bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Horizontal Neck Wrinkles with Hyaluronic Acid Filler: A Retrospective Case Series
Authors: Tseng Fangwen , Yu Hsiaoen 
Published: August 2019

Background:
Horizontal neck wrinkles are a common aesthetic deficiency but limited treatment options exist and none have been studied with follow-ups of over 2 months.

Methods:
This dual-center, retrospective case series (Apr 2016–Jan 2017) included adult patients receiving CPM-HA to treat horizontal neck wrinkles. Patients were followed up for 40 weeks. CPM-HA treatment efficacy was evaluated through the Horizontal Neck Wrinkle Severity Scale and Global Aesthetic Improvement Scale (GAIS). Adverse events (AEs) and pain on injection, as assessed on the visual analogue scale, were documented.

Results:
Sixty-four lateral neck halves from 32 women (23–61 years) were analyzed. Significant improvement in wrinkle intensity, as assessed by Horizontal Neck Wrinkle Severity Scale, was observed from the second week onwards (1.352 ± 0.682, P<0.05). This improvement was sustained throughout the study duration and remained statistically significant at week 36 (1.423 ± 0.796, P<0.05). Patient GAIS (92.3%–100% through 36 weeks) and physician GAIS (100% through 24 weeks) were both excellent. Visual analogue scale scores revealed more pain associated with blunt cannula use (2.72 ± 1.71) than with sharp needle use (1.75 ± 1.39). AEs included erythema (62.5%), pruritus (43.7%), ecchymosis (43.7%), and localized swelling (25%).

Conclusions:
Subdermal injection of CPM-HA is safe and effective for treating horizontal neck wrinkles. Sustained improvement of wrinkle intensity up to 36 weeks and minimal AEs with no Tyndall effect were observed.
A Rare Case of Persistent Unilateral Gestational Gigantomastia
Authors: Rutherford Claire L. , Hsieh Michael K.H. , Tan Hui-Min , Twoon Mark , Kong Tze-Yean 
Published: August 2019

Summary:
A 34-year-old para 2 + 0 Indonesian woman presented with persistent right-sided gestational gigantomastia some 24 months following delivery. This was severely debilitating her activities of daily living, including caring for her children. On examination, she was found to have extreme hypertrophy of her right breast, which was nodular throughout on palpation. Biochemical investigations were unremarkable and revealed no obvious etiology. Magnetic resonance imaging identified grossly enlarged right breast tissue with prominent vessels. Given the minimal involution of her breast over the 24 months postpartum, she elected for a breast reduction with free nipple grafting following appropriate counseling. This was performed through excision of breast parenchyma preserving superior-medial tissue, followed by a free nipple graft.
Withdrawal from an opioid induces a transferable memory trace in the cerebrospinal fluid
Authors: Drdla-Schutting Ruth , Heinl Céline , Hadschieff Viktoria , Sandkühler Jürgen 
Published: August 2019

Abstract
Opioids are the most powerful analgesics available to date. However, they may also induce adverse effects including paradoxical opioid-induced hyperalgesia. A mechanism that might underlie opioid-induced hyperalgesia is the amplification of synaptic strength at spinal C-fibre synapses after withdrawal from systemic opioids such as remifentanil (“opioid-withdrawal long-term potentiation [LTP]”). Here, we show that both the induction as well as the maintenance of opioid-withdrawal LTP were abolished by pharmacological blockade of spinal glial cells. By contrast, the blockade of TLR4 had no effect on the induction of opioid-withdrawal LTP. D-serine, which may be released upon glial cell activation, was necessary for withdrawal LTP. D-serine is the dominant coagonist for neuronal NMDA receptors, which are required for the amplification of synaptic strength on remifentanil withdrawal. Unexpectedly, opioid-withdrawal LTP was transferable through the cerebrospinal fluid between animals. This suggests that glial-cell-derived mediators accumulate in the extracellular space and reach the cerebrospinal fluid at biologically active concentrations, thereby creating a soluble memory trace that is transferable to another animal (“transfer LTP”). When we enzymatically degraded D-serine in the superfusate, LTP could no longer be transferred. Transfer LTP was insensitive to pharmacological blockade of glial cells in the recipient animal, thus representing a rare form of glial cell-independent LTP in the spinal cord.
Driving Simulator Performance After Administration of Analgesic Doses of Ketamine With Dexmedetomidine or Fentanyl
Authors: Hayley Amie C. , Downey Luke A. , Green Maja , Shiferaw Brook , Kenneally Michaela , Keane Michael , Adams Mark , Shehabi Yahya 
Published: August 2019

Abstract

Purpose/Background
As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear.

Methods/Procedures
Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg−1 h−1 infusion of ketamine (3-hour duration), in addition to either (i) 0.7 μg kg−1 h−1 infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 μg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV).

Findings/Results
Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F
1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t
37 = −5.21 [P < 0.001] and t
37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits.

Implications/Conclusions
Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.
Therapeutic advances in SMA
Authors: Ludolph Albert C. , Wurster Claudia D. 
Published: August 2019

Purpose of review
To review the advent of novel therapies and their impact on the field of chromosome 5q-associated spinal muscular atrophy (SMA).

Recent findings
Antisense oligonucleotides (ASOs) enhancing SMN2 function are delivered intrathecally and small molecules will also be available soon delivered by the oral route; alternatively, systemic injection of viral vectors in order to replace the SMN gene are likely to be available in the future. In summer 2019, it remains the core finding that intrathecally delivered ASOs convincingly change the natural history of the disease in children and that the treatment effect is the better, the earlier ASO treatment is started. Therefore, postnatal screening for deletions and mutations in the SMN gene is presently discussed. Much has to be learnt, however, both on the challenges of the intrathecal mode of delivery and the efficacy of ASOs in adolescent and adult patients. Therapeutic outcome measures mirroring this phenotype are difficult to assess in this group of patients.

Summary
Therapeutic advances in 5q-associated SMA have been convincing in the previous years and change the field. This includes newborn screening, changing phenotypes in the treated children, challenges for drug administration in adolescents and adults and the comparison of drug effects. Long-term studies are required.
Carbonic anhydrase VII regulates dendritic spine morphology and density via actin filament bundling
Authors: Bertling Enni , Blaesse Peter , Seja Patricia , Kremneva Elena , Gateva Gergana , Virtanen Mari A. , Summanen Milla , Spoljaric Inkeri , Blaesse Michael , Paavilainen Ville , Vutskits Laszlo , Kaila Kai , Hotulainen Pirta , Ruusuvuori Eva 
Published: August 2019

AbstractIntracellular pH is a potent modulator of neuronal functions. By catalyzing (de)hydration of CO2, intracellular carbonic anhydrase (CAi) isoforms CAII and CAVII contribute to neuronal pH buffering and dynamics. The presence of two highly active isoforms suggests that they form spatially distinct CAipools enabling subcellular modulation of pH. Here we show that CAVII, unlike CAII, is localized to the filamentous actin network, and its overexpression induces formation of thick actin bundles and membrane protrusions in fibroblasts. In neurons, CAVII is enriched in dendritic spines, and its over-expression causes aberrant spine morphology. We identified amino acids unique to CAVII that are required for direct actin interactions, promoting actin filament bundling and spine targeting. Lack of CAVII in neocortical neurons leads to reduced spine density and increased proportion of small spines. Thus, our work demonstrates highly distinct subcellular expression patterns of CAII and CAVII, and a novel, structural role of CAVII.
Detecting selection from linked sites using an F-model
Authors: Galimberti Marco , Leuenberger Christoph , Wolf Beat , Szilágyi Sándor Miklós , Foll Matthieu , Wegmann Daniel 
Published: August 2019

ABSTRACTAllele frequencies vary across populations and loci, even in the presence of migration. While most differences may be due to genetic drift, divergent selection will further increase differentiation at some loci. Identifying those is key in studying local adaptation, but remains statistically challenging. A particularly elegant way to describe allele frequency differences among populations connected by migration is theF-model, which measures differences in allele frequencies by population specificFSTcoefficients. This model readily accounts for multiple evolutionary forces by partitioningFSTcoefficients into locus and population specific components reflecting selection and drift, respectively. Here we present an extension of this model to linked loci by means of a hidden Markov model (HMM) that characterizes the effect of selection on linked markers through correlations in the locus specific component along the genome. Using extensive simulations we show that our method has up to two-fold the statistical power of previous implementations that assume sites to be independent. We finally evidence selection in the human genome by applying our method to data from the Human Genome Diversity Project (HGDP).
Growing old too early, automated assessment of skeletal muscle single fiber biomechanics in ageing R349P desmin knock-in mice using the MyoRobot technology
Authors: Meyer Charlotte , Haug Michael , Reischl Barbara , Prölß Gerhard , Pöschel Thorsten , Rupitsch Stefan J , Clemen Christoph S , Schröder Rolf , Friedrich Oliver 
Published: August 2019

AbstractMuscle biomechanics is determined by active motor-protein assembly and passive strain transmission through cytoskeletal structures. The extrasarcomeric desmin filament network aligns myofibrils at the z-discs, provides nuclear-sarcolemmal anchorage and may also serve as memory for muscle repositioning following large strains. Our previous analyses of R349P desmin knock-in mice, an animal model for the human R350P desminopathy, already depicted pre-clinical changes in myofibrillar arrangement and increased fiber bundle stiffness compatible with a pre-aged phenotype in the disease. Since the specific effect of R349P desmin on axial biomechanics in fully differentiated muscle fibers is unknown, we used our automated MyoRobot biomechatronics platform to compare passive and active biomechanics in single fibers derived from fast- and slow-twitch muscles from adult to senile mice hetero- or homozygous for this desmin mutation with wild-type littermates. Experimental protocols involved caffeine-induced Ca2+-mediated force transients, pCa-force curves, resting length-tension curves, visco-elasticity and ‘slack-tests’. We demonstrate that the presence of R349P desmin predominantly increased single fiber axial stiffness in both muscle types with a pre-aged phenotype over wild-type fibers. Axial viscosity was unaffected. Likewise, no systematic changes in Ca2+-mediated force properties were found. Notably, mutant single fibers showed faster unloaded shortening over wild-type fibers. Effects of ageing seen in the wild-type always appeared earlier in the mutant desmin fibers. Impaired R349P desmin muscle biomechanics is clearly an effect of a compromised intermediate filament network rather than secondary to fibrosis.
Fork Pausing Complex Engages Topoisomerases at the Replisome
Authors: Shyian Maksym , Albert Benjamin , Zupan Andreja Moset , Ivanitsa Vitalii , Charbonnet Gabriel , Dilg Daniel , Shore David 
Published: August 2019

ABSTRACTReplication forks temporarily or terminally pause at hundreds of hard-to-replicate regions around the genome. A conserved pair of budding yeast replisome components Tof1-Csm3 (fission yeast Swi1-Swi3 and human TIMELESS-TIPIN) acts as a ‘molecular brake’ and promotes fork slowdown at proteinaceous replication fork barriers (RFBs), while the accessory helicase Rrm3 assists the replisome in removing protein obstacles. Here we show that Tof1-Csm3 complex promotes fork pausing independently of Rrm3 helicase by recruiting topoisomerase I (Top1) to the replisome. Topoisomerase II (Top2) partially compensates for the pausing decrease in cells when Top1 is lost from the replisome. The C-terminus of Tof1 is specifically required for Top1 recruitment to the replisome and fork pausing but not for DNA replication checkpoint (DRC) activation. We propose that forks pause at proteinaceous RFBs through a ‘sTOP’ mechanism (‘slowing down with TOPoisomerases I-II’), which we show also contributes to protecting cells from topoisomerase-blocking agents.
A Custom Microcontrolled and Wireless-Operated Chamber for Auditory Fear Conditioning
Authors: Júnior Paulo Aparecido Amaral , Mourão Flávio Afonso Gonçalves , Amâncio Mariana Chamon Ladeira , Pinto Hyorrana Pereira , Carvalho Vinícius Rezende , de Oliveira Guarnieri Leonardo , Magalhães Hermes Aguiar , Moraes Márcio Flávio Dutra 
Published: August 2019

ABSTRACTAnimal behavioral paradigms, such as classical conditioning and operant conditioning, are an important tool to study the neural basis of cognition and behavior. These paradigms involve manipulating sensory stimuli in a way that learning processes are induced under controlled experimental conditions. However, the majority of the commercially available equipment did not offer flexibility to manipulate stimuli. Therefore, the development of most versatile devices would allow the study of more complex cognitive functions. The purpose of this work is to present a low-cost, customized and wireless-operated chamber for animal behavior conditioning, based on the joint operation of two microcontroller modules: Arduino Due and ESP8266-12E. Our results showed that the auditory stimulation system allows setting the carrier frequency in the range of 1 Hz up to more than 100 kHz and the sound stimulus can be modulated in amplitude, also over a wide range of frequencies. Likewise, foot-shock could be precisely manipulated regarding its amplitude (from ~200 μA to ~1500 μA) and frequency (up to 20 pulses per second). Finally, adult rats exposed to a protocol of cued fear conditioning in our device showed consistent behavioral response and electrophysiological evoked responses in the midbrain auditory pathway. Furthermore, the device developed in the current study represents an open source alternative to develop customized protocols to study fear memory under conditions of varied sensory stimuli.
Tonic GABAAconductance favors temporal over rate coding in the rat hippocampus
Authors: Dembitskaya Yulia , Wu Yu-Wei , Semyanov Alexey 
Published: August 2019

AbstractSynaptic plasticity is triggered by different patterns of neuronal network activity. Network activity leads to an increase in ambient GABA concentration and tonic activation of GABAAreceptors. How tonic GABAAconductance affects synaptic plasticity during temporal and rate-based coding is poorly understood. Here, we show that tonic GABAAconductance differently affects long-term potentiation (LTP) induced by different stimulation patterns. The LTP based on a temporal spike - EPSP order (spike-timing-dependent [st] LTP) was not affected by exogenous GABA application. Backpropagating action potential, which enables Ca2+entry through N-methyl-D-aspartate receptors (NMDARs) during stLTP induction, was only slightly reduced by the tonic conductance. In contrast, GABA application impeded LTP dependent on spiking rate (theta-burst-induced [tb] LTP) by reducing the EPSP bust response and, hence, NMDAR-mediated Ca2+entry during tbLTP induction. Our results may explain the changes in different forms of memory under physiological and pathological conditions that affect tonic GABAAconductance.
dsRNA-Seq: Identification of viral infection by purifying and sequencing dsRNA
Authors: Decker Carolyn J. , Steiner Halley R. , Hoon-Hanks Laura L. , Morrison James H. , Haist Kelsey C. , Stabell Alex C. , Poeschla Eric M. , Morrison Thomas E. , Stenglein Mark D. , Sawyer Sara L. , Parker Roy 
Published: August 2019

AbstractRNA viruses are a major source of emerging and re-emerging infectious diseases around the world. We developed a method to identify RNA viruses that is based on the fact that all RNA viruses produce dsRNA while replicating. Purifying and sequencing dsRNA from total RNA isolated from infected tissue allowed us to recover replicating viral sequences. We refer to this approach as dsRNA-Seq. By assembling dsRNA sequences into contigs we identified full length RNA viruses of varying genome types infecting mammalian culture samples, identified a known viral disease agent in laboratory infected mice, and successfully detected naturally occurring RNA viral infections in reptiles. Here we show that dsRNA-Seq is a preferable method for identifying viruses in organisms that don’t have sequenced genomes and/or commercially available rRNA depletion reagents. Similar to other metagenomic strategies, dsRNA-Seq has the potential to identify unknown viral disease agents that share little to no similarity to known viruses. However, the significant advantage of this method is the ability to identify replicated viral sequences, which is useful for distinguishing infectious viral agents from potential noninfectious viral particles or contaminants.
Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons
Authors: Naik Ankana S. , Lin Jennifer M. , Taroc Ed Zandro M. , Katreddi Raghu R. , Frias Jesus A. , Sammons Morgan , Forni Paolo E. 
Published: August 2019

SummaryThe accessory olfactory system is a unique model that can give insights on how the neurons can establish and maintain their identity, and connectivity. The vomeronasal organ (VNO) contains two distinct populations of vomeronasal sensory neurons (VSNs) each with specific innervation patterns to the accessory olfactory bulb (AOB). Though morphogenic signals are critical in defining various neuronal populations, the morphogenic signaling profiles that influence each VSN population remains unknown. Here, we found a pronounced BMP signaling gradient within the basal VSNs. By generating Smad4 conditional mutants, we disrupted canonical TGF-β/BMP signaling in maturing basal VSNs and in all mature VSNs. We show that Smad4 loss-of-function in immature basal neurons leads to a progressive loss of basal VSNs, reduced activation of the remnant basal VSNs, and aberrant glomeruli formation in posterior AOB. However, Smad4 ablation in all mature VSNs does not affect neuronal activity nor survival but causes aberrant glomeruli formation only in the posterior AOB. Our study reveals that Smad4 signaling plays a critical role in mediating development, function, and circuit formation of basal VSNs.
Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation
Authors: Rahman A. , Henry K. M. , Herman K. D. , Thompson A. A. R , Isles H. M. , Tulotta C. , Sammut D. , Rougeot J. J. Y. , Khoshaein N. , Reese A. E. , Higgins K. , Tabor C. , Sabroe I. , Zuercher W. J. , Savage C. O. , Meijer A. H. , Whyte M. K. B. , Dockrell D. H. , Renshaw S. A. , Prince L. R. 
Published: August 2019

AbstractNeutrophilic inflammation with prolonged neutrophil survival is common to many inflammatory conditions, including chronic obstructive pulmonary disease (COPD). There are few specific therapies that reverse neutrophilic inflammation, but uncovering mechanisms regulating neutrophil survival is likely to identify novel therapeutic targets. Screening of 367 kinase inhibitors in human neutrophils and a zebrafish tail fin injury model identified ErbBs as common targets of compounds that accelerated inflammation resolution. The ErbB inhibitors gefitinib, CP-724714, erbstatin and tyrphostin AG825 significantly accelerated apoptosis of human neutrophils, including neutrophils from people with COPD. Neutrophil apoptosis was also increased in Tyrphostin AG825 treated-zebrafishin vivo. Tyrphostin AG825 decreased peritoneal inflammation in zymosan-treated mice, and increased lung neutrophil apoptosis and macrophage efferocytosis in a murine acute lung injury model. Tyrphostin AG825 and knockdown ofegfraanderbb2by CRISPR/Cas9 reduced inflammation in zebrafish. Our work shows that inhibitors of ErbB kinases have therapeutic potential in neutrophilic inflammatory disease.
Protein-protein docking using learned three-dimensional representations
Authors: Derevyanko Georgy , Lamoureux Guillaume 
Published: August 2019

AbstractProtein-protein interactions are determined by a number of hard-to-capture features related to shape complementarity, electrostatics, and hydrophobicity. These features may be intrinsic to the protein or induced by the presence of a partner. A conventional approach to protein-protein docking consists in engineering a small number of spatial features for each protein, and in minimizing the sum of their correlations with respect to the spatial arrangement of the two proteins. To generalize this approach, we introduce a deep neural network architecture that transforms the raw atomic densities of each protein into complex three-dimensional representations. Each point in the volume containing the protein is described by 48 learned features, which are correlated and combined with the features of a second protein to produce a score dependent on the relative position and orientation of the two proteins. The architecture is based on multiple layers of SE(3)-equivariant convolutional neural networks, which provide built-in rotational and translational invariance of the score with respect to the structure of the complex. The model is trained end-to-end on a set of decoy conformations generated from 851 nonredundant protein-protein complexes and is tested on data from the Protein-Protein Docking Benchmark Version 4.0.