bluuebunny/crossref_metadata_2025_split huggingface dataset:
The research and evaluation of serious games: Toward a comprehensive methodology
Authors: Mayer Igor , Bekebrede Geertje , Harteveld Casper , Warmelink Harald , Zhou Qiqi , van Ruijven Theo , Lo Julia , Kortmann Rens , Wenzler Ivo 
Published: May 2013

AbstractThe authors present the methodological background to and underlying research design of an ongoing research project on the scientific evaluation of serious games and/or computer‐based simulation games (SGs) for advanced learning. The main research questions are: (1) what are the requirements and design principles for a comprehensive social scientific methodology for the evaluation of SGs?; (2) to what extent do SGs contribute to advanced learning?; (3) what factors contribute to or determine this learning?; and (4) to what extent and under what conditions can SG‐based learning be transferred to the real world? In the Netherlands between 2005 and 2012, several hundred SG sessions with 12 SGs were evaluated systematically, uniformly and quantitatively to create a dataset, which comprises data on 2488 respondents in higher education or work organizations. The authors present the research model, the quasi‐experimental design and the evaluation instruments. This focus in this paper is on the methodology and dataset, which form a sound foundation for forthcoming publications on the empirical results.
Image visibility of cancer to enhance targeting precision and spatial mapping biopsy for focal therapy of prostate cancer
Authors: Ukimura Osamu , de Castro Abreu Andre Luis , Gill Inderbir S. , Shoji Sunao , Hung Andrew J. , Bahn Duke 
Published: May 2013

Objective
To assess the advantages of cancer image visibility when using multiparametric transrectal ultrasonography (TRUS) in potential candidates for focal therapy for prostate cancer.
Patients and Methods
A total of 93 potential candidates for focal cryotherapy underwent grey‐scale and Doppler TRUS‐guided biopsy.
All real‐time TRUS images were recorded, allowing subsequent reviewing for the planning of targeted focal cryotherapy, and/or follow‐up targeted biopsy. The spatial mapping of TRUS‐visible lesions and targeted sampling areas were individually documented in schematic anatomic drawings of the prostate.
Data from the baseline imaging‐targeted biopsies were compared with systematic (non‐targeted) biopsies. Of the 93 patients, 73 patients with low‐ to intermediate‐risk disease were eventually considered to be candidates for hemi‐ablative focal cryosurgery, i.e. cryoablation of one lobe.
Results
Among the 93 patients, a total of 681 biopsy cores were available for analysis, including imaging‐targeted (n = 256, 37.5%) and systematic (n = 425, 62.5%) cores. Of the 256 targeted biopsy cores, 65% (n = 167) were positive for cancer, compared with 6.2% (26/425) in systematic (non‐targeted) cores (P < 0.001). A total of 88% (82/93) of the biopsy‐proven cancer index lesions were TRUS‐visible.
When comparing TRUS‐visible with image‐invisible index lesions, the cancer‐involved core length was 6.1 vs 1.5 mm (P < 0.001), respectively. Furthermore, the percent of core with involved cancer was 48 vs 16% (P < 0.001), and the mean Gleason score was 7.0 vs 6.2 (P < 0.001).
With increasing TRUS‐visible lesion size (<10, 11–15, 16–20, >20 mm), cancer‐involved core length and percent of core with cancer also significantly increased (P = 0.009 and P = 0.008, respectively).
Conclusions
TRUS‐guided targeted biopsies significantly improved the detection and staging of higher grade and larger volume cancer, compared with image‐blind (non‐targeted systematic) biopsies.
Image visibility enhanced the precise targeting and accurate spatial mapping of cancer to help identify more appropriate candidates for focal therapy.
Impact of tumour morphology on renal function decline after partial nephrectomy
Authors: Mehrazin Reza , Palazzi Kerrin L. , Kopp Ryan P. , Colangelo Caroline J. , Stroup Sean P. , Masterson James H. , Liss Michael A. , Cohen Seth A. , Jabaji Ramzi , Park Samuel K. , Patterson Anthony L. , L'Esperance James O. , Derweesh Ithaar H. 
Published: May 2013

Objective
To examine the association of renal morphology with renal function after partial nephrectomy (PN).
Patients and Methods
We conducted a multi‐institutional retrospective analysis of 322 PNs performed between 2003 and 2011.
The RENAL nephrometry score for each lesion was determined and the estimated glomerular filtration rate (eGFR) was calculated preoperatively and at last follow‐up.
We divided patients into two RENAL nephrometry score groups, low (<8) and high (≥8), and analysed and compared the outcomes of each group.
The primary outcome was median change in eGFR between preoperative and last follow‐up (ΔeGFR). The secondary outcome was eGFR <60 mL/min/1.73m2 at last follow‐up.
Multivariable analysis was conducted to evaluate the risk factors for eGFR <60 mL/min/1.73 m2 at last follow‐up.
Results
The median (interquartile range) follow‐up was 25.2 (13.5–39.3) months. Low (n = 165) and high (n = 157) RENAL score groups were well‐matched for baseline eGFR. The median tumour size (4.2 vs 2.4 cm, P < 0.001) was greater for the high group.
In all, 64% of the low and 88.2% of the high RENAL score group (P < 0.001) had decreased eGFR at last follow‐up. Median eGFR was −7 for the low vs −13.8 mL/min/1.73 m2 for the high group (P = 0.001); eGFR <60 mL/min/1.73 m2 at last follow‐up was 27.3% for the low vs 37.6% for the high group (P = 0.057).
Linear regression analysis showed that for each 1‐point increase in RENAL score, there was 2.5% decrease in eGFR (P = 0.002); for each 1‐cm increase in tumour size, there was 1.8% decrease in eGFR (P = 0.013). Area under curve analyses showed no significant difference between RENAL score and tumour size for prediction of de novo eGFR <60 mL/min/1.73 m2 (P = 0.920) and ΔeGFR ≥50% (P = 0.85).
Multivariable analysis showed that increasing RENAL score (odds ratio [OR] 1.24, P = 0.046) and decreasing preoperative eGFR (OR 1.10, P < 0.001) were risk factors for eGFR <60 mL/min/1.73 m2 at last follow‐up.
Conclusions
Increasing RENAL nephrometry score is an independent risk factor for eGFR <60 mL/min/1.73 m2 after PN.
RENAL nephrometry score may serve as an additional measure for risk stratification before PN, but further investigation is required.
Platelet‐mediated angiogenesis is independent of VEGF and fully inhibited by aspirin
Authors: Etulain J , Fondevila C , Negrotto S , Schattner M 
Published: May 2013

Background and PurposePlatelets are major players in every step of vessel development through the local delivery of angiogenesis‐modulating factors, including the pro‐angiogenic protein VEGF and the anti‐angiogenic endostatin. Although thrombin is a potent agonist and is highly elevated in angiogenesis‐related diseases, studies regarding its action on the release of platelet angiogenic factors are scarce and controversial. Herein, we have investigated the role of thrombin not only in VEGF and endostatin release but also in net platelet angiogenic activity.Experimental ApproachHuman platelets were stimulated with thrombin in the presence of the various inhibitors of the signalling pathways involved in platelet activation. Supernatants/releasates were used to determine the levels of angiogenic molecules and to induce angiogenic responses.Key ResultsWe found that thrombin induced the secretion of both VEGF and endostatin; however, the overall effect of the releasates was pro‐angiogenic as they promoted tubule‐like formation and increased the proliferation of endothelial cells. Both responses were only slightly suppressed in the presence of a VEGF receptor‐neutralizing antibody. Pharmacological studies revealed that while inhibitors of PKC, p38, ERK1/2, Src kinases or PI3K/Akt exerted only partial inhibitory effects, aspirin fully blocked the pro‐angiogenic activity of the releasate.Conclusions and ImplicationsIn contrast to current belief, platelet pro‐angiogenic responses are independent of VEGF and appear to be the result of the combined action of several molecules. Moreover, our data reinforce the notion that aspirin is a good candidate for a therapeutic agent to treat angiogenesis‐related diseases.
Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats
Authors: Zhang Xiao‐Yang , Yu Lei , Zhuang Qian‐Xing , Peng Shi‐Yu , Zhu Jing‐Ning , Wang Jian‐Jun 
Published: May 2013

Background and PurposeAnti‐histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms.Experimental ApproachHistamine‐induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole‐cell patch‐clamp recordings on rat brain slices. The distribution of postsynaptic histamine H1, H2 and H4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H1, H2 and H4 receptors and for subtypes of Na+–Ca2+ exchangers (NCXs) and hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels was assessed by quantitative real‐time RT‐PCR.Key ResultsA marked postsynaptic excitatory effect, co‐mediated by histamine H1 and H2 receptors, was involved in the histamine‐induced depolarization of MVN neurons. Postsynaptic H1 and H2 rather than H4 receptors were co‐localized in the same MVN neurons. NCXs contributed to the inward current mediated by H1 receptors, whereas HCN channels were responsible for excitation induced by activation of H2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2‐4 mRNAs, were abundantly expressed in MVN.Conclusion and ImplicationsNCXs coupled to H1 receptors and HCN channels linked to H2 receptors co‐mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders.Linked ArticlesThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Mouse models for Aicardi–Goutières syndrome provide clues to the molecular pathogenesis of systemic autoimmunity
Authors: Behrendt R , Roers A 
Published: May 2013

Summary
Aicardi–Goutières syndrome (AGS) is a hereditary autoimmune disease which overlaps clinically and pathogenetically with systemic lupus erythematosus (SLE), and can be regarded as a monogenic variant of SLE. Both conditions are characterized by chronic activation of anti-viral type I interferon (IFN) responses. AGS can be caused by mutations in one of several genes encoding intracellular enzymes all involved in nucleic acid metabolism. Mouse models of AGS-associated defects yielded distinct phenotypes and reproduced important features of the disease. Analysis of these mutant mouse lines stimulated a new concept of autoimmunity caused by intracellular accumulations of nucleic acids, which trigger a chronic cell-intrinsic antiviral type I IFN response and thereby autoimmunity. This model is of major relevance for our understanding of SLE pathogenesis. Findings in gene-targeted mice deficient for AGS associated enzymes are summarized in this review.
Blood pressure in Afghan male immigrants to Denmark
Authors: Asmar Ali , Bülow Jens , Simonsen Lene , Christensen Niels J. , Frandsen Erik , Norsk Peter 
Published: May 2013

SummaryPurposeImmigration from a Third‐World society to a Western society can be associated with higher blood pressure and salt sensitivity. We therefore tested whether immigrants from Afghanistan to Denmark compared with non‐immigrant Danes exhibit a (i) higher 24‐h ambulatory blood pressure (24‐h ABP) and (ii) blunted renin response to a change in salt intake.MethodsTwenty‐four‐hour ABP was measured in 40 men of Afghan (Afghans) and 40 men of Danish (Danes) origin. Each group was divided into young (20–30 years, n = 20) and middle aged (40–60 years, n = 20). A 3‐day low (70 mmol per 24‐h) and a 3‐day high (250 mmol per 24‐h) salt intake were in addition instituted in subgroups of the young groups (n = 18).ResultsYoung and middle‐aged Afghans exhibited a lower 24‐h mean arterial pressure (24‐h MAP) than the same respective age groups of Danes (83 ± 1 versus 90 ± 1 mm Hg, P<0·05, and 89 ± 2 versus 100 ± 1 mm Hg, P<0·05). 24‐h ABP did not change in any of the young groups during increased salt intake, whereas the Danes exhibited a greater decrease in plasma renin activity (PRA) (P<0·05). Plasma noradrenaline (PNA) was significantly higher among the young Afghans.ConclusionsAfghan immigrants to Denmark exhibit a lower 24‐h ABP than Danes. In young Afghans, PRA is less sensitive to changes in salt intake, while PNA is higher and may reflect their lower systolic blood pressure and/or arterial pulse pressure. Whether these hormonal differences can explain the lower 24‐h ABP in Afghans should be further explored.
The presence of a cytopathologist increases the diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration cytology for pancreatic adenocarcinoma: a meta‐analysis
Authors: Hébert‐Magee S. , Bae S. , Varadarajulu S. , Ramesh J. , Frost A. R. , Eloubeidi M. A. , Eltoum I. A. 
Published: May 2013

ObjectiveA meta‐analysis has not been previously performed to evaluate critically the diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) of solely pancreatic ductal adenocarcinoma and address factors that have an impact on variability of accuracy. The aim of this study was to determine whether the presence of a cytopathologist, variability of the reference standard and other sources of heterogeneity significantly impacts diagnostic accuracy.MethodsWe conducted a comprehensive search to identify studies, in which the pooled sensitivity, specificity, likelihood ratios for a positive or negative test (LR+, LR−) and summary receiver‐operating curves (SROC) could be determined for EUS‐FNA of the pancreas for ductal adenocarcinoma using clinical follow‐up, and/or surgical biopsy or excision as the reference standard.ResultsWe included 34 distinct studies (3644 patients) in which EUS‐FNA for a solid pancreatic mass was evaluated. The pooled sensitivity and specificity for EUS‐FNA for pancreatic ductal adenocarcinoma was 88.6% [95% confidence interval (CI): 87.2–89.9] and 99.3% (95% CI: 98.7–99.7), respectively. The LR+ and LR– were 33.46 (95% CI: 20.76–53.91) and 0.11 (95% CI: 0.08–0.16), respectively. The meta‐regression model showed rapid on‐site evaluation (ROSE) (P = 0.001) remained a significant determinant of EUS‐FNA accuracy after correcting for study population number and reference standard.ConclusionEUS‐FNA is an effective modality for diagnosing pancreatic ductal adencarcinoma in solid pancreatic lesions, with an increased diagnostic accuracy when using on‐site cytopathology evaluation.
Plasticity during childhood and adolescence: innovative approaches to investigating neurocognitive development
Authors: Kadosh Kathrin Cohen , Linden David E.J. , Lau Jennifer Y.F. 
Published: May 2013

AbstractAdolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging‐based neurofeedback) into a research approach that could help make the most of increased levels of plasticity during childhood and adolescence. We discuss how this powerful combination could be used to explore changing brain–behaviour relationships throughout development in the context of emotion processing, a cognitive domain that exhibits continuous development throughout the second decade of life. By targeting both behaviour and brain response, we would also be in an excellent position to define sensible time windows for enhancing plasticity, thereby allowing for targeted intervention approaches that can help improve emotion processing in both typically and atypically developing populations.
Undifferentiated facial electromyography responses to dynamic, audio‐visual emotion displays in individuals with autism spectrum disorders
Authors: Rozga Agata , King Tricia Z. , Vuduc Richard W. , Robins Diana L. 
Published: May 2013

AbstractWe examined facial electromyography (fEMG) activity to dynamic, audio‐visual emotional displays in individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals. Participants viewed clips of happy, angry, and fearful displays that contained both facial expression and affective prosody while surface electrodes measured corrugator supercilli and zygomaticus major facial muscle activity. Across measures of average and peak activity, the TD group demonstrated emotion‐selective fEMG responding, with greater relative activation of the zygomatic to happy stimuli and greater relative activation of the corrugator to fearful stimuli. In contrast, the ASD group largely showed no significant differences between zygomatic and corrugator activity across these emotions. There were no group differences in the magnitude and timing of fEMG response in the muscle congruent to the stimuli. This evidence that fEMG responses in ASD are undifferentiated with respect to the valence of the stimulus is discussed in light of potential underlying neurobiological mechanisms.
Selective and faithful imitation at 12 and 15 months
Authors: Hilbrink Elma E. , Sakkalou Elena , Ellis‐Davies Kate , Fowler Nia C. , Gattis Merideth 
Published: May 2013

AbstractResearch on imitation in infancy has primarily focused on what and when infants imitate. More recently, however, the question why infants imitate has received renewed attention, partly motivated by the finding that infants sometimes selectively imitate the actions of others and sometimes faithfully imitate, or overimitate, the actions of others. The present study evaluates the hypothesis that this varying imitative behavior is related to infants' social traits. To do so, we assessed faithful and selective imitation longitudinally at 12 and 15 months, and extraversion at 15 months. At both ages, selective imitation was dependent on the causal structure of the act. From 12 to 15 months, selective imitation decreased while faithful imitation increased. Furthermore, infants high in extraversion were more faithful imitators than infants low in extraversion. These results demonstrate that the onset of faithful imitation is earlier than previously thought, but later than the onset of selective imitation. The observed relation between extraversion and faithful imitation supports the hypothesis that faithful imitation is driven by the social motivations of the infant. We call this relation the King Louie Effect: like the orangutan King Louie in The Jungle Book, infants imitate faithfully due to a growing interest in the interpersonal nature of interactions.A video abstract of this article can be viewed at http://youtu.be/qlnIof1k-u8.
Environmental factors driving the effectiveness of European agri‐environmental measures in mitigating pollinator loss – a meta‐analysis
Authors: Scheper Jeroen , Holzschuh Andrea , Kuussaari Mikko , Potts Simon G. , Rundlöf Maj , Smith Henrik G. , Kleijn David 
Published: May 2013

AbstractIn Europe, agri‐environmental schemes (AES) have been introduced in response to concerns about farmland biodiversity declines. Yet, as AES have delivered variable results, a better understanding of what determines their success or failure is urgently needed. Focusing on pollinating insects, we quantitatively reviewed how environmental factors affect the effectiveness of AES. Our results suggest that the ecological contrast in floral resources created by schemes drives the response of pollinators to AES but that this response is moderated by landscape context and farmland type, with more positive responses in croplands (vs. grasslands) located in simple (vs. cleared or complex) landscapes. These findings inform us how to promote pollinators and associated pollination services in species‐poor landscapes. They do not, however, present viable strategies to mitigate loss of threatened or endangered species. This indicates that the objectives and design of AES should distinguish more clearly between biodiversity conservation and delivery of ecosystem services.
Fisetin inhibits growth, induces G2/M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation
Authors: Pal Harish C. , Sharma Samriti , Elmets Craig A. , Athar Mohammad , Afaq Farrukh 
Published: May 2013

AbstractNon‐melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non‐toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7‐tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti‐oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5–80 μm) resulted in a significant decrease in cell viability in a dose‐ and time‐dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G2/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti‐apoptotic proteins (Bcl2; Bcl‐xL and Mcl‐1); (ii) increased expression of pro‐apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP‐ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan‐caspase inhibitor (Z‐VAD‐FMK) blocked fisetin‐induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs.