bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA and miRNA expression profiles in an ectoderm-biased substate of human pluripotent stem cells
Authors: Mawaribuchi Shuuji , Aiki Yasuhiko , Ikeda Nozomi , Ito Yuzuru 
Published: August 2019

AbstractThe potential applications of human pluripotent stem cells, embryonic stem (ES) cells, and induced pluripotent stem (iPS) cells in cell therapy and regenerative medicine have been widely studied. The precise definition of pluripotent stem cell status during culture using biomarkers is essential for basic research and regenerative medicine. Culture conditions, including extracellular matrices, influence the balance between self-renewal and differentiation. Accordingly, to explore biomarkers for defining and monitoring the pluripotent substates during culture, we established different substates in H9 human ES cells by changing the extracellular matrix from vitronectin to Matrigel. The substate was characterised by low and high expression of the pluripotency marker R-10G epitope and the mesenchymal marker vimentin, respectively. Immunohistochemistry, induction of the three germ layers, and exhaustive expression analysis showed that the substate was ectoderm-biased, tended to differentiate into nerves, but retained the potential to differentiate into the three germ layers. Further integrated analyses of mRNA and miRNA microarrays and qPCR analysis showed that nine genes (COL9A2, DGKI, GBX2, KIF26B, MARCH1, PLXNA4, SLC24A4, TLR4, and ZHX3) were upregulated in the ectoderm-biased cells as ectoderm-biased biomarker candidates in pluripotent stem cells. Our findings provide important insights into ectoderm-biased substates of human pluripotent stem cells in the fields of basic research and regenerative medicine.
New tools for an old question: dependence of ATP and bicarbonate for branched-chain keto acids oxidation
Authors: Brunetta Henver S. , Holloway Graham P. 
Published: August 2019

Abstract
Branched-chain keto acids (BCKA) metabolism involves several well-regulated steps within mitochondria, requires cofactors, and is modulated according to the metabolic status of the cells. This regulation has made it challenging to utilize in vitro approaches to determine the contribution of branched-chain amino acid oxidation to energy production. These methodological issues were elegantly addressed in a recent publication within the Biochemical Journal. In this issue, Goldberg et al. [Biochem. J. (2019) 476, 1521–1537] demonstrated in a well-designed system the dependence of ATP and bicarbonate for BCKA full oxidation. In addition, the utilized system allowed the authors to characterize specific biochemical routes within mitochondria for each BCKA. Among them, a quantitative analysis of the participation of BCKA on mitochondrial flux was estimated between tissues. These findings are milestones with meaningful impact in several fields of metabolism.
Interactions between motor domains in kinesin-14 Ncd — a molecular dynamics study
Authors: Ludwiczak Jan , Szczęsna Ewa , da Silva Neto Antônio Marinho , Cieplak Piotr , Kasprzak Andrzej A. , Jarmuła Adam 
Published: August 2019

Abstract
Minus-end directed, non-processive kinesin-14 Ncd is a dimeric protein with C-terminally located motor domains (heads). Generation of the power-stroke by Ncd consists of a lever-like rotation of a long superhelical ‘stalk’ segment while one of the kinesin's heads is bound to the microtubule. The last ∼30 amino acids of Ncd head play a crucial but still poorly understood role in this process. Here, we used accelerated molecular dynamics simulations to explore the conformational dynamics of several systems built upon two crystal structures of Ncd, the asymmetrical T436S mutant in pre-stroke/post-stroke conformations of two partner subunits and the symmetrical wild-type protein in pre-stroke conformation of both subunits. The results revealed a new conformational state forming following the inward motion of the subunits and stabilized with several hydrogen bonds to residues located on the border or within the C-terminal linker, i.e. a modeled extension of the C-terminus by residues 675–683. Forming of this new, compact Ncd conformation critically depends on the length of the C-terminus extending to at least residue 681. Moreover, the associative motion leading to the compact conformation is accompanied by a partial lateral rotation of the stalk. We propose that the stable compact conformation of Ncd may represent an initial state of the working stroke.
An integrative bioinformatics analysis of microarray data for identifying hub genes as diagnostic biomarkers of preeclampsia
Authors: Liu Keling , Fu Qingmei , Liu Yao , Wang Chenhong 
Published: August 2019

Abstract
Preeclampsia (PE) is a disorder of pregnancy that is characterised by hypertension and a significant amount of proteinuria beginning after 20 weeks of pregnancy. It is closely associated with high maternal morbidity, mortality, maternal organ dysfunction or foetal growth restriction. Therefore, it is necessary to identify early and novel diagnostic biomarkers of PE. In the present study, we performed a multi-step integrative bioinformatics analysis of microarray data for identifying hub genes as diagnostic biomarkers of PE. With the help of gene expression profiles of the Gene Expression Omnibus (GEO) dataset GSE60438, a total of 268 dysregulated genes were identified including 131 up- and 137 down-regulated differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs suggested that DEGs were significantly enriched in disease-related biological processes (BPs) such as hormone activity, immune response, steroid hormone biosynthesis, metabolic pathways, and other signalling pathways. Using the STRING database, we established a protein–protein interaction (PPI) network based on the above DEGs. Module analysis and identification of hub genes were performed to screen a total of 17 significant hub genes. The support vector machines (SVMs) model was used to predict the potential application of biomarkers in PE diagnosis with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.958 in the training set and 0.834 in the test set, suggesting that this risk classifier has good discrimination between PE patients and control samples. Our results demonstrated that these 17 differentially expressed hub genes can be used as potential biomarkers for diagnosis of PE.
Allostatic load and ageing: linking the microbiome and nutrition with age-related health
Authors: Shiels Paul G. , Buchanan Sarah , Selman Colin , Stenvinkel Peter 
Published: August 2019

Abstract
Ageing is a process of decline in physiological function and capability over time. It is an anticipated major burden on societal health-care costs due to an increasingly aged global population. Accelerated biological ageing is a feature of age-related morbidities, which also appear to share common underpinning features, including low-grade persistent inflammation, phosphate toxicity, diminished Nrf2 activity, a depleted metabolic capability, depressed mitochondrial biogenesis and a low diversity gut microbiome.
Social, psychological, lifestyle and nutritional risk factors can all influence the trajectory of age-related health, as part of an individual's exposome, which reflects the interplay between the genome and the environment. This is manifest as allostatic (over)load reflecting the burden of lifestyle/disease at both a physiological and molecular level. In particular, age-related genomic methylation levels and inflammatory status reflect exposome differences. These features may be mediated by changes in microbial diversity. This can drive the generation of pro-inflammatory factors, such as TMAO, implicated in the ‘diseasome’ of ageing. Additionally, it can be influenced by the ‘foodome’, via nutritional differences affecting the availability of methyl donors required for maintenance of the epigenome and by the provision of nutritionally derived Nrf2 agonists. Both these factors influence age-related physiological resilience and health. This offers novel insights into possible interventions to improve health span, including a rage of emerging senotherapies and simple modifications of the nutritional and environmental exposome. In essence, the emerging strategy is to treat ageing processes common to the diseasome of ageing itself and thus preempt the development or progression of a range of age-related morbidities.
Looking for Mickey Mouse™ But Finding a Munchkin: The Perceptual Effects of Frequency Upshifts for Single-Sided Deaf, Cochlear Implant Patients
Authors: Dorman Michael F. , Natale Sarah C. , Zeitler Daniel M. , Baxter Leslie , Noble Jack H. 
Published: August 2019

Purpose
Our aim was to make audible for normal-hearing listeners the Mickey Mouse™ sound quality of cochlear implants (CIs) often found following device activation.

Method
The listeners were 3 single-sided deaf patients fit with a CI and who had 6 months or less of CI experience. Computed tomography imaging established the location of each electrode contact in the cochlea and allowed an estimate of the place frequency of the tissue nearest each electrode. For the most apical electrodes, this estimate ranged from 650 to 780 Hz. To determine CI sound quality, a clean signal (a sentence) was presented to the CI ear via a direct connect cable and candidate, and CI-like signals were presented to the ear with normal hearing via an insert receiver. The listeners rated the similarity of the candidate signals to the sound of the CI on a 1- to 10-point scale, with 10 being a complete match.

Results
To make the match to CI sound quality, all 3 patients need an upshift in formant frequencies (300–800 Hz) and a metallic sound quality. Two of the 3 patients also needed an upshift in voice pitch (10–80 Hz) and a muffling of sound quality. Similarity scores ranged from 8 to 9.7.

Conclusion

The formant frequency upshifts, fundamental frequency upshifts, and metallic sound quality experienced by the listeners can be linked to the relatively basal locations of the electrode contacts and short duration experience with their devices. The perceptual consequence was not the voice quality of Mickey Mouse™ but rather that of Munchkins in
The Wizard of Oz
for whom both formant frequencies and voice pitch were upshifted.

Supplemental Material

https://doi.org/10.23641/asha.9341651
Dynamics of cluster-forming hub-filament systems
Authors: Treviño-Morales S. P. , Fuente A. , Sánchez-Monge Á. , Kainulainen J. , Didelon P. , Suri S. , Schneider N. , Ballesteros-Paredes J. , Lee Y.-N. , Hennebelle P. , Pilleri P. , González-García M. , Kramer C. , García-Burillo S. , Luna A. , Goicoechea J. R. , Tremblin P. , Geen S. 
Published: August 2019

Context. High-mass stars and star clusters commonly form within hub-filament systems. Monoceros R2 (hereafter Mon R2), at a distance of 830 pc, harbors one of the closest of these systems, making it an excellent target for case studies.
Aims. We investigate the morphology, stability and dynamical properties of the Mon R2 hub-filament system.
Methods. We employed observations of the 13CO and C18O 1 →0 and 2 →1 lines obtained with the IRAM-30 m telescope. We also used H2 column density maps derived from Herschel dust emission observations.
Results. We identified the filamentary network in Mon R2 with the DisPerSE algorithm and characterized the individual filaments as either main (converging into the hub) or secondary (converging to a main filament). The main filaments have line masses of 30–100 M⊙ pc−1 and show signs of fragmentation, while the secondary filaments have line masses of 12–60 M⊙ pc−1 and show fragmentation only sporadically. In the context of Ostriker’s hydrostatic filament model, the main filaments are thermally supercritical. If non-thermal motions are included, most of them are transcritical. Most of the secondary filaments are roughly transcritical regardless of whether non-thermal motions are included or not. From the morphology and kinematics of the main filaments, we estimate a mass accretion rate of 10−4–10−3 M⊙ yr−1 into the central hub. The secondary filaments accrete into the main filaments at a rate of 0.1–0.4 × 10−4 M⊙ yr−1. The main filaments extend into the central hub. Their velocity gradients increase toward the hub, suggesting acceleration of the gas. We estimate that with the observed infall velocity, the mass-doubling time of the hub is ~2.5 Myr, ten times longer than the free-fall time, suggesting a dynamically old region. These timescales are comparable with the chemical age of the HII region. Inside the hub, the main filaments show a ring- or a spiral-like morphology that exhibits rotation and infall motions. One possible explanation for the morphology is that gas is falling into the central cluster following a spiral-like pattern.
Combining high-contrast imaging and radial velocities to constrain the planetary architectures of nearby stars
Authors: Boehle A. , Quanz S. P. , Lovis C. , Ségransan D. , Udry S. , Apai D. 
Published: August 2019

Context. Nearby stars are prime targets for exoplanet searches and characterization using a variety of detection techniques. Combining constraints from the complementary detection methods of high-contrast imaging (HCI) and radial velocity (RV) can further constrain the planetary architectures of these systems because these methods place limits at different regions of the companion mass and semi-major axis parameter space. Compiling a census of the planet population in the solar neighborhood is important to inform target lists for future space missions that will specifically target nearby stars to search for Earth analogs.
Aims. We aim to constrain the planetary architectures from the combination of HCI and RV data for six nearby stars within 6 pc: τ Ceti, Kapteyn’s star, AX Mic, 40 Eri, HD 36395, and HD 42581. We explored where HCI adds information to constraints from the long-term RV monitoring data for these stars.
Methods. We compiled the sample from stars with available archival VLT/NACO HCI data at L′ band (3.8 μm), where we expect substellar companions to be brighter for the typically older ages of nearby field stars (>1 Gyr). The NACO data were fully reanalyzed using the state-of-the-art direct imaging pipeline PynPoint and combined with RV data from HARPS, Keck/HIRES, and CORALIE. A Monte Carlo approach was used to assess the completeness in the companion mass and semi-major axis parameter space from the combination of the HCI and RV data sets.
Results. We find that the HCI data add significant information to the RV constraints, increasing the completeness for certain companions masses and semi-major axes by up to 68–99% for four of the six stars in our sample, and by up to 1–13% for the remaining stars. The improvements are strongest for intermediate semi-major axes (15–40 AU), corresponding to the semi-major axes of the ice giants in our own solar system. The HCI mass limits reach 5–20 MJup in the background-limited regime, depending on the age of the star.
Conclusions. Through the combination of HCI and RV data, we find that stringent constraints can be placed on the possible substellar companions in these systems. Applying these methods systematically to nearby stars will quantify our current knowledge of the planet population in the solar neighborhood and inform future observations.
Obstipation – Pathophysiologie, Diagnostik, Behandlung
Authors: Müller-Lissner Stefan 
Published: August 2019

AbstractThe most relevant risk factors for the development of chronic constipation are neurologic disorders such as Parkinson’s disease, immobility, and some drugs, in particular opioids. A proctologic exam and exclusion of red flags form part of the basic assessment. The currently available laxatives are effective and safe, habituation and tolerance (tachyphylaxis) being an exception. Also long-term intake of laxatives is of no concern when taken in recommended doses (no relevant hypokalemia!). Though the newer compounds (e. g., prucalopride, linaclotide, lubiprostone) are not more effective than the older ones, developing new drugs with alternative mode of action is reasonable since there are patients not satisfied with the currently available substances. Macrogol, Bisacodyl, and sodium picosulfate are the laxatives of first choice. Their selection depends on the individual preference of the patient. Opioids often induce constipation which can be ameliorated by laxatives or PAMORAs (peripherally acting µ-opioid antagonists).
Myokardiale Revaskularisation bei Patienten mit Diabetes mellitus
Authors: Haller Paul Michael , Westermann Dirk 
Published: August 2019

ZusammenfassungPatienten mit Diabetes mellitus stellen eine wesentliche Subgruppe aller Patienten mit koronarer Herzkrankheit dar. Unter anderem aufgrund des diabetesbedingten, oftmals aggressiven Voranschreitens der koronaren Herzkrankheit präsentiert sich diese Patientengruppe gewöhnlich mit einer komplexen Koronarmorphologie, unter anderem mit Befall mehrerer Gefäße und gegebenenfalls auch einer Beteiligung des linken Hauptstamms. Die Prognose dieser Patienten ist verglichen mit Patienten ohne Diabetes mellitus außerdem deutlich schlechter. Entsprechend herausfordernd ist die richtige Wahl der koronaren Revaskularisation bei symptomatischen Patienten. Zumal die meisten Patienten mit Diabetes mellitus einen Befall mehrerer Herzkranzgefäße aufweisen, sollte die Entscheidung über das weitere Vorgehen auf einer interdisziplinären Diskussion im Heart-Team beruhen. Denn vor allem im Langzeitverlauf profitieren Patienten mit Diabetes mellitus von einer Versorgung mittels aortokoronaren Bypasses, was sich mit einer Reduktion der Gesamtsterblichkeit und einer geringeren Rate an Myokardinfarkten zeigt.
Myokardrevaskularisierung im infarktbedingten kardiogenen Schock
Authors: Freund Anne , Desch Steffen , Thiele Holger 
Published: August 2019

ZusammenfassungCirca 10% der Patienten mit akutem Myokardinfarkt entwickeln einen kardiogenen Schock. Der wichtigste Eckpfeiler zur Therapie des infarktbedingten Schockes ist die frühzeitige Revaskularisierung. Es konnte in randomisierten Studien eine signifikante Verbesserung des Überlebens im Vergleich zu einer alleinigen medikamentösen Therapie belegt werden. Die perkutane Koronarintervention ist die dominierende Methode der Revaskularisierung. Bei mechanischen Komplikationen oder komplexer Koronaranatomie wird eine zeitnahe Konsultation des Heartteams empfohlen. Im Falle einer perkutanen Intervention bei koronarer Mehrgefäßerkrankung konnte in der randomisierten CULPRIT-SHOCK-Studie ein Überlebensvorteil für Patienten mit initial alleiniger Versorgung des infarktverursachenden Gefäßes im Vergleich zur sofortigen Mehrgefäßintervention gezeigt werden. Die Evidenz zu Therapieregimen bezüglich Antikoagulation und Thrombozytenaggregationshemmung ist gering.
Das retrobulbäre Hämatom – eine potenziell visusbedrohende Komplikation
Authors: Kopecky Adam , Rokohl Alexander Christopher , Nemcansky Jan , Koch Konrad R. , Matousek Petr , Heindl Ludwig M. 
Published: August 2019

ZusammenfassungDas retrobulbäre Hämatom (RBH) ist eine seltene, aber potenziell visusbedrohende Komplikation nach einem Trauma oder auch nach einem chirurgischen Eingriff. Die Diagnose muss dabei zeitnah gestellt werden, da nur eine rasche chirurgische Intervention irreversible Visusminderungen adäquat verhindern kann. Da es aufgrund der knöchernen orbitalen Begrenzung kaum Raum für das zunehmende, intraorbitale Volumen durch die retrobulbäre Blutung gibt, kommt es zu einer Erhöhung des intraorbitalen Drucks und konsekutiv zu einer Kompression des N. opticus. Mögliche Symptome umfassen insbesondere Motilitätsstörungen bis zur Ophthalmoplegie, eine Diplopie, eine Bindehautchemose, subkonjunktivale Blutungen, einen Exophthalmus, einen erhöhten intraokulären Druck, eine Verschlechterung der Sehschärfe sowie eine reduzierte direkte Lichtreaktion und ein relatives afferentes Pupillendefizit. Wenn die Ursache traumatisch oder iatrogen bedingt ist, ist eine zeitnahe, laterale Kanthotomie mit
Kantholyse das Mittel der Wahl und sorgt in den meisten Fällen für eine erfolgreiche Druckentlastung. Die Kanthotomie mit Kantholyse kann auch sehr gut in der Notaufnahme durch den Augenarzt durchgeführt werden und ist ggf. sogar ohne eine vorherige Bildgebung indiziert. Da die Rekonstruktion der Kantholyse meist unkompliziert möglich ist, empfehlen wir die Durchführung dieser Entlastung bereits, wenn klinisch der hochgradige Verdacht auf eine RBH gestellt wird. Sollte die Kanthotomie mit Kantholyse nicht für eine ausreichende Entlastung sorgen, muss eine chirurgische Orbitadekompression durchgeführt werden. Therapiebegleitend sollte immer eine pharmakologische Therapie mit Steroiden stattfinden.
Fixierung von Hauttransplantaten mit Vakuumversiegelung: Eine sinnvolle Option?
Authors: Meissner Markus 
Published: August 2019

ZusammenfassungDie Vakuumversiegelung (VS) ist eine seit circa 20 Jahren in der klassischen Wundversorgung nicht mehr wegzudenkende Therapieoption. Insbesondere im Bereich der Wundgrundkonditionierung von chronischen Wunden nimmt sie einen wichtigen Stellenwert ein. In den letzten Jahren wird die Vakuumversiegelung auch zur Fixierung und dem postoperativen Wundmanagement nach Hauttransplantation immer häufiger eingesetzt. Die vorliegende Übersichtsarbeit beschäftigt sich mit den Daten und Evidenzen eines solche Vorgehens und zeigt Möglichkeiten der Nutzung auf.
Convolutional neural networks for decoding of covert attention focus and saliency maps for EEG feature visualization
Authors: Farahat Amr , Reichert Christoph , Sweeney-Reed Catherine M , Hinrichs Hermann 
Published: August 2019

Abstract

Objective. Convolutional neural networks (CNNs) have proven successful as function approximators and have therefore been used for classification problems including electroencephalography (EEG) signal decoding for brain–computer interfaces (BCI). Artificial neural networks, however, are considered black boxes, because they usually have thousands of parameters, making interpretation of their internal processes challenging. Here we systematically evaluate the use of CNNs for EEG signal decoding and investigate a method for visualizing the CNN model decision process. Approach. We developed a CNN model to decode the covert focus of attention from EEG event-related potentials during object selection. We compared the CNN and the commonly used linear discriminant analysis (LDA) classifier performance, applied to datasets with different dimensionality, and analyzed transfer learning capacity. Moreover, we validated the impact of single model components by systematically altering the model. Furthermore, we investigated the use of saliency maps as a tool for visualizing the spatial and temporal features driving the model output. Main results. The CNN model and the LDA classifier achieved comparable accuracy on the lower-dimensional dataset, but CNN exceeded LDA performance significantly on the higher-dimensional dataset (without hypothesis-driven preprocessing), achieving an average decoding accuracy of 90.7% (chance level  =  8.3%). Parallel convolutions, tanh or ELU activation functions, and dropout regularization proved valuable for model performance, whereas the sequential convolutions, ReLU activation function, and batch normalization components reduced accuracy or yielded no significant difference. Saliency maps revealed meaningful features, displaying the typical spatial distribution and latency of the P300 component expected during this task. Significance. Following systematic evaluation, we provide recommendations for when and how to use CNN models in EEG decoding. Moreover, we propose a new approach for investigating the neural correlates of a cognitive task by training CNN models on raw high-dimensional EEG data and utilizing saliency maps for relevant feature extraction.