tbuckley/cabot-search huggingface dataset:
Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE)
Authors: R. Garcia-Carbonero, J. Capdevila, G. Crespo-Herrero, J.A. Díaz-Pérez, M.P. Martínez del Prado, V. Alonso Orduña, I. Sevilla-García, C. Villabona-Artero, A. Beguiristain-Gómez, M. Llanos-Muñoz, M. Marazuela, C. Alvarez-Escola, D. Castellano, E. Vilar, P. Jiménez-Fonseca, A. Teulé, J. Sastre-Valera, M. Benavent-Viñuelas, A. Monleon, R. Salazar
Journal: Annals of Oncology (2010)
Prevalence of Sjogren syndrome among Nagasaki atomic bomb survivors
Authors: A Hida, M Akahoshi, Y Takagi, K Ashizawa, M Imaizumi, M Soda, R Maeda, E Nakashima, H Ida, A Kawakami, T Nakamura, K Eguchi
Journal: Annals of the Rheumatic Diseases (2007)

Through a comprehensive epidemiological study, we determined Sjögren syndrome (SS) prevalence and examined the association between SS and ionising radiation dose.A total of 1008 atomic bomb survivors in Nagasaki agreed to undergo the tests comprising a questionnaire for xerophthalmia and xerostomia, Schirmer-I test, Saxon test, and tests of anti-SS-A/Ro and anti-SS-B/La antibodies, and, if necessary, Rose Bengal stain test, salivary ultrasonographic and MRI examination from November 2002 through October 2004. Diagnosis of SS was based on the American-European Consensus Group criteria, or a modified version thereof.Among the 1008 participants (male 398, female 610, average age 71.6 years), 154 participants (15.3%) complained of xerophthalmia, and 264 (26.2%) of xerostomia. Reduced tear flow as assessed by the Schirmer-I test was detected in 371 of 992 participants (37.4%) and reduced saliva flow as assessed by the Saxon test in 203 of 993 participants (20.4%). Among all participants, 38 (3.8%) and 10 (1.0%) participants tested positive for anti-SS-A/Ro and anti-SS-B/La antibodies, respectively. Taking into consideration all the results, 23 participants were diagnosed with SS (primary 20, secondary 3), yielding a prevalence of 2.3%. Although the association between SS and radiation dose was not significant, radiation dose was significantly associated with hyposalivation.The present comprehensive epidemiological study reveals that the prevalence of SS was 2.3% among Nagasaki atomic bomb survivors and was not associated with radiation dose. The association between radiation dose and hyposalivation supported the possibility that radiation exposure damaged salivary gland function.
Phase I Trial of Poly-<scp>l</scp>-Glutamate Camptothecin (CT-2106) Administered Weekly in Patients with Advanced Solid Malignancies
Authors: Jade Homsi, George R. Simon, Chris R. Garrett, Gregory Springett, Ronald De Conti, Alberto A. Chiappori, Pamela N. Munster, Michelle K. Burton, Scott Stromatt, Claudia Allievi, Patrizia Angiuli, Amy Eisenfeld, Daniel M. Sullivan, Adil I. Daud
Journal: Clinical Cancer Research (2007)

Abstract Purpose: CT-2106 is a 20(S)-camptothecin poly-l-glutamate conjugate. This linkage stabilizes the active lactone form of camptothecin and enhances aqueous solubility. In addition, poly-l-glutamate is postulated to increase tumor delivery of the active compound through enhanced permeability and retention effect in tumor. We studied a weekly schedule of CT-2106 in patients with refractory solid tumor malignancies. Experimental Design: CT-2106 was infused (10 min i.v. infusion) on days 1, 8, and 15 of each 28-day cycle. Plasma and urine were analyzed for total and unconjugated camptothecin by high-performance liquid chromatography equipped with a fluorescence detector. Toxicity and response assessments were done with Common Toxicity Criteria for Adverse Events version 3 and Response Evaluation Criteria in Solid Tumors, respectively. Results: Twenty-six patients were enrolled. Median age was 58 years (range, 36-83) and median number of doses was 6 (range, 1-9). The most frequent tumor type (50%) was melanoma. Dose limiting toxicities were thrombocytopenia and fatigue. A weekly dose of 25 mg/m2 given every 3 of 4 weeks was the maximum tolerated dose. The majority of grade 3 and 4 toxicities were hematologic. The pharmacokinetic profile of conjugated and unconjugated camptothecin showed a polyexponential decline with similar terminal half life (t1/2 range was 44-63 and 31-48 h for conjugated and unconjugated, respectively). Pharmacokinetics of conjugated and unconjugated camptothecin were dose and time independent in the tested dose range. Urinary excretion of conjugated and unconjugated camptothecin accounted for about 30% and 4% of the administered dose, respectively. Conclusions: CT-2106 has a more manageable toxicity profile compared with unconjugated camptothecin. The maximum tolerated dose is 25 mg/m2 weekly given 3 of 4 weeks. This compound results in prolonged release of unconjugated camptothecin.
Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants
Authors: Jihane Romanos, Anna Rosén, Vinod Kumar, Gosia Trynka, Lude Franke, Agata Szperl, Javier Gutierrez-Achury, Cleo C van Diemen, Roan Kanninga, Soesma A Jankipersadsing, Andrea Steck, Georges Eisenbarth, David A van Heel, Bozena Cukrowska, Valentina Bruno, Maria Cristina Mazzilli, Concepcion Núñez, Jose Ramon Bilbao, M Luisa Mearin, Donatella Barisani, Marian Rewers, Jill M Norris, Anneli Ivarsson, H Marieke Boezen, Edwin Liu, Cisca Wijmenga
Journal: Gut (2013)

<h3>Background</h3> The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. <h3>Objective</h3> We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. <h3>Design</h3> We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. <h3>Results</h3> Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. <h3>Conclusions</h3> Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.
Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial
Authors: T. H Rainer
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. <b>Design:</b> Double blind, randomised, controlled study and cost consequences analysis. <b>Setting:</b> Emergency department of a university hospital in the New Territories of Hong Kong. <b>Participants:</b> 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). <b>Main outcome measures:</b> Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients9 satisfaction, and time spent in the emergency department. <b>Results:</b> No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 (£4; $5.6) in the ketorolac group and $HK229 in the morphine group (P&lt;0.0001). The median score for patients9 satisfaction was 6.0 for ketorolac and 5.0 for morphine (P&lt;0.0001). <b>Conclusion:</b> Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy.
High Levels of Nrf2 Determine Chemoresistance in Type II Endometrial Cancer
Authors: Tao Jiang, Ning Chen, Fei Zhao, Xiao-Jun Wang, Beihua Kong, Wenxin Zheng, Donna D. Zhang
Journal: Cancer Research (2010)

Abstract Type II endometrial cancer, which mainly presents as serous and clear cell types, has proved to be the most malignant and recurrent carcinoma among various female genital malignancies. The transcription factor Nrf2 was first described as having chemopreventive activity. Activation of the Nrf2-mediated cellular defense response protects cells against the toxic and carcinogenic effects of environmental insults by upregulating an array of genes that detoxify reactive oxygen species and restore cellular redox homeostasis. However, the cancer-promoting role of Nrf2 has recently been revealed. Nrf2 is constitutively upregulated in several types of human cancer tissues and cancer cell lines. Furthermore, inhibition of Nrf2 expression sensitizes cancer cells to chemotherapeutic drugs. In this study, the constitutive level of Nrf2 was compared in different types of human endometrial tumors. It was found that Nrf2 was highly expressed in endometrial serous carcinoma (ESC), whereas complex hyperplasia and endometrial endometrioid carcinoma (EEC) had no or marginal expression of Nrf2. Likewise, the ESC-derived SPEC-2 cell line had a higher level of Nrf2 expression and was more resistant to the toxic effects of cisplatin and paclitaxel than the Ishikawa cell line, which was generated from EEC. Silencing of Nrf2 rendered SPEC-2 cells more susceptible to chemotherapeutic drugs, whereas it had a limited effect on Ishikawa cells. Inhibition of Nrf2 expression by overexpressing Keap1 sensitized SPEC-2 cells or SPEC-2–derived xenografts to chemotherapeutic treatments using both cell culture and severe combined immunodeficient mouse models. Collectively, we provide a molecular basis for the use of Nrf2 inhibitors to increase the efficacy of chemotherapeutic drugs and to combat chemoresistance, the biggest obstacle in chemotherapy. Cancer Res; 70(13); 5486–96. ©2010 AACR.
Organophosphorous pesticide exposure increases the frequency of sperm sex null aneuploidy.
Authors: R Recio, W A Robbins, V Borja-Aburto, J Morán-Martínez, J R Froines, R M Hernández, M E Cebrián
Journal: Environmental Health Perspectives (2001)

It has been estimated that 4 of 1,000 live births and 35% of spontaneous abortions are aneuploid and that an important proportion of embryo and newborn aneuploidy is of paternal origin. Exposure to organophosphorous pesticides (OP) has been associated with sperm hyperploidy/polyploidy. Therefore, we aimed to assess the frequency of sperm aneuploidy (X, Y, and 18) and its relationship with urinary OP metabolites in agricultural workers. We performed multicolor fluorescence in situ hybridization on samples from nine men obtained before and during the pesticide spraying season to assess sperm aneuploidy. We measured urinary OP metabolite levels by gas-liquid chromatography. Aneuploidies were found in 0.67% of total sperm nuclei. The most frequent aneuploidy was the lack of a sexual chromosome or sex null (0.19%), followed by XY18 (0.15%) and XY18-18 (0.06%). OP metabolites detected at higher concentrations were dimethylthiophosphate, dimethyldithiophosphate, and diethylphosphate (DEP). There were no differences in average aneuploidy frequency or urinary metabolite levels between samples collected before and after exposure. However, Poisson regression analysis adjusted for age, alcohol intake, and sperm concentration showed significant associations between OP metabolite concentrations and increased frequency of sperm aneuploidies. The association was more evident between DEP and sex null, and the risk increased further during the spraying season. Thus, OP exposure could interfere with sperm chromosome segregation and increase the risk for genetic syndromes, such as Turner's. Further studies are required to assess the prevalence of spontaneous abortions, birth defects, and genetic syndromes in agricultural communities.
Current physical activity guidelines for health are insufficient to mitigate long-term weight gain: more data in the fitness versus fatness debate (The HUNT study, Norway)
Authors: Trine Moholdt, Ulrik Wisløff, Stian Lydersen, Javaid Nauman
Journal: British Journal of Sports Medicine (2014)

Background To promote and maintain health, all adults are recommended to do moderate-intensity aerobic activity a minimum of 30 min on 5 days, or vigorous-intensity activity of 20 min on 3 days, each week. Whether these levels prevent long-term weight gain is uncertain. Objective To assess the relationship between physical activity and long-term weight gain. Study design An observational prospective cohort study. Methods Weight and physical activity were measured in the Nord-Trøndelag Health Study in 1984–1986, 1995–1997 and 2006–2008. Participants (n=19 127) were classified based on physical activity into inactive, below recommended level, recommended level or above recommended level. We carried out adjusted mixed model regression analyses with weight as outcome. Results Men maintaining physical activity above the recommendations for 33 years increased 5.6 kg, while inactive men increased 9.1 kg. For women, corresponding numbers were 3.8 kg in those above recommended physical activity levels, and 9.5 kg in inactive. In adjusted analyses, physical activity above the recommendations was associated with 2.1 kg (95% CI 1.8 to 2.4) less weight gain in men over any 11-year period, compared with inactive. Women exceeding the recommendations gained 1.8 kg (CI 1.5 to 2.2) less than inactive. Compared with inactive, the ORs of gaining meaningful weight of ≥2.3 kg were 0.79 (CI 0.69 to 0.91) and 0.70 (CI 0.60 to 0.81) if exceeding the recommendations in men and women, respectively. Conclusions Physical activity above the current recommendations for health benefits was associated with significantly lower risk of weight gain.
Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin® are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study
Authors: A. Sapino, F. Montemurro, C. Marchiò, G. Viale, J. Kulka, M. Donadio, A. Bottini, G. Botti, A.P. dei Tos, A. Bersiga, S. Di Palma, M. Truini, G. Sanna, M. Aglietta, G. Bussolati
Journal: Annals of Oncology (2007)
Mechanisms of L-Type Ca <sup>2+</sup> Current Downregulation in Rat Atrial Myocytes During Heart Failure
Authors: Christophe Boixel, Walter Gonzalez, Liliane Louedec, Stéphane N. Hatem
Journal: Circulation Research (2001)

Abstract— Downregulation of the L-type Ca 2+ current ( I Ca ) is an important determinant of the electrical remodeling of diseased atria. Using a rat model of heart failure (HF) due to ischemic cardiopathy, we studied I Ca in isolated left atrial myocytes with the whole-cell patch-clamp technique and biochemical assays. I Ca density was markedly reduced (1.7±0.1 pA/pF) compared with sham-operated rats (S) (4.1±0.2 pA/pF), but its gating properties were unchanged. Calcium channel α 1C -subunit quantities were not significantly different between S and HF. The β-adrenergic agonist isoproterenol (1 μmol/L) had far greater stimulatory effects on I Ca in HF than in S (2.5- versus 1-fold), thereby suppressing the difference in current density. Dialyzing cells with 100 μmol/L cAMP or pretreating them with the phosphatase inhibitor okadaic acid also increased I Ca and suppressed the difference in density between S and HF. Intracellular cAMP content was reduced more in HF than in S. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine had a greater effect on I Ca in HF than in S (76.0±11.2% versus 15.8±21.2%), whereas the inhibitory effect of atrial natriuretic peptide on I Ca was more important in S than in HF (54.1±4.8% versus 24.3±8.8%). Cyclic GMP extruded from HF myocytes was enhanced compared with S (55.8±8.0 versus 6.2±4.0 pmol · mL −1 ). Thus, I Ca downregulation in atrial myocytes from rats with heart failure is caused by changes in basal cAMP-dependent regulation of the current and is associated with increased response to catecholamines.
Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer
Authors: P. Karlsson, Z. Sun, D. Braun, K.N. Price, M. Castiglione-Gertsch, M. Rabaglio, R.D. Gelber, D. Crivellari, J. Collins, E. Murray, K. Zaman, M. Colleoni, B.A. Gusterson, G. Viale, M.M. Regan, A.S. Coates, A. Goldhirsch
Journal: Annals of Oncology (2011)
Nerve Growth Factor Promotes Angiogenesis and Arteriogenesis in Ischemic Hindlimbs
Authors: Costanza Emanueli, Maria B. Salis, Alessandra Pinna, Gallia Graiani, Luigi Manni, Paolo Madeddu
Journal: Circulation (2002)

Background— The neurotrophin nerve growth factor (NGF) regulates neuron survival and differentiation. Implication in neovascularization is supported by statement of NGF and its high-affinity receptor at vascular level and by NGF property of stimulating vascular endothelial cell proliferation. The present study investigated the involvement of endogenous NGF in spontaneous reparative response to ischemia. Mechanisms and therapeutic potential of NGF-induced neovascularization were examined. Methods and Results— Unilateral limb ischemia was produced in CD1 mice by femoral artery resection. By ELISA and immunohistochemistry, we documented that statement of NGF and its high-affinity receptor is upregulated in ischemic muscles. The functional relevance of this phenomenon was assessed by means of NGF-neutralizing antibody. Chronic NGF blockade abrogated the spontaneous capillarization response to ischemia and augmented myocyte apoptosis. Then we tested whether NGF administration may exert curative effects. Repeated NGF injection into ischemic adductors increased capillary and arteriole density, reduced endothelial cell and myofiber apoptosis, and accelerated perfusion recovery, without altering systemic hemodynamics. In normoperfused muscles, NFG-induced capillarization was blocked by vascular endothelial growth factor–neutralizing antibodies, dominant-negative Akt, or NO synthase inhibition. Conclusions— These results indicate that NGF plays a functional role in reparative neovascularization. Furthermore, supplementation of the growth factor promotes angiogenesis through a vascular endothelial growth factor-Akt-NO–mediated mechanism. In the setting of ischemia, potentiation of NGF pathway stimulates angiogenesis and arteriogenesis, thereby accelerating hemodynamic recovery. NGF might be envisaged as a utilitarian target for the treatment of ischemic vascular disease.
Pseudorenin: A NEW ANGIOTENSIN-FORMING ENZYME
Authors: Leonard T. Skeggs, Kenneth E. Lentz, Joseph R. Kahn, Frederic E. Dorer, Melvin Levine
Journal: Circulation Research (1969)

A new enzyme, pseudorenin, has been discovered which resembles renin in its ability to form angiotensin I from the synthetic tetradecapeptide renin substrate and from purified hog renin substrate A. Its maximal activity occurs at a much lower pH value than does that of renin. The two enzymes may be easily separated by DEAE-cellulose chromatography. Unlike renin, pseudorenin does not attack substrate A in the presence of serum, nor does it produce angiotensin I from renin substrate as it exists in serum. In contrast to renin, which occurs primarily in the kidney, pseudorenin has been found in every one of the 13 different tissues which have been tested, and also in the plasma. The natural substrate for the new enzyme as well as its physiological function are not known.
IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy
Authors: W. A. Verri, F. O. Souto, S. M. Vieira, S. C. L. Almeida, S. Y. Fukada, D. Xu, J. C. Alves-Filho, T. M. Cunha, A. T. G. Guerrero, R. B. Mattos-Guimaraes, F. R. Oliveira, M. M. Teixeira, J. S. Silva, I. B. McInnes, S. H. Ferreira, P. Louzada-Junior, F. Y. Liew, F. Q. Cunha
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Interleukin 33 (IL-33) is a new member of the IL-1 family of cytokines which signals via its receptor, ST2 (IL-33R), and has an important role in Th2 and mast cell responses. This study shows that IL-33 orchestrates neutrophil migration in arthritis. <h3>Methods and results</h3> Methylated bovine serum albumin (mBSA) challenge in the knee joint of mBSA-immunised mice induced local neutrophil migration accompanied by increased IL-33R and IL-33 mRNA expression. Cell migration was inhibited by systemic and local treatments with soluble (s)IL-33R, an IL-33 decoy receptor, and was not evident in IL-33R-deficient mice. IL-33 injection also induced IL-33R-dependent neutrophil migration. Antigen- and IL-33-induced neutrophil migration in the joint was dependent on CXCL1, CCL3, tumour necrosis factor α (TNFα) and IL-1β synthesis. Synovial tissue, macrophages and activated neutrophils expressed IL-33R. IL-33 induces neutrophil migration by activating macrophages to produce chemokines and cytokines and by directly acting on neutrophils. Importantly, neutrophils from patients with rheumatoid arthritis successfully treated with anti-TNFα antibody (infliximab) expressed significantly lower levels of IL-33R than patients treated with methotrexate alone. Only neutrophils from patients treated with methotrexate alone or from normal donors stimulated with TNFα responded to IL-33 in chemotaxis. <h3>Conclusions</h3> These results suggest that suppression of IL-33R expression in neutrophils, preventing IL-33-induced neutrophil migration, may be an important mechanism of anti-TNFα therapy of inflammation.