julilili42/papers huggingface dataset:
Optimization of rs‐fMRI parameters in the Seed Correlation Analysis (SCA) in DPARSF toolbox: A preliminary study
2018-12-21

Abstract There are a number of various methods of resting‐state functional magnetic resonance imaging (rs‐fMRI) analysis such as independent component analysis, multivariate autoregressive models, or seed correlation analysis however their results depend on arbitrary choice of parameters. Therefore, the aim of this work was to optimize the parameters in the seed correlation analysis using the Data Processing Assistant for Resting‐State fMRI (DPARSF) toolbox for rs‐fMRI data received from a Siemens Magnetom Skyra 3‐Tesla scanner using a whole‐brain, gradient‐echo echo planar sequence with a 32‐channel head coil. Different ranges of the following parameters: amplitude of low‐frequency fluctuation (ALFF), Gaussian kernel at FWHM and radius of spherical ROI for 109 regions were tested for 20 healthy volunteers. The highest values of functional connectivity (FC) correlations were found for ALFF 0.01–0.08, spherical ROIs with the 8‐mm radius and Gaussian kernel 8 mm at FWHM in all the studied areas that is, Auditory, Sensimotor, Visual, and Default Mode Network. The dominating influence of ALFF and smoothing on values of FC correlations was noted.
The neural dynamics of hierarchical Bayesian inference in multisensory perception
2018-12-21

Abstract Transforming the barrage of sensory signals into a coherent multisensory percept relies on solving the binding problem – deciding whether signals come from a common cause and should be integrated, or instead be segregated. Human observers typically arbitrate between integration and segregation consistent with Bayesian Causal Inference, but the neural mechanisms remain poorly understood. We presented observers with audiovisual sequences that varied in the number of flashes and beeps. Combining Bayesian modelling and EEG representational similarity analyses, we show that the brain initially represents the number of flashes and beeps and their numeric disparity mainly independently. Later, it computes them by averaging the forced-fusion and segregation estimates weighted by the probabilities of common and independent cause models (i.e. model averaging). Crucially, prestimulus oscillatory alpha power and phase correlate with observers’ prior beliefs about the world’s causal structure that guide their arbitration between sensory integration and segregation.
Generation of a homozygous CRISPR/Cas9-mediated knockout human iPSC line for the STUB1 locus
2018-12-21

STUB1/CHIP is a central component of cellular protein homeostasis and interacts with key proteins involved in the pathogenesis of many neurodegenerative diseases. Missense and truncating mutations in STUB1 lead to SCAR16. For ideal in vitro disease modelling with isogenic controls, we generated a CHIP knockout cell line from a healthy control with no CHIP functionality, but remaining genomic integrity and verified pluripotency.
Finite element error analysis of wave equations with dynamic boundary conditions: L2 estimates
2018-12-21

error estimates of semi- and full discretisations of wave equations with dynamic boundary conditions are studied, using bulk–surface finite elements and Runge–Kutta methods. The analysis resides on an abstract formulation and error estimates, via energy techniques, within this abstract setting. Four prototypical linear wave equations with dynamic boundary conditions are analysed within the abstract framework. For problems with velocity terms, or with acoustic boundary conditions we prove a spatial convergence order which is less than two. These can also be observed in the presented numerical experiments.
Is Santa Claus an evening owl?
2018-12-21

Case studies have a long tradition in biomedical research. Here, I will analyze an important person from a chronobiological aspect, Santa Claus. Although it might be dangerous for researchers to publish analyses about Santa Claus, because, given the possibility that he may be unsatisfied with my analysis, this could lead to an embargo of parcels for my whole family. Nevertheless, some intrepid researches already diagnosed Santa Claus, ending up in some important research results. A search in Web of Science revealed only N = 224 publications about Santa Claus, which is really low. The question, I am addressing here is, whether Santa Claus is an "evening owl" or a night chronotype. In this report, I summarize the facts known about Santa Claus on the one side and about evening chronotypes on the other and sum up these results in a "vote counting" manner as pros and cons. The results are summarized in Table 1. In total, there is 12 times support for the hypothesis, 2 times against and 1 equivocal (Table 1). This result is significant (binomial test, p = 0.013). Therefore, the conclusion is "Santa Claus is an evening type".
AQ-13 - an investigational antimalarial drug
2018-12-22

AQ-13 is a drug candidate in development for the treatment of Plasmodium falciparum infections. The chemical structure is similar to chloroquine, a 4-aminoquinoline, with a shorter diaminoalkane side chain. Chloroquine has been the standard of care for P.falciparum malaria for more than 40 years, but the spread of resistant parasites in all malaria endemic regions has led to abandonment of the drug. The outstanding attribute of AQ-13 is its retrieval of activity against chloroquine-resistant P.falciparum. Areas covered: We review preclinical and clinical studies on AQ-13 and summarize findings on pharmacokinetic, safety, potency and efficacy. Expert opinion: Based on its properties invivo, the most likely future indication of AQ-13 could be case management of uncomplicated falciparum malaria - as a partner drug in a combination therapy. Several 4-aminoquinolines combined with a partner drug are on the market and in development. The outstanding properties of AQ-13 should be identified to direct further clinical development.
A genome‐wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine
2018-12-23

Summary Objective To ascertain the clinical and genetic factors contributing to carbamazepine‐ and oxcarbazepine‐induced hyponatremia ( COIH ), and to carbamazepine ( CBZ ) metabolism, in a retrospectively collected, cross‐sectional cohort of people with epilepsy. Methods We collected data on serum sodium levels and antiepileptic drug levels in people with epilepsy attending a tertiary epilepsy center while on treatment with CBZ or OXC . We defined hyponatremia as Na+ ≤134 mEq/L. We estimated the CBZ metabolic ratio defined as the log transformation of the ratio of metabolite CBZ ‐diol to unchanged drug precursor substrate as measured in serum. Results Clinical and genetic data relating to carbamazepine and oxcarbazepine trials were collected in 1141 patients. We did not observe any genome‐wide significant associations with sodium level in a linear trend or hyponatremia as a dichotomous trait. Age, sex, number of comedications, phenytoin use, phenobarbital use, and sodium valproate use were significant predictors of CBZ metabolic ratio. No genome‐wide significant associations with CBZ metabolic ratio were found. Significance Although we did not detect a genetic predictor of hyponatremia or CBZ metabolism in our cohort, our findings suggest that the determinants of CBZ metabolism are multifactorial.
Predicting the Magnitude of σ-Holes Using VmaxPred, a Fast and Efficient Tool Supporting the Application of Halogen Bonds in Drug Discovery
2018-12-24

Halogen bonding as a modern molecular interaction has received increasing attention not only in materials sciences but also in biological systems and drug discovery. Thus, there is a growing demand for fast, efficient, and easily applicable tailor-made tools supporting the use of halogen bonds in molecular design and medicinal chemistry. The potential strength of a halogen bond is dependent on several properties of the σ-hole donor, e.g., a (hetero)aryl halide, and the σ-hole acceptor, a nucleophile with n or π electron density. Besides the influence of the interaction geometry and the type of acceptor, significant tuning effects on the magnitude of the σ-hole can be observed, caused by different (hetero)aromatic scaffolds and their substitution patterns. The most positive electrostatic potential on the isodensity surface ( V<sub>max</sub>), representing the σ-hole, has been widely used as the standard descriptor for the magnitude of the σ-hole and the strength of the halogen bond. Calculation of V<sub>max</sub> using quantum-mechanical methods at a reasonable level of theory is time-consuming and thus not applicable for larger numbers of compounds in drug discovery projects. Herein we present a tool for the prediction of this descriptor based on a machine-learned model with a speedup of 5 to 6 orders of magnitude relative to MP2 quantum-mechanical calculations. According to the test set, the squared correlation coefficient is greater than 0.94.
Stringy -functions of canonical toric Fano threefolds and their applications
2018-12-24

Abstract Let be a -dimensional lattice polytope containing exactly one interior lattice point. We give a simple combinatorial formula for computing the stringy -function of the -dimensional canonical toric Fano variety associated with . Using the stringy Libgober– Wood identity and our formula, we generalize the well-known combinatorial identity which holds for -dimensional reflexive polytopes .
It keeps on turning: Effects of prolonged long-term left ventricular assist device support as a bridge to heart transplantation
2018-12-24

Objectives: Increasing incidence of end-stage heart failure has moved the therapy with left ventricular assist devices to the forefront of surgical treatment. Moreover, continuous sophistication in this technology has resulted in increasing proportion of patients on prolonged support. Early and late complications after left ventricular assist device as a bridge to transplantation and present factors associated with long-term support and long-term outcomes of patients supported for at least 1 year were compared. Methods: A total of 163 consecutive patients who underwent left ventricular assist device implantation as bridge to transplantation were included. A total of 79 patients were supported for at least 1 year (long-term support), whereas 84 patients were supported for less than 1 year (short-term group). Results: Factors associated with a successful long-term support were male gender (p &lt; 0.001), cessation of smoking at least 6 months prior to surgery (p = 0.045), previous implantation of implantable cardioverter defibrillator (p = 0.001) and rapid postoperative extubation (p = 0.018). Regarding echocardiographic parameters, higher left ventricular mass (p = 0.013) and larger left ventricular–end systolic (p = 0.008) and diastolic (p = 0.005) diameters prior to left ventricular assist device implantation were associated with long-term support. Short-term group showed higher mortality and higher proportion of patients who underwent device exchange due to device failure, and left ventricular assist device explantation for myocardial recovery was less frequent in the long-term support (p &lt; 0.001). In addition, patients from the long-term support had significantly higher incidence of higher-grade aortic regurgitation (p = 0.005). Conclusion: Prolonged left ventricular assist device support as bridge to transplantation is associated with lower mortality and lower incidence of device failure requiring device exchange. However, long-term support reduces the chance of device explantation for myocardial recovery and increases the incidence of higher-grade aortic regurgitation in the follow-up.
“Kill Them Wherever You Find Them” - Radicalizing Narratives of the “So-Called” Islamic State Via the Online Magazine Rumiyah
2018-12-25

During the civil war in Syria and Iraq, numerous predominantly young Europeans joined the terrorist organization of the Islamic State and committed attacks in their homelands in the name of the Islamic State. The study “Westliche Jugendliche im Bann des Islamischen Staates” (Kiefer et al., 2016) examines the contents of the IS propaganda magazine Dabiq which was published until 2016. Dabiq was aimed at young people with the intention to radicalize them in the ideology of the IS. The Dabiq follow-up magazine Rumiyah appears at a time when the IS began losing ever larger parts of its former territories in Iraq and Syria and as signs of structural disintegration are appearing. It is upon the changes occurring within this period of transition that we focus our research efforts. We identify the radicalization strategies in Rumiyah and analyze whether, and to what extent, the IS adapts its propaganda to the changing political situation as compared to Dabiq. With the assistance of a deductively developed category system, this study uses a qualitative content analysis of all previous issues of Rumiyah to investigate the narratives Rumiyah utilizes in addressing its readers as well as the pathways proposed toward radicalization. Our research indicates that journeying to the Caliphate is no longer the primary objective of radicalization. In Rumiyah, young people are being asked to relocate the battle to their home countries, which we associate with the territorial losses of the IS. In addition, the frequent narration of enemy images and clear rules in Rumiyah magazine provides clues as to what action guidelines could be used to counter the radicalization of youth. Regarding the re-sults of this research, both the promotion of an interfaith and intra-Muslim dialogue as well as the support of parents whose children are looking for clearly communicated rules suitable to protect young people from radicalization by the IS and thus prevent terrorist attacks in their countries of origin.
C18-Coated Solid-Phase Microextraction Fibers for the Quantification of Partitioning of Organic Acids to Proteins, Lipids, and Cells
2018-12-26

The effects measured with in vitro cell-based bioassays are typically reported as nominal effect concentrations ( C<sub>nom</sub>), but the freely dissolved concentration in the exposure medium ( C<sub>w</sub>) and the total cellular concentration ( C<sub>cell</sub>) are considered more quantitative dose metrics that allow extrapolation to the whole-organism level. To predict C<sub>w</sub> and C<sub>cell</sub>, the partitioning of the test chemicals to medium proteins and lipids and cells has to be known. In this study, we developed a solid-phase microextraction (SPME) method based on C18-coated fibers to quantify the partitioning of diclofenac, 2,4-dichlorophenoxyacetic acid (2,4-D), ibuprofen, naproxen, torasemide, warfarin, and genistein to bovine serum albumin (BSA), phospholipid liposomes, fetal bovine serum (FBS), and cells. For ibuprofen, 2,4-D, naproxen, and warfarin, the partitioning to the SPME fibers was found to be concentration dependent, which had to be considered for the calculation of distribution ratios to biological materials. The sorption isotherms to FBS were nonlinear for diclofenac, 2,4-D, ibuprofen, naproxen, and warfarin. The FBS isotherms could be described by assuming that the total amount of chemical bound to FBS is the sum of the amount specifically bound to the binding sites of albumin and nonspecifically bound to all medium proteins and lipids. The determined cell-water distribution ratios ( D<sub>cell/w</sub>) differed considerably between four different cell lines (up to 1.83 log-units) and also between different batches of the same cell line (up to 0.48 log-units). The relative importance of protein and lipid content for D<sub>cell/w</sub> was evaluated with a mass balance model and different types of cellular proteins and lipids as input parameters. Existing in vitro mass balance models may underestimate C<sub>w</sub> because they do not account for saturable protein binding and overestimate C<sub>cell</sub> for organic acids, if BSA is used as surrogate for cellular proteins.
ATP binding without hydrolysis switches sulfonylurea receptor 1 (SUR1) to outward-facing conformations that activate KATP channels
2018-12-26

Neuroendocrine-type ATP-sensitive K<sup>+</sup> (K<sub>ATP</sub>) channels are metabolite sensors coupling membrane potential with metabolism, thereby linking insulin secretion to plasma glucose levels. They are octameric complexes, (SUR1/Kir6.2)<sub>4</sub>, comprising sulfonylurea receptor 1 (SUR1 or ABCC8) and a K<sup>+</sup>-selective inward rectifier (Kir6.2 or KCNJ11). Interactions between nucleotide-, agonist-, and antagonist-binding sites affect channel activity allosterically. Although it is hypothesized that opening these channels requires SUR1-mediated MgATP hydrolysis, we show here that ATP binding to SUR1, without hydrolysis, opens channels when nucleotide antagonism on Kir6.2 is minimized and SUR1 mutants with increased ATP affinities are used. We found that ATP binding is sufficient to switch SUR1 alone between inward- or outward-facing conformations with low or high dissociation constant, <i>K<sub>D</sub></i> , values for the conformation-sensitive channel antagonist [<sup>3</sup>H]glibenclamide ([<sup>3</sup>H]GBM), indicating that ATP can act as a pure agonist. Assembly with Kir6.2 reduced SUR1's <i>K<sub>D</sub></i> for [<sup>3</sup>H]GBM. This reduction required the Kir N terminus (KNtp), consistent with KNtp occupying a "transport cavity," thus positioning it to link ATP-induced SUR1 conformational changes to channel gating. Moreover, ATP/GBM site coupling was constrained in WT SUR1/WT Kir6.2 channels; ATP-bound channels had a lower <i>K<sub>D</sub></i> for [<sup>3</sup>H]GBM than ATP-bound SUR1. This constraint was largely eliminated by the Q1179R neonatal diabetes-associated mutation in helix 15, suggesting that a "swapped" helix pair, 15 and 16, is part of a structural pathway connecting the ATP/GBM sites. Our results suggest that ATP binding to SUR1 biases K<sub>ATP</sub> channels toward open states, consistent with SUR1 variants with lower <i>K<sub>D</sub></i> values causing neonatal diabetes, whereas increased <i>K<sub>D</sub></i> values cause congenital hyperinsulinism.
Ochre and pigment use at Hohle Fels cave: Results of the first systematic review of ochre and ochre-related artefacts from the Upper Palaeolithic in Germany
2018-12-27

Though many European Upper Palaeolithic sites document early examples of symbolic material expressions (e.g., cave art, personal ornaments, figurines), there exist few reports on the use of earth pigments outside of cave art-and occasionally Neanderthal-contexts. Here, we present the first in-depth study of the diachronic changes in ochre use throughout an entire Upper Palaeolithic sequence at Hohle Fels cave, Germany, spanning from ca. 44,000-14,500 cal. yr. BP. A reassessment of the assemblage has yielded 869 individual ochre artefacts, of which 27 show traces of anthropogenic modification. The ochre artefacts are from all Upper Palaeolithic layers, stemming from the earliest Aurignacian horizons to the Holocene. This wide temporal spread demonstrates the long-term presence and continuity of ochre use in a part of Europe where it has not been systematically reported before. The anthropogenic modifications present on the ochre artefacts from the Gravettian and Magdalenian are consistent with pigment powder production, whereas the only modified piece from the Aurignacian displays a possible engraved motif. The non-modified artefacts show that more hematite-rich specular ochres as well as fine-grained deep red iron oxide clays were preferred during the Gravettian and Magdalenian, while the Aurignacian layers contain a broader array of colours and textures. Furthermore, numerous other artefacts such as faunal elements, personal ornaments, shells, and an ochre grindstone further strengthen the conclusion that ochre behaviours were well established during the onset of the Aurignacian and subsequently flourished throughout the Upper Palaeolithic at Hohle Fels cave.
Review of first clinical experiences with a 1.5 Tesla ceiling-mounted moveable intraoperative MRI system in Europe
2018-12-27

High-field intraoperative MRI (iMRI) systems provide excellent imaging quality and are used for resection control and update of image guidance systems in a number of centers. A ceiling-mounted intraoperative MRI system has several advantages compared to a conventional iMRI system. In this article, we report on first clinical experience with using such a state-of-the-art, the 1.5T iMRI system, in Europe. A total of 50 consecutive patients with intracranial tumors and vascular lesions were operated in the iMRI unit. We analyzed the patients’ data, surgery preparation times, intraoperative scans, surgical time, and radicality of tumor removal.&#x0D; Patients’ mean age was 46 years (range 8 to 77 years) and the median surgical procedure time was 5 hours (range 1 to 11 hours). The lesions included 6 low-grade gliomas, 8 grade III astrocytomas, 10 glioblastomas, 7 metastases, 7 pituitary adenomas, 2 cavernomas, 2 lymphomas, 1 cortical dysplasia, 3 aneurysms, 1 arterio-venous malformation and 1 extracranial-intracranial bypass, 1 clival chordoma, and 1 Chiari malformation. In the surgical treatment of tumor lesions, intraoperative imaging depicted tumor remnant in 29.7% of the cases, which led to a change in the intraoperative strategy.&#x0D; The mobile 1.5T iMRI system proved to be safe and allowed an optimal workflow in the iMRI unit. Due to the fact that the MRI scanner is moved into the operating room only for imaging, the working environment is comparable to a regular operating room.
Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas
2018-12-27

Abstract Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM + ) non-fast-spiking neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM + neurons were non-Martinotti. These morphologically distinct SOM + interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are optionally used across the cortex as building blocks to assemble cortical circuits.
S2k Guidelines for Cutaneous Basal Cell Carcinoma – Part 1: Epidemiology, Genetics and Diagnosis
2018-12-28

Summary Basal cell carcinoma is the most common malignant tumor among fair‐skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.