tbuckley/cabot-search huggingface dataset:
The ageing athlete: screening prior to vigorous exertion in asymptomatic adults without known cardiovascular disease
Authors: J Freeman, V Froelicher, E Ashley
Journal: British Journal of Sports Medicine (2009)

The exercise electrocardiogram (ECG) is widely considered the best available test for screening asymptomatic adults without known cardiovascular (CV) disease prior to initiating a vigorous exercise programme due to its prognostic value, widespread availability and low cost. Observational studies have demonstrated an increased relative risk of CV events with positive screening exercise ECG tests in men with diabetes, advanced age, or multiple cardiac risk factors. Recent observational studies have not demonstrated similar prognostic value for exercise ECG testing in asymptomatic healthy women. Despite the predictive ability of exercise ECG testing in several groups, there have been no studies demonstrating a significant impact of screening on morbidity and mortality in completely asymptomatic patients, leading to significant discordance in consensus guidelines on screening. One prospective observational study is ongoing in Italy that may for the first time demonstrate the ability to decrease incident CV events using preparticipation screening exercise ECG testing in adult athletes with targeted exclusion from athletics. Until more conclusive data is available the authors currently recommend screening exercise ECG testing in asymptomatic men with diabetes and asymptomatic men over age 45 with two or more CV risk factors prior to initiating a vigorous exercise programme. Consideration should also be given to screening asymptomatic patients younger than 45 with particularly strong risk factor exposure or elderly patients with fewer than two risk factors.
Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults
Authors: Ulla A. Hvidtfeldt, Janne S. Tolstrup, Marianne U. Jakobsen, Berit L. Heitmann, Morten Grønbæk, Eilis O'Reilly, Katarina Bälter, Uri Goldbourt, Göran Hallmans, Paul Knekt, Simin Liu, Mark Pereira, Pirjo Pietinen, Donna Spiegelman, June Stevens, Jarmo Virtamo, Walter C. Willett, Eric B. Rimm, Alberto Ascherio
Journal: Circulation (2010)

Background— Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men &lt;40 years of age and in women &lt;50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. Methods and Results— In this pooled analysis of 8 prospective studies from North America and Europe including 192 067 women and 74 919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and ≥60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100 000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100 000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100 000; 90% CI, 44 to 140) adults. Similar results were observed in women. Conclusion— Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults.
Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring
Authors: K Ohnishi, H Yoshida, K Shigeno, S Nakamura, S Fujisawa, K Naito, K Shinjo, Y Fujita, H Matsui, N Sahara, A Takeshita, H Satoh, H Terada, R Ohno
Journal: Leukemia (2002)
Combinatorial Chemotherapeutic Efficacy in Non-Hodgkin Lymphoma Can Be Predicted by a Signaling Model of CD20 Pharmacodynamics
Authors: John M. Harrold, Robert M. Straubinger, Donald E. Mager
Journal: Cancer Research (2012)

Combination chemotherapy represents the standard-of-care for non-Hodgkin lymphoma. However, the development of new therapeutic regimens is empirical and this approach cannot be used prospectively to identify novel or optimal drug combinations. Quantitative system pharmacodynamic models could promote the discovery and development of combination regimens based upon first principles. In this study, we developed a mathematical model that integrates temporal patterns of drug exposure, receptor occupancy, and signal transduction to predict the effects of the CD20 agonist rituximab in combination with rhApo2L/TNF-related apoptosis inducing ligand or fenretinide, a cytotoxic retinoid, upon growth kinetics in non-Hodgkin lymphoma xenografts. The model recapitulated major regulatory mechanisms, including target-mediated disposition of rituximab, modulation of proapoptotic intracellular signaling induced by CD20 occupancy, and the relative efficacy of death receptor isoforms. The multiscale model coupled tumor responses to individual anticancer agents with their mechanisms of action in vivo, and the changes in Bcl-xL and Fas induced by CD20 occupancy were linked to explain the synergy of these drugs. Tumor growth profiles predicted by the model agreed with cell and xenograft data, capturing the apparent pharmacologic synergy of these agents with fidelity. Together, our findings provide a mechanism-based platform for exploring new regimens with CD20 agonists.
Auditory Startle Response in Trauma Survivors With Posttraumatic Stress Disorder: A Prospective Study
Authors: Arieh Y. Shalev, Tuvia Peri, Dalia Brandes, Sara Freedman, Scott P. Orr, Roger K. Pitman
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Previous studies have shown elevated autonomic responses to startling tones in trauma survivors with chronic posttraumatic stress disorder (PTSD). The origin of these abnormal responses is obscure. The present study attempted to clarify this issue by prospectively evaluating responses to sudden, loud tones in individuals who arrived at a hospital emergency room after psychologically traumatic events. METHOD: By using a previously established protocol, autonomic and muscular responses to the tones were evaluated at 1 week, 1 month, and 4 months after the traumatic event. Structured diagnostic interviews performed at 4 months classified subjects into groups with (N=36) and without (N=182) PTSD, which were further subdivided according to the presence or absence of major depressive disorder as follows: neither PTSD nor depression (N=166), depression alone (N=16), PTSD alone (N=21), and both PTSD and depression (N=15). RESULTS: The groups showed comparable physiological responses to the tones at 1 week posttrauma. However, at 1 and 4 months posttrauma, the subjects with PTSD showed a greater heart rate response and required more stimulus trials to reach the criteria of skin conductance and orbicularis oculi electromyogram nonresponse. These findings were not significantly influenced by comorbid depression and were not explained by the severity of the traumatic event or by the intensity of the initial symptoms. CONCLUSIONS: Differences in physiological response to startling tones develop along with PTSD in the months that follow a traumatic event. This pattern supports the theories that associate PTSD with progressive neuronal sensitization.
Endoscopic Drainage of Pancreatic Pseudocysts: Long-Term Outcome and Procedural Factors Associated with Safe and Successful Treatment
Authors: D. Cahen, E. Rauws, P. Fockens, G. Weverling, K. Huibregtse, M. Bruno
Journal: Endoscopy (2005)

Background and Study Aims: Endoscopic drainage is a widely used treatment modality for pancreatic pseudocysts and has challenged more traditional drainage techniques. This retrospective study evaluates the short-term and long-term results with this technique and aims to identify procedural modifications that may improve its safety and efficacy. Patients and Methods: All consecutive patients who underwent endoscopic drainage of pancreatic pseudocysts in our hospital between 1983 and 2000 were included in the study. The patients' charts were reviewed, and long-term follow-up data were obtained by written questionnaires sent to the patients at the end of the follow-up period in November 2002. Results: A total of 92 patients were included (66 men, 26 women; median age 49 years). The technical success rate of the drainage procedure was 97 % and the mortality rate was 1 %. Complications occurred in 31 patients (34 %), eight of which (9 %) were major and required surgery: hemorrhage in four cases (three of which were caused by erosion of a straight endoprosthesis through the cyst wall), secondary infection in three, and perforation in one. During a median follow-up period of 43 months, 10 patients (11 %) underwent additional (nonendoscopic) treatment for a persistent cyst and five (5 %) for a recurrent cyst. Overall, endoscopic drainage was successful in 65 patients (71 %). Conclusions: Endoscopic drainage is an effective treatment for pancreatic pseudocysts and offers a definitive solution in almost three-quarters of the cases. The majority of major complications might have been prevented by using pigtail stents instead of straight stents and by taking a more aggressive approach to the prevention and treatment of secondary cyst infection.
New Derivatives of Vitamin B12 Show Preferential Targeting of Tumors
Authors: Robert Waibel, Hansjörg Treichler, Niklaus G. Schaefer, Dave R. van Staveren, Stefan Mundwiler, Susanne Kunze, Martin Küenzi, Roger Alberto, Jakob Nüesch, Alexander Knuth, Holger Moch, Roger Schibli, Pius August Schubiger
Journal: Cancer Research (2008)

Abstract Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled (57Co and 111In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue. By abolishing the interaction of a tailored vitamin B12 derivative to its transport protein transcobalamin II and therefore interrupting transcobalamin II receptor and megalin mediated uptake in normal tissue, preferential accumulation of a radiolabeled vitamin in cancer tissue could be accomplished. We identified transcobalamin I on tumors as a possible new receptor for this preferential accumulation of vitamin-mediated targeting. The low systemic distribution of radioactivity and the high tumor to blood ratio opens the possibility of a more successful clinical application of vitamin B12 for imaging or therapy. [Cancer Res 2008;68(8):2904–11]
Proteinuria: is it all in the foot?
Authors: Pierre Ronco
Journal: Journal of Clinical Investigation (2007)

Despite significant advances in our understanding of the molecular structure and composition of the glomerular filtration barrier, the mechanisms underlying the presence of excess protein in the urine (proteinuria) in acquired human kidney diseases remain elusive. In a study appearing in this issue of the JCI, Sever and associates use a combination of biochemical, genetic, and in vivo approaches in mice to demonstrate a pivotal role of cathepsin L and its substrate the GTPase dynamin, in the induction of proteinuria and associated foot process effacement in glomerular podocytes (see the related article beginning on page 2095).
Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites
Authors: Sabrina Morelli, Simona Salerno, Antonella Piscioneri, Bernke J. Papenburg, Anna Di Vito, Giuseppina Giusi, Marcello Canonaco, Dimitrios Stamatialis, Enrico Drioli, Loredana De Bartolo
Journal: Biomaterials (2010)
The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning
Authors: Mónica B. Jiménez-Castro, Noelia Meroño, Mariana Mendes-Braz, Jordi Gracia-Sancho, Laia Martínez-Carreres, Maria Eugenia Cornide-Petronio, Araní Casillas-Ramirez, Juan Rodés, Carmen Peralta
Journal: Journal of Hepatology (2014)
Dihydroxyacetone for protection against long wavelength UVA radiation and blue light
Authors: J.A. Johnson
Journal: British Journal of Dermatology (1992)

Journal Article Dihydroxyacetone for protection against long wavelength UVA radiation and blue light Get access J.A. Johnson J.A. Johnson Department of Internal Medicine/Dermatology University of Nebraska Medical Center, Omaha, NE 68198‐4360, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 126, Issue 1, 1 January 1992, Page 94, https://doi.org/10.1111/j.1365-2133.1992.tb08417.x Published: 01 January 1992
CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues
Authors: Rosa Anna DeFilippis, Hang Chang, Nancy Dumont, Joseph T. Rabban, Yunn-Yi Chen, Gerald V. Fontenay, Hal K. Berman, Mona L. Gauthier, Jianxin Zhao, Donglei Hu, James J. Marx, Judy A. Tjoe, Elad Ziv, Maria Febbraio, Karla Kerlikowske, Bahram Parvin, Thea D. Tlsty
Journal: Cancer Discovery (2012)

Abstract Although high mammographic density is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high mammographic density share key histologic features with stromal components within malignant lesions of tumor tissues, specifically low adipocyte and high extracellular matrix (ECM) content. We show that CD36, a transmembrane receptor that coordinately modulates multiple protumorigenic phenotypes, including adipocyte differentiation, angiogenesis, cell–ECM interactions, and immune signaling, is greatly repressed in multiple cell types of disease-free stroma associated with high mammographic density and tumor stroma. Using both in vitro and in vivo assays, we show that CD36 repression is necessary and sufficient to recapitulate the above-mentioned phenotypes observed in high mammographic density and tumor tissues. Consistent with a functional role for this coordinated program in tumorigenesis, we observe that clinical outcomes are strongly associated with CD36 expression. Significance: CD36 simultaneously controls adipocyte content and matrix accumulation and is coordinately repressed in multiple cell types within tumor and high mammographic density stroma, suggesting that activation of this stromal program is an early event in tumorigenesis. Levels of CD36 and extent of mammographic density are both modifiable factors that provide potential for intervention. Cancer Discov; 2(9); 826–39. ©2012 AACR. Read the Commentary on this article by DeClerck, p. 772. This article is highlighted in the In This Issue feature, p. 753.
Motor Protein–Dependent Membrane Trafficking of KCl Cotransporter-4 Is Important for Cancer Cell Invasion
Authors: Yih-Fung Chen, Cheng-Yang Chou, Robert J. Wilkins, J. Clive Ellory, David B. Mount, Meng-Ru Shen
Journal: Cancer Research (2009)

Abstract The KCl cotransporter (KCC) is a major determinant of osmotic homeostasis and plays an emerging role in tumor biology. This study stresses the important role of KCC4 in tumor malignant behavior. Real-time reverse transcription-PCR on samples collected by laser microdissection and immunofluorescent stainings with different KCC isoform antibodies indicate that KCC4 is abundant in metastatic cervical and ovarian cancer tissues. Insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulate KCC4 recruitment from a presumably inactive cytoplasmic pool of endoplasmic reticulum and Golgi to plasma membrane along actin cytoskeleton that is significantly inhibited by LY294002 and wortmannin. Throughout the trafficking process, KCC4 is incorporated into lipid rafts that function as a platform for the association between KCC4 and myosin Va, an actin-dependent motor protein. KCC4 and ezrin, a membrane cytoskeleton linker, colocalize at lamellipodia of migratory cancer cells. Interference with KCC activity by either an inhibitor or a dominant-negative loss-of-function mutant profoundly suppressed the IGF-I–induced membrane trafficking of KCC4 and the structural interaction between KCC4 and ezrin near the cell surface. Endogenous cancer cell invasiveness was significantly attenuated by small interfering RNA targeting KCC4, and the residual invasiveness was much less sensitive to IGF-I or EGF stimulation. In the metastatic cancer tissues, KCC4 colocalizes with IGF-I or EGF, indicating a likely in vivo stimulation of KCC4 function by growth factors. Thus, blockade of KCC4 trafficking and surface expression may provide a potential target for the prevention of IGF-I– or EGF-dependent cancer spread. [Cancer Res 2009;69(22):8585–93]
Cell-Type-Specific Responses to Chemotherapeutics in Breast Cancer
Authors: Melissa A. Troester, Katherine A. Hoadley, Therese Sørlie, Brittney-Shea Herbert, Anne-Lise Børresen-Dale, Per Eystein Lønning, Jerry W. Shay, William K. Kaufmann, Charles M. Perou
Journal: Cancer Research (2004)

Abstract Recent microarray studies have identified distinct subtypes of breast tumors that arise from different cell types and that show statistically significant differences in patient outcome. To gain insight into these differences, we identified in vitro and in vivo changes in gene expression induced by chemotherapeutics. We treated two cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and two lines derived from luminal epithelium (MCF-7 and ZR-75–1) with chemotherapeutics used in the treatment of breast cancer and assayed for changes in gene expression using DNA microarrays. Treatment doses for doxorubicin and 5-fluorouracil were selected to cause comparable cytotoxicity across all four cell lines. The dominant expression response in each of the cell lines was a general stress response; however, distinct expression patterns were observed. Both cell types induced DNA damage-response genes such as p21waf1, but the response in the luminal cells showed higher fold changes and included more p53-regulated genes. Luminal cell lines repressed a large number of cell cycle-regulated genes and other genes involved in cellular proliferation, whereas the basal cell lines did not. Instead, the basal cell lines repressed genes that were involved in differentiation. These in vitro responses were compared with expression responses in breast tumors sampled before and after treatment with doxorubicin or 5-fluorouracil/mitomycin C. The in vivo data corroborated the cell-type-specific responses to chemotherapeutics observed in vitro, including the induction of p21waf1. Similarities between in vivo and in vitro responses help to identify important response mechanisms to chemotherapeutics.
TLR2 Agonist PSK Activates Human NK Cells and Enhances the Antitumor Effect of HER2-Targeted Monoclonal Antibody Therapy
Authors: Hailing Lu, Yi Yang, Ekram Gad, Carol Inatsuka, Cynthia A. Wenner, Mary L. Disis, Leanna J. Standish
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The therapeutic effect of trastuzumab monoclonal antibody (mAb) therapy has been shown to be partially dependent on functional natural killer (NK) cells. Novel agents that enhance NK cell function could potentially improve the antitumor effect of trastuzumab. We recently identified polysaccharide krestin (PSK), a natural product extracted from medicinal mushroom Trametes versicolor, as a potent toll-like receptor 2 (TLR2) agonist. This study was undertaken to evaluate the effect of PSK on human NK cells and the potential of using PSK to enhance HER2-targeted mAb therapy. Experimental Design: Human peripheral blood mononuclear cells were stimulated with PSK to evaluate the effect of PSK on NK cell activation, IFN-γ production, cytotoxicity, and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Whether the effect of PSK on NK cells is direct or indirect was also investigated. Then, in vivo experiment in neu transgenic (neu-T) mice was carried out to determine the potential of using PSK to augment the antitumor effect of HER2-targeted mAb therapy. Results: PSK activated human NK cells to produce IFN-γ and to lyse K562 target cells. PSK also enhanced trastuzumab-mediated ADCC against SKBR3 and MDA-MB-231 breast cancer cells. Both direct and interleukin-12–dependent indirect effects seem to be involved in the effect of PSK on NK cells. Oral administration of PSK significantly potentiated the antitumor effect of anti-HER2/neu mAb therapy in neu-T mice. Conclusion: These results showed that PSK activates human NK cells and potentiates trastuzumab-mediated ADCC. Concurrent treatment with PSK and trastuzumab may be a novel way to augment the antitumor effect of trastuzumab. Clin Cancer Res; 17(21); 6742–53. ©2011 AACR.
Increased urinary albumin/creatinine ratio is associated with atopic dermatitis in Korean males: The 2011-2013 Korea National Health and Nutrition Examination Survey
Authors: Young Soo Kim, Dong-Hee Lee, Hee Yeon Kim, Jae-Im Lee, Tae Seo Sohn, Tae-Kyu Lee, Jae Yen Song, Seong Cheol Jeong, Chang Dong Yeo, Hiun Suk Chae, Mihee Hong, Young Bok Lee
Journal: Journal of the American Academy of Dermatology (2015)
Water-based exercise in COPD with physical comorbidities: a randomised controlled trial
Authors: Renae J. McNamara, Zoe J. McKeough, David K. McKenzie, Jennifer A. Alison
Journal: European Respiratory Journal (2012)

Land-based exercise is often difficult for people with chronic obstructive pulmonary disease (COPD) who have coexisting obesity or musculoskeletal or neurological conditions. This randomised controlled trial aimed to determine the effectiveness of water-based exercise training in improving exercise capacity and quality of life compared to land-based exercise training and control (no exercise) in people with COPD and physical comorbidities. Participants referred to pulmonary rehabilitation were randomly allocated to a water-based exercise, land-based exercise or the control group. The two exercise groups trained for 8 weeks, completing three sessions per week. 45 out of 53 participants (mean ± SD age 72 ± 9 years; forced expiratory volume in 1 s 59 ± 15% predicted) completed the study. Compared to controls, water-based exercise training significantly increased 6-min walking distance, incremental and endurance shuttle walk distances, and improved Chronic Respiratory Disease Questionnaire (CRDQ) dyspnoea and fatigue. Compared to land-based exercise training, water-based exercise training significantly increased incremental shuttle walk distance (mean difference 39 m, 95% CI 5-72 m), endurance shuttle walk distance (mean difference 228 m, 95% CI 19-438 m) and improved CRDQ fatigue. Water-based exercise training was significantly more effective than land-based exercise training and control in increasing peak and endurance exercise capacity and improving aspects of quality of life in people with COPD and physical comorbidities.