bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Killer cells dampen the pathogenic features of recall responses to influenza infection
Authors: Mooney Jason P. , Qendro Tedi , Keith Marianne , Philbey Adrian W. , Groves Helen T. , Tregoning John S. , Goodier Martin R. , Riley Eleanor M.
Published: November 2019

Despite evidence of augmented Natural Killer (NK) cell responses after influenza vaccination, the role of these cells in vaccine-induced immunity remains unclear. Here, we hypothesized that NK cells might increase viral clearance but possibly at the expense of increased severity of pathology. On the contrary, we found that NK cells serve a homeostatic role during influenza virus infection of vaccinated mice, allowing viral clearance with minimal pathology. Using a diphtheria toxin receptor transgenic mouse model, we were able to specifically deplete NKp46+ NK cells through the administration of diphtheria toxin. Using this model, we assessed the effect of NK cell depletion prior to influenza challenge in vaccinated and unvaccinated mice. NK-depleted, vaccinated animals lost significantly more weight after viral challenge than vaccinated NK intact animals, indicating that NK cells ameliorate disease in vaccinated animals. However, there was also a significant reduction in viral load in NK-depleted, unvaccinated animals indicating that NK cells also constrain viral clearance. Depletion of NK cells after vaccination, but 21 days before infection, did not affect viral clearance or weight loss - indicating that it is the presence of NK cells during the infection itself that promotes homeostasis. Further work is needed to identify the mechanism(s) by which NK cells regulate adaptive immunity in influenza-vaccinated animals to allow efficient and effective virus control whilst simultaneously minimizing inflammation and pathology.
Hubs of long-distance co-alteration in brain pathology
Authors: Cauda Franco , Mancuso Lorenzo , Nani Andrea , Manuello Jordi , Liloia Donato , Gelmini Gabriele , Ficco Linda , Premi Enrico , Duca Sergio , Costa Tommaso
Published: November 2019

The exact mechanisms at the root of pathologic anatomical covariances are still unknown. It is nonetheless becoming clearer that the impact of brain diseases is more convincingly represented in terms of co-alterations rather than in terms of localization of alterations. According to this view, neurological and psychiatric conditions might be seen as whole-brain patterns of modifications. In this context, the physical distance between two co-altered areas may provide insightful information about how pathology develops across the brain, assuming that long-range co-alterations might be relevant features of pathological networks. To demonstrate this hypothesis, we calculated the probability of co-alteration between brain areas across a large database of voxel-based morphometry studies of psychiatric and neurological disorders, and we investigated the physical (Euclidean) distance of the edges of the resulting network. Such analysis produced a series of observations relevant for the understanding of pathology, which range from unanticipated results to the recognition of regions of well-known functional and clinical relevance. For instance, it emphasizes the importance of the anterior and dorsal prefrontal cortices in the distribution of the disease-related alterations, as well as a specular asymmetry of gray matter decreases and increases between the hemispheres. Also, the analyses of schizophrenia and Alzheimer’s disease show that long-distance co-alterations are able to identify areas involved in pathology and symptomatology. Moreover, the good concordance between the measure of the mean physical distance and that of functional degree centrality suggests that co-alterations and connectivity are intimately related. These findings highlight the importance of analyzing the physical distance in pathology, as the areas characterized by a long mean distance may be considered as hubs with a crucial role in the systems of alterations induced by brain diseases.
Transcription-replication conflicts as a source of common fragile site instability caused by BMI1-RNF2 deficiency
Authors: Sanchez Anthony , de Vivo Angelo , Tonzi Peter , Kim Jeonghyeon , Huang Tony T. , Kee Younghoon
Published: November 2019

Common fragile sites (CFSs) are breakage-prone genomic loci, and are considered to be hotspots for genomic rearrangements frequently observed in cancers. Understanding the underlying mechanisms for CFS instability will lead to better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 and RNF2 are suppressors of transcription-replication conflicts (TRCs) and CFS instability. Cells depleted of BMI1 or RNF2 showed slower replication forks and elevated fork stalling. These phenotypes are associated with increase occupancy of RNA Pol II (RNAPII) at CFSs, suggesting that the BMI1-RNF2 complex regulate RNAPII elongation at these fragile regions. Using proximity ligase assays, we showed that depleting BMI1 or RNF2 causes increased associations between RNAPII with EdU-labeled nascent forks and replisomes, suggesting increased TRC incidences. Increased occupancy of a fork protective factor FANCD2 and R-loop resolvase RNH1 at CFSs are observed in RNF2 CRISPR-KO cells, which are consistent with increased transcription-associated replication stress in RNF2-deficient cells. Depleting FANCD2 or FANCI proteins further increased genomic instability and cell death of the RNF2-deficient cells, suggesting that in the absence of RNF2, cells depend on these fork-protective factors for survival. These data suggest that the Polycomb proteins have non-canonical roles in suppressing TRC and preserving genomic integrity.

Author summary

Increasing evidence suggest that instabilities at common fragile sites (CFSs), breakage-prone genomic loci, may be source of genomic aberration seen in cancer cells. Among the proposed mechanisms that can cause CFSs instabilities is the conflict between transcription and replication, and the mechanisms or factors that resolve the possible conflicts are only beginning to be understood. Here we found that deficiency in the Polycomb group proteins BMI1 or RNF2 leads to the CFS instability, and is associated with transcription-associated replication fork stresses. We further found that in the absence of RNF2, cells depend on the Fanconi Anemia fork-protective proteins for genome maintenance and survival. These results underscore that the Polycomb proteins are important for genome maintenance.
A new long-acting GLP-1 derivative 6- KTP ameliorates body weight and lipid metabolism in DIO mice
Authors: Wang Peixiu , Ran Yanhong
Published: November 2019

As a global epidemic, obesity has become the biggest challenge facing global and public health. Glucagon-like peptide-1(GLP-1) has been able to inhibit appetite, slow gastric emptying and reduce body weight. We designed a novel long-acting GLP-1 derivative 6-KTP based on wild-type GLP-1 and performed its pharmacodynamics study on obesity in DIO mice. DIO mice were treated once daily with subcutaneous injections of 6-KTP (1.8 mg/kg body weight), Liraglutide (0.4 mg/kg body weight) or vehicle (phosphate buffered saline (PBS), pH 7.4) for 12 weeks. The results show that 6-KTP decreased food intake, induced anorexia and weight loss, and improved blood lipid and lipid metabolism in DIO mice.
Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
Authors: Apóstolo Nuno , Smukowski Samuel N. , Vanderlinden Jeroen , Condomitti Giuseppe , Rybakin Vasily , ten Bos Jolijn , Trobiani Laura , Portegies Sybren , Vennekens Kristel M. , Gounko Natalia V. , Comoletti Davide , Wierda Keimpe D. , Savas Jeffrey N. , de Wit Joris
Published: November 2019

Synaptic diversity is a key feature of neural circuits. The structural and functional diversity of closely spaced inputs converging on the same neuron suggests that cell-surface interactions are essential in organizing input properties. Here, we analyzed the cell-surface protein (CSP) composition of hippocampal mossy fiber (MF) inputs on CA3 pyramidal neurons to identify regulators of MF-CA3 synapse properties. We uncover a rich cell-surface repertoire that includes adhesion proteins, guidance cue receptors, extracellular matrix (ECM) proteins, and uncharacterized CSPs. Interactome screening reveals multiple ligand-receptor modules and identifies ECM protein Tenascin-R (TenR) as a ligand of the uncharacterized neuronal receptor IgSF8. Presynaptic Igsf8 deletion impairs MF-CA3 synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition of CA3 neurons. Consequently, loss of IgSF8 increases CA3 neuron excitability. Our findings identify IgSF8 as a regulator of CA3 microcircuit development and suggest that combinations of CSP modules define input identity.
The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies
Authors: Diaz Jennifer E. L. , Ahsen Mehmet Eren , Schaffter Thomas , Chen Xintong , Realubit Ronald B. , Karan Charles , Califano Andrea , Losic Bojan , Stolovitzky Gustavo
Published: November 2019

Our ability to predict the effects of drug combinations is limited, in part by limited understanding of how the transcriptional response of two monotherapies results in that of their combination. We performed the first analysis of matched time course RNAseq profiling of cells treated with both single drugs and their combinations. The transcriptional signature of the synergistic combination we studied had unique gene expression not seen in either constituent monotherapy. This can be explained mechanistically by the sequential activation of transcription factors in time in the gene regulatory network. The nature of this transcriptional cascade suggests that drug synergy may ensue when the transcriptional responses elicited by two unrelated individual drugs are correlated. We used these results as the basis of a simple prediction algorithm attaining an AUROC of 0.84 in the prediction of synergistic drug combinations in an independent dataset.
Structured hierarchical models for probabilistic inference from perturbation screening data
Authors: Dirmeier Simon , Beerenwinkel Niko
Published: November 2019

Genetic perturbation screening is an experimental method in biology to study cause and effect relationships between different biological entities. However, knocking out or knocking down genes is a highly error-prone process that complicates estimation of the effect sizes of the interventions. Here, we introduce a family of generative models, called thestructured hierarchical model(SHM), for probabilistic inference of causal effects from perturbation screens. SHMs utilize classical hierarchical models to represent heterogeneous data and combine them with categorical Markov random fields to encode biological prior information over functionally related biological entities. The random field induces a clustering of functionally related genes which informs inference of parameters in the hierarchical model. The SHM is designed for extremely noisy data sets for which the true data generating process is difficult to model due to lack of domain knowledge or high stochasticity of the interventions. We apply the SHM to a pan-cancer genetic perturbation screen in order to identify genes that restrict the growth of an entire group of cancer cell lines and show that incorporating prior knowledge in the form of a graph improves inference of parameters.
Enhanced Cerebral Blood Volume under Normobaric Hyperoxia in the J20-hAPP Mouse Model of Alzheimer’s Disease
Authors: Shabir Osman , Sharp Paul , Rebollar Monica A , Boorman Luke , Howarth Clare , Wharton Stephen B , Francis Sheila E , Berwick Jason
Published: November 2019

Early impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer’s disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6-9 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy by driving an increased baseline blood flow to the brain, thereby potentially enhancing the clearance of beta-amyloid.
Structure refinement of (NH4)3Al2(PO4)3 prepared by ionothermal synthesis in phosphonium based ionic liquids – a redetermination
Authors: Nicholas Christopher P. , Mowat John P.S. , Broach Robert W.
Published: November 2019

After crystallization during ionothermal syntheses in phosphonium-containing ionic liquids, the structure of (NH4)3Al2(PO4)3 [triammonium dialuminum tris(phosphate)] was refined on the basis of powder X-ray diffraction data from a synchrotron source. (NH4)3Al2(PO4)3 is a member of the structural family with formula A
3Al2(PO4)3, where A is a group 1 element, and of which the NH4, K, and Rb forms were previously known. The NH4 form is isostructural with the K form, and was previously solved from single-crystal X-ray data when the material (SIZ-2) crystallized from a choline-containing eutectic mixture [Cooper et al. (2004). Nature, 430, 1012–1017]. Our independent refinement incorporates NH4 groups and shows that these NH4 groups are hydrogen bonded to framework O atoms present in rings containing 12 T sites in a channel along the c-axis direction. We describe structural details of (NH4)3Al2(PO4)3 and discuss differences with respect to isostructural forms.
Entrepreneurial orientation and performance of small and medium-sized enterprises
Authors: Shah Syed Zulfiqar Ali , Ahmad Maqsood
Published: November 2019

Purpose

This paper aims to investigate the effects of entrepreneurial orientation (EO) on the performance of small and medium-sized enterprises (SMEs) with mediating role of differentiation strategy in Pakistan.

Design/methodology/approach

A theoretical framework has been developed to base the hypotheses, as also to determine the exact approach in this study. To establish the influence of EO on the performance of SME, a five-point Likert scale questionnaire has been used to collect data from middle and senior managers who operate in SMEs in the manufacturing sectors. The sample illustrates 166 incumbents, comprising 68.07 per cent from middle management and 31.93 per cent from senior management operating in manufacturing sector of SMEs, by means of a stratified random sampling technique. The collected data were analyzed using SPSS and Amos graphics software. Hypotheses were tested by using structural equation modeling (SEM) technique.

Findings

EO, as a whole, presents a significant positive effect on the performance of SMEs. Moreover, differentiation strategy partially mediated the relationship between EO and performance of SMEs. Two dimensions of EO, proactiveness and risk-taking propensity, strongly increased firm performance while innovativeness, competitive aggressiveness, autonomy and competitive energy did not cause any significant change. The findings differ from the current view of western enterprises that innovativeness (INO) played a major role by increasing performance of SMEs. The results transpired that innovativeness (INO) tends to reduce performance of SMEs, but the p-value did not reach a high significance value.

Research limitations/implications

The main limitation of this empirical study is comparatively a small size of the sample. The analysis of power suggests that a larger sample could have provided more reliable and extensive results. Regardless of that, the analysis of reliability, using the Cronbach's alpha, exhibited the consistency of outcomes in providing an accurate portrait of the EO influences on the performance of SME.

Practical implications

The study verifies that two dimensions of EO have considerable effects on the performance of SMEs, while the others have not, whereas, the EO, as whole, has significant positive effect on performance of SMEs. These findings should be helpful for researchers looking for appropriate performance measures, and for entrepreneurs aiming at getting support for their decisions and evaluating their performance.

Originality/value

The current study appears to be first of its kind focusing on the link between EOs, as whole, and its dimensions, to performance of SMEs and differentiation strategies within the specific context of Pakistan.
Prioritize the key parameters of Vietnamese coffee industries for sustainability
Authors: Do Thi-Nga , Kumar Vimal , Do Manh-Hoang
Published: November 2019

Purpose

The purpose of this paper is to identify the critical parameters of the Vietnam coffee industry and develop a comprehensive structural relationship to rank them for effective sustainable development.

Design/methodology/approach

The team of ten experts, having experience of over eight years in the field of various coffee industries in Vietnam, was created to give scores to multiple parameters. Technique for order of preference by similarity to ideal solution (TOPSIS) technique is used to develop the model for fifteen key parameters and then to rank them.

Findings

From the data analysis and results, marketing and brand innovation, product quality, strategic planning and implementation have emerged as top three key parameters while new technology development, supply chain and logistics management, and alliance-joint venture are identified as the bottom three parameters. The findings provide a rank of parameters that help to other coffee industries to identify their key parameters. Besides, the key parameters defined as necessary inputs show the firms more active and well-prepared comprised of ten companies.

Practical implications

The key parameters of the success of any organization are essential contributions. Aiming to improve organizational performance, metrics should be identified as the source of strength to achieve high productivity, profitability and sustainable business performance.

Originality/value

The emphasis of study on key parameters will help organizations to achieve competitive advantage and high productivity for high sustainability in an organizational context.
CmVVD is involved in fruiting body development and carotenoid production and the transcriptional linkage among three blue‐light receptors in edible fungus Cordyceps militaris
Authors: Zhang Jiaojiao , Wang Fen , Yang Ying , Wang Ying , Dong Caihong
Published: November 2019

Fruiting body development and carotenoid production are light‐induced in Cordyceps militaris. Our previous studies have shown that two blue‐light receptors, CmWC‐1 and CmCRY‐DASH, regulate fruiting body development and secondary metabolism. However, the photosensory system of C. militaris remains unclear. Here, gene deletion of Cmvvd, coding for another blue‐light receptor, resulted in reduced conidiation level and significant promotion of carotenoid content. Cmvvd transcription levels at fruiting body stages were higher than at other stages, and fruiting bodies could not develop normally in ΔCmvvd strains, indicating that Cmvvd might play an important role in fruiting body development. Rhythm loops were not affected in ΔCmvvd strains but were regulated by Cmwc‐1, and the expression of the rhythm regulator gene Cmfrq was dependent on CmWC‐1. Chromatin immunoprecipitation assay confirmed that Cmvvd is the direct target of CmWC‐1 in this fungus. Our results also revealed interdependent transcriptional relationships between Cmwc‐1 and Cmvvd, and between Cmwc‐1 and Cmcry‐DASH. Cmcry‐DASH expression was affected by Cmvvd, and the function‐loss of Cmcry‐DASH might be compensated by the high transcription of Cmvvd. This is the first report of the transcriptional linkage among the three blue‐light receptors in edible fungi and will be helpful for studies of multicellular development in this fungus.
Mbp1, a component of the MluI cell cycle box‐binding complex, contributes to morphological transition and virulence in the filamentous entomopathogenic fungus Beauveria bassiana
Authors: Ding Jin‐Li , Lin Hai‐Yan , Feng Ming‐Guang , Ying Sheng‐Hua
Published: November 2019

The Mbp1 protein functions as a DNA‐binding protein in the MluI cell cycle box‐binding complex and plays significant roles in yeast development. In this study, an ortholog of yeast Mbp1, BbMbp1, was characterized in a filamentous insect mycopathogen, Beauveria bassiana. BbMbp1 plays an important role in morphological changes under aerial and liquid environments. On the aerial surface, BbMbp1 was indispensable for the biogenesis of conidiophores and conidiation. Under submerged conditions, the ∆BbMbp1 mutant displayed abnormal spore‐producing structures, with a dramatic decrease in blastospore yield (~95%). The virulence of the ∆BbMbp1 mutant was notably weakened, which might be due to the defect in in vivo blastospore formation in the insect. Moreover, disruption of BbMbp1 resulted in a substantial reduction in hyphal growth on cadavers. Comparative transcriptomics revealed that BbMbp1 mediated different transcriptomes during the formation processes of conidia and blastospores. Yeast one‐hybrid assays demonstrated that BbMbp1 was required for transcriptional control of a cell wall protein gene, BbCwp, and an integral membrane protein gene, BbImp that played significant roles in conidiation and blastospore formation respectively. Our results demonstrate that BbMbp1 contributes to the morphological transitions in the pathogenic and saprophytic growth of B. bassiana via different genetic pathways.
Corporate social responsibility and financial fraud: evidence from China
Authors: Liao Lin , Chen Guanting , Zheng Dengjin
Published: November 2019

This paper investigates the impact of corporate social responsibility (CSR) on corporate financial fraud in China. We find that CSR scores are negatively associated with fraudulent financial activities, suggesting that CSR firms are less likely to engage in financial fraud. The results also indicate that the negative relation is more significant for CSR performance than CSR disclosure. Additionally, we demonstrate that the negative effect of CSR is more pronounced for firms with voluntary CSR practices, continuous CSR engagements, financial pressure and internal control weaknesses. Overall, we find that CSR is an ethical behaviour that reduces financial misconduct.
Voluntary stopping of eating and drinking in advance directives for adults with late‐stage dementia
Authors: Trowse Philippa
Published: November 2019

Objective

The objective of this paper is to explore the ethical and legal validity of advance directives that request the voluntary stopping of eating and drinking against a backdrop of late‐stage dementia.

Method

Doctrinal research and analysis of primary and secondary materials including Australian legislation, Australian case law and journal articles was undertaken.

Results

There is legal uncertainty in Australia around whether an advance directive to voluntarily stop eating and drinking will be followed should the adult become incompetent.

Conclusion

Voluntary stopping of eating and drinking should be viewed in law as a form of “treatment” that competent adults can nominate in advance directives, thereby providing dementia patients with the opportunity to choose in advance, if they wish, to end their life legally, with dignity and comfort, and in a manner that does not implicate others in criminal behaviour such as assisted suicide, acceleration of death or euthanasia.
Sharp bounds on the relative treatment effect for ordinal outcomes
Authors: Lu Jiannan , Zhang Yunshu , Ding Peng
Published: November 2019

For ordinal outcomes, the average treatment effect is often ill‐defined and hard to interpret. Echoing Agresti and Kateri, we argue that the relative treatment effect can be a useful measure, especially for ordinal outcomes, which is defined as , with and being the potential outcomes of unit under treatment and control, respectively. Given the marginal distributions of the potential outcomes, we derive the sharp bounds on which are identifiable parameters based on the observed data. Agresti and Kateri focused on modeling strategies under the assumption of independent potential outcomes, but we allow for arbitrary dependence.
Quantifying contributions to tournament catches among resident, stocked and hybrid black basses (Micropterus spp.)
Authors: Hargrove John S. , Rogers Mark W. , Kacmar Phillip T.
Published: November 2019

Millions of Florida bass, Micropterus floridanus Lesueur, are stocked annually into populations of largemouth bass, Micropterus salmoides Lacepède, to increase trophy fish abundance. However, little effort has related the role that resultant hybrids make to angler catches. Largemouth bass were sampled from an important recreational fishery subject to extensive Florida bass stocking to address the hypothesis that anglers capture Florida bass, largemouth bass and hybrids at rates equivalent to their overall abundance in the population. Fin clips obtained from tournament angling events (n = 348) and boat‐mounted electrofishing sampling (n = 219) were screened at 38 species‐diagnostic markers and individuals were assigned to genealogical classes using Bayesian clustering algorithms. No significant differences were identified between angler and electrofishing catches providing evidence that hybridised individuals stemming from a long‐term stocking programme may constitute an important contribution to tournament angling catch.
Migration among East and Southeast Asian Economies
Authors: Fong Eric , Shibuya Kumiko , Chen Xi
Published: November 2019

Conventional studies focus on why migration occurs between a particular pair of places. Our study asks a different question: what characteristics of the origin and destination places can explain migration flows between any two places in a region. Our study explores how economic, political, and geographic factors influence bilateral migration flows within a region in which various countries are increasingly being integrated into the regional as well as into the global economy. Drawing from diverse data sources, we explore migration flows among various economies in East and Southeast Asia between 2000 and 2005 and 2005 and 2010. Our analyses yielded two major findings. First, the relationship between economic factors and the volume of migration flows depends on the overall economy in the region. Second, the findings reveal a consistently robust and significant relationship between geographic proximity and migration flow. Implications of these findings are discussed.
How Many Parents Should There Be in a Family?
Authors: Grill Kalle
Published: November 2019

In this article, I challenge the widespread presumption that a child should have exactly two parents. I consider the pros and cons of various numbers of parents for the people most directly affected – the children themselves and their parents. The number of parents, as well as the ratio of parents to children, may have an impact on what resources are available, what relationships can develop between parents and children, what level of conflict can be expected in the family, as well as the costs involved in parenting and the experience of parenting a child. Indirectly, there is also an effect on who will have the opportunity to be a parent, as well as on wider social issues that I mention but do not discuss. Having considered all these factors, I conclude that there is some reason to believe that three or more parents is usually better than one or two, especially if children are to have siblings, which is typically beneficial. However, these reasons are not strong enough to support a general presumption in favor of any particular number. We should therefore jettison the two‐parent presumption and make different numbers of parents more socially accepted as well as legally possible.
Plantaricin bacteriocins: As safe alternative antimicrobial peptides in food preservation—A review
Authors: Abdulhussain Kareem Raghda , Razavi Seyed Hadi
Published: November 2019

Many peptides are excreted by gram‐positive (+) and gram‐negative (−) bacteria, possessing antimicrobial properties, called bacteriocins. Common bacterial species produce bacteriocins are called lactic acid bacteria. Nowadays, plantaricins are natural antimicrobial peptides produced byLactobacillus plantarumstrains have obtained special attention. TheL. plantarumand their bacteriocins have got great importance in different areas as food biopreservatives and/or starters in dairy products, meat products, and fish products also, were used for treating diseases caused by pathogenic bacteria that is, reducing symptoms of irritable bowel syndrome disease (IBS) and decreasing the number of colonies of pathogenic bacteria in the wound‐burning model in mice. Moreover, plantaricins have got a potent protective role against urinary tract infection (UTI). Although there are many studies on the types of bacteriocins and their purification and uses, such as Nisin and Pediocin, there have been no reports in the literature on the characterizations, production, and purification of plantaricins. The present review aims to describe plantaricins and some of their features and applications in general. Also mentioned are the most common methods of isolation and purification.
Evaluation of the Interaction Model of Client Health Behavior‐based multifaceted intervention on patient activation and osteoarthritis symptoms
Authors: Ahn Yang Heui , Ham Ok Kyung
Published: November 2019

Purpose

This study evaluated a multifaceted intervention for osteoarthritis symptoms.

Methods

A cluster randomized controlled trial was conducted with a convenience sample of 90 patients aged between 45 and 82 years, who were recruited from three Community Health Posts (CHPs). The CHPs were randomized into two experimental groups (E1 and E2) and one control group (C). The intervention included health education and counseling combined with exercise classes based on the Interaction Model of Client Health Behavior. Trained community health nurse practitioners led the intervention. Stretching exercise (E1) and walking (E2) combined with muscle strengthening exercise were provided. The instruments included the Patient Activation Measure (PAM), Korean version of the Western Ontario and McMaster Universities Osteoarthritis Index (K‐WOMAC), Stanford Health Assessment Questionnaire Disability Scale (HAQDS), and Center for Epidemiologic Studies Depression Scale (CES‐D). The HAQDS was measured using an ordinal scale, and Likert scales were used for the other instruments. Chi‐square test and analysis of covariance were used;Pvalues <.05 were considered significant. The study was conducted in 2014.

Results

The groups were similar at the baseline (P> .05) except for joint pain and patient activation (P< .05). At post‐test, the changes in the mean scores were significant for joint pain and stiffness, and physical functioning. E2 with walking exercise showed better improvements in joint pain and physical functioning than the other groups (P< .01).

Conclusions

Eight sessions of multifaceted intervention improved the osteoarthritis symptoms. Follow‐up studies will be needed to determine the intermediate and long‐term effects of the multifaceted intervention.
Therapeutic effects of Aconiti Lateralis Radix Praeparata combined with Zingiberis Rhizoma on doxorubicin-induced chronic heart failure in rats based on an integrated approach
Authors: Wen Jian-Xia , Li Rui-Sheng , Wang Jian , Hao Jun-Jie , Qin Wei-Han , Yang Tao , Wang Rui-Lin , Wei Shi-Zhang , Liu Xiao-Yi , Li Hao-Tian , Wang Jia-Bo , Liu Hong-Hong , Zhao Yan-Ling
Published: November 2019

Objectives

This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches.

Methods

Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR.

Key findings

ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e.

Conclusions

The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.
Dehydrodiconiferyl alcohol from Silybum marianum (L.) Gaertn accelerates wound healing via inactivating NF-κB pathways in macrophages
Authors: Hu Xu , Qin Ningbo , Xue Jingjing , Li Siqi , Huang Xiaofang , Sun Jianan , Xu Fanxing , Li Zhanlin , Li Dahong , Hua Huiming
Published: November 2019

Objectives

The aim of this study was to investigate the molecular mechanisms of the efficacy of lignin compound dehydrodiconiferyl alcohol (DHCA) isolated from Silybum marianum (L.) Gaertn in improving wound healing. These findings preliminarily brought to light the promising therapeutic potential of DHCA in skin wound healing.

Methods

First, the effect of DHCA on healing in vivo was studied using a full-thickness scalp wound model of mice by topical administration. Histopathological examinations were then conducted by haematoxylin and eosin (H&E), Masson’s trichrome staining and the immunofluorescence assay. Second, we further examined the anti-inflammatory mechanism of DHCA in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by immunofluorescence assay and Western blot analysis.

Key findings

DHCA could promote scalp wound healing in mice by enhancing epithelial cell proliferation and collagen formation and reducing inflammatory cells infiltration. Moreover, the NF-κB nuclear translocation was suppressed remarkably by DHCA administration in connective tissue of healing area. DHCA was also shown to inhibit production of nitric oxide (NO) and interleukin (IL)-1β with downregulated inducible nitric oxide synthase (iNOS) expression in LPS-induced RAW 246.7 cells. More importantly, DHCA administration upregulated p-IκBα expression and induced nuclear translocation of NF-κB without affecting its expression.

Conclusions

Our study indicated that DHCA exerted anti-inflammatory activity through inactivation of NF-κB pathways in macrophages and subsequently improved wound healing.
Examining the Impact of Religious Initiation Rites on Religiosity and Disaffiliation over Time
Authors: Perry Samuel L. , Longest Kyle C.
Published: November 2019

Early religion scholars stressed the importance of institutionalized “rites of passage” to integrate and reinvigorate groups themselves. Surprisingly, little work, however, has explored the efficacy of such rites for the religious lives of individuals. Although research has examined the transformative role of semi‐institutionalized rites like short‐term mission trips and pilgrimages, we shift the focus to consider the potential influence of more fundamental initiation rites such as baptism, first communion, and bar/bat mitzvahs. Utilizing surveys 1 and 4 of the National Study of Youth and Religion and focusing on overall religiosity and disaffiliation as the outcomes, we examine whether experiencing a religious rite of passage during or before one's teenage years predicts the religious outcomes of young adults. We find no difference in religiosity over time between persons who experienced a religious rite passage and those who did not. However, those who underwent a religious rite of passage were 30 percent less likely to disaffiliate between data collection points. Tests for interactions show that the influence of such initiation rites does not vary across religious traditions. Findings suggest the experience of baptism, bar/bat mitzvah, confirmation, or other rites of passage matter primarily as durable markers of social identity, binding adherents to their faith community, if only nominally.
Nonlinear Factor‐Augmented Predictive Regression Models with Functional Coefficients
Authors: Li Degui , Tosasukul Jiraroj , Zhang Wenyang
Published: November 2019

This article introduces a new class of functional‐coefficient predictive regression models, where the regressors consist of auto‐regressors and latent factor regressors, and the coefficients vary with certain index variable. The unobservable factor regressors are estimated through imposing an approximate factor model on high dimensional exogenous variables and subsequently implementing the classical principal component analysis. With the estimated factor regressors, a local linear smoothing method is used to estimate the coefficient functions (with appropriate rotation) and obtain a one‐step ahead nonlinear forecast of the response variable, and then a wild bootstrap procedure is introduced to construct the prediction interval. Under regularity conditions, the asymptotic properties of the proposed methods are derived, showing that the local linear estimator and the nonlinear forecast using the estimated factor regressors are asymptotically equivalent to those using the true latent factor regressors. The developed model and methodology are further generalized to the factor‐augmented vector predictive regression with functional coefficients. Finally, some extensive simulation studies and an empirical application to forecast the UK inflation are given to examine the finite‐sample performance of the proposed model and methodology.
Assessing the acceptability and efficacy of teens taking charge: Transplant—A pilot randomized control trial
Authors: Korus Moira , Cruchley Elizabeth , Calic Masa , Gold Anna , Anthony Samantha J. , Parekh Rulan S. , Stinson Jennifer N.
Published: November 2019

Background

Adolescents who have undergone SOT are at heightened risk for graft failure. This pilot randomized controlled trial aimed to determine the feasibility and obtain preliminary estimates of efficacy of the online TTC program.

Methods

TTC is a web‐based self‐management program for adolescent SOT patients. Participants—kidney or liver transplant candidates or recipients—were enrolled over a 2‐year period and randomized to either an intervention group that accessed TTC or a control group that did not access the program. Outcome measures included feasibility, how much the program was utilized, and pre‐ and post‐intervention health‐related outcomes evaluating self‐management, self‐efficacy, mood, use of healthcare services, and knowledge. Semi‐structured interviews were conducted with participants post‐intervention.

Results

Forty‐two participants were enrolled in the study. Participants in the intervention group expressed that they enjoyed learning about other teens’ experiences, but reported barriers to accessing the site, such as being too busy, computer being too slow, and not being able to access the site on their mobile device. Time spent using the website was low for the majority of participants. Patients less than 1‐year post‐transplant accessed TTC more than patients who had their transplant for longer. No significant differences were found for health‐related outcomes between groups.

Conclusions

No differences in health‐related outcomes were found between groups. Further studies that examine barriers to engagement with web‐based education tools are warranted.
Long‐Circulating Prostate‐Specific Membrane Antigen‐Targeted NIR Phototheranostic Agent
Authors: Overchuk Marta , Damen Martha P.F. , Harmatys Kara M. , Pomper Martin G. , Chen Juan , Zheng Gang
Published: November 2019

Targeted photodynamic therapy (PDT) combined with image‐guided surgical resection is a promising strategy for precision cancer treatment. Prostate‐specific membrane antigen (PSMA) is an attractive target due to its pronounced overexpression in a variety of tumors, most notably in prostate cancer. Recently, we reported a pyropheophorbide‐based PSMA‐targeted agent, which exhibited long plasma circulation time and effective tumor accumulation. To further advance PSMA‐targeted photodynamic therapy by harvesting tissue‐penetrating properties of the NIR light, we developed a bacteriochlorophyll‐based PSMA‐targeted photosensitizer (BPP), consisting of three building blocks: (1) a PSMA‐affinity ligand, (2) a peptide linker to prolong plasma circulation time and (3) a bacteriochlorophyll photosensitizer for NIR fluorescence imaging and photodynamic therapy (Qy absorption maximum at 750 nm). BPP exhibited excellent PSMA‐targeting selectivity in both subcutaneous and orthotopic mouse models. The nine D‐peptide linker in BPP structure prolonged its plasma circulation time (12.65 h). Favorable pharmacokinetic properties combined with excellent targeting selectivity enabled effective BPP tumor accumulation, which led to effective PDT in a subcutaneous prostate adenocarcinoma mouse model. Overall, bright NIR fluorescence of BPP enables effective image guidance for surgical resection, while the combination of its targeting capabilities and PDT activity allows for potent and precise image‐guided photodynamic treatment of PSMA‐expressing tumors.
Effects of cultural institutes on bilateral trade and FDI flows: Cultural diplomacy or economic altruism?
Authors: Demir Firat , Im Hyeonjin
Published: November 2019

The number of cultural institutes from major developed and developing countries increased significantly in the last twenty years. In this paper, using cross‐sectional and panel data analysis on bilateral trade in goods and services, and FDI inflows and outflows, we examine the economic effects of 1,266 cultural institutes from China, France, Germany, Japan, Portugal, Spain, Turkey and UK for the period of 1990–2015. The empirical results suggest that cultural institutes have significantly positive trade and FDI enhancing effects, which are persistent over time. However, these effects are most robust only with goods exports and FDI outflows. Furthermore, the economic effects of cultural institutes are not homogenous across destinations and are the strongest for developed rather than developing host countries. There is also significant heterogeneity among cultural institutes with significant differences in their economic effects on different types of bilateral trade and FDI flows.
Trade configurations in Asia: Assessing de facto and de jure regionalism
Authors: Gopalan Sasidaran , Nguyen Trieu Duong Luu , Rajan Ramkishen S.
Published: November 2019

Given the backdrop of significant uncertainties largely propelled by the ongoing trade spat between the United States and China, to what degree can the Asian region move forward in terms of de facto trade integration? Drawing on the new economic geography literature, this paper offers new insights into the literature on trade regionalism in Asia by empirically illustrating how Asian economies can tap into the regional market potential. Specifically, the paper examines the scope for further de facto integration among the Asian countries engaged in the negotiation for the Regional Comprehensive Economic Partnership (RCEP) Agreement by estimating foreign market potential (FMP) indices. To preview the main findings, the empirical analysis demonstrates that the share of intra‐regional trade in total RCEP trade flows and, consequently, the ratio between within‐ and outside‐RCEP trades are significantly lower than what they could potentially be. The paper makes a case that the enhancement of de jure integration among these economies through the RCEP must be accompanied by efforts to improve de facto integration.
Challenge to Collect Empirical Data for Human Reliability Analysis—Illustrated by the Difficulties in Collecting Empirical Data on the Performance-Shaping Factor Complexity
Authors: Laumann Karin , Skogstad Martin Rasmussen
Published: November 2019

This paper discusses the challenges with collecting positivistic empirical data (objective, observable, reliable, replicable, experimental, and true) in human reliability analysis (HRA), and illustrates it by presenting the difficulties in collecting empirical data on the performance-shaping factor (PSF) complexity. The PSF complexity was chosen to illustrate the difficulties with empirically collecting data because it is included in many HRA guidelines and it has been discussed as an important PSF to understand error rates in large accident scenarios. This paper discusses the challenges with collecting empirical data from a pure positivistic paradigm with experiments, as well as from literature reviews and data from event reports, training, and operations. The paper concludes that because of all the challenges with the positivistic empirical data collections methods in HRA, we should discuss whether experts' judgements could be a better approach to obtain HRA data and error rates. In a postpositivistic view, qualitative data or experts' judgments could also be looked at as empirical data if the data were collected in a systematic and transparent way.
Analysis and Estimation of Human Errors From Major Accident Investigation Reports
Authors: Morais Caroline , Moura Raphael , Beer Michael , Patelli Edoardo
Published: November 2019

Risk analyses require proper consideration and quantification of the interaction between humans, organization, and technology in high-hazard industries. Quantitative human reliability analysis approaches require the estimation of human error probabilities (HEPs), often obtained from human performance data on different tasks in specific contexts (also known as performance shaping factors (PSFs)). Data on human errors are often collected from simulated scenarios, near-misses report systems, and experts with operational knowledge. However, these techniques usually miss the realistic context where human errors occur. The present research proposes a realistic and innovative approach for estimating HEPs using data from major accident investigation reports. The approach is based on Bayesian Networks used to model the relationship between performance shaping factors and human errors. The proposed methodology allows minimizing the expert judgment of HEPs, by using a strategy that is able to accommodate the possibility of having no information to represent some conditional dependencies within some variables. Therefore, the approach increases the transparency about the uncertainties of the human error probability estimations. The approach also allows identifying the most influential performance shaping factors, supporting assessors to recommend improvements or extra controls in risk assessments. Formal verification and validation processes are also presented.