tbuckley/cabot-search huggingface dataset:
Smoking cessation and reduction in people with chronic mental illness
Authors: Jennifer W Tidey, Mollie E Miller
Journal: BMJ (2015)

The high prevalence of cigarette smoking and tobacco related morbidity and mortality in people with chronic mental illness is well documented. This review summarizes results from studies of smoking cessation treatments in people with schizophrenia, depression, anxiety disorders, and post-traumatic stress disorder. It also summarizes experimental studies aimed at identifying biopsychosocial mechanisms that underlie the high smoking rates seen in people with these disorders. Research indicates that smokers with chronic mental illness can quit with standard cessation approaches with minimal effects on psychiatric symptoms. Although some studies have noted high relapse rates, longer maintenance on pharmacotherapy reduces rates of relapse without untoward effects on psychiatric symptoms. Similar biopsychosocial mechanisms are thought to be involved in the initiation and persistence of smoking in patients with different disorders. An appreciation of these common factors may aid the development of novel tobacco treatments for people with chronic mental illness. Novel nicotine and tobacco products such as electronic cigarettes and very low nicotine content cigarettes may also be used to improve smoking cessation rates in people with chronic mental illness.
The gene expression profile of matrix metalloproteinases and their inhibitors in children with Henoch-Schönlein purpura
Authors: J.I. Shin, K.S. Song, H. Kim, N.H. Cho, J. Kim, H.S. Kim, J.S. Lee
Journal: British Journal of Dermatology (2011)

Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis.To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction.MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.
A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems
Authors: Daniel L Cook, Joel F Farley, Stephen J Tapscott
Journal: Genome biology (2001)

We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease.We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet.Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.
LSC 2012 abstract - FOXO transcription factors regulate innate immune mechanisms in respiratory epithelial cells during bacterial infection
Authors: Christoph Beisswenger, Frederik Seiler, Philipp Lepper, Robert Bals, Christian Herr
Journal: European Respiratory Journal (2012)

Bacterial pathogens are a leading cause of lung infections and contribute to acute exacerbations in patients with respiratory tract diseases. The innate immune system of the lung controls and prevents colonization of the respiratory tract with bacterial pathogens. Here, we show that FOXO transcription factors regulate innate immune mechanism of respiratory epithelial cells in response to bacterial pathogens such as Haemophilus influenzae and Pseudomoas aeruginosa. Infection with bacterial pathogens led to the activation of FOXO transcription factors in respiratory epithelial cells in vivo and in vitro. siRNA mediated knock down of FOXO3 in bronchial epithelial cells resulted in reduced expression of factors of the innate immune system such as antimicrobial peptides and factors involved in a proinflammatory response. In addition, FOXO3 plays a role in the internalization of bacterial pathogens. These data show that FOXO transcription factors are involved in the cellular response to bacterial stimuli and have a central role in regulating innate immune functions of respiratory epithelial cells.
Correlation between time to positivity of blood cultures with clinical presentation and outcomes in patients with Klebsiella pneumoniae bacteraemia: prospective cohort study
Authors: C.-H. Liao, C.-C. Lai, M.-S. Hsu, Y.-T. Huang, F.-Y. Chu, H.-S. Hsu, P.-R. Hsueh
Journal: Clinical Microbiology and Infection (2009)
Biatrial Enlargement and Recurrent Cardioembolism in a 55 Year-Old Man With Atrial Fibrillation
Authors: Shriram Nallamshetty
Journal: Circulation (2008)

Abstract 1124 Shriram Nallamshetty, Byungdoo A Yi, James Stone, Massachusetts General Hosp, Boston, MA; Patrick T O’Gara, Brigham and Women’s Hosp, Boston, MA; Calum A MaCare, Massachusetts General Hosp, Boston, MA Shriram Nallamshetty, 2008 Finalist and Presenting Author
Percutaneous Mitral Valve Interventions in the Real World
Authors: Francesco Maisano, Olaf Franzen, Stephan Baldus, Ulrich Schäfer, Jörg Hausleiter, Christian Butter, Gian Paolo Ussia, Horst Sievert, Gert Richardt, Julian D. Widder, Tiziano Moccetti, Wolfgang Schillinger
Journal: Journal of the American College of Cardiology (2013)
Discordance between the QuantiFERON-TB Gold In-Tube and Tuberculin Skin Test: need for a further step?
Authors: Michele Spinicci, Jessica Mencarini, Delia Goletti, Antonia Mantella, Nunzia Della Malva, Alessandro Bartoloni, Filippo Bartalesi
Journal: European Respiratory Journal (2015)

Screening for latent tuberculosis infection (LTBI) in patients with immune-mediated inflammatory diseases (IMID), candidates for treatment with biological agents, is currently recommended by several national and international guidelines. In addition to the older tuberculin skin test (TST), in the past decade, in vitro interferon-γ release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT) (Qiagen, Hilden, Germany) and T-SPOT.TB (TSPOT) (Oxford Immunotec, Abingdon, UK), have also been available for diagnosing LTBI. IGRAs are supposed to be less affected by prior vaccination with bacille Calmette–Guérin (BCG) or exposure to non-tuberculous mycobacteria than the TST, resulting in a higher specificity of IGRAs compared to the TST [1, 2]. Due to the lack of a gold standard, the diagnostic accuracy of IGRAs and TSTs cannot be definitely established. Data from the literature show a reduced sensitivity in immunocompromised patients and a low predictive value for progression to active TB for both TST and IGRA [1–4]. In the last years, several studies evaluated the accuracy of the IGRA and TST in IMID populations, but the findings are conflicting [5]. In this context, different LTBI screening strategies have been recommended [5, 6]. Considering the suboptimal sensitivity of the available tests, and according to data from a previous study showing a good association of both the QFT and TST with LTBI risk factors, our centre used a screening strategy based on the simultaneous performance of the QFT and TST, in addition to a chest radiograph (CXr) [7]. This strategy, also supported by the European Centre for Disease Prevention and Control guidance, is meant to maximise the sensitivity in immune-compromised individuals, and is especially suited for areas where BCG coverage is low [8]. However, in a considerable number of cases, these tests provide discordant results, giving way to uncertain interpretation in clinical practice. To address this issue, we assessed the performance of a second level of LTBI screening tests for IMID patients, who are candidates for biological agents, if TST/QFT discordant results should occur. T-SPOT.TB is useful in discordant QFT/TST immune-mediated inflammatory diseases patients candidates for biological drugs <http://ow.ly/OZsLx> We would like to thank Andrea Baker, English mother tongue speaker, whose work has been very helpful in editing this paper.
Abstract 3130: Body Mass Index and Risk of Adverse Cardiac Events in Elderly Hip Fracture Patients: A Population-Based Study
Authors: John A Batsis, Jeanne M Huddleston, Lee J Melton, Paul M Huddleston, Francisco Lopez-Jimenez, Dirk R Larson, Rachel E Gullerud, M M McMahon
Journal: Circulation (2008)
Abstract 5149: Statin Use and Risk of Developing Type 2 Diabetes: A Meta-Analysis
Authors: Swapnil Rajpathak, Dharam J Kumbhani, Jill P Crandall
Journal: Circulation (2008)

Background : The beneficial effects of statin therapy may extend well beyond its cholesterol-lowering properties. Such ‘pleiotropic’ effects of statins may include reducing systemic inflammation, improving endothelial function and lowering cellular oxidative stress. Since these mechanisms are implicated in the pathogenesis of type 2 diabetes, statin therapy may, therefore, potentially reduce the risk of developing diabetes. Methods : We conducted a meta-analysis of randomized controlled clinical trials (RCTs) that evaluated the effect of statin therapy on the incidence of type 2 diabetes. Effect estimates were calculated using a random effects model. Results : We identified 5 clinical trials of statin treatment that reported incident diabetes, which included 42,860 patients without preexisting diabetes. Intervention in these trials included four different statins with a dose range of 10 to 40 mg/d. There was a significant heterogeneity between the studies in terms of ascertainment of diabetes, which was not the primary outcome in these RCTs. We found no difference between the incidence of type 2 diabetes among patients randomized to statins (3.6%) compared to placebo (3.4%) during an average (weighted mean) follow-up of 47.2 months (Relative Risk: 1.05; 95% confidence intervals: 0.95–1.16; p=0.36). The results were similar when stratified by age or specific statin used. Conclusion : Current evidence from RCTs does not support a beneficial effect of statin therapy on the risk of developing type 2 diabetes. RCTs of statin therapy with diabetes as a primary outcome are required to definitively determine the role of statins in the primary prevention of diabetes.
Incidence and Predictors of Hyperkalemia in Patients With Heart Failure
Authors: Akshay S. Desai, Karl Swedberg, John J.V. McMurray, Christopher B. Granger, Salim Yusuf, James B. Young, Mark E. Dunlap, Scott D. Solomon, James W. Hainer, Bertil Olofsson, Eric L. Michelson, Marc A. Pfeffer
Journal: Journal of the American College of Cardiology (2007)
Macrolide-resistance mechanisms in Streptococcus pneumoniae isolates from Belgium
Authors: J. Van Eldere, E. Meekers, K. Lagrou, C. Massonet, A. Canu, I. Devenyns, J. Verhaegen, G. Syrogiannopoulos, R. Leclercq
Journal: Clinical Microbiology and Infection (2005)
Structure-Based DNA-Targeting Strategies with Small Molecule Ligands for Drug Discovery
Authors: Jia Sheng, Jianhua Gan, Zhen Huang
Journal: Medicinal Research Reviews (2013)

Nucleic acids are the molecular targets of many clinical anticancer drugs. However, compared with proteins, nucleic acids have traditionally attracted much less attention as drug targets in structure-based drug design, partially because limited structural information of nucleic acids complexed with potential drugs is available. Over the past several years, enormous progresses in nucleic acid crystallization, heavy-atom derivatization, phasing, and structural biology have been made. Many complicated nucleic acid structures have been determined, providing new insights into the molecular functions and interactions of nucleic acids, especially DNAs complexed with small molecule ligands. Thus, opportunities have been created to further discover nucleic acid-targeting drugs for disease treatments. This review focuses on the structure studies of DNAs complexed with small molecule ligands for discovering lead compounds, drug candidates, and/or therapeutics.
Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma
Authors: Joal D Beane, Gary Lee, Zhili Zheng, Matthew Mendel, Daniel Abate-Daga, Mini Bharathan, Mary Black, Nimisha Gandhi, Zhiya Yu, Smita Chandran, Martin Giedlin, Dale Ando, Jeff Miller, David Paschon, Dmitry Guschin, Edward J Rebar, Andreas Reik, Michael C Holmes, Philip D Gregory, Nicholas P Restifo, Steven A Rosenberg, Richard A Morgan, Steven A Feldman
Journal: Molecular Therapy (2015)

Programmed cell death-1 (PD-1) is expressed on activated T cells and represents an attractive target for gene-editing of tumor targeted T cells prior to adoptive cell transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the gene encoding human PD-1 (PDCD-1) to gene-edit melanoma tumor infiltrating lymphocytes (TIL). We show that our clinical scale TIL production process yielded efficient modification of the PD-1 gene locus, with an average modification frequency of 74.8% (n = 3, range 69.9-84.1%) of the alleles in a bulk TIL population, which resulted in a 76% reduction in PD-1 surface-expression. Forty to 48% of PD-1 gene-edited cells had biallelic PD-1 modification. Importantly, the PD-1 gene-edited TIL product showed improved in vitro effector function and a significantly increased polyfunctional cytokine profile (TNFα, GM-CSF, and IFNγ) compared to unmodified TIL in two of the three donors tested. In addition, all donor cells displayed an effector memory phenotype and expanded approximately 500-2,000-fold in vitro. Thus, further study to determine the efficiency and safety of adoptive cell transfer using PD-1 gene-edited TIL for the treatment of metastatic melanoma is warranted.
American Cancer Society Colorectal Cancer Survivorship Care Guidelines
Authors: Khaled El‐Shami, Kevin C. Oeffinger, Nicole L. Erb, Anne Willis, Jennifer K. Bretsch, Mandi L. Pratt‐Chapman, Rachel S. Cannady, Sandra L. Wong, Johnie Rose, April L. Barbour, Kevin D. Stein, Katherine B. Sharpe, Durado D. Brooks, Rebecca L. Cowens‐Alvarado
Journal: CA A Cancer Journal for Clinicians (2015)

Answer questions and earn CME/CNE Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two‐thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short‐term and long‐term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long‐term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk‐based health care for CRC survivors who have completed active therapy. CA Cancer J Clin 2015;65:427–455 . © 2015 American Cancer Society.
Abstract 14349: CaMKII-Dependent Troponin-I Phosphorylation Contributes to the Frequency-Dependent Acceleration of Relaxation in Ventricular Myocytes
Authors: Arnaud Guilbert, Hyun Joung Lim, Jun Cheng, Catherine Passariello, Yanggan Wang
Journal: Circulation (2011)

Background: Frequency-dependent acceleration of relaxation (FDAR) is an intrinsic mechanism in ventricular myocytes allowing a faster ventricular relaxation (and diastolic filling) at fast heart ra...
Borderline rage and the therapist's reponse
Authors: Theodore Nadelson
Journal: American Journal of Psychiatry (1977)

Borderline patients often engender feelings ranging from apathy to rage in therapists. The author views the borderline patient's rage as defensive against fear of total negation resulting from projective identification with hostile part objects. The therapist's withdrawal or anger parallels the patient's projection of affect. Countertransference offers the potential for understanding a patient's terror, but therapists may become fixed in identifications that distort their understanding. Clarity often comes slowly as the therapist directs attention to his/her own affective state in order to understand the patient's vulnerability.
Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.
Authors: G P Canellos, G R Petroni, M Barcos, D B Duggan, B A Peterson
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.
Smoking, haemophilus influenzae and hospital readmission
Authors: Rajesh Kumar Yadavilli, Rosalind Benson, Elijah Matovu, Madhur Vardhan, Sanjeev Agarwal
Journal: European Respiratory Journal (2012)

Background: 

Patients with chronic lung diseases are well known to have colonisation of lower respiratory tract with Haemophilus Influenza (HI). D Roberts et al have demonstrated increased growth of HI invitro in the presence of nicotine1. However, it is not known if that leads to increased risk of clinical infection requiring hospital readmission.

Hypothesis: 

Smoking increases the risk of acute clinical infections and hospital readmission due to HI.

Methods: 

Retrospective study of adult patients admitted with acute HI infection over a 2 year period in an acute teaching hospital setting.

Results : 

N= 133, mean age 70 yrs., male 57%, Smokers 89%; Respiratory co-morbidities 83% (COPD 79%, Bronchiectasis 7%, Asthma 7% and Combined 7%).

Current smokers had increased risk of recurrent admissions 17/29(59%) compared to Ex-smokers 33/89(37%). P = 0.05 Fisher's exact test.

Patients with >40 pack years smoking history had increased risk of recurrent admissions 34/63(54%) compared to <40 pack year group 15/50(30%). P = 0.01 Fisher's exact test.

Smokers with background chronic lung disease had a tendency to have a higher number of recurrent admissions (46% vs 25%), but this was not statistically significant. P = 0.09 Fisher's exact test.

Conclusions : 

This study shows a significant association with smoking and increased HI related hospital readmissions. Smokers should be informed of this risk and strongly advised to quit smoking.

Reference :

1. Effect of tobacco and nicotine on growth of Haemophilus influenzae in vitro; J Clin Pathol. 1979 July; 32(7): 728–731.
Clinical findings in patients with anorexia nervosa and affective illness in their relatives
Authors: Elliot S Gershon, Judith L. Schreiber, Joel R. Hamovit, Eleanor D. Dibble, Walter Kaye, John I. Nurnberger, Arnold E. Andersen, Michael Ebert
Journal: American Journal of Psychiatry (1984)

The most prevalent psychiatric disorders in the families of patients with anorexia nervosa are bipolar and unipolar major affective disorder. The presence of affective disorder, self-induced vomiting, or bulimia in the patient is not predictive of affective illness in the relatives. Thus these features do not define genetic heterogeneity within anorexia nervosa. There may be genetic factors shared between anorexia nervosa and affective disorders.