bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond sleepy: structural and functional changes of the default-mode network in idiopathic hypersomnia
Authors: Pomares Florence B , Boucetta Soufiane , Lachapelle Francis , Steffener Jason , Montplaisir Jacques , Cha Jungho , Kim Hosung , Dang-Vu Thien Thanh 
Published: July 2019

AbstractIdiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness but, in contrast to narcolepsy, does not involve cataplexy, sleep-onset REM periods, or any consistent hypocretin-1 deficiency. The pathophysiological mechanisms of IH remain unclear. Because of the involvement of the default-mode network (DMN) in alertness and sleep, our aim was to investigate the structural and functional modifications of the DMN in IH. We conducted multimodal magnetic resonance imaging (MRI) in 12 participants with IH and 15 good sleeper controls (mean age ± SD: 32 ± 9.6 years, range 22–53 years, nine males). Self-reported as well as objective measures of daytime sleepiness were collected. Gray matter volume and cortical thickness were analyzed to investigate brain structural differences between good sleepers and IH. Structural covariance and resting-state functional connectivity were analyzed to investigate changes in the DMN. Participants with IH had greater volume and cortical thickness in the precuneus, a posterior hub of the DMN. Cortical thickness in the left medial prefrontal cortex was positively correlated with thickness of the precuneus, and the strength of this correlation was greater in IH. In contrast, functional connectivity at rest was lower within the anterior DMN (medial prefrontal cortex) in IH, and correlated with self-reported daytime sleepiness. The present results show that IH is associated with structural and functional differences in the DMN, in proportion to the severity of daytime sleepiness, suggesting that a disruption of the DMN contributes to the clinical features of IH. Larger volume and thickness in this network might reflect compensatory changes to lower functional connectivity in IH.
Bidirectional associations between insomnia, posttraumatic stress disorder, and depressive symptoms among adolescent earthquake survivors: a longitudinal multiwave cohort study
Authors: Geng Fulei , Liang Yingxin , Li Yuanyuan , Fang Yi , Pham Tien Sy , Liu Xianchen , Fan Fang 
Published: July 2019

Abstract

Study Objectives
To assess insomnia symptoms in adolescents with probable posttraumatic stress disorder (PTSD) and to determine whether there are longitudinal and reciprocal associations between insomnia, PTSD, and depressive symptoms.

Methods
Participants were 1,492 adolescent survivors who had been exposed to the 2008 Wenchuan earthquake in China. Insomnia, PTSD, and depressive symptoms were measured at 12 months (T1, n = 1407), 18 months (T2, n = 1335), and 24 months (T3, n = 1361) postearthquake by self-report questionnaires. Generalized estimating equation (GEE) models were used to examine the cross-sectional and longitudinal associations of insomnia with PTSD and depression.

Results
Insomnia, PTSD, and depressive symptoms were common among adolescent survivors. Among participants with probable PTSD, approximately 47% (48.5%, T1; 48.1%, T2; and 44.2%, T3) reported difficulty falling asleep or difficulty maintaining sleep. Cross-sectional analyses showed that insomnia co-occurred with PTSD (odds ratio [OR] = 2.04) and depressive symptoms (OR = 2.10). Longitudinal analyses revealed that probable PTSD (OR = 1.50) and depression (OR = 1.42) predicted the incidence of insomnia; in turn, insomnia predicted the incidence of depression (OR = 1.65) over time. Furthermore, PTSD predicted (OR = 3.11) and was predicted (OR = 3.25) by depressive symptoms.

Conclusions
There is a bidirectional relationship between insomnia, PTSD, and depressive symptoms. This suggests that insomnia, PTSD, and depression are intertwined over time.
Development and evaluation of the SPeeding Research-tested INTerventions (SPRINT) training program
Authors: Gaysynsky Anna , Vinson Cynthia A , Oh April 
Published: July 2019

Abstract
The National Cancer Institute established a dissemination and implementation accelerator program called SPeeding Research-tested INTerventions (SPRINT) to improve the uptake of evidence-based interventions. The purpose of this study was to describe the origin, structure, and goals of the SPRINT program, and present evaluation results from the first two cohorts of the program. Qualitative (focus group) and quantitative (survey) data collected from participants were used to evaluate the course and inform program improvement efforts. The majority of the participants (over 90% in both cohorts) rated the course highly, and over 80% would recommend the course to other researchers. Most participants indicated knowing relatively little about business model concepts before SPRINT, but after SPRINT, nearly all respondents felt that they had at least “some” knowledge of each business model component. Participants also indicated that they learned about the product–market fit of their intervention and gained insights from customer discovery interviews that would enable them to make their intervention more “stakeholder focused”. Participants also indicated that they plan to use the knowledge and skills they gained during the SPRINT program in their future work. Feedback from participants was used by the management team to implement various program improvements to better serve the next cohort of participants. While behavioral researchers face significant barriers to commercializing their interventions, they recognize the importance of translating their research into practice. Training researchers to consider scale-up, implementation, and commercialization from the outset can help reduce the number of proven interventions that are never used in practice.
Acting together, destabilizing influences can stabilize human balance
Authors: Milton John , Insperger Tamas 
Published: July 2019

The causes of falling in the elderly are multi-factorial. Three factors that influence balance stability are the time delay, a sensory dead zone and the maximum ankle torque that can be generated by muscular contraction. Here, the effects of these contributions are evaluated in the context of a model of an inverted pendulum stabilized by time-delayed proportional–derivative (PD) feedback. The effect of the sensory dead zone is to produce a hybrid type of control in which the PD feedback is switched ON or OFF depending on whether or not the controlled variable is larger or smaller than the detection threshold,Π. It is shown that, asΠincreases, the region in the plane of control parameters where the balance time (BT) is greater than 60 s is increased slightly. However, when maximum ankle torque is also limited, there is a dramatic increase in the parameter region associated with BTs greater than 60 s. This increase is due to the effects of a torque limitation on over-control associated with bang-bang type switching controllers. These observations show that acting together influences, which are typically thought to destabilize balance, can actually stabilize balance.This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Complex partial synchronization patterns in networks of delay-coupled neurons
Authors: Nikitin D. , Omelchenko I. , Zakharova A. , Avetyan M. , Fradkov A. L. , Schöll E. 
Published: July 2019

We study the spatio-temporal dynamics of a multiplex network of delay-coupled FitzHugh–Nagumo oscillators with non-local and fractal connectivities. Apart from chimera states, a new regime of coexistence of slow and fast oscillations is found. An analytical explanation for the emergence of such coexisting partial synchronization patterns is given. Furthermore, we propose a control scheme for the number of fast and slow neurons in each layer.
This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Geometric analysis of synchronization in neuronal networks with global inhibition and coupling delays
Authors: Ryu Hwayeon , Campbell Sue Ann 
Published: July 2019

We study synaptically coupled neuronal networks to identify the role of coupling delays in network synchronized behaviour. We consider a network of excitable, relaxation oscillator neurons where two distinct populations, one excitatory and one inhibitory, are coupled with time-delayed synapses. The excitatory population is uncoupled, while the inhibitory population is tightly coupled without time delay. A geometric singular perturbation analysis yields existence and stability conditions for periodic solutions where the excitatory cells are synchronized and different phase relationships between the excitatory and inhibitory populations can occur, along with formulae for the periods of such solutions. In particular, we show that if there are no delays in the coupling, oscillations where the excitatory population is synchronized cannot occur. Numerical simulations are conducted to supplement and validate the analytical results. The analysis helps to explain how coupling delays in either excitatory or inhibitory synapses contribute to producing synchronized rhythms.
This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Fast consensus in a large-scale multi-agent system with directed graphs using time-delayed measurements
Authors: Ramírez Adrián , Sipahi Rifat , Mondié Sabine , Garrido Rubén 
Published: July 2019

This article is on fast-consensus reaching in a class of multi-agent systems (MAS). We present an analytical approach to tune controllers for the agents based on the premise that delayed measurements in the controller can be preferable to standard controllers relying only on current measurements. Controller tuning in this setting is however challenging due to the presence of delays. To tackle this problem, we propose an analytic geometry approach. The key contribution is that the tuning can be implemented for complex eigenvalues of the arising graph Laplacian of the network, complementing the current state of the art, which is limited to real eigenvalues. Results, therefore, extend our knowledge beyond symmetric graphs and enable the study of the MAS under directed graphs.
This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Nonlinear dynamics of delay systems: an overview
Authors: Otto A. , Just W. , Radons G. 
Published: July 2019

Time delays play an important role in many fields such as engineering, physics or biology. Delays occur due to finite velocities of signal propagation or processing delays leading to memory effects and, in general, infinite-dimensional systems. Time delay systems can be described by delay differential equations and often include non-negligible nonlinear effects. This overview article introduces the theme issue ‘Nonlinear dynamics of delay systems’, which contains new fundamental results in this interdisciplinary field as well as recent developments in applications. Fundamentally, new results were obtained especially for systems with time-varying delay and state-dependent delay and for delay system with noise, which do often appear in real systems in engineering and nature. The applications range from climate modelling over network dynamics and laser systems with feedback to human balancing and machine tool chatter.
This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Homologous recombination-based genome editing by clade F AAVs is inefficient in the absence of a targeted DNA break
Authors: Rogers Geoffrey L. , Chen Hsu-Yu , Morales Heidy , Cannon Paula M. 
Published: July 2019

AbstractAdeno-associated virus (AAV) vectors are frequently used as donor templates for genome editing by homologous recombination. Although modification rates are typically under 1%, they are greatly enhanced by targeted double-stranded DNA breaks (DSBs). A recent report described clade F AAVs mediating high-efficiency homologous recombination-based editing in the absence of DSBs. The clade F vectors included AAV9 and a series isolated from human hematopoietic stem/progenitor cells (HSPCs). We evaluated these vectors by packaging homology donors into AAV9 and an AAVHSC capsid and examining their ability to insert GFP at the CCR5 or AAVS1 loci in human HSPCs and cell lines. As a control we used AAV6, which effectively edits HSPCs, but only when combined with a targeted DSB. Each AAV vector promoted GFP insertion in the presence of matched CCR5 or AAVS1 zinc finger nucleases (ZFNs), but none supported detectable editing in the absence of the nucleases. Rates of editing with ZFNs correlated with transduction efficiencies for each vector, implying no differences in the ability of donor sequences delivered by the different vectors to direct genome editing. Our results therefore do not support that clade F AAVs can perform high efficiency genome editing in the absence of a DSB.
Reduced sleep pressure in young children with autism
Authors: Arazi Ayelet , Meiri Gal , Danan Dor , Michaelovski Analya , Flusser Hagit , Menashe Idan , Tarasiuk Ariel , Dinstein Ilan 
Published: July 2019

AbstractStudy ObjectivesSleep disturbances and insomnia are highly prevalent in children with Autism Spectrum Disorder (ASD). Sleep homeostasis, a fundamental mechanism of sleep regulation that generates pressure to sleep as a function of wakefulness, has not been studied in children with ASD so far, and its potential contribution to their sleep disturbances remains unknown. Here, we examined whether slow wave activity (SWA), a measure that is indicative of sleep pressure, differs in children with ASD.MethodsIn this case-control study, we compared overnight electroencephalogram (EEG) recordings that were performed during Polysomnography (PSG) evaluations of 29 children with ASD and 23 typically developing children.ResultsChildren with ASD exhibited significantly weaker SWA power, shallower SWA slopes, and a decreased proportion of slow wave sleep in comparison to controls. This difference was largest during the first two hours following sleep onset and decreased gradually thereafter. Furthermore, SWA power of children with ASD was significantly, negatively correlated with the time of their sleep onset in the lab and at home, as reported by parents.ConclusionsThese results suggest that children with ASD may have a dysregulation of sleep homeostasis that is manifested in reduced sleep pressure. The extent of this dysregulation in individual children was apparent in the amplitude of their SWA power, which was indicative of the severity of their individual sleep disturbances. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances in children with ASD.Statement of significanceSleep disturbances are apparent in 40-80% of children with autism. Homeostatic sleep regulation, a mechanism that increases the pressure to sleep as a function of prior wakefulness, has not been studied in children with autism. Here, we compared Polysomnography exams of 29 children with autism and 23 matched controls. We found that children with autism exhibited reduced slow-wave-activity power and shallower slopes, particularly during the first two hours of sleep. This suggests that they develop less pressure to sleep. Furthermore, the reduction in slow-wave-activity was associated with the severity of sleep disturbances as observed in the laboratory and as reported by parents. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances of children with autism.
The genomics of mimicry: gene expression throughout development provides insights into convergent and divergent phenotypes in a Müllerian mimicry system
Authors: Stuckert Adam M M , Chouteau Mathieu , McClure Melanie , LaPolice Troy M , Linderoth Tyler , Nielsen Rasmus , Summers Kyle , MacManes Matthew D 
Published: July 2019

AbstractA common goal in evolutionary biology is to discern the mechanisms that produce the astounding diversity of morphologies seen across the tree of life. Aposematic species, those with a conspicuous phenotype coupled with some form of defense, are excellent models to understand the link between vivid color pattern variations, the natural selection shaping it, and the underlying genetic mechanisms underpinning this variation. Mimicry systems in which multiple species share the same conspicuous phenotype can provide an even better model for understanding the mechanisms of color production in aposematic species, especially if comimics have divergent evolutionary histories. Here we investigate the genetic mechanisms by which vivid color and pattern are produced in a Müllerian mimicry complex of poison frogs. We did this by first assembling a high-quality de novo genome assembly for the mimic poison frogRanitomeya imitator. This assembled genome is 6.8 Gbp in size, with a contig N50 of 300 Kbp and 93% of expected tetrapod genes. We then leveraged this genome to conduct gene expression analyses throughout development of four color morphs ofR. imitatorand two color morphs from bothR. fantasticaandR. variabiliswhichR. imitatormimics. We identified a large number of pigmentation and patterning genes that are differentially expressed throughout development, many of them related to melanocyte development, melanin synthesis, iridophore development, and guanine synthesis. In addition, we identify the pteridine synthesis pathway (including genes such asqdprandxdh) as a key driver of the variation in color between morphs of these species. Finally, we hypothesize that genes in the keratin family are important for producing different structural colors within these frogs.
How many different clonotypes do immune repertoires contain?
Authors: Mora Thierry , Walczak Aleksandra M. 
Published: July 2019

AbstractImmune repertoires rely on diversity of T-cell and B-cell receptors to protect us against foreign threats. The ability to recognize a wide variety of pathogens is linked to the number of different clonotypes expressed by an individual. Out of the estimated ∼ 1012different B and T cells in humans, how many of them express distinct receptors? We review current and past estimates for these numbers. We point out a fundamental limitation of current methods, which ignore the tail of small clones in the distribution of clone sizes. We show that this tail strongly affects the total number of clones, but it is impractical to access experimentally. We propose that combining statistical models with mechanistic models of lymphocyte clonal dynamics offers possible new strategies for estimating the number of clones.
A Minimally Invasive Technique for Serial Intraosseous Perfusion Measurements in the Murine Tibia Using Laser Doppler Flowmetry
Authors: Hanne Nicholas J , Easter Elizabeth D , Stangeland-Molo Sandra , Cole Jacqueline H 
Published: July 2019

AbstractIn biomedical and preclinical research, the current standard method for measuring blood perfusion inside murine bone, radiolabeled microspheres, is a terminal procedure that cannot be used to monitor longitudinal perfusion changes. Laser Doppler flowmetry (LDF) can quantify perfusion within the proximal tibial metaphysis of mice in vivo but requires a surgical procedure to place the measurement probe directly onto the bone surface. Sustained inflammation for over a month following this technique was previously reported, and previous studies have used LDF as an endpoint-only procedure. We developed a modified, minimally invasive LDF procedure to measure intraosseous perfusion in the murine tibia without stimulating local or systemic inflammation or inducing gait abnormalities. This modified technique can be used to measure perfusion weekly for up to at least a month.
Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibiaThe modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery
Quantitative three-dimensional nondestructive imaging of whole anaerobic ammonium-oxidizing bacteria
Authors: Peng M-W. , Guan Y. , Liu J-H. , Chen L. , Wang H. , Xie Z-Z. , Li H-Y. , Chen Y-P. , Liu P. , Yan P. , Guo J-S. , Liu G. , Shen Y. , Fang F. 
Published: July 2019

AbstractAnaerobic ammonium-oxidizing (anammox) bacteria play a key role in the global nitrogen cycle and the treatment of nitrogenous wastewater. These functions are closely related to the unique biophysical structure of anammox bacteria. However, the research on the biophysical ultrastructure of intact anammox bacteria is lacking. In this study,in-situthree-dimensional nondestructive ultrastructure imaging of whole anammox cell was performed using synchrotron soft X-ray nano-computed tomography and the total variation-based simultaneous algebraic reconstruction technique (TV-SART). Statistical and quantitative analyses of the ultrastructures of intact anammox bacteria were performed. The linear absorption coefficient values of the ultrastructures of anammox bacteria were calculated and the asymmetric structure of the anammox bacteria was quantified. On this basis, the shape adaptation of the anammox bacteria responses to Fe2+were explored, and the underlying regulation mechanism of Fe2+on anammox bacteria was explored. Furthermore, a promising method to study the biophysical properties of cells in different environments and engineering processes was proposed.Graphical AbstractStatement of SignificanceAnaerobic ammonium-oxidizing (anammox) bacteria play key role in global nitrogen cycle, and this physiological function depends on the unique morphology of anammox bacteria. In this study, synchrotron soft-X ray imaging technique coupled with simultaneous algebraic reconstruction technique with total variation (SART-TV) algorithm were performed to quantify the three-dimensional ultrastructure of the whole anammox bacteria for the first time. On this basis, the shape adaptation and mechanism of the anammox bacteria responses to Fe2+ were explored and a promising method for detecting the physiological properties of anammox bacteria was proposed.
Acidic fibroblast growth factor underlies microenvironmental regulation of MYC in pancreatic cancer
Authors: Bhattacharyya Sohinee , Oon Chet , Kothari Aayush , Horton Wesley , Link Jason , Sears Rosalie C. , Sherman Mara H. 
Published: July 2019

AbstractDespite a critical role for MYC as an effector of oncogenic RAS, strategies to target MYC activity in RAS-driven cancers are lacking. Oncogenic KRAS is insufficient to drive tumorigenesis, while addition of modest overexpression of MYC drives robust tumor formation, suggesting that mechanisms beyond the RAS pathway play key roles in MYC regulation and RAS-driven tumorigenesis. Here we show that acidic fibroblast growth factor (FGF1) derived from cancer-associated fibroblasts (CAFs) cooperates with cancer cell-autonomous signals to increase MYC level, promoter occupancy, and activity. FGF1 is necessary and sufficient for paracrine regulation of MYC protein stability, signaling through AKT and GSK-3β. These signals cooperate with, but are distinct from, cell-autonomous signals from oncogenic KRAS which stabilize MYC. Human pancreatic cancer specimens reveal a strong correlation between stromal CAF content and MYC protein level in the neoplastic compartment, and identify CAFs as the specific source of FGF1 in the tumor microenvironment. Together, our findings demonstrate that MYC is coordinately regulated by cell-autonomous and microenvironmental signals, and establish CAF-derived FGF1 as a novel paracrine regulator of oncogenic transcription.Statement of significanceOur work highlights an unanticipated role for the tumor microenvironment in the regulation of MYC protein stability in pancreatic cancer cells and identifies CAF-derived FGF1 as a novel, specific paracrine regulator of MYC.