bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keep It Simple
Authors: Klemke Roland , van Rosmalen Peter , Ternier Stefaan , Westera Wim 
Published: July 2015

Background. Despite the continuous and abundant growth of the game market the uptake of serious games in education has been limited. Games require complex technologies and are difficult to organise and to embed in the curriculum. Aim. This article explores to what extent game templates and game authoring processes can be designed so that they can easily be adopted and adapted by teachers while only using openly available tools. Method. It discusses the design and first evaluation of two game platforms: ARGUMENT, based on a wiki, and ARLEARN, a toolkit based on openly available Google technologies. ARGUMENT is a text-based game challenging students to take a position on a given topic. ARLEARN offers an explicit mobile and virtual gameplay environment and a defined authoring process to create game scripts. Results. ARGUMENT and ARLEARN have been evaluated in four small-scale studies, where educators designed game scenarios and students played the resulting games. Conclusions. The results indicate that both tools are useful instruments that can be operated by teachers to build games and game-alike educational activities and, additionally, are a valuable step to gain experience with serious games.
β3-Adrenoceptor Impairs Mitochondrial Biogenesis and Energy Metabolism During Rapid Atrial Pacing-Induced Atrial Fibrillation
Authors: Dong Jingmei , Zhao Jingjing , Zhang Miaomiao , Liu Guangzhong , Wang Xiaobing , Liu Yixi , Yang Ning , Liu Yongwu , Zhao Guanqi , Sun Jiayu , Tian Jingpu , Cheng Cheping , Wei Lin , Li Yue , Li Weimin 
Published: July 2015

Background: The β3-adrenoceptor (β3-AR) is implicated in cardiac remodeling. Since metabolic dysfunction due to loss of mitochondria plays an important role in heart diseases, we examined the effects of β3-AR on mitochondrial biogenesis and energy metabolism in atrial fibrillation (AF). Methods: Atrial fibrillation was created by rapid atrial pacing in adult rabbits. Rabbits were randomly divided into 4 groups: control, pacing (P7), β3-AR antagonist (L748337), and β3-AR agonist (BRL37344) groups. Atrial effective refractory period (AERP) and AF induction rate were measured. Atrial concentrations of adenine nucleotides and phosphocreatine were quantified through high-performance liquid chromatography. Mitochondrial DNA content was determined. Real-time polymerase chain reaction and Western blot were used to examine the expression levels of signaling intermediates related to mitochondrial biogenesis. Results: After pacing for 7 days, β3-AR was significantly upregulated, AERP was reduced, and the AF induction rate was increased. The total adenine nucleotides pool was significantly reduced due to the decrease in adenosine triphosphate (ATP). The P7 group showed decreased activity of F0F1-ATPase. Mitochondrial DNA content was decreased and mitochondrial respiratory chain subunits were downregulated after pacing. Furthermore, expression of transcription factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (Tfam), was lower in the P7 group in response to β3-AR activation. Further stimulation of β3-AR with BRL37344 exacerbated these effects, together with a significant decrease in the levels of phosphocreatine. In contrast, inhibition of β3-AR with L748337 partially restored mitochondrial biogenesis and energy metabolism of atria in the paced rabbits. Conclusion: The activation of β3-AR contributes to atrial metabolic remodeling via transcriptional downregulation of PGC-1α/NRF-1/Tfam pathway that are involved in mitochondrial biogenesis, which ultimately perturbs mitochondrial function in rapid pacing-induced AF. The β3-AR is therefore a potential novel therapeutic target for the treatment or prevention of AF.
The RSK Inhibitor BIX02565 Limits Cardiac Ischemia/Reperfusion Injury
Authors: Shi Xi , O’Neill Margaret M. , MacDonnell Scott , Brookes Paul S. , Yan Chen , Berk Bradford C. 
Published: July 2015

Aims: During ischemia/reperfusion (I/R), ribosomal S6 kinase (RSK) activates Na+/H+ exchanger 1 (NHE1) by phosphorylating NHE1 at serine 703 (pS703-NHE1), which promotes cardiomyocyte death and injury. Pharmacologic inhibition of NHE1 effectively protects animal hearts from I/R. However, clinical trials using NHE1 inhibitors failed to show benefit in patients with acute myocardial infarction (MI). One possible explanation is those inhibitors block both agonist-stimulated activity (increasing I/R injury) and basal NHE1 activity (necessary for cell survival). We previously showed that dominant-negative RSK (DN-RSK) selectively blocked agonist-stimulated NHE1 activity. Therefore, we hypothesized that a novel RSK inhibitor (BIX02565) would blunt agonist-stimulated NHE1 and protect hearts from I/R. Methods and Results: Serum/angiotensin II-stimulated pS703-NHE1 was significantly decreased by BIX02565 in cultured cells. Intracellular pH recovery assay showed that BIX02565 selectively inhibited serum-stimulated NHE1 activity. Ischemia/reperfusion decreased left ventricular–developed pressure (LVDP; inhibited) to 8.7% of the basal level in non-transgenic littermate control (NLC) mouse hearts, which was significantly improved (44.6%) by BIX02565. Similar protection was observed in vehicle-treated, cardiac-specific DN-RSK-Tg mice (43%). No additional protective effect was seen in BIX02565-treated DN-RSK-Tg hearts. BIX02565 also improved LVDP in cardiac-specific wild-type (WT)-RSK-Tg mouse hearts (7.4%-40.9%, P < .01). Finally, Western Blotting results confirmed DN-RSK and BIX02565 significantly decreased I/R-induced pS703-NHE1. Conclusion: The RSK plays a crucial role in I/R-induced activation of NHE1 and cardiac injury. The RSK inhibition may provide an alternative target for patients with MI.
Failed Surgical Management of Acute Proximal Fifth Metatarsal (Jones) Fractures
Authors: Granata Jaymes D. , Berlet Gregory C. , Philbin Terrence M. , Jones Grant , Kaeding Christopher C. , Peterson Kyle S. 
Published: July 2015

Nonunion, delayed union, and refracture after operative treatment of acute proximal fifth metatarsal fractures in athletes is uncommon. This study was a failure analysis of operatively managed acute proximal fifth metatarsal fractures in healthy athletes. We identified 149 patients who underwent operative treatment for fifth metatarsal fractures. Inclusion criteria isolated skeletally mature, athletic patients under the age of 40 with a minimum of 1-year follow-up. Patients were excluded with tuberosity fractures, fractures distal to the proximal metaphyseal-diaphyseal region of the fifth metatarsal, multiple fractures or operative procedures, fractures initially treated conservatively, and medical comorbidities/risk factors for nonunion. Fifty-five patients met the inclusion/exclusion criteria. Four (7.3%) patients required a secondary operative procedure due to refracture. The average time to refracture was 8 months. All refractures were associated with bent screws and occurred in male patients who participated in professional basketball, professional volleyball, and college football. The average time for release to progressive weight-bearing was 6 weeks. Three patients were revised to a bigger size screw and went on to union. One patient was revised to the same-sized screw and required a second revision surgery for nonunion. All failures were refractures in competitive athletes who were initially treated with small diameter solid or cannulated stainless steel screws. The failures were not associated with early postoperative weight-bearing protocol. Maximizing initial fixation stiffness may decrease the late failure rate in competitive athletes. More clinical studies are needed to better understand risk factors for failure after screw fixation in the competitive, athletic population. Level of Evidence: Prognostic, Level IV: Case series
Perioperative Glycemic Control and the Effect on Surgical Site Infections in Diabetic Patients Undergoing Foot and Ankle Surgery
Authors: Sadoskas David , Suder Natalie C. , Wukich Dane K. 
Published: July 2015

Introduction. Diabetes mellitus is one of the leading causes of hyperglycemia in the perioperative setting. Hyperglycemia has been shown to cause increased risk of surgical site infections (SSIs) in multiple surgical specialties, but to our knowledge it has not been investigated for orthopaedic foot and ankle surgery. The aim of this study was to determine if hyperglycemia increased the rate of SSI in elective, diabetic patients that required perioperative hospitalization. Methods. A total of 348 consecutive inpatients after foot and ankle surgery were retrospectively evaluated. Patients who had a random serum glucose ≥200 mg/dL during the admission (Group 1) were compared to patients whose serum glucose never exceeded 200 mg/dL (Group 2). Results. Our 2 groups were similar with regard to age, gender, and body mass index. Twenty-one of 176 patients (11.9%) whose serum glucose was ≥200 mg/dL during the admission developed an SSI as compared to 9 of 172 patients (5.2%) whose serum glucose remained <200 mg/dL (odds ratio = 2.45; 95% confidence interval = 1.09-5.52;, P = .03). Discussion. Perioperative hyperglycemia ≥200 mg/dL is associated with increased rates of SSI after foot and ankle surgery. Communication with medical consultants is paramount in an effort to improve perioperative glycemic management and reduce the rate of SSI. Levels of Evidence: Prognostic, Level III: Case Control
Full Implementation of Screening for Nutritional Risk and Dysphagia in an Acute Stroke Unit
Authors: Kampman Margitta T. , Eltoft Agnethe , Karaliute Migle , Børvik Margrethe T. , Nilssen Hugo , Rasmussen Ida , Johnsen Stein H. 
Published: July 2015

Background and Purpose: In patients with acute stroke, undernutrition and aspiration pneumonia are associated with increased mortality and length of hospital stay. Formal screening for nutritional risk and dysphagia helps to ensure optimal nutritional management in all patients with stroke and to reduce the risk of aspiration in patients with dysphagia. We developed a national guideline for nutritional and dysphagia screening in acute stroke, which was introduced in our stroke unit on June 1, 2012. The primary objective was to audit adherence to the guideline and to achieve full implementation. Second, we assessed the prevalence of nutritional risk and dysphagia. Methods: We performed a chart review to assess performance of screening for nutritional risk and dysphagia in all patients with stroke hospitalized for ≥48 hours between June 1, 2012, and May 31, 2013. Next we applied a “clinical microsystems approach” with rapid improvement cycles and audits over a 6-month period to achieve full implementation. Results: The chart review showed that nutritional risk screening was performed in 65% and swallow testing in 91% of eligible patients (n = 185). Proactive implementation resulted in >95% patients screened (n = 79). The overall prevalence of nutritional risk was 29%, and 23% of the patients failed the initial swallow test. Conclusions: Proactive implementation is required to obtain high screening rates for nutritional risk and swallowing difficulties using validated screening tools. The proportion of patients at nutritional risk and the prevalence of dysphagia at initial swallow test were in the lower range of previous reports.
Mentoring as a Way to Change a Culture of Academic Bullying and Mobbing in the Humanities
Authors: Metzger Angela M. , Petit Angela , Sieber Sharon 
Published: July 2015

In 2009, the Chronicle of Higher Education defined ‘academic mobbing’ as ‘a form of bullying in which members of a department gang up to isolate or humiliate a colleague’. In their call for a special issue on mobbing for Workplace: A Journal for Academic Labor, editors Stephen Petrina and E. Wayne Ross explain that if rumors are circulating about the target’s supposed misdeeds, if the target is excluded from meetings or not named to committees, or if people are saying the target needs to be punished formally ‘to be taught a lesson’, it’s likely that mobbing is under way. This article addresses academic mobbing at colleges and universities in the United States (US), surveying current literature on the topic and discussing three instances of mobbing in the humanities at a regional state university in the US. The article also proposes an innovative mentoring programme as a long-term solution to this problem of bullying. Specifically, this article presents a mentoring model designed by a doctoral humanities student who has herself been mobbed; this model proposes mentoring at the graduate level to counteract and, it is hoped, eventually eliminate a culture of mobbing in the humanities at the doctoral student’s current university and other schools. The graduate mentoring programme presented in this article seeks to change a culture of mobbing into one of cooperation and support, by helping the next generation of academics live up to the true creative, collaborative potential of the humanities.
Flipping the Foreign Language Classroom and Critical Pedagogies
Authors: Correa Maite 
Published: July 2015

Since the foundation of the Khan Academy (2006), a great deal of attention has been generated to the term flipped classrooms (also known as reverse or backwards classrooms), which is a (new) pedagogical movement that reverses the traditional paradigm of class lecture and homework. This approach subordinates teacher-centred lectures to a secondary level of importance and proposes that lectures should be carried outside of class time in the form of screencasts/video recordings that students can watch at home. As a consequence, this newly freed class time can be used for discussion, questions and assisting students with meaningful practice and hands-on activities. This article first defines what a flipped foreign language (FL) classroom is, and what it is not. The discussion then moves to the fundamental tenets of critical pedagogy (following Vygotsky and Freire), namely: (a) the opposition between banking education and problem-posing education, (b) scaffolding and the zone of proximal development (ZPD) and (c) accountability of the student’s own learning. It is argued that flipped classrooms and problem-posing models of education are in fact two sides of the same coin. Then, the author addresses some of the most common concerns among FL instructors regarding the flip and proposes possible solutions. Finally, the limitations are discussed.
Genome-wide investigation and expression analysis of Sodium/Calcium exchanger gene family in rice and Arabidopsis
Authors: Singh Anil Kumar , Kumar Ritesh , Tripathi Amit K. , Gupta Brijesh K. , Pareek Ashwani , Singla-Pareek Sneh L. 
Published: July 2015

Abstract

Background
The Na+/Ca2+ Exchanger (NCX) protein family is a member of the Cation/Ca2+ exchanger superfamily and its members play important roles in cellular Ca2+ homeostasis. While the functions of NCX family of proteins is well understood in humans, not much is known about the total complement of Na+/Ca2+ exchangers in plants and their role in various physiological and developmental processes. In the present study, we have identified all the NCX proteins encoded in the genomes of rice and Arabidopsis and studied their phylogeny, domain architecture and expression profiles across different tissues, at various developmental stages and under stress conditions.

Results
Through whole genome investigation, we identified twenty-two NCX proteins encoded by fifteen genes in rice and sixteen NCX proteins encoded by thirteen genes in Arabidopsis. Based on phylogenetic reconstruction, these could be classified into five clades, members of most of which were found to possess distinct domain architecture. Expression profiling of the identified NCX genes using publicly available MPSS and microarray data showed differential expression patterns under abiotic stresses, and at various development stages. In rice, OsNCX1, OsNCX8, OsNCX9 and OsNCX15 were found to be highly expressed in all the plant parts and various developmental stages. qRT-PCR based expression analysis revealed that OsNCX3, OsNCX10 and OsNCX15 were highly induced by salt and dehydration stress. Besides, expression profiling showed differential regulation of rice NCX genes in response to calcium and EGTA. Interestingly, expression of none of the NCX genes was found to be co-regulated by NaCl and calcium.

Conclusions
Together, our results present insights into the potential role of NCX family of proteins in abiotic stresses and development. Findings of the present investigation should serve as a starting point for future studies aiming functional characterization of plant NCX family proteins.
BALL-SNP: combining genetic and structural information to identify candidate non-synonymous single nucleotide polymorphisms
Authors: Mueller Sabine C. , Backes Christina , Kalinina Olga V. , Meder Benjamin , Stöckel Daniel , Lenhof Hans-Peter , Meese Eckart , Keller Andreas 
Published: July 2015

Abstract
Background
High-throughput genetic testing is increasingly applied in clinics. Next-Generation Sequencing (NGS) data analysis however still remains a great challenge. The interpretation of pathogenicity of single variants or combinations of variants is crucial to provide accurate diagnostic information or guide therapies.

Methods
To facilitate the interpretation of variants and the selection of candidate non-synonymous polymorphisms (nsSNPs) for further clinical studies, we developed BALL-SNP. Starting from genetic variants in variant call format (VCF) files or tabular input, our tool, first, visualizes the three-dimensional (3D) structure of the respective proteins from the Protein Data Bank (PDB) and highlights mutated residues, automatically. Second, a hierarchical bottom up clustering on the nsSNPs within the 3D structure is performed to identify nsSNPs, which are close to each other. The modular and flexible implementation allows for straightforward integration of different databases for pathogenic and benign variants, but also enables the integration of pathogenicity prediction tools. The collected background information of all variants is presented below the 3D structure in an easily interpretable table format.

Results
First, we integrated different data resources into BALL-SNP, including databases containing information on genetic variants such as ClinVar or HUMSAVAR; third party tools that predict stability or pathogenicity in silico such as I-Mutant2.0; and additional information derived from the 3D structure such as a prediction of binding pockets. We then explored the applicability of BALL-SNP on the example of patients suffering from cardiomyopathies. Here, the analysis highlighted accumulation of variations in the genes JUP, VCL, and SMYD2.

Conclusion
Software solutions for analyzing high-throughput genomics data are important to support diagnosis and therapy selection. Our tool BALL-SNP, which is freely available at http://www.ccb.uni-saarland.de/BALL-SNP, combines genetic information with an easily interpretable and interactive, graphical representation of amino acid changes in proteins. Thereby relevant information from databases and computational tools is presented. Beyond this, proximity to functional sites or accumulations of mutations with a potential collective effect can be discovered.
Prognostic factors in the acute respiratory distress syndrome
Authors: Chen Wei , Ware Lorraine B 
Published: July 2015

AbstractDespite improvements in critical care, acute respiratory distress syndrome (ARDS) remains a devastating clinical problem with high rates of morbidity and mortality. A better understanding of the prognostic factors associated with ARDS is crucial for facilitating risk stratification and developing new therapeutic interventions that aim to improve clinical outcomes. In this article, we present an up‐to‐date summary of factors that predict mortality in ARDS in four categories: (1) clinical characteristics; (2) physiological parameters and oxygenation; (3) genetic polymorphisms and biomarkers; and (4) scoring systems. In addition, we discuss how a better understanding of clinical and basic pathogenic mechanisms can help to inform prognostication, decision‐making, risk stratification, treatment selection, and improve study design for clinical trials.
Quantitative analysis of 3-dimensional facial soft tissue photographic images: technical methods and clinical application
Authors: Nanda Vikrum , Gutman Boris , Bar Ehab , Alghamdi Suha , Tetradis Sotirios , Lusis Aldons J , Eskin Eleazar , Moon Won 
Published: July 2015

Abstract

Background
The recent advent of 3D photography has created the potential for comprehensive facial evaluation. However, lack of practical true 3D analysis of the information collected from 3D images has been the factor limiting widespread utilization in orthodontics. Current evaluation of 3D facial soft tissue images relies on subjective visual evaluation and 2D distances to assess facial disharmony. The objectives of this project strive to map the surface and define boundaries of 3D facial soft tissue, modify mathematical functions to average multiple 3D facial images, and mathematically average 3D facial images allowing generation of color-coded surface deviation relative to a true average.

Methods
Collaboration headed by UCLA Orthodontics with UCLA Neuroimaging was initiated to modify advanced brain mapping technology to accurately map the facial surface in 3D. 10 subjects were selected as a sample for development of the technical protocol. 3dMD photographic images were segmented, corrected using a series of topology correcting algorithms, and process to create close meshes. Shapes were mapped to a sphere using conformal and area preserving maps, and were then registered using a spherical patch mapping approach. Finally an average was created using 7-parameter procrustes alignment.

Results
Size-standardized average facial images were generated for the sample population. A single patient was then superimposed on the average and color-coded displacement maps were generated to demonstrate the clinical applicability of this protocol. Further confirmation of the methods through 3D superimposition of the initial (T0) average to the 4 week (T4) average was completed and analyzed.

Conclusions
The results of this investigation suggest that it is possible to average multiple facial images of highly variable topology. The immediate application of this research will be rapid and detailed diagnostic imaging analysis for orthodontic and surgical treatment planning. There is great potential for application to anthropometrics and genomics. This investigation resulted in establishment of a protocol for mapping the surface of the human face in three dimensions.