tbuckley/cabot-search huggingface dataset:
Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction
Authors: Robert O. Bonow, Gerald Maurer, Kerry L. Lee, Thomas A. Holly, Philip F. Binkley, Patrice Desvigne-Nickens, Jaroslaw Drozdz, Pedro S. Farsky, Arthur M. Feldman, Torsten Doenst, Robert E. Michler, Daniel S. Berman, Jose C. Nicolau, Patricia A. Pellikka, Krzysztof Wrobel, Nasri Alotti, Federico M. Asch, Liliana E. Favaloro, Lilin She, Eric J. Velazquez, Robert H. Jones, Julio A. Panza
Journal: New England Journal of Medicine (2011)

The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain.In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of prespecified thresholds.Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P=0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P=0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P=0.53).The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone. (Funded by the National Heart, Lung, and Blood Institute; STICH ClinicalTrials.gov number, NCT00023595.).
Cyclosporin A in cadaveric organ transplantation.
Authors: R Y Calne, D J White, D B Evans, S Thiru, R G Henderson, D V Hamilton, K Rolles, P McMaster, T J Duffy, B R MacDougall, R Williams
Journal: BMJ (1981)

The use of cyclosporin A (CyA) with a protocol designed to avoid the effects of nephrotoxicity resulted in a one-year survival of 86% in recipients of renal allografts from unmatched cadaveric donors. The drug also controlled rejection of liver and pancreatic allografts. It was possible to change patients initially treated with CyA to azathioprine and corticosteroids and vice versa, thus enlarging the potential value of CyA in organ allografting. Of 34 recipients of renal allografts, 29 were currently receiving only CyA as immunosuppressive treatment. Twelve patients never required any adjuvant steroid treatment. These results suggest that CyA is an effective immunosuppressant, and if used with care side effects need not be severe.
Tumor-Derived Cyr61(CCN1) Promotes Stromal Matrix Metalloproteinase-1 Production and Protease-Activated Receptor 1–Dependent Migration of Breast Cancer Cells
Authors: Nga Nguyen, Athan Kuliopulos, Roger A. Graham, Lidija Covic
Journal: Cancer Research (2006)

Abstract Matrix metalloproteinases (MMPs) play a central role in remodeling the tumor-stromal microenvironment. We recently determined that stromal-derived MMP-1 also acts as a signaling molecule by cleaving protease-activated receptor 1 (PAR1) to cause breast cancer cell migration and invasion. Here, we show that ectopic PAR1 expression induces expression of the angiogenic factor Cyr61(CCN1) in breast cancer cells. The tumor-derived Cyr61 acts as an invasogenic signaling molecule that induces MMP-1 expression in adjacent stromal fibroblasts. Gene silencing of Cyr61 in breast cancer cells suppresses MMP-1 induction in stromal fibroblasts resulting in a major loss in migration of the cancer cells toward the fibroblasts. Cyr61-dependent loss of migration was complemented by exogenous MMP-1 and required the presence of the functional PAR1 receptor on the breast cancer cells. These results suggest that interrupting tumor-stromal cell communication by targeting Cyr61 may provide an alternative therapeutic approach for the treatment of invasive breast cancer. (Cancer Res 2006; 66(5): 2658-65)
World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline
Authors: Bo Reményi, Nigel Wilson, Andrew Steer, Beatriz Ferreira, Joseph Kado, Krishna Kumar, John Lawrenson, Graeme Maguire, Eloi Marijon, Mariana Mirabel, Ana Olga Mocumbi, Cleonice Mota, John Paar, Anita Saxena, Janet Scheel, John Stirling, Satupaitea Viali, Vijayalakshmi I. Balekundri, Gavin Wheaton, Liesl Zühlke, Jonathan Carapetis
Journal: Nature Reviews Cardiology (2012)
The effectiveness of exercise interventions to prevent sports injuries: a systematic review and meta-analysis of randomised controlled trials
Authors: Jeppe Bo Lauersen, Ditte Marie Bertelsen, Lars Bo Andersen
Journal: British Journal of Sports Medicine (2013)

Background Physical activity is important in both prevention and treatment of many common diseases, but sports injuries can pose serious problems. Objective To determine whether physical activity exercises can reduce sports injuries and perform stratified analyses of strength training, stretching, proprioception and combinations of these, and provide separate acute and overuse injury estimates. Material and methods PubMed, EMBASE, Web of Science and SPORTDiscus were searched and yielded 3462 results. Two independent authors selected relevant randomised, controlled trials and quality assessments were conducted by all authors of this paper using the Cochrane collaboration domain-based quality assessment tool. Twelve studies that neglected to account for clustering effects were adjusted. Quantitative analyses were performed in STATA V.12 and sensitivity analysed by intention-to-treat. Heterogeneity (I 2 ) and publication bias (Harbord's small-study effects) were formally tested. Results 25 trials, including 26 610 participants with 3464 injuries, were analysed. The overall effect estimate on injury prevention was heterogeneous. Stratified exposure analyses proved no beneficial effect for stretching (RR 0.963 (0.846–1.095)), whereas studies with multiple exposures (RR 0.655 (0.520–0.826)), proprioception training (RR 0.550 (0.347–0.869)), and strength training (RR 0.315 (0.207–0.480)) showed a tendency towards increasing effect. Both acute injuries (RR 0.647 (0.502–0.836)) and overuse injuries (RR 0.527 (0.373–0.746)) could be reduced by physical activity programmes. Intention-to-treat sensitivity analyses consistently revealed even more robust effect estimates. Conclusions Despite a few outlying studies, consistently favourable estimates were obtained for all injury prevention measures except for stretching. Strength training reduced sports injuries to less than 1/3 and overuse injuries could be almost halved.
The association between diet and chronic obstructive pulmonary disease in subjects selected from general practice
Authors: L. Watson, B. Margetts, P. Howarth, M. Dorward, R. Thompson, P. Little
Journal: European Respiratory Journal (2002)

It is unclear why some smokers develop chronic obstructive pulmonary disease (COPD) whilst the majority do not. Antioxidants found in food may protect against lung tissue injury, but previous epidemiological studies are inconsistent and do not focus on those most at risk of COPD, namely smokers. This case-controlled study measured the difference in dietary intake between smokers and exsmokers with and without COPD. Cases were patients &gt;45 yrs of age with &gt;10 pack-yrs of smoking, a forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) of ≤70% and a FEV 1 of ≤80% of predicted. Controls were patients &gt;45 yrs of age with &gt;10 pack-yrs of smoking, a FEV 1 /FVC of &gt;70% and a FEV 1 &gt;80% pred. Data were collected using validated questionnaires. Logistic regression analysis for an unmatched case-controlled study was performed. After controlling for other independent predictors of COPD, those with vegetable intake of ≥1 portion·day −1 (93 g) were less likely to have COPD, as were those consuming ≥1.5 portions·day −1 of fruit. This was not due to an overall reduction in food/calorie intake caused by the disease because: 1) adjusting for body mass index did not alter the estimates; 2) the effect was specific to fruit and vegetables, i.e. not other food groups; and 3) the estimates from incident cases were similar. In conclusion, fruit and vegetable consumption is inversely associated with chronic obstructive pulmonary disease and may explain why some smokers do not develop chronic obstructive pulmonary disease.
Preventable Exposures Associated With Human Cancers
Authors: V. J. Cogliano, R. Baan, K. Straif, Y. Grosse, B. Lauby-Secretan, F. El Ghissassi, V. Bouvard, L. Benbrahim-Tallaa, N. Guha, C. Freeman, L. Galichet, C. P. Wild
Journal: JNCI Journal of the National Cancer Institute (2011)

Information on the causes of cancer at specific sites is important to cancer control planners, cancer researchers, cancer patients, and the general public. The International Agency for Research on Cancer (IARC) Monograph series, which has classified human carcinogens for more than 40 years, recently completed a review to provide up-to-date information on the cancer sites associated with more than 100 carcinogenic agents. Based on IARC's review, we listed the cancer sites associated with each agent and then rearranged this information to list the known and suspected causes of cancer at each site. We also summarized the rationale for classifications that were based on mechanistic data. This information, based on the forthcoming IARC Monographs Volume 100, offers insights into the current state-of-the-science of carcinogen identification. Use of mechanistic data to identify carcinogens is increasing, and epidemiological research is identifying additional carcinogens and cancer sites or confirming carcinogenic potential under conditions of lower exposure. Nevertheless, some common human cancers still have few (or no) identified causal agents.
Targeted overexpression of elafin protects mice against cardiac dysfunction and mortality following viral myocarditis
Authors: Syed H.E. Zaidi, Chi-Chung Hui, Alexander Y.L. Cheah, Xiao-Mang You, Mansoor Husain, Marlene Rabinovitch
Journal: Journal of Clinical Investigation (1999)

Serine elastases degrade elastin, stimulate vascular smooth muscle cell migration and proliferation, and are associated with myocardial damage. To evaluate the impact of elastase inhibition on cardiovascular development and disease, transgenic mice were created in which the mouse preproendothelin-1 promoter was used to target elafin overexpression to the cardiovascular system. To distinguish the transgene from endogenous elafin, constructs were made incorporating a FLAG sequence; the COOH-terminus FLAG-tagged elafin construct produced a stable, functionally active gene product and was used to create transgenic mice. Consistent with endothelin expression, abundant elafin mRNA was observed in transgenic F1 embryos (embryonic day 13.5) and in adult transgenic mice heart, trachea, aorta, kidney, lung, and skin, but not in liver, spleen, and intestine. Functional activity of the transgene was confirmed by heightened myocardial elastase inhibitory activity. No tissue abnormalities were detected by light microscopy or elastin content. However, injection of 10 plaque-forming units (PFU) of encephalomyocarditis virus resulted in death within 11 days in 10 out of 12 nontransgenic mice compared with one out of nine transgenic littermates. This reduced mortality was associated with better cardiac function and less myocardial inflammatory damage. Thus, elafin expression may confer a protective advantage in myocarditis and other inflammatory diseases.
In Search of a Human Self-Regulation System
Authors: William M. Kelley, Dylan D. Wagner, Todd F. Heatherton
Journal: Annual Review of Neuroscience (2015)

The capacity for self-regulation allows people to control their thoughts, behaviors, emotions, and desires. In spite of this impressive ability, failures of self-regulation are common and contribute to numerous societal problems, from obesity to drug addiction. Such failures frequently occur following exposure to highly tempting cues, during negative moods, or after self-regulatory resources have been depleted. Here we review the available neuroscientific evidence regarding self-regulation and its failures. At its core, self-regulation involves a critical balance between the strength of an impulse and an individual's ability to inhibit the desired behavior. Although neuroimaging and patient studies provide consistent evidence regarding the reward aspects of impulses and desires, the neural mechanisms that underlie the capacity for control have eluded consensus, with various executive control regions implicated in different studies. We outline the necessary properties for a self-regulation control system and suggest that the use of resting-state functional connectivity analyses may be useful for understanding how people regulate their behavior and why they sometimes fail in their attempts.
The rationale for combination therapy
Authors: E.G.V. Evans
Journal: British Journal of Dermatology (2008)

Fungal infections of the nail are common in European populations. There are a number of clinical presentations usually resulting from an infection by one of the dermatophyte species, notably Trichophyton rubrum. A number of modern treatment strategies are available and are generally well tolerated and effective. However, a significant proportion of patients, 20-30%, can expect treatment failure and/or relapse following treatment. The search for new treatment modalities and drugs is hampered by our lack of understanding of the basic pathophysiological mechanisms that underlie these frequently encountered infections. A correct diagnosis is key to the implementation of successful treatment. Even then, some infections do appear to be more recalcitrant than others. This may be the result of a number of interacting factors: patient susceptibility, fungal growth patterns that resist treatment and the occurrence of dormant fungal spores (arthrospores) in the nail. Increasingly, research is turning towards the identification of clinical indicators of poor prognosis and the development of new treatment strategies to overcome them. The combination of drugs to produce synergistic activity is one possible advance towards achieving higher cure rates.
Ascl2 and 11p15.5 amplification in colorectal cancer
Authors: A. M. Jubb, K. P. Hoeflich, P. M. Haverty, J. Wang, H. Koeppen
Journal: Gut (2010)

We read with interest the recent article by Stange et al 1 describing gain of 11p or 11p15.5 in approximately one-quarter of colorectal cancer liver metastases compared with matched primary adenocarcinomas. Stange et al speculated that this event may be targeting several putative oncogenes and focused on achaete scute-like (Ascl)2 in particular.1 However, on examining our own published2 3 and unpublished data, we reached different conclusions regarding the role of Ascl2 in colorectal cancer.

We queried two series of primary colorectal cancers with both expression microarray and array comparative genomic hybridisation data. The first dataset relates to 37 cases (experiments conducted at Genentech; 100 k single nucleotide polymorphism array and HG-U133B GeneChip expression microarray (Affymetrix, Santa Clara, California, USA)). The second dataset relates to 30 cases from the commercial GeneLogic (Gaithersburg, Maryland, USA) database available at …
Treatment Response Evaluation Using 18F-FDOPA PET in Patients with Recurrent Malignant Glioma on Bevacizumab Therapy
Authors: Johannes Schwarzenberg, Johannes Czernin, Timothy F. Cloughesy, Benjamin M. Ellingson, Whitney B. Pope, Tristan Grogan, David Elashoff, Cheri Geist, Daniel H.S. Silverman, Michael E. Phelps, Wei Chen
Journal: Clinical Cancer Research (2014)

Abstract Purpose: This study compares the value of 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA) positron emission tomography (PET) and MRI in assessing outcome during antiangiogenic treatment in patients with recurrent high-grade gliomas. Experimental Design: Thirty patients were prospectively studied with 18F-FDOPA PET scans immediately before, and two and six weeks after start of bevacizumab therapy. 18F-FDOPA metabolic tumor volumes (MTV) as well as max and mean standardized uptake values (SUV) within this MTV were obtained. MRI treatment response was assessed at six weeks. The predictive ability of 18F-FDOPA PET and MRI response assessment were evaluated with regard to progression-free survival (PFS) and overall survival (OS). Results: A total of 30, 28, and 24 18F-FDOPA PET scans at baseline, two weeks, and six weeks, were available for analysis, respectively. 18F-FDOPA PET SUVs as well as their changes through therapy were not predictive of outcome. However, MTV parameters such as MTV changes were highly prognostic. Interestingly, absolute MTV at the first follow up scan provides the most significant prediction for increased OS (P &amp;lt; 0.0001) as well as PFS (P = 0.001). This surprising result was scrutinized with cross-validation and simulation analysis. Responders based on 18F-FDOPA PET data survived 3.5 times longer (12.1 months vs. 3.5 months, median OS, P &amp;lt; 0.001) than nonresponders (17 patients vs. 11 patients, respectively). In comparison, responders based on MRI data lived 1.5 times longer (11.4 months vs 7.7 months, P = 0.03) than nonresponders (22 patients vs. 7 patients, respectively). Conclusions: 18F-FDOPA PET identifies treatment responders to antiangiogenic therapy as early as two weeks after treatment initiation. Clin Cancer Res; 20(13); 3550–9. ©2014 AACR.
Ionic Mechanisms of Acquired QT Prolongation and Torsades de Pointes in Rabbits With Chronic Complete Atrioventricular Block
Authors: Yukiomi Tsuji, Tobias Opthof, Kenji Yasui, Yasuya Inden, Haruki Takemura, Noriko Niwa, Zhibo Lu, Jong-Kook Lee, Haruo Honjo, Kaichiro Kamiya, Itsuo Kodama
Journal: Circulation (2002)

The ionic basis of acquired QT prolongation and torsade de pointes (TdP) unrelated to drugs is not fully understood.We created a rabbit model with chronic complete atrioventricular block (AVB) (n=34), which showed prominent QT prolongation (by 120%), high incidence of spontaneous TdP (71%), and cardiac hypertrophy. Patch-clamp experiments were performed in left ventricular myocytes from 9 rabbits (8 with TdP, 1 without TdP) at approximately 21 days of AVB and from 8 sham-operated controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (+61% at 0.5 Hz, +21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K(+) current (I(Kr) and I(Ks)) in AVB myocytes were significantly smaller than in control by 50% and 55%, respectively. There was no significant difference in Ca(2+)-independent transient outward current (I(to1)). L-type Ca(2+) current (I(Ca,L)) in control and AVB myocytes was similar in peak amplitude, but the half voltage for activation was shifted to the negative direction (5.9 mV) in AVB myocytes. Voltage dependence of I(Ca,L) inactivation was not different in control and AVB myocytes. The inward rectifier K(+) current (I(K1)) significantly increased in AVB myocytes compared with control.In the rabbit, chronic AVB leads to prominent QT prolongation and high incidence of spontaneous TdP. Downregulation of both I(Kr) and I(Ks) in association with altered I(Ca,L) activation kinetics may underlie the arrhythmogenic ventricular remodeling.
Rapid Switching Between Transdermal Fentanyl and Methadone in Cancer Patients
Authors: Sebastiano Mercadante, Patrizia Ferrera, Patrizia Villari, Alessandra Casuccio
Journal: Journal of Clinical Oncology (2005)

Purpose The aim of this study was to examine the clinical effects of switching from transdermal (TTS) fentanyl to methadone, or vice versa, in patients with a poor response to the previous opioid. Patients and Methods A prospective study was carried out on 31 patients who switched from TTS fentanyl to oral methadone, or vice versa, because of poor opioid response. A fixed conversion ratio of fentanyl to methadone of 1:20 was started and assisted by rescue doses of opioids, and then doses were changed according to clinical response. Pain and symptom intensity, expressed as distress score, were recorded before switching doses of the two opioids and after subsequent doses. The number of changes of the daily doses, time to achieve stabilization, and hospital stay were also recorded. Results Eighteen patients were switched from TTS fentanyl to methadone, and seven patients were switched from methadone to TTS fentanyl. A significant decrease in pain and symptom intensity, expressed as symptom distress score, was found within 24 hours after switching took place in both directions. Unsuccessful switching occurred in six patients, who were subsequently treated with an alternative therapy. Conclusion A rapid switching using an initial fixed ratio of fentanyl to methadone of 1:20 is an effective method to improve the balance between analgesia and adverse effects in cancer patients with poor response to the previous opioid. No relationship between the final opioid dose and the dose of the previous opioid has been found.
Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function
Authors: Insa M. Schmidt, Isaac E. Hall, Sujata Kale, Sik Lee, Chuan-Hua He, Yashang Lee, Geoffrey L. Chupp, Gilbert W. Moeckel, Chun Geun Lee, Jack A. Elias, Chirag R. Parikh, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2013)

Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death via necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are not well understood. Using a urine proteomic screen in mice, we identified the macrophage-secreted chitinase-like protein Brp-39, the murine protein product of the chitinase 3-like 1 gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death via activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both Chi3l1/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood from allografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.
Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients
Authors: S. Marieke van Ham, Kirstin M. Heutinck, Tineke Jorritsma, Fréderike J. Bemelman, Merel C.M. Strik, Wim Vos, Jettie J.F. Muris, Sandrine Florquin, Ineke J.M. ten Berge, Ajda T. Rowshani
Journal: Kidney International (2010)