa, we found an increase of only twofold to fivefold. Furthermore, analyses of sequence data from human and orangutan PAR and X-linked regions and from autosomal regions showed a weak effect of recombination on mutation rate (a slope of less than 0.2% per cM/Mb), although a much stronger effect on GC content (1% to 2% per cM/Mb). Because typical recombination rates in mammals are much lower than those in PARs, the mutagenicity of recombination is weak or, at best, moderate, although its effect on GC% is much stronger. In addition, contrary to a previous study, we found no Fxy duplicate in Mus spretus.
Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity.
Authors: T Onodera, A Toniolo, U R Ray, A B Jenson, R A Knazek, A L Notkins
Journal: The Journal of Experimental Medicine (1981)

Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH.
THE SERUM-TREATMENT OF TYPHOID FEVER.
Authors: C. J. Mcsweeney
Journal: JAMA (1904)

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THE RORSCHACH AND CENTRAL NERVOUS SYSTEM PATHOLOGY: A CROSS-VALIDATION STUDY
Authors: JEROME FISHER, THOMAS A. GONDA, KENNETH B. LITTLE
Journal: American Journal of Psychiatry (1955)

Four Rorschach systems for determining the presence or absence of brain pathology are compared using a sample of 118 patients. Representativeness of the sample was secured by selecting only patients admitted to a neurology ward with complaints, signs, and/or symptoms referrable to the nervous system. The sample was divided, on the basis of the combined judgments of 2 neurologists, into cases presumably having brain pathology above the foramen magnum (84 cases) and those presumably having no such pathology (34 cases). The patients in both groups had undergone thorough and equivalent neurologic investigation. Results of the comparison of the 4 Rorschach systems with this criterion indicate that 3 of the 4 systems can distinguish between persons with and those without brain pathology with better than chance accuracy. The Piotrowski and Hughes systems are highly accurate (94% and 91%, respectively) when they identify a case as "organic" (only 6% and 9% false positives). However, when these systems identify a case as "nonorganic" the finding is inconclusive in that they fail to identify 62% of the organic cases (false negatives). The Ross and Ross system is slightly less accurate. The Dörken and Kral system yields results that can be explained in terms of chance and shows a systematic tendency to identify too many cases as "organics," resulting in 76% false positives. Only l of the 4 systems, Piotrowski's, maintains a validity level comparable to that obtained in previous studies. The results are discussed and recommendations for derivation of more efficient Rorschach diagnostic systems advanced.
Could postinterferon treatment α-fetoprotein levels truly predict hepatocarcinogenesis?
Authors: Gin-Ho Lo
Journal: Hepatology (2014)

I read with interest the article by Asahina et al.1 regarding the levels of α-fetoprotein (AFP) and alanine aminotransferase (ALT) after interferon therapy that could predict the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. The authors made a great effort to evaluate the levels of AFP and ALT in a cohort of 1,818 patients after interferon therapy and found that cutoff values for ALT and AFP for prediction HCC development were 40 IU/L and 6.0 ng/mL, respectively. These findings may be helpful for clinicians to closely follow-up high-risk patients to detect early-stage HCC. However, these data may also be misleading and need further clarification. The levels of AFP and ALT were measured every 1-6 months. It is unknown which timepoint of AFP and ALT levels were selected for calculation. Serum AFP levels usually fluctuate during serial observation. Some patients may present with an AFP >6 ng/mL before therapy, which decreased to <6 ng/mL within a few months after interferon therapy, and became elevated to >6 ng/mL at long-term follow-up. Should these patients be classified as AFP ≧6 ng/mL decreased group or AFP ≧6 ng/mL unchanged group? The mean follow-up period of this study was 6.1 years. The follow-up period in this study has been as long as 20 years. If the interval of AFP measurement was as short as 1 month, too many unnecessary measurements could have been performed. As shown in the results, postinterferon therapy AFP level ≧6.0 ng/mL had a positive predictive value of only 0.262. Consistent with previous observation, this may evoke inappropriate suspicion of malignancy in 74 out of 100 patients with AFP above this cutoff value.2 A total of 179 patients developed HCC, accounting for 9.8% of the entire cohort of 1,818 patients. Based on the HALT-C trial, patients with persistent elevation of AFP after interferon therapy, only 2% were noted to develop HCC.3 We believe that a large proportion of patients still did not have elevated AFP levels on detection of HCC occurrence. Thus, the applicability and cost-effectiveness of this policy merits further investigation. Gin-Ho Lo, M.D. Department of Medical Research E-DA Hospital School of Medicine for International Students I-Shou University Kaohsiung, Taiwan