bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principal mode of Syndecan‐4 mechanotransduction for the endothelial glycocalyx is a scissor‐like dimer motion
Authors: Jiang Xi Zhuo , Luo Kai H. , Ventikos Yiannis 
Published: September 2019

AbstractAimEndothelial glycocalyx (EG) plays a pivotal role in a plethora of diseases, like cardiovascular and renal diseases. One hallmark function of the EG as a mechanotransducer which transmits mechanical signals into cytoplasm has been documented for decades. However, the basic question ‐ how the glycocalyx transmits the flow shear stress— is unanswered so far. Our aim is to shed light on the fundamental mode of signal transmission from flow to the endothelial cytoskeleton.MethodsWe conduct a series of large‐scale molecular dynamics computational experiments to investigate the dynamics of glycocalyx under varying conditions (changing blood flow velocities and shedding of glycocalyx sugar chains).ResultsWe have identified that the main pathway of signal transmission in this system manifests as a scissors‐like motion of the Syndecan‐4 core protein. Results have suggested that the force transmitted into the cytoskeleton with an order of 10 ~ 100 pN, and the main function of sugar chains of a glycocalyx element is to protect the core proteins from severe conformational changes thereby maintaining the functionality of the EG.ConclusionThis research provides a reconciling explanation for a longstanding debate about the force transmission threshold based on our findings. A new explanation has also been provided to relate the role of the EG as a mechanotransducer to its function as a microvascular barrier: the EG regulates the mechanotransduction by altering the median value and variation range of the scissor angle, and the EG governs the microvascular barrier via controlling the scissor angle which will affect the intercellular cleft.
Stakeholder Engagement in Sustainability Reporting: Evidence of Reputation Risk Management in Large Australian Companies
Authors: Ardiana Putu Agus 
Published: September 2019

AbstractThe objective of this research is to examine whether stakeholder engagement in sustainability reporting constitutes the process of managing reputational risk. This research utilises Shrives and Brennan's (2017) framework of rhetorical strategies of non‐compliance to obtain empirical evidence of reputation risk management (RRM) in the context of stakeholder engagement in sustainability reporting. Quantitative and qualitative content analysis was undertaken on 154 sustainability disclosures in both the annual and sustainability reports of large Australian companies. This research finds that large Australian companies engage with their stakeholders to manage reputational risk: to increase market share and pre‐empt social issues. It is evident that large Australian companies use several forms of rhetorical statements in their sustainability disclosures with respect to RRM. However, there is no evidence that they shirk their responsibilities.
Confidence interval‐based sample size determination formulas and some mathematical properties for hierarchical data
Authors: Usami Satoshi 
Published: September 2019

The use of hierarchical data (also called multilevel data or clustered data) is common in behavioural and psychological research when data of lower‐level units (e.g., students, clients, repeated measures) are nested within clusters or higher‐level units (e.g., classes, hospitals, individuals). Over the past 25 years we have seen great advances in methods for computing the sample sizes needed to obtain the desired statistical properties for such data in experimental evaluations. The present research provides closed‐form and iterative formulas for sample size determination that can be used to ensure the desired width of confidence intervals for hierarchical data. Formulas are provided for a four‐level hierarchical linear model that assumes slope variances and inclusion of covariates under both balanced and unbalanced designs. In addition, we address several mathematical properties relating to sample size determination for hierarchical data via the standard errors of experimental effect estimates. These include the relative impact of several indices (e.g., random intercept or slope variance at each level) on standard errors, asymptotic standard errors, minimum required values at the highest level, and generalized expressions of standard errors for designs with any‐level randomization under any number of levels. In particular, information on the minimum required values will help researchers to minimize the risk of conducting experiments that are statistically unlikely to show the presence of an experimental effect.
Prognostic value of blood and lymphatic vessel markers in tongue cancer: A systematic review
Authors: Almahmoudi Rabeia , Kasanen Merimaija , Sieviläinen Meri , Salem Abdelhakim , Pirinen Matti , Salo Tuula , Al‐Samadi Ahmed 
Published: September 2019

AbstractTongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis through blood and lymphatic vessels. We undertook a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We carried out a systematic search in Ovid Medline, Scopus, and Cochrane libraries. All studies that evaluated the prognostic significance of MVD/LVD markers in TSCC were systematically retrieved. Our results showed that MVD/LVD markers, CD31, CD34, CD105, factor VIII, lymphatic vessel endothelial hyaluronan receptor‐1, and D2‐40 were evaluated in TSCC patients until 28 June 2018. Six out of 13 studies reported markers that were associated with poor prognosis in TSCC. Two out of three studies suggested that a high number of D2‐40+ vessels predicated low overall survival (OS); the third study reported that the ratio of D2‐40+ over factor VIII+ vessels is associated with low OS. Most of the other markers had controversial results for prognostication. We found higher expression of MVD/LVD markers were commonly, but not always, associated with shorter survival in TSCC patients. It is therefore not currently possible to recommend implementation of these markers as reliable prognosticators in clinical practice. More studies (especially for D2‐40) with larger patient cohorts are needed.
Dissection of gastric cancer heterogeneity for precision oncology
Authors: Ho Shamaine Wei Ting , Tan Patrick 
Published: September 2019

AbstractGastric cancer (GC) remains the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. Comprehensive ‐omic studies have unveiled a heterogeneous GC landscape, with considerable molecular diversity both between and within tumors. Given the complex nature of GC, a long‐sought goal includes effective identification of distinct patient subsets with prognostic and/or predictive outcomes to enable tailoring of specific treatments (“precision oncology”). In this review, we highlight various approaches to molecular classification in GC, covering recent genomic, transcriptomic, proteomic and epigenomic features. We pay special attention to the translational significance of classifier systems and examine potential confounding factors which deserve further investigation. In particular, we discuss recent advancements in our knowledge of intra‐subtype, intra‐patient and intra‐tumor heterogeneity, and the pivotal role of the tumor stromal microenvironment.
A kojic acid derivative promotes intrinsic apoptotic pathway of hepatocellular carcinoma cells without incurring drug resistance
Authors: Oncul Selin , Karakaya Gulsah , Dilsiz Aytemir Mutlu , Ercan Ayse 
Published: September 2019

AbstractHepatocellular carcinoma is one of the most pervasive cancers with low prognosis, high frequency of recurrence, and metastasis. Studies conducted have focused on extricating novel strategies for successful treatment. Kojic acid and its derivatives are already proven to have depigmenting, anti‐inflammatory, and anti‐neoplastic properties. In the present study, kojic acid and its 10 distinct derivatives were tested on HEPG2 cell line for their possible anti‐cancer effect and seven of them were observed to be cytotoxic. Compound 6 was chosen to proceed as the IC50 dosage for HEPG2 cells was lower in comparison with the other derivatives and kojic acid itself. Further experiments pointed out that intrinsic apoptotic pathway was triggered with the exposure of the cells to IC50 concentration of the derivative as the treatment led to escalation of intracellular ROS, induction of TP53 gene, and activation of caspase 3/7. Pro‐apoptotic Jnk and Bax genes were not triggered suggesting that the apoptotic pathway advance through an alternative route. Complementary experiments are in need; howbeit, the current findings suggest that the derivative offers a novel promising approach against hepatocellular carcinoma as it is not detrimental to healthy cells within the concentrations applied, and it does not induce drug resistance.
Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics
Authors: Ishii Takashi , Muroi Masashi , Horiguchi Kazuhide , Tanamoto Ken‐ichi , Nagase Takahide , Yamashita Naomi 
Published: September 2019

AbstractBackgroundType 2 innate lymphoid cells (ILC2s) are one of the sources of IL‐5 and IL‐13 in allergic airway inflammation. Innate immune receptors such as Toll‐like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL‐33 production, but a direct effect of TLRs on ILC2s remains to be elucidated.ObjectivesWe hypothesized that TLRs can directly activate lung ILC2s and participate in the pathogenesis of asthma.MethodsAfter intranasal administration of IL‐33 to wild‐type (WT), TLR2KO and TLR4KO female mice, ILC2s were isolated from harvested lungs. ILC2s were incubated with IL‐2 and TLR stimulants (pam3csk4 (PAM), house dust mite extract (HDM)). In some experiments, TLR2 or dectin‐1 signalling inhibitors were used. As an in vivo model, the mice were treated with IL‐33 and rested until lung recruitment of eosinophils regressed. Then they were treated intranasally with PAM + HDM or vehicle and analysed.ResultsIn vitro stimulation of isolated ILC2s showed that PAM could induce IL‐13 and IL‐5 production, and HDM had a synergistic effect on this stimulation. Both effects were dependent on TLR2 and NF‐κB signalling. PAM + HDM stimulation of WT mice led to increased ILC2s, airway hyperresponsiveness and increased levels of both neutrophils and eosinophils in bronchoalveolar lavage fluid. These observations were dependent on TLR2.Conclusions & clinical relevanceTLR2 can directly activate lung ILC2s, an effect that is augmented by HDM. Asthmatic characteristics mediated through the TLR2 pathway were evident in the in vivo mice model. These data implicate a new pathway of ILC2 activation in the pathogenesis of asthma.
Associations of gene polymorphisms in interferon‐alpha signature‐related genes with autoimmune thyroid diseases
Authors: Lin Jiunn‐Diann , Yang Shun‐Fa , Wang Yuan‐Hung , Fang Wen‐Fang , Tang Kam‐Tsun , Cheng Chao‐Wen 
Published: September 2019

AbstractSummaryInterferon (IFN)‐α treatment predisposes patients to the occurrence of autoimmune thyroid disease (AITD).MethodsWe investigated associations of single nucleotide polymorphisms (SNPs) of molecules participating in the IFN‐α signature, including rs2304204 and rs2304206 of IFN regulatory factor 3 (IRF3), rs1061501 of IRF7, and rs7708392 of TNFA1P3‐interacting protein 1 with serum IFN‐α levels and AITD in an ethnic Chinese (ie Taiwanese) population. Totally, 319 patients with Graves' disease (GD), 83 patients with Hashimoto's thyroiditis (HT) and 351 healthy controls were recruited.ResultsThere were increased percentages of the C allele, and CC and TC + CC genotypes of rs1061501 in GD patients compared to the controls. HT patients had higher serum IFN‐α levels compared to the controls, while there was no difference in serum IFN‐α levels between patients with GD and controls. However, patients with GD in a remission status had lower serum IFN‐α levels than those without remission. On the other hand, the C allele of rs1061501 was only associated with serum IFN‐α levels in patients with HT.ConclusionsThe SNP rs1061501 of IRF7 was associated with the development of GD. Serum IFN‐α levels were associated with HT, while they might modify the disease status of GD. Moreover, a genetic effect of rs1061501 on regulating serum IFN‐α production was observed in HT.
Can implants move in bone? A longitudinal in vivo micro‐CT analysis of implants under constant forces in rat vertebrae
Authors: Becker Kathrin , Schwarz Frank , Rauch Nicole Jasmin , Khalaph Silava , Mihatovic Ilja , Drescher Dieter 
Published: September 2019

AbstractObjectivesWhereas stationary stability of implants has been postulated for decades, recent studies suggested a phenomenon termed implant migration. This describes a change in position of implants as a reaction to applied forces. The present study aims at employing image registration of in vivo micro‐CT scans from different time points and to assess (a) if migration of continuously loaded implants is possible and (b) migration correlates with the force magnitude.Material and methodsTwo customized machined implants were placed in the dorsal portion of caudal vertebrae in n = 61 rats and exposed to standardized forces (0.5 N, 1.0 N, and 1.5 N) applied through a flat nickel–titanium contraction spring, or no forces (control). Micro‐CT scans were performed at 0, 1, 2, 4, 6, and 8 weeks after surgery. The baseline image was registered with the forthcoming scans. Implant migration was measured as the Euclidean distance between implant tips. Bone remodeling was assessed between the baseline and the forthcoming scans.ResultsThe findings confirmed a positional change of the implants at 2 and 8 weeks of healing, and a linear association between applied force and velocity of movement (anterior implant: χ2 = 12.12, df = 3, and p = .007 and posterior implant: χ2 = 20.35, df = 3, and p < .001). Bone apposition was observed around the implants and accompanied by formation of load‐bearing trabeculae and a general cortical thickening close and also distant to the implants.ConclusionThe present analysis confirmed that implants can migrate in bone. The applied forces seemed to stimulate bone thickening, which could explain why implants migrate without affecting stability.
The Analytic Truth and Falsity of Disjunctions
Authors: Quelhas Ana Cristina , Rasga Célia , Johnson‐Laird P.N. 
Published: September 2019

AbstractDisjunctive inferences are difficult. According to the theory of mental models, it is because of the alternative possibilities to which disjunctions refer. Three experiments corroborated further predictions of the mental model theory. Participants judged that disjunctions, such as Either this year is a leap year or it is a common year are true. Given a disjunction such as Either A or B, they tended to evaluate the four cases in its ‘partition’: A and B, A and not‐B, not‐A and B, not‐A and not‐B, as ‘possible’ or ‘impossible’ in ways that bore out the difference between inclusive disjunctions (‘or both’) and exclusive disjunctions (‘but not both’). Knowledge usually concerns what is true, and so when participants judge that a disjunction is false, or contingent, and evaluate the cases in its partition, they depend on inferences that yield predictable errors. They tended to judge that disjunctions, such as follows: Either the food is cold or else it is tepid, but not both, are true, though in fact they could be false. They tended to infer ‘mirror‐image’ evaluations that yield the same possibilities for false disjunctions as those for true disjunctions. The article considers the implications of these results for alternative theories based on classical logic or on the probability calculus.
The Influence of Shared Visual Context on the Successful Emergence of Conventions in a Referential Communication Task
Authors: Müller Thomas F. , Winters James , Morin Olivier 
Published: September 2019

AbstractHuman communication is thoroughly context bound. We present two experiments investigating the importance of the shared context, that is, the amount of knowledge two interlocutors have in common, for the successful emergence and use of novel conventions. Using a referential communication task where black‐and‐white pictorial symbols are used to convey colors, pairs of participants build shared conventions peculiar to their dyad without experimenter feedback, relying purely on ostensive‐inferential communication. Both experiments demonstrate that access to the visual context promotes more successful communication. Importantly, success improves cumulatively, supporting the view that pairs establish conventional ways of using the symbols to communicate. Furthermore, Experiment 2 suggests that dyads with access to the visual context successfully adapt the conventions built for one color space to another color space, unlike dyads lacking it. In linking experimental pragmatics with language evolution, the study illustrates the benefits of exploring the emergence of linguistic conventions using an ostensive‐inferential model of communication.
Immunosuppression reduction in kidney transplant recipients during bacterial infection—A retrospective study
Authors: Yahav Dafna , Sulimani Omri , Green Hefziba , Margalit Ili , Ben‐Zvi Haim , Mor Eytan , Rozen‐Zvi Benaya 
Published: September 2019

AbstractBackgroundImmunosuppression reduction is a common practice in the management of bacterial infection among kidney transplant recipients (KTRs). This practice, however, is based on limited evidence.MethodsRetrospective study comparing clinical outcomes of KTRs whose antimetabolite was discontinued vs continued during hospitalization due to bacterial infection, considering calcineurin inhibitors (CNI) levels. Primary outcome was a composite of clinical failure at day 5; all‐cause mortality; and/or re‐hospitalization at 90 days. Multivariable analysis of risk factors for the primary outcome was performed using a propensity‐matched cohort.ResultsWe included 183 KTRs hospitalized with bacterial infection. Neither discontinuation of antimetabolites nor lower levels of CNI at infection onset were associated with a significant decrease the composite primary outcome. No significant difference in graft loss or rejection was demonstrated between patients with low vs high CNI levels or discontinuation vs continuation of antimetabolite. In multivariable analysis, CNI levels and management of antimetabolite were not significantly associated with adverse outcome.ConclusionsImmunosuppression reduction in hospitalized KTRs with bacterial infection did not offer a clinical advantage in terms of mortality, re‐hospitalization, or clinical success. An interventional study evaluating continuation of immunosuppression vs reduction should be considered.
Rabbit antithymocyte globulin for the treatment of chronic lung allograft dysfunction
Authors: January Spenser E. , Fester Keith A. , Bain Karen Bennett , Kulkarni Hrishikesh S. , Witt Chad A. , Byers Derek E. , Alexander‐Brett Jennifer , Trulock Elbert P. , Hachem Ramsey R. 
Published: September 2019

AbstractBackgroundChronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. Several treatments have been used to prevent the progression or reverse the effects of CLAD. Cytolytic therapy with rabbit antithymocyte globulin (rATG) has previously shown to be a potential option. However, the effect on patients with restrictive allograft syndrome (RAS) versus bronchiolitis obliterans syndrome (BOS) and the effect of cumulative dosing are unknown.MethodsThe charts of lung transplant patients treated with rATG at Barnes‐Jewish Hospital from 2009 to 2016 were retrospectively reviewed. The primary outcome was response to rATG; patients were deemed responders if their FEV1 improved in the 6 months after rATG treatment. Safety endpoints included incidence of serum sickness, cytokine release syndrome, malignancy, and infectious complications.Results108 patients were included in this study; 43 (40%) patients were responders who experienced an increase in FEV1 after rATG therapy. No predictors of response to rATG therapy were identified. Serum sickness occurred in 22% of patients, 15% experienced cytokine release syndrome, and 19% developed an infection after therapy.Conclusion40% of patients with CLAD have an improvement in lung function after treatment with rATG although the improvement was typically minimal.
Evidence for the origin of the binaural interaction component of the auditory brainstem response
Authors: Tolnai Sandra , Klump Georg M. 
Published: September 2019

AbstractThe binaural interaction component (BIC) represents the mismatch between auditory brainstem responses (ABR) obtained with binaural stimulation and the sum of ABRs obtained with monaural left and right stimulation. It is generally assumed that the BIC reflects binaural integration. Its potential use as a diagnostic tool, however, is hampered by the lack of direct evidence about its origin. While an origin at the initial site of binaural integration seems likely, there is no general agreement on the contribution of the two primary candidate nuclei, the lateral and medial superior olives (LSO and MSO, respectively). Here, we recorded local field potentials (LFP) and responses of units in the LSO and MSO of Mongolian gerbils (Meriones unguiculatus), presenting clicks with an interaural time or level difference (ITD and ILD, respectively), while simultaneously recording ABR. We determined the BIC from the ABR and, importantly, from LFP and responses of units in the LSO and MSO. If stimulus‐induced changes in the ABR‐derived BIC have their source in the LSO and/or MSO, we expect coherent changes in the unit‐derived and the ABR‐derived BIC. We find that BIC obtained from LSO units exhibits the same ITD and ILD dependence as the ABR‐derived BIC. Neither BIC obtained from MSO units nor LFP‐derived BIC recorded in either LSO or MSO did. The data thus strongly suggest that it is the activity of LSO units in the gerbil that is decisive for the generation of the ABR‐derived BIC, determining its properties.
Nitric oxide regulates the firing rate of neuronal subtypes in the guinea pig ventral cochlear nucleus
Authors: Hockley Adam , Berger Joel I. , Smith Paul A. , Palmer Alan R. , Wallace Mark N. 
Published: September 2019

AbstractThe gaseous free radical, nitric oxide (NO) acts as a ubiquitous neuromodulator, contributing to synaptic plasticity in a complex way that can involve either long term potentiation or depression. It is produced by neuronal nitric oxide synthase (nNOS) which is presynaptically expressed and also located postsynaptically in the membrane and cytoplasm of a subpopulation of each major neuronal type in the ventral cochlear nucleus (VCN). We have used iontophoresis in vivo to study the effect of the NOS inhibitor L‐NAME (L‐NG‐Nitroarginine methyl ester) and the NO donors SIN‐1 (3‐Morpholinosydnonimine hydrochloride) and SNOG (S‐Nitrosoglutathione) on VCN units under urethane anaesthesia. Collectively, both donors produced increases and decreases in driven and spontaneous firing rates of some neurones. Inhibition of endogenous NO production with L‐NAME evoked a consistent increase in driven firing rates in 18% of units without much effect on spontaneous rate. This reduction of gain produced by endogenous NO was mirrored when studying the effect of L‐NAME on NMDA(N‐Methyl‐D‐aspartic acid)‐evoked excitation, with 30% of units showing enhanced NMDA‐evoked excitation during L‐NAME application (reduced NO levels). Approximately 25% of neurones contain nNOS and the NO produced can modulate the firing rate of the main principal cells: medium stellates (choppers), large stellates (onset responses) and bushy cells (primary‐like responses). The main endogenous role of NO seems to be to partly suppress driven firing rates associated with NMDA channel activity but there is scope for it to increase neural gain if there were a pathological increase in its production following hearing loss.