bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical salvage improves overall survival for patients with HPV‐positive and HPV‐negative recurrent locoregional and distant metastatic oropharyngeal cancer
Authors: Guo Theresa , Qualliotine Jesse R. , Ha Patrick K. , Califano Joseph A. , Kim Young , Saunders John R. , Blanco Ray G. , D'Souza Gypsyamber , Zhang Zhe , Chung Christine H. , Kiess Ana , Gourin Christine G. , Koch Wayne , Richmon Jeremy D. , Agrawal Nishant , Eisele David W. , Fakhry Carole 
Published: March 2015

BACKGROUNDHuman papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited.METHODSA retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan‐Meier and Cox proportional hazards methods.RESULTSThe current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV‐positive (80 patients). HPV‐positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV‐positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09‐0.58 [P = .002]), longer time to disease recurrence (≥1 year; aHR, 0.36; 95% CI, 0.18‐0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12‐0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04‐0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05‐0.75 [P = .018]) metastatic disease recurrences.CONCLUSIONSSurgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases. Cancer 2015;121:1977–1984. © 2015 American Cancer Society.
Patient characteristics associated with the level of patient‐reported care coordination among male patients with colorectal cancer in the Veterans Affairs health care system
Authors: Jackson George L. , Zullig Leah L. , Phelan Sean M. , Provenzale Dawn , Griffin Joan M. , Clauser Steven B. , Haggstrom David A. , Jindal Rahul M. , van Ryn Michelle 
Published: March 2015

BACKGROUNDThe current study was performed to determine whether patient characteristics, including race/ethnicity, were associated with patient‐reported care coordination for patients with colorectal cancer (CRC) who were treated in the Veterans Affairs (VA) health care system, with the goal of better understanding potential goals of quality improvement efforts aimed at improving coordination.METHODSThe nationwide Cancer Care Assessment and Responsive Evaluation Studies survey involved VA patients with CRC who were diagnosed in 2008 (response rate, 67%). The survey included a 4‐item scale of patient‐reported frequency (“never,” “sometimes,” “usually,” and “always”) of care coordination activities (scale score range, 1‐4). Among 913 patients with CRC who provided information regarding care coordination, demographics, and symptoms, multivariable logistic regression was used to examine odds of patients reporting optimal care coordination.RESULTSVA patients with CRC were found to report high levels of care coordination (mean scale score, 3.50 [standard deviation, 0.61]). Approximately 85% of patients reported a high level of coordination, including the 43% reporting optimal/highest‐level coordination. There was no difference observed in the odds of reporting optimal coordination by race/ethnicity. Patients with early‐stage disease (odds ratio [OR], 0.60; 95% confidence interval [95% CI], 0.45‐0.81), greater pain (OR, 0.97 for a 1‐point increase in pain scale; 95% CI, 0.96‐0.99), and greater levels of depression (OR, 0.97 for a 1‐point increase in depression scale; 95% CI, 0.96‐0.99) were less likely to report optimal coordination.CONCLUSIONSPatients with CRC in the VA reported high levels of care coordination. Unlike what has been reported in settings outside the VA, there appears to be no racial/ethnic disparity in reported coordination. However, challenges remain in ensuring coordination of care for patients with less advanced disease and a high symptom burden. Cancer 2015;121:2207–2213. © 2015 American Cancer Society.
An HLA‐based framework for simulation of large‐scale critical systems
Authors: Ficco Massimo , Avolio Giovanni , Palmieri Francesco , Castiglione Aniello 
Published: March 2015

SummaryEvaluating the dependability of large‐scale critical infrastructures is a very difficult task that requires sophisticated modeling practices and experimentation environments/infrastructures. In particular, simulation of complex distributed systems require the integration of several different simulation tools and real‐time prototypes or emulated subsystems, which have to inter‐operate in a coordinated way. This paper presents a framework integrating simulation and emulation‐based subsystems, which is able to provide greater realism of the scenario under test. However, integrating simulation and emulation is a challenging issue because of the different time domains and to the communication overhead between the different time models, as well as to the large number of involved entities. Therefore, the high level architecture has been used to perform integration in a robust and standardized scenario. A cloud‐based virtualization platform has been adopted in order to reproduce complex system architectures on an elastic and adaptive locally controlled testbed. Copyright © 2015 John Wiley & Sons, Ltd.
A provably secure and efficient two‐party password‐based explicit authenticated key exchange protocol resistance to password guessing attacks
Authors: Farash Mohammad Sabzinejad , Islam SK Hafizul , Obaidat Mohammad S. 
Published: March 2015

SummaryPassword‐based two‐party authenticated key exchange (2PAKE) protocol enables two or more entities, who only share a low‐entropy password between them, to authenticate each other and establish a high‐entropy secret session key. Recently, Zheng et al. proposed a password‐based 2PAKE protocol based on bilinear pairings and claimed that their protocol is secure against the known security attacks. However, in this paper, we indicate that the protocol of Zheng et al. is insecure against the off‐line password guessing attack, which is a serious threat to such protocols. Consequently, we show that an attacker who obtained the users' password by applying the off‐line password guessing attack can easily obtain the secret session key. In addition, the protocol of Zheng et al. does not provide the forward secrecy of the session key. As a remedy, we also improve the protocol of Zheng et al. and prove the security of our enhanced protocol in the random oracle model. The simulation result shows that the execution time of our 2PAKE protocol is less compared with other existing protocols. Copyright © 2015 John Wiley & Sons, Ltd.
Reversible Logic Gates Based on Enzyme‐Biocatalyzed Reactions and Realized in Flow Cells: A Modular Approach
Authors: Fratto Brian E. , Katz Evgeny 
Published: March 2015

AbstractReversible logic gates, such as the double Feynman gate, Toffoli gate and Peres gate, with 3‐input/3‐output channels are realized using reactions biocatalyzed with enzymes and performed in flow systems. The flow devices are constructed using a modular approach, where each flow cell is modified with one enzyme that biocatalyzes one chemical reaction. The multi‐step processes mimicking the reversible logic gates are organized by combining the biocatalytic cells in different networks. This work emphasizes logical but not physical reversibility of the constructed systems. Their advantages and disadvantages are discussed and potential use in biosensing systems, rather than in computing devices, is suggested.
Heat Stroke
Authors: Leon Lisa R. , Bouchama Abderrezak 
Published: March 2015

ABSTRACTHeat stroke is a life‐threatening condition clinically diagnosed as a severe elevation in body temperature with central nervous system dysfunction that often includes combativeness, delirium, seizures, and coma. Classic heat stroke primarily occurs in immunocompromised individuals during annual heat waves. Exertional heat stroke is observed in young fit individuals performing strenuous physical activity in hot or temperature environments. Long‐term consequences of heat stroke are thought to be due to a systemic inflammatory response syndrome. This article provides a comprehensive review of recent advances in the identification of risk factors that predispose to heat stroke, the role of endotoxin and cytokines in mediation of multi‐organ damage, the incidence of hypothermia and fever during heat stroke recovery, clinical biomarkers of organ damage severity, and protective cooling strategies. Risk factors include environmental factors, medications, drug use, compromised health status, and genetic conditions. The role of endotoxin and cytokines is discussed in the framework of research conducted over 30 years ago that requires reassessment to more clearly identify the role of these factors in the systemic inflammatory response syndrome. We challenge the notion that hypothalamic damage is responsible for thermoregulatory disturbances during heat stroke recovery and highlight recent advances in our understanding of the regulated nature of these responses. The need for more sensitive clinical biomarkers of organ damage is examined. Conventional and emerging cooling methods are discussed with reference to protection against peripheral organ damage and selective brain cooling. Published 2015.Compr Physiol5:611‐647, 2015.
Autonomic Adjustments to Exercise in Humans
Authors: Fisher James P. , Young Colin N. , Fadel Paul J. 
Published: March 2015

ABSTRACTAutonomic nervous system adjustments to the heart and blood vessels are necessary for mediating the cardiovascular responses required to meet the metabolic demands of working skeletal muscle during exercise. These demands are met by precise exercise intensity‐dependent alterations in sympathetic and parasympathetic nerve activity. The purpose of this review is to examine the contributions of the sympathetic and parasympathetic nervous systems in mediating specific cardiovascular and hemodynamic responses to exercise. These changes in autonomic outflow are regulated by several neural mechanisms working in concert, including central command (a feed forward mechanism originating from higher brain centers), the exercise pressor reflex (a feed‐back mechanism originating from skeletal muscle), the arterial baroreflex (a negative feed‐back mechanism originating from the carotid sinus and aortic arch), and cardiopulmonary baroreceptors (a feed‐back mechanism from stretch receptors located in the heart and lungs). In addition, arterial chemoreceptors and phrenic afferents from respiratory muscles (i.e., respiratory metaboreflex) are also capable of modulating the autonomic responses to exercise. Our goal is to provide a detailed review of the parasympathetic and sympathetic changes that occur with exercise distinguishing between the onset of exercise and steady‐state conditions, when appropriate. In addition, studies demonstrating the contributions of each of the aforementioned neural mechanisms to the autonomic changes and ensuing cardiac and/or vascular responses will be covered. © 2015 American Physiological Society.Compr Physiol5:475‐512, 2015.
Energetics of Contraction
Authors: Barclay C. J. 
Published: March 2015

ABSTRACTMuscles convert energy from ATP into useful work, which can be used to move limbs and to transport ions across membranes. The energy not converted into work appears as heat. At the start of contraction heat is also produced when Ca2+binds to troponin‐C and to parvalbumin. Muscles use ATP throughout an isometric contraction at a rate that depends on duration of stimulation, muscle type, temperature and muscle length. Between 30% and 40% of the ATP used during isometric contraction fuels the pumping Ca2+and Na+out of the myoplasm. When shortening, muscles produce less force than in an isometric contraction but use ATP at a higher rate and when lengthening force output is higher than the isometric force but rate of ATP splitting is lower. Efficiency quantifies the fraction of the energy provided by ATP that is converted into external work. Each ATP molecule provides 100 zJ of energy that can potentially be converted into work. The mechanics of the myosin cross‐bridge are such that at most 50 zJ of work can be done in one ATP consuming cycle; that is, the maximum efficiency of a cross‐bridge is ∼50%. Cross‐bridges in tortoise muscle approach this limit, producing over 90% of the possible work per cycle. Other muscles are less efficient but contract more rapidly and produce more power. © 2015 American Physiological Society.Compr Physiol5:961‐995, 2015.
Metabolic Shifts during Aging and Pathology
Authors: Ma Yina , Li Ji 
Published: March 2015

ABSTRACTThe heart is a very special organ in the body and has a high requirement for metabolism due to its constant workload. As a consequence, to provide a consistent and sufficient energy a high steady‐state demand of metabolism is required by the heart. When delicately balanced mechanisms are changed by physiological or pathophysiological conditions, the whole system's homeostasis will be altered to a new balance, which contributes to the pathologic process. So it is no wonder that almost every heart disease is related to metabolic shift. Furthermore, aging is also found to be related to the reduction in mitochondrial function, insulin resistance, and dysregulated intracellular lipid metabolism. Adenosine monophosphate‐activated protein kinase (AMPK) functions as an energy sensor to detect intracellular ATP/AMP ratio and plays a pivotal role in intracellular adaptation to energy stress. During different pathology (like myocardial ischemia and hypertension), the activation of cardiac AMPK appears to be essential for repairing cardiomyocyte's function by accelerating ATP generation, attenuating ATP depletion, and protecting the myocardium against cardiac dysfunction and apoptosis. In this overview, we will talk about the normal heart's metabolism, how metabolic shifts during aging and different pathologies, and how AMPK regulates metabolic changes during these conditions. © 2015 American Physiological Society.Compr Physiol5:667‐686, 2015.
Extracellular Matrix Communication and Turnover in Cardiac Physiology and Pathology
Authors: Takawale Abhijit , Sakamuri Siva S.V.P. , Kassiri Zamaneh 
Published: March 2015

ABSTRACTDespite significant advances in treating heart disease, heart failure remains a major cause of morbidity and mortality. Regardless of the initiating cause(s), heart failure is associated with disruptions in the myocardial extracellular matrix (ECM). ECM is a dynamic structure and its physiological turnover is mediated by matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Research in the past two decades has revealed that the function of ECM extends beyond its role in providing structural support. Similarly, ECM regulatory proteins, MMPs and TIMPs, have been demonstrated to play diverse and ECM‐independent roles in tissue remodeling and homeostasis. ECM is a network structure that in addition to providing structural support, serves as an extracellular reservoir for a number of growth factors and cytokines, and plays a central role in interstitial transport of different molecules (hormones, growth factors, drugs, etc.). This is mainly through the action of nonstructural ECM components, proteoglycans and matricellular proteins, which are also critical in cell‐ECM interactions and overall ECM remodeling. As such, sustaining the ECM integrity is not only critical in preserving cardiac geometry and function, it is essential in ensuring optimal delivery of different molecules to their site of action. Further, ECM composition and integrity in disease should be considered in designing drugs with a specific site of action. In this review article, we provide an overview of the ECM structure, components, its function in interstitial transport, heart disease‐dependent ECM remodeling, and the potential therapeutic approaches in preserving the diseased myocardial ECM and cardiac function. © 2015 American Physiological Society.Compr Physiol5:687‐719, 2015.
Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions
Authors: Pellman Jason , Sheikh Farah 
Published: March 2015

ABSTRACTAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P‐wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure‐associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L‐type Ca2+current, various K+currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF‐prone substrate which is able to produce AF‐associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. © 2015 American Physiological Society.Compr Physiol5:649‐665, 2015.
Solvent‐Enabled Nonenyzmatic Sugar Production from Biomass for Chemical and Biological Upgrading
Authors: Luterbacher Jeremy S. , Alonso David Martin , Rand Jacqueline M. , Questell‐Santiago Ydna M. , Yeap Jher Hau , Pfleger Brian F. , Dumesic James A. 
Published: March 2015

AbstractWe recently reported a nonenzymatic biomass deconstruction process for producing carbohydrates using homogeneous mixtures of γ‐valerolactone (GVL) and water as a solvent. A key step in this process is the separation of the GVL from the aqueous phase, enabling GVL recycling and the production of a concentrated aqueous carbohydrate solution. In this study, we demonstrate that phenolic solvents—sec‐butylphenol, nonylphenol, and lignin‐derived propyl guaiacol—are effective at separating GVL from the aqueous phase using only small amounts of solvent (0.5 g per g of the original water, GVL, and sugar hydrolysate). Furthermore, using nonylphenol, we produced a hydrolysate that supported robust growth and high yields of ethanol (0.49 g EtOH per g glucose) at an industrially relevant concentration (50.8 g L−1 EtOH). These results suggest that using phenolic solvents could be an interesting solution for separating and/or detoxifying aqueous carbohydrate solutions produced using GVL‐based biomass deconstruction processes.
Public Participation and Environmental Justice in Biodiversity Governance in Finland, Greece, Poland and the UK
Authors: Paloniemi Riikka , Apostolopoulou Evangelia , Cent Joanna , Bormpoudakis Dimitrios , Scott Anna , Grodzińska‐Jurczak Malgorzata , Tzanopoulos Joseph , Koivulehto Miska , Pietrzyk‐Kaszyńska Agata , Pantis John D. 
Published: March 2015

AbstractThe novel articulations between the state, markets and civil society arising from the shift to networked environmental governance highlight the importance of creating equal participation opportunities. Relevant questions from an environmental justice perspective are not only who participates, but also with whom, in what, why and how. In this paper, we explore public participation in biodiversity governance that has emerged after the initial designation of a Natura 2000 network in Finland, Greece, Poland and the UK by focusing on distributive and procedural justice. Our analysis, based on focus groups and document analysis, shows that new participatory arrangements have taken the modes of project‐based, market, interest group and e‐governance. These arrangements have been marked by problems in power and knowledge sharing, and in the distribution of conservation costs and benefits, reflecting serious deficits regarding environmental justice. Calls for public participation and wider stakeholder engagement in conservation across Europe should be followed by an acknowledgment of the diversity of perspectives, conflicting interests and social positions and their integration into biodiversity governance. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Thermally Stable Four‐Coordinate Silicon(IV) Complexes with an Si=N Double Bond and an SiN3El Skeleton (El = O, S, Se, Te)
Authors: Mück Felix M. , Ulmer Anna , Baus Johannes A. , Burschka Christian , Tacke Reinhold 
Published: March 2015

AbstractThe donor‐stabilized silylene 1 reacts with N2O and PhElElPh (El = S, Se, Te) to form the respective silicon(IV) complexes 2–5 with an Si=N double bond. Compounds 2–5 were structurally characterized by crystal structure analyses and NMR spectroscopic studies in the solid state and in solution.
Insight into O2‐Promoted Base‐Catalyzed N‐Alkylation of Amines with Alcohols
Authors: Wang Chao , Chen Changpeng , Han Jian , Zhang Jingyu , Yao Yingming , Zhao Yingsheng 
Published: March 2015

AbstractA highly efficient and practical transition‐metal‐free CsOH/O2 catalyst system was developed for the N‐alkylation of amines with alcohols under argon. This strategy was compatible with many alcohols and exhibits excellent functional group tolerance. More significantly, the selective formation of secondary amines was achieved in excellent yields. The detailed mechanistic study gave a clear understanding of the role of base and oxygen in the catalytic cycle.
Pinene‐Derived Monodentate Phosphoramidites for Asymmetric Hydrogenation
Authors: Schmitz Christian , Leitner Walter , Franciò Giancarlo 
Published: March 2015

AbstractPhosphoramidite ligands based on pinene‐derived chiral amines have been prepared by a straightforward procedure in good yields. The key step of the synthetic protocol is a stereoselective hydrogenation of annulated pinene–pyridine derivatives leading to (diastereoisomeric) secondary amines that were separated and treated with different chlorophosphites to yield the envisaged phosphoramidites. The absolute configurations of the ligands were assigned on the basis of NMR analyses and corroborated by X‐ray diffraction analysis of a borane adduct of a typical ligand. The new ligands were employed in the asymmetric hydrogenation of imines and olefins. The iridium‐catalyzed hydrogenation of imines provided up to 81 % ee, whereas in the rhodium‐catalyzed hydrogenation of functionalized olefins enantioselectivities of up to 99 % ee were achieved. In this particular application, the different chiral elements of the ligand structure led to synergistic effects and the enantioselectivity is dominated by the chiral diol moiety.