tbuckley/cabot-search huggingface dataset:
P262 Age and Gender Specific Differences in Excessive Daytime Sleepiness
Authors: P Drakatos, I Jarrold, J Harris, A Abidi, A Douiri, N Hart, C Kosky, A Williams, J Steier
Journal: Thorax (2012)

<h3>Introduction</h3> The pictorial Epworth Sleepiness Scale (ESS) (Ghiassi et al., Thorax 2011) has been developed and validated against the traditional ESS and allows subjects to intuitively answer the questions related to daytime sleepiness with pictorial items. Although non-specific, the ESS has been validated for sleep apnoea patients and it is widely used for screening patients. We hypothesised that the use of an online pictorial ESS can promote public awareness and help to screen for patients with undiagnosed sleep disorders. <h3>Methods</h3> Between 2011 and 2012, we collected the pictorial ESS data of 24,272 subjects on the official webpage of the British Lung Foundation. Following a short explanation to the questionnaire, eight items are marked and given a score from `0` (not likely todoze) to `3` (very likely to doze) using pictorial items, the range of the total score for the pictorial ESS being `0` to `24`. The cut-off for excessive daytime sleepiness (EDS, more than 10 points) was chosen in line with the traditional ESS. In 3,265 questionnaires the subjects’ age and gender were also recorded (starting from 03/2012). Chi-square test was used to compare the proportion of different groups. <h3>Results</h3> The total 24,272 subjects scored a mean of 9.3 (5.1) points on the pictorial ESS. Of those, 38.0% were excessively sleepy (14.6 (3.2) points) and 62.0% had normal levels of sleepiness (5.9 (2.7) points, p&lt;0.001). In the 3,265 subjects with age and gender recorded, there was no significant difference in the prevalence of excessive daytime sleepiness between genders (42.8% vs 43.9%, p=0.68). When age was considered, females tended to be sleepier than males in their 3rd and 4th lifetime decade (p&lt;0.02), whilst males scored significantly higher in the 7th decade (p&lt;0.0001, Figure); there was a statistically significant trend with age (p-value for trend p&lt;0.001) <h3>Conclusion</h3> The online pictorial ESS identifies gender differences in EDS on a large scale and reveals more severe levels of sleepiness associated with higher age. The use of modern media facilitates reaching out to the general population to raise awareness of conditions associated with daytime sleepiness such as sleep apnoea.
AB1098 Autoimmune Disease and Cancer: Results from A Retrospective Cohort
Authors: S. Pier Paolo, E. Boggio, M. Gentile, E. Merlotti, D. Sola, R. Luca, M. Pirisi, M. Bellan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The pathogenetical association between autoimmunity and cancer has been previously described. <h3>Objectives</h3> In this study we aimed to better describe the complex relationship between autoimmunity and neoplastic diseases in a retrospective cohort from our outpatient Immunorheumatology clinic. In particular we aimed to identify those immune conditions the diagnosis of which is associated to an increased risk of being diagnosed for a cancer within 2 years before and after the rheumatological syndrome onset. <h3>Methods</h3> We evaluated 3975 clinical records from 1st January 2005 to 30th November 2012. We used non immune-mediated conditions (fibromyalgia and osteoarthritis) as controls. We included in the analysis only patients with at least 2 years of follow-up. <h3>Results</h3> We reported 144/1750 cases of cancer in the general population (8.2% [6.91 – 9.49]), 41/702 of which (5.9% [4.16–7.64]) in control group. The prevalence of cancer was increased in patients affected by Sjogren9s Syndrome (18.3% [8.52–28.08]; OR 3.62 [1.75–7.48]), Dermatomyositis/Polimyositis (42.9% [6.24–79.56]; 12.09 [2.65–55.8]), Vasculitis (18.8% [9.23–28.37]; 3.70 [1.81–7.52]) and Polimyalgia Rheumatica (24.0% [15.63–32.37]; 5.09 [2.92–8.88]). Logistic regression identified all these diagnosis, age &gt;65 and male sex as independent risk factors for neoplastic disease. <h3>Conclusions</h3> DM/PM, vasculitis and PMR show an increased risk of neoplasms during the whole observation period and a high prevalence of symptoms remission after cancer treatment as expected for a paraneoplastic manifestation; vice versa Sjogren9s Syndrome seems to be more likely a causal factor for cancer (in particular lymphoma), since the risk is increased exclusively in the prospective follow-up and the treatment of cancer is not associated to a remission of rheumatological symptoms. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1955
SP0059 The Role of Nutrition Upon Osteoarthritis and Inflammation
Authors: M. T. Hannan
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> This session will discuss the role that nutrition has in osteoarthritis. The speaker will cover 4 aspects of the links between nutrition and OA, specifically: 1: to describe latest advances in the understanding of nutrition upon OA 2: to present evidence on the relationship between nutrition and pre- and post-OA onset, specifically with insights on patient characteristics 3: to discuss how nutrition may interact with joint pain, inflammation and limitations in OA 4: to critique the use of patient-oriented nutritional assessment and OA in clinical practice The key message of this session is that nutritional intakes influence OA and play a role in the management of the disease, patient decisions about inclusion or exclusion of specific foods, and influences the major components of OA, namely pain, inflammation, physical activity and physical limitations and possibly bony growths. <h3>Disclosure of Interest</h3> None Declared
Consumer-Choice Health Plan
Authors: Alain C. Enthoven
Journal: New England Journal of Medicine (1978)

The financing system for medical costs in this country suffers from severe inflation and inequity. The tax-supported system of fee for service for doctors, third-party intermediaries and cost reimbursement for hospitals produces inflation by rewarding cost-increasing behavior and failing to provide incentives for economy. The system is inequitable because the government pays more on behalf of those who choose more costly systems of care, because tax benefits subsidize the health insurance of the well-to-do, while not helping many low-income people, and because employment health insurance does not guarantee continuity of coverage and is regressive in its financing. Analysis of previous proposals for national health insurance shows none to be capable of solving most of these problems. Direct economic regulation by government will not improve the situation. Cost controls through incentives and regulated competition in the private sector are most likely to be effective.
Abstract 4847: CD95/Fas protects cancer cells from cell death
Authors: Abbas Hadji, Annika Hau, Marcus E. Peter
Journal: Cancer Research (2012)

Abstract CD95 (also called Fas and APO-1) is a prototypical death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis. During cancer progression CD95 is frequently downregulated or cells are rendered apoptosis resistant, raising the possibility that loss of CD95 is part of a mechanism for tumor evasion. However, complete loss of CD95 is rarely seen in human cancer and many cancer cells express large quantities of CD95 and are highly sensitive to CD95-mediated apoptosis in vitro. Furthermore, cancer patients frequently have raised levels of the physiological ligand for CD95, CD95L. These data raise the possibility that CD95 could actually promote the growth of tumors through its non-apoptotic activities. We have recently shown that cancer cells in general, regardless of their CD95 apoptosis sensitivity, depend on constitutive activity of CD95, stimulated by cancer-produced CD95L, for optimal growth (1). Consistently, loss of CD95 in mouse models of ovarian cancer and liver cancer reduces cancer incidence as well as the size of the tumors. We have now generated inducible CD95 and CD95L knock down cell lines to characterize the molecular mechanisms of the dependency of cancer cells on CD95. In all cancer cells knocking down CD95 or CD95L slows down growth and in many cells causes cell cycle arrest and even cell death. In CT26L cells knock down of CD95L causes all cells to die within 2 days. This form of cell death cannot be inhibited by inhibitors of apoptosis or necroptosis and has features of mitotic catastrophe. The data suggest that CD95 maintains viability of cancer cells by preventing DNA damage. 1. Chen et al (2010) CD95 promotes tumor growth. Nature, 465, 492-496. 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 4847. doi:1538-7445.AM2012-4847
Impaired c-Met Receptor Degradation Mediated by <i>MET</i> Exon 14 Mutations in Non–Small-Cell Lung Cancer
Authors: Mark M. Awad
Journal: Journal of Clinical Oncology (2016)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations. July 27, 2015 ARTICLE CITATION DOI: 10.1200/JCO.2015.64.2777 Journal of Clinical Oncology - published online before print January 19, 2016 PMID: 26786927 Impaired c-Met Receptor Degradation Mediated by MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Mark M. AwadxMark M. AwadSearch for articles by this author Show More Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2015.64.2777 First Page Full Text PDF Figures and Tables © 2016 by American Society of Clinical Oncology Companion Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations
Rosette Inhibition Test for the Demonstration of Thymus-Dependent Lymphocyte Sensitization in Graves's Disease and Hashimoto's Thyroiditis
Authors: Nadir R. Farid, Robert E. Munro, Vas V. Row, Robert Volpé
Journal: New England Journal of Medicine (1973)

Abstract To study subpopulations of peripheral sensitized thymus-dependent lymphocytes (in addition to total thymus-dependent lymphocyte counts) in Graves's  and Hashimoto's thyroiditis, we employed a nonimmune-rosette  test, using antihuman thymocyte globulin; the thymocyte globulin concentration causing 25 per cent rosette  (relative to nonimmune-rosette counts without globulin) was taken as the end point (inhibition concentration). Mean inhibition concentrations (± S.D.) were as follows: in 11 controls, 482 ± 31 ng per milliliter; in 12 untreated patients with Graves's disease, 1098 ± 162; and in 11 with Hashimoto's thyroiditis, 2436 ± 661. Despite normal total thymus-dependent lymphocyte counts, smaller (but statistically significant) elevations were also found in euthyroid ophthalmic Graves's disease and in apparently normal persons with circulating thyroid antibodies. Hyperthyroidism due to toxic adenoma yielded normal results. Patients with Graves's  in remis...
Regulators of Mitotic Transition Determine Paclitaxel Resistance <i>In Vitro</i> and Predict Poor Prognosis in Breast Cancer <i>In Vivo.</i>
Authors: R. Burrell, S. McClelland, N. Juul, J. Downward, Z. Szallasi, Z. Szallasi, C. Swanton, C. Swanton
Journal: Cancer Research (2009)

Abstract We have previously identified 25 kinases that regulate sensitivity to the microtubule-stabilising drug, paclitaxel (Swanton et al., 2007). Silencing these kinases by small-interfering RNA (siRNA), results in resistance to paclitaxel-induced cytotoxicity and dramatic alterations in DNA ploidy, multinucleation and centrosome amplification independent of drug treatment. These data suggest that the molecular pathways that maintain chromosome stability and mitotic fidelity are required for paclitaxel sensitivity. To further address this, we have investigated the function of the 25 kinases in mitosis, using a combination of fixed and live-cell microscopy. Several of these genes regulate mitotic progression and the formation of a bipolar mitotic spindle, and upon depletion, lead to increased rates of chromosome missegregation during anaphase. This supports the hypothesis that mechanisms of chromosomal instability that are common in cancer cells, predispose to paclitaxel resistance. In order to assess the in vivo relevance of these kinases we examined whether lower expression held prognostic power across several breast cancer datasets. Notably low expression of MAST3, CAMK1 and SKAP1 correlates with poor prognosis in breast cancer in vivo (P&amp;lt;0.05). Interestingly, MAST3 and CAMK1 have strikingly similar mitotic phenotypes after silencing; cells arrest in early mitosis and show an increased frequency of anaphase errors that may contribute to chromosomal instability. In summary, we have identified novel regulators of mitotic transition that may be important for maintaining chromosomal stability. These kinases influence taxane sensitivity in vitro and hold prognostic power in breast cancer patients in vivo.ReferencesSwanton, C., Marani, M., Pardo, O., Warne, P.H., Kelly, G., Sahai, E., Elustondo, F., Chang, J., Temple, J., Ahmed, A.A., et al. (2007). Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell 11, 498-512 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2151.
Spontaneous disappearance of a giant colonic lipoma after endoscopic biopsy
Authors: S. Ishiyama, Y. Tashiro, K. Nagayasu, K. Niwa, S. Ono, K. Sugimoto, M. Hata, H. Kamiyama, H. Komiyama, M. Takahashi, Y. Yaginuma, Y. Kojima, M. Goto, M. Tanaka, H. Sengoku, A. Okuzawa, Y. Tomiki, K. Sakamoto
Journal: Endoscopy (2011)

A giant colonic lipoma was found in a 38-year-old man who presented with hematochezia and intermittent abdominal pain. Colonoscopy revealed a submucosal tumor with ulceration in the transverse colon ([Fig. 1 a]).
Are gods and good governments culturally and psychologically interchangeable?
Authors: Robert N McCauley
Journal: Behavioral and Brain Sciences (2016)

Abstract Cognitive by-product theorists maintain that standard cognitive development facilitates the acquisition of religion. Citing secularization, Norenzayan et al. qualify that theory, proposing that gods and good governments are psychologically and culturally interchangeable. That contention, though, occasions questions about the psychological dynamics involved, about what qualifies as religiosity, and about asymmetries between gods and good governments in the face of catastrophes.
P660Molecular insight in apoM-S1P-induced cardioprotection against ischemia/reperfusion injury
Authors: S Morel, C Christoffersen, V Rochemont, F Montecucco, M Frias, G Pelli, F Mach, RW James, LB Nielsen, BR Kwak
Journal: Cardiovascular Research (2014)

Purpose: Apolipoprotein M (apoM) is a plasma lipoprotein that mainly associates with high-density lipoproteins (HDL) and that serves as a carrier of the bioactive lipid Sphingosine-1-Phosphate (S1P). Recent studies indicate that S1P binding to G-protein-coupled receptors, known as S1P-receptors, in the heart activates signalling pathways promoting cardiomyocyte survival, but downstream targets are largely unknown. Here, we investigate the putative role of the apoM-S1P axis in relation to cardioprotection against ischemia/reperfusion (IR) injury. Methods and Results: ApoM transgenic (Apom-Tg) mice, in which plasma S1P is increased by >250%, and wild-type (WT) mice were subjected to 30 min of left coronary artery ligation and 24 hrs reperfusion in vivo. We found a reduction of infarct size in Apom-Tg mice (15±1%) in comparison with WT mice (29±4%, N=8-9, p<0.01). In agreement, neutrophil infiltration into the infarcted area was lower in Apom-Tg mice (14.8±0.2% vs. 25.9±5.1 in WT, N=3, p<0.05). Interestingly, 5 min of S1P treatment at the onset of reperfusion reduced infarct size in response to 30 min of no-flow global ischemia (control: 23±3%, S1P-treated: 11±2%, N=5, p<0.05) in ex vivo Langendorff perfused hearts, suggesting that S1P exerts a direct protective effect on cardiomyocytes. Moreover, the sensitivity to ex vivo IR of Apom-Tg mice was not different from WT mice, further supporting that the cardioprotective effect observed in vivo is due to increased plasmatic S1P in these mice. To obtain further insight into the mechanism underlying S1P-induced cardioprotection, neonatal rat ventricular cardiomyocytes were treated for 5 min with S1P after pre-incubation with PKC kinase inhibitors or with specific antagonists of S1P receptors. We found by Western blot that S1P induced phosphorylation of the gap junction protein Connexin43 (Cx43) on Serine 368 by a PKC-dependent mechanism and that this phosphorylation was mediated by S1P2 and S1P3 but not by S1P1 receptors. Finally, 5 min of S1P treatment reduced gap junctional communication between cardiomyocytes (9±1 cells, N=29) in comparison to control conditions (15±2 cells, N=34, p<0.01), as assessed by dye coupling assay. Conclusion: Increased plasma apoM-S1P in mice protects the heart against IR injury. The molecular mechanism might involve reduced cardiomyocyte death by activation of S1P2 and S1P3 receptors, which leads to PKC-dependent phosphorylation of Cx43 and reduction of cell-to-cell coupling.
SAT0573 Spatial Association of Subchondral Osteosclerosis and Immune Cell Infiltration in Osteoarthritis
Authors: J. Geurts, B. Pippenger, M.T. Hirschmann, M. Müller-Gerbl, V. Valderrabano, T. Hügle
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Subchondral bone sclerosis is a well known and potentially reversible feature of knee osteoarthritis (OA). The infiltration of immune cells into the subchondral bone in OA has been demonstrated previously. However, the exact assocation between immune cell infiltration and osteosclerosis, as well as their functional connection, remain elusive. <h3>Objectives</h3> To investigate whether the interaction between bone and immune systems might be involved in the regulation of subchondral osteosclerosis in human OA. <h3>Methods</h3> Computed tomography osteoabsorptiometry (CT-OAM) mapping of subchondral bone mineralization density (BMD) distribution was used to guide tissue preparation from nonsclerotic and sclerotic areas of explanted OA tibial plateaus. Cartilage degeneration and subchondral bone area fraction (B.Ar./T.Ar.) were evaluated using histomorphometric analyses. Presence of lymphocytes, macrophages and osteoclasts in subchondral bone marrow tissue was investigated using (immuno)histological and flow cytometry analyses for expression of CD3, CD20, CD68 and tartrateresistant acid phosphatase (TRAP). Alkaline phosphatase (ALP) activity was assessed in primary OA osteoblasts stimulated with conditioned medium from nonsclerotic and sclerotic subchondral bone. <h3>Results</h3> Subchondral BMD distribution was heterogeneous and displayed focal areas of high density that macroscopically showed severe cartilage degeneration. Histomorphometry demonstrated a strong positive correlation between Mankin score and subchondral B.Ar/T.Ar. Immunohistological and flow cytometry analyses of subchondral bone marrow tissue showed a highly specific increase in CD68pos macrophages and multinucleated cells and CD20pos B-lymphocytes in sclerotic compared with nonsclerotic subchondral bone. Correspondingly, increased numbers of functional TRAPpos osteoclasts associating with CD34pos vascular structures were detected. Sclerotic OA osteoblasts showed increased basal alkaline (ALP) phosphate activity. Conditioned medium from sclerotic bone pieces, unlike nonsclerotic bone pieces, failed to induce osteoblastic ALP activity. <h3>Conclusions</h3> Enhanced marrow immune cell infiltration and osteoclast activity, along with phenotypic alterations in osteoblasts are involved in uncoupled and aberrant bone remodeling. This indicates that immune cells induce a 9resorbtive state9 as a potential repair mechanism. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2863
Pseudoaneurysm of a Pancreas Allograft Artery Detected by 99mTc Red Blood Cell SPECT/CT
Authors: Muge Tamam, Akiva Mintz
Journal: Clinical Nuclear Medicine (2015)

We present a case of obscure gastrointestinal bleeding associated with a large pseudoaneurysm in the splenic artery after simultaneous kidney-pancreas transplantation. Planar 99mTc red blood cell (RBC) scintigraphy demonstrated a focus of increased activity in the mid-abdomen, which was confirmed by SPECT/CT to be in the region of the pancreatic transplant. Subsequent diagnostic CT angiography of the abdomen identified a large pseudoaneurysm of the pancreas allograft splenic artery. At surgery, an arterial-enteric fistula was confirmed at the site of aneurysm coiling, and this segment of bowel was removed.
Abstract PD04-03: Circulating Tumor Cells as Predictor of Metastatic Disease Spread in Patients with Breast Cancer
Authors: M Giuliano, A Giordano, BC Handy, NT Ueno, RH Alvarez, GN Hortobagyi, JM Reuben, V Valero, M. Cristofanilli
Journal: Cancer Research (2010)

Abstract Background. The formation of distant metastases in each tissue is a tightly regulated biological event. The characteristic organ distribution of metastasis in the various cancers was first recognized in 1889 by Paget and gave rise to the “ seed and soil “ hypothesis. Several reports demonstrate that the presence of more than 5 circulating tumor cells (CTC) in peripheral blood is associated with short survival in patients (pts) with metastatic breast cancer (MBC). Interestingly, pts with bone metastasis had higher absolute number and percentage of ≥5 CTC (De Giorgi et al. 2010). Because of the correlation between CTC detection, metastatic site and prognosis, we hypothesized that the baseline detection of ≥5 CTC at the time of initial recurrence can predict the development of new metastatic sites, when progression of disease occurs. Methods. We retrospectively evaluated a cohort of 516 MBC pts who had a CTC assessment before starting systemic treatment at the M.D. Anderson Cancer Center between September 2004 and November 2009. CTC were enumerated using the CellSearch™ technology. Among all pts, we selected 408 women with documented radiological progression of disease defined according to RECIST. Pts were divided in 2 categories: subjects who experienced progression of the pre-existing metastatic site(s) and those who developed new metastatic site(s). The rate of development of new metastatic sites was compared between groups according to baseline value of CTC (&amp;lt;5 vs of ≥5), by Fisher Exact Test. Results. At a median follow-up of 16 months (range, 1-58), 168 (41%) pts had died. The estimated overall survival was 28.6 months for pts with &amp;lt;5 CTC and 19.1 months for those with ≥5 CTC (log-rank P=.001). The rates of development of new metastatic sites according to baseline value of CTC, and stratified by the original sites of disease are shown in table 1. Fifty-three (22%) pts with &amp;lt;5 CTC and 52 (32%) with ≥5 CTC developed new metastatic sites when progression of disease was documented (P=.028). Pts presenting with baseline CTC ≥5, and bone metastases without visceral involvement had the highest rate of development of new metastatic sites. Conclusions. Our analysis indicates that the presence of a high number of CTC before starting systemic treatment can predict for a higher probability to develop new metastatic sites on progression. This finding seems to be largely limited to pts with bone involvement at baseline. Our results may suggest the need to evaluate more effective bone-directed therapies for MBC pts with ≥5 CTC in order to prevent further progression of disease. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-03.