julilili42/papers huggingface dataset:
Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study
2018-07-30

Abstract We aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical‐grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset ( n = 2280) mostly representing HGSC ( n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis‐associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47–2.77, p &lt; 0.001] and endometrioid (HR: 1.88, 95% CI 1.30–2.75, p = 0.004), while absence was associated with shorter OS in low‐grade serous carcinomas (HR: 2.95, 95% CI 1.61–5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype‐specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low‐grade serous carcinoma justifies CDK4 inhibition.
Molecular characterization of Treponema pallidum subsp. pallidum in Switzerland and France with a new multilocus sequence typing scheme
2018-07-30

Syphilis is an important public health problem and an increasing incidence has been noted in recent years. Characterization of strain diversity through molecular data plays a critical role in the epidemiological understanding of this re-emergence. We here propose a new high-resolution multilocus sequence typing (MLST) scheme for Treponema pallidum subsp. pallidum (TPA). We analyzed 30 complete and draft TPA genomes obtained directly from clinical samples or from rabbit propagated strains to identify suitable typing loci and tested the new scheme on 120 clinical samples collected in Switzerland and France. Our analyses yielded three loci with high discriminatory power: TP0136, TP0548, and TP0705. Together with analysis of the 23S rRNA gene mutations for macrolide resistance, we propose these loci as MLST for TPA. Among clinical samples, 23 allelic profiles as well as a high percentage (80% samples) of macrolide resistance were revealed. The new MLST has higher discriminatory power compared to previous typing schemes, enabling distinction of TPA from other treponemal bacteria, distinction between the two main TPA clades (Nichols and SS14), and differentiation of strains within these clades.
Accelerating infall and rotational spin-up in the hot molecular core G31.41+0.31
2018-07-30

\\nAs part of our effort to search for circumstellar disks around high-mass stellar objects, we observed the well-known core G31.41 +0.31 with ALMA at 1.4 mm with an angular resolution of ~0.′′22 (~1700 au). The dust continuum emission has been resolved into two cores namely Main and NE. The Main core, which has the stronger emission and is the more chemically rich, has a diameter of ~5300 au, and is associated with two free-free continuum sources. The Main core looks featureless and homogeneous in dust continuum emission and does not present any hint of fragmentation. Each transition of CH3CN and CH3OCHO, both ground and vibrationally excited, as well as those of CH3CN isotopologues, shows a clear velocity gradient along the NE–SW direction, with velocity linearly increasing with distance from the center, consistent with solid-body rotation. However, when comparing the velocity field of transitions with different upper level energies, the rotation velocity increases with increasing energy of the transition, which suggests that the rotation speeds up toward the center. Spectral lines towardtoward the dust continuum peak show an inverse P-Cygni profile that supports the existence of infall in the core. The infall velocity increases with the energy of the transition suggesting that the infall is accelerating toward the center of the core, consistent with gravitational collapse. Despite the monolithic appearance of the Main core, the presence of red-shifted absorption, the existence of two embedded free-free sources at the center, and the rotational spin-up are consistent with an unstable core undergoing fragmentation with infall and differential rotation due to conservation of angular momentum. Therefore, the most likely explanation for the monolithic morphology is that the large opacity of the dust emission prevents the detection of any inhomogeneity in the core.\\n
Boosting competence-orientation in undergraduate medical education – A web-based tool linking curricular mapping and visual analytics
2018-07-30

<b>Objectives:</b> Transition to competency-based medical education is a highly challenging endeavor. Students, teachers and institutions need curricular transparency for understanding the build-up of competencies in terms of coverage, sequence and consistence of learning objectives and assessment. The project aim was to develop and implement a web-based interactive platform for curriculum mapping, diagnostics, and development. The tool should be transferable to other faculties and allow description and visualization of medical curricula in comparison to given national competency-based standards. <b>Methods:</b> In a design-based multi-center approach, four German medical faculties cooperated and developed a standardized, common mapping tool (MER<i>lin</i> database). Implemented are techniques for big data handling and visual analytics. <b>Results:</b> The platform profile is adapted closely to user needs. Intuitive data entry and comfortable quality maintenance support teacher engagement. Individual navigation for curricular diagnostics is guided by practice-oriented questions. Sophisticated, easy-understandable visualizations show curricular strengths and weaknesses. Transparency in contributing departments facilitates goal-oriented dialogs. Currently, 14 of 38 German faculties use the platform. <b>Conclusions:</b> In view of huge amounts of data and complex curricular structures, the MER<i>lin</i> database facilitates effective curriculum mapping, goal-oriented curriculum development, comparison to national competency-based standards, effective data sharing and benchmarking across faculties with different curriculum management systems.
Image content is more important than Bouma’s Law for scene metamers
2018-07-30

Abstract We subjectively perceive our visual field with high fidelity, yet large peripheral distortions can go unnoticed and peripheral objects can be difficult to identify (crowding). A recent paper proposed a model of the mid-level ventral visual stream in which neural responses were averaged over an area of space that increased as a function of eccentricity (scaling). Human participants could not discriminate synthesised model images from each other (they were metamers) when scaling was about half the retinal eccentricity. This result implicated ventral visual area V2 and approximated “Bouma’s Law” of crowding. It has subsequently been interpreted as a link between crowding zones, receptive field scaling, and our rich perceptual experience. However, participants in this experiment never saw the original images. We find that participants can easily discriminate real and model-generated images at V2 scaling. Lower scale factors than even V1 receptive fields may be required to generate metamers. Efficiently explaining why scenes look as they do may require incorporating segmentation processes and global organisational constraints in addition to local pooling.
Gating of miRNA movement at defined cell-cell interfaces governs their impact as positional signals
2018-07-31

Abstract Mobile small RNAs serve as local positional signals in development and coordinate stress responses across the plant. Despite its central importance, an understanding of how the cell-to-cell movement of small RNAs is governed is lacking. Here, we show that miRNA mobility is precisely regulated through a gating mechanism polarised at defined cell–cell interfaces. This generates directional movement between neighbouring cells that limits long-distance shoot-to-root trafficking, and underpins domain-autonomous behaviours of small RNAs within stem cell niches. We further show that the gating of miRNA mobility occurs independent of mechanisms controlling protein movement, identifying the small RNA as the mobile unit. These findings reveal gate-keepers of cell-to-cell small RNA mobility generate selectivity in long-distance signalling, and help safeguard functional domains within dynamic stem cell niches while mitigating a ‘signalling gridlock’ in contexts where developmental patterning events occur in close spatial and temporal vicinity.
Noise Affects Multimodal Communication During Courtship in a Marine Fish
2018-07-31

Selection pressures on signals can be substantially modified by a changing environment, but we know little about how modified selection pressures act on multimodal signals. The currently increasing levels of anthropogenic noise in the ocean may affect the use of acoustic signaling relative to other modalities. In the Painted Goby (Pomatoschistus pictus), visual and acoustic signals are associated during courtship behavior, but females usually rely more heavily on acoustic signals than on visual signals in mate choice. In an aquarium experiment, we compared male courtship behavior and female spawning decisions between silent treatments and treatments with additional noise. We found that the relationships between male characteristics, male visual and acoustic courtship, and spawning success were affected by noise. A path analysis revealed that females pay more attention to visual courtship in noisy circumstances compared to control. We conclude that environmental stressors can cause shifts in the use of different signaling modalities for spawning decisions and discuss how selection pressures on multimodal signals may change with increasing noise-levels.
Novel Technique for Improving Graft Unfolding in Vitrectomized Eyes Using a Temporary Diaphragm in Descemet Membrane Endothelial Keratoplasty
2018-07-31

Purpose: To describe a new surgical technique for performing Descemet membrane endothelial keratoplasty (DMEK) using a temporary hydrophilic methacrylate sheet in the anterior chamber in cases of previous vitrectomy with complete removal of the vitreous body. Methods: Medical records were reviewed for baseline and follow-up best spectacle-corrected visual acuity, endothelial cell count, and indication for DMEK using a temporary hydrophilic methacrylate sheet. Operative notes were analyzed in all cases to identify any specific intraoperative event. Results: Seven eyes of 7 patients were included in this analysis. Mean age was 65.7 ± 18.2 years, and the mean follow-up duration was 11.5 months. All 7 patients had previously received pars plana vitrectomy with complete vitreous removal. All patients were pseudophakic. For 5 patients, it was their first DMEK surgery and 2 patients had DMEK surgery for a second time, due to a failed outcome in previous surgery. Best spectacle-corrected visual acuity improved from 1.5 ± 0.5 logMAR before surgery to 0.76 ± 0.37 logMAR after surgery during follow-up ( P &lt; 0.001). The mean endothelial cell count was 2442 ± 304 cells/mm 2 and decreased to 1484 ± 279 cells/mm 2 during follow-up ( P &lt; 0.001). No complications were observed in any of the cases at the unfolding stage using this method. All grafts remained clear at the last follow-up visit. Conclusions: This modified approach of DMEK surgery, using a temporary hydrophilic methacrylate sheet for flattening the anterior chamber and facilitating graft unfolding, could help overcome possible complications of DMEK in completely vitrectomized eyes.
Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity
2018-07-31

Activity-dependent BDNF (brain-derived neurotrophic factor) expression is hypothesized to be a cue for the context-specificity of memory formation. So far, activity-dependent BDNF cannot be explicitly monitored independently of basal BDNF levels. We used the BLEV ( <b><i>B</i></b> DNF- <b><i>l</i></b><i>ive-</i><b><i>e</i></b><i>xon</i>- <b><i>v</i></b><i>isualization</i>) reporter mouse to specifically detect activity-dependent usage of <i>Bdnf</i> exon-IV and -VI promoters through bi-cistronic co-expression of CFP and YFP, respectively. Enriching acoustic stimuli led to improved peripheral and central auditory brainstem responses, increased Schaffer collateral LTP, and enhanced performance in the Morris water maze. Within the brainstem, neuronal activity was increased and accompanied by a trend for higher expression levels of <i>Bdnf</i> exon-IV-CFP and exon-VI-YFP transcripts. In the hippocampus BDNF transcripts were clearly increased parallel to changes in parvalbumin expression and were localized to specific neurons and capillaries. Severe acoustic trauma, in contrast, elevated neither <i>Bdnf</i> transcript levels, nor auditory responses, parvalbumin or LTP. Together, this suggests that critical sensory input is essential for recruitment of activity-dependent auditory-specific BDNF expression that may shape network adaptation.
Immune Cell Induced Migration of Osteoprogenitor Cells Is Mediated by TGF-β Dependent Upregulation of NOX4 and Activation of Focal Adhesion Kinase
2018-07-31

The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and focal adhesion kinase (FAK) as possible regulators. Monocyte- and macrophage (THP-1 cells ± phorbol 12-myristate 13-acetate (PMA) treatment)-conditioned media, other than the granulocyte-conditioned medium (HL-60 cells + dimethyl sulfoxide (DMSO) treatment), induce migration of phOBs. Monocyte- and macrophage (THP-1 cells)-conditioned media activate Smad3-dependent TGF-β signaling in the phOBs. Stimulation with TGF-β promotes migration of phOBs. Furthermore, TGF-β treatment strongly induces NOX4 expression on both mRNA and protein levels. The associated reactive oxygen species (ROS) accumulation results in phosphorylation (Y397) of FAK. Blocking TGF-β signaling, NOX4 activity and FAK signaling effectively inhibits the migration of phOBs towards TGF-β. In summary, our data suggest that monocytic- and macrophage-like cells induce migration of phOBs in a TGF-β-dependent manner, with TGF-β-dependent induction of NOX4, associated production of ROS and resulting activation of FAK as key mediators.
Electronic Structure of Hexacene and Interface Properties on Au(110)
2018-07-31

Although hexacene was first synthesized in 1939, the thin film properties, which are interesting for future applications and fundamental research, have never been investigated. Therefore, we synthesized hexacene by reduction of 6,15-hexacenequinone, evaporated hexacene, and grew films of variable thicknesses on Au(110). This allowed us to study the electronic properties and molecular orientations in the bulk as well as at the molecule–metal interface by X-ray absorption spectroscopy (XAS) and photoelectron spectroscopy. Valence band spectra of a multilayer hexacene film are compared to those of electronic states obtained from density functional theory calculations. C 1s core-level spectra show typical satellite structures of the extended aromatic π-system, similar to pentacene. XAS shows that anisotropy rises with decreasing film thickness and indicates that hexacene is almost flat lying on the Au(110) substrate. The different peak shapes of XAS spectra as a function of the film thickness, as well as changes in valence band spectra and C 1s satellite structures, indicate a strong electronic coupling of the molecular states with the states of the Au(110) substrate at the interface.
Choice of progestogen for endometrial protection in combination with transdermal estradiol in menopausal women
2018-07-31

Abstract Transdermal estradiol (TE) application (using gels, patches or a novel spray) is now a preferred route of hormone therapy (HT) in menopausal women, because various risks such as venous thromboembolism, stroke and unwanted hepatic effects can be reduced compared with oral HT. However, in the presence of an intact uterus, concurrent administration of progestogen is needed for endometrial protection. Due to the variety of progestogens available and differences in their clinical effects, the selection of the most appropriate substance and dosing for individual combination therapy can be difficult. This is especially true for TE gels and the novel spray because no fixed combination products are commercially available, meaning all progestogens must be added separately, and even for patches only two transdermal synthetic progestogens are available. The aim of this review was to summarize data on the endometrial effects of the different progestogens and to provide practical recommendations for the choice of progestogen (type and dosing), with a focus on endometrial protection when using TE, especially when using the novel estradiol (E2) spray.
Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing
2018-07-31

We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing. We therefore investigated the sample of 17 healthy males in a mean age of 23.8 years again by functional magnetic resonance imaging (fMRI), to explore the noradrenergic effects on neural reward prediction error signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and placebo each for 7 days within a randomized, double-blind, within-subject cross-over design. During fMRI, we used an established monetary incentive task to assess neural reward expectation and prediction error signals within the bilateral Nacc using an independent anatomical mask for a region of interest (ROI) analysis. Activations within the same ROI were also assessed for the erotic picture paradigm. We confirmed our previous results from the whole brain analysis for the selected ROI by significant (p &lt; 0.05 FWE-corrected) attenuated activations within the Nacc during visual sexual stimulation under reboxetine compared to placebo. However, activations in the Nacc concerning prediction error processing and monetary reward expectation were unimpaired under reboxetine compared to placebo, along with unimpaired reaction times in the reward task. For both tasks, neural activations and behavioral processing were not altered by amisulpride compared to placebo. The observed attenuated neural activations within the Nacc during visual erotic stimulation along with unimpaired neural prediction error and monetary reward expectation processing provide evidence for a differential modulation of the neural reward system by the noradrenergic agent reboxetine depending on the presence of primary reinforcers such as erotic stimuli in contrast to secondary such as monetary rewards.
The C-type lectin Schlaff ensures epidermal barrier compactness inDrosophila
2018-07-31

Abstract The stability of extracellular matrices is in general ensured by cross-linking of its components. Previously, we had shown that the integrity of the layered Drosophila cuticle relies on the presence of a covalent cuticular dityrosine network. Production and composition of this structure remained unstudied. In this work, we present our analyses of the schlaff ( slf ) gene coding for a C-type lectin that is needed for the adhesion between the horizontal cuticle layers. The Slf protein mainly localizes between the two layers called epicuticle and procuticle that separate from each other when the function of Slf is reduced or eliminated paralleling the phenotype of a cuticle with reduced extracellular dityrosine. Localisation of the dityrosinylated protein Resilin to the epicuticle-procuticle interface suggests that the dityrosine network mediates the adhesion of the epicuticle to the procuticle. Ultimately, compromised Slf function is associated with massive water loss. In summary, we propose that Slf is implied in the stabilisation of a dityrosine layer especially between the epicuticle and the procuticle that in turn constitutes an outward barrier against uncontrolled water flow. Summary statement Extracellular matrices adopt a stereotypic organisation for function during development. The lectin Schlaff assists adhesion reactions to ensure compactness of the epidermal cuticle in Drosophila.
Commentary: Inpatient and Postdischarge Outcomes Following Elective Craniotomy for Mass Lesions
2018-07-31

Department of Neurosurgery, University Hospital Tuebingen, Eberhard-Karls-University, Tuebingen, Germany Center for CNS Tumors, Comprehensive Cancer Center Tuebingen Stuttgart, University Hospital Tuebingen, Eberhard-Karls University Tuebingen, Tuebingen, Germany Correspondence: Felix Behling, MD, Department of Neurosurgery, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler Street 3, Tuebingen, Germany. E-mail: [email protected]