tbuckley/cabot-search huggingface dataset:
Blood T regulatory lymphocytes number is decreased in severe COPD
Authors: Virginija Sileikiene, Edvardas Danila, Laimute Jurgauskiene
Journal: European Respiratory Journal (2013)

The aim of the study.  To evaluate the count of regulatory T lymphocytes (CD4+CD25+), as cells, possibly decreasing inflammation, in the patients suffering from different severity COPD and compare with the healthy subjects.   Materials and methods.  CD4+CD25+ and CD4+CD25+ bright blood cells were examined for 43 COPD patients and 26 healthy persons. The control group consisted of smokers and non smokers. In accordance with spirometrical severity of the disease COPD patients were distributed into two groups: a group (I) of patients with mild and moderate obstruction and group (II) consisted of patients with severe and very severe obstruction.   Results.  The comparison of COPD and control groups demonstrated no statistically significant difference either in total number of CD4+CD25+ cells, or in CD4+CD25+ bright (Treg). However, in the group of patients with severe and very severe COPD, the count of CD4+CD25+ and CD4+CD25+ bright  cells was found to be significantly lower, in comparison with healthy smokers (376±235  vs  610±217 p = 0.01 and 47±26  vs  75±27, p = 0.03).The difference between smoking and non-smoking controls was found to be statistically significant, also: CD4+CD25+ and CD4+CD25+ bright  lymphocytes was markedly higher in healthy smokers than in non-smokers (610±217  vs  392±157, p = 0.02 and 59±29  vs  42±19, p = 0.03).   Conclusion.  Our results confirmed the proposition that the dysfunction of immune system plays the role in development of COPD. Inflammation of the airways during COPD may be supressed inadequately due to insufficiency of CD4+CD25+ (T regulatory) lymphocytes.
Irinotecan plus carboplatin versus etoposide plus carboplatin in extensive disease small cell lung cancer: Results of the German randomized phase III trial
Authors: A. H. Schmittel, M. Sebastian, L. Fischer von Weikersthal, T. Gauler, P. Hortig, J. R. Fischer, H. Link, D. Binder, W. Eberhardt, U. Keilholz
Journal: Journal of Clinical Oncology (2009)

8029 Background: Superiority of irinotecan over etoposide in combination with cis- or carboplatin was demonstrated in a Japanese and a Scandinavian phase III trial. However, both cisplatin-based North American phase III studies could not detect any difference in efficacy. We report the final results of the German randomized phase III trial comparing etoposide/carboplatin (PE) to irinotecan/carboplatin (IP) in small cell lung cancer (SCLC) extensive disease. Methods: Chemotherapy-naïve extensive disease SCLC patients were randomly assigned to receive carboplatin AUC 5 mg × min/mL either in combination with 50 mg/m 2 of irinotecan on days 1, 8 and 15 (IP, Arm A) or with etoposide 140mg/m 2 days 1–3 (EP). IP treatment was repeated every 4 weeks, EP every 3 weeks. Response assessment was performed after cycles 2, 4 and 6 and every 3 months thereafter. Toxicity was assessed once weekly. Primary endpoint was detection of progression free survival (PFS), secondary endpoints were overall survival (OS), response rate, and toxicity. Results: A total of 216 patients from 8 centres were randomized. No significant differences in survival or response rate could be detected. Median PFS was 6 months in both arms. Median OS was 10 months (95% confidence interval (CI) 8.3 -11.7) in the IP arm and 9 months (95% CI 7.6 -10.4) in the EP arm. 1 year survival was 37% (95% CI 25.6 - 47.6) and 28% (95% CI 18.2 - 37.4) in the IP and EP arm. 62% of patients in the IP and 63% in the EP arm had a confirmed complete or partial remission according to RECIST criteria. Significant differences in grade 3 and 4 toxicity were observed for thrombopenia (22% IP vs 47% EP) and neutropenia (23% IP vs 61% PE) without differences in the rate of febrile neutropenia. Grade 3 and 4 diarrhea was manageable and as expected significantly more frequent with IP (15%) than with EP (6%). Conclusions: Our phase III trial shows equivalent efficacy of irinotecan when compared to etoposide in combination with carboplatin. [Table: see text]
MicroRNA profiling of the murine hematopoietic system.
Authors: Silvia Monticelli, K Mark Ansel, Changchun Xiao, Nicholas D Socci, Anna M Krichevsky, To-Ha Thai, Nikolaus Rajewsky, Debora S Marks, Chris Sander, Klaus Rajewsky, Anjana Rao, Kenneth S Kosik
Journal: Genome biology (2005)

MicroRNAs (miRNAs) are a class of recently discovered noncoding RNA genes that post-transcriptionally regulate gene expression. It is becoming clear that miRNAs play an important role in the regulation of gene expression during development. However, in mammals, expression data are principally based on whole tissue analysis and are still very incomplete.We used oligonucleotide arrays to analyze miRNA expression in the murine hematopoietic system. Complementary oligonucleotides capable of hybridizing to 181 miRNAs were immobilized on a membrane and probed with radiolabeled RNA derived from low molecular weight fractions of total RNA from several different hematopoietic and neuronal cells. This method allowed us to analyze cell type-specific patterns of miRNA expression and to identify miRNAs that might be important for cell lineage specification and/or cell effector functions.This is the first report of systematic miRNA gene profiling in cells of the hematopoietic system. As expected, miRNA expression patterns were very different between hematopoietic and non-hematopoietic cells, with further subtle differences observed within the hematopoietic group. Interestingly, the most pronounced similarities were observed among fully differentiated effector cells (Th1 and Th2 lymphocytes and mast cells) and precursors at comparable stages of differentiation (double negative thymocytes and pro-B cells), suggesting that in addition to regulating the process of commitment to particular cellular lineages, miRNAs might have an important general role in the mechanism of cell differentiation and maintenance of cell identity.
Effect of a mouth rinse formulation with human trefoil factor 1-secreting <i>Lactococcus lactis</i> in experimental oral mucositis in hamsters
Authors: P. Rottiers, S. Caluwaerts, L. Steidler, K. Vandenbroucke, B. Watkins, S. Sonis, B. Coulie
Journal: Journal of Clinical Oncology (2009)

e14570 Background: Oral mucositis (OM) is a painful and dose-limiting toxicity of cancer chemotherapy and irradiation, characterized by breakdown of the oral mucosa. Trefoil factors (TFFs) are involved in protecting and healing mucosal tissue, and might thus represent a pharmacological tool for treatment of OM. Local delivery of recombinant TFFs at the oral mucosa by living, genetically modified Lactococcus (L.) lactis bacteria (ActoBiotics) seems a promising, safe and cost-effective clinical approach for the prevention and attenuation of oral mucositis. Methods: An environmentally contained Lactococcus lactis strain (AG013), engineered to express human (h)TFF1, was formulated for topical administration in the form of a mouth rinse. Efficacy of AG013 was assessed in a clinically relevant hamster model of acute, radiation-induced OM. The dosing regimen was 1.3 x 10 9 CFU/dose, once (qd) or three rinses (tid) daily, from day 0 (=day of radiation) to day 18. OM was scored from day 6 to day 28 using the WHO grading scale, and compared to the score of placebo-treated hamsters. The viability and survival of live L. lactis and the pharmacokinetics of the hTFF1 secreted were studied in healthy and OM hamsters. Results: Topical application of AG013 to the oral mucosa significantly reduced the severity and course of radiation-induced OM. In the AG013-treated groups, the number of animals days with ulcerative mucositis (grade 3 or higher) was significantly reduced to 27.5% and 30.8% (qd and tid respectively; P &lt; 0.001), compared to 45.8 % in the placebo-treated group. Based on the observed survival and weight changes, AG013 appeared to be well-tolerated. Pharmacokinetic studies demonstrated that both living L. lactis and the hTFF1 secreted could be recovered from the administration site, for maximum 24 hours post-dosing, without systemic exposure. Conclusions: Oral administration of AG013 is safe and effective in reducing the severity and the course of OM in the hamster model, and therefore supports proof-of-concept for a mouth rinse formulation of AG013 to treat OM patients. [Table: see text]
Effects of rosemary and platanus extracts on asthmatic subjects resistant to traditional treatments
Authors: Majid Mirsadraei, Afsaneh Tavakoli, Sakineh Ghaffari
Journal: European Respiratory Journal (2013)

Recent studies showed some benefit for Rosemary in allergic disorders. Objective of this study was to determine the effects of Rosemary and Platanus extracts on asthma.  Materials and methods:  Design: Active comparator study, Registered in Iranian clinical trial registry.  Participants: Forty asthmatic subjects (F/M=3/2) who were not controlled with at least four drugs of asthma (ICS, LABA, Montelukast and Theophilline).  The subjects were randomly divided in to four groups which herbal medicine (platanus or rosemary extract) were used in two groups and placebo in two other groups. The extracts were provided from especial herbal medicine factory from Birjand city. Packages were similar and physician and pharmacist were blind to the type of treatment. Clinical findings, spirometry, Exhaled Nitric Oxide (FENO) and asthma control test (ACT) were measured before trial and after one month of treatment.  Results: Six subjects showed side effects (2 Rosemary, 4 Platanus). Overall patient satisfaction and ACT score showed significant improve with Rosemary but not with Platanus. Clinical evaluation showed significant improvement of cough, sputum production, chest pain and wheezing in Rosemary group and cough and chest pain in Platanus group. Spirometry results showed significant improving in FEV1 percent predicted and FEV1/VC in Platanus group but other parameters and Rosemary spirometry didn’t showed significant difference. FENO was decreased in both groups but the results were not statistically significant.  Conclusion: Rosemary and Platanus extract showed promising result in resistant asthma. Further studies about most effective gradient of these herbal medicines are recommended.
Atorvastatin–Clopidogrel Interaction
Authors: Paul T. Martin, Russell Denman
Journal: Circulation (2003)

Atorvastatin-Clopidogrel InteractionTo the Editor:We read with some fascination the paper by Lau et al 1 exploring the possibility of an interaction between atorvastatin and clopidogrel.Unfortunately, the authors do not make clear whether the patients in the first study received aspirin, which would be the normal standard of care in patients undergoing percutaneous coronary interventions.The two subsequent studies did not use aspirin, a fact that the authors could have elaborated on in their discussion.Given the well-characterized effects of aspirin on platelet aggregation and its widespread clinical use, we feel this omission limits the clinical concerns raised by this study.
Molecular dynamics of Staphylococcus aureus nasal carriage in Hajj pilgrims
Authors: P.O. Verhoeven, P. Gautret, C.H. Haddar, S. Benkouiten, J. Gagnaire, K. Belhouchat, F. Grattard, R. Charrel, B. Pozzetto, T. Drali, F. Lucht, P. Brouqui, Z.A. Memish, P. Berthelot, E. Botelho-Nevers
Journal: Clinical Microbiology and Infection (2015)
Ostarine increases lean body mass and improves physical performance in healthy elderly subjects: Implications for cancer cachexia patients
Authors: W. Evans, M. R. Smith, J. E. Morley, K. G. Barnette, D. Rodriguez, M. S. Steiner, J. T. Dalton
Journal: Journal of Clinical Oncology (2007)

9119 Background: Cancer cachexia results in selective loss of skeletal muscle resulting in weakness, reduced physical activity and a lower quality of life. Cancer cachexia also diminishes response to chemotherapy and survival. Anabolic steroids appear to increase weight and muscle mass in cancer patients, but have the potential for masculinization in women and prostate stimulation in men. A new class of non-steroidal selective androgen receptor modulators (SARMs) is being developed for use in cancer cachexia. SARMs are designed to have predominately anabolic activity in muscle and bone with minimal androgenic effects in most other tissues. We conducted a randomized phase II proof of concept study of ostarine, the first-in-class SARM, in healthy postmenopausal women and elderly men prior to intitiating a phase II study in cancer patients. Methods: Sixty elderly men (mean age 66 years) and 60 postmenopausal women (mean age 63 years) were randomly assigned to ostarine 0.1, 0.3, 1 mg, 3 mg or placebo for three months. The primary end point was change from baseline to three months in total lean body mass (LBM) measured by dual energy x-ray absorptiometry (DXA). The key secondary end point was a stair climb functional performance test that measured speed and power exerted. Evaluations included laboratory safety assessments and additional assessments of androgenic activity including PSA, sebum production and luteinizing hormone. Results: Ostarine treatment resulted in a dose dependent increase in total LBM, with an increase of 1.4 kg compared to placebo (p&lt;0.001) at the 3 mg dose. Increased LBM translated to an improvement in the stair climb test in both speed (+15.5% ± 12.9 faster time, p=0.006) and power (+25.5% ± 20.3 watts, p=0.005). There were no serious adverse events reported. There were no significant changes in PSA, sebum production or luteinizing hormone. Conclusions: Ostarine improves LBM and physical performance in healthy older men and women. Ostarine had no unwanted androgenic side effects. A phase II study is planned to evaluate the safety and efficacy of ostarine in patients with cancer cachexia. No significant financial relationships to disclose.
Evolution of Base Composition in T-DNA Genes from Agrobacterium
Authors: JM Martinez-Zapater, A Marin, JL Oliver
Journal: Molecular Biology and Evolution (1993)

T-DNA genes on Ti and Ri plasmids from Agrobackrium are replicated and repaired in bacteria but expressed in plant cells.Therefore, they can be useful tools to disclose the relative roles played by the two main mechanisms involved in the evolution of DNA base composition: ( 1) mutational bias along DNA replication/repair processes and (2) selective gene expression constraints.We compare the base-compositional features of 15 T-DNA genes with those of ( 1) other genes located on Ti or Ri plasmids but outside the T-DNA region (non-T-DNA genes) and (2) a sample of nuclear genes from a natural host plant species (tobacco).The similarity in G+C content found between T-DNA and plant genes at replacement sites, as well as the similar stronger avoidance of CpG at II-III codon positions, support an ancestral plant origin for T-DNA genes.When G+C content and codon usage are considered, T-DNA genes are more similar to non-T-DNA genes than to those of plants, indicating that the mutational bias along replication and repair processes in bacteria is the major factor driving the global compositional properties of T-DNA genes.However, when the reduction in the available CpG methylation targets and the distribution of these avoidances on the different codon positions are considered, T-DNA genes are more similar to those of plants than they are to the other plasmid genes.The requirements for expression of T-DNA genes in the plant cells would have modulated the compositional features of their sequences, mainly CpG avoidance.
Use of psychopathology vignettes by patients with schizophrenia or schizoaffective disorder and by mental health professionals to judge patients' insight
Authors: J P McEvoy, N R Schooler, E Friedman, S Steingard, M Allen
Journal: American Journal of Psychiatry (1993)

The goal of this study was to clarify more precisely where patients with psychotic disorders and the mental health professionals who care for them disagree regarding whether the patient is ill or needs treatment.The authors prepared brief vignettes in everyday descriptive language that provided examples of the classical positive and negative psychopathological features of schizophrenia. Fifteen men and 11 women diagnosed as having schizophrenia or schizoaffective disorder and one physician used these vignettes as a common frame of reference to rate 1) the degree to which the patients demonstrated the features described in each vignette and 2) the degree to which the features signified the presence of mental illness.Disagreements between the physician's and patients' ratings, indicating deficits in insight, were associated with the recognition of the presence of conceptual disorganization, avolition-apathy, and affective blunting in the patients by the physician but not the patients and with the conceptualization of hallucinatory behavior and suspiciousness as signs of mental illness by the physician but not the patients.The authors conclude that the failure to acknowledge conceptual disorganization, avolition-apathy, and affective blunting and the failure to view hallucinatory behavior and suspiciousness as signs of mental illness, which proved to be additive in this study, contribute to deficits in insight.
Dose-Dense Doxorubicin, Docetaxel, and Granulocyte Colony-Stimulating Factor Support With or Without Tamoxifen as Preoperative Therapy in Patients With Operable Carcinoma of the Breast: A Randomized, Controlled, Open Phase IIb Study
Authors: Gunter von Minckwitz, Serban D. Costa, Günter Raab, Jens-Uwe Blohmer, Holger Eidtmann, Jörn Hilfrich, Elisabeth Merkle, Christian Jackisch, Günther Gademann, Augustinos H. Tulusan, Wolfgang Eiermann, Erika Graf, Manfred Kaufmann
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size ≥ 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 , either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of −1.2% in favor of ADoc, with a 95% confidence interval of −8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.
Abstract 2573: Viral Endomyocardial Infection is an Independent Predictor of Graft Loss in Pediatric Cardiac Transplant Recipients
Authors: Mousumi Moulik, John P Breinholt, William J Dreyer, Debra L Kearney, Jack F Price, Sarah K Clunie, Brady S Moffett, Jeffrey J Kim, Joseph Rossano, John L Jefferies, Anne K Thomas, Brandy A Harbes, Karla R Bowles, E O Smith, Neil E Bowles, Susan W Denfield, Jeffrey A Towbin
Journal: Circulation (2006)

Background: Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survi...
Book: Dementia Reconsidered: the Person Comes First
Authors: L. Flicker
Journal: BMJ (1999)

Tom Kitwood Open University Press, £14.95, pp 176 ISBN 0335198554 Rating: ![Graphic][1]</img> The burden of dementia is borne not only by people with dementia, but by their carers, both informal and professional. The major direct financial costs are managed by the welfare sector, through the provision of community services and residential care, whereas indirect costs are largely attributed to informal carers. Advances in care practices would be of considerable benefit. The health sector has had its main impact in the area of dementia by providing skills and expertise necessary for comprehensive, holistic assessments. Kitwood challenges this medical model, which he labels as … [1]: /embed/inline-graphic-1.gif
High Court rejects claim that a GP trainee's sentence was too lenient
Authors: C. Dyer
Journal: BMJ (2015)

<h3>Abstract</h3> <h3>Motivation</h3> While it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging. Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning. However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem. <h3>Results</h3> We present DrDimont, <b>D</b>rug <b>r</b>esponse prediction from <b>Di</b>fferential analysis of <b>m</b>ulti-<b>o</b>mics <b>n</b>e<b>t</b>works. It allows for comparative conclusions between two conditions and translates them into differential drug response predictions. DrDimont focuses on molecular interactions. It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks. DrDimont’s predictions are explainable, i.e., molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite, and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response. <h3>Availability</h3> DrDimont is available on CRAN: https://cran.r-project.org/package=DrDimont. <h3>Contact</h3> katharina.baum@hpi.de
The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation
Authors: Dan Lu, Liang Liu, Xin Ji, Yanan Gao, Xi Chen, Yu Liu, Yang Liu, Xuyang Zhao, Yan Li, Yunqiao Li, Yan Jin, Yu Zhang, Michael A McNutt, Yuxin Yin
Journal: Nature Immunology (2015)
Resilience and psychiatric epidemiology: Implications for a conceptual framework
Authors: Joseph M. Boden, Geraldine F. H. McLeod
Journal: Behavioral and Brain Sciences (2015)

Abstract Kalisch and colleagues present a conceptual framework for the study of resilience, using a neurobiological approach. The present commentary examines issues arising for the study of resilience from epidemiological data, which suggest that resilience is most likely a normative function that may operate as a kind of psychological immune system. The implications of the epidemiological data on the development of a neurobiological theory of resilience are discussed.