tbuckley/cabot-search huggingface dataset:
Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin
Authors: Yohei Natsuaki, Gyohei Egawa, Satoshi Nakamizo, Sachiko Ono, Sho Hanakawa, Takaharu Okada, Nobuhiro Kusuba, Atsushi Otsuka, Akihiko Kitoh, Tetsuya Honda, Saeko Nakajima, Soken Tsuchiya, Yukihiko Sugimoto, Ken J Ishii, Hiroko Tsutsui, Hideo Yagita, Yoichiro Iwakura, Masato Kubo, Lai guan Ng, Takashi Hashimoto, Judilyn Fuentes, Emma Guttman-Yassky, Yoshiki Miyachi, Kenji Kabashima
Journal: Nature Immunology (2014)
Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial
Authors: David Cameron, Julia Brown, Rebecca Dent, Christian Jackisch, John Mackey, Xavier Pivot, Guenther G Steger, Thomas M Suter, Masakazu Toi, Mahesh Parmar, Rita Laeufle, Young-Hyuck Im, Gilles Romieu, Vernon Harvey, Oleg Lipatov, Tadeusz Pienkowski, Paul Cottu, Arlene Chan, Seock-Ah Im, Peter S Hall, Lida Bubuteishvili-Pacaud, Volkmar Henschel, Regula J Deurloo, Celine Pallaud, Richard Bell
Journal: The Lancet Oncology (2013)
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Authors: Kian Fan Chung, Sally E. Wenzel, Jan L. Brozek, Andrew Bush, Mario Castro, Peter J. Sterk, Ian M. Adcock, Eric D. Bateman, Elisabeth H. Bel, Eugene R. Bleecker, Louis-Philippe Boulet, Christopher Brightling, Pascal Chanez, Sven-Erik Dahlen, Ratko Djukanovic, Urs Frey, Mina Gaga, Peter Gibson, Qutayba Hamid, Nizar N. Jarjour, Thais Mauad, Ronald L. Sorkness, W. Gerald Teague
Journal: European Respiratory Journal (2013)

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
Treatment of psoriatic arthritis with antitumour necrosis factor-α antibody clears skin lesions of psoriasis resistant to treatment with methotrexate
Authors: A.L.J. Ogilvie, C. Antoni, C. Dechant, B. Manger, J.R. Kalden, G. Schuler, M. Lüftl
Journal: British Journal of Dermatology (2001)

Background In inflamed skin, keratinocytes and inflammatory cells both produce large amounts of tumour necrosis factor (TNF) -α, a cytokine with broad effects that are relevant to inflammation. Blockade of this proinflammatory cytokine by a monoclonal anti-TNF-α antibody might be effectively used in the treatment of inflammatory skin diseases. Objectives To gather information about the efficacy of an anti-TNF-α antibody (infliximab) in the treatment of skin lesions of psoriatic arthritis. Methods Six patients with progressive joint disease and psoriatic skin lesions unresponsive to methotrexate therapy were treated with anti-TNF-α antibody. The Psoriasis Area and Severity Index was determined before and 10 weeks after initiation of therapy. Results Improvement of psoriatic skin lesions was observed in all patients. In addition, a marked improvement of the joint disease was noted. Conclusions Therapy with anti-TNF-α antibody may be an effective treatment regimen for both psoriatic arthritis and psoriatic skin lesions.
Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.
Authors: C Gérard, C Bruyns, A Marchant, D Abramowicz, P Vandenabeele, A Delvaux, W Fiers, M Goldman, T Velu
Journal: The Journal of Experimental Medicine (1993)

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.
In Vivo and In Vitro Studies Support That a New Splicing Isoform of <i>OLR1</i> Gene Is Protective Against Acute Myocardial Infarction
Authors: Ruggiero Mango, Silvia Biocca, Francesca del Vecchio, Fabrizio Clementi, Federica Sangiuolo, Francesca Amati, Antonio Filareto, Sandro Grelli, Paola Spitalieri, Ilaria Filesi, Cartesio Favalli, Renato Lauro, Jawahar L. Mehta, Francesco Romeo, Giuseppe Novelli
Journal: Circulation Research (2005)

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, is a scavenger receptor that plays a fundamental role in the pathogenesis of atherosclerosis. LOX-1 activation is associated with apoptosis of endothelial cells, smooth muscle cells (SMCs), and macrophages. This process is an important underlying mechanism that contributes to plaque instability and subsequent development of acute coronary syndromes. Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction (MI) susceptibility. Because single nucleotide polymorphisms (SNPs) linked to MI are located in intronic sequences of the gene, it remains unclear as to how they determine their biological effects. Using quantitative real-time PCR and minigene approach, we show that intronic SNPs, linked to MI, regulate the expression of a new functional splicing isoform of the OLR1 gene, LOXIN, which lacks exon 5. Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene have an increased expression of LOXIN at mRNA and protein level, which results in a significant reduction of apoptosis in response to oxLDL. Expression of LOXIN in different cell types results in loss of surface staining, indicating that truncation of the C-terminal portion of the protein has a profound effect on its cellular trafficking. Furthermore, the proapoptotic effect of LOX-1 receptor in cell culture is specifically rescued by the coexpression of LOXIN in a dose-dependent manner. The demonstration that increasing levels of LOXIN protect cells from LOX-1 induced apoptosis sets a groundwork for developing therapeutic approaches for prevention of plaque instability.
BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–β-catenin signaling
Authors: Xi C He, Jiwang Zhang, Wei-Gang Tong, Ossama Tawfik, Jason Ross, David H Scoville, Qiang Tian, Xin Zeng, Xi He, Leanne M Wiedemann, Yuji Mishina, Linheng Li
Journal: Nature Genetics (2004)
Myopia and later physical activity in adolescence: a prospective study: Table 1
Authors: K Deere, C Williams, S Leary, C Mattocks, A Ness, S N Blair, C Riddoch
Journal: British Journal of Sports Medicine (2009)

Objectives: To investigate associations between objectively measured physical activity (PA) and myopia in children. Methods: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were asked to wear a uniaxial accelerometer for 7 days. Measures of counts per minute (cpm), minutes spent in moderate to vigorous activity (MVPA) and minutes of sedentary behaviour (msed) were derived from the accelerometer worn at age 12. Children were also examined, at age 10, using an autorefractor to estimate myopia. Social and parental factors were collected from pregnancy and physical measures of the child were recorded at age 12. Results: 4880 children had valid PA and autorefraction data. In minimally adjusted models (age and gender) myopic children were less active than the other children: β = −49.9 cpm (95% CI −73.5 to −26.4, p = &lt;0.001). The myopic group spent less time in MVPA than the other children: β = −3.2 minutes MVPA (95% CI −5.2 to −1.1, p = 0.003) and more time sedentary: β = 15.8 minutes (95% CI 5.8 to 25.8, p = 0.002). The effect sizes were attenuated by adjustment for social and behavioural confounders although myopia status in the better (less myopic on autorefraction) eye remained strongly associated with cpm and MVPA but less so for sedentary behaviour: β = −36.8 cpm (95% CI –67.8 to −5.8, p = 0.02), β = −2.7 MVPA (95% CI −5.3 to −0.1, p = 0.04), β = 10.1 msed (95% CI –2.9 to 23.1, p = 0.13). Conclusion: Myopic children may be more at risk of having lower levels of PA than their non-myopic peers, although the difference was modest.
Network medicine, multimorbidity and the lung in the elderly
Authors: Rosa Faner, Tamara Cruz, Alejandra López-Giraldo, Alvar Agustí
Journal: European Respiratory Journal (2014)

Noncommunicable diseases, including cardiovascular, metabolic and respiratory diseases, among others, are the major medical challenge of the 21st century. Most noncommunicable diseases are related to the ageing process and often co-occur in the same individual. However, it is unclear whether the index disease is somehow influencing the development of the other ones (comorbidity) or whether all of them (including the index disease) simply represent the clinical expression of pathological ageing (multimorbidity). The pathobiology of ageing, chronic obstructive pulmonary disease (COPD) and concomitant disorders is complex. A new field of research, known as systems biology if applied to model systems or network medicine if applied to human beings, has emerged over the past decade or so, to address biological complexity in a holistic, integrated way. It offers, therefore, great potential to decipher the relationship between ageing, COPD and comorbidities/multimorbidities. In this State of the Art review we present the basic concepts of systems biology, use some examples to illustrate the potential of network medicine to address complex medical problems, and review some recent publications that show how a systems-based research strategy can contribute to improve our understanding of multimorbidity and age-related respiratory diseases.
Myocardial mechanics in aortic and mitral valvular regurgitation: the concept of instantaneous impedance as a determinant of the performance of the intact heart
Authors: Charles W. Urschel, James W. Covell, Edmund H. Sonnenblick, John Ross, Eugene Braunwald
Journal: Journal of Clinical Investigation (1968)

The effects on myocardial mechanics of acute, artificial aortic and mitral regurgitation were studied in the dog to determine the manner in which the changes in load induced by valvular regurgitation alter ventricular performance. With mitral and aortic regurgitant volumes of approximately the same magnitude as the forward stroke volume, immediate increases occurred in total stroke volume, left ventricular enddiastolic pressure, and peak ejection velocity, whereas contractility remained unchanged. Although calculated myocardial fiber tension rose, the rate of decline of tension during ejection was accelerated with regurgitation due to the more rapid decrease in ventricular size. Average tension therefore decreased relative to average pressure. As a consequence of the increased fiber length and this unloading, contractile element velocity, work, and power were increased. Despite unchanged contractility of the myocardium, the ejection fraction rose with both aortic and mitral regurgitation.When regurgitant beats were compared with control beats at a constant end-diastolic volume, ventricular stroke volume, work, power, and ejection fraction, as well as contractile element velocity, work, and power consistently increased. Thus, reduction of instantaneous impedance to ejection allowed the ventricle to empty further, reducing ventricular wall tension with a resultant increase in the velocity of shortening. External energy output was increased despite unchanged contractility and diastolic fiber length. It is concluded that the impedance to ejection and myocardial fiber tension during ejection govern the velocity and extent of contractile element shortening, and hence affect stroke volume, peak aortic flow rate, and ejection fraction. The alterations of ventricular function accompanying valvular regurgitation can be explained by an evaluation of the effects of these lesions on the instantaneous impedance to left ventricular ejection.
Retardation of Atherosclerosis by Overexpression of Catalase or Both Cu/Zn-Superoxide Dismutase and Catalase in Mice Lacking Apolipoprotein E
Authors: Hong Yang, L. Jackson Roberts, Ming Jian Shi, Li Chun Zhou, Billy R. Ballard, Arlan Richardson, Zhong Mao Guo
Journal: Circulation Research (2004)

Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and/or catalase on atherosclerosis and lipid peroxidation in mice lacking apolipoprotein E ( ApoE −/− ). Based on lipid staining of the en face of the aorta tree and the serial sections of the proximal aorta, ApoE −/− mice overexpressing catalase or both Cu/Zn-SOD and catalase had smaller and relatively early stages of atherosclerotic lesions (eg, foam cells and free lipids) when compared with ApoE −/− mice, who developed more advanced lesions (eg, fibrous caps and acellular areas). In addition, the retarded development of atherosclerosis was correlated with a reduced F 2 -isoprostanes in the plasma and aortas in ApoE −/− mice overexpressing catalase or both Cu/Zn-SOD and catalase. In contrast, the levels of F 2 -isoprostanes and atherosclerosis in the ApoE −/− mice overexpressing Cu/Zn-SOD alone were comparable to ApoE −/− control mice. These observations implied that endogenously produced hydrogen peroxide, but not superoxide anions, contributed to the formation of oxidized lipids and the development of atherosclerosis in ApoE −/− mice.
Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values
Authors: E. Inoue, H. Yamanaka, M. Hara, T. Tomatsu, N. Kamatani
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To estimate the disease activity score (DAS)28-C-reactive protein (CRP) threshold values that correspond to DAS28-erythrocyte sedimentation rate (ESR) values for remission, low disease activity and high disease activity in patients with rheumatoid arthritis. <b>Methods:</b> DAS28 data were analysed using a large observational study (Institute of Rheumatology Rheumatoid Arthritis) database of 6729 patients with rheumatoid arthritis. Firstly, the relationship between the DAS28-ESR and the DAS28-CRP values was analysed. Secondly, the best DAS28-CRP trade-off values for each threshold were calculated using receiver operating characteristic (ROC) curves. <b>Results:</b> The correlation coefficient of ESR versus CRP was 0.686, whereas that of DAS28-ESR versus DAS28-CRP was 0.946, showing the strong linear relationship between DAS28-ESR and DAS28-CRP values. DAS28-CRP threshold values corresponding to remission, low disease activity and high disease activity were 2.3, 2.7 and 4.1, respectively. The sensitivity and specificity from the ROC curves were gradually reduced as DAS28 values became lower. <b>Conclusions:</b> This study showed that DAS28-CRP and DAS28-ESR were well correlated, but the threshold values should be reconsidered. As the results were derived from only Japanese patients, it is essential to compare DAS28-CRP threshold values in people of other ethnic groups.
The magnetocardiogram as derived from electrocardiographic data.
Authors: A van Oosterom, T F Oostendorp, G J Huiskamp, H J ter Brake
Journal: Circulation Research (1990)

Magnetocardiographic signals, as present outside the thorax and generated by the depolarization process within the ventricles of the human heart, have been computed by using a model that incorporates the uniform double layer as the exclusive primary source. The volume conductor effects are treated by using an inhomogeneous, multicompartmental model of the thorax, based on "tailored" geometry derived from magnetic resonance imaging. The required activation function, specifying the timing of the ventricular depolarization process, was derived from an inverse procedure that uses as input data electric signals measured at the body surface. Next, the magnetic signals from the same subjects were measured. A close correspondence between computed and measured magnetic signals was observed (relative root mean square residual difference of 0.37). These results demonstrate that magnetocardiograms and electrocardiograms have a common basis and that it is unlikely that prominent sources exist that are electrically silent and yet active in the genesis of the magnetic fields associated with the depolarization process of the heart. Moreover, fresh support is implied for the usefulness of the classical uniform double layer as the electrical source model during ventricular depolarization. The contributions of the secondary sources have previously been found to be a major component of the electric signals; they are now also shown to be a major component of the magnetic signals.
Long-Term Effects of Nonsteroidal Anti-Inflammatory Drugs and Cyclooxygenase-2 Selective Agents on the Small Bowel: A Cross-Sectional Capsule Enteroscopy Study
Authors: Laurence Maiden, Bjarni Thjodleifsson, Anna Seigal, Ingvar Iain Bjarnason, David Scott, Sigurbjorn Birgisson, Ingvar Bjarnason
Journal: Clinical Gastroenterology and Hepatology (2007)
Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.
Authors: E Colle, R D Guttmann, T Seemayer
Journal: The Journal of Experimental Medicine (1981)

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.
Day-night pattern of defibrillator shocks in patients with chronic heart failure: The impact of Cheyne-Stokes respiration and obstructive sleep apnoea
Authors: Thomas Bitter, Andrea Zwenke, Natalie Prib, Zisis Dimitriadis, Christian Prinz, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2013)

Introduction : This study aims to clarify the impact of obstructive (OSA) or central (CSA) sleep apnoea on the circadian pattern of malignant arrhythmic events.   Methods : In total 146 patients (pts) with chronic heart failure (CHF; LVEF ≤45%, NYHA-class ≥2) and implanted defibrillator (ICD) were screened for the coexistence of OSA and CSA (Apnoea-Hypopnea-Index ≥10/h). During follow-up (median 48 months) time of day of adequate ICD-shocks and overall ICD-therapies were recorded by device logs.   Results : In total 171 appropriate ICD-therapies including 57 shocks were delivered. From 0 to 6 am, ICD-shocks occurred in 50% of pts with OSA, 16% of pts with CSA, and 11% of pts with no sleep-disordered breathing (noSDB; OSA vs. noSDB: P=0.02; CSA vs. noSDB: P=0.68). ICD therapies from 0 to 6 am were delivered to 35% of pts with OSA, 23% of pts with CSA, and 20% with noSDB (OSA vs. noSDB: P=0.13; CSA vs. noSDB: P=0.86). For people with OSA, the relative risk (RR) of ICD-shocks from 0 to 6 am was 3.00 (95% CI 1.28 to 7.06, P=0.03) and of ICD therapies 1.60 (95% CI 0.96 to2.66, P=0.12), respectively. For CSA pts the RR of ICD shocks from 0 to 6 am was 0.60 (95% CI 0.22 to 1.58, P=0.41) and of ICD therapies 0.91 (95% CI 0.53 to 1.45, P=0.74), respectively.   Conclusion : In pts with CHF coexistence of OSA is associated with an enhanced risk for ICD-shocks during sleeping hours. Contrastingly, in CSA pts no such altered circadian variation was seen. As underlying respiratory instability and neurohumoral disorders are not exclusively found during sleep, nocturnal treatment of CSA might be insufficient to completely abolish adverse effects.