tbuckley/cabot-search huggingface dataset:
Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock
Authors: R. Phillip Dellinger, Jean M. Carlet, Henry Masur, Herwig Gerlach, Thierry Calandra, Jonathan Cohen, Juan Gea-Banacloche, Didier Keh, John C. Marshall, Margaret M. Parker, Graham Ramsay, Janice L. Zimmerman, Jean-Louis Vincent, M. M. Levy
Journal: Intensive Care Medicine (2004)
Troublesome Symptoms in Cancer Survivors: Fatigue, Insomnia, Neuropathy, and Pain
Authors: Deirdre R. Pachman, Debra L. Barton, Keith M. Swetz, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2012)

Patients with cancer suffer from a variety of symptoms associated with both cancer and its treatment. These symptoms may lead to a decreased quality of life for patients and can affect compliance with cancer therapies. The importance of adequately treating cancer-related symptoms is gaining more attention but, overall, many symptoms remain underdiagnosed and undertreated. Fatigue, insomnia, neuropathy, and pain are among the most common troublesome symptoms experienced by cancer survivors. This article will focus on the management of these symptoms, including an assessment of the current research and proposed best- management practices.
Dominance runs deep
Authors: Valerie J. Grant
Journal: Behavioral and Brain Sciences (1998)

Seen in its historical context, Mazur &amp; Booth's (M&amp;B's) target article may come to be viewed as a turning point in the study of the biological basis of human behavior in general, and dominance in particular. To facilitate further research, suggestions are offered for making the definition of dominance more precise. From an evolutionary point of view, the testosterone-dominance link may be as important in women as it is in men.
Breast cancer patients' expectations in respect of the physician–patient relationship and treatment management results of a survey of 617 patients
Authors: G. Oskay-Özcelik, W. Lehmacher, D. Könsgen, H. Christ, M. Kaufmann, W. Lichtenegger, M. Bamberg, D. Wallwiener, F. Overkamp, K. Diedrich, G. von Minckwitz, K. Höffken, S. Seeber, R. Mirz, J. Sehouli
Journal: Annals of Oncology (2007)
Endoscopic necrosectomy in necrotising pancreatitis: indication is the key
Authors: H. C. van Santvoort, M. G. Besselink, O. J. Bakker, F. P. Vleggaar, R. Timmer, B. L. Weusten, H. G. Gooszen
Journal: Gut (2010)

We read with great interest the paper by Seifert et al on the outcome of endoscopic necrosectomy in 93 patients with necrotising pancreatitis.1 We congratulate the authors in completing a multicentre study in such a complicated group of patients. The authors conclude that endoscopic necrosectomy has good initial success and favourable long-term outcome. Complication rate and mortality rate were 25% and 7.5%, respectively. Although it was suggested that these results may compare favourably with recent series on surgical necrosectomy, we feel these data should be interpreted with caution.

The primary indication for necrosectomy in patients with necrotising pancreatitis is infected necrosis, as is stated in international guidelines.2–4 Intervention in …
Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial
Authors: J Smolen, R B Landewe, P Mease, J Brzezicki, D Mason, K Luijtens, R F van Vollenhoven, A Kavanaugh, M Schiff, G R Burmester, V Strand, J Vencovsky, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. <h3>Objective:</h3> To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). <h3>Methods:</h3> An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. <h3>Results:</h3> Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. <h3>Conclusion:</h3> Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. <h3>Trial registration number:</h3> NCT00175877
IMPAIRED HYPEREMIC MYOCARDIAL BLOOD FLOW IS ASSOCIATED WITH INDUCIBILITY OF VENTRICULAR ARRHYTHMIA IN ISCHEMIC CARDIOMYOPATHY
Authors: Mischa Rijnierse, Stefan de Haan, Hendrik Harms, Lourens Robbers, LiNa Wu, Ibrahim Danad, Aernout Beek, Martijn Heymans, Albert van Rossum, Adriaan Lammertsma, Cornelis Allaart, Paul Knaapen
Journal: Journal of the American College of Cardiology (2014)
R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair
Authors: Mario Federico, Catherine E Symonds, Luigi Bagella, Flavio Rizzolio, Daniele Fanale, Antonio Russo, Antonio Giordano
Journal: Molecular Cancer (2010)

CDK-inhibitors can diminish transcriptional levels of cell cycle-related cyclins through the inhibition of E2F family members and CDK7 and 9. Cyclin A1, an E2F-independent cyclin, is strongly upregulated under genotoxic conditions and functionally was shown to increase NHEJ activity. Cyclin A1 outcompetes with cyclin A2 for CDK2 binding, possibly redirecting its activity towards DNA repair. To see if we could therapeutically block this switch, we analyzed the effects of the CDK-inhibitor R-Roscovitine on the expression levels of cyclin A1 under genotoxic stress and observed subsequent DNA damage and repair mechanisms. We found that R-Roscovitine alone was unable to alter cyclin A1 transcriptional levels, however it was able to reduce protein expression through a proteosome-dependent mechanism. When combined with DNA damaging agents, R-Roscovitine was able to prevent the DNA damage-induced upregulation of cyclin A1 on a transcriptional and post-transcriptional level. This, moreover resulted in a significant decrease in non-homologous end-joining (NHEJ) paired with an increase in DNA DSBs and overall DNA damage over time. Furthermore, microarray analysis demonstrated that R-Roscovitine affected DNA repair mechanisms in a more global fashion. Our data reveal a new mechanism of action for R-Roscovitine on DNA repair through the inhibition of the molecular switch between cyclin A family members under genotoxic conditions resulting in reduced NHEJ capability.
Self-Recognition of Cd1 by γ/δ T Cells
Authors: Franca M. Spada, Ethan P. Grant, Peter J. Peters, Masahiko Sugita, Augustín Melián, David S. Leslie, Hoi K. Lee, Elly van Donselaar, Dennis A. Hanson, Alan M. Krensky, Otto Majdic, Steven A. Porcelli, Craig T. Morita, Michael B. Brenner
Journal: The Journal of Experimental Medicine (2000)

The specificity of immunoglobulins and α/β T cell receptors (TCRs) provides a framework for the molecular basis of antigen recognition. Yet, evolution has preserved a separate lineage of γ/δ antigen receptors that share characteristics of both immunoglobulins and α/β TCRs but whose antigens remain poorly understood. We now show that T cells of the major tissue γ/δ T cell subset recognize nonpolymorphic CD1c molecules. These T cells proliferated in response to CD1+ presenter cells, lysed CD1c+ targets, and released T helper type 1 (Th1) cytokines. The CD1c-reactive γ/δ T cells were cytotoxic and used both perforin- and Fas-mediated cytotoxicity. Moreover, they produced granulysin, an important antimicrobial protein. Recognition of CD1c was TCR mediated, as recognition was transferred by transfection of the γ/δ TCR. Importantly, all CD1c-reactive γ/δ T cells express Vδ1 TCRs, the TCR expressed by most tissue γ/δ T cells. Recognition by this tissue pool of γ/δ T cells provides the human immune system with the capacity to respond rapidly to nonpolymorphic molecules on professional antigen presenting cells (APCs) in the absence of foreign antigens that may activate or eliminate the APCs. The presence of bactericidal granulysin suggests these cells may directly mediate host defense even before foreign antigen-specific T cells have differentiated.
The Hypocholesterolizing Effect of Gallogen and its Potentiation by Soybean Sterols
Authors: THOMAS B. CLARKSON, J. STANTON KING, NELTA HYDBR WARNOCK
Journal: Circulation Research (1956)

Gallogen (the diethanolamine salt of the mono-(+)-camphoric acid ester of α,4-dimethylbenzyl alcohol) and soybean sterols have been tested for their effect, singly and in combination, on hypercholesterolemia and aortic cholesterol in cholesterol-fed cockerels. Gallogen alone was found to impede the rise of serum and aortic cholesterol, and also to potentiate these effects of soybean sterols.
BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway
Authors: Andrew Craxton, Kevin E. Draves, Adriana Gruppi, Edward A. Clark
Journal: The Journal of Experimental Medicine (2005)

The B cell activating factor belonging to the tumor necrosis factor family (BAFF) is required for B cell survival and maturation. The mechanisms by which BAFF mediates B cell survival are less understood. We found that BAFF and a proliferation-inducing ligand (APRIL), which are related, block B cell antigen receptor (BCR)–induced apoptosis upstream of mitochondrial damage, which is consistent with a role for Bcl-2 family proteins. BCR ligation strongly increased expression of the proapoptotic Bcl-2 homology 3–only Bcl-2 protein Bim in both WEHI-231 and splenic B cells, and increases in Bim were reversed by BAFF or APRIL. Small interfering RNA vector–mediated suppression of Bim blocked BCR-induced apoptosis. BAFF also induced Bim phosphorylation and inhibited BCR-induced association of Bim with Bcl-2. BAFF induced delayed but sustained stimulation of extracellular signal–regulated kinase (ERK) and its activators, mitogen-activated protein kinase/ERK activating kinase (MEK) and c-Raf, and MEK inhibitors promoted accumulation and dephosphorylation of Bim. These results suggest that BAFF inhibits BCR-induced death by down-regulating Bim via sustained ERK activation, demonstrating that BAFF directly regulates Bim function. Although transitional immature type 1 (T1) B cell numbers are normal in Bim−/− mice, T2 and follicular mature B cells are elevated and marginal zone B cells are reduced. Our results suggest that mature B cell homeostasis is maintained by BAFF-mediated regulation of Bim.
Complete Atrioventricular Block Due to Potassium
Authors: CHARLES FISCH, KALMAN GREENSPAN, ROBERT E. EDMANDS
Journal: Circulation Research (1966)

Intravenous infusion of KC1 at a rate of 1.22 or 2.45 mEq per minute to anesthetized dogs frequently resulted in complete A-V block at a time when P waves were still recorded in the ECG. Furthermore, some of the observations suggest that in hyperkalemia a regular idioventricular rhythm may not be essential for the diagnosis of complete atrioventricular (A-V) block. Thus, with complete A-V block induced during a rapidly changing plasma K + , the ventricular pacemaker may be irregular. In addition, evidence was obtained that some parts of the atrial tissue, the automatic ventricular focus and the ventricular myocardium, are more resistant to K + than is the A-V conduction tissue. The relative sensitivity of the various tissues of the heart seems to depend, among other factors, on the rate of KCl infusion.
Tumor Suppressor Maspin Is Up-Regulated during Keratinocyte Senescence, Exerting a Paracrine Antiangiogenic Activity
Authors: Brian J. Nickoloff, Mark W. Lingen, Bey-Dih Chang, Mei Shen, Mari Swift, Jonathan Curry, Patricia Bacon, Barbara Bodner, Igor B. Roninson
Journal: Cancer Research (2004)

Abstract Cell senescence is a physiological program of terminal growth arrest, which is believed to play an important role in cancer prevention. Senescent cells secrete multiple growth-regulatory proteins, some of which can affect tumor growth, survival, invasion, or angiogenesis. Changes in expression of different senescence-associated genes were analyzed in cultured human skin keratinocytes (KCs) that underwent replicative senescence or confluence-induced accelerated senescence. Senescent KC cultures showed a strong increase in mRNA and protein expression of maspin, a member of serine protease inhibitor family and an epithelial cell tumor suppressor with anti-invasive and antiangiogenic activities. Immunohistochemical analysis of 14 normal human skin samples (age range from 3 months to 84 years) showed that maspin is expressed by KCs in vivo and that the extent and intensity of maspin expression in the skin is significantly (P = 0.01) correlated with chronological age. Antiangiogenic activity of maspin secreted by senescent KCs was investigated in vitro by testing the effect of conditioned media from different KC cultures on endothelial cell migration in the presence or absence of several angiogenic factors. Media conditioned by senescent cultures (undergoing replicative or accelerated senescence), but not by proliferating KCs, strongly inhibited the stimulation of endothelial cell migration by all of the tested angiogenic factors. Neutralizing antibody against maspin abrogated this effect of conditioned media. These findings indicate that senescent KCs exert a paracrine antiangiogenic activity, and maspin is the principal contributor to this potentially tumor-suppressive effect of cellular senescence.
Validity of Models for Predicting BRCA1 and BRCA2 Mutations
Authors: Giovanni Parmigiani
Journal: Annals of Internal Medicine (2007)

Background: Deleterious mutations of the BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. At least 7 models for estimating the probabilities of having a mutation are used widely in clinical and scientific activities; however, the merits and limitations of these models are not fully understood. Objective: To systematically quantify the accuracy of the following publicly available models to predict mutation carrier status: BRCAPRO, family history assessment tool, Finnish, Myriad, National Cancer Institute, University of Pennsylvania, and Yale University. Design: Cross-sectional validation study, using model predictions and BRCA1 or BRCA2 mutation status of patients different from those used to develop the models. Setting: Multicenter study across Cancer Genetics Network participating centers. Patients: 3 population-based samples of participants in research studies and 8 samples from genetic counseling clinics. Measurements: Discrimination between individuals testing positive for a mutation in BRCA1 or BRCA2 from those testing negative, as measured by the c-statistic, and sensitivity and specificity of model predictions. Results: The 7 models differ in their predictions. The better-performing models have a c-statistic around 80%. BRCAPRO has the largest c-statistic overall and in all but 2 patient subgroups, although the margin over other models is narrow in many strata. Outside of high-risk populations, all models have high false-negative and false-positive rates across a range of probability thresholds used to refer for mutation testing. Limitation: Three recently published models were not included. Conclusions: All models identify women who probably carry a deleterious mutation of BRCA1 or BRCA2 with adequate discrimination to support individualized genetic counseling, although discrimination varies across models and populations.
Overexpression of von Hippel–Lindau protein synergizes with doxorubicin to suppress hepatocellular carcinoma in mice
Authors: Jizhou Wang, Yong Ma, Hongchi Jiang, Huaqiang Zhu, Lianxin Liu, Bei Sun, Shangha Pan, Geoffrey W. Krissansen, Xueying Sun
Journal: Journal of Hepatology (2010)
Factors associated with illness in athletes participating in the London 2012 Paralympic Games: a prospective cohort study involving 49 910 athlete-days
Authors: Martin Schwellnus, Wayne Derman, Esme Jordaan, Cheri A Blauwet, Carolyn Emery, Pia Pit-Grosheide, Norma-Angelica Patino Marques, Oriol Martinez-Ferrer, Jaap Stomphorst, Peter Van de Vliet, Nick Webborn, Stuart E Willick
Journal: British Journal of Sports Medicine (2013)

Background The incidence and factors associated with illness in Paralympic athletes have not been documented. Aim To determine the factors associated with illness in athletes participating in the London 2012 Paralympic Games. Methods A cohort of 3565 athletes from 160 of the 164 participating countries in the London 2012 Paralympic Games were followed over a 14-day period (precompetition period=3 days, competition period=11 days; 49 910 athlete-days). Daily illness data were obtained from (1) teams with their own medical support who completed a daily illness log (78 teams, 3329 athletes) on a novel web-based system and (2) teams without their own medical support through the local organising committee database (82 teams, 236 athletes). Illness information from all athletes included age, gender, type of sport and the main system affected. Main outcome measurement Incidence rate (IR) of illness (illness per 1000 athlete-days) and factors associated with IR (time period, gender, age and sport). Results The IR of illness was 13.2 (95% CI 12.2 to 14.2). The highest IR of illness was in the respiratory system, followed by the skin, digestive, nervous and genitourinary systems. The IR in the precompetition period was similar to that in the competition period, but the IR was significantly higher in athletics compared with other sports. Age and gender were not independent predictors of illness. Conclusions Illness is common in Paralympic athletes and the main factor associated with higher IR of illness was the type of sport (athletics).
Rat Sodium Iodide Symporter for Radioiodide Therapy of Cancer
Authors: Elena Mitrofanova, Robert Unfer, Nick Vahanian, Wayne Daniels, Erica Roberson, Tatiana Seregina, Prem Seth, Charles Link
Journal: Clinical Cancer Research (2004)

Design and development of new approaches for targeted radiotherapy of cancer and improvement of therapeutic index by more local radiation therapy are very important issues. Adenovirus-mediated delivery of the sodium iodide symporter (NIS) gene to cancer cells is a powerful technique to concentrate lethal radiation in tumor cells and eradicate tumors with increased therapeutic index. A replication-defective adenoviral vector expressing the rat NIS gene (Ad-rNIS) was used for in vitro gene delivery and into human prostate cancer xenografts to study antitumor effect. Robust function of the rat symporter was detected in DU145, T47D, and HCT-15 human cancer cell lines transduced with Ad-rNIS. All three cancer cell lines successfully transferred functionally active rat symporter to the plasma membrane, resulting in very high levels of iodine-125 accumulation. Three-dimensional multicellular tumor spheroids derived from DU145 human prostate cancer cells were transduced with Ad-rNIS and incubated with (131)I for 24 hours. After treatment, spheroids rapidly decreased in size and disappeared within 10 days. In vivo data revealed an inhibition of tumor growth in athymic nude mice after intratumoral Ad-rNIS injection followed by (131)I administration. Eighty-eight percent of experimental mice survived >30 days, whereas control groups had only 18% survival >30 days. This is the first report that demonstrates the rat NIS gene can effectively induce growth arrest of human tumor xenografts after in vivo adenoviral gene delivery and (131)I administration. The data confirm our hypothesis that the rat NIS gene is an attractive suicide gene candidate for cancer treatment.
Shrinkage of skin excision specimens: formalin fixation is not the culprit
Authors: J.N. Dauendorffer, S. Bastuji-Garin, S. Guéro, N. Brousse, S. Fraitag
Journal: British Journal of Dermatology (2009)

Discrepancies between cutaneous specimen sizes reported by the dermatosurgeon and the pathologist are important to evaluate because of their legal implications for malignant tumours and the downcoding of surgical acts.The objective of this study was to determine the magnitude of changes in size and the factors influencing the retraction of routine skin excision specimens.Three measurements of 82 skin excision specimens--consisting of length and width of the planned surgical excision (in vivo), length, width and depth of the specimens following excision (ex vivo) and of the specimens after formalin fixation (in vitro)--were performed and compared using a nonparametric paired test. Factors (age, sex, type and location of the lesions and initial measures) that could influence the amount of shrinkage were analysed using multiple linear regression models.The mean in vivo to in vitro shrinkage was 16% for length and 18% for width (P<0.001). The shrinkage was significant between in vivo and ex vivo measures (P<0.001), while no difference was observed between ex vivo to in vitro measures. In multivariate analysis, length shrinkage increased significantly with initial length (regression coefficient of 0.24, P=0.001) and limb location (1.25, P=0.048), and decreased significantly with initial width (-0.19, P=0.016). After adjusting for initial width, width shrinkage was neither significantly associated with type of lesion (malignant or not, P=0.20), nor with location (P=0.35).Shrinkage of skin excision specimens occurred immediately after surgical excision and prior to formalin fixation. Patients' age, sex and type of skin lesion did not influence the amount of shrinkage. Length shrinkage was more important for specimens excised from the extremities and increased with initial length and smaller width.
Deposition and metabolism of inhaled ciclesonide in the human lung
Authors: R. Nave, H. Watz, H. Hoffmann, H. Boss, H. Magnussen
Journal: European Respiratory Journal (2010)

Ciclesonide is an inhaled corticosteroid, administered as a prodrug <i>via</i> a metered-dose inhaler. Following deposition in the lung, ciclesonide is hydrolysed by esterases to form the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Formation of des-CIC, as well as reversible esterification of des-CIC with fatty acids, has been demonstrated <i>in vitro</i>. The aim of this study was to investigate the <i>in vivo</i> metabolism of ciclesonide in the human lung. This single-dose, open-label, nonrandomised study was performed in 20 patients undergoing planned lung surgery for treatment of malignant pulmonary lesions. Patients inhaled a single dose of 1,280 μg ciclesonide at various time-points between 2 and 24 h prior to lung tissue resection. The concentration of ciclesonide, des-CIC and fatty acid conjugates of des-CIC in tissue samples was determined. Serum samples for pharmacokinetic analysis were taken at several time-points after inhalation. The pharmacokinetics in serum indicated that the inhalation by the patients was adequate. Metabolites (des-CIC, des-CIC oleate and des-CIC palmitate) were detected in the resected central and peripheral lung tissues. A substantial portion of ciclesonide was already activated to des-CIC at the first time-point of tissue analysis. Activation of ciclesonide and formation of des-CIC fatty acid conjugates was confirmed <i>in vivo</i> in the human lung.