tbuckley/cabot-search huggingface dataset:
GIMAP and Behçet disease: no association in the European population: Table 1
Authors: Lourdes Ortiz-Fernández, Marta Conde-Jaldón, José Raul García-Lozano, Marco Antonio Montes-Cano, Norberto Ortego-Centeno, María Jesús Castillo-Palma, Gerard Espinosa, Genaro Graña-Gil, Juan Sánchez-Bursón, Miguel Angel González-Gay, Ana Celia Barnosi-Marín, Roser Solans, Patricia Fanlo, Mónica Rodríguez Carballeira, Teresa Camps, Santos Castañeda, Javier Martín, María Francisca González-Escribano
Journal: Annals of the Rheumatic Diseases (2014)

Behcet disease (BD) is a multifactorial disorder with a highest prevalence among people with Mediterranean or Asian ancestry having association with HLA-B51 and other HLA and non-HLA loci.1–4 Very recently, one genome-wide association study (GWAS) identified the GIMAP locus, which encoded proteins involved in development of the T and B lymphocytes, as associated with the disease in the Asian populations.5 To investigate whether this association is replicated in Europeans, a total of 1086 (326 patients and 760 controls) Spanish individuals of European origin were genotyped after obtaining written informed consent and approval from the local ethical committees of all the institutions involved. Patients fulfilled the 1990 International Study Group classification criteria for Behcet’s disease,6 and the group was composed of 44.5% men with the following clinical features: 100% had oral ulcers, 63.6% genital ulcers, 58.7% uveitis, 48% arthritis, 20.2% vascular, 21.9% neurological and 19.2% gastrointestinal involvement. Regarding HLA association, in addition to B*51 (p<10−7, OR=4.11, 95% CI 2.79 to 6.06), B*57 was found to be risk factor in this cohort with an OR similar to that provided by B*51 …
Dose-Dependent Effects of Focal Fractionated Irradiation on Secondary Malignant Neoplasms in <i>Nf1</i> Mutant Mice
Authors: Jean L. Nakamura, Connie Phong, Emile Pinarbasi, Scott C. Kogan, Scott Vandenberg, Andrew E. Horvai, Bruce A. Faddegon, Dorothea Fiedler, Kevan Shokat, Benjamin T. Houseman, Richard Chao, Russell O. Pieper, Kevin Shannon
Journal: Cancer Research (2011)

Abstract Secondary malignant neoplasms (SMN) are increasingly common complications of cancer therapy that have proven difficult to model in mice. Clinical observations suggest that the development of SMN correlates with radiation dose; however, this relationship has not been investigated systematically. We developed a novel procedure for administering fractionated cranial irradiation (CI) and investigated the incidence and spectrum of cancer in control and heterozygous Nf1 mutant mice irradiated to a moderate (15 Gy) or high dose (30 Gy). Heterozygous Nf1 inactivation cooperated with CI to induce solid tumors and myeloid malignancies, with mice developing many of the most common SMNs found in human patients. CI-induced malignancies segregated according to radiation dose as Nf1+/− mice developed predominately hematologic abnormalities after 15 Gy, whereas solid tumors predominated at 30 Gy, suggesting that radiation dose thresholds exist for hematologic and nonhematologic cancers. Genetic and biochemical studies revealed discrete patterns of somatic Nf1 and Trp53 inactivation and we observed hyperactive Ras signaling in many radiation-induced solid tumors. This technique for administering focal fractionated irradiation will facilitate mechanistic and translational studies of SMNs. Cancer Res; 71(1); 106–15. ©2011 AACR.
Inflammatory and Microbiologic Markers in Induced Sputum after Intravenous Antibiotics in Cystic Fibrosis
Authors: Claudia L. Ordoñez, Noreen R. Henig, Nicole Mayer-Hamblett, Frank J. Accurso, Jane L. Burns, James F. Chmiel, Cori L. Daines, Ronald L. Gibson, Sharon McNamara, George Z. Retsch-Bogart, Pamela L. Zeitlin, Moira L. Aitken
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Induced sputum has been used to study airway inflammation. We sought to determine whether markers of infection and inflammation in induced sputum were a useful and safe outcome measure in cystic fibrosis. We hypothesized that bacterial density and inflammatory content of induced sputum would decrease after antibiotic therapy. Induced sputum was assayed for bacterial density, cell count, and differential and inflammatory markers before and after treatment with intravenous antibiotics. Fifty-five of the 72 subjects enrolled (mean age ± SD 18.2 ± 7.9 years) completed the study. FEV1 increased by an average 0.3 ± 0.3 L (10.4 ± 8.7% predicted FEV1), p < 0.0001; density of Pseudomonas aeruginosa and Staphylococcus aureus decreased by 2.4 ± 3.1 log10 cfu/g (p < 0.0005) and 4.0 ± 2.3 log10 cfu/ml (p < 0.0001), respectively; neutrophil count decreased by 0.4 ± 0.6 log10 cells/ml (p < 0.0001), interleukin-8 concentration by 0.5 ± 1.3 log10 pg/ml (p < 0.05), and neutrophil elastase by 0.4 ± 0.7 log10 μg/ml (p < 0.005). Seven of 127 (6%) sputum induction procedures showed a decrease in FEV1 of 20% or more. We conclude that markers in induced sputum may be useful, noninvasive outcome measures to assess response to therapies in cystic fibrosis studies.
A population-based evaluation of the seventh edition of the TNM system for lung cancer
Authors: T-E. Strand, H. Rostad, T. Wentzel-Larsen, C. Von Plessen
Journal: European Respiratory Journal (2010)

Our study describes the new seventh edition of the TNM system for lung cancer in a national population and its clinical implications. We classified 1,885 operated patients with lung cancer, reported to the Cancer Registry of Norway (Oslo, Norway) from 2001 to 2005, according to the sixth and the seventh edition of the TNM system. We compared survival differences adjusting for known prognostic factors. Furthermore, we evaluated the overall predictive ability of both editions using Harrell's concordance index. Survival curves by stage for each of the editions were similar; however, a better description of stage IIIB was observed in the seventh edition. Survival rates of T1b and T2a tumours were similar (log rank p = 0.94). The concordance index was 0.68 for both editions, indicating no overall difference in their predictive accuracy. In the seventh edition, 211 (29%) stage IB patients migrated to stage II and 161 (48%) patients migrated from stage IIB to IIA. Stage migrations could change the treatment for up to 326 (17.3%) of the study patients. The seventh edition did not improve the overall predictive ability of the TNM system; however, the new classification implies changes in treatment for nearly one-fifth of the cases. The implications of the seventh TNM edition for the outcomes of patients should be studied further.
'Alarmins' S100A8 and A9 determine synovial activation and joint destruction during experimental osteoarthritis
Authors: P. L. E. M. van Lent, A. B. Blom, R. Schelbergen, A. W. Sloetjes, T. Vogl, J. Roth, W. B. van den Berg
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Prominent proteins released by activated macrophages are the 'alarmins' S100A8 and S100A9 which can further reactivate macrophages via toll-like receptor 4 forming an autocrine positive feedback loop. There is increasing belief that synovial tissue activation contributes to osteoarthritis (OA) cartilage pathology The aim is to evaluate active involvement of S100A8/A9 in cartilage destruction in experimental OA models that differ in degree of synovial activation. <h3>Methods</h3> Experimental OA was either induced by transection of the medial anterior meniscotibial ligament which leads to destabilisation of the medial meniscus (DMM) or by injection of collagenase into murine knee joints, which causes overall ligament damage and broad instability. Collagenase-induced-OA involves chronic synovial activation in contrast to DMM. Synovial expression of S100A8 and S100A9 was measured using immunolocalisation. Both models were induced in S100A9<sup>−/−</sup> deficient mice (myeloid cells also lack S100A8 at the protein level). Primary chondrocytes were stimulated with S100A8 and S100A9 and matrix metalloproteinase (MMP) levels were measured using RT-PCR. <h3>Results</h3> The function of S100A8 and S100A9 was further studied in experimental OA models. Kinetic studies show that in surgically induced DMM model, S100A8 and S100A9 was marginally expressed within the synovium, only evident at day 7 after induction and consistent with limited synovial thickening. The degree of OA cartilage pathology was similar in S100A9<sup>−/−</sup> and wild-type (WT) mice at day 42 after induction of DMM. In contrast, during the course of collagenase-induced OA, S100A8 and S100A9 was strongly upregulated in synovium at day 7 and remained high at days 14, 28 and 42. Expression of these proteins nicely correlated with thickening of the synovial lining layer comprising macrophages with an activated phenotype. When collagenase-induced-OA was elicited in S100A9<sup>−/−</sup> mice, significantly lower synovial activation was observed when compared to WT mice. Synovial activation was 62% lower at day 42. Cartilage destruction was significantly lower in all surfaces and ranged from a 45% reduction in the lateral tibia to 73% reduction in the medial femur. When primary mouse chondrocytes were stimulated with S100A8 or S100A9, a strong upregulation of particularly MMP3 mRNA level was found indicating a direct role of S100A8/A9 in cartilage destruction. <h3>Conclusions</h3> Alarmins S100A8/A9 play a crucial role in synovial activation and cartilage destruction in an OA model that shows clear synovial involvement. S100A8/A9 expression in the synovium causes pathology probably by stimulating MMP-mediated damage in the cartilage matrix. <h3>Topic</h3> Myeloid cells and innate immune receptors.
Game theory for reformation of behavioral science based on a mistake
Authors: Jeffrey Foss
Journal: Behavioral and Brain Sciences (2007)

Gintis assumes the behavioral (=social) sciences are in disarray, and so proposes a theory for their unification. Examination of the unity of the physical sciences reveals he misunderstands the unity of science in general, and so fails to see that the social sciences are already unified with the physical sciences. Another explanation of the differences between them is outlined.
Prognostic and Predictive Significance of Plasma HGF and IL-8 in a Phase III Trial of Chemoradiation with or without Tirapazamine in Locoregionally Advanced Head and Neck Cancer
Authors: Quynh-Thu Le, Richard Fisher, Kelly S. Oliner, Richard J. Young, Hongbin Cao, Christina Kong, Edward Graves, Rodney J. Hicks, Grant A. McArthur, Lester Peters, Brian O'Sullivan, Amato Giaccia, Danny Rischin
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Hepatocyte growth factor (HGF) is a hypoxia-induced secreted protein that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the role of circulating HGF and IL-8 as prognostic and predictive factors for efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin. Experimental Design: Patients with stages III to IV head and neck cancer were randomized to receive radiotherapy with cisplatin (CIS) or CIS plus TPZ (TPZ/CIS). Eligibility for the substudy included plasma sample availability for HGF and IL-8 assay by ELISA and no major radiation deviations (N = 498). Analyses included adjustment for major prognostic factors. p16INK4A staining (human papillomavirus surrogate) was carried out on available tumors. Thirty-nine patients had hypoxia imaging with 18F-fluoroazomycin arabinoside (18FAZA)–positron emission tomography. Results: Elevated IL-8 level was associated with worse overall survival (OS) irrespective of treatment. There was an interaction between HGF and treatment arm (P = 0.053); elevated HGF was associated with worse OS in the control but not in the TPZ/CIS arm. Similar trends were observed in analyses restricted to p16INK4A-negative patients. Four subgroups defined by high and low HGF/IL-8 levels were examined for TPZ effect; the test for interaction with arm was P = 0.099. TPZ/CIS seemed to be beneficial for patients with high HGF and IL-8 but adverse for low HGF and high IL-8. Only HGF correlated with 18FAZA tumor standard uptake value. Conclusions: IL-8 is an independent prognostic factor irrespective of treatment. There is an interaction between HGF and treatment arm. Certain subgroups based on IL-8/HGF levels seemed to do better with TPZ/CIS while others did worse, highlighting the complexity of hypoxia targeting in unselected patients. Clin Cancer Res; 18(6); 1798–807. ©2012 AACR.
Comparison of Primary Percutaneous Coronary Intervention and Fibrinolytic Therapy in ST-Segment-Elevation Myocardial Infarction
Authors: Thao Huynh, Stephane Perron, Jennifer O'Loughlin, Lawrence Joseph, Michel Labrecque, Jack V. Tu, Pierre Théroux
Journal: Circulation (2009)

Background— Published meta-analyses comparing primary percutaneous coronary intervention with fibrinolytic therapy in patients with ST-segment-elevation myocardial infarction include only randomized controlled trials (RCTs). We aim to obviate the limited applicability of RCTs to real-world settings by undertaking meta-analyses of both RCTs and observational studies. Methods and Results— We included all RCTs and observational studies, without language restriction, published up to May 1, 2008. We completed separate bayesian hierarchical random-effect meta-analyses for 23 RCTs (8140 patients) and 32 observational studies (185 900 patients). Primary percutaneous coronary intervention was associated with reductions in short-term (≤6-week) mortality of 34% (odds ratio, 0.66; 95% credible interval, 0.51 to 0.82) in randomized trials, and 23% lower mortality (odds ratio, 0.77; 95% credible interval, 0.62 to 0.95) in observational studies. Primary percutaneous coronary intervention was associated with reductions in stroke of 63% in RCTs and 61% in observational studies. At long-term follow-up (≥1 year), primary percutaneous coronary intervention was associated with a 24% reduction in mortality (odds ratio, 0.76; 95% credible interval, 0.58 to 0.95) and a 51% reduction in reinfarction (odds ratio, 0.49; 95% credible interval, 0.32 to 0.66) in RCTs. However, there was no conclusive benefit of primary percutaneous coronary intervention in the long term in the observational studies. Conclusions— Compared with fibrinolytic therapy, primary percutaneous coronary intervention was associated with short-term reductions in mortality, reinfarction, and stroke in ST-segment-elevation myocardial infarction. Primary percutaneous coronary intervention was associated with long-term reductions in mortality and reinfarction in RCTs, but there was no conclusive evidence for a long-term benefit in mortality and reinfarction in observational studies.
Response to Stevens and Harper
Authors: Bruce Perkins, Vera Bril
Journal: Diabetes Care (2002)

We thank Stevens and Harper (1) for their response to our study and for identifying citations that help to highlight the important issues associated with research in this field. The aim of our study (2) was to determine the best standard nerve conduction study (NCS) marker of clinical carpal tunnel syndrome (CTS), in diabetic subjects, under the hypothesis that at least one parameter would reliably identify CTS. Surprisingly, the results indicated that standard NCS techniques fail to reliably distinguish the presence or absence of CTS in subjects with diabetes. From the results, we were able to infer that the electrophysiological changes at the wrist most likely arise from diffuse nerve injury associated with diabetes rather than signifying the specific symptomatic entrapment of the median nerve. Stevens and Harper express two main concerns with the study: the methods of electrophysiological evaluation and the potential for misclassification bias in clinical CTS cases.

Stevens and Harper recommend and cite specific methods for which they suggest exclusion from the NCS evaluation invalidates our study results. We strongly feel, however, that the recommended methods either do not diverge significantly from our protocol or do not …
Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG
Authors: D. Schadendorf, S. Ugurel, B. Schuler-Thurner, F.O. Nestle, A. Enk, E.-B. Bröcker, S. Grabbe, W. Rittgen, L. Edler, A. Sucker, C. Zimpfer-Rechner, T. Berger, J. Kamarashev, G. Burg, H. Jonuleit, A. Tüttenberg, J.C. Becker, P. Keikavoussi, E. Kämpgen, G. Schuler
Journal: Annals of Oncology (2006)
Diabetes Is Not Treated as a Coronary Artery Disease Risk Equivalent
Authors: Baiju R. Shah, Janet E. Hux, Peter C. Austin
Journal: Diabetes Care (2007)

Observational studies (1–3) have suggested that the risk of mortality is equivalent for patients with myocardial infarction (MI) without previous diabetes and for diabetic patients without previous MI. Because vascular risk-reduction targets are based on a patient’s future risk, clinical practice guidelines (4–9) recommend that the same or lower blood pressure and lipid targets be applied to diabetic patients as would be applied for secondary prevention following MI. Patients newly diagnosed with diabetes and those with first MIs enter a high-risk category for subsequent coronary events. Therefore, if diabetes were treated as a coronary artery disease risk equivalent, we would expect that both groups of patients should have similar increases in utilization of antihypertensive and lipid-lowering medications following their index events.

The study used administrative health databases from Ontario, Canada, including hospital discharge abstracts, physician service claims, and records from the government drug insurance program, which covers all prescriptions filled for individuals aged ≥65 years. Individuals are linked between databases via an anonymous identification number. The study also used the Ontario Diabetes Database, a validated registry of all individuals with diabetes, derived from these administrative databases (10).

All individuals with no history of MI or diabetes were identified, and two cohorts were assembled: those …
Effects of terbutaline in combination with mannitol on mucociliary clearance
Authors: E. Daviskas, S.D. Anderson, S. Eberl, H-K. Chan, I.H. Young, J.P. Seale
Journal: European Respiratory Journal (2002)

β 2 -agonists and osmotic agents stimulate mucociliary clearance (MCC) via different mechanisms which could potentially interact. The effects of inhaling terbutaline in combination with mannitol on MCC were investigated in nine healthy (aged 19±1 yrs) and 11 mild (aged 21±4 yrs) asthmatic subjects. Using 99m Tc-sulphur colloid radioaerosol and a gamma camera, MCC was studied on four separate days with each of the following interventions: 1) terbutaline or its placebo inhaled 10 min before mannitol (in random, double blind); 2) terbutaline inhaled 5 min after mannitol; and 3) terbutaline inhaled 10 min before the control for mannitol. Lung images were collected over a period of 120 min postintervention and over 150 min in total. The mannitol-induced increase in clearance was transiently inhibited by terbutaline pretreatment and transiently enhanced when terbutaline was administered after mannitol both in asthmatic and healthy subjects. The order of administration of mannitol and terbutaline did not affect the total clearance of radioactive mucus over 140 min from the start of intervention in both groups. The pathways through which terbutaline and mannitol increase mucociliary clearance may transiently interact in an inhibitory or synergistic way, depending on the order of administration. However, this did not affect the overall increase in mucociliary clearance over 140 min.
Psychosocial Distress Screening Implementation in Cancer Care: An Analysis of Adherence, Responsiveness, and Acceptability
Authors: Brad Zebrack, Karen Kayser, Laura Sundstrom, Sue Ann Savas, Chris Henrickson, Chiara Acquati, Rebecca L. Tamas
Journal: Journal of Clinical Oncology (2015)

The American College of Surgeons Commission on Cancer has mandated implementation of a systematic protocol for psychosocial distress screening and referral as a condition for cancer center accreditation beginning in 2015. Compliance with standards requires evidence that distress screening protocols are carried out as intended and result in appropriate referral and follow-up when indicated. The purpose of this study was to examine the fidelity of distress screening protocols at two tertiary cancer treatment centers.A retrospective review and analysis of electronic medical records over a 12-week period examined clinic adherence to a prescribed distress screening protocol and responsiveness to patients whose scores on the National Comprehensive Cancer Network Distress Thermometer (DT) indicated clinically significant levels of distress requiring subsequent psychosocial contact. A weekly online survey assessed clinician perspectives on the acceptability of the protocol.Across clinics, rates of adherence to the distress screening protocol ranged from 47% to 73% of eligible patients. For patients indicating clinically significant distress (DT score ≥ 4), documentation of psychosocial contact or referral occurred, on average, 50% to 63% of the time, and was more likely to occur at one of two participating institutions when DT scores were high (DT score of 8 to 10). Clinician assessments of the protocol's utility in addressing patient concerns and responding to patient needs were generally positive.Systematic tracking of distress screening protocols is needed to demonstrate compliance with new standards of care and to demonstrate how well institutions are responding to their clinical obligation to address cancer patients' emotional and psychosocial needs.
Definition of an Immunologic Response Using the Major Histocompatibility Complex Tetramer and Enzyme-Linked Immunospot Assays
Authors: Begoña Comin-Anduix, Antonio Gualberto, John A. Glaspy, Elisabeth Seja, Maribel Ontiveros, Deborah L. Reardon, Roberto Renteria, Brigitte Englahner, James S. Economou, Jesus Gomez-Navarro, Antoni Ribas
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Define an immunologic response using the tetramer and enzyme-linked immunospot (ELISPOT) assays. Experimental Design: Ten healthy subjects and 21 patients with melanoma (all HLA-A*0201) donated a total of 121 blood samples to determine the lower limit of detection (LLD), analytic coefficient of variation (aCV), and physiologic CV (pCV) of the tetramer and ELISPOT assays. The mean, SD, and reference change value (RCV) were calculated to define changes beyond the assay imprecision, and its application was tested in the monitoring of T-cell expansion after CTLA4 blockade with ticilimumab (CP-675,206). Results: The LLD for the tetramer assay was 0.038% CD8+ cells and seven spots per 105 peripheral blood mononuclear cells for the ELISPOT assay. The aCV of the tetramer assay was &amp;lt;10% and was higher for the ELISPOT (24.69-36.32%). There was marked between-subject variability on baseline homeostatic values, which was correlated to prior antigen exposure. An immunologic response was defined as an increase beyond the mean + 3 SD in antigen-specific cells for subjects with baseline levels below the LLD, or beyond the assay RCV for baseline levels above the LLD. In four patients receiving ticilimumab, expansions of antigen-specific T cells beyond the assay variability were noted for EBV and MART1 antigens. Conclusions: A combined approach of change from negative (below the LLD) to positive (above the LLD) and a percentage change beyond the assay variability using the RCV score can be computed to define which change in circulating antigen-specific T cells represents a response to immunotherapy.