bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological support for patients with cancer: evidence review and suggestions for future directions
Authors: Hulbert-Williams Nicholas J. , Beatty Lisa , Dhillon Haryana M. 
Published: July 2018

Purpose of review
Psychological distress and mental health comorbidity are common in cancer. Various therapeutic frameworks have been used for interventions to improve psychological wellbeing and quality of life in cancer patients with mixed results. This article reviews contributions to that literature published since January 2017.

Recent findings
The majority of new psychological intervention research in cancer has used cognitive behavioural therapy (CBT) or mindfulness-based interventions. CBT has been considered a gold-standard intervention and recent evidence justifies continuation of this. Recent reviews call into question the validity of evidence for mindfulness-based interventions. A smaller number of trials using acceptance and commitment therapy, meta-cognitive therapy, dignity therapy and coaching have emerged, and whereas findings are promising, additional fully powered trials are required. Weaker evidence exists for counselling, support-based and narrative therapy interventions.

Summary
Efficacious, timely and acceptable psychological interventions are a necessary component of comprehensive cancer care. There is some way to go before the evidence conclusively points towards which interventions work for which cancer groups and for which specific outcomes. Methodological limitations must be addressed in future trials; at the forefront remains the need for fully powered, head-to-head comparison trials.
Reduced repertoire of cortical microstates and neuronal ensembles in medically-induced loss of consciousness
Authors: Wenzel Michael , Han Shuting , Smith Elliot H. , Hoel Erik , Greger Bradley , House Paul A. , Yuste Rafael 
Published: July 2018

SUMMARYMedically-induced loss of consciousness (mLOC) has been linked to a macroscale break-down of brain connectivity, yet the neural microcircuit correlates of mLOC remain unknown. We applied non-linear t-stochastic neighbor embedding (t-SNE) and Lempel-Ziv-Welch complexity analysis to two-photon calcium imaging and local field potential (LFP) measurements of cortical microcircuit activity across anesthetic depth in mice, and to micro-electrode array recordings in human subjects. We find that mLOC disrupts population activity patterns by i) a reduction of discriminable network microstates and ii) a reduction of independent neuronal ensembles. These alterations are not explained by a simple reduction of neuronal activity and reveal abnormal functional microcircuits. Thus, normal neuronal ensemble dynamics could contribute to the emergence of conscious states.
Motion and physiological noise effects on amygdala real-time fMRI neurofeedback learning
Authors: Hellrung Lydia , Borchardt Viola , Götting Florian N. , Stadler Jörg , Tempelmann Claus , Tobler Philippe N. , Walter Martin , van der Meer Johan N. 
Published: July 2018

AbstractReal-time fMRI neurofeedback allows to learn control over activity in a localized brain region. However, with fMRI, physiological factors such as the cardiac cycle and respiration interfere with the measurement of brain activation. In conventional fMRI studies this is usually mitigated by inclusion of motion parameters and/or physiological parameters as nuisance regressors at the analysis stage, allowing to correct for and filter out such confounders. In real-time fMRI, however, such an approach is not routinely feasible due to the necessity to process all signals during the runtime of an experiment. The absence of on-line correction can therefore compromise real-time fMRI study outcomes reporting volitional self-regulation capability as BOLD signal changes. This is especially true for BOLD signal changes in subcortical regions situated close to blood vessels or air cavities, such as the amygdala. We therefore aimed to establish the effects of motion, heart rate, heart rate variability, and respiratory volume on learning effects, which means here an increase in BOLD signal change over NF training, in an amygdala neurofeedback experiment. Specifically, we investigate motion parameters from two emotion regulation studies - performed at 3T and 7T scanners - and additionally acquired physiological variance for the latter one. Our results revealed differences in these parameters between groups and especially between regulation and resting periods within each participant. However, strictly considering these parameters as nuisance regressors in data analysis revealed that the learning of volitional self-regulation of the amygdala is not driven by motion and physiological changes. As validation of our real-time findings, we compare them to the gold standard of assessment of motion and physiology from the Human Connectome Project. Based on this, we recommend to carefully report neurofeedback study results including physiological nuisance regression. To our knowledge, this is the first study investigating the effects of motion and physiological noise correction on neurofeedback BOLD effects.
Motor cortex can modulate somatosensory processing via cortico-thalamo-cortical pathway
Authors: Lohse Michael , Cooper Matthew , Sader Elie , Langfelder Antonia , Kahn Martin , Baxter Luke , Bartram Julian , Phillips James W. , Upton A. Louise , Mann Edward O. 
Published: July 2018

AbstractThe somatosensory and motor systems are intricately linked, providing several routes for the sensorimotor interactions necessary for haptic processing. Here, we used electrical and optogenetic stimulation to study the circuits that enable primary motor cortex (M1) to exert top-down modulation of whisker-evoked responses, at the levels of brain stem, thalamus and somatosensory cortex (S1). We find that activation of M1 drives somatosensory responsive cells at all levels, and that this excitation is followed by a period of tactile suppression, which gradually increases in strength along the ascending somatosensory pathway. Using optogenetic stimulation in the layer-specific Cre driver lines, we find that activation of layer VI cortico-thalamic neurons is sufficient to drive spiking in higher order thalamus, and that this is reliably followed by excitation of S1, suggesting a cross-modal cortico-thalamo-cortical pathway. Cortico-thalamic excitation predicts the degree of subsequent tactile suppression, consistent with a strong role for thalamic circuits in the expression of inhibitory sensorimotor interactions. These results provide evidence of a role for M1 in dynamic modulation of S1, largely under cortico-thalamic control.
The effect of spatial variation for predicting aphid epidemics
Authors: Damgaard Christian , Bruus Marianne , Axelsen Jørgen Aagaard 
Published: July 2018

AbstractIn order to improve forecasting of aphid epidemics, it is important to know the spatial scale at which specific forecasts are reliable. To investigate the spatial scale of aphid epidemics, we have developed a spatio-temporal stochastic aphid population growth model, and fitted the model to empirical spatial time-series aphid population data using a Bayesian hierarchical fitting procedure. Furthermore, detailed spatial data of the initial phases of epidemic development was investigated in a semivariogram. Our results suggest that there is limited spatial variation in the initial occurrence probability at a spatial scale of 10 km. Consequently, the results support the hypothesis that initial aphid population sizes and epidemics may be predicted in fields within a 10 km radius. For farmers, this may imply that they can rely their decision of whether to spray against aphids on observations made by other nearby farmers or by the consultancy service.
MTrack: Automated Detection, Tracking, and Analysis of Dynamic Microtubules
Authors: Kapoor Varun , Hirst William G. , Hentschel Christoph , Preibisch Stephan , Reber Simone 
Published: July 2018

AbstractMicrotubules are polar, dynamic filaments fundamental to many cellular processes. In vitro reconstitution approaches with purified tubulin are essential to elucidate different aspects of microtubule behavior. To date, deriving data from fluorescence microscopy images by manually creating and analyzing kymographs is still commonplace. Here, we present MTrack, implemented as a plug-in for the open-source platform Fiji, which automatically identifies and tracks dynamic microtubules with sub-pixel resolution using advanced objection recognition. MTrack provides automatic data interpretation yielding relevant parameters of microtubule dynamic instability together with population statistics. The application of our software produces unbiased and comparable quantitative datasets in a fully automated fashion. This helps the experimentalist to achieve higher reproducibility at higher throughput on a user-friendly platform. We use simulated data and real data to benchmark our algorithm and show that it reliably detects, tracks, and analyzes dynamic microtubules and achieves sub-pixel precision even at low signal-to-noise ratios.
Whole genome sequencing identifies high-impact variants in well-known pharmacogenomic genes
Authors: Choi Jihoon , Tantisira Kelan G. , Duan Qing Ling 
Published: July 2018

AbstractMore than 1,100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project. We identified 69,319 genetic variations within 160 pharmacogenomic genes, of which 8,207 variants are in strong LD (r2 > 0.8) with known pharmacogenomic variants. Of the latter, 8 are coding or structural variants predicted to have high-impact, with 19 additional missense variants that are predicted to have moderate-impact. In conclusion, we identified putatively functional variants within known pharmacogenomics loci that could account for the association signals and represent the missing causative variants underlying drug response phenotypes.
A systems and treatment perspective of models of influenza virus-induced host responses
Authors: Mochan Ericka , Ackerman Emily , Shoemaker Jason E. 
Published: July 2018

AbstractSevere influenza infections are often characterized as having unique host responses (e.g. early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model’s response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interferon concentrations. These results suggest that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response. Specifically, the method used to model virus-resistant cells may need to be adapted in future work to more realistically represent the immune response to viral infection.
Parameterization of Proximal Humerus Locking Plate Impingement with In Vitro, In Silico, and In Vivo Techniques
Authors: Bachner Emily M. , Schmidt Elaine C , Chin Matthew , Namdari Surena , Baxter Josh R. , Hast Michael W. 
Published: July 2018

AbstractBackgroundLocked plating of displaced proximal humerus fractures is common, but rates of subacromial impingement remain high. Computational predictions of implant impingement have yet to be sufficiently explored in proximal humerus fixation. The goal of this study was to utilize a multidisciplinary approach to elucidate the relationships between common surgical parameters, anatomical variability, and the likelihood of plate impingement.MethodsThe experiment was completed in three phases. First, a controlled in vitro experiment was conducted to simulate impingement. Second, a dynamic in silico musculoskeletal model was developed to simulate changes to implant geometry, surgical techniques, and acromial anatomy, where a collision detection algorithm was used to simulate contact between the plate and acromion. Finally, in vivo shoulder kinematics were recorded for nine activities of daily living and motions that created a high likelihood of impingement were identified.ResultsImpingement was measured at 73.3±14.5° abduction in the cadaveric model and 92.0°±34.0° with computational simulations. Impingement events were limited to ranges of motion between 10–40° of cross-body adduction. Activities of daily living, such as combing one’s hair, lifting and object overhead, and reaching behind one’s head are likely to cause impingement.Discussion and ConclusionThis multidisciplinary experiment quantified key preoperative factors to assist with implantation decisions. Results demonstrated that proximal implant placement, superior translation of the humeral center of rotation, increases in plate thickness, and increases in acromial tilt all increase the likelihood of impingement. Careful preoperative planning that includes these factors could help guide operative decision making and improve clinical outcomes.Level of Evidence: V
Effects of thermal stress on amount, composition, and antibacterial properties of coral mucus
Authors: Wright Rachel M. , Strader Marie E. , Genuise Heather M. , Matz Mikhail V. 
Published: July 2018

AbstractThe surface mucus layer of reef-building corals supports several essential functions including feeding, sediment clearing, and protection from pathogenic invaders. For the reef ecosystem, coral mucus provides energy to support heterotrophic benthic communities. Mucus production represents a substantial metabolic investment on behalf of the coral: as much as half of the fixed carbon supplied by the corals’ algal symbionts is incorporated into expelled mucus. In this study, we examined if bleaching (disruption of the coral–algal symbiosis) has the potential to indirectly disturb reef ecosystem function by impacting the nutritional composition of coral mucus. In a controlled laboratory thermal stress challenge, visibly paled corals produced mucus with higher protein and lipid content and increased antibacterial activity relative to healthy corals. These results are likely explained by the expelled symbionts in the mucus of bleached individuals. This study illuminates how the immediate effects of coral bleaching could impact the reef-ecosystem indirectly through modulation of available nutrients within the ecosystem.
Fibroblast growth factor is predicted to dominate MAPK activation by pro-angiogenic factors
Authors: Song Min , Finley Stacey D. 
Published: July 2018

AbstractAngiogenesis is important in physiological and pathological conditions, as blood vessels provide nutrients and oxygen needed for tissue growth and survival. Therefore, targeting angiogenesis is a prominent strategy in both tissue engineering and cancer treatment. However, not all of the approaches to promote or inhibit angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation, and there is a limited understanding of how these promoters combine together to stimulate angiogenesis. Thus, more quantitative insight is needed to understand their interactions. In this study, we have trained and validated a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling and phosphorylation of extracellular regulated kinase (ERK), which promote cell proliferation. We apply the model to predict the dynamics of phosphorylated ERK (pERK) in response to the stimulation by FGF and VEGF individually and in combination. The model predicts that FGF plays a dominant role in promoting ERK phosphorylation, compared to VEGF. The modeling predictions show that VEGFR2 density and trafficking parameters significantly influence the level of VEGF-induced pERK. The model matches experimental data and is a framework to synthesize and quantitatively explain experimental studies. Ultimately, the model provides mechanistic insight into FGF and VEGF interactions needed to identify potential targets for pro-or anti-angiogenic therapies.
Local Enrichment of HP1alpha at Telomeres Alters Their Structure and Regulation of Telomere Protection
Authors: Chow Tracy T. , Shi Xiaoyu , Wei Jen-Hsuan , Guan Juan , Stadler Guido , Huang Bo , Blackburn Elizabeth H. 
Published: July 2018

AbstractEnhanced telomere maintenance is evident in malignant cancers. While telomeres are thought to be inherently heterochromatic, detailed mechanisms of how epigenetic modifications impact telomere protection and structures are largely unknown in human cancers. Here we develop a molecular tethering approach to experimentally enrich heterochromatin protein HP1α specifically at telomeres. This results in increased deposition of H3K9me3 at cancer cell telomeres. Telomere extension by telomerase is attenuated, and damage-induced foci at telomeres are reduced, indicating augmentation of telomere stability. Super resolution STORM imaging shows an unexpected increase in irregularity of telomeric structure. Telomere-tethered chromo shadow domain (CSD) mutant I165A of HP1α abrogates both the inhibition of telomere extension and the irregularity of telomeric structure, suggesting the involvement of at least one HP1α-ligand in mediating these effects. This work presents a new approach to specifically manipulate the epigenetic status locally at telomeres to uncover insights into molecular mechanisms underlying telomere structural dynamics.
Dorsal Premotor Contributions to Auditory Rhythm Perception: Causal Transcranial Magnetic Stimulation Studies of Interval, Tempo, and Phase
Authors: Ross Jessica , Iversen John , Balasubramaniam Ramesh 
Published: July 2018

AbstractIt has been suggested that movement planning networks are critical for time perception. The Action Simulation for Auditory Prediction (ASAP) hypothesis proposes that the dorsal auditory stream is involved in predictive beat-based timing through bidirectional interchange between auditory perception and dorsal premotor (dPMC) prediction via parietal regions, as has been supported by brain imaging and transcranial magnetic stimulation (TMS). However, causal impact of dPMC on time perception has not been tested directly. We used a TMS protocol that down-regulates cortical activity, continuous theta burst stimulation (cTBS), to test for causal contributions of left dPMC to time perception. Three experiments measured (1) discrete interval timing perception, and relative beat-based musical timing for (2) tempo perception and (3) phase perception. Perceptual acuity was tested pre- and post-cTBS using a test of sub-second interval discrimination and the Adaptive Beat Alignment Test (A-BAT). We show (N = 30) that cTBS down-regulation of left dPMC interferes with interval timing perception and the ability to detect differences in musical tempo, but not phase. Our data support causal involvement of premotor networks in perceptual timing, supporting a causal role of the left dPMC in accurate interval and musical tempo perception, possibly via dorsal stream interactions with auditory cortex.
Parl Deficiency in Mouse Causes Coenzyme Q Depletion, Complex III Defects, and Leigh-like Syndrome
Authors: Spinazzi Marco , Radaelli Enrico , Horré Katrien , Arranz Amaia M. , Gounko Natalia , Agostinis Patrizia , Impens Francis , Alexandra Morais Vanessa , Lopez-Lluch Guillermo , Serneels Lutgarde , Navas Placido , De Strooper Bart 
Published: July 2018

ABSTRACTThe mitochondrial intramembrane rhomboid protease Parl has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a striking necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional Parl deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline Parl knockouts demonstrating the vital role of Parl in neurological homeostasis. Genetic modification of two major Parl substrates, Pink1 and Pgam5, do not modify this severe neurological phenotype. Parl-/- brain mitochondria are affected by defects in Complex III activity and in coenzyme Q biosynthesis. Parl is necessary for the stable expression of Ttc19, required for Complex III activity, and of Coq4, essential in coenzyme Q biosynthesis. Thus, Parl plays a previously overseen constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and Leigh-like syndrome.
High-throughput yeast two-hybrid library screening using next generation sequencing
Authors: Erffelinck Marie-Laure , Ribeiro Bianca , Perassolo Maria , Pauwels Laurens , Pollier Jacob , Storme Veronique , Goossens Alain 
Published: July 2018

AbstractYeast two-hybrid (Y2H) is a well-established genetics-based system that uses yeast to selectively display binary protein-protein interactions (PPIs). To meet the current need to unravel complex PPI networks, several adaptations have been made to establish medium- to high-throughput Y2H screening platforms, with several having successfully incorporated the use of the next-generation sequencing (NGS) technology to increase the scale and sensitivity of the method. However, these have been to date mainly restricted to the use of fully annotated custom-made open reading frame (ORF) libraries and subject to complex downstream data processing. Here, a streamlined high-throughput Y2H library screening strategy, based on integration of Y2H with NGS, called Y2H-seq, was developed, which allows efficient and reliable screening of Y2H cDNA libraries. To generate proof of concept, the method was applied to screen for interaction partners of two key components of the jasmonate signaling machinery in the model plantArabidopsis thaliana, resulting in the identification of several previously reported as well as hitherto unknown interactors. Our Y2H-seq method offers a user-friendly, specific and sensitive screening method that allows high-throughput identification of PPIs without prior knowledge of the organism’s ORFs, thereby extending the method to organisms of which the genome has not entirely been annotated yet. The quantitative NGS readout and the incorporation of background controls allow to increase genome coverage and ultimately dispose of recurrent false positives, thereby overcoming some of the bottlenecks of current Y2H technologies, which will further strengthen the value of the Y2H technology as a discovery platform.