tbuckley/cabot-search huggingface dataset:
Cytochrome c oxidase sequence comparisons suggest an unusually high rate of mitochondrial DNA evolution in Mytilus (Mollusca: Bivalvia)
Authors: W. R. Hoeh, D. T. Stewart, B. W. Sutherland, E. Zouros
Journal: Molecular Biology and Evolution (1996)

Blue mussels of the genus Mytilus have an unusual mode of mitochondrial DNA (mtDNA) transmission: males receive mtDNA from both parents and transmit their paternal mtDNA to their sons; females receive mtDNA only from their mother (Skibinski, Gallagher, and Beynon 1994~2, 1994b; Zouros et al. 1994~2, 1994b). This mode of mtDNA transmission has been termed “doubly uniparental inheritance” (DUI; Zouros et al. 1994a). It is known from the work of Hoffmann, Boore, and Brown (1992) and Boore and Brown (1994) that the gene order of Mytilus mtDNA is much more different from that of vertebrates, insects, or the chiton Katharina (itself a mollusk) than these other mtDNA gene orders are from each other. Here we report another exceptional feature of the Mytilus mtDNA genome, specifically, an accelerated rate of sequence divergence. Based on a comparison of nucleotide and amino acid sequences, we demonstrate that the Mytilus mtDNA is the most divergent metazoan mtDNA known today and that it evolves at a higher rate than is typical for animals. We suggest that the fast rate of mtDNA evolution in Mytilus is causally related to DUI. Nucleotide sequences of both the “female” (F) and “male” (M) mitotypes of Mytilus edulis for cytochrome c oxidase subunits I (COI, 660 bp) and III (COIII, 762 bp) were obtained as described elsewhere (Folmer et al. 1994; Stewart et al. 1995). Ten additional sequences representing major metazoan lineages were either obtained from Genbank or communicated to us. Estimates of sequence divergence and the construction of neighborjoining trees were carried out using MEGA version 1.02 (Kumar, Tamura, and Nei 1993) and were based on the combined COI/COIII data set. Pairwise proportional distances for first and second nucleotide positions and for amino acids are shown in table 1. Given the taxonomic distance of the compared taxa, nucleotide substitutions at third positions were saturated and were excluded from nucleotide distance calculations.
Asymptomatic Fatigue Fracture of the Proximal Ulna Associated With Symptomatic Fatigue Fractures of the Lower Limbs
Authors: WLADIMIR SOPOV, DAVID GROSHAR
Journal: Clinical Nuclear Medicine (1999)

Fatigue fractures usually involve the lower extremities after unaccustomed or inappropriate exercise. Although unusual in the upper extremity, symptomatic fatigue fractures of the ulna have been described in tennis players, volleyball players, weight lifters, and softball pitchers. The mechanism is thought to be due to overuse of the flexor muscles, with subsequent loss of mechanical integrity of the proximal ulna. The following case is representative of four similar cases of soldiers with asymptomatic fatigue fractures of the ulna shown by whole-body bone scintigraphy performed to evaluate lower limb pain.
Abstract 134: Smoking duration before first childbirth: An emerging risk factor for breast cancer? Results from the Norwegian National Health Service Cohort (NHHS).
Authors: Eivind Bjerkaas, Ranjan Parajuli, Anders Engeland, Gertraud Mascarinec, Randi Selmer, Elisabete Weiderpass, Inger Torhild Gram
Journal: Cancer Research (2013)

Abstract Purpose - Recent studies suggest that the period before the first childbirth is important in the relation between smoking and risk of breast cancer. We wanted to examine this association with focus on smoking duration before the first childbirth. Methods - We followed 302,865 Norwegian women born between 1899 -1975 and identified 7,490 cases of primary invasive breast cancer cases during &amp;gt; 4.1 million person years of observation (mean 14 person years). We used Cox proportional hazard models to find hazard ratios (HR) with 95 % confidence intervals (CIs) adjusting for age, education, parity, age at first childbirth, BMI and physical activity. Information came from a questionnaire and a physical examination at enrolment, and from linkages to national registries. Results - Compared with women who had never smoked, current smokers had a 14% [HR= 1.14 (95% CI 1.08-1.20)] and former smokers a 17% [HR=1.17 (95% CI 1.10-1.24)] increased risk of breast cancer. Ever smokers who started to smoke after their first childbirth did not have an increased risk [HR=0.93 (95% CI 0.86-1.02)], compared with never smokers. Those who had smoked for more than 20 years, and who had smoked 11 or more of those years before the first childbirth, showed a doubling in risk [HR=1.97 (95% CI 1.33-2.93)] compared with those starting to smoke after the first childbirth. Conclusions - Our study suggests that duration of smoking before the first childbirth is a key factor in the relationship between smoking and breast cancer. Citation Format: Eivind Bjerkaas, Ranjan Parajuli, Anders Engeland, Gertraud Mascarinec, Randi Selmer, Elisabete Weiderpass, Inger Torhild Gram. Smoking duration before first childbirth: An emerging risk factor for breast cancer? Results from the Norwegian National Health Service Cohort (NHHS). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 134. doi:10.1158/1538-7445.AM2013-134
F-18 FDG Uptake in a Patient with Psoriatic Arthritis
Authors: MIJIN YUN, WOOJIN KIM, LARS E. ADAM, NAHEEL ALNAFISI, CATHRYN HERMAN, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2001)

The authors describe a patient with psoriatic arthritis in whom an increased level of F-18 fluorodeoxyglucose (F-18 FDG) uptake was seen in the joints of the hands. The areas of increased activity correlated well with the regions of symptoms reported by the patient. This case illustrates the potential use of F-18 FDG positron emission tomography to quantitatively assess the degree of arthritis activity.
AB0242 Effect of Rheumatoid Factor on Arterial Stiffness in General Population without Joint Symptoms
Authors: G.-T. Kim, E.-K. Park, S.-G. Lee, S.-H. Baek, S.-H. Kim, J.-H. Lee, J.-W. Lee
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid factor (RF) has been suggested as an independent risk factor for ischemic heart disease in the general population by some studies, but the role of RF on arterial stiffness and cardiovascular risk in the subjects without joint symptoms is not defined. <h3>Objectives</h3> We investigated the arterial stiffness in the subjects without joint symptom using pulse wave velocity (PWV), calculated Framingham risk score (FRS), which is used to estimate the cardiovascular risk, and analyzed whether arterial stiffness and FRS were affected by RF. <h3>Methods</h3> 242 subjects (164 men, 78 women, 51.2±8.9 years) were included in this population-based study. RF was quantified using turbid immunometry (Advia 1800, Siemens) with cut-off &gt;15 IU/ml for positive values. Information obtained on joint symptoms. Brachial ankle PWV (baPWV) was measured with an automated device. Adjusted comparison of baPWV in RF-positive and RF-negative subjects was performed. <h3>Results</h3> Of 242 subjects, 15 had positive RF. RF-positive subjects without joint symptoms had higher baPWV than RF-negative subjects (1472.6±251.0/1408.6±226.1 cm/s, p=0.293), and higher FRS (16.2±10.2/11.9±9.7), but both figures did not reach the statistical significance. However, when we divided the subjects into 2 groups (group A – high RF, ≥40, group B – low RF, &lt;40), group A showed significantly higher baPWV and higher FRS (1640.7±179.6/1405.7±225.7 cm/s, p=0.007, 25.7±4.87/11.8±9.6, p = &lt;0.001). Multiple regression analysis was used to adjust for any potential confounding influences including age, total cholesterol, LDL cholesterol, and RF exhibited significant effect on baPWV (adjusted R=0.038, p=0.030). <h3>Conclusions</h3> In general population without joint symptoms, higher RF was associated with increased arterial stiffness, suggesting a pathophysiologic link between RF and endothelial dysfunction. <h3>References</h3> Tomasson G, Aspelund T, Jonsson T, et al. The effect of rheumatoid factor on mortality and coronary heart disease. Ann Rheum Dis 2010;69(9):1649-54 Del Rincon ID, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001;44(12):2737-45 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2930
Abstract 5088: Identification of effective genotype-selective drug combinations in melanoma
Authors: Matthew Held, Casey Langdon, James Platt, Tisheeka Steed, Ashok Chakraborty, Antonella Bachiocchi, Zonghzhi Liu, Marcus Bosenberg, David F. Stern
Journal: Cancer Research (2012)

Abstract Resistance and partial responses to individual therapeutic agents are major obstacles in cancer treatment. In certain cases, combination therapies are clearly more effective, but systematic approaches to the identification of synergistic combinations of drugs are not well established. Here we present a bioinformatics-guided, high-throughput combinatorial screening platform that tests an array of small molecule drug combinations. A panel of over one hundred fifty agents was curated for compounds that inhibit receptors and signaling pathways active in melanoma, and broader groups of conventional cell cycle-active and genotoxic agents. Sixteen-point dose-effect curves were determined. Forty of the compounds exhibiting activity and representing the major classes tested were further analyzed. Three doses each were chosen, set up in all pair-wise combinations using a hit-picking robot, and analyzed against cell lines with activated BRAF, activated RAS, or neither mutation. Several combinations were selectively effective for melanomas containing activating mutations in BRAF, but were ineffective for mutant RAS melanomas, which were most susceptible to a small group of other drug combinations. Work is underway to validate the effective combinations in animal models, and to mine transcriptome and phosphoproteomic data associated with the cell lines to better predict sensitivity and resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5088. doi:1538-7445.AM2012-5088
Prognostic Significance of Survivin Expression in Patients with Gastric Cancer
Authors: M. Terashima, K. Hatakeyama, Y. Yamakawa, Y. Miki, R. Makuuchi, S. Honda, T. Tatsubayashi, M. Tokunaga, Y. Tanizawa, E. Bando, T. Kawamura, K. Oshima, T. Mochizuki
Journal: Annals of Oncology (2014)
Diagnostic and Prognostic Value of Gated SPECT MIBI Early Post-Stress Imaging in Patients With Intermediate Duke Treadmill Score
Authors: Dragana P Sobic-Saranovic, Ljiljana Bojic, Zorica Petrasinovic, Isidora T Grozdic-Milojevic, Smiljana Pavlovic, Vera Artiko, Emilija Jaksic, Vladimir Obradovic, Maurizio Dondi
Journal: Clinical Nuclear Medicine (2013)

Purpose of the Report The aims of this study were to compare perfusion and functional parameters between early (ES) and standard (SS) post-stress gated SPECT MIBI, to validate ES against coronary angiography, and to determine whether ES parameters can predict future cardiac events. Patients and Methods The sample included 63 patients with normal or mildly impaired left ventricular function and intermediate Duke Treadmill Score. They underwent a 2-day stress-rest gated SPECT MIBI with the post-stress data acquired at 15 minutes (ES) and 60 minutes (SS) after i.v. injection of 740 MBq of 99mTc-MIBI. The ES findings were compared to SS and against coronary angiography to determine their sensitivity/specificity for detecting >70% stenosis. The information about new-onset cardiac events was collected 26 ± 6 months later. Results Perfusion parameters did not significantly differ between ES and SS. Ejection fraction was significantly lower and regional wall motion abnormalities were significantly higher on ES than SS. The corresponding perfusion and functional parameters were strongly related (linear regression slope 0.65–1.00, intercept −0.36–8.5, R2 0.98–0.75). ES parameters had high sensitivity (96%) and specificity (83%) for detecting >70% stenosis. Lower early stress than rest EF (>5%), higher early stress than rest EDV, and early SSS >8 emerged as significant predictors of new-onset cardiac events. Conclusions Early post-stress gated SPECT MIBI yields comparable perfusion and functional parameters as the standard post-stress protocol. ES parameters are useful for detecting the existing coronary disease and for predicting future cardiac events. ES protocol is recommended for improving patient compliance and efficiency of nuclear cardiology services.
P18 * LONG TERM SURVIVAL OF HIGH GRADE GLIOMA: A SINGLE INSTITUTION STUDY
Authors: F. Newman, G. Critchley
Journal: Neuro-Oncology (2014)

INTRODUCTION: Despite advances in treatment, median survival of adult glioblastoma is between 12 and 15 months. Our unit has, on average, 83 malignant brain tumours diagnosed per year. We have noticed an apparent increase in numbers of long term survivors of high grade glioma, and wanted to evaluate this in order to guide appropriate future service provision for these patients. METHOD: A retrospective review of the high grade glioma patients in our neurosurgical centre. Notes were requested for all patients who attended the High Grade Glioma (HGG) clinic from 2003 to 2008; this ensured a population with a minimum of 5 years follow-up. A standardised data collection form was used for demographic, clinical and treatment-associated parameters. RESULTS: 79 patients were identified, of which 69 notes were reviewed. 42 of these had HGG; 28 survived more than 5 years. 14 of these were grade 4 glioma, and 14 grade 3. 5.6 cases per year survived >5yrs, equating to 6.7% of patients with primary malignant brain tumours per annum. The median age of survivors > 5yrs was 41.5yrs. Survival ranged from 5 years to 13 years. Recurrence rate was 43% and reoperation rate 10%. Karnofsky Performance Score (KPS) at diagnosis was 90 in 89%, and >70 in 75% at time of last clinic. CONCLUSION: Patients with high grade gliomas can survive greater than 5 years. Survivorship studies are therefore increasingly important not only to guide treatment and management of a condition which is typically thought of as having poor prognosis with short life span, but also to increase resources for patients accordingly.
A1.01 Activation of TLR4 by dysbiotic intestinal microbiota following IL-1 receptor antagonist deficiency triggers TH17-mediated arthritis
Authors: R Rogier, T Ederveen, J Boekhorst, H Wopereis, S Frambach, J Garssen, P van der Kraan, M Koenders, W van den Berg, S van Hijum, S Abdollahi-Roodsaz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Interleukin-1 receptor antagonist deficient (IL-1Ra<sup>-/-</sup>) mice spontaneously develop a T cell-driven autoimmune arthritis, which depends on the presence of commensal microbiota and Toll-like receptor 4 (TLR4). The aim of this study was to elucidate the role of IL-1 receptor signalling and TLR4 in defining the intestinal microbiota and the associated mucosal and systemic immune response during arthritis. <h3>Methods</h3> 16S rRNA 454-pyrosequencing meta-genome analysis was used to define intestinal microbial communities&nbsp;in BALB/c wild type (WT), IL-1Ra<sup>-/-</sup> and IL-1Ra/TLR4 double knock-out (DKO) mice. IL-1Ra<sup>-/-</sup> mice were treated with antibiotics and re-colonised with segmented filamentous bacteria (SFB). T cell differentiation and cytokine production was assessed in small intestine lamina propria (SI-LP) and draining lymph nodes. <h3>Results</h3> IL-1Ra<sup>-/-</sup> mice had a significant reduction in microbial diversity compared to WT mice. Interestingly, the species diversity was restored&nbsp;in IL-1Ra/TLR4 DKO, suggesting that IL-1R-driven skewing of bacterial diversity depends on TLR4. IL-1Ra<sup>-/-</sup> mice had greatly increased intestinal Th17 levels, which significantly correlated with arthritis scores. Relevance of intestinal microbiota in arthritis was underlined by significant long-term suppression of arthritis by one-week oral treatment with broad-spectrum antibiotics. Re-colonisation of antibiotic-treated IL-1Ra<sup>-/-</sup> mice by SFB, a potent intestinal Th17 inducer, was sufficient to cause full-blown arthritis. Absence of TLR4 resulted in the sustained reduction of arthritis in IL-1Ra<sup>-/-</sup> mice. TLR4 is known to play a major role in recognition of Gram-negative bacteria. Interestingly, treatment with tobramycin, specifically eliminating Gram-negative bacteria, significantly reduced arthritis severity. SI-LP mononuclear cells from IL-1Ra<sup>-/-</sup>TLR4<sup>-/-</sup> mice <i><i>ex vivo</i></i> cultured with PMA and ionomycin produced substantially less IL-17. In addition, production of IL-23, IL-1β and IL-6 upon <i>ex vivo</i> stimulation with intestinal microbial antigens was reduced in the absence of TLR4. This suggests that TLR4 plays a role in microbiota-induced production of cytokines involved in intestinal Th17 differentiation. <h3>Conclusions</h3> Our data suggest that activation of TLR4 by commensal intestinal microbiota drives arthritis in IL-1Ra<sup>-/-</sup> mice via intestinal IL-1, IL-23, IL-6production and subsequent Th17 induction. Understanding the mechanisms linking the intestinal T cell response with arthritis may help identifying novel therapeutic targets in rheumatoid arthritis.
Visual control – evaluation of the most suitable visualization angle for NOTES platforms
Authors: D Wilhelm, EM Losher, A Schneider, T Baude, A Meining, H Feussner
Journal: Endoscopy (2012)

Objective of the study: A perfect visualization of the operative field is essential for efficient and secure manipulation during any intervention. While in laparoscopic surgery a top view with an angle of 30 – 60° is preferred, flexible endoscopes and NOTES platforms currently provide an in-axis visualization (o°-angle). Interestingly, in open surgery the visualization angle is even steeper. The impact of different visualization angles on the operative performance and the mental work load has not yet been investigated, but would be important for the construction of future NOTES platforms
Abstract 4505: Polymorphisms in <i>vascular endothelial growth factor</i> (<i>VEGF</i>) and associated receptors as prognostic and predictive factors in advanced solid tumors
Authors: Lawson Eng, Eitan Amir, Abul Kalam Azad, Steven Habbous, Vincent Pang, Anke-Hilse Maitland van der Zee, Sevtap Savas, Helen Mackay, Geoffrey Liu
Journal: Cancer Research (2012)

Abstract Introduction: Angiogenesis is an important host factor that is utilized by cancer cells to both grow and metastasize. In an attempt to halt the progression of cancer growth, new agents, such as bevacizumab, have been developed to target VEGF. Host genetic variability in the VEGF pathway may influence angiogenesis-dependent signalling during cancer development, cancer biology and therefore may impact on sensitivity to various therapies and survival. Here, we conducted a systematic review of the predictive and prognostic significance of polymorphisms in VEGF and VEGF receptor (VEGFR) and their isoforms. Materials and Methods: We performed a literature search of PubMed in July 2011 using the keywords and MeSH terms: {“angiogenesis,” “VEGF,” “VEGFR1,” “FLT1,” “KDR,” “VEGFR2,” “VEGFA,” “VEGFB,” “bevacizumab”} and “cancer” and “polymorphism”. Eligible studies were those comparing wild-type and variant polymorphisms and reporting one or more of the following outcomes: overall survival (OS), progression free survival, time to progression, time to recurrence, disease free survival, response rate or drug toxicities. Meta-analysis was performed for studies reporting identical outcome data for pre-specified polymorphisms. Results: We identified 44 prognostic studies and 12 predictive studies. There was marked inter and intra-disease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analysis was possible for six polymorphisms (VEGF +936C&amp;gt;T, VEGF –460T&amp;gt;C, VEGF +405G&amp;gt;C, VEGF –1154G&amp;gt;A, VEGF –2578C&amp;gt;A and VEGF –634G&amp;gt;C) each of which reported the effect of wild-type and variant forms on OS. VEGF –634G&amp;gt;C showed a statistically significant improvement in OS (HR: 0.75, 95% CI: 0.57-0.98, p=0.03). There were non-significant associations between VEGF +936C&amp;gt;T with worse OS and VEGF +405G&amp;gt;C with improved survival (HR: 1.38, 95% CI: 0.96-1.97, p=0.08 and HR: 0.85, 95% CI: 0.72-1.01, p=0.07, respectively). There were no significant differences between homozygosity and heterozygosity for these polymorphisms. Conclusions: VEGF –634G&amp;gt;C appears to predict for improved outcome while VEGF +936C&amp;gt;T and +405G&amp;gt;C both show non-significant associations with outcome. These polymorphisms should be investigated in prospective studies to ensure standardization of measurement and reporting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4505. doi:1538-7445.AM2012-4505