bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cross-Sectional Study of the Prevalence and Factors Associated With Tinnitus and/or Hyperacusis in Children
Authors: Nemholt Susanne , Schmidt Jesper Hvass , Wedderkopp Niels , Baguley David M. 
Published: July 2019

Objectives:
The aim of this study was to determine the prevalence of tinnitus and/or hyperacusis in Danish children aged 10 to 16 years, and to assess associations between tinnitus or hyperacusis and other relevant factors.

Design:
A cross-sectional study based on a previously established child cohort. A total of 501 children were enrolled in the project. The study was performed in eight mainstream schools and data were collected during an 8-week period from October 27, 2014 to December 16, 2014.

Results:
Using broad tinnitus research questions, the prevalence of any tinnitus was 66.9%; of noise-induced tinnitus (NIT) was 35.7%; and of spontaneous tinnitus (ST) was 53.7%. Bothersome tinnitus was reported by 34.6% of the children with any tinnitus, 23.2% of the whole population. Few children were severely bothered (2.4%, 1.6%, respectively). It was significantly more common for children with NIT to report tinnitus episodes lasting for minutes or longer than for children with ST (p = 0.01). Girls were more likely than boys to be bothered by tinnitus [Odds ratio (OR) = 2.96; 95% confidence interval (CI) 1.34 to 6.51; p = 0.01]. 14.6% of the children reported hyperacusis, and 72.6% of those reporting hyperacusis were bothered by it, 10.6% of the whole population. The odds of having hyperacusis were 4.73 (1.57, 14.21) times higher among those with ST compared with those without ST. Furthermore, hyperacusis was associated with sound avoidance behaviors such as experience of sound-induced pain in the ear (OR = 2.95, 95% CI 1.65 to 5.27; p < 0.001), withdrawal from places or activities (OR = 3.33; 95% CI 1.44 to 7.69; p = 0.01), or concerns about sound could damage the hearing (OR = 1.85, 95% CI 1.06 to 3.31; p = 0.03).

Conclusions:
Tinnitus and hyperacusis are common in children but prevalence is dependent on tinnitus definitions. Only a few children are severely bothered by tinnitus. In the case of hyperacusis, children may exhibit sound avoidance behavior.
Personal and Societal Impact of Low Back Pain
Authors: Dutmer Alisa L. , Schiphorst Preuper Henrica R. , Soer Remko , Brouwer Sandra , Bültmann Ute , Dijkstra Pieter U. , Coppes Maarten H. , Stegeman Patrick , Buskens Erik , van Asselt Antoinette D.I. , Wolff André P. , Reneman Michiel F. 
Published: July 2019

Study Design.
Cross-sectional study.

Objective.
The aim of this study was to study the personal and societal impact of low back pain (LBP) in patients admitted to a multidisciplinary spine center.

Summary of Background Data.
The socioeconomic burden of LBP is very high. A minority of patients visit secondary or tertiary care because of severe and long-lasting complaints. This subgroup may account for a major part of disability and costs, yet could potentially gain most from treatment. Currently, little is known about the personal and societal burden in patients with chronic complex LBP visiting secondary/tertiary care.

Methods.
Baseline data were acquired through patient-reported questionnaires and health insurance claims. Primary outcomes were LBP impact (Impact Stratification, range 8–50), functioning (Pain Disability Index, PDI; 0–70), quality of life (EuroQol-5D, EQ5D; −0.33 to 1.00), work ability (Work Ability Score, WAS; 0–10), work participation, productivity costs (Productivity Cost Questionnaire), and healthcare costs 1 year before baseline. Healthcare costs were compared with matched primary and secondary care LBP samples. Descriptive and inferential statistics were applied.

Results.
In total, 1502 patients (age 46.3 ± 12.8 years, 57% female) were included. Impact Stratification was 35.2 ± 7.5 with severe impact (≥35) for 58% of patients. PDI was 38.2 ± 14.1, EQ5D 0.39 (interquartile range, IQR: 0.17–0.72); WAS 4.0 (IQR: 1.0–6.0) and 17% were permanently work-disabled. Mean total health care costs (€4875, 95% confidence interval [CI]: 4309–5498) were higher compared to the matched primary care sample (n = 4995) (€2365, 95% CI: 2219–2526, P < 0.001), and similar to the matched secondary care sample (n = 4993) (€4379, 95% CI: 4180–4590). Productivity loss was estimated at €4315 per patient (95% CI: 3898–4688) during 6 months.

Conclusion.
In patients seeking multidisciplinary spine care, the personal and societal impact of LBP is very high. Specifically, quality of life and work ability are poor and health care costs are twice as high compared to patients seeking primary LBP care.

Level of Evidence: 3
Nerve growth factor–mediated photoablation of nociceptors reduces pain behavior in mice
Authors: Nocchi Linda , Portulano Carla , Franciosa Federica , Doleschall Balint , Panea Mirela , Roy Nainika , Maffei Mariano , Gargano Alessandra , Perlas Emerald , Heppenstall Paul A. 
Published: July 2019

Abstract
Nerve growth factor (NGF) and its receptors TrkA and p75 play a key role in the development and function of peripheral nociceptive neurons. Here, we describe novel technology to selectively photoablate TrkA-positive nociceptors through delivery of a phototoxic agent coupled to an engineered NGF ligand and subsequent near-infrared illumination. We demonstrate that this approach allows for on demand and localized reversal of pain behaviors in mouse models of acute, inflammatory, neuropathic, and joint pain. To target peripheral nociceptors, we generated a SNAP-tagged NGF derivative NGFR121W that binds to TrkA/p75 receptors but does not provoke signaling in TrkA-positive cells or elicit pain behaviors in mice. NGFR121W-SNAP was coupled to the photosensitizer IRDye700DX phthalocyanine (IR700) and injected subcutaneously. After near-infrared illumination of the injected area, behavioral responses to nociceptive mechanical and sustained thermal stimuli, but not innocuous stimuli, were substantially reduced. Similarly, in models of inflammatory, osteoarthritic, and neuropathic pain, mechanical hypersensitivity was abolished for 3 weeks after a single treatment regime. We demonstrate that this loss of pain behavior coincides with the retraction of neurons from the skin which then reinnervate the epidermis after 3 weeks corresponding with the return of mechanical hypersensitivity. Thus NGFR121W-SNAP-mediated photoablation is a minimally invasive approach to reversibly silence nociceptor input from the periphery, and control pain and hypersensitivity to mechanical stimuli.
Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity
Authors: Fernandes Carina , Pidal-Miranda Marina , Samartin-Veiga Noelia , Carrillo-de-la-Peña María T. 
Published: July 2019

Abstract
Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research.
Ribosolve: Rapid determination of three-dimensional RNA-only structures
Authors: Kappel Kalli , Zhang Kaiming , Su Zhaoming , Kladwang Wipapat , Li Shanshan , Pintilie Grigore , Topkar Ved V. , Rangan Ramya , Zheludev Ivan N. , Watkins Andrew M. , Yesselman Joseph D. , Chiu Wah , Das Rhiju 
Published: July 2019

AbstractThe discovery and design of biologically important RNA molecules is dramatically outpacing three-dimensional structural characterization. To address this challenge, we present Ribosolve, a hybrid method integrating moderate-resolution cryo-EM maps, chemical mapping, and Rosetta computational modeling, and demonstrate its application to thirteen previously unknown 119-to 338-nucleotide protein-free RNA-only structures: full-length Tetrahymena ribozyme, hc16 ligase with and without substrate, full-length V. cholerae and F. nucleatum glycine riboswitch aptamers with and without glycine, Mycobacterium SAM-IV riboswitch with and without S-adenosylmethionine, and computer-designed spinach-TTR-3, eterna3D-JR_1, and ATP-TTR-3 with and without AMP. Blind challenges, prospective compensatory mutagenesis, internal controls, and simulation benchmarks validate the Ribosolve models and establish that modeling convergence is quantitatively predictive of model accuracy. These results demonstrate that RNA-only 3D structure determination can be rapid and routine.
Consistency and identifiability of the polymorphism-aware phylogenetic models
Authors: Borges Rui , Kosiol Carolin 
Published: July 2019

AbstractPolymorphism-aware phylogenetic models (PoMo) constitute an alternative approach for species tree estimation from genome-wide data. PoMo builds on the standard substitution models of DNA evolution but expands the classic alphabet of the four nucleotide bases to include polymorphic states. By doing so, PoMo accounts for ancestral and current intra-population variation, while also accommodating population-level processes ruling the substitution process (e.g. genetic drift, mutations, allelic selection). PoMo has shown to be a valuable tool in several phylogenetic applications but a proof of statistical consistency (and identifiability, a necessary condition for consistency) is lacking. Here, we prove that PoMo is identifiable and, using this result, we further show that the maximuma posteriori(MAP) tree estimator of PoMo is a consistent estimator of the species tree. We complement our theoretical results with a simulated data set mimicking the diversity observed in natural populations exhibiting incomplete lineage sorting. We implemented PoMo in a Bayesian framework and show that the MAP tree easily recovers the true tree for typical numbers of sites that are sampled in genome-wide analyses.
Dynamics of Auxilin1 and GAK in clathrin-mediated traffic
Authors: He Kangmin , Song Eli , Upadhyayula Srigokul , Dang Song , Gaudin Raphael , Skillern Wesley , Bu Kevin , Capraro Benjamin R. , Rapoport Iris , Kusters Ilja , Ma Minghe , Kirchhausen Tom 
Published: July 2019

ABSTRACTClathrin coated vesicles formed at the plasma membrane lose their clathrin lattice within seconds of pinching off, through the action of the Hsc70 “uncoating ATPase”. The J-domain containing proteins, auxilin1 (Aux1) and auxilin2/cyclin-G dependent kinase (GAK), recruit Hsc70. Aux1 and GAK are closely related homologs, each with a phosphatase- and tensin-like (PTEN-like) domain, a clathrin-binding region, and a C-terminal J-domain; GAK has an additional, N-terminal Ser/Thr kinase domain. The PTEN-like domain has no phosphatase activity, but it can recognize phosphatidylinositol phosphate head groups. Aux1 and GAK appear on coated vesicles in successive transient bursts, immediately after dynamin mediated membrane scission has released the vesicle from the plasma membrane. We show here that these bursts represent recruitment of a very small number of auxilins such that even 4-6 molecules are sufficient to mediate uncoating. In contrast, we could not detect auxilins in abortive pits or at any time during coated-pit assembly. We have also shown previously that clathrin coated vesicles have a dynamic phosphoinositide landscape, and we have proposed that lipid head group recognition might determine the timing of Aux1 and GAK appearance. We now show that differential recruitment of Aux1 and GAK correlates with temporal variations in phosphoinositide composition, consistent with a lipid-switch timing mechanism.
Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia
Authors: Prakash Nandkishore , Stark Christiana J. , Keisler Maria N. , Luo Lily , Der-Avakian Andre , Dulcis Davide 
Published: July 2019

ABSTRACTChronic stress induces anhedonia in susceptible, but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in adult male rats using social defeat and intracranial self-stimulation (ICSS), while changes in serotonergic phenotype were investigated using immunohistochemistry and in situ hybridization. Susceptible, but not resilient, rats displayed an increased number of neurons expressing the biosynthetic enzyme for serotonin, tryptophan-hydroxylase-2 (TPH2), in the ventral subnucleus of the dorsal raphe nucleus (DRv). Further, a decrease in the number of DRv glutamatergic neurons was observed in all stressed animals. This neurotransmitter plasticity is dependent on DR activity, as was revealed by chemogenetic manipulation of the central amygdala, a stress-sensitive nucleus that forms a major input to the DR. Activation of amygdalar corticotropin releasing hormone (CRH)+ neurons abolished the increase in DRv TPH2+ neurons and ameliorated stress-induced anhedonia in susceptible animals. These findings show that activation of amygdalar projections induces resilience, and suppresses the gain of serotonergic phenotype in the DR that is characteristic of susceptible animals. This molecular signature of vulnerability to stress-induced anhedonia and the active nature of resilience could be a target of new treatments for stress-related disorders like depression.SIGNIFICANCE STATEMENTDepression and other mental disorders can be induced by chronic or traumatic stressors. However, some individuals are resilient and do not develop depression in response to chronic stress. A complete picture of the molecular differences between susceptible and resilient individuals is necessary to understand how plasticity of limbic circuits is associated with the pathophysiology of stress-related disorders. Using a rodent model, our study identifies a novel molecular marker of susceptibility to stress-induced anhedonia, a core symptom of depression, and a means to modulate it. These findings will guide further investigation into cellular and circuit mechanisms of resilience, and the development of new treatments for depression.
CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling
Authors: Ziak Jakub , Weissova Romana , Jeřábková Kateřina , Janikova Martina , Maimon Roy , Petrasek Tomas , Pukajova Barbora , Wang Mengzhe , Brill Monika S. , Kleisnerova Marie , Kasparek Petr , Zhou Xunlei , Alvarez-Bolado Gonzalo , Sedlacek Radislav , Misgeld Thomas , Stuchlik Ales , Perlson Eran , Balastik Martin 
Published: July 2019

ABSTRACTRegulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins is key to development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating Semaphorin 3A (Sema3A) signaling and its dysfunction has been linked to schizophrenia, however, nothing is known about its role in the synapse pruning. Here, using newly generatedcrmp2−/−mice we demonstrate that while CRMP2 has only a moderate effect on Sema3A-dependent axon guidancein vivo, it is essential for Sema3F-dependent axon pruning and dendritic spine remodeling. We first demonstrate that CRMP2 deficiency interferes with Sema3A signaling in compartmentalized neuron cultures and leads to a mild defect in axon guidance in peripheral nerves and corpus callosum. Strikingly, we show thatcrmp2−/−mice display more prominent defects in dendritic spine pruning and stereotyped axon pruning in hippocampus and visual cortex consistent with impaired Sema3F signaling and with autism spectrum disorder (ASD)-rather than schizophrenia-like phenotype. Indeed, we demonstrate that CRMP2 mediates Sema3F-induced axon retraction in primary neurons and thatcrmp2−/−mice display early postnatal behavioral changes linked to ASD. In conclusion, we demonstrate that CRMP2 is an essential mediator of Sema3F-dependent synapse pruning and its dysfunction in early postnatal stages shares histological and behavioral features of ASD.
Limits and constraints on mechanisms of cell-cycle regulation imposed by cell sizehomeostasis measurements
Authors: Willis Lisa , Jönsson Henrik , Huang Kerwyn Casey 
Published: July 2019

SummaryHigh-throughput imaging has led to an explosion of observations regarding cell-size homeostasis across the kingdoms of life. Among bacteria, “adder” behavior in which a constant size appears to be added during each cell cycle is ubiquitous, while various eukaryotes show other size-homeostasis behaviors. Since interactions between cell-cycle progression and growth ultimately determine size-homeostasis behaviors, we developed a general model of cell proliferation to: 1) discover how the requirement of cell-size homeostasis limits mechanisms of cell-cycle control; 2) predict how features of cell-cycle control translate into size-homeostasis measurements. Our analyses revealed plausible cell-cycle control scenarios that nevertheless fail to regulate cell size, conditions that generate apparent adder behavior without underlying adder mechanisms, cell-cycle features that play unintuitive roles in causing deviations from adder, and distinguishing predictions for extended size-homeostasis statistics according to the underlying control mechanism. The model thus provides holistic insight into the mechanistic implications of cell-size homeostasis measurements.
Inefficient ZAP70-Signaling Blunts Antigen Detection by CAR-T-Cells
Authors: Gudipati Venugopal , Rydzek Julian , Perez Iago Doel , Scharf Lydia , Königsberger Sebastian , Einsele Hermann , Stockinger Hannes , Hudecek Michael , Huppa Johannes B. 
Published: July 2019

ABSTRACTRational design of chimeric antigen receptors (CARs) with optimized anti-cancer performance mandates detailed knowledge of how CARs engage tumor antigens and how antigen-engagement triggers activation. We analyzed CAR-mediated antigen recognition via quantitative single molecule live-cell imaging and found the sensitivity of CAR-T-cells towards antigen approximately 1000-times reduced when compared to T-cell antigen receptor (TCR)-mediated recognition of nominal peptide/MHC complexes. While CARs outperformed TCRs with regard to antigen binding within the immunological synapse, proximal signaling was significantly attenuated due to inefficient recruitment of the tyrosine-kinase ZAP70 to ligated CARs and its reduced concomitant activation and subsequent release. Our study exposes signaling deficiencies of state-of-the-art CAR-designs, which limit at present the efficacy of CAR-T-cell therapies to target tumors with diminished antigen expression.
Determining factors of tourists’ loyalty to beach tourism destinations: a structural model
Authors: Hasan Md. Kamrul , Abdullah Shamsul Kamariah , Lew Tek Yew , Islam MD. Faridul 
Published: July 2019

Purpose
The purpose of this paper is to investigate and develop an integrated theoretical relationship by including destination image and attitudes into the quality-value-satisfaction-loyalty paradigm in the context of beach tourism.

Design/methodology/approach
A personal-administered survey was conducted using a convenient sampling technique to collect data from 601 tourists who had visited popular beach destinations in Bangladesh. Then, the structural relationships between the factors likely to affect tourist attitudes and loyalty were examined.

Findings
The findings reveal that both service quality and perceived values have a direct effect on destination image, tourist attitudes and satisfaction. Additionally, destination image and satisfaction significantly affect tourist attitudes and loyalty.

Research limitations/implications
The direct relationship of perceived service quality and perceived value with tourist loyalty was ignored in the model due to reporting consecutive indirect relationship between them in prior studies.

Practical implications
These findings contribute to the extension of theoretical and managerial knowledge, especially in a beach tourism setting, where little research has been done to investigate the proposed relationships.

Originality/value
The originality of this study lies in providing theoretical and empirical evidence regarding the effect of service quality and perceived value, especially on destination image and tourist attitude to behaviour in the loyalty model, which has been scarcely examined in the prior tourism literature.
Leveraging the technology acceptance model for mobile commerce adoption under distinct stages of adoption
Authors: Pipitwanichakarn Tanikan , Wongtada Nittaya 
Published: July 2019

PurposeThe purpose of this paper is to investigate the role of trust and perceived enjoyment in the technology acceptance model by distinguishing distinct stages of adoption among street vendors (initial and advanced adoption stage).Design/methodology/approachFace-to-face interviews using a structured questionnaire were conducted with 430 street vendors in Bangkok; 415 usable surveys were analyzed. By applying K-means cluster analysis, two segments were found with 200 initial and 215 advanced adopters. A multi-group analysis was employed to investigate differences of relationships between the two groups.FindingsThe findings reveal significant similarities and dissimilarities between the two groups of vendors. Both initial and advanced adopters emphasize trust of service providers. The first group relies more on perceived ease of use and perceived enjoyment in motivating m-commerce adoption but depends less on perceived usefulness. On the contrary, for the latter group, the influence of perceived ease of use and perceived enjoyment significantly decreases, but the effect of perceived usefulness significantly increases.Practical implicationsThis study sheds light on the managerial implications related to how service providers can tailor their marketing strategies to target vendors in disparate diffusion stages, and it encourages building trust between partners over time.Originality/valueDue to the lack of theoretical and managerial understanding of factors that drive m-commerce adoption for micro businesses, this study identifies distinct adoption stages and offers valuable insights into the similarities and differences among initial and advanced adopters.