tbuckley/cabot-search huggingface dataset:
Chimpanzee Adenovirus Vector Ebola Vaccine
Authors: Julie E. Ledgerwood, Adam D. DeZure, Daphne A. Stanley, Emily E. Coates, Laura Novik, Mary E. Enama, Nina M. Berkowitz, Zonghui Hu, Gyan Joshi, Aurélie Ploquin, Sandra Sitar, Ingelise J. Gordon, Sarah A. Plummer, LaSonji A. Holman, Cynthia S. Hendel, Galina Yamshchikov, Francois Roman, Alfredo Nicosia, Stefano Colloca, Riccardo Cortese, Robert T. Bailer, Richard M. Schwartz, Mario Roederer, John R. Mascola, Richard A. Koup, Nancy J. Sullivan, Barney S. Graham
Journal: New England Journal of Medicine (2014)

The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3–vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation.
Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings
Authors: Cristina Basso, Fiorella Calabrese, Domenico Corrado, Gaetano Thiene
Journal: Cardiovascular Research (2001)

Time for primary review 29 days. 

When sudden death (SD) occurs in adults and elderly persons, coronary atherosclerosis is the usual cause [1,2]. On the contrary, a large spectrum of cardiovascular diseases, both congenital and acquired, may account for SD in the young [3–10]. These diseases are frequently concealed and discovered with surprise only at postmortem by means of a thorough macroscopic and microscopic investigation. This review will address the spectrum of structural substrates of cardiac SD with particular emphasis given to the possible role of molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability.

SD is defined as a natural, unexpected fatal event occurring within 1 h of the beginning of symptoms, in an apparently healthy subject or one whose disease was not so severe enough as to predict such an abrupt outcome [11]. In the USA, the annual incidence of SD in people aged 35–74 years is 191/100 000 in men and 57/100 000 in women; almost half of all SDs occur in people with known coronary artery disease [12]. In the Veneto region, Northeast of Italy, we recently calculated an overall prevalence of SD of 0.8/100 000/year in the young, based only upon autopsy reports [13]. When focusing the attention only on young athletes the prevalence was twice that in young non athletes, i.e. 1.6/100 000/year; these figures are explained by the existence of cardiovascular diseases which cause a risk of SD during effort, such as hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and congenital coronary anomalies.

As far as pathophysiology is concerned, cardiac arrest may be either mechanical, when the heart and circulatory functions are suddenly impeded by mechanical factors (i.e. cardiac tamponade, pulmonary thromboembolism, etc.) or arrhythmic (mostly ventricular fibrillation) [9].

Based … 

* Corresponding author. Tel.: +39-49-827-2283; fax: +39-49-827-2284 cardpath{at}ux1.unipd.it
Genome-Wide Analysis of Core Cell Cycle Genes in the Unicellular Green Alga Ostreococcus tauri
Authors: Steven Robbens, Basheer Khadaroo, Alain Camasses, Evelyne Derelle, Conchita Ferraz, Dirk Inzé, Yves Van de Peer, Hervé Moreau
Journal: Molecular Biology and Evolution (2004)

The cell cycle has been extensively studied in various organisms, and the recent access to an overwhelming amount of genomic data has given birth to a new integrated approach called comparative genomics. Comparing the cell cycle across species shows that its regulation is evolutionarily conserved; the best-known example is the pivotal role of cyclin-dependent kinases in all the eukaryotic lineages hitherto investigated. Interestingly, the molecular network associated with the activity of the CDK-cyclin complexes is also evolutionarily conserved, thus, defining a core cell cycle set of genes together with lineage-specific adaptations. In this paper, we describe the core cell cycle genes of Ostreococcus tauri, the smallest free-living eukaryotic cell having a minimal cellular organization with a nucleus, a single chloroplast, and only one mitochondrion. This unicellular marine green alga, which has diverged at the base of the green lineage, shows the minimal yet complete set of core cell cycle genes described to date. It has only one homolog of CDKA, CDKB, CDKD, cyclin A, cyclin B, cyclin D, cyclin H, Cks, Rb, E2F, DP, DEL, Cdc25, and Wee1. We have also added the APC and SCF E3 ligases to the core cell cycle gene set. We discuss the potential of genome-wide analysis in the identification of divergent orthologs of cell cycle genes in different lineages by mining the genomes of evolutionarily important and strategic organisms.
Accessing the Neural Drive to Muscle and Translation to Neurorehabilitation Technologies
Authors: D. Farina, F. Negro
Journal: IEEE Reviews in Biomedical Engineering (2012)

This review describes methods for interfacing motor neurons from muscle recordings and their applications in studies on the neural control of movement and in the design of technologies for neurorehabilitation. After describing methods for accessing the neural drive to muscles in vivo in humans, we discuss the mechanisms of transmission of synaptic input into motor neuron output and of force generation. The synaptic input received by a motor neuron population is largely common among motor neurons. This allows linear transmission of the input and a reduced dimensionality of control by the central nervous system. Force is generated by low-pass filtering the neural signal sent to the muscle. These concepts on neural control of movement are used for the development of neurorehabilitation technologies, which are discussed with representative examples on movement replacement, restoration, and neuromodulation. It is concluded that the analysis of the output of spinal motor neurons from muscle signals provides a unique means for understanding the neural coding of movement in vivo in humans and thus for reproducing this code artificially with the aim of restoring lost or impaired motor functions.
Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease
Authors: N Dalbeth, T Smith, S Gray, A Doyle, P Antill, M Lobo, E Robinson, A King, J Cornish, G Shalley, A Gao, F M McQueen
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. Methods: Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. Results: The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). Conclusions: The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.
Uncovering the Molecular Secrets of Inflammatory Breast Cancer Biology: An Integrated Analysis of Three Distinct Affymetrix Gene Expression Datasets
Authors: Steven J. Van Laere, Naoto T. Ueno, Pascal Finetti, Peter Vermeulen, Anthony Lucci, Fredika M. Robertson, Melike Marsan, Takayuki Iwamoto, Savitri Krishnamurthy, Hiroko Masuda, Peter van Dam, Wendy A. Woodward, Patrice Viens, Massimo Cristofanilli, Daniel Birnbaum, Luc Dirix, James M. Reuben, François Bertucci
Journal: Clinical Cancer Research (2013)

Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported.
Digoxin Therapy During T-Tube Biliary Drainage in Man
Authors: S. George Carruthers
Journal: JAMA (1978)

BILIARY excretion and enterohepatic recirculation of digitoxin has been demonstrated in man.<sup>1</sup>Recently it has been recognized that digoxin may also undergo biliary elimination and enterohepatic recycling.<sup>2,3</sup>We report the consequence of biliary excretion of digoxin in a patient subjected to bile drainage after cholecystectomy. <h3>Report of a Case</h3> An 82-year-old man weighing 59 kg was taking digoxin, 0.125 mg/day; 1-thyroxine, 0.2 mg/day; and furosemide, 40 mg/day. He was jaundiced and dyspneic. Moist rales at both lung bases and gallop rhythm were present. The right upper quadrant was tender to deep palpation. Sonography demonstrated a distended gallbladder with numerous small calculi. Blood cell counts showed leukocytosis with an increased number of polymorphonuclear leukocytes. There was a threefold elevation of the normal serum bilirubin and alkaline phosphatase levels; BUN levels ranged from 29 to 48 mg/dl, and serum creatinine levels ranged from 1.3 to 2.0 mg/dl. Creatinine clearance calculated
Obligatory role of gamma interferon in T cell-replacing factor-dependent, antigen-specific murine B cell responses.
Authors: M Brunswick, P Lake
Journal: The Journal of Experimental Medicine (1985)

The role of gamma interferon (IFN-gamma) in T cell-replacing factor (TRF) activity for antigen-specific plaque-forming cell (PFC) responses in vitro was studied using antibodies to murine IFN-gamma (Mu IFN-gamma). TRF activity was present in supernatants (Sn) of Con A- or mixed leukocyte reaction-stimulated murine spleen cells as well as in an IL-2-rich fraction of phytohemagglutinin-stimulated human peripheral blood lymphocyte Sn and in the Sn of the Gibbon T lymphoma MLA-144. The human TRF was highly active with cells from nu/nu mice and normal mice but not with cells from animals with the xid immunologic defect, similar to the activity of murine TRF. Antibodies to IFN-gamma consisted of hyper-immune rabbit antisera, IFN-gamma affinity-purified rabbit immunoglobulin and an interspecies hybridoma specific for Mu IFN-gamma. The results show that the activities of all preparations of TRF are markedly diminished or abrogated by antibody to Mu IFN-gamma but not by antibodies to human IFN-gamma (Hu IFN-gamma), nor by normal rabbit sera or purified rabbit Ig. The degree of inhibition was dose dependent and was quantitatively reversed by the addition to the cultures of recombinant-derived Mu IFN-gamma (Mu rIFN-gamma) but not Hu rIFN-gamma. This reversal was fully antigen specific and thus not attributable to polyclonal B cell activation by IFN-gamma, which is inactive alone in the TRF assay. Kinetic analysis shows that IFN-gamma must act by 24-48 h to produce PFC responses at 4 d. Together, the data demonstrate that IFN-gamma is a necessary mediator for TRF effects and that IFN-gamma is induced by TRF from T-depleted murine spleen cells in sufficient quantity to support large antibody responses. The source of this IFN-gamma may be the potent natural killer cells that are induced in cultures stimulated with TRF.
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009
Authors: A. Goldhirsch, J.N. Ingle, R.D. Gelber, A.S. Coates, B. Thürlimann, H.-J. Senn
Journal: Annals of Oncology (2009)

The 11(th) St Gallen (Switzerland) expert consensus meeting on the primary treatment of early breast cancer in March 2009 maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers. Any positive level of estrogen receptor (ER) expression is considered sufficient to justify the use of endocrine adjuvant therapy in almost all patients. Overexpression or amplification of HER2 by standard criteria is an indication for anti-HER2 therapy for all but the very lowest risk invasive tumours. The corollary is that ER and HER2 must be reliably and accurately measured. Indications for cytotoxic adjuvant therapy were refined, acknowledging the role of risk factors with the caveat that risk per se is not a target. Proliferation markers, including those identified in multigene array analyses, were recognised as important in this regard. The threshold for indication of each systemic treatment modality thus depends on different criteria which have been separately listed to clarify the therapeutic decision-making algorithm.
Multiple Overlapping Drug-Eluting Stents to Treat Diffuse Disease of the Left Anterior Descending Coronary Artery
Authors: Eleftheria Tsagalou, Alaide Chieffo, Ioannis Iakovou, Lei Ge, Giuseppe M. Sangiorgi, Nicola Corvaja, Flavio Airoldi, Matteo Montorfano, Iassen Michev, Antonio Colombo
Journal: Journal of the American College of Cardiology (2005)
The impact performance of headguards for combat sports
Authors: Andrew S McIntosh, Declan A Patton
Journal: British Journal of Sports Medicine (2015)

Background/aim To assess the impact energy attenuation performance of a range of headguards for combat sports. Methods Seven headguards worn during combat sport training or competition, including two Association Internationale de Boxe Amateur (AIBA)-approved boxing models, were tested using drop tests. An International Organization for Standardization (ISO) rigid headform was used with a 5.6 kg drop assembly mass. Tests were conducted against a flat rigid anvil both with and without a boxing glove section. The centre forehead and lateral headguard areas were tested. Peak headform acceleration was measured. Tests from a selection of drop heights and repeated tests on the same headguard were conducted. Results Headguard performance varied by test condition. For the 0.4 m rigid anvil tests, the best model headguard was the thickest producing an average peak headform acceleration over 5 tests of 48 g compared with 456 g for the worst model. The mean peak acceleration for the 0.4, 0.5 and 0.6 frontal and lateral rigid anvil impact tests was between 32% and 40% lower for the Top Ten boxing model compared with the Adidas boxing model. The headguard performance deterioration observed with repeat impact against the flat anvil was reduced for impacts against the glove section. The overall reduction in acceleration for the combination of glove and headguard in comparison to the headguard condition was in the range of 72–93% for 0.6 and 0.8 m drop tests. Conclusions The impact tests show the benefits of performance testing in identifying differences between headguard models.
P38 Which patients with pulmonary arteriovenous malformations are dyspnoeic? Retrospective analysis of a single centre 2005-2010 cohort
Authors: V. Santhirapala, J. Springett, H. Wolfenden, H. Tighe, C. Shovlin
Journal: Thorax (2010)

<h3>Introduction/objectives</h3> Pulmonary arteriovenous malformations (PAVMs) are aberrant connections between pulmonary arteries and veins, creating a right-to-left shunt. Hypoxaemia is common,1 but dyspnoea is usually not the presenting complaint.2 We hypothesised this may be relevant to dyspnoea mechanisms in the general population. <h3>Methods</h3> With ethical approval, new patients presenting with CT-proven PAVMs between June 2005 and July 2010 were studied retrospectively. Based on self-reported exercise tolerance at presentation, and blinded to physiological measurements, two investigators assigned patients to the MRC dyspnoea scale, grading dyspnoea on strenuous exertion only (normal, Grade 1); on incline/stairs (2); and on the level (3–5 according to severity). Individuals undertaking regular/intense sport were reclassified as Grade ‘0’. Four separate SpO<sub>2</sub> measurements, after standing for 7, 8, 9 and 10 min, were used for statistical calculations using GraphPad software. Interim analyses were performed on the first 88 patients. <h3>Results</h3> In the absence of severe pulmonary hypertension or emphysema, only 18% of patients were dyspnoeic (Abstract P38 Table 1). To determine which factors might influence dyspnoea, single variables were examined. There was considerable overlap in the SpO<sub>2</sub> values between the three groups of Grade ‘0’, 1 and 2, and no relationship between dyspnoea grade and SpO<sub>2</sub> demonstrated by Spearman9s rank correlation coefficient (r=0.09; p=0.39). The patients however, ranged in age from 17 to 87 years, and older patients were more dyspnoeic (Spearman r=0.33; p=0.0016). Multiple regression analyses were therefore performed to determine whether there was a relationship between SpO<sub>2</sub> and dyspnoea that was masked by differences in age. These suggested SpO<sub>2</sub> may make an independent contribution to dyspnoea (p=0.064), although age was still more strongly associated (p=0.0044). However, these factors alone did not account for most of the population variation in dyspnoea grade (overall model: r<sup>2</sup>=11.37%, p=0.0073). <h3>Summary</h3> These data imply that it is unusual for PAVMs alone to account for moderate to severe dyspnoea, and that there is less of an influence of SpO<sub>2</sub> than expected. Further study is warranted.
Expression of Pro- and Antiapoptotic Proteins in Circulating CD8+ T Cells of Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Jeong-Whun Kim, Takashi Tsukishiro, Jonas T. Johnson, Theresa L. Whiteside
Journal: Clinical Cancer Research (2004)

Abstract Objective: Apoptosis of T lymphocytes in the circulation of patients with squamous cell carcinoma of the head and neck (SCCHN) was shown to target effector CD8+ rather than CD4+ T cells. This study evaluates the contribution of pro- and antiapoptotic components of the mitochondria-dependent pathway to apoptosis of circulating CD8+ T cells in these patients. Experimental Design: Blood samples were obtained from 77 patients with SCCHN and 51 normal control(s) (NC). Percentages of CD8+Annexin V+ (ANX+) and CD8+CD95+ cells, changes in mitochondrial membrane potential and levels of expression of Bcl-2, Bcl-XL, and Bax in CD8+ T lymphocytes were measured by quantitative flow cytometry. Results: Elevated percentages (P &amp;lt; 0.001) of early apo-ptotic (CD8+ANX+ CD95+) T cells in the circulation distinguish SCCHN patients from NCs but not patients with no evidence of disease (NED) from those with active disease (AD). Circulating CD8+ but not CD4+ T cells in patients were found to contain higher levels of proapoptotic Bax and antiapoptotic Bcl-XL (P &amp;lt; 0.01) than NC cells. The Bax/Bcl-2 ratio was elevated in CD8+ T cells of patients relative to NCs (P &amp;lt; 0.01), and it correlated with the percentage of ANX+CD8+ T cells (P = 0.007). The Bax/Bcl-XL ratio discriminated AD from NED patients. Conclusion: Apoptosis of circulating CD8+T cells is found in SCCHN patients with AD or NED. Up-regulated Bax and Bcl-XL expression, the elevated Bax/Bcl-2 ratio and its association with ANX binding implicate the mitochondrial pathway in death of CD8+ T cells of patients with SCCHN. Understanding of molecular mechanisms of T-cell death and survival is essential for the development of more effective biotherapies for SCCHN.
Neurological Development of 5-Year-Old Children Receiving a Low–Saturated Fat, Low-Cholesterol Diet Since Infancy
Authors: L Rask-Nissilä, E Jokinen, P Terho, A Tammi, H Lapinleimu, T Rönnemaa, J Viikari, R Seppänen, T Korhonen, J Tuominen, I Välimäki, O Simell
Journal: JAMA (2000)

ContextEarly childhood introduction of nutritional habits aimed at atherosclerosis prevention is compatible with normal growth, but its effect on neurological development is unknown.ObjectiveTo analyze how parental counseling aimed at keeping children's diets low in saturated fat and cholesterol influences neurodevelopment during the first 5 years of life.DesignRandomized controlled trial conducted between February 1990 and November 1996.SettingOutpatient clinic of a university department in Turku, Finland.ParticipantsA total of 1062 seven-month-old infants and their parents, recruited at well-baby clinics between 1990 and 1992. At age 5 years, 496 children still living in the city of Turku were available to participate in neurodevelopmental testing.InterventionParticipants were randomly assigned to receive individualized counseling aimed at limiting the child's fat intake to 30% to 35% of daily energy, with a saturated:monounsaturated:polyunsaturated fatty acid ratio of 1:1:1 and a cholesterol intake of less than 200 mg/d (n = 540) or usual health education (control group, n = 522).Main Outcome MeasuresNutrient intake, serum lipid concentrations, and neurological development at 5 years, among children in the intervention vs control groups.ResultsAbsolute and relative intakes of fat, saturated fatty acids, and cholesterol among children in the intervention group were markedly less than the respective values of control children. Mean (SD) percentages of daily energy at age 5 years for the intervention vs control groups were as follows: for total fat, 30.6% (4.5%) vs 33.4% (4.4%) (P<.001); and for saturated fat, 11.7% (2.3%) vs 14.5% (2.4%) (P<.001). Mean intakes of cholesterol were 164.2 mg (60.1 mg) and 192.5 mg (71.9 mg) (P<.001) for the intervention and control groups, respectively. Serum cholesterol concentrations were continuously 3% to 5% lower in children in the intervention group than in children in the control group. At age 5 years, mean (SD) serum cholesterol concentration of the intervention group was 4.27 (0.63) mmol/L (165 [24] mg/dL) and of the control group, 4.41 (0.74) mmol/L (170 [29] mg/dL) (P = .04). Neurological development of children in the intervention group was at least as good as that of children in the control group. Relative risks for children in the intervention group to fail tests of speech and language skills, gross motor functioning plus perception, and visual motor skills were 0.95 (90% confidence interval [CI], 0.60-1.49), 0.95 (90% CI, 0.58-1.55), and 0.65 (90% CI, 0.39-1.08), respectively (P = .85, .86, and .16, respectively, vs control children).ConclusionOur data indicate that repeated child-targeted dietary counseling of parents during the first 5 years of a child's life lessens age-associated increases in children's serum cholesterol and is compatible with normal neurological development.