tbuckley/cabot-search huggingface dataset:
Survival in adults and children with systemic lupus erythematosus: a systematic review and Bayesian meta-analysis of studies from 1950 to 2016
Authors: Maria G Tektonidou, Laura B Lewandowski, Jinxian Hu, Abhijit Dasgupta, Michael M Ward
Journal: Annals of the Rheumatic Diseases (2017)

To determine trends in survival among adult and paediatric patients with systemic lupus erythematosus (SLE) from 1950 to the present.We performed a systematic literature review to identify all published cohort studies on survival in patients with SLE. We used Bayesian methods to derive pooled survival estimates separately for adult and paediatric patients, as well as for studies from high-income countries and low/middle-income countries. We pooled contemporaneous studies to obtain trends in survival over time. We also examined trends in major causes of death.We identified 125 studies of adult patients and 51 studies of paediatric patients. Among adults, survival improved gradually from the 1950s to the mid-1990s in both high-income and low/middle-income countries, after which survival plateaued. In 2008-2016, the 5-year, 10-year and 15-year pooled survival estimates in adults from high-income countries were 0.95, 0.89 and 0.82, and in low/middle-income countries were 0.92, 0.85 and 0.79, respectively. Among children, in 2008-2016, the 5-year and 10-year pooled survival estimates from high-income countries were 0.99 and 0.97, while in low/middle-income countries were 0.85 and 0.79, respectively. The proportion of deaths due to SLE decreased over time in studies of adults and among children from high-income countries.After a period of major improvement, survival in SLE has plateaued since the mid-1990s. In high-income countries, 5-year survival exceeds 0.95 in both adults and children. In low/middle-income countries, 5-year and 10-year survival was lower among children than adults.
PREVENTION OF ACL INJURIES IN OLYMPIC SPORTS – FIRST STEPS FOR A NATIONAL "ACL REGISTRY IN FOOTBALL"
Authors: Werner Krutsch, Christian Gündisch, Michael Nerlich, Peter Angele
Journal: British Journal of Sports Medicine (2017)

Background Prevention strategies for ACL injuries in Olympic sports are mandatory and the collection of data about risk factors and injury characteristics have highest priority. Objective What are the main risk and influencing factors on ACL injuries and safe return to play in different sports, beginning with worl's number one sport football? Design A prospective analysis of ACL injuries in German amateur and professional football. Setting ACL injury registration over two football seasons and investigation of ACL injured player by 2 questionnaire after injury and after one year. Patients Players of German football divisions were investigated, including all divisions, both gender and all age levels. Interventions Beside typical influencing and risk factors for ACL injuries, circumstances for a return to play decision were investigated. Main Outcome Measurements Investigated variables are anthropometric data, football exposure data, training and warm up data, regeneration data and return to play decision-making. Results 512 ACL injuries in football were registered in the first season with 71.1% non-contact injuries, 85.5% match injuries, younger female players and 93.5% surgical treatment rate. 68% of ACL injuries occurred in the preseason period, 60% of 1st division players were internationals and the first professional division revealed a higher ACL rate than the 2nd and 3rd division. Balancing exercises (&lt;40%) or trunk stability exercises (&lt;20%) were rare. Small pre-injuries were seen in 30% of all players directly before ACL injury. Over 50% had directly before the ACL injury changes of the training program or football level. Changing of football shoes before ACL injury was seen in 33.3%. A mean of 9.2 months for return to competition was seen in the male professional football players, which was earlier than in amateurs. Conclusions To improve injury prevention strategies for ACL injuries, a detailed knowledge about injury characteristics is necessary in all sports.
Evaluation of the presence of IGF1R overexpression in wild-type and kinase mutant GI stromal tumors
Authors: C. L. Corless, C. Beadling, E. Justusson, M. C. Heinrich
Journal: Journal of Clinical Oncology (2009)

10506 Background: Most adult GI stromal tumors have gain-of-function mutations in KIT (80%) or PDGFRA (5–7%). These pathogenetic mutations are the target for kinase inhibitor therapy. The pathogenesis of the 10–15% of GISTs lacking kinase mutations (WT GIST) is unknown; this includes most pediatric GISTs. Recently, Tarn et al. (PNAS 2008) identified IGF1R over-expression in all WT GIST in their series of cases, including one pediatric case. IGF1R may represent a novel therapeutic target for WT GISTs. Methods: We developed a quantitative RQ-PCR assay for IGF1R and GAPDH transcripts that is linear over 5 logs (R 2 values of 0.99 and 0.98, respectively). We prepared cDNA from RNA isolated from 79 archival, formalin-fixed, paraffin-embedded GIST specimens and quantified IGF1R expression as the % ratio of IGF1R/GAPDH transcripts. We had previously genotyped the tumors to identify any kinase mutations. Results: Adult WT GIST had a 10–15 fold higher expression of IGF1R transcript than kinase mutant GISTs (WT GIST 13.7 ±18, n=35; KIT exon 11 mutant GIST 1.0 ± 1.1, n=26; PDGFRA mutant GIST 0.9 ± 1.0, n=8; KIT 9 or 13 mutation 0.8 ± 0.6, n=5). Interestingly, the WT GIST group could be further divided into tumors with low vs. high IGF1R expression. The low IGF1R expression group (mean 0.6, range 0.1–1.9, n=14), had similar IGF1R expression to kinase mutant GISTs. In contrast, the high expression group had more than 30-fold higher levels of IGF1R transcript (mean 22.5, range 7.3–76.5, n=21). We also examined IGF1R expression in 5 WT pediatric GISTs. The mean IGF1R expression in pediatric GISTs resembled that of the adult high expression group, with 4 of 5 cases showing IGF1R over-expression. Conclusions: WT GISTs are heterogeneous with regard to IGF1R expression and can be divided into two subgroups. One third of the WT GISTs overlap with kinase-mutant GISTs, while the remainder express IGF1R at more than 30-fold higher levels. These results have implications for evolving models of GIST pathogenesis and the clinical testing of IGF1R monoclonal antibodies for treatment of metastatic GIST. [Table: see text]
GOOD EYESIGHT – A BASIC PRECONDITION FOR SAFETY AND PERFORMANCE IN SPORTS
Authors: Gernot Jendrusch, Vanessa Oertzen-Hagemann
Journal: British Journal of Sports Medicine (2017)

Background Good eyesight is a basic precondition for safety but also for performance in sports. Vision has a crucial importance for movement control and balance regulation. Vision helps anticipating, e.g. fast movements in ball games as well as potential accident risks e.g. in one-on-one-situations in football or handball. Investigations show that about 20% of all elite athletes exert their sport ametropic. Nevertheless regular and meaningful visual tests for the analysis of the multidimensional visual performance and the detection of ametropia are only integrated in the health diagnostics of a few sports. Objective Aim of the study was to analyze current data of German elite athletes concerning ametropia or different parameters of visual performance; especially considering parameters that are also tested by optometrists or ophthalmologists. Participants The study is based on a retrospective analysis of cross-sectional eye test data from different national teams (n=553; age: 21.0±4.0 years) which were collected in the annual routine health check in the last three years (2013–2015). Results About 27.5% of athletes use visual aids in daily life, whereas 33.3% of athletes with ametropia are practicing their sports without an optical correction. The median of the (monocular) visual acuity is about 1.85 for men and 1.80 for women (maximum-values considerably above 2.50). Altogether there are 22.6% athletes that are detected as ametropic and thus in need of correction. Conclusions All results mentioned and further literature searches show that good eyesight is important from the perception physiology and injury prevention point of view. Visual acuity, contrast sensitivity, depth and motion perception etc. have a significant influence on performance and quality of sports – depending on the specific demands of the discipline. Visual function tests should be included in health diagnostics in order to be able to detect and subsequently correct visual deficiencies at an early stage.
Spontaneous Tumors in a Subline of Strain C3H Mice
Authors: H. B. Andervont, W. J. McEleney
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Spontaneous Tumors in a Subline of Strain C3H Mice Get access H. B. Andervont, H. B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar W. J. McEleney W. J. McEleney technical assistance of assistant scientific aide National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 6, June 1941, Pages 737–744, https://doi.org/10.1093/jnci/1.6.737 Published: 01 June 1941
05.12 Gene expression profiling of tg197 mouse synovial joints, treated with four different anti-tnf biologics, reveals robust and predictive drug-specific signatures
Authors: Panagiotis Chouvardas, Niki Karagianni, Xanthi Kranidioti, Maria C Denis, Christoforos Nikolaou, George Kollias
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> TNF was the first cytokine to be validated as a molecular target of Rheumatoid Arthritis (RA) and still remains at the first-line of therapeutic interventions with biologics. Even though widely used anti-TNF agents, such as infliximab, etanercept, adalimumab and certolizumab pegol all target the same protein, they nonetheless exhibit differences, likely due to their biological origin (humanised or fully human) and biochemical properties (antibody or receptor). In this work, we sought to characterise this variability, at the molecular level, through the creation of robust gene and functional signatures from reproducible gene expression profiles of drug intervention in the huTNFTg model of RA (Tg197). <h3>Materials and methods</h3> Global gene expression of aqueous extracts from synovial joints of untreated and treated Tg197 mice were compared with wild-type controls in 10 biological replicates for each condition. Profiles were analysed with ANOVA, coupled with Dunnett's multiple comparison test using wild-type as control, giving rise to robust lists of differentially expressed genes. <h3>Results</h3> Preliminary analysis of untreated samples resulted in the definition of a broad subset of &gt;850 differentially expressed genes, which we used to define a disease signature at both gene and functional levels. Functions linked to this gene subset included both known (TNF and NF-kB signalling, Inflammatory response, RA and Inflammatory Bowel Disease) and less obvious pathways (Fatty Acid Metabolism, Oxidative Phosporylation, Autophagy). Functional dissection also revealed interesting links to various types of cardiomypathy phenotypes, a common comorbidity of RA patients. We found that etanercept, adalimumab and certolizumab pegol shared extensive similarities in the way they restore expression of disease signature genes, while infliximab diversified exhibiting increased efficiency in the modulation of over-expressed genes. The latter appears to predominantly modify genes of inflammatory and cytokine-related functions while the former show particular efficacy for genes associated with various types of cardiomypathy phenotypes. <h3>Conclusions</h3> Combined, our analyses reveal modest, yet detailed and significant discrepancies between gene expression of different anti-TNF agents and may provide a valuable framework for the benchmarking of novel biosimilars or the repositioning of existing substances at a preclinical stage.
Associations of Insomnia with Prognosis in Hospitalized Heart Failure Patients
Authors: Kanno Yuki, Yoshihisa Akiomi, Takiguchi Mai, Miura Shunsuke, Sato Akihiko, Shimizu Takeshi, Nakamura Yuichi, Yamauchi Hiroyuki, Owada Takashi, Abe Satoshi, Suzuki Satoshi, Oikawa Masayoshi, Sakamoto Nobuo, Yamaki Takayoshi, Sugimoto Koichi, Kunii Hiroyuki, Nakazato Kazuhiko, Suzuki Hitoshi, Saitoh Shuichi, Takeishi Yasuchika
Journal: Circulation (2016)
Complementary Value of Contralateral Parenchymal Enhancement on DCE-MRI to Prognostic Models and Molecular Assays in High-risk ER+/HER2− Breast Cancer
Authors: Bas H.M. van der Velden, Sjoerd G. Elias, Tycho Bismeijer, Claudette E. Loo, Max A. Viergever, Lodewyk F.A. Wessels, Kenneth G.A. Gilhuijs
Journal: Clinical Cancer Research (2017)

Abstract Purpose: To determine whether markers of healthy breast stroma are able to select a subgroup of patients at low risk of death or metastasis from patients considered at high risk according to routine markers of the tumor. Experimental Design: Patients with ER+/HER2− breast cancer were consecutively included for retrospective analysis. The contralateral parenchyma was segmented automatically on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), where upon the average of the top-10% late enhancement was calculated. This contralateral parenchymal enhancement (CPE) was analyzed with respect to routine prognostic models and molecular assays (Nottingham Prognostic Index, Dutch clinical chemotherapy-selection guidelines, 70-gene signature, and 21-gene recurrence score). CPE was split in tertiles and tested for overall and distant disease-free survival. CPE was adjusted for patient and tumor characteristics, as well as systemic therapy, using inverse probability weighting (IPW). Subanalyses were performed in patients at high risk according to prognostic models and molecular assays. Results: Four-hundred-and-fifteen patients were included, constituting the same group in which the association between CPE and survival was discovered. Median follow-up was 85 months, 34/415(8%) patients succumbed. After IPW-adjustment for patient and tumor characteristics, patients with high CPE had significantly better overall survival than those with low CPE in groups at high risk according to the Nottingham Prognostic Index [HR (95% CI): 0.08 (0.00–0.40), P &amp;lt; 0.001]; Dutch clinical guidelines [HR (95% CI): 0.22 (0.00–0.81), P = 0.021]; and 21-gene recurrence score [HR (95% CI): 0.14 (0.00–0.84), P = 0.030]. One group showed a trend [70-gene signature: HR (95% CI): 0.25 (0.00–1.02), P = 0.054]. Conclusions: In patients at high risk based on the tumor, subgroups at relatively low risk were identified using pretreatment enhancement of the stroma on breast DCE-MRI. Clin Cancer Res; 23(21); 6505–15. ©2017 AACR.
SERUM AMYLASE LEVEL IS A RELIABLE PREDICTOR OF POST-ERCP PANCREATITIS AFTER ENDOBILIARY STENTING
Authors: Milan Kujundžić, Branko Bilić, Tomislav Bokun, Žarko Babić, Marko Banić, Željko Čabrijan, Marija Crnčević-Urek, Ivica Grgurević, Duško Kardum, Lidija Petričušić, Mario. Tadić
Journal: Endoscopy (2009)

INTRODUCTION: Acute pancreatitis is a frequent complication following sphincterotomy and biliary stenting. The aim of our study was to evaluate the usefulness of serum amylase levels and peak activity time, for prediction of onset and estimation of severity of pancreatitis, after biliary stent placement. AIMS & METHODS: We analysed 781 inpatients, in a tertiary care hospital, in whom were placed one or more biliary stents for various indications. Of these, 123 had pancreatic stents implanted in addition to biliary stents. Serum amylase levels were measured 6, 12 and 24 hours after stent placement. We studied the significance of the amount of increase in serum amylase levels and peak activity time on prediction of onset and estimation of the severity of pancreatitis. RESULTS: At 24 hours after biliary stenting, 71 patients had a seven-fold (or more) increase in serum amylase levels (9%), and 52 of those had mild/moderate pancreatitis (73 % ; or 6.6% of all 781 patients). Of those 52 who developed acute pancreatitis, 48 had the highest level of serum amylase at 6 hours after the procedure (92%). In three patients we had to remove the stents for a couple of days to enable the acute pancreatitis to improve. In the group of patients in whom were placed both biliary and pancreatic stents, only three had a seven-fold (or more) increase in serum amylase levels (2, 4%), and of those, only two developed mild/moderate pancreatitis (66% ; or 1, 6% of all 123 patients). CONCLUSION: Measuring serum amylase levels at 6 hours after ERCP may be a significant predictor of the onset of post-ERCP pancreatitis. In our study, preventative pancreatic stenting significantly reduced serum amylase levels and post-ERCP pancreatitis.
喘息:NETosisによって放出された宿主DNAは,ライノウイルスが誘導する2型免疫によるアレルギー性喘息増悪を促進する
Authors: Toussaint Marie, Jackson David J, Swieboda Dawid, Guedan Anabel, Ching Yee Man, Makrinioti Heidi, Aniscenko Julia, Edwards Michael R, Solari Roberto, Johnston Sebastian L, Tsourouktsoglou Theodora‐Dorita, Papayannopoulos Venizelos, Radermecker Coraline, Bureau Fabrice, Marichal Thomas, Farnir Frederic
Journal: Nature Medicine (2017)
The effects of sirolimus on Kasabach-Merritt phenomenon coagulopathy
Authors: O. Boccara, E. Puzenat, S. Proust, T. Leblanc, D. Lasne, S. Hadj-Rabia, C. Bodemer
Journal: British Journal of Dermatology (2017)

Kasabach-Merritt phenomenon (KMP) is a very rare life-threatening condition that combines a vascular tumor belonging to the kaposiform hemangioendothelioma (KHE) spectrum lesions, and thrombocytopenia.1,2 Thrombocytopenia results from platelet trapping within the tumor. Platelet activation leads to various degrees of decreased fibrinogen and elevated D-dimer levels. This coagulopathy is frequently protracted after thrombocytopenia resolution. Several treatments have been proposed with variable efficiency.

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07.06 Smoc2, a secreted calcium-binding protein affects chondrogenic differentiation of precursor cells and homeostasis of cartilage
Authors: Tine Peeters, Rik Lories, Frédéric Cailotto
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> SMOC2, a secreted calcium-binding protein of the BM-40/SPARC family was identified from a chondrogenic extract of articular cartilage and is increased in osteoarthritic cartilage. Previous research demonstrated that Wnt signalling needs to be carefully balanced in cartilage to ensure homeostasis. We evaluated the effect of SMOC2 on <i>in vitro</i> chondrogenesis and its relationship with Wnt signalling. <h3>Materials and methods</h3> <i>Smoc2</i> was stably overexpressed or knocked down in ATDC5 cells cultured as micromasses. Impact of SMOC2 on chondrogenesis was evaluated by gene expression analysis of chondrogenic markers (<i>Acan</i>, <i>Col2a1</i>, <i>Col10a1)</i> and by Sirius red, Alcian Blue and Alizarin red staining to evaluate collagens, proteoglycans and mineralization. Femoral head caps of 6 weeks old mice were isolated and stimulated with IL-1β to induce cartilage breakdown. Influence of SMOC2 on cartilage breakdown was evaluated by co-stimulating femoral head caps with recombinant SMOC2 protein. Glycosaminoglycan release in the culture medium was measured by performing a DMMB assay. The influence of SMOC2 on canonical Wnt signalling was assessed by performing a TOP/FOP-flash reporter assay in ATDC5 cells. Human articular chondrocytes were stimulated with Wnt agonist CHIR99021 and recombinant SMOC2 protein to validate the effect of SMOC2 on Wnt signalling. Gene expression of canonical Wnt markers was analysed. <h3>Results</h3> Gene expression of chondrogenic markers and staining intensity of Alcian blue and Alizarin red in ATDC5 micromasses was strongly reduced in <i>Smoc2</i> overexpressing cells compared to control. Mice femoral head caps stimulated with recombinant SMOC2 protein showed an increased glycosaminoglycan release after IL-1β treatment in culture medium in comparison to IL-1β stimulation alone. ATDC5 cells stimulated with recombinant SMOC2 exhibit decreased luciferase activity in the Wnt reporter assay. In contrast we observed an increased luciferase activity in ATDC5 cells with transient Smoc2 knockdown. This inhibitory effect of Smoc2 on canonical Wnt signalling was also observed in human articular chondrocytes. <h3>Conclusion</h3> Smoc2 negatively affects chondrogenic differentiation of precursor cells and increases IL-1β induced breakdown in mice cartilage. Inhibition of canonical Wnt signalling is identified as contributing mechanism.
Endothelin-1 expression is increased upon doxorubicin exposure in vitro and in vivo
Authors: Sandra Bien, Alexander Riad, Florian Olshausen, Markus Grube, Stefan Felix, Carsten Tschöpe, Christoph A. Ritter, Heyo K. Kroemer
Journal: Cancer Research (2006)

4674   Because of its broad antitumor activity doxorubicin is one of the most important anticancer agents. However, the major limiting factor of doxorubicin therapy is its cardiotoxicity involving acute myocardial injury and chronic cardiomyopathy. The molecular basis of doxorubicin-induced cardiomyopathy is not fully understood. In the last decade it was ascertained that endothelin-1 (ET-1), not only expressed in vascular endothelial cells but also in cardiomyocytes, might play an essential role in the pathogenesis of cardiovascular diseases including cardiomyopathies. ET-1 acts as an autocrine/paracrine factor through binding on ET A  and ET B  receptors present in myocardial tissue. Therefore we investigated the regulation of ET-1 by doxorubicin  in vitro  and  in vivo . As  in vitro  models we used the murine cardiac muscle cell line HL-1 and the cervix carcinoma cell line HeLa. ET-1 expression was analyzed on mRNA level by Real Time PCR and on protein level by ELISA technique. Incubation of HeLa and HL-1 cells with doxorubicin resulted in a concentration and time dependent induction of ET-1 expression with a 30-fold and 8-fold increase on mRNA level at 1 μM doxorubicin, respectively. In accordance with the mRNA level the ET-1 peptide in the lysate and supernatant was also increased by doxorubicin, but to a slightly lower extent. By the use of pharmacological inhibitors (MG132, Lactacystin, PD98059, AG1478) we could show that the induction of ET-1 by doxorubicin involves degradation of an unknown factor by the proteasome as well as activation of the MEK-ERK cascade and EGF receptor signaling. These results could be verified by immunoblot analysis of total MEK/ERK and phosphorylated MEK/ERK. For investigation of ET-1 expression  in vivo  we used the C57BL/10 mice treated intraperitoneally with doxorubicin (20 mg/kg body weight). After 1, 3 and 5 days the heart function was analyzed and the mice were sacrificed for removal of hearts and measurement of ET-1 expression in the left ventricle. Already after 24 h both on mRNA and to a lesser extent on protein level we could find a significant increase of ET-1 expression up to about 300% and 170%, respectively. At this time the function of the left ventricle was already impaired but the extent of heart damage was stronger at day 3 and 5. In summary, our data demonstrate an induction of ET-1 expression  in vitro  and  in vivo  with involvement of EGF receptor and MEK-ERK cascade. Based on our findings we postulate a participitation of ET-1 in the pathogenesis of doxorubicin mediated cardiac toxicity.
Controversies in Management: Important progress in treatment
Authors: D Cunningham
Journal: BMJ (1995)

more recently, paclitaxel for ovarian carcinoma, have surprisingly, been licensed on the basis of response rate without published randomised trial data that allow clinicians to place the efficacy of these drugs in an understandable clinical context.Media and patient pressure for such new and expensive therapies seems in danger of dominating clinical science and sense.