bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis of Morbid Obesity Patients With Advanced Heart Failure
Authors: Nagarajan Vijaiganesh , Cauthen Clay A. , Starling Randall C. , Tang Wai Hong Wilson 
Published: August 2013

Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m2), obese (30.1–40 kg/m2), and morbidly obese (≥40 kg/m2). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event‐free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09–1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40–4.30; P=.002) had significantly higher risk of all‐cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re‐emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon
Alternatives to islet transplantation: future cell sources of beta‐like cells
Authors: Bruns Helge , Schultze Daniel , Schemmer Peter 
Published: August 2013

AbstractCell transplantation is a treatment option for diabetes, metabolic liver disease in children, and leukemia. Except for the latter indication, solid organ transplantation is one of the available therapies but can be replaced by cell transplantation. However, due to the limited amount of cells that can be transplanted and due to rejection, results of cell transplants are still inferior to solid organ transplantation; there is a general shortage of donor organs, and cell isolation is limited to organs which cannot be transplanted as a whole for anatomic reasons. Therefore, alternatives to islets and beta cells are needed. There are some cells which can be generated from the recipient and would not be rejected; still, immunosuppression would be required to prevent reoccurrence of type I diabetes unless durable tolerance to beta cells could be induced. Generating beta cells for transplant from the recipient would help to overcome the lack of available organs. Moreover, understanding the underlying mechanisms of differentiation of these cells into beta‐like cells would deepen our understanding of both pathophysiology and development of diabetes mellitus type I. This article examines embryonal stem cells, induced pluripotent cells, mesenchymal stromal cells, and hepatocytes as potential alternatives to beta‐cell transplantation.
Efficacy, usability and sequence of operations of a workflow‐integrated algorithm for basal–bolus insulin therapy in hospitalized type 2 diabetes patients
Authors: Mader J. K. , Neubauer K. M. , Schaupp L. , Augustin T. , Beck P. , Spat S. , Höll B. , Treiber G. M. , Fruhwald F. M. , Pieber T. R. , Plank J. 
Published: August 2013

AimsTo evaluate glycaemic control and usability of a workflow‐integrated algorithm for basal–bolus insulin therapy in a proof‐of‐concept study to develop a decision support system in hospitalized patients with type 2 diabetes.MethodsIn this ward‐controlled study, 74 type 2 diabetes patients (24 female, age 68 ± 11 years, HbA1c 8.7 ± 2.4% and body mass index 30 ± 7) were assigned to either algorithm‐based treatment with a basal–bolus insulin therapy or to standard glycaemic management. Algorithm performance was assessed by continuous glucose monitoring and staff's adherence to algorithm‐calculated insulin dose.ResultsAverage blood glucose levels (mmol/l) in the algorithm group were significantly reduced from 11.3 ± 3.6 (baseline) to 8.2 ± 1.8 (last 24 h) over a period of 7.5 ± 4.6 days (p < 0.001). The algorithm group had a significantly higher percentage of glucose levels in the ranges from 5.6 to 7.8 mmol/l (target range) and 3.9 to 10.0 mmol/l compared with the standard group (33 vs. 23% and 73 vs. 53%, both p < 0.001). Physicians' adherence to the algorithm‐calculated total daily insulin dose was 95% and nurses' adherence to inject the algorithm‐calculated basal and bolus insulin doses was high (98 and 93%, respectively). In the algorithm group, significantly more glucose values <3.9 mmol/l were detected in the afternoon relative to other times (p < 0.05), a finding mainly related to pronounced morning glucose excursions and requirements for corrective bolus insulin at lunch.ConclusionsThe workflow‐integrated algorithm for basal–bolus therapy was effective in establishing glycaemic control and was well accepted by medical staff. Our findings support the implementation of the algorithm in an electronic decision support system.
A direct comparison of long‐ and short‐acting GLP‐1 receptor agonists (taspoglutide once weekly and exenatide twice daily) on postprandial metabolism after 24 weeks of treatment
Authors: Gastaldelli A. , Balas B. , Ratner R. , Rosenstock J. , Charbonnel B. , Bolli G. B. , Boldrin M. , Balena R. 
Published: August 2013

AbstractAimsT‐emerge 2 was a randomized, open‐label, 24‐week trial comparing subcutaneous taspoglutide 10 mg weekly (Taspo10), taspoglutide 20 mg weekly (Taspo20; titrated after 4 weeks of Taspo10), with exenatide 10 mcg BID (Exe; after 4 weeks of Exe 5 mcg) in patients inadequately controlled on metformin, a thiazolidinedione, or both. T‐emerge 2 showed that once‐weekly Taspo provided better glycaemic control than Exe. This report focuses on a subset of T‐emerge 2 participants undergoing a standardized liquid meal comparing Taspo to Exe, which has been previously shown to lower postprandial glucose.MethodsMeal tolerance tests (MTT) were performed at baseline and at week 24 in a subset of Taspo10, Taspo20 and Exe patients (n = 42, 39 and 67, respectively). Blood samples for glucose, insulin, glucagon and C‐peptide were obtained before and after (30, 60, 90, 120 and 180 min) ingestion of a standardized liquid meal.ResultsThe 2‐h postprandial, mean 0–3 h and iAUC0‐3 h glucose during the MTT was reduced to a similar extent in all groups and the time profile of the postprandial glucose showed a similar pattern. Taspo10 and Taspo20, but not Exe, significantly increased insulin from baseline (both mean and iAUC0‐3 h). Although changes from baseline in C‐peptide were not significant within any treatment group, the mean change from baseline (both mean 0–3 h and iAUC0‐3 h) was significantly increased in Taspo10 vs. Exe. Mean glucagon showed significant decreases in all groups.ConclusionTaspoglutide and Exe improved postprandial glucose tolerance to a similar extent but possibly with different intimate mechanisms.
Does dimethyl sulfoxide increase protein immunomarking efficiency for dispersal and predation studies?
Authors: Williams Livy , Hagler James R. , Tonkel Kirk C. 
Published: August 2013

AbstractMarking biological control agents facilitates studies of dispersal and predation. This study examines the effect of a biological solvent, dimethyl sulfoxide (DMSO), on retention of immunoglobulin G (IgG) protein solutions applied to Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae), an important biological control agent of saltcedar, either internally by feeding them protein‐labeled foliage or externally by immersing them in a protein solution. In addition, we determined whether internally or externally marked DMSO‐IgG labels could be transferred via feeding from marked D. carinulata to its predator, Perillus bioculatus (Fabricius) (Heteroptera: Pentatomidae). The presence of rabbit and chicken IgG proteins was detected by IgG‐specific enzyme‐linked immunosorbent assays (ELISA). DMSO‐IgG treatments showed greater label retention than IgG treatments alone, and this effect was stronger for rabbit IgG than for chicken IgG. Fourteen days after marking, beetles immersed in rabbit IgG showed 100% internal retention of label, whereas beetles immersed in chicken IgG showed 65% internal retention. Immersion led to greater initial (time 0) label values, and longer label retention, than feeding beetles labeled foliage. The DMSO‐IgG label was readily transferred to P. bioculatus after feeding on a single marked prey insect. This investigation shows that addition of DMSO enhances retention of IgG labels, and demonstrates that protein marking technology has potential for use in dispersal and predator–prey studies with D. carinulata. Moreover, our observation of P. bioculatus feeding on D. carinulata is, to our knowledge, a new predator–prey association for the stink bug.
Epilepsy therapy development: Technical and methodologic issues in studies with animal models
Authors: Galanopoulou Aristea S. , Kokaia Merab , Loeb Jeffrey A. , Nehlig Astrid , Pitkänen Asla , Rogawski Michael A. , Staley Kevin J. , Whittemore Vicky H. , Edward Dudek F. 
Published: August 2013

SummaryThe search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting practices that will enhance the uniformity, reliability, and reporting of early stage preclinical studies with animal seizure and epilepsy models that aim to develop and evaluate new therapies for seizures or epilepsies, using multidisciplinary approaches. The topics considered include the following: (1) implementation of better study design and reporting practices; (2) incorporation in the study design and analysis of covariants that may influence outcomes (including species, age, sex); (3) utilization of approaches to document target relevance, exposure, and engagement by the tested treatment; (4) utilization of clinically relevant treatment protocols; (5) optimization of the use of video‐electroencephalography (EEG) recordings to best meet the study goals; and (6) inclusion of outcome measures that address the tolerability of the treatment or study end points apart from seizures. We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
Issues related to development of new antiseizure treatments
Authors: Wilcox Karen S. , Dixon‐Salazar Tracy , Sills Graeme J. , Ben‐Menachem Elinor , Steve White H. , Porter Roger J. , Dichter Marc A. , Moshé Solomon L. , Noebels Jeffrey L. , Privitera Michael D. , Rogawski Michael A. 
Published: August 2013

SummaryThis report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)–funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address what we believe is necessary, going forward, to achieve the goal of stopping seizures in all patients, with a call to arms for funding agencies, the pharmaceutical industry, and basic researchers.
Issues related to symptomatic and disease‐modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy
Authors: Brooks‐Kayal Amy R. , Bath Kevin G. , Berg Anne T. , Galanopoulou Aristea S. , Holmes Gregory L. , Jensen Frances E. , Kanner Andres M. , O'Brien Terence J. , Whittemore Vicky H. , Winawer Melodie R. , Patel Manisha , Scharfman Helen E. 
Published: August 2013

SummaryMany symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.
Epilepsy biomarkers
Authors: Engel Jerome , Pitkänen Asla , Loeb Jeffrey A. , Edward Dudek F. , Bertram Edward H. , Cole Andrew J. , Moshé Solomon L. , Wiebe Samuel , Jensen Frances E. , Mody Istvan , Nehlig Astrid , Vezzani Annamaria 
Published: August 2013

SummaryA biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost‐effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Assessment of the equine neonate in ambulatory practice
Authors: Austin S. M. 
Published: August 2013

SummaryThe ambulatory practitioner is usually the first to evaluate the equine neonate and must assess the foal and determine its health status. If there is suspicion of one or more abnormalities, then the ambulatory veterinarian must initiate appropriate treatment and determine if the foal can be successfully treated in the field or should be referred to a specialty hospital. This article will describe the examination procedure including an accurate history, a comprehensive physical examination, laboratory evaluation and application of point‐of‐care diagnostics. The initial examination is the basis for the correct determination of health or illness and informing the owner of the correct course of action for the neonatal foal.
Evasin‐4, a tick‐derived chemokine‐binding protein with broad selectivity can be modified for use in preclinical disease models
Authors: Déruaz Maud , Bonvin Pauline , Severin India C. , Johnson Zoë , Krohn Sonja , Power Christine A. , Proudfoot Amanda E. I. 
Published: August 2013

Rhipicephalus sanguineus, the common brown dog tick, produces several chemokine‐binding proteins which are secreted into the host in its saliva to modulate the host response during feeding. Two of these demonstrate very restricted selectivity profiles. Here, we describe the characterization of the third, which we named Evasin‐4. Evasin‐4 was difficult to produce recombinantly using its native signal peptide in HEK cells, but expressed very well using the urokinase‐type plasminogen activator signal peptide. Using SPR, Evasin‐4 was shown to bind most CC chemokines. Investigation of the neutralization properties by inhibition of chemokine‐induced chemotaxis showed that binding and neutralization did not correlate in all cases. Two major anomalies were observed: no binding was observed to CCL2 and CCL13, yet Evasin‐4 was able to inhibit chemotaxis induced by these chemokines. Conversely, binding to CCL25 was observed, but Evasin‐4 did not inhibit CCL25‐induced chemotaxis. Size‐exclusion chromatography confirmed that Evasin‐4 forms a complex with CCL2 and CCL18. In accordance with the standard properties of unmodified small proteins, Evasin‐4 was rapidly cleared following in vivo administration. To enhance the in vivo half‐life and optimize its potential as a therapeutic agent, Fc fusions of Evasin‐4 were created. Both the N‐ and C‐terminal fusions were shown to retain binding activity, with the C‐terminal fusion showing a modest reduction in potency.
Understanding allosteric and cooperative interactions in enzymes
Authors: Cornish‐Bowden Athel 
Published: August 2013

The paper that introduced biochemists to the idea of allosteric feedback inhibition [Monod J, Changeux J‐P & Jacob F (1963) J Mol Biol 6, 306–329] is now 50 years old, and the two papers on models for enzyme cooperativity that followed it [Monod J, Wyman J & Changeux J‐P (1965) J Mol Biol 12, 88–118; Koshland DE, Némethy G & Filmer D (1966) Biochemistry 5, 365–385] are almost as old. All of these papers continue to be heavily cited today – more in the 21st century than they were in the last two decades of the 20th. This is because they continue to be central for understanding enzyme regulation, and increasingly important in the age of systems biology.
Breakout of a slab as the result of changes in the thermophysical properties of continuously cast steel
Authors: Kavicka F. , Dobrovska J. , Stransky K. , Sekanina B. , Stetina J. , Mauder T. , Masarik M. 
Published: August 2013

ABSTRACTThe so‐called secondary cooling zone is an important part of the continuous casting machine. In this zone, a breakout may occur because of an increase of the local and temperature heterogeneity of steel, resulting from an increase of the stress caused by bending of the slab and by high local concentration of nonmetallic slag inclusions. Changes of the chemical composition of steel during continuous casting are particularly dangerous. In the event that two melts are cast one after another, that is, if the melt of steel with chemical composition A ends and is immediately followed by the steel B, it may automatically stop the continuous casting machine, and an atypical breakout may take place. It has happened during continuous casting of the slab, 250 × 1530 mm in the area of straightening, 20 min after flying change of tundish. In the present paper, by employing the dimensional analysis, eight dimensionless numbers are derived. If the values of these dimensionless numbers for two followed steels significantly differ, the atypical breakout may take place.
Feminist Geopolitics
Authors: Massaro Vanessa A. , Williams Jill 
Published: August 2013

AbstractThis paper traces the development of feminist geopolitics as a distinct analytical, epistemological, and methodological approach in geography. Feminist geopolitics is explained as an analytic approach that connects seemingly disparate people, places, events, and issues to show the connections across various operations of power and productions of inequality and exploitation. In so doing, we demonstrate the ways in which feminist geopolitics challenges the scales of geopolitics and refocuses on the mundane, everyday reproductions of geopolitical power. We further discuss recent work in the field that examines issues of security and insecurity to illustrate what insights can be gained by employing a feminist geopolitical framework.
A disparity of words: racial differences in oncologist–patient communication about clinical trials
Authors: Eggly Susan , Barton Ellen , Winckles Andrew , Penner Louis A. , Albrecht Terrance L. 
Published: August 2013

AbstractBackgroundAfrican Americans are consistently underrepresented in cancer clinical trials. Minority under‐enrolment may be, in part, due to differences in the way clinical trials are discussed in oncology visits with African American vs. White patients.ObjectiveTo investigate differences in oncologist–patient communication during offers to participate in clinical trials in oncology visits with African American and White patients.MethodsFrom an archive of video‐recorded oncology visits, we selected all visits with African American patients that included a trial offer (n = 11) and a matched sample of visits with demographically/medically comparable White patients (n = 11). Using mixed qualitative–quantitative methods, we assessed differences by patient race in (i) word count of entire visits and (ii) frequency of mentions and word count of discussions of clinical trials and key elements of consent.ResultsVisits with African American patients, compared to visits with White patients, were shorter overall and included fewer mentions of and less discussion of clinical trials. Also, visits with African Americans included less discussion of the purpose and risks of trials offered, but more discussion of voluntary participation.Discussion and conclusionsAfrican American patients may make decisions about clinical trial participation based on less discussion with oncologists than do White patients. Possible explanations include a less active communication style of African Americans in medical visits, oncologists' concerns about patient mistrust, and/or oncologist racial bias. Findings suggest oncologists should pay more conscious attention to developing the topic of clinical trials with African American patients, particularly purpose and risks.