tbuckley/cabot-search huggingface dataset:
Diabetes Mellitus and Breast Cancer Outcomes: A Systematic Review and Meta-Analysis
Authors: Kimberly S. Peairs, Bethany B. Barone, Claire F. Snyder, Hsin-Chieh Yeh, Kelly B. Stein, Rachel L. Derr, Frederick L. Brancati, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2010)

Purpose The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer–related outcomes. Methods We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes. Results Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy. Conclusion Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.
Metabolomics for rheumatic diseases: has the time come?
Authors: Luca Semerano, Paul-Henri Roméo, Marie-Christophe Boissier
Journal: Annals of the Rheumatic Diseases (2015)

The last decade of biomedical research has been impacted by the appearance of systems biology, an analytical approach to complex biological systems that makes use of the ‘-omics’, that is, high-throughput technologies that allow the comprehensive characterisation of genes (genomics), RNA transcripts (transcriptomics) or proteins (proteomics). Since their appearance, the ‘omics’ held promise of a radical change in the research paradigms. The classical research strategy adopts a ‘bottom-up’ approach, that is, a scientific hypothesis is tested in an isolated system (a cell type, a tissue) or in an animal model, and then extrapolated to the systemic level. Conversely, systems biology uses a ‘top-down’ approach in which data are gathered at systemic level and scientific hypotheses are subsequently derived and tested in a controlled, limited setting.1 The latter approach has been defined as data-driven or hypothesis-forming. Although genomics, transcriptomics and proteomics have generated a large amount of data, translation of these data into useful information, and in turn into beneficial outcomes for the patient, is only starting.2

The newcomer in the -omics family is metabolomics. The metabolome is defined as the complete set of metabolites present in a given biological system. Complementary to transcriptomics or proteomics, the metabolome analysis describes both qualitatively and quantitatively the final products of cellular regulatory pathways. As such, the metabolome reflects the ultimate response of a biological system to genetic and/or environmental changes.

Metabolites that are characterised in metabolomics studies are small molecules with size ranging from 100 to 1000 Da.3 Although the concept that metabolites in biological fluids may …
The Legitimacy of Placebo Treatments in Clinical Practice: Evidence and Ethics
Authors: Franklin G. Miller, Luana Colloca
Journal: The American Journal of Bioethics (2009)

Physicians commonly recommend 'placebo treatments', which are not believed to have specific efficacy for the patient's condition. Motivations for placebo treatments include complying with patient expectations and promoting a placebo effect. In this article, we focus on two key empirical questions that must be addressed in order to assess the ethical legitimacy of placebo treatments in clinical practice: 1) do placebo treatments have the potential to produce clinically significant benefit? and 2) can placebo treatments be effective in promoting a therapeutic placebo response without the use of deception? We examine evidence from clinical trials and laboratory experiments bearing on these two questions. The conclusion is reached that based on currently available evidence, it is premature to judge whether placebo treatments are ethically justifiable, with the possible exception of acupuncture for pain relief.
The autoantigen Ku is indistinguishable from NF IV, a protein forming multimeric protein-DNA complexes.
Authors: M H Stuiver, F E Coenjaerts, P C van der Vliet
Journal: The Journal of Experimental Medicine (1990)

We have isolated a cDNA encoding the 84-kD subunit of NFIV. Tryptic peptide sequences were identified within the coding sequences, confirming its proper identity. The primary sequence of the protein is identical to that of the large subunit of the Ku autoantigen. A missing NFIV peptide sequence was identified within the sequence of the small subunit of Ku. In addition, the proteins are identical in immunological aspects. We suggest that the Ku and NFIV proteins are identical. This connection adds new biochemical data to our knowledge of the Ku autoantigen.
Fluorescence Visualization Detection of Field Alterations in Tumor Margins of Oral Cancer Patients
Authors: Catherine F. Poh, Lewei Zhang, Don W. Anderson, J. Scott Durham, P. Michele Williams, Robert W. Priddy, Ken W. Berean, Samson Ng, Olivia L. Tseng, Calum MacAulay, Miriam P. Rosin
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Genetically altered cells could become widespread across the epithelium of patients with oral cancer, often in clinically and histologically normal tissue, and contribute to recurrent disease. Molecular approaches have begun to yield information on cancer/risk fields; tissue optics could further extend our understanding of alteration to phenotype as a result of molecular change. Experimental Design: We used a simple hand-held device in the operating room to directly visualize subclinical field changes around oral cancers, documenting alteration to fluorescence. A total of 122 oral mucosa biopsies were obtained from 20 surgical specimens with each biopsy being assessed for location, fluorescence visualization (FV) status, histology, and loss of heterozygosity (LOH; 10 markers on three regions: 3p14, 9p21, and 17p13). Results: All tumors showed FV loss (FVL). For 19 of the 20 tumors, the loss extended in at least one direction beyond the clinically visible tumor, with the extension varying from 4 to 25 mm. Thirty-two of 36 FVL biopsies showed histologic change (including 7 squamous cell carcinoma/carcinomas in situ, 10 severe dysplasias, and 15 mild/moderate dysplasias) compared with 1 of the 66 FV retained (FVR) biopsies. Molecular analysis on margins with low-grade or no dysplasia showed a significant association of LOH in FVL biopsies, with LOH at 3p and/or 9p (previously associated with local tumor recurrence) present in 12 of 19 FVL biopsies compared with 3 of 13 FVR biopsies (P = 0.04). Conclusions: These data have, for the first time, shown that direct FV can identify subclinical high-risk fields with cancerous and precancerous changes in the operating room setting.
Measurement of Circulating Desialylated Glycoproteins and Correlation with Hepatocellular Damage
Authors: James S. Marshall, Allan M. Green, Jack Pensky, Stanford Williams, Arthur Zinn, Don M. Carlson
Journal: Journal of Clinical Investigation (1974)

Addition of increasing amounts of (125)I-labeled desialylated thyroxine-binding globulin (DTBG) to hepatic cell membranes resulted in a progressive increase in binding. Saturability of membrane sites was indicated by a concentration beyond which further increases in [(125)I]DTBG resulted in no further binding. The binding curve for [(125)I]DTBG was similar to binding curves of desialylated orosomucoid, fetuin, and ceruloplasmin. An inhibition assay system using hepatic cell membranes showed that desialylated orosomucoid had a greater affinity for membrane binding sites than did DTBG but desialylated fetuin and ceruloplasmin bound less avidly than DTBG. Serum from normal persons and patients with a variety of illnesses was tested for its ability to inhibit [(125)I]DTBG binding. The inhibitory activity of 1 ml of normal serum was equivalent to that of 0.2-2 mug DTBG. Patients with Laënnec's cirrhosis, biliary cirrhosis, and hepatic metastases had greatly increased inhibitory activity in their serum. Patients with jaundice due to extrahepatic obstruction had inhibitory activity not significantly different from that found in normal serum. Column chromatography of normal serum on Sephadex G-200 resulted in inhibitory activity throughout the range of protein molecular weight. Desialylation of normal serum with neuraminidase enhanced the inhibitory activity but did not change the distribution of the activity. Gel chromatography of cirrhotic serum showed markedly increased inhibitory activity associated with the macroglobulins and the 4.5S peak and a new peak of inhibitory activity in the low molecular weight area was also seen. Inhibition of desialylated glycoprotein binding to liver cell membranes by serum from patients with hepatocellular disease raises the possibility that desialylated serum glycoproteins accumulate in the circulation and that patients with compromised hepatocellular function may no longer be able to clear them from the circulation. Alternatively, accumulation of desialylated glycoproteins in the circulation could result from defective protein synthesis by the diseased liver.
Proapoptotic protein Siva binds to the muscle protein telethonin in cardiomyocytes during coxsackieviral infection
Authors: K. Mihatsch, M. Nestler, H.-P. Saluz, A. Henke, T. Munder
Journal: Cardiovascular Research (2008)

Coxsackievirus B3 (CVB3) is known to cause a variety of human diseases including acute and chronic myocarditis as well as dilated cardiomyopathy (DCM). However, the mechanisms by which CVB3 causes diseases are not well understood. Studies identifying protein–protein interactions during CVB3 infection are useful in delineating the pathogenesis of acute or chronic myocarditis. Screening a human heart cDNA library revealed a yet unknown interaction partner of the proapoptotic protein Siva. We demonstrate that Siva specifically interacts with the heart and skeletal muscle protein telethonin. The expression of Siva is increased in heart tissue of CVB3-infected mice and the proteins colocalize in cardiomyocytes. telethonin might be involved in CVB3-mediated cell damage and in the resulting cardiac dysfunction due to the interaction with Siva. We suggest a molecular mechanism through which coxsackieviral infection contributes to the pathogenesis of chronic myocarditis and in particular of acquired forms of DCM.
The Relation of Fasting and 2-h Postchallenge Plasma Glucose Concentrations to Mortality
Authors: John D. Sorkin, Denis C. Muller, Jerome L. Fleg, Reubin Andres
Journal: Diabetes Care (2005)

OBJECTIVE—Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1–6.9 mmol/l as impaired fasting glucose (IFG) and &amp;lt;6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6–6.9 mmol/l and normal fasting glucose to &amp;lt;5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG. RESEARCH DESIGN AND METHODS—We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality. RESULTS—Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by ∼40% in the 6.1–6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased. CONCLUSIONS—These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results.
AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL MEASUREMENTS
Authors: Hugh K. Ward
Journal: The Journal of Experimental Medicine (1932)

1. Type III antipneumococcus serum, after absorption with the specific carbohydrate, no longer forms a precipitate with the carbohydrate, but still has a definite, though diminished bactericidal action on virulent pneumococci in a bactericidal test. 2. Such an absorbed antiserum still retains some of its power to neutralize the antibactericidal effect of the specific carbohydrate in a bactericidal test, showing that absorption with the carbohydrate does not remove all the anticarbohydrate antibody from an antiserum. 3. This carbohydrate neutralization test is a very much more delicate method for detecting the anticarbohydrate antibody (precipitin) than the precipitin test. 4. There is therefore no necessity to predicate another antibody to explain the bactericidal action of a carbohydrate-absorbed antiserum, or a similar result in a mouse protection test. 5. The specific carbohydrate has a definite antibactericidal action, but it is demonstrated that, were it present in this form in the body during pneumonia, it could not conceivably be produced in sufficient quantity to influence the disease.
Reform of the Public Health Act
Authors: C VAN DEN BOSCH, T SUNDKVIST, W WEIR, D O'SULLIVAN, R HEATHCOCK, J STRANGEWAYS, T ELLAM, C SENG
Journal: Thorax (1999)

We agree with Richard Coker 1 that the vast majority of non-compliant cases of tuberculosis can be dealt with by a mixture of directly observed therapy (DOT) and inducements.However, when DOT fails in a few cases each year, despite intensive team eVort and carrots such as housing or food vouchers, the Public Health Act may have to be invoked.We have had recourse to this measure four times in the past six months but, though providing valuable breathing space, it is extremely costly and proved ineVectual as a solution each time.Once the patient is admitted there are still potential problems.Treatment cannot be enforced and patients can abscond.There have also been instances of patients assaulting staV, physically and sexually, issuing death threats, breaking hospital property, and terrorising other patients, even interfering with others' oxygen therapy.Dealing with such patients puts hospital staV and patients under unacceptable pressure and requires extra staYng for security purposes.NHS hospitals were not designed for, nor are they staVed adequately for, custodial purposes.There is an urgent need to review the Public Health Act and make provisions for small specialist units staVed by nurses with training in and an aptitude for interpersonal skills.Admission to the unit would usually only be required for short periods of time until precipitating circumstances were resolved and alternative arrangements made.The threat of compulsory admission, or a short period thereof, may induce a behavioural change in the patient, allowing DOT to be successful after failing previously.In addition, a centrally based mobile unit of trained staV could be available to help tide teams over emergencies and could reduce the need for the specialist unit, enabling more non-adherent patients to be managed in the community.We call upon the Department of Health to examine and implement these proposals.
Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis
Authors: Tahaniyat Lalani, Christopher H. Cabell, Daniel K. Benjamin, Ovidiu Lasca, Christoph Naber, Vance G. Fowler, G. Ralph Corey, Vivian H. Chu, Michael Fenely, Orathai Pachirat, Ru-San Tan, Richard Watkin, Adina Ionac, Asuncion Moreno, Carlos A. Mestres, José Casabé, Natalia Chipigina, Damon P. Eisen, Denis Spelman, Francois Delahaye, Gail Peterson, Lars Olaison, Andrew Wang
Journal: Circulation (2010)

The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery.Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] -5.9%, P<0.001). With a combined instrument, the instrumental-variable-adjusted ARR in mortality associated with early surgery was -11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR -10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR -17.3%, P<0.001), systemic embolization (ARR -12.9%, P=0.002), S aureus NVE (ARR -20.1%, P<0.001), and stroke (ARR -13%, P=0.02) but not those with valve perforation or congestive heart failure.Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.
Antigen receptor-regulated exocytosis in cytotoxic T lymphocytes.
Authors: H Takayama, M V Sitkovsky
Journal: The Journal of Experimental Medicine (1987)

We demonstrate here that T cell receptor for antigen (TCR)-triggered exocytosis in cytotoxic T lymphocytes (CTL) is not constitutive and is regulated through crosslinking of the TCR by antigen or monoclonal anti-TCR antibodies. Morphological and biochemical data using three different biochemical markers of granules and Percoll gradient fractionation analysis are presented, suggesting that TCR-triggered exocytosis is accompanied by the loss of granules from CTL and appearance of intragranular proteins and enzymatic activities in the incubation medium. The strict requirement for crosslinking of the TCR in exocytosis triggering could be bypassed by protein kinase C activators (phorbol esters or bryostatin I and II) acting in synergy with Ca2+ ionophores. It is shown that external Ca2+ is obligatory for both the TCR-triggered and for the PMA/A23187-triggered exocytosis, since Ca2+ chelators and divalent cations that compete with Ca2+ for A23187 can inhibit exocytosis of granules. These data suggest that Ca2+ from intracellular stores is not sufficient to support exocytosis in CTL. Ca2+ channel blockers and calmodulin antagonists significantly inhibited TCR-triggered exocytosis without affecting the basal level of secretion. The described results are consistent with a model in which exocytosis of granules in CTL is triggered by the crosslinking of TCR, transmembrane protein kinase C activation, and external Ca2+ translocation through CTL plasma membrane Ca2+ channels and modulation of activity of Ca2+, calmodulin-dependent enzymes, and cytoskeletal proteins.
Appropriateness of Imaging for Lung Cancer Staging in a National Cohort
Authors: Leah M. Backhus, Farhood Farjah, Thomas K. Varghese, Aaron M. Cheng, Xiao-Hua Zhou, Douglas E. Wood, Larry Kessler, Steven B. Zeliadt
Journal: Journal of Clinical Oncology (2014)

Optimizing evidence-based care to improve quality is a critical priority in the United States. We sought to examine adherence to imaging guideline recommendations for staging in patients with locally advanced lung cancer in a national cohort.
Synbindin in Extracellular Signal-Regulated Protein Kinase Spatial Regulation and Gastric Cancer Aggressiveness
Authors: Xuan Kong, Jin Qian, Li-Sha Chen, Ying-Chao Wang, Ji-Lin Wang, Haoyan Chen, Yu-Rong Weng, Shu-Liang Zhao, Jie Hong, Ying-Xuan Chen, Weiping Zou, Jie Xu, Jing-Yuan Fang
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundThe molecular mechanisms that control the aggressiveness of gastric cancer (GC) remain poorly defined. Here we show that synbindin contributes to the aggressiveness of GC by activating extracellular signal-regulated protein kinase (ERK) signaling on the Golgi apparatus.
The Clinical Outcome Using Axitinib for Advanced Renal Cell Carcinoma in Nagoya University
Authors: Naoto Sassa, Tokunori Yamamto, Yasushi Yoshino, Masashi Kato, Yoshihisa Matsukawa, Takashi Fujita, Yasuhito Funahashi, Katsuhisa Tsuruta, Momokazu Gotoh
Journal: Annals of Oncology (2014)