tbuckley/cabot-search huggingface dataset:
Nitrogen dioxide and mortality: review and meta-analysis of long-term studies
Authors: Annunziata Faustini, Regula Rapp, Francesco Forastiere
Journal: European Respiratory Journal (2014)

Exposure to ambient nitrogen dioxide (NO2) has been linked to increased mortality in several epidemiological studies but the question remains of whether NO2 is directly responsible for the health effects or is only an indicator of other pollutants, including particulate matter. The aim of the present review was to provide pooled estimates of the long-term effects of NO2 on mortality, which are potentially useful for health impact assessment. We selected 23 papers, published from 2004 to 2013, evaluating the relationship between NO2 and mortality, also including an assessment of the effect of particulate matter exposure. A random-effects meta-analysis was carried out on 19 studies. The pooled effect on mortality was 1.04 (95% CI 1.02-1.06) with an increase of 10 μg · m(-3) in the annual NO2 concentration and 1.05 (95% CI 1.01-1.09) for particulate matter <2.5 μm in diameter (PM2.5) (10 μg · m(-3)). The effect on cardiovascular mortality was 1.13 (95% CI 1.09-1.18) for NO2 and 1.20 (95% CI 1.09-1.31) for PM2.5. The NO2 effect on respiratory mortality was 1.03 (95% CI 1.02-1.03) and 1.05 (95% CI 1.01-1.09) for PM2.5. Four bipollutant analyses with particulate matter and NO2 in the same models showed minimal changes in the effect estimates of NO2. There is evidence of a long-term effect of NO2 on mortality as great as that of PM2.5. An independent effect of NO2 emerged from multipollutant models.
SP-05 * VENOUS THROMBOEMBOLISM AND GLIOBLASTOMA
Authors: S. Yust-Katz, J. Mandel, Y. Ying, J. Wu, C. Courtney, H. Ladha, T. Pawar, M. Gilbert, T. Armstrong
Journal: Neuro-Oncology (2014)

The risk of venous thromboembolism (VTE) is very high for patients with brain tumors; Glioblastoma (GB) specifically is one of the most at risk cancers. The aim of this study is to estimate the frequency and identify potential risk factors of GB patients developing VTE during adjuvant chemotherapy and to test if the Khorana scale accurately predicts the risk of VTE among this patient population. We retrospectively reviewed patients with GB treated at MD Anderson during the years 2005-2011. The target population of our study was patients who developed VTE after starting adjuvant chemotherapy. Patients were excluded if they did not start treatment with the established standard of care, had less than 6 months follow up or if they developed VTE before starting adjuvant treatment. The study sample included 440 patients. 64 (14.5%) of them developed VTE. The median time to develop VTE was 6.5 months. On multivariate analysis male sex, BMI≥ 35, KPS ≤80, history of VTE and steroid therapy were significantly associated with the development of VTE. We also found that in this patient sample, the Khorana scale was not a valid predictive model in GB patients due to very poor specificity. Of the 64 patients who developed a VTE, 36 were treated with anticoagulation, 2 with an IVC filter, and 21 with both. Complications secondary to anticoagulation were reported in 16% (n = 10) of patients. The complications included intracranial hemorrhage, bleeding to other organs and thrombocytopenia. VTE is very common in patients with GB. Currently, we are lacking a scale that accurately predicts the risk of VTE among GB patients. Predictive scales used for other cancers do not seem valid for GB due to the unique nature of the disease. Future studies are needed to create an accurate predictive model for VTE in GB patients.
Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution
Authors: Jeramiah J Smith, Shigehiro Kuraku, Carson Holt, Tatjana Sauka-Spengler, Ning Jiang, Michael S Campbell, Mark D Yandell, Tereza Manousaki, Axel Meyer, Ona E Bloom, Jennifer R Morgan, Joseph D Buxbaum, Ravi Sachidanandam, Carrie Sims, Alexander S Garruss, Malcolm Cook, Robb Krumlauf, Leanne M Wiedemann, Stacia A Sower, Wayne A Decatur, Jeffrey A Hall, Chris T Amemiya, Nil R Saha, Katherine M Buckley, Jonathan P Rast, Sabyasachi Das, Masayuki Hirano, Nathanael McCurley, Peng Guo, Nicolas Rohner, Clifford J Tabin, Paul Piccinelli, Greg Elgar, Magali Ruffier, Bronwen L Aken, Stephen M J Searle, Matthieu Muffato, Miguel Pignatelli, Javier Herrero, Matthew Jones, C Titus Brown, Yu-Wen Chung-Davidson, Kaben G Nanlohy, Scot V Libants, Chu-Yin Yeh, David W McCauley, James A Langeland, Zeev Pancer, Bernd Fritzsch, Pieter J de Jong, Baoli Zhu, Lucinda L Fulton, Brenda Theising, Paul Flicek, Marianne E Bronner, Wesley C Warren, Sandra W Clifton, Richard K Wilson, Weiming Li
Journal: Nature Genetics (2013)

Jeramiah Smith, Weiming Li and colleagues report the whole-genome sequence of the sea lamprey, Petromyzon marinus, representing a vertebrate lineage diverged from humans ~500 million years ago. Their analyses define key evolutionary events in vertebrate lineages and provide evidence for two whole-genome duplication events occurring before the divergence of the ancestral lamprey and jawed vertebrate (gnathostome) lineages. Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.
Delivery of subunit vaccines in maize seed
Authors: Barry J Lamphear, Stephen J Streatfield, Joseph M Jilka, Christopher A Brooks, Donna K Barker, Debra D Turner, Donna E Delaney, Martin Garcia, Barry Wiggins, Susan L Woodard, Elizabeth E Hood, Ian R Tizard, Bruce Lawhorn, John A Howard
Journal: Journal of Controlled Release (2002)
Request for slimming tablets
Authors: S W Mercer, M E J Lean
Journal: BMJ (2008)

Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (<i>F</i><sub>e,NO</sub>) and urinary biomarkers of airway inflammation. Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and <i>F</i><sub>e,NO</sub> and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine. Despite no change in pulmonary function (forced expiratory volume in one second mean±sem fall 0.3±0.7 <i>versus</i> 0.6±1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in <i>F</i><sub>e,NO</sub> (up to a doubling from baseline) and a small increase in the mast cell marker 9α11β-prostaglandin F<sub>2</sub> after adenosine challenge. In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.
Biochemical energetics of simulated platelet plug formation
Authors: Simon Karpatkin, Richard M. Langer
Journal: Journal of Clinical Investigation (1968)

Washed human platelets were incubated in a modified Ringer's solution, pH 7.1, at 37°C for 1 hr. Intracellular basal levels for glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and orthophosphate were 31.1, 2.52, 1.39, 0.36, and 1.2 μmoles/ml of platelets, respectively. Extracellular ATP, ADP, and AMP remained fairly constant and represented 4, 2, and 4% of total adenine nucleotide content. Total adenine nucleotide content remained unchanged during the period of control incubation. Glycogen depletion was 17.8 μmoles/ml at the end of 1 hr; lactate production was 20.7 μmoles/ml per hr. In the presence of glucose, lactate production increased 100%, and glycogen depletion was spared 13%. Approximately 55% of glucose or glycogen fuel was converted to lactate.
Public health implications of using various case definitions in The Netherlands during the worldwide SARS outbreak
Authors: A. Timen, G.J.J. van Doornum, M. Schutten, M.A.E. Conyn-van Spaendonck, J.W.M. van der Meer, A.D.M.E. Osterhaus, J.E. van Steenbergen
Journal: Clinical Microbiology and Infection (2006)
Accuracy of Adult Recall of Childhood Attention Deficit Hyperactivity Disorder
Authors: Salvatore Mannuzza, Rachel G. Klein, Donald F. Klein, Abrah Bessler, Patrick Shrout
Journal: American Journal of Psychiatry (2002)

Although reports of childhood status are necessary for making a diagnosis of adult attention deficit hyperactivity disorder (ADHD), systematic investigation of the accuracy of retrospective self-reports has been limited. This study examined accuracy of adult recall of childhood ADHD.Participants were from a controlled, prospective 16-year follow-up of children with ADHD. At a mean age of 25 years, 176 probands (85% of the 207 subjects in the initial cohort) and 168 non-ADHD comparison subjects were interviewed by clinicians who were unaware of the subjects' childhood status. Subjects were asked about specific childhood ADHD behaviors, and the diagnosis of childhood ADHD was retrospectively established.Seventy-eight percent of the probands and 11% of the comparison subjects were identified as having childhood ADHD. Six symptoms demonstrated high discriminating power in differentiating the subject groups: distractibility, concentration difficulties, complaints of inattention, acting before thinking, being on the go, and fidgeting/squirming. When findings were adjusted for the prevalence of ADHD in the general population, the power of prediction was low. Positive predictive value was 0.27, i.e., of all adults retrospectively given a diagnosis of childhood ADHD, only 27% would be correctly identified. As expected, positive predictive value increased with increases in the estimated prevalence of ADHD.Retrospective diagnoses of childhood ADHD made on the basis of self-reports will in most cases be invalid in settings such as epidemiological surveys and primary care facilities. Greater accuracy can be expected in settings in which childhood ADHD is frequent. The results stress the importance of obtaining contemporaneous information on childhood symptoms in establishing a childhood history of ADHD. Future directions and implications for DSM-V are discussed.
Shorthand for Medical Students
Authors: P. E. Kingsford
Journal: BMJ (1889)

It has been well documented that neurotrophins, including brain-derived neurotrophic factor (BDNF), are severely affected in Alzheimer9s disease (AD), but their administration faces a myriad of technical challenges. Here we took advantage of the early astrogliosis observed in an amyloid mouse model of AD (5xFAD) and used it as an internal sensor to administer BDNF conditionally and locally. We first demonstrate the relevance of BDNF release from astrocytes by evaluating the effects of coculturing WT neurons and BDNF-deficient astrocytes. Next, we crossed 5xFAD mice with pGFAP:BDNF mice (only males were used) to create 5xFAD mice that overexpress BDNF when and where astrogliosis is initiated (5xF:pGB mice). We evaluated the behavioral phenotype of these mice. We first found that BDNF from astrocytes is crucial for dendrite outgrowth and spine number in cultured WT neurons. Double-mutant 5xF:pGB mice displayed improvements in cognitive tasks compared with 5xFAD littermates. In these mice, there was a rescue of BDNF/TrkB downstream signaling activity associated with an improvement of dendritic spine density and morphology. Clusters of synaptic markers, PSD-95 and synaptophysin, were also recovered in 5xF:pGB compared with 5xFAD mice as well as the number of presynaptic vesicles at excitatory synapses. Additionally, experimentally evoked LTP <i>in vivo</i> was increased in 5xF:pGB mice. The beneficial effects of conditional BDNF production and local delivery at the location of active neuropathology highlight the potential to use endogenous biomarkers with early onset, such as astrogliosis, as regulators of neurotrophic therapy in AD. <b>SIGNIFICANCE STATEMENT</b> Recent evidence places astrocytes as pivotal players during synaptic plasticity and memory processes. In the present work, we first provide evidence that astrocytes are essential for neuronal morphology via BDNF release. We then crossed transgenic mice (5xFAD mice) with the transgenic pGFAP-BDNF mice, which express BDNF under the GFAP promoter. The resultant double-mutant mice 5xF:pGB mice displayed a full rescue of hippocampal BDNF loss and related signaling compared with 5xFAD mice and a significant and specific improvement in all the evaluated cognitive tasks. These improvements did not correlate with amelioration of β amyloid load or hippocampal adult neurogenesis rate but were accompanied by a dramatic recovery of structural and functional synaptic plasticity.
Health and climate change: policy responses to protect public health
Authors: Nick Watts, W Neil Adger, Paolo Agnolucci, Jason Blackstock, Peter Byass, Wenjia Cai, Sarah Chaytor, Tim Colbourn, Mat Collins, Adam Cooper, Peter M Cox, Joanna Depledge, Paul Drummond, Paul Ekins, Victor Galaz, Delia Grace, Hilary Graham, Michael Grubb, Andy Haines, Ian Hamilton, Alasdair Hunter, Xujia Jiang, Moxuan Li, Ilan Kelman, Lu Liang, Melissa Lott, Robert Lowe, Yong Luo, Georgina Mace, Mark Maslin, Maria Nilsson, Tadj Oreszczyn, Steve Pye, Tara Quinn, My Svensdotter, Sergey Venevsky, Koko Warner, Bing Xu, Jun Yang, Yongyuan Yin, Chaoqing Yu, Qiang Zhang, Peng Gong, Hugh Montgomery, Anthony Costello
Journal: The Lancet (2015)
Précis of <i>How Children Learn the Meanings of Words</i>
Authors: Paul Bloom
Journal: Behavioral and Brain Sciences (2001)

Normal children learn tens of thousands of words, and do so quickly and efficiently, often in highly impoverished environments. In How Children Learn the Meanings of Words, I argue that word learning is the product of certain cognitive and linguistic abilities that include the ability to acquire concepts, an appreciation of syntactic cues to meaning, and a rich understanding of the mental states of other people. These capacities are powerful, early emerging, and to some extent uniquely human, but they are not special to word learning. This proposal is an alternative to the view that word learning is the result of simple associative learning mechanisms, and it rejects as well the notion that children possess constraints, either innate or learned, that are specifically earmarked for word learning. This theory is extended to account for how children learn names for objects, substances, and abstract entities, pronouns and proper names, verbs, determiners, prepositions, and number words. Several related topics are also discussed, including naïve essentialism, children's understanding of representational art, the nature of numerical and spatial reasoning, and the role of words in the shaping of mental life.
Eight-Signature Classifier for Prediction of Nasopharyngeal Carcinoma Survival
Authors: Hai-Yun Wang, Bing-Yu Sun, Zhi-Hua Zhu, Ellen T. Chang, Ka-Fai To, Jacqueline S.G. Hwang, Hao Jiang, Michael Koon-Ming Kam, Gang Chen, Shie-Lee Cheah, Ming Lee, Zhi-Wei Liu, Jing Chen, Jia-Xing Zhang, Hui-Zhong Zhang, Jie-Hua He, Fa-Long Chen, Xiao-Dong Zhu, Ma-Yan Huang, Ding-Zhun Liao, Jia Fu, Qiong Shao, Man-Bo Cai, Zi-Ming Du, Li-Xu Yan, Chun-Fang Hu, Ho-Keung Ng, Joseph T.S. Wee, Chao-Nan Qian, Qing Liu, Ingemar Ernberg, Weimin Ye, Hans-Olov Adami, Anthony T. Chan, Yi-Xin Zeng, Jian-Yong Shao
Journal: Journal of Clinical Oncology (2011)

Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC.We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM)--based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients.The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort.As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.
The Translational Research Working Group Developmental Pathway for Anticancer Agents (Drugs or Biologics)
Authors: Richard L. Schilsky, Gary Gordon, Tona M. Gilmer, Sara A. Courtneidge, Lynn M. Matrisian, Oren Grad, William G. Nelson
Journal: Clinical Cancer Research (2008)

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the National Cancer Institute's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of agents-both small molecules and biologics-for the treatment and prevention of cancer. The Agents Developmental Pathway was conceived not as a comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of an agent through the translational process to the point where it can begin definitive clinical testing. This article presents the Agents Developmental Pathway and discusses key challenges associated with the processes described.
The burden of asthma: weighing the community risk against individual risk
Authors: A. VON SCHLEGELL, E. N GRANT, K. B WEISS
Journal: Thorax (1999)

During the past few years findings from two studies-the International Study of Asthma and Allergies in Childhood (ISAAC) 1 and the European Community Respiratory Health Survey (ECRHS) 2 -seem to have dominated much of the thinking about the geographical variations in the prevalence of asthma.These studies suggest important variations by geographical site in diVerent countries and, to a lesser extent, in study centres within countries.However, these studies only raise new questions as to how geographical factors contribute to the aetiology of asthma.For example, are the geographical variations in the prevalence of asthma caused by unique exposures to disease causing agents found only in local environments?Do diVerences in geographical location in some way alter host susceptibility?Do local environmental conditions, either physical or sociocultural, alter the host/agent interactions in ways that are critical to the expression of this condition?In this issue of Thorax Duran-Tauleria and Rona 3 further elucidate how social and physical environmental factors may explain some of the geographical expression of asthma prevalence.Their study focuses on the diVerences in asthma and respiratory symptoms among three populations-two nationally representative samples of English and Scottish children and a third sample of children living within the inner cities of England.The authors found a higher prevalence of children with persistent (as opposed to occasional) wheeze within the inner city population than in the other two sampled populations.They also found that the prevalence of asthma attacks was higher in the non-inner city sample of English children than in the other two groups.Social and physical environmental factors-mainly social deprivation (as measured by the Townsend score)-seemed to explain much of the geographical variation in children with persistent wheezing.This finding held even after adjusting the analysis for many of the well known risk factors that might otherwise have explained these diVerences such as age, sex, parental atopy, and maternal smoking.The importance of social and physical environmental factors in disease expression is well known and has been studied extensively for many health conditions, including asthma.A number of studies suggest an association between higher asthma morbidity/mortality rates and geographical areas of lower socioeconomic standing.The literature on the eVects of social environmental factors on the prevalence of asthma is less definitive, but there have been several studies that suggest findings similar to those of Duran-Tauleria and Rona.Yet this current study also provides new insights into the possible mechanisms by which poverty may influence the development of asthma based on its impact on communities independent of its eVect on individuals.
Allergic Skin and Systemic Reactions in a Patient with Pure Red Cell Aplasia and Anti-Erythropoietin Antibodies Challenged with Different Epoetins
Authors: Gertrud Weber, Johann Gross, Arno Kromminga, Hans-H. Loew, Kai-Uwe Eckardt
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Recent concern has arisen about the development of neutralizing anti-erythropoietin (EPO) antibodies during the course of treatment with recombinant EPO. The underlying mechanisms are poorly understood. A patient was observed who developed wheals at the sites of subcutaneous injections of epoetin-α before the manifestation of pure red cell aplasia (PRCA). Intravenous application of different epoetins evoked skin reactions at the sites of former subcutaneous injections, indicating local persistence of sensitized cells, and eventually a systemic anaphylactoid response. Anti-EPO antibodies crossreactive with epoetin-β and darbepoetin-α were demonstrated in patient serum. PRCA gradually improved after treatment with prednisolone.