tbuckley/cabot-search huggingface dataset:
The importance of cultural variables for explaining suicide terrorism
Authors: C. Dominik Güss, Ma. Teresa Tuason
Journal: Behavioral and Brain Sciences (2014)

Abstract Lankford criticizes the notion that suicide terrorists are “normal” and argues that they are suicidal. We have two misgivings about this. First, he puts sole focus on the personal side of suicidality and ignores the individual's context. Second, he fails to elaborate on the intent to harm others, which must also include the cultural, political, religious/ideological, and social-organizational factors of suicide terrorism.
Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
Authors: Ben Parker, Murray B Urowitz, Dafna D Gladman, Mark Lunt, Rachelle Donn, Sang-Cheol Bae, Jorge Sanchez-Guerrero, Juanita Romero-Diaz, Caroline Gordon, Daniel J Wallace, Ann E Clarke, Sasha Bernatsky, Ellen M Ginzler, David A Isenberg, Anisur Rahman, Joan T Merrill, Graciela S Alarcón, Barri J Fessler, Paul R Fortin, John G Hanly, Michelle Petri, Kristjan Steinsson, Mary Anne Dooley, Susan Manzi, Munther A Khamashta, Rosalind Ramsey-Goldman, Asad A Zoma, Gunnar K Sturfelt, Ola Nived, Cynthia Aranow, Meggan Mackay, Manuel Ramos-Casals, Ronald F van Vollenhoven, Kenneth C Kalunian, Guillermo Ruiz-Irastorza, S Sam Lim, Diane L Kamen, Christine A Peschken, Murat Inanc, Ian N Bruce
Journal: Annals of the Rheumatic Diseases (2014)

The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE.Recently diagnosed (<15 months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression.We studied 1150 patients with a mean (SD) age of 34.9 (13.6) years and disease duration at enrolment of 24.2 (18.0) weeks. In those with complete data, MetS prevalence was 38.2% at enrolment, 34.8% at year 1 and 35.4% at year 2. In a multivariable random effects model that included data from all visits, prior MetS status, baseline renal disease, SLICC Damage Index >1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort.MetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course.
Upper Airway Resistance Syndrome
Authors: JED E. BLACK, CHRISTIAN GUILLEMINAULT, IAN M. COLRAIN, OSCAR CARRILLO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Upper airway resistance syndrome (UARS) is defined by excessive daytime sleepiness and tiredness, and is associated with increased breathing effort. Its polygraphic features involve progressive increases in esophageal pressure (Pes), terminated by arousal (AR) as defined by the American Sleep Disorders Association (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal. However, Pes reversal can be seen without the presence of an AR. We performed spectral analysis on electroencephalographic data from a central lead for both AR and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven women). Delta band activity was increased before and surrounding Pes reversal regardless of the presence or absence of AR. In the period after Pes reversal, alpha, sigma, and beta activity showed a greater increase in AR events than in N-AR events. The Pes measures were identical leading up to the point of reversal, but showed a longer-lasting and significantly greater decrease in respiratory effort after an AR. The data indicate that substantial electroencephalographic changes can be identified in association with Pes events, even when ARs cannot be detected according to standard criteria; however, visually identifiable electroencephalographic arousals clearly have a greater impact on ongoing inspiratory effort.
Reply to the Letter to the Editor on “Topotecan versus paclitaxel in second-line therapy: a lost opportunity for quality-of-life evaluation?”, by G. Apolone &amp; A. Buda (Ann Oncol 2004; 15: 1443–1444)
Authors: G.A. Ross, J.A. Kettels
Journal: Annals of Oncology (2004)
Cardiac remodeling after long term norepinephrine treatment in rats
Authors: W Briest
Journal: Cardiovascular Research (2001)

Objective: In this study we have tested the hypothesis that degradation of collagen by matrix metalloproteinase 2 (MMP-2) precedes the deposition of extracellular matrix (ECM) after long term norepinephrine (NE) treatment. Methods: Female Sprague–Dawley rats received continuous i.v. infusion of NE (0.1 mg/kg·h) for 1, 2, 3, 4 and 14 days. Heart function and weight as well as expression of cardiac colligin and of collagen I and III were examined. Furthermore, we have assessed the degradation pathway of collagen by measuring the mRNA and activity of myocardial MMP-2 and tissue inhibitor of metalloproteinase 2 (TIMP-2) as well as the protein level of TIMP-2. Results: NE induced hypertrophy predominantly of the left ventricle (LV) in a time-dependent manner. It increased the mRNAs of colligin, collagen I and III, and of MMP-2 and TIMP-2 as well as MMP-2 activity in two phases: In the initial phase, at 3 and 4 days, the mRNA of colligin and of collagen I and III was elevated predominantly in the LV, MMP-2 and TIMP-2 mRNA, as well as TIMP-2 protein and MMP-activity were increased in both ventricles. The second phase, after 14 days, was characterized by a less pronounced increase in colligin, collagen I and III and in MMP-2 activity which occurred exclusively in the LV. Finally, long-term treatment with NE induced a 37% increase in interstitial fibrosis which was shown to occur exclusively in the LV after 14 days. Conclusion: NE treatment induced fibrosis exclusively in the LV which was associated with hypertrophy predominantly of the LV. The elevated MMP-2 activity seems to be necessary for the ECM to adapt to the enlargement of myocytes and to reduce overproduction of collagen.
Human Vascular Smooth Muscle Cells Express Functionally Active Endothelial Cell Protein C Receptor
Authors: Ellen Bretschneider, Barbara Uzonyi, Artur-Aron Weber, Jens W. Fischer, Robert Pape, Katharina Lötzer, Karsten Schrör
Journal: Circulation Research (2006)

The endothelial cell protein C receptor (EPCR) is expressed on endothelial cells and regulates the protein C anticoagulant pathway via the thrombin-thrombomodulin complex. Independent of its anticoagulant activity, activated protein C (APC) can directly signal to endothelial cells and upregulate antiapoptotic and antiinflammatory genes. Here we show that vascular smooth muscle cells (SMCs) also express EPCR. EPCR protein on SMCs was detected by flow cytometry and Western blotting. EPCR mRNA was identified by quantitative RT-PCR. To examine the functionality of EPCR, intracellular signaling in APC-stimulated SMCs was analyzed by determination of intracellular free calcium transients using confocal laser scanning microscopy. Phosphorylation of extracellular signal–regulated kinases 1 and 2 (ERK-1/2) was detected by immunoblotting. APC-induced ERK-1/2 phosphorylation was inhibited by an anti-EPCR antibody and by a cleavage site blocking anti–PAR-1 antibody, indicating that binding of APC to EPCR and cleavage of protease-activated receptor-1 (PAR-1) were involved. APC elicited an increase in [ 3 H]-thymidine incorporation. The mitogenic effect of APC was significantly enhanced in the presence of thrombin. EPCR expression was also detected in SMCs in the fibrous cap of human carotid artery plaques. The present data demonstrate functionally active EPCR in SMCs and suggest that EPCR-bound APC might modulate PAR-1-mediated responses of SMCs to vascular injury.
Idiosyncratic Toxicity: A Convergence of Risk Factors
Authors: Roger G. Ulrich
Journal: Annual Review of Medicine (2006)

The therapeutic margin for any drug is based on both toxicity and efficacy. Generally, toxicity is dose-dependent and is driven either by the therapeutic target or by an untoward target. However, idiosyncratic toxicities are usually not observed until a drug has been on the market and has gained broad exposure. Except in the case of pharmacokinetic interactions, these toxicities are not driven solely by drug exposure but rather depend on several drug- and patient-related risk factors. Drug-related risk factors include metabolism, bioactivation and covalent binding, and the inhibition of key cell functions. Patient-related risk factors include underlying disease, age, gender, comedications, nutritional status, activation of the innate immune system, physical activity, and genetic predispositions. Idiosyncratic toxicity can occur when a convergence of risk factors, including drug exposure, tips the risk-benefit balance away from benefit and toward risk.
Preferences of patients for patient centred approach to consultation in primary care: observational study
Authors: P. Little
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To identify patient9s preferences for patient centred consultation in general practice. <b>Design:</b> Questionnaire study. <b>Setting:</b> Consecutive patients in the waiting room of three doctors9 surgeries. <b>Main outcome measures:</b> Key domains of patient centredness from the patient perspective. Predictors of preferences for patient centredness, a prescription, and examination. <b>Results:</b> 865 patients participated: 824 (95%) returned the pre-consultation questionnaire and were similar in demographic characteristic to national samples. Factor analysis identified three domains of patient preferences: communication (agreed with by 88-99%), partnership (77-87%), and health promotion (85-89%). Fewer wanted an examination (63%), and only a quarter wanted a prescription. As desire for a prescription was modestly associated with desire for good communication (odds ratio 1.20; 95% confidence interval 0.85 to 1.69), partnership (1.46; 1.01 to 2.09), and health promotion (1.61; 1.12 to 2.31) this study may have underestimated preferences for patient centredness compared with populations with stronger preferences for a prescription. Patients who strongly wanted good communication were more likely to feel unwell (very, moderately, and slightly unwell; odds ratios 1, 0.56, 0.39 respectively, z trend P&lt;0.001), be high attenders (1.70; 1.18 to 2.44), and have no paid work (1.84; 1.21 to 2.79). Strongly wanting partnership was also related to feeling unwell, worrying about the problem, high attendance, and no paid work; and health promotion to high attendance and worry. <b>Conclusion:</b> Patients in primary care strongly want a patient centred approach, with communication, partnership, and health promotion. Doctors should be sensitive to patients who have a strong preference for patient centredness—those vulnerable either psychosocially or because they are feeling unwell.
Quality of Life and Survival in the 2 Years After Surgery for Non–Small-Cell Lung Cancer
Authors: Patricia M. Kenny, Madeleine T. King, Rosalie C. Viney, Michael J. Boyer, Christine A. Pollicino, Jocelyn M. McLean, Michael J. Fulham, Brian C. McCaughan
Journal: Journal of Clinical Oncology (2007)

Although surgery for early-stage non-small-cell lung cancer (NSCLC) is known to have a substantial impact on health-related quality of life (HRQOL), there are few published studies about HRQOL in the longer term. This article examines HRQOL and survival in the 2 years after surgery.Patients with clinical stage I or II NSCLC (n = 173) completed HRQOL questionnaires before surgery, at discharge, 1 month after surgery, and then every 4 months for 2 years. HRQOL was measured with a generic cancer questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ] C30) and a lung cancer-specific questionnaire (EORTC QLQ-LC13). Data were analyzed to examine the impact of surgery and any subsequent therapy, and to describe the trajectories of those who remained disease free at 2 years and those with recurrent cancer diagnosed during follow-up.Disease recurred within 2 years for 36% of patients and 2-year survival was 65%. Surgery substantially reduced HRQOL across all dimensions except emotional functioning. HRQOL improved in the 2 years after surgery for patients without disease recurrence, although approximately half continued to experience symptoms and functional limitations. For those with recurrence within 2 years, there was some early postoperative recovery in HRQOL, with subsequent deterioration across most dimensions.Surgery had a substantial impact on HRQOL, and although many disease-free survivors experienced recovery, some lived with long-term HRQOL impairment. HRQOL generally worsened with disease recurrence. The study results are important for informed decision making and ongoing supportive care for patients with operable NSCLC.
Anti-inflammatory role of sympathetic nerves in chronic intestinal inflammation
Authors: R H Straub, F Grum, U Strauch, S Capellino, F Bataille, A Bleich, W Falk, J Scholmerich, F Obermeier
Journal: Gut (2008)

<h3>Background:</h3> Substance P (SP) is a pro-inflammatory neuropeptide in colitis, whereas sympathetic neurotransmitters are anti-inflammatory at high concentrations. <h3>Aim and methods:</h3> In all layers of the colon, nerve fibre densities of SP<sup>+</sup> and sympathetic nerve fibres were investigated (22 Crohn's disease, six diverticulitis, and 22 controls). In addition, the nerve fibre repellent factor semaphorin 3C (SEMA3C) was studied. The functional role of the sympathetic nervous system was tested in dextran sodium sulfate (DSS) and <i>Il10</i><sup>−/−</sup> colitis. <h3>Results:</h3> In all layers, Crohn's disease patients demonstrated a loss of sympathetic nerve fibres. Sprouting of SP<sup>+</sup> nerve fibres was particularly observed in the mucosa and muscular layer in Crohn's disease. SEMA3C was detected in epithelial cells, and there was a marked increase of SEMA3C-positive crypts in the mucosa of Crohn's disease patients compared to controls. In Crohn's disease, the number of SEMA3C-positive crypts was negatively related to the density of mucosal sympathetic nerve fibres. Sympathectomy reduced acute DSS colitis but increased chronic DSS colitis. Sympathectomy also increased chronic colitis in <i>Il10</i><sup>−/−</sup> mice. <h3>Conclusions:</h3> This study demonstrated a loss of sympathetic and an increase of SP<sup>+</sup> nerve fibres in Crohn's disease. SEMA3C, a sympathetic nerve repellent factor, is highly expressed in the epithelium of Crohn's disease patients. In chronic experimental colitis, the sympathetic nervous system confers an anti-inflammatory influence. Thus, the loss of sympathetic nerve fibres in the chronic phase of the disease is most probably a pro-inflammatory signal, which might be related to repulsion of these fibres by SEMA3C and other repellents.
Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial
Authors: Bernard Zinman, Greg Fulcher, Paturi V Rao, Nihal Thomas, Lars A Endahl, Thue Johansen, Rebecka Lindh, Andrew Lewin, Julio Rosenstock, Michel Pinget, Chantal Mathieu
Journal: The Lancet (2011)
Independent Signals Control Expression of the Calcineurin Inhibitory Proteins MCIP1 and MCIP2 in Striated Muscles
Authors: John Yang, Beverly Rothermel, Rick B. Vega, Norbert Frey, Timothy A. McKinsey, Eric N. Olson, Rhonda Bassel-Duby, R. Sanders Williams
Journal: Circulation Research (2000)

Calcineurin, a calcium/calmodulin-regulated protein phosphatase, modulates gene expression in cardiac and skeletal muscles during development and in remodeling responses such as cardiac hypertrophy that are evoked by environmental stresses or disease. Recently, we identified two genes encoding proteins (MCIP1 and MCIP2) that are enriched in striated muscles and that interact with calcineurin to inhibit its enzymatic activity. In the present study, we show that expression of MCIP1 is regulated by calcineurin activity in hearts of mice with cardiac hypertrophy, as well as in cultured skeletal myotubes. In contrast, expression of MCIP2 in the heart is not altered by activated calcineurin but responds to thyroid hormone, which has no effect on MCIP1. A approximately 900-bp intragenic segment located between exons 3 and 4 of the MCIP1 gene functions as an alternative promoter that responds to calcineurin. This region includes a dense cluster of 15 consensus binding sites for NF-AT transcription factors. Because MCIP proteins can inhibit calcineurin, these results suggest that MCIP1 participates in a negative feedback circuit to diminish potentially deleterious effects of unrestrained calcineurin activity in cardiac and skeletal myocytes. Inhibitory effects of MCIP2 on calcineurin activity may be pertinent to gene switching events driven by thyroid hormone in striated muscles. The full text of this article is available at http://www. circresaha.org.
Addition of Primary Care–Based Retinal Imaging Technology to an Existing Eye Care Professional Referral Program Increased the Rate of Surveillance and Treatment of Diabetic Retinopathy
Authors: Charlton Wilson, Mark Horton, Jerry Cavallerano, Lloyd M. Aiello
Journal: Diabetes Care (2005)

Digital retinal imaging is a relatively new technology that can be used to assess patients for diabetic retinopathy. We evaluated the impact of adding a primary care-based retinal imaging technology to an existing eye care professional referral process on the rate of surveillance and treatment of diabetic retinopathy in a large, well-defined patient population over a 5-year period.We performed systematic performance evaluations using a computerized patient information system and a comprehensive procedure log to describe annually the patient population, the number of patients with diabetes, and the proportion of patients with diabetes who received appropriate eye care services, including surveillance and laser treatment for diabetic retinopathy before and after implementation of a digital retinal imaging system at the Phoenix Indian Medical Center Primary Care Medical Clinic.The rate of annual retinal examinations increased from 50% (95% CI 44-56%) to 75% (70-80%; P < 0.000001), representing a 50% increase in the retinal examination rate. The rate of laser therapy increased from 19.6 per 1,000 patients with diabetes in 1999 to 29.5 per 1,000 in 2003 for a 51% increase in the laser treatment rate.Implementing retinal imaging technology in a primary care setting resulted in a significant increase in the rate of diabetic retinopathy surveillance and a proportional increase in the rate of laser treatment for diabetic retinopathy for a large patient population. Application of this technology in primary care settings holds the potential to extend sight-preserving care by increasing access to appropriate retinal care.
Lung Tumor Suppressor GPRC5A Binds EGFR and Restrains Its Effector Signaling
Authors: Shuangshuang Zhong, Huijing Yin, Yueling Liao, Feng Yao, Qi Li, Jie Zhang, Huike Jiao, Yongxu Zhao, Dongliang Xu, Shuli Liu, Hongyong Song, Yong Gao, Jingyi Liu, Lina Ma, Zhi Pang, Ruixu Yang, Chengyi Ding, Beibei Sun, Xiaofeng Lin, Xiaofeng Ye, Wenzheng Guo, Baohui Han, Binhua P. Zhou, Y. Eugene Chin, Jiong Deng
Journal: Cancer Research (2015)

Abstract GPRC5A is a G-protein–coupled receptor expressed in lung tissue but repressed in most human lung cancers. Studies in Gprc5a−/− mice have established its role as a tumor-suppressor function in this setting, but the basis for its role has been obscure. Here, we report that GPRC5A functions as a negative modulator of EGFR signaling. Mouse tracheal epithelial cells (MTEC) from Gprc5a−/− mice exhibited a relative increase in EGFR and downstream STAT3 signaling, whereas GPRC5A expression inhibited EGFR and STAT3 signaling. GPRC5A physically interacted with EGFR through its transmembrane domain, which was required for its EGFR inhibitory activity. Gprc5a−/− MTEC were much more susceptible to EGFR inhibitors than wild-type MTEC, suggesting their dependence on EGFR signaling for proliferation and survival. Dysregulated EGFR and STAT3 were identified in the normal epithelia of small and terminal bronchioles as well as tumors of Gprc5a−/− mouse lungs. Moreover, in these lungs EGFR inhibitor treatment inhibited EGFR and STAT3 activation along with cell proliferation. Finally, overexpression of ectopic GPRC5A in human non–small cell lung carcinoma cells inhibited both EGF-induced and constitutively activated EGFR signaling. Taken together, our results show how GPRC5A deficiency leads to dysregulated EGFR and STAT3 signaling and lung tumorigenesis. Cancer Res; 75(9); 1801–14. ©2015 AACR.
The Rise of Direct-to-Consumer Advertising of Prescription Drugs in the United States
Authors: Alison J. Huang
Journal: JAMA (2000)

DIRECT-TO-CONSUMER(DTC)ADVERTISING OF PRESCRIPTION MEDICATIONS has rapidly become one of the most contentious issues facing the medical profession in the United States. Prior to the early 1980s, pharmaceutical companies promoted their prescription products exclusively to physicians, who were expected to act as “learned intermediaries” interpreting drug information for the general public. During the past 2 decades, however, changes in the political and regulatory climate, cultural shifts emphasizing the patient’s role in making medical decisions, and expanding profits from drug sales have encouraged the industry to pursue more direct marketing strategies. Today, advertisements for prescription drugs dot the pages of popular magazines and punctuate television programs. A survey of 18 diverse laymagazines from1989to1998revealeda totalof320distinctDTCads, representing 101 brands and 14 categories of medical conditions. This year, pharmaceutical companies will spend more than a billion dollars marketing their drug products directly to consumers, compared to only $55 million in 1991. According to a recent survey, more than one third of patients have asked their physicians for information on drugs they have seen in a DTC ad, and nearly one fourth have asked for the drug itself. Perhaps more significantly, three quarters of the patients requesting drug prescriptions received them from their physicians. Proponents argue that DTC promotion provides a service by increasing public awareness of medical conditions and encouraging informed communication between patients and providers. Furthermore, DTC ads encourage consumers to act as autonomous decision-makers, able to weigh the benefits and risks of their health choices. At the same time, critics fear that drug companies will trade on the public’s lack of medical knowledge to obscure products’ risks and adverse effects. Physicians complain that they must devote increasing amounts of scarce time to dissuading patients from taking drugs that advertising has led them to believe are unproblematic. This month, MSJAMA explores some of the issues raised by the growth of DTC advertising of pharmaceutical products in the United States. How does DTC marketing affect the relationship between patients and physicians? What is the role of the government in ensuring that DTC advertisements are accurate and complete? Should the rise of DTC advertising change physicians’ liability in suits brought by drug consumers? How does the rise of DTC advertising change our perspective on drug companies’ traditional practice of marketing drugs to physicians?