tbuckley/cabot-search huggingface dataset:
Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning
Authors: Philippe Armand, Supriya Gannamaneni, Haesook T. Kim, Corey S. Cutler, Vincent T. Ho, John Koreth, Edwin P. Alyea, Ann S. LaCasce, Eric D. Jacobsen, David C. Fisher, Jennifer R. Brown, George P. Canellos, Arnold S. Freedman, Robert J. Soiffer, Joseph H. Antin
Journal: Journal of Clinical Oncology (2008)

Inhibitors of the mammalian target of rapamycin (mTOR) kinase have shown clinical activity in several lymphoma subtypes. Sirolimus, an mTOR inhibitor, also has activity in the treatment and prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation (HSCT). We hypothesized that the use of sirolimus for GVHD prophylaxis in patients with lymphoma might lead to improved survival after transplantation through a decreased incidence of disease progression.We retrospectively analyzed 190 patients who underwent transplantation for lymphoma. We compared the outcomes of patients who received sirolimus for GVHD prophylaxis with those of patients who received transplantation with a combination of a calcineurin inhibitor and methotrexate without sirolimus.Overall survival (OS) after transplantation was significantly superior in the sirolimus group, which was confirmed in multivariable analysis. The benefit was restricted to patients undergoing reduced-intensity conditioning (RIC) HSCT (3-year OS, 66% for sirolimus group v 38% for no-sirolimus group; P = .007; hazard ratio [HR] for mortality in multivariable analysis = 0.5, P = .042). Patients who received sirolimus had a similar incidence of nonrelapse mortality but a decreased incidence of disease progression compared with patients who did not receive sirolimus (3-year cumulative incidence of progression, 42% v 74%, respectively; P < .001; HR for progression in multivariable analysis = 0.4, P = .01). The effect of sirolimus persisted after adjusting for the occurrence of GVHD. No such survival advantage was apparent in a similar comparison of patients who underwent transplantation for diseases other than lymphoma.This study suggests that sirolimus can independently decrease the risk of lymphoma progression after RIC HSCT, paving the way for prospective clinical trials.
Underconstrained thalamic activation + underconstrained top-down modulation of cortical input processing = underconstrained perceptions
Authors: Martin Sarter, Gary G. Berntson
Journal: Behavioral and Brain Sciences (2004)

Behrendt &amp; Young's (B&amp;Y's) theory offers a potentially important perspective on the neurobiology of schizophrenia, but it remains incomplete. In addition to bottom-up contributions, such as those associated with disturbances in sensory constraints on cognitive processes, a comprehensive model requires the integration of the consequences of abnormal top-down modulation of input processing for the evolution of “underconstrained” perceptions. Dysfunctional cholinergic modulation of input functions represents a necessary mechanism for the generation of false perceptions.
Half of the UK population can expect a diagnosis of cancer
Authors: I. Torjesen
Journal: BMJ (2015)

Half of people in the United Kingdom will get a diagnosis of cancer at some point in their lifetime, say forecasts from Cancer Research UK published in the British Journal of Cancer on Wednesday 4 February.1

A person’s lifetime risk is typically calculated using current risks at different ages, but this relies on age specific cancer rates and all cause mortality to remain stable over a long time. Instead, for their projections, researchers based at Queen Mary University of London estimated the probability of receiving a diagnosis of cancer (excluding non-melanoma skin cancers) among people born from 1930 to 1960 by estimating the future risks for those people born in each year at specific ages …
Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
Authors: Mikayel Mkrtichyan, Namju Chong, Rasha Abu Eid, Anu Wallecha, Reshma Singh, John Rothman, Samir N Khleif
Journal: Journal for ImmunoTherapy of Cancer (2013)

One of the significant tumor immune escape mechanisms and substantial barrier for successful immunotherapy is tumor-mediated inhibition of immune response through cell-to-cell or receptor/ligand interactions. Programmed death receptor-1 (PD-1) interaction with its ligands, PD-L1 and PD-L2, is one of the important strategies that many tumors employ to escape immune surveillance. Upon PD-Ls binding to PD-1, T cell receptor (TCR) signaling is dampened, causing inhibition of proliferation, decreased cytokine production, anergy and/or apoptosis. Thus PD-Ls expression by tumor cells serves as a protective mechanism, leading to suppression of tumor-infiltrating lymphocytes in the tumor microenvironment. Lm-LLO immunotherapies have been shown to be therapeutically effective due to their ability to induce potent antigen-specific immune responses. However, it has been demonstrated that infection with Lm leads to up-regulation of PD-L1 on mouse immune cells that can inhibit effector T cells through PD-1/PD-L1 pathway.Therapeutic and immune efficacy of Listeria-based vaccine (Lm-LLO-E7) in combination with anti-PD-1 antibody was tested in E7 antigen expressing TC-1 mouse tumor model. Tumor growth, survival, as well as peripheral and tumor-infiltrating immune cell profiles after immunotherapy were assessed.Here we demonstrate that the combination of an Lm-LLO immunotherapy with anti-PD-1 antibody that blocks PD-1/PD-L1 interaction, significantly improves immune and therapeutic efficacy of treatment in TC-1 mouse tumor model. Importantly, we show that in addition to significant reduction of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) in both spleen and tumor microenvironment that are mediated solely by the Lm-LLO immunotherapy, the addition of anti-PD-1 antibody to the treatment results in significant increase of antigen-specific immune responses in periphery and CD8 T cell infiltration into the tumor. As a result, this combinational treatment leads to significant inhibition of tumor growth and prolonged survival/complete regression of tumors in treated animals. We also demonstrate that in vitro infection with Lm results in significant upregulation of surface PD-L1 expression on human monocyte-derived dendritic cells suggesting the translational capacity of this finding.Our findings demonstrate that combination of Lm-LLO-based vaccine with blocking of PD-1/PD-L1 interaction is a feasible approach with clinical translation potential that can lead to overall enhancement of the efficacy of anti-tumor immunotherapy.
Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study
Authors: Christine M. Segeren, Pieter Sonneveld, Bronno van der Holt, Edo Vellenga, Alexandra J. Croockewit, Gregor E. G. Verhoef, Jan J. Cornelissen, Martijn R. Schaafsma, Marinus H. J. van Oers, Pierre W. Wijermans, Wim E. Fibbe, Shulamit Wittebol, Harry C. Schouten, Marinus van Marwijk Kooy, Douwe H. Biesma, Joke W. Baars, Rosalyn Slater, Monique M. C. Steijaert, Ivon Buijt, Henk M. Lokhorst
Journal: Blood (2003)
Oxygen Administration upon Ventricular Tachycardia and Blood Pressure in Animals with Acute Myocardial Infarction
Authors: A. SIDNEY HARRIS, ROY W. OLSEN, ANTONIO ESTANDÍA, TEDROE J. FORD
Journal: Circulation Research (1953)

The administration of oxygen, 60 to 70 per cent in inspired air, to dogs with ectopic ventricular tachycardia resulting from myocardial infarction produced no consistent changes in ectopic frequency, but the blood pressure was elevated during oxygen administration in every trial.
Sonographic septation: a predictor of sequelae of tuberculous pleurisy after treatment
Authors: Y-F Lai, M-C Su, H-H Weng, J-T Wu, C-T Chiu
Journal: Thorax (2009)

Findings in the literature have been quite conflicting with respect to predicting residual pleural thickening (RPT) in tuberculous pleurisy (TP). The aim of this study was to determine which sonographic feature of TP might help in predicting the development of RPT.Eighty-seven patients with TP were enrolled prospectively. The initial sonographic features were classified as anechoic, homogenously echogenic, complex non-septated and complex septated. The RPT level was measured 12 months after the start of antituberculosis (TB) treatment. Spirometry was performed 6 and 12 months after the start of anti-TB treatment.A higher odds of an RPT level >10 mm was found in patients with positive TB bacillus culture in pleural fluid (OR, 20.9; 95% CI, 2.2 to 198.0) and a complex septated sonographic pattern (OR, 145.0; 95% CI, 22.3 to 942.3). A complex septated sonographic pattern can predict RPT with a sensitivity of 80%, specificity of 96%, positive predictive value of 84% and negative predictive value of 94%. Patients with an RPT level >10 mm had a lower forced vital capacity than those without (75.4% (9.2%) predicted vs 83.2% (9.5%) predicted, p<0.01)A complex septated sonographic pattern is a useful sign to predict an RPT level >10 mm 1 year after the start of anti-TB treatment. An RPT level >10 mm is associated with a high probability of decreased lung volumes. Therefore, the initial sonographic feature is beneficial in predicting the sequelae of TP after treatment.
Documentation of off-label use of biologics in Rheumatoid Arthritis
Authors: Daniel E Furst, Roy Fleischman, Joachim Kalden, Arthur Kavanaugh, Joachim Sieper, Philip Mease, Josef Smolen, Ferrie Breedveld
Journal: Annals of the Rheumatic Diseases (2013)

The ‘Updated Consensus Statement on Biological Agents for the Treatment of Rheumatic Diseases’ represents the consensus and efforts of a worldwide group of experts regarding the use of biologics in Rheumatoid Arthritis. That document details the use of biologics in registered uses for those drugs.

However, the biologic agents are used ‘off label’ in a very large array of other rheumatic diseases. To some degree, those uses are based on animal studies and mechanistic rationale but they often …
Respiratory Syncytial Virus and Rhinovirus Contribute to the First Wheeze Episodes in Japanese Infants
Authors: Kazuko Sugai, Yumiko Miyaji, Masakazu Yoshizumi, Hiroyuki Tsukagoshi, Masahiro Noda, Yumi Yamada, Masanori Ikeda, Kunihisa Kozawa, Hirokazu Kimura, Shigemi Yoshihara, Yoshimichi Okayama
Journal: Journal of Allergy and Clinical Immunology (2015)
Twist Overexpression Induces <i>In vivo</i> Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer
Authors: Yelena Mironchik, Paul T. Winnard, Farhad Vesuna, Yoshinori Kato, Flonne Wildes, Arvind P. Pathak, Scott Kominsky, Dmitri Artemov, Zaver Bhujwalla, Paul Van Diest, Horst Burger, Carlotta Glackin, Venu Raman
Journal: Cancer Research (2005)

Abstract Aggressive cancer phenotypes are a manifestation of many different genetic alterations that promote rapid proliferation and metastasis. In this study, we show that stable overexpression of Twist in a breast cancer cell line, MCF-7, altered its morphology to a fibroblastic-like phenotype, which exhibited protein markers representative of a mesenchymal transformation. In addition, it was observed that MCF-7/Twist cells had increased vascular endothelial growth factor (VEGF) synthesis when compared with empty vector control cells. The functional changes induced by VEGF in vivo were analyzed by functional magnetic resonance imaging (MRI) of MCF-7/Twist-xenografted tumors. MRI showed that MCF-7/Twist tumors exhibited higher vascular volume and vascular permeability in vivo than the MCF-7/vector control xenografts. Moreover, elevated expression of Twist in breast tumor samples obtained from patients correlated strongly with high-grade invasive carcinomas and with chromosome instability, particularly gains of chromosomes 1 and 7. Taken together, these results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an aggressive breast cancer phenotype.
The results of the second year of carotid stenting
Authors: Erkan Köklü, Şakir Arslan, İsa Öner Yüksel, Göksel Çağırcı, Nermin Bayar, Akar Yılmaz, Zehra Erkal, Deniz Demirci, Selçuk Küçükseymen, Yasemin Biçer Gömceli
Journal: Journal of the American College of Cardiology (2013)
Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel genome-wide analysis
Authors: Robbert M. Spaapen, Henk M. Lokhorst, Kelly van den Oudenalder, Brith E. Otterud, Harry Dolstra, Mark F. Leppert, Monique C. Minnema, Andries C. Bloem, Tuna Mutis
Journal: The Journal of Experimental Medicine (2008)

Some minor histocompatibility antigens (mHags) are expressed exclusively on patient hematopoietic and malignant cells, and this unique set of antigens enables specific targeting of hematological malignancies after human histocompatability leucocyte antigen (HLA)–matched allogeneic stem cell transplantation (allo-SCT). We report the first hematopoietic mHag presented by HLA class II (HLA-DQA1*05/B1*02) molecules to CD4+ T cells. This antigen is encoded by a single-nucleotide polymorphism (SNP) in the B cell lineage-specific CD19 gene, which is an important target antigen for immunotherapy of most B cell malignancies. The CD19L-encoded antigen was identified using a novel and powerful genetic strategy in which zygosity-genotype correlation scanning was used as the key step for fine mapping the genetic locus defined by pairwise linkage analysis. This strategy was also applicable for genome-wide identification of a wide range of mHags. CD19L-specific CD4+ T cells provided antigen-specific help for maturation of dendritic cells and for expansion of CD8+ mHag-specific T cells. They also lysed CD19L-positive malignant cells, illustrating the potential therapeutic advantages of targeting this novel CD19L-derived HLA class II–restricted mHag. The currently available immunotherapy strategies enable the exploitation of these therapeutic effects within and beyond allo-SCT settings.
Integrated breathing and relaxation training (the Papworth method) for adults with asthma in primary care: a randomised controlled trial
Authors: E. A Holloway, R. J West
Journal: Thorax (2007)

An integrated breathing and relaxation technique known as the Papworth method has been implemented by physiotherapists since the 1960s for patients with asthma and dysfunctional breathing, but no controlled trials have been reported. This study evaluated the effectiveness of the Papworth method in a randomised controlled trial.Eighty-five patients (36 men) were individually randomised to the control group (n = 46) or to the intervention group receiving five sessions of treatment by the Papworth method (n = 39). Both groups received usual medical care. Assessments were undertaken at baseline, post-treatment (6 months after baseline) and at 12 months. The primary outcome measure was the St George's Respiratory Symptoms Questionnaire (SGRQ). Secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the Nijmegen dysfunctional breathing questionnaire and objective measures of respiratory function.Post-treatment and 12 month data were available for 78 and 72 patients, respectively. At the post-treatment assessment the mean (SD) score on the SGRQ Symptom subscale was 21.8 (18.1) in the intervention group and 32.8 (20.1) in the control group (p = 0.001 for the difference). At the 12 month follow-up the corresponding figures were 24.9 (17.9) and 33.5 (15.9) (p = 0.007 for the difference). SGRQ Total scores and HADS and Nijmegen scores were similarly significantly lower in the intervention group than in the control group. The groups did not differ significantly following the treatment on objective measures of respiratory function except for relaxed breathing rate.The Papworth method appears to ameliorate respiratory symptoms, dysfunctional breathing and adverse mood compared with usual care. Further controlled trials are warranted to confirm this finding, assess the effect in other patient groups and determine whether there is some effect on objective measures of respiratory function.
Circulating Tumor Cells: Not All Detected Cells Are Bad and Not All Bad Cells Are Detected
Authors: Max S. Wicha, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2011)

More than 90% of cancer deaths result from the development of hematogenously disseminated metastasis. The presence of circulating tumor cells (CTCs) in patients with cancer was first reported in 1869. 1 More recently, methods have been developed to detect, isolate, and characterize CTCs in multiple different malignancies that arise in solid organs. 2 The most widely used method, designated CellSearch (Veridex, Raritan, NJ), relies on immunomagnetic capture of CTCs using antibodies against the epithelial cell adhesion molecule (EpCam), which is expressed on the cell surface of many epithelial malignancies, followed by additional characterization with 4,6-diamidino-2-phenylindole staining (to
Remembrance of Things (Hopefully) Past
Authors: M. Therese Southgate
Journal: JAMA (1975)

IT IS generally held that physicians, and especially psychiatrists, kill themselves at a rate higher than that of the rest of the population.<sup>1</sup>It has been further suggested, both by Craig and Pitts,<sup>1</sup>and by Steppacher and Mausner,<sup>2</sup>that among physicians the suicide rate of the women exceeds that of the men, regardless of specialty.<sup>1</sup>This excess was limited by women physicians under 45 years of age; after age 45 their rate was somewhat less than the rate of men physicians.<sup>2</sup> Steppacher and Mausner's<sup>2</sup>study group comprised all physicians who had committed suicide during the 5 1/2-year period, 1965 to 1970. Of the 41 women suicides, nearly two thirds died before age 45. Half of the total group of women had never married; almost one third were still in training. Mausner and Steppacher<sup>3</sup>place the contributory stresses primarily in the training years, that
The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia
Authors: Luciana Teofili, Francesco Pierconti, Annalaura Di Febo, Nicola Maggiano, Nicola Vianelli, Stefano Ascani, Elena Rossi, Stefano Pileri, Giuseppe Leone, Luigi Maria Larocca, Valerio De Stefano
Journal: Blood (2002)
Aspirin for Primary Prevention of Cardiovascular Events in Diabetes
Authors: John A. Colwell
Journal: Diabetes Care (2003)

Aspirin is probably the most widely used and least expensive drug in existence. The value of extracts of willow bark in controlling pain and fever was recognized in 400 BC by Hippocrates. In the 19th century, salicylic acid was identified as the active principle, and in 1899, Felix Hoffman synthesized acetylsalicylic acid. Shortly thereafter, Heinrich Dreser, director of pharmacological research for Bayer and Company, led the clinical trials that demonstrated efficacy and named this new drug aspirin.

In the 20th century, aspirin attracted the attention of physicians interested in cardiovascular disease after it was found that platelet cyclooxygenase, the enzyme that converts arachidonic acid to prostaglandins G2 and H2, was irreversibly inhibited in man by very low doses of aspirin. This blockade would inhibit thromboxane production, platelet aggregation, and vasoconstriction. Meta-analyses of large-scale clinical trials have shown that aspirin will reduce the risk for major cardiovascular events by ∼25% in high-risk individuals (1).

People with type 2 diabetes have a risk of myocardial infarction, stroke, and cardiovascular death that is at least two- to fourfold greater than that of age- and sex-matched control subjects. Individuals with diabetes have been shown to have platelets that are unusually sensitive to aggregating agents and manufacture prostaglandin metabolites and thromboxane in excess. Platelets from diabetic subjects also display increased adhesiveness via nonprostaglandin-mediated pathways. Two of these pathways are mediated by the ADP receptor and fibrinogen binding to the GPIIb/IIIa complex. Fibrinolytic activity is often suppressed in type 2 diabetes, predominantly via inhibitory actions of plasminogen activator inhibitor (PAI-1) on fibrinolysis. Approximately 90% of the …
Benzodiazepine-associated delirium in critically ill adults
Authors: Irene J. Zaal, John W. Devlin, Marijn Hazelbag, Peter M. C. Klein Klouwenberg, Arendina W. van der Kooi, David S. Y. Ong, Olaf L. Cremer, Rolf H. Groenwold, Arjen J. C. Slooter
Journal: Intensive Care Medicine (2015)
HER2 Inhibition: From Discovery to Clinical Practice
Authors: Jenny C. Chang
Journal: Clinical Cancer Research (2007)

In this issue of Clinical Cancer Research, Buzdar et al. ([1][1]) report on the success of trastuzumab, a humanized monoclonal antibody against the proto-oncogene HER2 (c-erbB2, HER-2/ neu ), when administered with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) and paclitaxel chemotherapy,
The Meaning of Stress, Anxiety and Collective Panic in Clinical Settings
Authors: J J López-Ibor
Journal: Psychotherapy and Psychosomatics (1987)

The physician is often confronted with questions about the meaning of symptoms or diseases. One of the tasks of those practicing psychosomatic medicine is to delve into the answers to these questions. Anxiety is a common phenomenon in everyday practice, and it is evoked in the most different situations. The relationship of this kind of anxiety (i.e. when having to consider painful or life-threatening diseases or medical or surgical procedures) to both neurotic anxiety and normal anxiety (i.e. the one expressed in poetry or artistic creativity or present in the biographies of outstanding men and women who by no means could be considered as psychiatric cases) leads to define anxiety as the psychological equivalent of stress. Anxiety is the unspecific response to a threat induced by too sudden or too extreme variations in the environment (life changes, stressful situations, life events). Such mechanisms, so important for survival, can become self-destructive, paving the way for the appearance of diseases represented by unsuccessful coping mechanisms. The analogy with the diseases of the general adaptation syndrome of Selye (i.e. autoimmune diseases) and with reactions in collective panics in disasters becomes evident under this perspective. The physician has to face anxiety with the same attitude that he faces pain, that is to say, going beyond a consideration of its 'normality' (it is quite normal to feel chest pain in acute heart infarct), keeping in mind its role in survival. Most creative men and women are, as many psychohistorical studies have shown, individuals who have been able to find a solution to internal conflicts which were conflicts of the society in which they lived, leading to a solution of this same external conflict. The anxiety which is often expressed in this situation has an element of restlessness, which is lacking in anxiety and related disorders which are dominated by feelings of inability to cope expressed time and again as 'Dr., I can't' (go out in the street, in elevators, live, love, work, and so on).