tbuckley/cabot-search huggingface dataset:
Abstract 1510: Transcriptional profiling of a lethal breast cancer tumor microenvironment
Authors: Agnieszka K. Witkiewicz, Jessica Kline, Maria Queenan, Jonathan Brody, Federica Sotgia, Aristotelis Tsirigos, Michael P. Lisanti
Journal: Cancer Research (2011)

Abstract Breast cancer growth and progression are governed by complex and reciprocal interactions between tumor cells and surrounding stromal elements. We have previously shown that a loss of stromal Cav-1 expression is associated with an increased risk of early tumor recurrence, metastasis and decreased overall survival. To identify and characterize the signaling pathways activated in Cav-1 negative tumor stroma, we performed gene expression profiling using laser micro-dissected breast cancer associated stroma. Methods: Tumor stroma was laser capture micro-dissected using a Leica LCM system from 4 cases showing high stromal Cav-1 expression and 7 cases with loss of stromal Cav-1. Total RNA was amplified using the NuGEN™ WT-Ovation™ FFPE RNA Amplification System V2 and cDNA was hybridized to Affymetrix GeneChip® arrays. One-way ANOVA was setup to extract differentially expressed genes between Cav-1 positive and negative stromal samples. Results: We identified 238 genes that were up-regulated and 232 genes that were down-regulated in the stroma of tumors showing a loss of Cav-1 expression (p-value &amp;lt; = 0.01 and fold change &amp;gt; = 1.5) Gene set enrichment analysis revealed “stemness”, inflammation, DNA damage, oxidative stress, hypoxia, autophagy, and mitochondrial dysfunction in the tumor stroma of patients lacking stromal Cav-1. Conclusions: Our findings are consistent with the recently proposed “Autophagic Tumor Stroma Model of Cancer Metabolism”. In this model, cancer cells induce oxidative stress in adjacent stromal cells, which then forces these stromal cells to undergo autophagy. This, in turn, produces recycled nutrients to feed “hungry” cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1510. doi:10.1158/1538-7445.AM2011-1510
Abstract 1415: Anti-metastatic properties of tumor-entrained neutrophils
Authors: Zvi Granot, Erik Henke, Elizabeth A. Comen, Tari A. King, Larry Norton, Robert Benezra
Journal: Cancer Research (2012)

Abstract Metastasis represents the final stage in cancer progression and is the primary cause of cancer related mortality. Disseminated cells that are capable of colonizing distant organs and forming metastases therefore present an important therapeutic challenge. In recent years, primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells (BMDCs). Here, using mouse models of breast cancer, we demonstrate that neutrophils accumulate in the lung prior to the arrival of metastatic cells. In contrast to other BMDCs that promote metastatic colonization, tumor-entrained neutrophils (TENs), but not control neutrophils, inhibit seeding of metastatic tumor cells in the lungs. TENs protect the pre-metastatic lung by initiating physical contact, generating H2O2 and killing tumor cells. While tumor secreted CCL2 has a pro-tumorigenic effect at the primary site, our data show that it is both required and sufficient for optimal anti-metastatic entrainment at the metastatic site. As tumor-secreted TGFβ blocks cytotoxicity at the primary site, TENs cytotoxicity is limited to the pre-metastatic site where TGFβ levels are low. Additionally, we find that TENs are also present in the peripheral blood of human breast cancer patients prior to surgical resection but not in healthy individuals. Several chemokines known to be increased in the circulation of breast cancer patients have the capacity to induce a cytotoxic phenotype in naïve human neutrophils, providing a possible mechanism for neutrophil entrainment in cancer patients. Taken together, our data show that while tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site. 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 1415. doi:1538-7445.AM2012-1415
The Continuing Unethical Use of Placebo Controls
Authors: K J Rothman, K B Michels
Journal: New England Journal of Medicine (1994)

Is it ethical to use a placebo? The answer to this question will depend, I suggest, upon whether there is already available an orthodox treatment of proved or accepted value. If there is such an orthodox treatment the question will hardly arise, for the doctor will wish to know whether a new treatment is more, or less, effective than the old, not that it is more effective than nothing.-- A. Bradford Hill1 Unaccountably, in these times of raised ethical consciousness, placebo treatments are still commonly used in medical research in circumstances in which their use is unethical. We refer . . .
Case 19-2014
Authors: Mark P. Gorman, Sandra P. Rincon, Virginia M. Pierce
Journal: New England Journal of Medicine (2014)

A 19-year-old woman was admitted to the pediatric ICU because of a headache, fever, photophobia, neck stiffness, and mental-status changes. She was drowsy and disoriented with respect to year. She had truncal ataxia and rotatory nystagmus, and her face and right arm were numb.
Case 49-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Andrew A. Colin, Eugene J. Mark
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 21-year-old woman was admitted to the hospital for lung transplantation because of lifelong respiratory difficulties.The patient had been born after an uncomplicated pregnancy lasting 37 weeks, weighing 2.9 kg. At two hours of age respiratory distress developed, and she was transferred to a neonatal intensive care unit. The clinical and radiologic features were consistent with hyaline membrane disease. The patient was intubated and underwent mechanical ventilation for two weeks. At the time of discharge, radiographs of the chest were reported to show that the lungs were clear. The first three years of life were characterized . . .
SP0105 Women Health Issues in Patients with Rheumatic Diseases
Authors: G. Bertsias
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Rheumatic diseases occur preferentially in women, often during the childbearing years. Women’s health may be affected by the underlying rheumatic disorder and vice versa, and this interaction is further complicated by the effects of used treatments. Important issues which often pose significant challenges to the patient and the treating physician include preservation of gonadal function and fertility, safety of contraceptive measures, in vitro fertilization and other assisted fertility measures, the management of rheumatic diseases during pregnancy and avoidance of pregnancy morbidity, and finally, management of menopause, assessment of cardiovascular morbidity, and cancer surveillance. Importantly, a multidisciplinary approach which involves rheumatologist/internists and gynecologist/obstetricians is important for proper counseling and optimal care of women with rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
THE IMPACT OF ATRIAL FIBRILLATION ON EXERCISE CAPACITY AND MORTALITY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: INSIGHTS FROM CARDIOPULMONARY STRESS TESTING
Authors: Mohamed Badreldin Elshazly, Yuping Wu, Walid Saliba, Oussama Wazni, Leslie Cho
Journal: Journal of the American College of Cardiology (2016)
Randomized Trial Comparing Aminoglutethimide With High-Dose Medroxyprogesterone Acetate in Therapy for Advanced Breast Carcinomau
Authors: P. A. Canney, T. J. Priestman, T. Griffiths, T. N. Latief, J. J. Mould, D. Spooner
Journal: JNCI Journal of the National Cancer Institute (1988)

A total of 218 postmenopausal patients were entered in a prospective randomized trial comparing aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA) as second-line hormonal therapy for advanced breast carcinoma. All responses were assessed by the criteria of the International Union Against Cancer. The response rates were 27% (29 of 106 patients) for AG and 31% (35 of 112) for MPA, but if stabilization of previously progressive disease is included, then the overall response rates were 51% (54 of 106) and 54% (61 of 112) for patients receiving AG or MPA, respectively. There was no difference in response to the two drugs at any site of disease, and the durations of response and survival were identical for the two drugs. The time to response was significantly shorter for patients treated with MPA (median, 8.7 wk) than for those treated with AG (median, 15.3 wk) (×2=9.96, 1 df, P=.0016). The percentage of patients experiencing toxic effects was equivalent in both arms, although the patterns and time courses of these effects were different [J Natl Cancer Inst 1988;80:1147–151]
Scintigraphic Pattern of Intestinal Duplication on a Meckel's Diverticulum Scan
Authors: ABDEL MONEIM OMAR, TAHANI AHMED AL-SAEE'D, ABDELHAMID ELGAZZAR
Journal: Clinical Nuclear Medicine (1998)

A 10-month-old boy had rectal bleeding. A Meckel's diverticulum radionuclide scan showed a peculiar pattern. At surgery, an intestinal duplication with cystic dilatation and perforation were found. Awareness of this pattern is important when interpreting Meckel's diverticulum scans.
Age at onset and familial risk in Alzheimer's disease
Authors: G Li, J M Silverman, C J Smith, M L Zaccario, J Schmeidler, R C Mohs, K L Davis
Journal: American Journal of Psychiatry (1995)

The authors investigated the relationship between probands' age at onset of Alzheimer's disease with the risk of primary progressive dementia in the probands' first-degree relatives.Two hundred probands with clinically diagnosed Alzheimer's disease and 179 nondemented elderly probands were recruited from the Mount Sinai Alzheimer's Disease Research Center, located at Mount Sinai Hospital and the Bronx Veterans Affairs Medical Center. Demographic and diagnostic data were collected on 1,398 of the first-degree relatives of the probands with Alzheimer's disease and 955 first-degree relatives of the nondemented probands.Cox proportional hazards regression analysis showed a significant inverse relationship between age at onset of Alzheimer's disease in probands and greater familial risk in their relatives. Follow-up analyses indicated that the most commonly used age at onset cutoff point--65 years--was one of the points where an association with familial aggregation is least likely to be revealed; other onset cutoff ages (e.g., 55, 70, and 75) better identified Alzheimer's disease groups with differing familial/genetic risks.The authors conclude that patients with an earlier age at onset of Alzheimer's disease are more likely to have relatives with Alzheimer's disease than are patients with a later age at onset of the disease. An onset age of 70 best differentiated probands whose relatives were at higher risk from those whose relatives were at lower risk.
A RANDOMIZED, ACTIVE- AND PLACEBO-CONTROLLED, THREE-PERIOD CROSSOVER TRIAL TO INVESTIGATE SHORT-TERM EFFECTS OF THE DIPEPTIDYL PEPTIDASE-4 INHIBITOR LINAGLIPTIN ON ENDOTHELIAL FUNCTION IN TYPE 2 DIABETES
Authors: Thomas W. Jax, Maximilian von Eynatten, Alin Stirban, Arne Terjung, Habib Esmaeili, Andreas Berk, Sandra Thiemann, Robert Chilton, Nikolaus Marx
Journal: Journal of the American College of Cardiology (2015)
An IMRT technique to increase therapeutic ratio of breast irradiation in patients with early stage left breast cancer: Limiting second malignancies
Authors: R. S. Ahmed, J. B. Fiveash, R. A. Popple, S. A. Spencer, J. F. De Los Santos
Journal: Journal of Clinical Oncology (2006)

10791 Background: The clinical application of IMRT for adjuvant treatment of breast cancer has been the subject of increasing study in recent years. IMRT plans have improved target coverage and reduced dose inhomogeneities observed within the breast in standard plans. IMRT was able to reduce doses delivered to the heart, lungs, and right breast at clinically significant doses, but this has been at the cost of larger volumes of low dose radiation to these structures and thus, increasing the risk for second malignancy. Our goal was to develop an IMRT beam arrangement that did not result in additional low dose spill to risk organs while maintaining equal or better target coverage. Methods: Five patients with early stage left-sided breast cancer, who underwent breast conservation surgery, and adjuvant radiation using standard wedged tangential fields, were chosen for this comparative study. An IMRT plan consisting of 6 tangential beams (3 medial and 3 lateral) was generated by using the gantry, collimator and table angles of the standard plan used for the conventional radiation (CRT), and moving the table +10 and −10 degrees on each side. The prescription dose for both CRT and IMRT plans was 45 Gy, 1.8 Gy/fraction, prescribed to the isocenter which was placed near the center of the breast. Results: IMRT plans provided significantly better coverage of the left breast than CRT plans, (p=0.03). Although dose heterogeneity was greater with the IMRT plans, the difference was not significant (p = 0.68). The mean volumes of the heart, lung, and right breast were lower in patients planned with IMRT at all dose levels from 5% to 100% dose (5% increments). This difference was significant for volumes receiving 2.25 Gy for the heart (p = 0.003), volumes receiving 2.25 Gy, 4.5 Gy, 6.75 Gy, 33.75 Gy, 36 Gy, 38.25 Gy, and 42.75 Gy for the lung (p = 0.014, 0.04, 0.044, 0.05, 0.049, 0.045, 0.05, respectively). Surprisingly, breast IMRT resulted in significantly lower right breast volumes irradiated at all dose levels compared to CRT. Conclusions: A six-tangential field IMRT technique achieved significantly better left breast coverage while maintaining lower doses to risk organs at all dose levels and therefore, reducing the potential for induction of a second malignancy. No significant financial relationships to disclose.
CATHETER-BASED RENAL DENERVATION FOR RESISTANT HYPERTENSION: 24 MONTH RESULTS OF THE ENLIGHTN I STUDY USING A MULTIELECTRODE ABLATION SYSTEM
Authors: Konstantinos P. Tsioufis, Vasilios Papademetriou, Kyriakos Dimitriadis, Alexandros Kasiakogias, Dimitrios Tsiachris, Matthew Worthley, Ajay Sinhal, Derek Chew, Ian Meredith, Yuvaraj Malaiapan, Costas Thomopoulos, Ioannis Kallikazaros, Dimitris Tousoulis, Stephen Worthley
Journal: Journal of the American College of Cardiology (2016)
PWE-072 The Effects Of Anti-tnf Therapy On Growth In Ibd In Scottish Children
Authors: FL Cameron, M Al-Towati, WM Bisset, SF Ahmed, DC Wilson, RK Russell
Journal: Gut (2014)

<h3>Introduction</h3> Growth failure is well-recognised in paediatric IBD (PIBD; &lt;18 years). Evidence (usually case series from single/multiple centres) shows anti-TNF therapies improve linear growth. We aimed to examine if anti-TNF therapy improves growth in a PIBD population-based cohort. <h3>Methods</h3> Retrospective review of all children receiving anti-TNF (infliximab (IFX) and adalimumab (ADA)) from 2000–2012 in paediatric services in Scotland. Height (Ht), weight and Tanner stage were collected at 3 times: 12 months before anti-TNF (T-12), start of anti-TNF (T0) and 12 (T+12) months after anti-TNF. Ht and growth were converted into standard deviation scores (SDS) and height velocity (HV, cm/ year) were calculated. <h3>Results</h3> 97/201 PIBD cases (3ADA, 94 IFX) had 12 month growth data, 58 (59%) males and 90 (93%) Crohn’s disease (CD); 84 (87%) received immunomodulators and 47 (48%) corticosteroids at T0. Median age at diagnosis was 10.3 years. In IFX treated, mean Ht SDS T-12 was -0.67 +/-1.1; improvement was then seen from T0 -0.82 +/-1.1 to T+12 -0.74 +/-1.1 (p = 0.031). Mean ΔHtSDS improved from -0.16 +/-0.38 at T0 to 0.08 +/- 0.36 at T+12 (p &lt; 0.001) with HV improving from 3.9 cm/yr +/-2.5 at T0 to 5.0 cm/yr +/-2.9 (p = 0.003). 56 (60%) entered remission, HtSDS improved from -0.77 +/- 1.1 at T0 to -0.56 (+/-1.1) at T+12 (p = 0.0004). ΔHtSDS improved from T0 -0.14 (+/-0.04) to 0.21 (+/-0.04) at T+12 (p &lt; 0.001) and HV from 4.0 cm/yr (+/-2.3) at T0 to 5.6cm/yr (+/-2.9) at T12 (p = 0.003). 44/94 IFX (48%) were Tanner stage 1–3; 40 CD. Mean HtSDS decreased from -1.0 (+/- 1.1) at T-12 to -1.2 (+/-1.3) at T+12 but, HV 3.6 cm/yr (+/-2.1) at T0 improved to 5.5cm/yr (+/-2.7) at T12 (p &lt; 0.001). In Tanner 4and5, no change in HtSDS or ΔHtSDS was seen. 61 (65%) had disease for ≥2 years at start of IFX, HtSDS improved from -0.77+/-1.2 at T0 to -0.65+/-1.2 at T+12 (p = 0.007) whilst disease &lt;2 years (n = 33) had no change; HtSDS -0.93+/- 0.97 at T0 and -0.92+/-0.89 at T+12 (p = 0.89). Improvement was seen in height velocity in ≥ 2; years HV 4.1+/-2.5 at T0 and 5.0+/-2.9 at T+12 (p = 0.039) compared to HV &lt;2 years 3.6+/-2.3 at T0 and 4.8+/-3.0 at T+12 (p = 0.08). Greater improvement in ΔHtSDS in ≥2 yrs; ΔHtSDS at T0 -0.12+/-0.35 improved to 0.12+/-0.33 at T+12 (p &lt; 0.001) vs. -0.22+/-0.43 at T0 to 0.16+/-0.4 (p = 0.018) for &lt;2 yrs. In UC (n = 7) no change was seen in ΔHtSDS or HV at T-12, T0 or T+12 (p 0 &gt;0.05). <h3>Conclusion</h3> Improvements in HtSDS and height velocity at 12 months were seen in the whole cohort. In Tanner 1–3 improvement was only seen in HV after 12 months with no improvement in Ht sSDS. No improvement in height noted in UC. Further follow up will determine if growth improvement is maintained or further improves. <h3>Disclosure of Interest</h3> None Declared.
Managing Scarcity: Priority Setting and Rationing in the National Health Service, by Rudolf Klein, Patricia Day, Sharon Redmayne
Authors: I. Heath
Journal: BMJ (1997)

Rudolf Klein, Patricia Day, Sharon Redmayne /Open University Press, £13.99, pp 161/ISBN 0 335 19446 X

How should individual doctors rank the needs of the different patients they encounter? In daily practice my endeavours feel very imprecise. I attempt to allocate my time roughly in proportion to the level of patients' distress and the complexity of their problem. If there is too much to do, I ration, mostly by dilution–I spread myself a little thinner, giving a little less to everyone but probably in much the same proportions. I strive not to close the door completely on anyone because to do so is to belittle their distress and their fear.

At least …
OP0023 Analysis of the Effect of Adipokines on WNT Signaling in Osteoarthritis Osteoblasts
Authors: S. Junker, G. Krumbholz, K.W. Frommer, S. Rehart, U. Lange, G. Schett, U. Müller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) is primarily characterized by cartilage and bone erosion as well as the formation of osteophytes. These processes are mediated by an increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is a recognized risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors including adipokines and bone formation. Histological analysis of OA osteophytes showed the presence of adiponectin, resistin and visfatin in osteophytes. In addition, OA osteoblasts respond to adipokines in a specific manner, e.g. adiponectin induces inflammatory mediators in these cells. These effects can be further modulated by activation of the Wnt-signaling pathway. Hence, in this context, the effects of adiponectin, resistin and visfatin on Wnt signaling in OA osteoblasts were analyzed. <h3>Methods</h3> Osteoblasts were isolated from OA bone tissue obtained during joint replacement surgery. Cultured osteoblasts were stimulated with adiponectin, resistin and visfatin. Additionally, a co-stimulation with Wnt3a or DKK1 was performed. The Wnt signaling pathway of stimulated vs. non-stimulated osteoblasts was analyzed for adipokine-mediated effects using immunoassays for IL-6, DKK1 and sclerostin, and by real-time PCR for <i>axin2</i>. <h3>Results</h3> Stimulation of OA osteoblasts with adiponectin, resistin or visfatin did not alter the release of the Wnt inhibitor DKK1 compared to the unstimulated controls. The level of the secreted Wnt inhibitor sclerostin was below the detection level of the immunoassay for both, adipokine-stimulated osteoblasts as well as for unstimulated control cells. Also, the expression of <i>axin2</i>, a direct target gene of the Wnt signaling showed no significant differences in OA osteoblasts after adipokine-stimulation compared to the unstimulated control. A co-stimulation with adiponectin, resistin or visfatin in combination with Wnt3a or DKK1 had no synergistic influence on the Wnt-mediated IL-6 release of OA osteoblasts. <h3>Conclusions</h3> The adipokines adiponectin, resistin and visfatin are present in osteoblasts in OA osteophytes, and adipokines such as adiponectin increase the release of inflammatory mediators by OA osteoblasts. However, the observed adipokine-mediated effects do not include induction of Wnt-signaling. Therefore, the involvement of adipokines in OA osteophyte formation via osteoblasts appear to be independent of Wnt signaling. <h3>Acknowledgements</h3> Funded by the ANCYLOSS project of the German Ministry of Research and Education (BMBF). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3701
Fasting makes little difference to results of lipid tests
Authors: L. Anekwe
Journal: BMJ (2012)

Fasting before routine lipid level tests might be unnecessary, suggests a study that found that fasting time had little association with lipid subclass levels in a large population.

The researchers, from Calgary in Alberta, Canada, looked at the relationship between fasting duration and lipid test results over a six month period in 2011 in 209 180 people.

They found that among average cholesterol levels the mean levels of total cholesterol and high-density lipoprotein (HDL) differed little among …