bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informative gene selection and the direct classification of tumors based on relative simplicity
Authors: Chen Yuan , Wang Lifeng , Li Lanzhi , Zhang Hongyan , Yuan Zheming 
Published: January 2016

Abstract
Background
Selecting a parsimonious set of informative genes to build highly generalized performance classifier is the most important task for the analysis of tumor microarray expression data. Many existing gene pair evaluation methods cannot highlight diverse patterns of gene pairs only used one strategy of vertical comparison and horizontal comparison, while individual-gene-ranking method ignores redundancy and synergy among genes.

Results
Here we proposed a novel score measure named relative simplicity (RS). We evaluated gene pairs according to integrating vertical comparison with horizontal comparison, finally built RS-based direct classifier (RS-based DC) based on a set of informative genes capable of binary discrimination with a paired votes strategy. Nine multi-class gene expression datasets involving human cancers were used to validate the performance of new method. Compared with the nine reference models, RS-based DC received the highest average independent test accuracy (91.40 %), the best generalization performance and the smallest informative average gene number (20.56). Compared with the four reference feature selection methods, RS also received the highest average test accuracy in three classifiers (Naïve Bayes, k-Nearest Neighbor and Support Vector Machine), and only RS can improve the performance of SVM.

Conclusions
Diverse patterns of gene pairs could be highlighted more fully while integrating vertical comparison with horizontal comparison strategy. DC core classifier can effectively control over-fitting. RS-based feature selection method combined with DC classifier can lead to more robust selection of informative genes and classification accuracy.
Approach to Hyponatremia in Congestive Heart Failure: A Survey of Canadian Specialist Physicians and Trainees
Authors: Miller Amanda , Kuehl Bonnie , Tennankore Karthik , Soroka Steven 
Published: January 2016

Background: Hyponatremia is a recognized complication of congestive heart failure (CHF) and is associated with reduced survival. Therefore, early identification and appropriate management of hyponatremia is important. The aim of this study was to determine the general approach amongst Canadian healthcare practitioners and trainees to the identification and management of hyponatremia complicating CHF. Methods: Respondents completed 15 multiple-choice style questions in 3 case scenarios regarding the approach to management of hyponatremia complicating CHF using an online survey on UKidney.com between November 2012 and May 2013. Results were presented as a proportion of averaged correct/incorrect responses amongst Canadian nephrologists, cardiologists, internists and trainees in each of two domains; pathophysiology and management. Management was further subdivided into correct and incorrect use of diuretic therapy, hypertonic saline, oral urea tablets, vasopressin receptor antagonists (vaptans) and rate of sodium correction. Correct responses were determined by an expert panel of Canadian nephrologists and cardiologists based on review of evidence informed guidelines and current recommendations. Results: There were 1757 responses to our online survey amongst 455 Canadian respondents, 1139 of which were from cardiologists, nephrologists, general internists, or trainees. Overall, the pathophysiology governing hyponatremia in CHF was correctly identified 68.7 % of the time ( n = 380 responses, averaged over 4 questions). Hyponatremia was managed inappropriately 43.6 % of the time, with trainees scoring best overall with correct responses 60.3 % of the time ( n = 759 responses, over 11 questions). Importantly, an incorrect rate for sodium correction was selected 61.1 % of the time overall, ( n = 211 responses, averaged over 3 questions). Conclusions: This study identified that there are differences in the understanding of pathophysiology and management strategies for hyponatremia in the context of CHF amongst Canadian specialist physicians and trainees. A more consistent approach to hyponatremia is required and might best be achieved through formal knowledge translation.
Inferring the Effects of Cancer Treatment: Divergent Results From Early Breast Cancer Trialists’ Collaborative Group Meta-Analyses of Randomized Trials and Observational Data From SEER Registries
Authors: Henson Katherine E. , Jagsi Reshma , Cutter David , McGale Paul , Taylor Carolyn , Darby Sarah C. 
Published: January 2016

Purpose To compare the effect of breast cancer radiotherapy as estimated from observational data with findings from randomized trials. Materials and Methods Rate ratios were obtained for selected end points among 13,932 women randomly assigned to receive radiotherapy or not in trials contributing to recent meta-analyses by the Early Breast Cancer Trialists’ Collaborative Group. Estimates of the same quantities were derived for 393,840 women registered with breast cancer in the US SEER registries between 1973 and 2008. Results In the randomized trials, radiotherapy after breast-conserving surgery reduced mortality from both breast cancer (rate ratio, 0.82; 95% CI, 0.75 to 0.90) and all causes (rate ratio, 0.92; 95% CI, 0.86 to 0.99). Reductions of similar magnitude were seen in the trials of radiotherapy after mastectomy in node-positive disease (rate ratios, breast cancer 0.84; 95% CI, 0.76 to 0.94; all causes, 0.89; 95% CI, 0.81 to 0.97). In the observational data, radiotherapy after breast-conserving surgery was associated with much larger mortality reductions (rate ratios, breast cancer, 0.64; 95% CI, 0.62 to 0.66; all causes, 0.63; 95% CI, 0.62 to 0.65), whereas radiotherapy after mastectomy in node-positive disease was associated with substantial increases in mortality (rate ratios, breast cancer, 1.34; 95% CI, 1.31 to 1.37; all causes, 1.23; 95% CI, 1.22 to 1.25). Detailed adjustment of the observational data for potential confounders did not reduce the divergence from the randomized data. Conclusion This study of mortality after radiotherapy for breast cancer found strikingly divergent results between the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of randomized data and the SEER observational data, even when efforts had been made to remove confounding and selection biases. Nonrandomized comparisons are liable to provide misleading estimates of treatment effects. Therefore, they need careful justification every time they are used.
Impact of Adjuvant Endocrine Therapy on Quality of Life and Symptoms: Observational Data Over 12 Months From the Mind-Body Study
Authors: Ganz Patricia A. , Petersen Laura , Bower Julienne E. , Crespi Catherine M. 
Published: January 2016

Purpose To examine patterns of health and symptoms associated with the initiation of adjuvant endocrine therapy (ET) for primary breast cancer treatment. Patients and Methods The mind-body study (MBS) observational cohort participants provided self-reported data on physical and mental health, ET-related symptoms, as well as depression, fatigue, and sleep obtained at enrollment (after primary treatment, prior to initiation of ET) and 6 and 12 months later. Longitudinal trajectories of outcome variables among three patient groups (no ET, aromatase inhibitor [AI], or tamoxifen) were compared by using linear mixed models. Results Two-thirds of the 186 women initiated ET, which was evenly split between AI and tamoxifen, and no significant differences were observed in self-reported measures among the groups at baseline or in covariate-adjusted analyses. Physical health scores were below normative levels initially and improved over time, but the AI group had a significantly lower score at 12 months (P = .05); mental health scores were within the normal range, were similar in each group, and did not change over time. The no-ET group showed either stable or declining symptom severity, whereas the ET groups often showed increased severity over time, and the AI group reported more severe musculoskeletal (P = .02), hot flash (P = .02), and cognitive problems (P = .006) at one or both of the follow-up time points compared with the no-ET group. The tamoxifen group had higher levels of hot flashes (P = .002), cognitive problems (P = .016), and bladder problems (P = .02) than the no-ET group. Conclusion Attention should be given to the increased symptom burden associated with ET, and better efforts should be made to address patient-reported outcomes.
Conditional Survival of Patients With Metastatic Testicular Germ Cell Tumors Treated With First-Line Curative Therapy
Authors: Ko Jenny J. , Bernard Brandon , Tran Ben , Li Haocheng , Asif Tehmina , Stukalin Igor , Lee Margaret , Day Daphne , Alimohamed Nimira , Sweeney Christopher J. , Bedard Philippe L. , Heng Daniel Y.C. 
Published: January 2016

Purpose The International Germ Cell Cancer Collaborative Group (IGCCCG) criteria prognosticate survival outcomes in metastatic testicular germ cell tumor (MT-GCT), but how the initial risk changes over time for those who survived since curative treatment is unknown. Patients and Methods We assessed patients eligible for first-line therapy for MT-GCT at five tertiary cancer centers from 1990 to 2012 for 2-year conditional overall survival (COS) and conditional disease-free survival (CDFS), defined as the probability of surviving, or surviving and being disease free, respectively, for an additional 2 years at a given time point since the initial diagnosis. Results For all patients (N = 942), 2-year COS increased from 92% (95% CI, 91% to 94%) at 0 months to 98% (95% CI, 97% to 99%), and 2-year CDFS increased from 83% (95% CI, 81% to 86%) at baseline to 98% (95% CI, 97% to 99%) at 24 months after diagnosis. Two-year COS improved by 2% (97% at 0 months, 99% at 24 months) in the IGCCCG favorable-risk group, by 5% (94% at 0 months, 99% at 24 months) in the intermediate-risk group, and by 22% (71% at 0 months to 93% at 24 months) in the poor-risk group. Two-year CDFS improved significantly at 12 months for each risk group (favorable, 91% baseline v 95% at 12 months; intermediate, 84% v 95%; poor, 55% v 85%). Baseline IGCCCG risk stratification was not associated with long-term COS or CDFS for patients who survived to greater than 2 years post therapy. No significant differences in COS and CDFS were noted between seminoma and nonseminoma; patients ≥ 40 years old had inferior 2-year COS from 0 to 12 months, but no differences were noted at 18 months. Conclusion Our data suggest that the concept of conditional survival applies to patients with MT-GCT treated with curative therapy. Patients with MT-GCT who survived and remained disease free more than 2 years after the diagnosis had an excellent chance of staying alive and disease free in additional subsequent years, regardless of the initial IGCCCG risk stratification.
Intestinal Bile Acid Composition Modulates Prohormone Convertase 1/3 (PC1/3) Expression and Consequent GLP-1 Production in Male Mice
Authors: Morimoto Kohkichi , Watanabe Mitsuhiro , Sugizaki Taichi , Irie Jun-ichiro , Itoh Hiroshi 
Published: January 2016

AbstractBesides an established medication for hypercholesterolemia, bile acid binding resins (BABRs) present antidiabetic effects. Although the mechanisms underlying these effects are still enigmatic, glucagon-like peptide-1 (GLP-1) appears to be involved. In addition to a few reported mechanisms, we propose prohormone convertase 1/3 (PC1/3), an essential enzyme of GLP-1 production, as a potent molecule in the GLP-1 release induced by BABRs. In our study, the BABR colestimide leads to a bile acid-specific G protein-coupled receptor TGR5-dependent induction of PC1/3 gene expression. Here, we focused on the alteration of intestinal bile acid composition and consequent increase of total TGR5 agonistic activity to explain the TGR5 activation. Furthermore, we demonstrate that nuclear factor of activated T cells mediates the TGR5-triggered PC1/3 gene expression. Altogether, our data indicate that the TGR5-dependent intestinal PC1/3 gene expression supports the BABR-stimulated GLP-1 release. We also propose a combination of BABR and dipeptidyl peptidase-4 inhibitor in the context of GLP-1-based antidiabetic therapy.
Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3
Authors: Xu Hongliang , Hertzel Ann V. , Steen Kaylee A. , Bernlohr David A. 
Published: January 2016

AbstractActivation of proinflammatory macrophages plays an important role in the pathogenesis of insulin resistance, type 2 diabetes, and atherosclerosis. Previous work using high fat-fed mice has shown that ablation of the adipocyte fatty acid binding protein (FABP4/aP2) in macrophages leads to an antiinflammatory state both in situ and in vivo, and the mechanism is linked, in part, to increased intracellular monounsaturated fatty acids and the up-regulation of uncoupling protein 2. Here, we show that loss of FABP4/aP2 in macrophages additionally induces sirtuin 3 (SIRT3) expression and that monounsaturated fatty acids (C16:1, C18:1) lead to increased SIRT3 protein expression. Increased expression of SirT3 in FABP4/aP2 null macrophages occurs at the protein level with no change in SirT3 mRNA. When compared with controls, silencing of SIRT3 in Raw246.7 macrophages leads to increased expression of inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase 2. In contrast, loss of SIRT3 in FABP4/aP2-deficient macrophages attenuates the suppressed inflammatory signaling, reduced reactive oxygen species production, lipopolysaccharide-induced mitochondrial dysfunction, and increased fatty acid oxidation. These results suggest that the antiinflammatory phenotype of FABP4/aP2 null mice is mediated by increased intracellular monounsaturated fatty acids leading to the increased expression of both uncoupling protein 2 and SirT3.
Desmin enters the nucleus of cardiac stem cells and modulates Nkx2.5 expression by participating in transcription factor complexes that interact with thenkx2.5gene
Authors: Fuchs Christiane , Gawlas Sonja , Heher Philipp , Nikouli Sofia , Paar Hannah , Ivankovic Mario , Schultheis Martina , Klammer Julia , Gottschamel Teresa , Capetanaki Yassemi , Weitzer Georg 
Published: January 2016

ABSTRACTThe transcription factor Nkx2.5 and the intermediate filament protein desmin are simultaneously expressed in cardiac progenitor cells during commitment of primitive mesoderm to the cardiomyogenic lineage. Up-regulation of Nkx2.5 expression by desmin suggests that desmin may contribute to cardiogenic commitment and myocardial differentiation by directly influencing the transcription of the nkx2.5 gene in cardiac progenitor cells. Here, we demonstrate that desmin activates transcription of nkx2.5 reporter genes, rescues nkx2.5 haploinsufficiency in cardiac progenitor cells, and is responsible for the proper expression of Nkx2.5 in adult cardiac side population stem cells. These effects are consistent with the temporary presence of desmin in the nuclei of differentiating cardiac progenitor cells and its physical interaction with transcription factor complexes bound to the enhancer and promoter elements of the nkx2.5 gene. These findings introduce desmin as a newly discovered and unexpected player in the regulatory network guiding cardiomyogenesis in cardiac stem cells.
Eccentric contraction: unraveling mechanisms of force enhancement and energy conservation
Authors: Nishikawa Kiisa 
Published: January 2016

ABSTRACTDuring the past century, physiologists have made steady progress in elucidating the molecular mechanisms of muscle contraction. However, this progress has so far failed to definitively explain the high force and low energy cost of eccentric muscle contraction. Hypotheses that have been proposed to explain increased muscle force during active stretch include cross-bridge mechanisms, sarcomere and half-sarcomere length non-uniformity, and engagement of a structural element upon muscle activation. The available evidence suggests that force enhancement results from an interaction between an elastic element in muscle sarcomeres, which is engaged upon activation, and the cross-bridges, which interact with the elastic elements to regulate their length and stiffness. Similarities between titin-based residual force enhancement in vertebrate muscle and twitchin-based ‘catch’ in invertebrate muscle suggest evolutionary homology. The winding filament hypothesis suggests plausible molecular mechanisms for effects of both Ca2+ influx and cross-bridge cycling on titin in active muscle. This hypothesis proposes that the N2A region of titin binds to actin upon Ca2+ influx, and that the PEVK region of titin winds on the thin filaments during force development because the cross-bridges not only translate but also rotate the thin filaments. Simulations demonstrate that a muscle model based on the winding filament hypothesis can predict residual force enhancement on the descending limb of the length–tension curve in muscles during eccentric contraction. A kinematic model of titin winding based on sarcomere geometry makes testable predictions about titin isoforms in different muscles. Ongoing research is aimed at testing these predictions and elucidating the biochemistry of the underlying protein interactions.
Skeletal muscle tissue in movement and health: positives and negatives
Authors: Lindstedt Stan L. 
Published: January 2016

ABSTRACT
The history of muscle physiology is a wonderful lesson in ‘the scientific method’; our functional hypotheses have been limited by our ability to decipher (observe) muscle structure. The simplistic understanding of how muscles work made a large leap with the remarkable insights of A. V. Hill, who related muscle force and power to shortening velocity and energy use. However, Hill's perspective was largely limited to isometric and isotonic contractions founded on isolated muscle properties that do not always reflect how muscles function in vivo. Robert Josephson incorporated lengthening contractions into a work loop analysis that shifted the focus to dynamic muscle function, varying force, length and work done both by and on muscle during a single muscle work cycle. It became apparent that muscle is both a force generator and a spring. Titin, the missing filament in the sliding filament model, is a muscle spring, which functions very differently in cardiac versus skeletal muscle; its possible role in these two muscle types is discussed relative to their contrasting function. The good news for those of us who choose to work on skeletal muscle is that muscle has been reluctant to reveal all of its secrets.
Myosin isoforms and the mechanochemical cross-bridge cycle
Authors: Walklate Jonathan , Ujfalusi Zoltan , Geeves Michael A. 
Published: January 2016

ABSTRACT
At the latest count the myosin family includes 35 distinct groups, all of which have the conserved myosin motor domain attached to a neck or lever arm, followed by a highly variable tail or cargo binding region. The motor domain has an ATPase activity that is activated by the presence of actin. One feature of the myosin ATPase cycle is that it involves an association/dissociation with actin for each ATP hydrolysed. The cycle has been described in detail for a large number of myosins from different classes. In each case the cycle is similar, but the balance between the different molecular events in the cycle has been altered to produce a range of very different mechanical activities. Myosin may spend most of the ATPase cycle attached to actin (high duty ratio), as in the processive myosin (e.g. myosin V) or the strain-sensing myosins (e.g. myosin 1c). In contrast, most muscle myosins spend 80% of their ATPase cycle detached from actin. Within the myosin IIs found in human muscle, there are 11 different sarcomeric myosin isoforms, two smooth muscle isoforms as well as three non-muscle isoforms. We have been exploring how the different myosin isoforms have adapted the cross-bridge cycle to generate different types of mechanical activity and how this goes wrong in inherited myopathies. The ideas are outlined here.
Mitochondria to motion: optimizing oxidative phosphorylation to improve exercise performance
Authors: Conley Kevin E. 
Published: January 2016

ABSTRACT
Mitochondria oxidize substrates to generate the ATP that fuels muscle contraction and locomotion. This review focuses on three steps in oxidative phosphorylation that have independent roles in setting the overall mitochondrial ATP flux and thereby have direct impact on locomotion. The first is the electron transport chain, which sets the pace for oxidation. New studies indicate that the electron transport chain capacity per mitochondria declines with age and disease, but can be revived by both acute and chronic treatments. The resulting higher ATP production is reflected in improved muscle power output and locomotory performance. The second step is the coupling of ATP supply from O2 uptake (mitochondrial coupling efficiency). Treatments that elevate mitochondrial coupling raise both exercise efficiency and the capacity for sustained exercise in both young and old muscle. The final step is ATP synthesis itself, which is under dynamic control at multiple sites to provide the 50-fold range of ATP flux between resting muscle and exercise at the mitochondrial capacity. Thus, malleability at sites in these subsystems of oxidative phosphorylation has an impact on ATP flux, with direct effects on exercise performance. Interventions are emerging that target these three independent subsystems to provide many paths to improve ATP flux and elevate the muscle performance lost to inactivity, age or disease.
Sound Transmission between Rooms with Curtain Wall Façades: A Case Study
Authors: Secchi Simone , Cellai Gianfranco , Fausti Patrizio , Santoni Andrea , Martello Nicolò Zuccherini 
Published: January 2016

Curtain walls have reached good performances in terms of façade sound and thermal insulation, as well as solar protection. Nevertheless, the sound insulation performance of the partition between adjoining rooms with continuous curtain wall façades is often reduced by the presence of direct and flanking transmission through the junction with the façade itself. In this work, flanking and direct structural transmissions are analysed with reference to the joints of the mullion of the curtain wall with lightweight plasterboard partitions. Airborne sound insulation and vibration measurements were made in two adjacent rooms affected by the acoustic problems determined by the curtain wall joint. Traditional acoustic measurements, carried out according to EN ISO 16283–1, highlighted problems in sound insulation between rooms, but without any indication on different sound transmission paths through the wall. Vibration measurements were made for every part of the system (frame columns and beams, window panes, plasterboard wall, plasterboard false ceiling, etc.) to better understand the sound transmission paths in these kinds of structures. In this paper the results of this analysis are presented. Moreover, taking into account previous works and measurements made in this research field, different solutions for curtain wall structures are analysed and technical suggestions are given to improve airborne sound insulation between rooms separated by partitions mounted up to metal frames.