julilili42/papers huggingface dataset:
Development of a competency-based formative progress test with student-generated MCQs: Results from a multi-centre pilot study
2015-10-15

Introduction: Progress tests provide students feedback on their level of proficiency over the course of their medical studies. Peer-assisted learning and competency-based education have become increasingly important in medical education. Although progress tests have been proven to be useful as a longitudinal feedback instrument, there are currently no progress tests that have been created in cooperation with students or that focus on competency in medical education. In this study, we investigated the extent to which students can be included in the development of a progress test and demonstrated that aspects of knowledge related to competency can be represented on a competency-based progress test. Methods: A two-dimensional blueprint for 144 multiple-choice questions (MCQs) covering groups of medical subjects and groups of competency areas was generated by three expert groups for developing the competency-based progress test. A total of 31 students from seven medical schools in Germany actively participated in this exercise. After completing an intensive and comprehensive training programme, the students generated and reviewed the test questions for the competency-based progress test using a separate platform of the ItemManagementSystem (IMS). This test was administered as a formative test to 469 students in a pilot study in November 2013 at eight medical schools in Germany. The scores were analysed for the overall test and differentiated according to the subject groups and competency areas. Results: A pool of more than 200 MCQs was compiled by the students for pilot use, of which 118 student-generated MCQs were used in the progress test. University instructors supplemented this pool with 26 MCQs, which primarily addressed the area of scientific skills. The post-review showed that student-generated MCQs were of high quality with regard to test statistic criteria and content. Overall, the progress test displayed a very high reliability. When the academic years were compared, the progress test mapped out over the course of study not only by the overall test but also in terms of the subject groups and competency areas. Outlook: Further development in cooperation with students will be continued. Focus will be on compiling additional questions and test formats that can represent competency at a higher skill level, such as key feature questions, situational judgement test questions and OSCE. In addition, the feedback formats will be successively expanded. The intention is also to offer the formative competency-based progress test online.
Quantification of the Visual Field Loss in Retinitis Pigmentosa Using Semi-Automated Kinetic Perimetry
2015-10-15

To assess quantitatively the natural course of the visual field (VF) loss in patients with retinitis pigmentosa (RP) during 2-year period of observation.VFs were obtained by semi-automated kinetic perimetry (SKP) during four examinations of 16 patients suffering from RP. Three stimulus conditions (V4e, III4e and I4e) with a constant stimulus angular velocity of 3°/s were used to assess the hill of vision in both eyes of each patient. The area of each isopter was measured in square degrees and corrected for the individual reaction time (RT).There were four patients with mild restriction of VF, six with ring scotomas and six with advanced concentric constrictions of VF. Only I4e isopter area decreased significantly from the first to the last session (p = 0.006), the difference was 154 deg(2) being 13% of initial isopter area. The difference was not significant for V4e and III4e isopters. RT values did not differ significantly between four sessions.Only I4e isopter's area was decreased significantly during two years of observation. SKP provides a method of assessment of progression of the VF loss in patients suffering from RP by measurement of the isopters' area over time.
Large-Scale Purification of r28M: A Bispecific scFv Antibody Targeting Human Melanoma Produced in Transgenic Cattle
2015-10-15

Summing up, we managed to purify monomeric r28M from bovine plasma in a large-scale preparation and could prove that its biological activity is unaffected and still highly specific and thus, might be applicable for the treatment of melanoma.
Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases
2015-10-16

The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.
Insertable cardiac monitors after cryptogenic stroke – a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation
2015-10-16

Background and purpose Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation ( AF ) in 12.4% of patients after cryptogenic ischaemic stroke ( IS ) or cryptogenic transient ischaemic attack ( TIA ) by an insertable cardiac monitor ( ICM ) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre‐selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection. Methods Seventy‐five patients with cryptogenic IS / TIA were consecutively enrolled if at least one of the following AF risk factors was present: a CHA 2 DS 2 ‐ VAS c score ≥4, atrial runs, left atrium ( LA ) size &gt;45 mm, left atrial appendage ( LAA ) flow ≤0.2 m/s, or spontaneous echo contrast in the LAA . The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF ; the same applies for four of the six items of the CHA 2 DS 2 ‐ VAS c score. The study end‐point was the detection of one or more episodes of AF (≥2 min). Results Seventy‐four patients underwent implantation of an ICM ; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size &gt;45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval 1.6–8.4), P = 0.002, and 2.7 (1.2–6.7), P = 0.023, respectively]. Conclusions The detection rate of AF is one‐third after 1 year if candidates for an ICM after cryptogenic IS / TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF .
Emotional facial expressions evoke faster orienting responses, but weaker emotional responses at neural and behavioural levels compared to scenes: A simultaneous EEG and facial EMG study
2015-10-16

In the current study, electroencephalography (EEG) was recorded simultaneously with facial electromyography (fEMG) to determine whether emotional faces and emotional scenes are processed differently at the neural level. In addition, it was investigated whether these differences can be observed at the behavioural level via spontaneous facial muscle activity. Emotional content of the stimuli did not affect early P1 activity. Emotional faces elicited enhanced amplitudes of the face-sensitive N170 component, while its counterpart, the scene-related N100, was not sensitive to emotional content of scenes. At 220-280ms, the early posterior negativity (EPN) was enhanced only slightly for fearful as compared to neutral or happy faces. However, its amplitudes were significantly enhanced during processing of scenes with positive content, particularly over the right hemisphere. Scenes of positive content also elicited enhanced spontaneous zygomatic activity from 500-750ms onwards, while happy faces elicited no such changes. Contrastingly, both fearful faces and negative scenes elicited enhanced spontaneous corrugator activity at 500-750ms after stimulus onset. However, relative to baseline EMG changes occurred earlier for faces (250ms) than for scenes (500ms) whereas for scenes activity changes were more pronounced over the whole viewing period. Taking into account all effects, the data suggests that emotional facial expressions evoke faster attentional orienting, but weaker affective neural activity and emotional behavioural responses compared to emotional scenes.
Brain state-dependent robotic reaching movement with a multi-joint arm exoskeleton: combining brain-machine interfacing and robotic rehabilitation
2015-10-16

While robot-assisted arm and hand training after stroke allows for intensive task-oriented practice, it has provided only limited additional benefit over dose-matched physiotherapy up to now. These rehabilitation devices are possibly too supportive during the exercises. Neurophysiological signals might be one way of avoiding slacking and providing robotic support only when the brain is particularly responsive to peripheral input. We tested the feasibility of three-dimensional robotic assistance for reaching movements with a multi-joint exoskeleton during motor imagery (MI)-related desynchronization of sensorimotor oscillations in the β-band. We also registered task-related network changes of cortical functional connectivity by electroencephalography via the imaginary part of the coherence function. Healthy subjects and stroke survivors showed similar patterns-but different aptitudes-of controlling the robotic movement. All participants in this pilot study with nine healthy subjects and two stroke patients achieved their maximum performance during the early stages of the task. Robotic control was significantly higher and less variable when proprioceptive feedback was provided in addition to visual feedback, i.e., when the orthosis was actually attached to the subject's arm during the task. A distributed cortical network of task-related coherent activity in the θ-band showed significant differences between healthy subjects and stroke patients as well as between early and late periods of the task. Brain-robot interfaces (BRIs) may successfully link three-dimensional robotic training to the participants' efforts and allow for task-oriented practice of activities of daily living with a physiologically controlled multi-joint exoskeleton. Changes of cortical physiology during the task might also help to make subject-specific adjustments of task difficulty and guide adjunct interventions to facilitate motor learning for functional restoration, a proposal that warrants further investigation in a larger cohort of stroke patients.
Effects of Processing on the Acceptability of “Frozen” Extraposed Constituents
2015-10-16

Abstract In syntactic theory, “freezing” refers to the idea that a constituent extraposed to a noncanonical position is resistant to extraction of any of its subconstituents ( What did Terry see a movie yesterday about ——— ? ). The unacceptability of such examples, compared to minimally different sentences without extraposition, has been claimed to be a result of a grammatical constraint on dependency formation, such as Ross's (1967) Frozen Structure Constraint. Here, we argue that the gradient pattern of acceptability associated with such examples is better explained in terms of processing complexity. Experimental evidence from a controlled acceptability task shows that the total penalty for extraction from extraposed constituents is predictable from the summed acceptability penalties independently linked to extraction and extraposition. As prior research links both of these displacement phenomena to increased processing costs, we conclude that a grammar of unbounded dependencies in English does not require a “freezing” constraint for the explanation of these cases.
Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity
2015-10-16

&lt;div&gt;&lt;p&gt;Murine polyomavirus (MuPyV) causes tumors of various origins in newborn mice and hamsters. Infection is initiated by attachment of the virus to ganglioside receptors at the cell surface. Single amino acid exchanges in the receptor-binding pocket of the major capsid protein VP1 are known to drastically alter tumorigenicity and spread in closely related MuPyV strains. The virus represents a rare example of differential receptor recognition directly influencing viral pathogenicity, although the factors underlying these differences remain unclear. We performed structural and functional analyses of three MuPyV strains with strikingly different pathogenicities: the low-tumorigenicity strain RA, the high-pathogenicity strain PTA, and the rapidly growing, lethal laboratory isolate strain LID. Using ganglioside deficient mouse embryo fibroblasts, we show that addition of specific gangliosides restores infectability for all strains, and we uncover a complex relationship between virus attachment and infection. We identify a new infectious ganglioside receptor that carries an additional linear [α-2,8]-linked sialic acid. Crystal structures of all three strains complexed with representative oligosaccharides from the three main pathways of ganglioside biosynthesis provide the molecular basis of receptor recognition. All strains bind to a range of sialylated glycans featuring the central [α-2,3]-linked sialic acid present in the established receptors GD1a and GT1b, but the presence of additional sialic acids modulates binding. An extra [α-2,8]-linked sialic acid engages a protein pocket that is conserved among the three strains, while another, [α-2,6]-linked branching sialic acid lies near the strain-defining amino acids but can be accommodated by all strains. By comparing electron density of the oligosaccharides within the binding pockets at various concentrations, we show that the [α-2,8]-linked sialic acid increases the strength of binding. Moreover, the amino acid exchanges have subtle effects on their affinity for the validated receptor GD1a. Our results indicate that both receptor specificity and affinity influence MuPyV pathogenesis.&lt;/p&gt;&lt;/div&gt;
Factors Associated with Retention to Care in an HIV Clinic in Gabon, Central Africa
2015-10-16

Retention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care.
The communicative construction of FEMEN: naked protest in self-mediation and German media discourse
2015-10-16

In this article, we investigate how FEMEN employs female nudity to raise public attention in their mediatized strategies and how this form of naked protest is represented and interpreted in German media discourse. We will show that the significant media presence of FEMEN's naked protest actions and its self-portrayal as the new feminism of our days have become increasingly ambivalent over time. As this is of great importance with regards to public perceptions of feminism, feminist activists, and feminist agency in general, our analysis provides a detailed investigation of the processes of appreciation and devaluation of FEMEN as an expression of contemporary feminists and feminism. Employing a qualitative discourse analysis, the article highlights the interwoven processes of contextualization and decontextualization in FEMEN's self-mediation and news coverage in Germany. It is shown that FEMEN's protests from 2008 to 2013 materialize in "local" actions, but are increasingly constructed and interpreted on a transcultural level. In this analysis, we identify the core interpretative scheme of decontextualization that becomes apparent in three forms of detachments. As we show, these forms of detachment are a core issue in the media's devaluation and depolitization of FEMEN and feminism in general.
BiGG Models: A platform for integrating, standardizing and sharing genome-scale models
2015-10-17

Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories of high-quality models must be established, models must adhere to established standards and model components must be linked to relevant databases. Tools for model visualization further enhance their utility. To meet these needs, we present BiGG Models (http://bigg.ucsd.edu), a completely redesigned Biochemical, Genetic and Genomic knowledge base. BiGG Models contains more than 75 high-quality, manually-curated genome-scale metabolic models. On the website, users can browse, search and visualize models. BiGG Models connects genome-scale models to genome annotations and external databases. Reaction and metabolite identifiers have been standardized across models to conform to community standards and enable rapid comparison across models. Furthermore, BiGG Models provides a comprehensive application programming interface for accessing BiGG Models with modeling and analysis tools. As a resource for highly curated, standardized and accessible models of metabolism, BiGG Models will facilitate diverse systems biology studies and support knowledge-based analysis of diverse experimental data.
Online Coping After Negative Life Events
2015-10-17

This article explores how individuals use online coping strategies after experiencing a negative life event. Many studies have shown that online coping is of rising importance. However, these studies have not provided all pieces of the puzzle because they tend to focus on one particular online venue (e.g., an online support group or social network site [SNS]) and on a limited number of coping strategies. This article aims to provide a more complete picture, by simultaneously examining multiple online and off-line coping strategies, using a survey administered to a representative sample of the 16+ population of the Netherlands. Furthermore, we analyze what kind of Internet activities are related to online coping and whether online coping is associated with well-being. Some 57% of our sample mentioned some form of online coping. Using the Internet for mental disengagement, active coping and planning were the most reported online coping strategies, whereas strategies aimed at emotional coping were reported less frequently. Online coping encompassed several activities: online gaming, which was associated with mental disengagement; searching for information, which was associated with problem-focused coping; and SNS and online support groups, which were associated with mental disengagement, problem-focused coping, and socioemotional coping. Finally, we examined the correlations between online coping and well-being. Controlling for off-line coping, we found online mental disengagement and online socioemotional coping to be inversely related to life satisfaction, self-esteem, and optimism, whereas correlations between online problem-focused coping and well-being were nonsignificant. The implications of these findings are discussed.
BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury
2015-10-17

For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF (Pax2) -KO) versus the auditory cortex and hippocampus (BDNF (TrkC) -KO). We demonstrate that BDNF (Pax2) -KO but not BDNF (TrkC) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF (Pax2) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF (Pax2) -KO, but not of BDNF (TrkC) -KO mice. Also, BDNF (Pax2) -WT but not BDNF (Pax2) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise.