tbuckley/cabot-search huggingface dataset:
Abstract 1113: The comprehensive mutational profiling of lung adenocarcinoma through large-scale RNA sequencing analysis.
Authors: Won-Chul Lee, Young Seok Ju, Jong-Yeon Shin, June Koo Lee, Thomas Bleazard, Jun-Ho Lee, Jung-Oh Kim, Saet-Byeol Yu, Jihye Kim, Hwanseok Rhee, Se-Hoon Lee, Jong-Il Kim, Jin-Hyoung Kang, Young Tae Kim, Jeong-Sun Seo
Journal: Cancer Research (2013)

Abstract All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2 and SMARCA4. We found 45 fusion genes, 8 of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches. Citation Format: Won-Chul Lee, Young Seok Ju, Jong-Yeon Shin, June Koo Lee, Thomas Bleazard, Jun-Ho Lee, Jung-Oh Kim, Saet-Byeol Yu, Jihye Kim, Hwanseok Rhee, Se-Hoon Lee, Jong-Il Kim, Jin-Hyoung Kang, Young Tae Kim, Jeong-Sun Seo. The comprehensive mutational profiling of lung adenocarcinoma through large-scale RNA sequencing analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1113. doi:10.1158/1538-7445.AM2013-1113
Down's Syndrome: Mongolism and Its Management
Authors: George A. Jervis
Journal: JAMA (1970)

Dr. Benda's contributions to the study of mongolism (Down's syndrome), which are based on personal observation of over 1,000 patients, are well known. His first book,<i>Mongolism and Cretinism</i>, was published in 1946 and was followed by a second edition in 1949. A third edition under the title,<i>The Child With Mongolism</i>, appeared in 1960. The present revised edition includes much material previously published and adds several new observations. The chapters on epidemiology and clinical aspects follow on the whole previous editions and conclude with the reaffirmation that Down's syndrome represents a "decelerated development" and an "arrest of differentiation" of most systems of the body. The 38-page chapter on hematology and biochemistry deals with tests which are mostly routine. The results show a wide range of values but no consistent major abnormalities are apparent from the detailed data presented by the author. Almost one third of the book is devoted
A Widespread Bacterial Type VI Secretion Effector Superfamily Identified Using a Heuristic Approach
Authors: Alistair B. Russell, Pragya Singh, Mitchell Brittnacher, Nhat Khai Bui, Rachel D. Hood, Mike A. Carl, Danielle M. Agnello, Sandra Schwarz, David R. Goodlett, Waldemar Vollmer, Joseph D. Mougous
Journal: Cell Host & Microbe (2012)
P166 Patients With Confirmed And Suspected Pulmonary Emboli Have The Same Two-year Mortality
Authors: A. Williams, C. Burford, R. Poyner, H. Nair, D. Menzies
Journal: Thorax (2014)

<h3>Introduction</h3> There is limited information regarding long-term survival following Pulmonary Embolism (PE), and no data on survival of patients that have undergone CT Pulmonary Angiography (CTPA) but found to be thrombus negative. The positive rate of PE detection in patients undergoing CTPA is variable, ranging from 4.7–25.8% and there is a high reported incidence of incidental pathology discovered during this investigation. We sought to determine the comparative survival of patient undergoing CTPA that were thrombus positive compared with those without a PE. We also sought to determine the rate of PE detection and characterise the nature of incidental findings found in patients undergoing CTPA. <h3>Methods</h3> We retrospectively reviewed data on all CTPA investigations conducted between April 2010 and April 2012. All abnormalities reported on CTPA were reviewed and compared with previous imaging from the last 6 months to determine if they were new findings. Follow-up investigations and out-patient attendances were obtained for all new findings reported on the index CTPA, and 2 year mortality rates were established from regional registry data. <h3>Results</h3> Of the 1043 patients suitable for analysis, 241 (22.4%) were thrombus positive. The thrombus positive cohort consisted of 47.7% males compared with 40.7% in the thrombus negative group (difference 7.1% [-0.0 to 14.2, p = 0.52]). Survival at 2 years following CTPA was 67.6% in thrombus positive patients and 65.9% in thrombus negative patients with a hazard ratio of 0.96 (95% CI, 0.74 to 1.23, p = 0.721) (Figure). Incidental findings were detected in 51.1% of CTPA examinations including: consolidation/collapse (19.5%), effusion (16.7%), neoplasia (13.5%), lymphadenopathy (9.8%), heart failure (7.6%) and pulmonary nodules (6.6%). 47.7% of incidental findings were deemed significant as determined by the need for further follow-up of clinical intervention. <h3>Conclusion</h3> There is no difference in the 2 year mortality between thrombus positive and thrombus negative patients undergoing CTPA. Many incidental findings found on CTPA are clinically significant.
The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus
Authors: Fumihiko Matsuda, Kazuo Ishii, Patrice Bourvagnet, Kei-ichi Kuma, Hidenori Hayashida, Takashi Miyata, Tasuku Honjo
Journal: The Journal of Experimental Medicine (1998)

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (VH) region locus was determined and 43 novel VH segments were identified. The region contains 123 VH segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 VH segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of VH region was calculated to be ∼6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional VH segments than in pseudogenes. Phylogenetic analysis of 114 VH segments clearly showed clustering of the VH segments of each family. However, an independent branch in the tree contained a single VH, V4-44.1P, sharing similar levels of homology to human VH families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region.
Polycythemia and Nuclear 'Exposure'-Reply
Authors: Glyn C. Caldwell
Journal: JAMA (1985)

In Reply.—  In reporting an apparent excess of polycythemia vera among participants of a nuclear weapons test, we did not consider it unscientific to conclude that  small individual whole-body doses of radiation reported for these four participants makes the association with ionizing radiation tenuous, although this was the only unusual risk factor. Such a conclusion is only prudent because we lacked information on potential confounding factors (eg, race, religion, marital status, and other radiation exposures) that might explain the observed excess.  We never stated that the exposure potentially received from inhaled or ingested radionuclides absorbed by these participants was minimal, only that no data were available for measuring such exposure. If such data were available, we might or might not have found that the reported patients had a higher total exposure than anyone else. Without such data, we still believe it important to have alerted the medical community by
Evaluating the reliability of causes of death in published clinical research
Authors: R D Start, J P Bury, A G Strachan, S S Cross, J C E Underwood
Journal: BMJ (1997)

Objective: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).Design: Randomised controlled trial.Setting: Specialist clinic for recurrent miscarriages.Subjects: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.Intervention: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly.All women started treatment with low dose aspirin when they had a positive urine pregnancy test.Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography.Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. Main outcome measures: Rate of live births with the two treatments.Results: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages.The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)).More than 90% of miscarriages occurred in the first trimester.There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation.Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation.Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). Conclusion:Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.
Indian drug maker cuts price of three cancer drugs by between 50% and 63%
Authors: M. Kay
Journal: BMJ (2012)

Taking a step forward in making drugs “affordable and accessible,” Cipla, one of the largest Indian drug makers, recently announced cuts of between 50% and 63% in the price of three cancer drugs—erlotinib, docetaxel, and capecitabine.1

The announcement comes six months after the first such announcement by Cipla, when it slashed the price of three major anti-cancer drugs—sorafenib, gefitinib, and temozolomide—by 76%, cutting across the drug pricing barrier in India.2

“Following the …
Airway smooth muscle prostaglandin-EP1 receptors directly modulate 2-adrenergic receptors within a unique heterodimeric complex
Authors: D. W. McGraw
Journal: Journal of Clinical Investigation (2006)

Multiple and paradoxical effects of airway smooth muscle (ASM) 7-transmembrane–spanning receptors activated during asthma, or by treatment with bronchodilators such as β2–adrenergic receptor (β2AR) agonists, indicate extensive receptor crosstalk. We examined the signaling of the prostanoid-EP1 receptor, since its endogenous agonist prostaglandin E2 is abundant in the airway, but its functional implications are poorly defined. Activation of EP1 failed to elicit ASM contraction in mouse trachea via this Gαq-coupled receptor. However, EP1 activation markedly reduced the bronchodilatory function of β2AR agonist, but not forskolin, indicating an early pathway interaction. Activation of EP1 reduced β2AR-stimulated cAMP in ASM but did not promote or augment β2AR phosphorylation or alter β2AR trafficking. Bioluminescence resonant energy transfer showed EP1 and β2AR formed heterodimers, which were further modified by EP1 agonist. In cell membrane [35S]GTPγS binding studies, the presence of the EP1 component of the dimer uncoupled β2AR from Gαs, an effect accentuated by EP1 agonist activation. Thus alone, EP1 does not appear to have a significant direct effect on airway tone but acts as a modulator of the β2AR, altering Gαs coupling via steric interactions imposed by the EP1:β2AR heterodimeric signaling complex and ultimately affecting β2AR-mediated bronchial relaxation. This mechanism may contribute to β-agonist resistance found in asthma.
Outcome of Investigation of Patients with Presenile Dementia
Authors: C. D. Marsden, M. J. G. Harrison
Journal: BMJ (1972)

Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.
PRECIPITIN REACTIONS OF HIGHLY PURIFIED INFLUENZA VIRUSES AND RELATED MATERIALS
Authors: C. A. Knight
Journal: The Journal of Experimental Medicine (1946)

Antisera to purified PR8 virus, to purified protein from normal allantoic fluid, and to purified normal mouse lung particles were obtained from hyper-immunized rabbits and used in quantitative precipitin tests employing various purified preparations of influenza virus and related materials as antigens. The results of those tests indicated that the most highly purified preparations of PR8 or of Lee influenza virus obtained from infectious allantoic fluid contain an antigen characteristic of normal allantoic fluid and likewise that highly purified mouse lung PR8 virus contains an antigen characteristic of normal mouse lungs. Since the infectivity of virus preparations which were ultracentrifugally and electrochemically homogeneous was precipitated by the appropriate antisera to normal antigens, it was concluded that the normal antigens constitute a part of the 100 mµ particles with which influenza virus activity is at present deemed to be associated. It was estimated from quantitative precipitin data that the most highly purified preparations of PR8 and of Lee influenza viruses obtained from infectious allantoic fluid contain at least about 20 and 30 per cent, respectively, of an antigenic structure characteristic of the sedimentable protein of normal allantoic fluid.
Parametric v non-parametric statistical tests
Authors: P. Sedgwick
Journal: BMJ (2012)

Researchers investigated five year mortality in patients with chronic heart failure by comparing those with impaired left ventricular function (n=359) with those with preserved function (n=163).1 A prospective cohort study design was used, with patients enrolled if they had had stable symptomatic chronic heart failure for at least three months. Characteristics of patients measured at recruitment included age and heart rate. Patients with preserved function were a similar age to those with impaired function (62.5 (standard deviation 10.7) v 62.3 (9.10) years; independent samples t test: P=0.80). Those with preserved function had a lower median heart rate (69 (interquartile range 63-82) v 76 (66-89) beats/min; Mann-Whitney U test P<0.001). Five year mortality was significantly greater in patients with impaired left ventricular systolic function (41.5% v 25.2%; P<0.001). Which of the following statements, if any, are true?
Acquired free protein S deficiency associated with multiple myeloma: A case report
Authors: Steven R. Deitcher, John K. Erban, Steven A. Limentani
Journal: American Journal of Hematology (1996)

Investigation of recurrent venous thromboembolic events in a 46-year-old man with progressive IgG kappa (total serum IgG, 74.3 mg/ml) multiple myeloma revealed profound reductions in free protein S (PS) antigen (<0.1 U/ml) and PS activity (0.33 U/ml). Total PS antigen, protein C, antithrombin III, and C4b-binding protein levels were within normal limits. The patient had no family history suggestive of a congenital PS deficiency and no history of thrombosis predating the diagnosis of his plasma cell dyscrasia. Patient IgG was isolated from serum using a protein A-sepharose affinity column and characterized. PS-dependent clotting assays (Staclot Protein S, Diagnostica Stago, Asnleres sur-Seine, France) performed on normal pooled plasma mixed with dilutions of patient IgG (0.0–33.0 mg/ml) revealed a dose-dependent neutralization of PS activity by 43%. Total and free PS antigen levels were measured using Laurell rocket electroimmunodiffusion (Assera-Plate Protein S, Diagnostica Stago), which revealed a similar dose-dependent reduction in free PS antigen but preserved normal total PS antigen. Free PS antigen was reduced by 77% to 0.23 U/ml using an IgG concentration (16.5 mg/ml) less than one-fourth of that of the patient at time of serum collection. Specific binding of the patient IgG to commercially available purified human PS was demonstrated by Western Immunoblot analysis. Whereas acquired free PS deficiency has been previously reported in association with nephrotic syndrome, inflammatory bowel disease, HIV infection, and varicella infection, this is the first reported case of a hypercoagulable syndrome associated with acquired free PS deficiency and multiple myeloma. © 1996 Wiley-Liss, Inc.
Comparative body fat assessment in elite footballers
Authors: L Özçakar, A Çetin, B Kunduracýo∂lu, B Ülkar
Journal: British Journal of Sports Medicine (2003)

Much attention is directed to measuring body composition, particularly fat mass, the aim being to estimate the untoward health consequences of excessive amounts of fat or to assess physical fitness. There are two main types of method of measurement: reference and prediction techniques. The former consist of measuring body density or total body water and dual energy x ray absorptiometry, and the latter include measurement of skinfold thickness and bioelectrical impedance analysis.1 The Tanita body fat analyser is a commercially available foot to foot bioelectrical impedance analysis system.2 It is a novel method because it measures the weight and percentage of body fat simultaneously while the subject stands …
Elevated C-reactive protein in diabetics with acute coronary syndrome: culprit or innocent bystander?
Authors: Harish R. Chandra, Cindy L. Grines, Carol S. O'Neill, Nivedita Choudhary, Judith Boura, Kishore J. Harjai, H.Mehrdad Sadeghi, James A. Goldstein, William W. O'Neill
Journal: Journal of the American College of Cardiology (2002)
Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response
Authors: Kate Sidaway-Lee, Maria J Costa, David A Rand, Bärbel Finkenstadt, Steven Penfield
Journal: Genome biology (2014)

Abstract Background Sensing and responding to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes in transcription or decay rates, and whether passive or active temperature regulation is involved. Results Using a base analog labelling method, we directly measured the temperature coefficient, Q 10 , of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes, transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional process exists that controls mRNA abundance by temperature. This is partly accounted for by gene body H2A.Z which is associated with low transcription rate Q 10 , but is also influenced by other marks and transcription factor activities. Conclusions Our data show that less frequent chromatin states can produce temperature responses simply by virtue of their rarity and the difference between their thermal properties and those of the most common states, and underline the advantages of directly measuring transcription rate changes in dynamic systems, rather than inferring rates from changes in mRNA abundance.
Coronary Heart Disease in the Western Collaborative Group Study
Authors: Ray H. Rosenman
Journal: JAMA (1966)

A prospective study on coronary heart disease (CHD) was initiated in 1960 among 3,524 subjects at risk for its subsequent occurrence. The findings of the first two years of follow-up are presented, during which (mean 2 1/2 years of risk exposure) 70 subjects incurred the advent of manifest CHD. These findings indicate that the presence of (1) abnormalities in lipoprotein pattern, (2) hypertension, or (3) exhibition of a specific overt behavior pattern (type A) each possessed significant prognostic import. The exhibition of the behavior pattern furnished the most important single prognostic entity. Furthermore, the enhanced prognostic risk associated with hypertension or with an abnormal lipoprotein pattern became significant only when either or both of these findings occurred in the subject with type A behavior pattern.
Endothelial cell induced modulation of cardiac fibroblast collagen metabolism
Authors: E. Guarda, P. R Myers, C. G Brilla, S. C Tyagi, K. T Weber
Journal: Cardiovascular Research (1993)

The aim was to examine the influence of vascular endothelial cells on rat cardiac fibroblast collagen synthesis and collagenase activity under co-culture conditions, and to determine whether angiotensin II or aldosterone influence endothelial cell induced modulation of fibroblast collagen metabolism.Bovine aortic endothelial cells were grown to confluence on microporous membrane inserts and then co-cultured with cardiac fibroblasts obtained from adult rats, previously grown to confluence in 35 mm dishes supplemented with 0.4% fetal bovine serum. Collagen synthesis was measured by 3H-proline incorporation. Experiments were also conducted under similar conditions to quantitate collagenase activity by zymography in conditioned medium from fibroblasts co-cultured with endothelial cells.After 48 h co-culture, there was a 1.9-fold increase in fibroblast collagen synthesis when compared to fibroblasts alone (p < 0.001). Aldosterone (10(-8) M) or angiotensin II (10(-7) M) added to endothelial cells did not increase fibroblast collagen synthesis over co-cultures alone. Neither the aldosterone receptor antagonist spironolactone (10(-8) M) nor type I (DuP 753, 10(-8) M) or type II (PD 123319, 10(-8) M) angiotensin II receptor antagonists altered fibroblast collagen synthesis in co-cultures. A significant increment in collagenase activity was observed in co-cultured fibroblasts relative to collagenase activity of fibroblasts alone.Endothelial cells modulate both cardiac fibroblast collagen synthesis and degradation. The nature of the responsible signal(s) remains to be defined, but does not appear to be mediated or regulated by angiotensin II or aldosterone.