tbuckley/cabot-search huggingface dataset:
Understanding self-deception demands a co-evolutionary framework
Authors: Steven W. Gangestad
Journal: Behavioral and Brain Sciences (2011)

Abstract The foundational theme of the target article is that processes of self-deception occur in a functional context: a social one through which self-deceptive processes enhance fitness by affecting an actor's performances. One essential component of this context not addressed explicitly is that audiences should have been selected to resist, where possible, enhancements falsely bolstered by self-deception. Theoretical implications follow.
Tolerable Risks? Physicians and Youth Tackle Football
Authors: Kathleen E. Bachynski
Journal: New England Journal of Medicine (2016)

Interview with Dr. Steven DeKosky on youth football, head injuries, and a recent American Academy of Pediatrics policy statement. (12:53)Download Despite finding that eliminating tackling from youth football would probably reduce the incidence of concussions and other severe injuries, the American Academy of Pediatrics has merely proposed enhancing adult supervision of the sport.
Risk Factors for Injury to Women from Domestic Violence
Authors: Demetrios N. Kyriacou, Deirdre Anglin, Ellen Taliaferro, Susan Stone, Toni Tubb, Judith A. Linden, Robert Muelleman, Erik Barton, Jess F. Kraus
Journal: New England Journal of Medicine (1999)

Domestic violence is the most common cause of nonfatal injury to women in the United States. To identify risk factors for such injuries, we examined the socioeconomic and behavioral characteristics of women who were victims of domestic violence and the men who injured them.
SP0003 What is New in Spondyloarthritis
Authors: R. Lories
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The recent seminal discovery that an interleukin-23 (IL23) receptor positive T cell population is present in tendon and ligament attachment sites and that these cells contribute to spondyloarthritis-like joint inflammation in mice, has transformed current paradigms of the human disease. These attachment sites, commonly referred to as entheses, were earlier suggested as primary disease localization in SpA but their role in the development of chronic inflammation remained elusive. The IL23 responsive T cell population identified by Sherlock et al., is proposed as a key mediator or masterswitch in the disease process by triggering downstream inflammatory cascades as well as joint remodeling, the Janus-faced characteristics of spondyloarthritis. Interestingly the novel paradigm centered around this unexpected cell population is corroborated by further progress in genetics of spondyloarthritis, highlighted by clearly mapped molecular interactions and pathway integration. From the clinical perspective, accumulating datasets on non-radiographic axial spondyloarthritis not only support the success of anti-TNF strategies in case of failure to achieve symptom control with classical anti-inflammatory drug, but additionally trigger novel questions on the epidemiology of disease. Data obtained in cohorts of early disease patients shed new light on the demographics and likely evolution of the disease. Biomarker research is rapidly growing and a number of novel molecules may find their way into clinical practice over time provided that the original datasets linking serum levels to radiographic progression of disease can be confirmed. With regards to the much feared radiographic progression and evolution towards ankylosis, additional evidence for a structural effect associated with non-steroidal anti-inflammatory drugs has been presented. From the therapeutic perspective, novel strategies are eagerly awaited with preliminary evidence suggesting clinical responses in patients treated with anti-interleukin 17 strategies. Early phase clinical trial data also point towards apremilast, a phosphodiesterase inhibitor as a drug that needs to be further studied. In summary, over the last year, paradigm-shifting data have been published in the field of spondyloarthritis not only leading to novel insights into the pathophysiology but also defining novel and attractive therapeutic targets thereby suggesting that the next phase in spondyloarthritis research and therapy may be on the horizon. <h3>Disclosure of Interest</h3> None Declared
Mechanism of adenosine-mediated decreases in glomerular filtration rate in dogs.
Authors: H Osswald, W S Spielman, F G Knox
Journal: Circulation Research (1978)

This study evaluates the contributions of pre-and postglomerular resistances and glomerular capillary ultrafiltration coefficient (K f ) in adenosine-induced decreases in glomerular filtration rate (GFR).Experiments were performed on 19 dogs prepared for micropuncture.Whole kidney and superficial nephron functions were measured before and during adenosine infusion (0.1 /umol/min) into the renal artery.Whole kidney GFR decreased from 29.0 ± 1.7 to 23.1 ± 1.6 (SE) ml/min (P< 0.003).Renal plasma flow (RPF) increased slightly from 98 ± 6 to 108 ± 8 ml/min (P< 0.05), resulting in a decreased filtration fraction from 0.30 ± 0.02 to 0.22 ± 0.02.Superficial single nephron GFR and plasma flow decreased from 68.8 ± 5.2 to 39.9 ± 6.4 nl/min (P < 0.001) and from 206 ± 28 to 128 ± 17 nl/min (P < 0.01), respectively.Free flow and stop flow pressures in proximal tubules decreased from 23 ± 1 to 16 ± 1 mm Hg and from 44 ± 1 to 31 ± 2 mm Hg, respectively.K f was not significantly changed (2.55 ± 0.22 vs. 3.12 ± 0.88 nl/min per mm Hg).The hydrostatic pressures in efferent arterioles decreased from 14 ± 0.6 to 10.4 ± 1.8 mm Hg (P < 0.01).The resistance in the afferent arterioles increased more than 2-fold from 1.38 ± 0.25 to 3.04 ± 0.42 • 10 10 dynes • sec • cm" 5 (P < 0.003), whereas efferent arteriolar resistance was only slightly increased from 1.35 ± 0.18 to 1.76 ± 0.17.We conclude that intrarenal infusion of adenosine preferentially constricts the afferent arterioles of the superficial cortex and thereby decreases superficial GFR without decreases in glomerular capillary ultrafiltration coefficient.
Gabexate for the Prevention of Pancreatic Damage Related to Endoscopic Retrograde Cholangiopancreatography
Authors: Giorgio Cavallini, Alberto Tittobello, Luca Frulloni, Enzo Masci, Alberto Mariani, Vincenzo Di Francesco
Journal: New England Journal of Medicine (1996)

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP.
Website of the week: Drivers' visual acuity
Authors: Douglas Carnall
Journal: BMJ (2000)

Adequate vision is plainly a prerequisite for driving a motor vehicle, but this week a paper in the BMJ shows that measuring adequacy is far from straightforward. Snellen charts are used to assess visual acuity in the clinic, but the actual standard required—reading a car licence plate at 20.5 metres—does not correlate perfectly with acuity measured by a Snellen chart. This is a problem, as about a quarter of people with 6/9 vision would fail the Driver and Vehicle Licensing Agency's test, and about a third of people with only 6/12 vision would still pass.

The ability to read a licence plate is a straightforward objective test. The Driver and Vehicle Licensing Agency makes its booklet Medical Aspects of Fitness to Drive available on the internet: www.dvla.gov.uk/at_a_glance/ch6_visual.htm. Plainly it is sensible that people with poor visual acuity or visual field defects do not drive. Internationally, the rules seem similar: the Canadians, for example, seem to require the slightly laxer standard of 6/15 for personal driving (www.eyesite.ca/info/Drivingstd.html), but there seems to be little empirical evidence for the standards that are set, although simulator studies suggest that reducing visual acuity is likely to reduce driving skill (www.lighthouse.org/vresearch_program_driving.htm).

Impaired eyesight often accompanies increasing age. At www.howtocare.com/driving.html relatives who care for elderly people are advised that “unexplained dents in the car” may be among the signs of unfitness to drive.

Let's hope the dents aren't child shaped. Road traffic fatalities are the eighth commonest cause of death worldwide (www.trl.co.uk/dumas/accident.htm), and many are caused by drivers whose visual acuity is fine but who drive too fast. There are none so blind as those who will not see.
LONG TERM OUTCOMES IN DOUBLE INLET LEFT VENTRICLE AND TRICUSPID ATRESIA WITH TRANSPOSED GREAT VESSELS
Authors: David S. Winlaw, Lotte Franken, Manouk Admiraal, Julian Ayer, Ajay Iyengar, Andrew Cole, Christian Brizard, Gary Sholler, Yves d’Udekem
Journal: Journal of the American College of Cardiology (2015)
Metabolic Syndrome in Breast Cancer: Paracrine Mediators in Mammary Adipose Tissue Mediated by Metabolic Dysfunction Influence Tumour Cell Proliferation.
Authors: P. Carroll, P. Carroll, L. Healy, J. Lysaght, D. Ennis, B. Dunne, M. Griffin, T. Boyle, J. Kennedy, G. Pidgeon, G. Pidgeon, E. Connolly, E. Connolly
Journal: Cancer Research (2009)

Abstract Introduction:Obesity and it's associated metabolic syndrome are known epidemiological risk factors for breast cancer.¹ Adipose tissue is a potent endocrine organ secreting many factors that can potentially regulate tumour growth. The breast constitutes an excellent model to determine the paracrine mediators of adiposity on breast cancer. The aim of this preliminary study was thus to describe the adipocytokine milieu in the breast and determine what influence adiposity and metabolic dysfunction played in tumour progression.Methods:Adipose conditioned media (ACM) was produced by harvesting adipose tissue from sites adjacent to (peritumoural PT) and distal (D) to tumour in 20 fresh mastectomy specimens and cultured in serum free media for 72hrs. MDA-MB 231 and MCF-7 cell lines were then cultured with this ACM for 24-48hrs. Cell survival/proliferation was determined by BrDU assay. An in depth characterisation of adipocytokine production from each adipose depot was performed using multiplex bead arrays.Results:ACM from peritumoural/distal adipose tissue promoted cell proliferation in both cell lines. The greatest proliferative effect was observed in ER+ve MCF-7 cell line relative to controls (151.9±7.3% and 150.8±9.8% in peritumoural and distal ACM respectively), compared to ER-ve MDA-MB-231 cells (111.4±5.0, 112.0±2.5%).PT ACM from metabolically unhealthy/obese patients significantly increased proliferation in MCF-7 cells, compared to normal weight cancer patients (171±12.6% vs 135.3±9.3%, p=0.034). Similarly, adipocytokine expression reflected these changes with expression differences in IL-6 (6.72±0.09, 6.31±0.16 ng/ml p=0.028), HGF (7.5±1.3, 3.98±0.43 ng/ml p=0.028).Conclusion:Peritumoural adipose tissue from metabolically unhealthy and obese patients increased cell proliferation compared to normal weight patients. Metabolic dysfunction influenced expression of several adipocytokines in ACM. A thorough analysis of this milieu should lead to a greater understanding of how obesity/metabolic dysfunction regulate tumourigenesis in breast cancer.References:1: Lahmann PH et al: Body size and breast cancer risk: findings from the European Prospective Investigation into cancer and Nutrition (EPIC) International J Cancer 111: 762-771 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5150.
Abstract LB-408: NAT2 polymorphisms, tobacco smoking, and breast cancer risk in the Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: David G. Cox, Lucie Dostal, David J. Hunter, Regina G. Ziegler, Loïc LeMarchand, Michael J. Thun
Journal: Cancer Research (2010)

Abstract Aromatic and heterocyclic amines are carcinogens in tobacco smoke that cause mammary tumors in rodents. N-acetyltransferase 2 (NAT2) can detoxy aromatic amines and polymorphisms in the NAT2 gene result in slow, intermediate and rapid acetylation phenotypes. Slow NAT2 acetylation has been hypothesized to potentiate the risk of smoking for both breast and bladder cancer. Whereas this hypothesis is reasonably well-established for bladder cancer, the data for breast cancer are still being evaluated, most recently in a meta-analysis of up to 13 studies. In a subset of these studies including 4,264 cases, a ∼1.4 fold increase in risk of breast cancer was observed among women exposed to more than 20 pack-years of cigarette smoking. This increase in risk was confined to slow acetylators, and no statistically significant increase in risk was observed among rapid acetylators. We sought to replicate this finding in a consortium of six large prospective cohorts in the United States and Europe. We genotyped the three most common polymorphisms that define NAT2 acetylation phenotype in populations of European origin among approximately 7,750 breast cancer cases and 9,900 matched controls with prospectively collected information on tobacco smoking and established risk factors for breast cancer. Nested case-control analyses showed no association between NAT2 acetylation phenotype (rapid, intermediate, slow) and breast cancer risk. Furthermore, no interaction was observed between smoking status (specifically never, former or current) and NAT2 acetylation phenotype on breast cancer risk (likelihood ratio test p-interaction 0.58). Ongoing analyses are examining more detailed measures of cigarette smoking such as duration, intensity, pack years, and smoking during the potentially critical period between menarche and first full term pregnancy, as well as subsets of patients defined by menopausal or steroid hormone receptor status. These data contribute substantially to resolving the longstanding debate over whether smoking affects breast cancer risk particularly in women with limited capacity to acetylate tobacco carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-408.
FRI0180 Higher likelihood of response in rheumatoid arthritis patients treated in a real-life setting with adalimumab in combination with methotrexate, but not with other dmards, versus adalimumab monotherapy
Authors: P. Kiely, S. Florentinus, S. Keidel, A. Lacerda, M. Karunaratne, R. McCaskill
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Clinical trial data support the superiority of combining adalimumab (ADA) with DMARD(s) vs ADA alone. The use and effectiveness of ADA + DMARD(s) over monotherapy require confirmation in real-life settings. <h3>Objectives</h3> To compare the use and response of ADA taken with or without DMARD(s) in a real-life setting. <h3>Methods</h3> Biologic-naïve rheumatoid arthritis (RA) patients (pts) registered through the BSRBR (Sep '02-Mar '10) who received their 1<sup>st</sup> ADA dose were followed for 6 months. At enrollment, pts required a DAS28 &gt;5.1 and ≥2 DMARD failures. Pts were categorized by baseline DMARD use: combination therapy without MTX (non-MTX DMARD), with MTX (MTX DMARD), and ADA monotherapy. Clinical and functional responses were assessed as the proportions achieving 1) clinically meaningful reductions from baseline (Δ) in DAS28 (&gt;1.2) and HAQ (&gt;0.22), respectively, or 2) the more stringent targets, DAS28 &lt;3.2 and HAQ &lt;0.5, respectively. Logistic regression modeled the odds of response for the non-MTX DMARD and MTX DMARD groups relative to ADA monotherapy, following adjustment for baseline differences. <h3>Results</h3> Of 4470 pts initiating ADA, 3123 (70%) received ≥1 DMARD (727 non-MTX DMARD, 2396 MTX DMARD) and 1347 (30%) received ADA monotherapy. At month 6, mean DAS28 and HAQ improved in all 3 groups (Table), with the greatest improvements observed for pts receiving MTX. There was a significantly higher likelihood of achieving ΔDAS28 &gt;1.2, DAS28 &lt;3.2, and ΔHAQ &gt;0.22 in the MTX DMARD group compared with ADA monotherapy, with a trend for the non-MTX DMARD group. A trend for a higher likelihood of achieving HAQ &lt;0.5 was observed in both DMARD groups. <h3>Conclusions</h3> In this cohort with severe RA, ADA improved overall disease activity and function at 6 months, both as monotherapy and in combination with DMARD(s). Combining ADA with MTX, but not with other DMARDs, appeared to increase the likelihood of response vs monotherapy in this real-life setting. <h3>Acknowledgements</h3> AbbVie Inc. is a co-sponsor of the BSRBR. AbbVie Inc. participated in the analysis and interpretation of the data, and in the writing, reviewing, and approval of the final version of the abstract. Medical writing support was provided by Benjamin Wolfe, PhD, of AbbVie Inc. <h3>Disclosure of Interest</h3> P. Kiely Consultant for: AbbVie Inc., BMS, MSD, UCB, Pfizer, Roche, Savient, S. Florentinus Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., S. Keidel Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., A. Lacerda Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., M. Karunaratne Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., R. McCaskill Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.
P468Proteasomal-dependent defects in apoptosis pathways and apoptosis resistance underlie the expansion of CD4+CD28null T cells in patients with coronary atherosclerosis
Authors: I E Dumitriu, E Kovalcsik, P Baruah, R Antunes, JC Kaski
Journal: Cardiovascular Research (2014)

Aim: Atherosclerosis is now widely recognized as a disease with an underlying immune deregulation. Patients with coronary atherosclerosis that develop myocardial infarction (MI) have an expansion of a unique subset of T lymphocytes, the CD4+CD28null (CD28null) T cells, characterized by the lack of the CD28 co-stimulatory receptor. These cells have a pro-inflammatory and cell-lytic phenotype. Patients harbouring high numbers of CD28null T have increased risk of recurrent severe acute coronary events (i.e. MI) and unfavourable prognosis. Why CD28null T cells accumulate preferentially in patients with MI compared to patients with stable angina (SA) and healthy individuals is currently unknown. T cell homeostasis is maintained by elimination of unwanted T cells via apoptotic cell death. We hypothesized that apoptosis pathways that mediate elimination of T cells are dysregulated in CD28null T cells in patients with MI. Our aim was to investigate molecules involved in apoptosis regulation in CD28null T cells in patients with coronary atherosclerosis (MI and SA).
Abstract 1278: Simultaneous downregulation of uPAR and cathepsin B inhibits angiogenesis and migration and induces caspase 8-mediated apoptosis in U87 stem cells and 4910 glioma xenograft stem cells
Authors: Sreelatha Gopinath, Rama Rao Malla, Christopher S. Gondi, Daniel Fassett, Jeffrey D. Klopfenstein, Dzung H. Dinh, Meena Gujrati, Jasti S. Rao
Journal: Cancer Research (2010)

Abstract Malignant gliomas are characterized by invasive and infiltrative behavior. Gliomas are considered to be heterogeneous bulk tumors that comprise differentiated and undifferentiated cells with self-renewal and partial differentiation capabilities. These glioma-initiating cells (GIC) are responsible for the initiation and recurrence of gliomas even after various treatments. As such, novel therapies should target GIC. Cathepsin B and urokinase-type plasminogen activator receptor (uPAR) are overexpressed in gliomas, including GIC. We isolated GIC from U87 (U87S) and 4910 (4910S) by sorting the cells for both CD133 and STRO-1 by FACS analysis. The stem cell nature of these cells was confirmed by neurosphere formation assay and western blot analysis for CD133 and STRO-1 expression. GIC cells expressed 2 to 3-fold increased levels of CD133 and STRO-1 as compared to glioma cells (U87N and 4910N). By isolating and utilizing GIC, we demonstrate that downregulation of uPAR (pU) and cathepsin B (pC) individually and simultaneously (pCU) lead to remarkable inhibition of angiogenesis and migration and activated caspase 8-mediated apoptosis in GIC and U87N and 4910N cells. The treatment retarded the expression of pro-angiogenic molecules in both stem cells and glioma cells but responded differently in terms of expression of certain molecules, such as angiogenin and TIMP-1. Similarly, an apoptotic antibody array revealed that stem cells and glioma cells respond differently to pCU treatment, but both sets of cells exhibited increased expression of pro-apoptotic molecules. This induction of apoptosis was also confirmed by cleavage of caspase 8, caspase 3 and PARP as well as TUNEL assay. Similarly, spheroid migration and matrigel invasion assays, revealed that downregulation of uPAR and cathepsin B inhibited cell migration by 70-75% and 45-50% and invasion by 75-80% and 45-50% in GIC and normal glioma cells, respectively. Untreated glioma stem cells were more migratory (∼30%) and invasive (30-40%) as compared to normal glioma cells. In vivo studies showed few to no tumor cells in brain sections of mice implanted with either GIC or normal glioma cells treated with pCU as determined by H&amp;E staining. These results indicate the potential of RNAi-mediated downregulation of uPAR and cathepsin B in developing new therapeutics for GIC in particular and gliomas in general. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1278.
Quantitative Determination of Antibody in Idiopathic Thrombocytopenic Purpura
Authors: Richard Dixon, Wendell Rosse, Larry Ebbert
Journal: New England Journal of Medicine (1975)

We studied the clinical applicability of a recently developed technic that determines antiplatelet antibody directly on the platelet surface or in serum. The technic is a quantitative complement lysis-inhibition assay. Normal platelets have less than 0.4 pg of surface IgG. All patients with idiopathic thrombocytopenic purpura who were studied had greater than that value. Surface IgG was increased in inverse proportion to the platelet count. Surface levels of greater than 1.1 pg correlated with failure to respond to prednisone therapy. Incubation of normal serums with normal platelets did not increase surface IgG of such platelets, but their incubation with thrombocytopenic serums increased their surface IgG 0.5 to 100 times. The degree of increase did not predict response to treatment. However, quantitation of surface IgG of thrombocytopenic platelets was useful in predicting response to treatment. (N Engl J Med 292:230–236,1975)
Emergence of Multiply Resistant Pneumococci
Authors: Michael R. Jacobs, Hendrik J. Koornhof, Roy M. Robins-Browne, Carolyne M. Stevenson, Zoë A. Vermaak, Ida Freiman, G. Bennie Miller, Maurice A. Witcomb, Margaretha Isaäcson, Joel I. Ward, Robert Austrian
Journal: New England Journal of Medicine (1978)

Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.