bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma
Authors: Happold Caroline , Gorlia Thierry , Chinot Olivier , Gilbert Mark R. , Nabors L. Burt , Wick Wolfgang , Pugh Stephanie L. , Hegi Monika , Cloughesy Timothy , Roth Patrick , Reardon David A. , Perry James R. , Mehta Minesh P. , Stupp Roger , Weller Michael 
Published: January 2016

Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use. Conclusion The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.
Puerarin Protects Pancreatic β-Cells in Obese Diabetic Mice via Activation of GLP-1R Signaling
Authors: Yang Lei , Yao Dongdong , Yang Haiyuan , Wei Yingjie , Peng Yunru , Ding Yongfang , Shu Luan 
Published: January 2016

Abstract
Diabetes is characterized by a loss and dysfunction of the β-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in β-cell survival and function. It is meaningful to identify promising agents from natural products which might activate GLP-1R signaling. In this study, puerarin, a diet isoflavone, was evaluated its beneficial effects on β-cell survival and GLP-1R pathway. We showed that puerarin reduced the body weight gain, normalized blood glucose, and improved glucose tolerance in high-fat diet-induced and db/db diabetic mice. Most importantly, increased β-cell mass and β-cell proliferation but decreased β-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immunostaining of mice pancreatic sections. The protective effect of puerarin on β-cell survival was confirmed in isolated mouse islets treated with high glucose. Further mechanism studies showed that the circulating level of GLP-1 in mice was unaffected by puerarin. However, puerarin enhanced GLP-1R signaling by up-regulating expressions of GLP-1R and pancreatic and duodenal homeobox 1, which subsequently led to protein kinase B (Akt) activation but forkhead box O1 inactivation, and promoted β-cell survival. The protective effect of puerarin was remarkably suppressed by Exendin(9–39), an antagonist of GLP-1R. Our study demonstrated puerarin improved glucose homeostasis in obese diabetic mice and identified a novel role of puerarin in protecting β-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.
Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity
Authors: Kumar Dhivya , Blaby-Haas Crysten E. , Merchant Sabeeha S. , Mains Richard E. , King Stephen M. , Eipper Betty A. 
Published: January 2016

ABSTRACT
Ciliary axonemes and basal bodies were present in the last eukaryotic common ancestor and play crucial roles in sensing and responding to environmental cues. Peptidergic signaling, generally considered a metazoan innovation, is essential for organismal development and homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) is crucial for the last step of bioactive peptide biosynthesis. However, identification of a complete PAM-like gene in green algal genomes suggests ancient evolutionary roots for bioactive peptide signaling. We demonstrate that the Chlamydomonas reinhardtii PAM gene encodes an active peptide-amidating enzyme (CrPAM) that shares key structural and functional features with the mammalian enzyme, indicating that components of the peptide biosynthetic pathway predate multicellularity. In addition to its secretory pathway localization, CrPAM localizes to cilia and tightly associates with the axonemal superstructure, revealing a new axonemal enzyme activity. This localization pattern is conserved in mammals, with PAM present in both motile and immotile sensory cilia. The conserved ciliary localization of PAM adds to the known signaling capabilities of the eukaryotic cilium and provides a potential mechanistic link between peptidergic signaling and endocrine abnormalities commonly observed in ciliopathies.
Locomotion as an emergent property of muscle contractile dynamics
Authors: Biewener Andrew A. 
Published: January 2016

ABSTRACT
Skeletal muscles share many common, highly conserved features of organization at the molecular and myofilament levels, giving skeletal muscle fibers generally similar and characteristic mechanical and energetic properties; properties well described by classical studies of muscle mechanics and energetics. However, skeletal muscles can differ considerably in architectural design (fiber length, pinnation, and connective tissue organization), as well as fiber type, and how they contract in relation to the timing of neuromotor activation and in vivo length change. The in vivo dynamics of muscle contraction is, therefore, crucial to assessing muscle design and the roles that muscles play in animal movement. Architectural differences in muscle–tendon organization combined with differences in the phase of activation and resulting fiber length changes greatly affect the time-varying force and work that muscles produce, as well as the energetic cost of force generation. Intrinsic force–length and force–velocity properties of muscles, together with their architecture, also play important roles in the control of movement, facilitating rapid adjustments to changing motor demands. Such adjustments complement slower, reflex-mediated neural feedback control of motor recruitment. Understanding how individual fiber forces are integrated to whole-muscle forces, which are transmitted to the skeleton for producing and controlling locomotor movement, is therefore essential for assessing muscle design in relation to the dynamics of movement.
Bridging the myoplasmic gap II: more recent advances in skeletal muscle excitation–contraction coupling
Authors: Bannister Roger A. 
Published: January 2016

ABSTRACT
In skeletal muscle, excitation–contraction (EC) coupling relies on the transmission of an intermolecular signal from the voltage-sensing regions of the L-type Ca2+ channel (CaV1.1) in the plasma membrane to the channel pore of the type 1 ryanodine receptor (RyR1) nearly 10 nm away in the membrane of the sarcoplasmic reticulum (SR). Even though the roles of CaV1.1 and RyR1 as voltage sensor and SR Ca2+ release channel, respectively, have been established for nearly 25 years, the mechanism underlying communication between these two channels remains undefined. In the course of this article, I will review current viewpoints on this topic with particular emphasis on recent studies.
Non-crossbridge stiffness in active muscle fibres
Authors: Colombini Barbara , Nocella Marta , Bagni Maria Angela 
Published: January 2016

ABSTRACT
Stretching of an activated skeletal muscle induces a transient tension increase followed by a period during which the tension remains elevated well above the isometric level at an almost constant value. This excess of tension in response to stretching has been called ‘static tension’ and attributed to an increase in fibre stiffness above the resting value, named ‘static stiffness’. This observation was originally made, by our group, in frog intact muscle fibres and has been confirmed more recently, by us, in mammalian intact fibres. Following stimulation, fibre stiffness starts to increase during the latent period well before crossbridge force generation and it is present throughout the whole contraction in both single twitches and tetani. Static stiffness is dependent on sarcomere length in a different way from crossbridge force and is independent of stretching amplitude and velocity. Static stiffness follows a time course which is distinct from that of active force and very similar to the myoplasmic calcium concentration time course. We therefore hypothesize that static stiffness is due to a calcium-dependent stiffening of a non-crossbridge sarcomere structure, such as the titin filament. According to this hypothesis, titin, in addition to its well-recognized role in determining the muscle passive tension, could have a role during muscle activity.
Molecular networks in skeletal muscle plasticity
Authors: Hoppeler Hans 
Published: January 2016

ABSTRACT
The skeletal muscle phenotype is subject to considerable malleability depending on use as well as internal and external cues. In humans, low-load endurance-type exercise leads to qualitative changes of muscle tissue characterized by an increase in structures supporting oxygen delivery and consumption, such as capillaries and mitochondria. High-load strength-type exercise leads to growth of muscle fibers dominated by an increase in contractile proteins. In endurance exercise, stress-induced signaling leads to transcriptional upregulation of genes, with Ca2+ signaling and the energy status of the muscle cells sensed through AMPK being major input determinants. Several interrelated signaling pathways converge on the transcriptional co-activator PGC-1α, perceived to be the coordinator of much of the transcriptional and post-transcriptional processes. Strength training is dominated by a translational upregulation controlled by mTORC1. mTORC1 is mainly regulated by an insulin- and/or growth-factor-dependent signaling cascade as well as mechanical and nutritional cues. Muscle growth is further supported by DNA recruitment through activation and incorporation of satellite cells. In addition, there are several negative regulators of muscle mass. We currently have a good descriptive understanding of the molecular mechanisms controlling the muscle phenotype. The topology of signaling networks seems highly conserved among species, with the signaling outcome being dependent on the particular way individual species make use of the options offered by the multi-nodal networks. As a consequence, muscle structural and functional modifications can be achieved by an almost unlimited combination of inputs and downstream signaling events.
Οι γονείς πηγή πληροφοριών για την επικοινωνιακή και γλωσσική ανάπτυξη των παιδιών τους: μελέτη συγχρονικής εγκυρότητας του Τεστ Επικοινωνιακής ως Ανάπτυξης (ΤΕΑ)
Authors: Καρούσου Αλεξάνδρα , Νικολαΐδου Κυριακή 
Published: January 2016

<p>Η πρώιμη εκτίμηση της επικοινωνιακής και γλωσσικής ανάπτυξης των παιδιών αποτελεί σημαντική ανάγκη τόσο της εκπαιδευτικής όσο και της κλινικής πρακτικής. Τα ψυχομετρικά ερωτηματολόγια γονέων έχουν αναδειχθεί τα τελευταία χρόνια ως μία αξιόπιστη πηγή πληροφοριών σχετικά με τις επικοινωνιακές δεξιότητες των πολύ μικρών παιδιών. Στόχος της μελέτης που παρουσιάζεται είναι o έλεγχος της συγχρονικής εγκυρότητας του Τεστ Επικοινωνιακής Ανάπτυξης (ΤΕΑ, Καρούσου &amp; Πετρογιάννης, υπό έκδοση), ενός ερωτηματολογίου γονέων το οποίο αναπτύχθηκε και σταθμίστηκε στη χώρα μας για την εκτίμηση της επικοινωνίας παιδιών 7 μηνών έως 30 μηνών. Για τις ανάγκες της μελέτης, 54 παιδιά βιντεοσκοπήθηκαν σύμφωνα με ένα πρωτόκολλο παρατήρησης που αναπτύχθηκε ειδικά για τους σκοπούς της έρευνας. Την ίδια ημέρα οι γονείς τους συμπλήρωσαν το ΤΕΑ. Παρουσιάζονται οι δείκτες συσχέτισης των δύο ανεξάρτητων αξιολογήσεων, οι οποίοι κυμαίνονται σε υψηλά επίπεδα για όλες τις διαστάσεις επικοινωνιακής ανάπτυξης που εκτιμά το ΤΕΑ (προλεκτική επικοινωνία, γλωσσική κατανόηση, εκφραστικό λεξιλόγιο, μορφολογία και σύνταξη). Επιπροσθέτως, διερευνάται η επίδραση του μορφωτικού επιπέδου των γονέων και της ηλικίας των παιδιών στις συσχετίσεις αυτές. Συνολικά, τα αποτελέσματα στηρίζουν την εγκυρότητα του ψυχομετρικού αυτού εργαλείου και την ικανότητα των γονέων να παρέχουν αξιόπιστες πληροφορίες σχετικά με τις πρώιμες επικοινωνιακές και γλωσσικές δεξιότητες των παιδιών τους, ανεξάρτητα από το μορφωτικό τους επίπεδο. </p>
‘Labels or love’: The problem of the white wedding in Charlotte Brontë’s Jane Eyre and Sex and the City: The Movie
Authors: Varadi Anna 
Published: January 2016

Abstract
This article looks at the failure of the white ‘fairy-tale’ wedding in both a protofeminist and a post-feminist text (Charlotte Brontë’s Jane Eyre and Sex and the City: The Movie, respectively). It suggests that the pressure put on brides by the wedding and fashion industries – to have a lavish ceremony and an expensive designer dress – threatens the independence and identity of both Jane Eyre and Carrie Bradshaw. This threat is exacerbated since both women are marrying men who have been married before. The failure of their lavish wedding ceremonies is due to problems that arise from consumerist bridal ideals; the threat to female identity can only be eliminated by a second, ‘quiet’ ceremony that allows Jane and Carrie to enter into marriage outside of the consumerist ideology behind traditional weddings. The article concludes that the representation of ‘fairy-tale’ weddings and bridal fashion in the popular print media constitutes an ongoing feminist problem since the eighteenth century until today: there appears to be a continued consumerist push towards ‘spectacular’ ceremonies, which forces brides to choose between ‘labels or love’, and threatens the authenticity of marriage.
Ethics, Emotion, and Aesthetics: Architecture After the Crisis of Modern Science
Authors: Pérez Gómez Alberto 
Published: January 2016

Alberto Pérez Gómez first came to prominence as an architectural theorist and historian with his 1983 publication, Architecture and the Crisis of Modern Science; a book that won the Alice Davis Hitchcock Award for distinguished scholarship in architectural history the following year. Having established himself as one of the architecture world’s leading thinkers and most original historical theorists, he offered a book that completely broke all norms of either academic or architectural discourse; his 1992 treatise Polyphilo, or, The Dark Forest Revisited: An Erotic Epiphany of Architecture. The author and editor of numerous publications since, in 2007 he co-authored Towards an Ethical Architecture: Issues Within the Work of Gregory Henriquez, a publication “seeking to remind architects of the critical role they play in leading the creation of a community’s collective space”.
In the first of these seminal texts he illustrated how architecture was profoundly transformed by the scientific revolution of the eighteenth century - and how the consequences of that revolution are still dominant in architectural practice and discourse today. The second investigates architectural ‘beauty’ through the prism of erotic desire. Described as treading the borders of fiction, theory, and pornography, it epitomizes Pérez-Gómez’s desire to reframe architecture as an emotive, corporeal and visceral phenomenon in the context of today’s scientific and material society.
Running through these works is a constant argument that blurs the intellectual divisions of modern thinking – whether they be based on drawing a sharp distinction between the role of emotion and logic in architectural design; the part sentiments and feelings play in our use and understanding of the spaces we inhabit; or the divisions that have emerged in aesthetic and ethical theory that see the former as type of theorised formula and the latter as an isolated and fully quantifiable set of social practices. In addressing these issues, he begins this interview-article with comments on the phenomenological underpinnings in this thinking and his interest in both Edmund Husserl and Maurice Merleau-Ponty.
Social Practice and the Laissez-faire Metropolis: Dwight Perkins in Chicago, 1895 - 1915
Authors: Gray Jennifer 
Published: January 2016

At the turn of the twentieth century, the Chicago-based architect Dwight Perkins designed a prescient metropolitan plan for the American city that reimagined the polis as a terrain for sociological investigation and political activism. He collaborated with social scientists affiliated with the University of Chicago and with local, grass-roots activists to leverage design as a vehicle for social change. He argued that strategically placed, small-scale interventions would ameliorate the devastating impact that unplanned growth had on the urban poor and that these spaces would advance democratic social ideals in a city highly segregated by race, ethnicity, and wealth.
Not only was Perkins a pioneer in understanding the city as a heterogeneous collection of cultural groups, he also rethought the manner in which the city was visualized by mediating its architectural representation through the lens of the social sciences. He abandoned illusionistic rendering techniques and illustrated the city as a series of sociological data-maps that combined statistical facts on population density, disease transmission, mortality rates, and criminal activity with geographic projections of Chicago. This new cartographic strategy helped him to identify and create public spaces and social services that benefited underprivileged communities. In doing so, Perkins was one of the first American architects to challenge the socio-economic conditions of the laissez-faire metropolis. Although largely ignored in histories of urban planning and architecture, his nascent social practice contributes to a critical reappraisal of cities that remains relevant today.
The Prevalence of Contact Dermatitis Among Occupational and Work-related Diseases. Correlation between Atopy and Allergic or Irritative Contact Dermatitis
Authors: Codruta-Dana Pitis , Alexandru Tataru 
Published: January 2016

Abstract
The prevalence of contact dermatitis (CD) in Europe varies between 6.7% and 10.6% depending on the sector of activity. Professional CD (PCD) has an important economic impact − 30% of the budget compensation for occupational disease. In Romania, the prevalence of PCD is underestimated, with an even distribution of cases with respect to the allergic or irritative mechanism. A retrospective clinical study was conducted; target population being the patients admitted in Occupational Medicine Clinic Cluj-Napoca between 2003 and 2011. Objectives of study were: specifying the prevalence range of allergic CD (ACD) / irritative CD (ICD) among occupational/work-related diseases, the distribution of allergic/irritative CD (A/ICD) for different sectors of activity and establishing the correlation between atopy and A/ICD. We have applied allergy skin tests - prick (environmental allergens) and patch (occupational allergens). Inclusion criteria were: -documented occupational exposure at skin allergens/irritants; -the atopy state; -diagnostic established at discharge. Patients with recurrent chronic urticaria, angioedema, hypereosinophilic syndrome have been excluded. Statistical analysis was done using SPSS software. The study indicated a similar prevalence for A/ICD, with similar distribution. Prevalence above average has been recorded in the metallurgy sector (A/ICD), in health care sector (ACD), respectively, textile industry (ICD). The correlation atopy-ACD has proved to be lower compared to previous reports. Regarding ICD, the diagnostic was confirmed frequently to non-atopic persons. We strongly recommend the compliance with a multidisciplinary protocol for the management of A/ICD, individualized for specific activity sectors or even work stations.
The Risk/Benefit Analysis of Oral Anticoagulant Treatment in Atrial Fibrillation Using HAS-BLED and CHA2DS2-VASc Score
Authors: Ionela Silivastru (Cozlea) , Laurentiu Cozlea Daniel , Attila Keresztesi Arthur , Gabriela Asofie , Laurentiu Cozlea , Galafteon Oltean , Daniela Dobru 
Published: January 2016

Abstract

Introduction. The purpose of this study is to evaluate the risk and the benefit of oral anticoagulant treatment in nonvalvular atrial fibrillation (AF) patients, using the two scores recommended by the guidelines: the CHA2DS2-VASc score and HAS-BLED score.

Material and method. We conducted a retrospective observational study on 144 patients with nonvalvular atrial fibrillation, admitted between 1st of July 2013 and 30th September 2013 in the 3rd Medical Clinic of Tîrgu Mureș with a prospectiv follow-up at 6 months.
Based on the data collected from the patient charts, the thromboembolic risk was assessed using the CHA2DS2-VASc score and the hemorrhage risk was assessed using the HAS-BLED score. At 6 months, the patients were contacted via telephone and were questioned regarding their state of health, the existence of hospitalizations in the last 6 months, the international normalized ratio (INR) value, the existence of hemorrhagic or thromboembolic events.

Results. The group of patients was composed of 70 female and 74 male with the mean age of 70 ±11 years. From the total number of patients 13 (11.7%) had a history of stroke and the CHA2DS2-VASc score revealed that these 13 were in the high risk class. The presence of arterial hypertension and vascular disease were statistically associated with stroke.
Hemorrhagic events were encountered in 19 patients (13.19%) and 16 of them had a higher than 3 HAS-BLED score. A history of bleeding, anemia and labile INR were the factors statistically associated with bleeding.

Conclusions. The CHA2DS2-VASc score is useful in stratifying patients with AF in risk groups for thromboembolic events while the HAS-BLED score proved to be a useful tool in predicting bleeding events in anticoagulated patients.