bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial lipopolysaccharide induces settlement and metamorphosis in a marine larva
Authors: Freckelton Marnie L. , Nedved Brian T. , Cai You-Sheng , Cao Shugeng , Turano Helen , Alegado Rosanna A. , Hadfield Michael G.
Published: December 2019

How larvae of the many phyla of marine invertebrates find places appropriate for settlement, metamorphosis, growth and reproduction is an enduring question in marine science. Biofilm induced metamorphosis has been observed in marine invertebrate larvae from nearly every major marine phylum. Despite the widespread nature of this phenomenon the mechanism of induction remains poorly understood. The serpulid polychaeteHydroides elegansis a well-established model for investigating bacteria-induced larval development. A broad range of biofilm bacterial species elicit larval metamorphosis inH. elegansvia at least two mechanisms, including outer membrane vesicles and phage-tail bacteriocins. We investigated the interaction between larvae ofH. elegansand the inductive bacteriumCellulophaga lytica, which produces an abundance of OMVs but not phage-tail bacteriocins. We asked whether the OMVs ofC. lyticainduce larval settlement due to cell membrane components or through delivery of specific cargo. Employing a biochemical structure-function approach with a strong ecological focus, the cells and outer membrane vesicles produced byC. lyticawere interrogated to determine the nature of the inductive molecule. Here we report that the cue produced byC. lyticathat induces larvae ofH. elegansto metamorphose is lipopolysaccharide (LPS). The widespread prevalence of LPS and its associated taxonomic and structural variability suggest it may be a broadly employed cue for bacterially induced larval settlement of marine invertebrates.

Significance Statement

New surfaces in the sea are quickly populated by dense communities of invertebrate animals, whose establishment and maintenance require site-specific settlement of larvae from the plankton. Although it is recognized that larvae selectively settle in sites where they can metamorphose and thrive, and that the biofilm bacteria residing on these surfaces supply inductive cues, the nature of the cues used to identify ‘right places’ has remained enigmatic. In this paper, we reveal that lipopolysaccharide (LPS) from the outer membrane of a marine Gram-negative bacterium cue metamorphosis for a marine worm and discuss the likelihood that LPS provides the variation necessary to explain settlement site selectivity for many of the bottom-living invertebrate animals that metamorphose in response to bacterial biofilms.
Management, Analyses, and Distribution of the MaizeCODE Data on the Cloud
Authors: Wang Liya , Lu Zhenyuan , delaBastide Melissa , Van Buren Peter , Wang Xiaofei , Ghiban Cornel , Regulski Michael , Drenkow Jorg , Xu Xiaosa , Ortiz-Ramirez Carlos , Fernandez-Marco Cristina , Goodwin Sara , Dobin Alexander , Birnbaum Kenneth D. , Jackson David P. , Martienssen Robert A. , McCombie William R. , Micklos David A. , Schatz Michael C. , Ware Doreen H. , Gingeras Thomas R.
Published: November 2019

MaizeCODE is a project aimed at identifying and analyzing functional elements in the maize genome. In its initial phase, MaizeCODE assayed up to five tissues from four maize strains (B73, NC350, W22, TIL11) by RNA-Seq, Chip-Seq, RAMPAGE, and small RNA sequencing. To facilitate reproducible science and provide both human and machine access to the MaizeCODE data, we enhanced SciApps, a cloud-based portal, for analysis and distribution of both raw data and analysis results. Based on the SciApps workflow platform, we generated new components to support the complete cycle of MaizeCODE data management. These include publicly accessible scientific workflows for the reproducible and shareable analysis of various functional data, a RESTful API for batch processing and distribution of data and metadata, a searchable data page that lists each MaizeCODE experiment as a reproducible workflow, and integrated JBrowse genome browser tracks linked with workflows and metadata. The SciApps portal is a flexible platform that allows the integration of new analysis tools, workflows, and genomic data from multiple projects. Through metadata and a ready-to-compute cloud-based platform, the portal experience improves access to the MaizeCODE data and facilitates its analysis.
Spatial organization of the mouse chromosomes influences the landscape of intrachromosomal exchange aberration breakpoints
Authors: Eidelman Y.A. , Salnikov I.V. , Slanina S.V. , Andreev S.G.
Published: November 2019

How 3D chromosome organization affects chromosomal aberrations is an important unresolved question in cell and radiation biology. In interphase the chromosomes form territories where chromatin folds into quite heterogeneous states. The mechanisms determining the spectrum of chromosome conformations remain poorly understood. We introduced the polymer model of mouse chromosome and generated the ensemble of 3D conformations. The chromosome model was validated against independent Hi-C (high-throughput chromosome conformation capture) data. The model described well Hi-C contact heatmap for chromosome 18 in pro-B mouse cells, both ATM-deficient and wild-type. We used the chromosome model to assess the role of chromosome structure in breakpoint distribution for intrachromosomal exchange aberrations. We investigated the effect of elevated frequency of breakpoints outside of the region of enzymatic breaksite. Chromosome aberration model explained breakpoint distribution under recurrent and ionizing radiation-induced DNA double-strand breaks in mouse chromosome 18 on the basis of contact-first mechanism. Overall, our results provide a framework for assessment of role of chromosome 3D organization on chromosome aberrations following DNA damage of different origin.
Estimating animal density in three dimensions using capture-frequency data from remote detectors
Authors: Vargas Soto Juan S. , Castañeda Rowshyra A. , Mandrak Nicholas E. , Molnár Péter K.
Published: November 2019

Remote detectors are being used increasingly often to study aquatic and aerial species, for which movement is significantly different from terrestrial species. While terrestrial camera-trapping studies have shown that capture frequency, along with the species’ movement speed and detector specifications can be used to estimate absolute densities, the approach has not yet been adapted to cases where movement occurs in three dimensions. Frameworks based on animal movement patterns allow estimating population density from camera-trapping data when animals are not individually distinguishable.

Here we adapt one such framework to three-dimensional movement to characterize the relationship between population density, animal speed, characteristics of a remote sensor’s detection zone, and detection frequency. The derivation involves defining the detection zone mathematically and calculating the mean area of the profile it presents to approaching individuals.

We developed two variants of the model – one assuming random movement of all individuals, and one allowing for different probabilities for each approach direction (e.g. that animals more often swim/fly horizontally than vertically). We used computer simulations to evaluate model performance for a wide range of animal and detector densities. Simulations show that in ideal conditions the method approximates true density well, and that estimates become increasingly accurate using more detectors, or sampling for longer. Moreover, the method is robust to invalidation of assumptions, accuracy is decreased only in extreme cases where all detectors are facing the same way.

We provide equations for estimating population density from detection frequency and outline how to estimate the necessary parameters. We discuss how environmental variables and species-specific characteristics affect parameter estimates and how to account for these differences in density estimations.

Our method can be applied to common remote detection methods (cameras and acoustic detectors), which are currently being used to study a diversity of species and environments. Therefore, our work may significantly expand the number and diversity of species for which density can be estimated.
Nucleosides rescue replication-mediated genome instability of human pluripotent stem cells
Authors: Halliwell Jason A. , Frith Thomas J. R. , Laing Owen , Price Christopher J , Bower Oliver J. , Stavish Dylan , Gokhale Paul J. , Hewitt Zoe , El-Khamisy Sherif F. , Barbaric Ivana , Andrews Peter W.
Published: November 2019

Human pluripotent stem cells (PSC) often acquire genetic changes on prolonged culture, which pose concerns for their use in research and regenerative medicine (Amps et al., 2011, Seth et al., 2011). The acquisition of these changes during culture necessarily first requires mutation and then selection of those mutations that provide a growth advantage. Whilst selection accounts for the recurrent nature of the variants commonly reported (Draper et al., 2004, Olariu et al., 2010), the mechanisms of mutation in PSC remain largely elusive. Here we show that, in contrast to somatic cells, human PSC have an increased susceptibility to DNA damage and mitotic errors, both of which are caused by heightened replication stress in PSC and this can be alleviated by culture with exogenous nucleosides. These results reflect the requirement for rapid replication of human PSC enabled by a truncated G1 (Becker et al., 2006, Becker et al., 2010) that impairs the preparation of these cells for the ensuing DNA replication. A similar relationship has been shown in relation to chromosomal instability in cancer cells (Burrell et al., 2013, Wilhelm et al., 2019) but PSC differ by replication stress triggering apoptosis (Desmarais et al., 2012, Desmarais et al., 2016). Nevertheless, evasion of this response still leads to the appearance of genetic variants that are of concern for regenerative medicine. The inclusion of nucleosides into culture media greatly improves the efficiency of human PSC culture and minimises the acquisition of genomic damage.
Molecular mechanisms behind global distribution of earthworm revealed by the genome
Authors: Wang Xing , Zhang Yi , Zhang Yufeng , Kang Mingming , Li Yuanbo , James Samuel W , Yang Yang , Bi Yanmeng , Jiang Hao , Zhou Xin , Zhao Yi , Sun Zhenjun
Published: November 2019

Earthworms (Annelida: Crassiclitellata), are widely distributed around the world due to their great adaptability. However, lack of a high-quality genome sequence prevents gaining the many insights into physiology, phylogeny, and genome evolution that could come from a good earthworm genome. Herein, we report a complete genome assembly of the earthworm Amynthas corticis of about 1.2 Gb, based on a strategy combining third-generation long-read sequencing and Hi-C mapping. A total of 29,256 protein-coding genes are annotated in this genome. Analysis of resequencing data indicates that this earthworm is a triploid species. Furthermore, gene family evolution analysis shows that comprehensive expansion of gene families in the earthworm genome has produced more defensive functions compared with other species in Annelida. Quantitative proteomic iTRAQ analysis shows 97 immune related proteins and 16S rDNA sequences shows 88 microbes with significantly response to pathogenic Escherichia coli O157:H7. Our genome assembly provides abundant and valuable resources for the earthworm research community, serving as a first step toward uncovering the mysteries of this species, may explain its powerful defensive functions adapt to complex environment and invasion from molecular level.
RIF1-Long promotes G1 phase 53BP1 nuclear bodies to protect against replication stress
Authors: Watts Lotte P. , Natsume Toyoaki , Saito Yuichiro , Garzón Javier , Kanemaki Masato T. , Hiraga Shin-ichiro , Donaldson Anne D.
Published: December 2019

Human cells lacking RIF1 are highly sensitive to replication inhibitors, but the reasons for this sensitivity have been enigmatic. Here we show that RIF1 must be present both during replication stress and in the ensuing recovery period to promote cell survival. Of two isoforms produced by alternative splicing, we find that RIF1-Long alone can protect cells against replication inhibition, but RIF1-Short is incapable of mediating protection. Consistent with this isoform-specific role, RIF1-Long is required to promote the formation of the 53BP1 nuclear bodies that protect unrepaired damage sites in the G1 phase following replication stress. Overall, our observations show that RIF1 is needed at several cell cycle stages after replication insult, with the RIF1-Long isoform playing a specific role during the ensuing G1 phase in damage site protection.
Skin Lesions Classification Using Deep Learning Based on Dilated Convolution
Authors: Ratul Md. Aminur Rab , Mozaffari M. Hamed , Lee Won-Sook , Parimbelli Enea
Published: December 2019

The prediction of skin lesions is a challenging task even for experienced dermatologists due to a little contrast between surrounding skin and lesions, the visual resemblance between skin lesions, fuddled lesion border, etc. An automated computer-aided detection system with given images can help clinicians to prognosis malignant skin lesions at the earliest time. Recent progress in deep learning includes dilated convolution known to have improved accuracy with the same amount of computational complexities compared to traditional CNN. To implement dilated convolution, we choose the transfer learning with four popular architectures: VGG16, VGG19, MobileNet, and InceptionV3. The HAM10000 dataset was utilized for training, validating, and testing, which contains a total of 10015 dermoscopic images of seven skin lesion classes with huge class imbalances. The top-1 accuracy achieved on dilated versions of VGG16, VGG19, MobileNet, and InceptionV3 is 87.42%, 85.02%, 88.22%, and 89.81%, respectively. Dilated InceptionV3 exhibited the highest classification accuracy, recall, precision, and f-1 score and dilated MobileNet also has high classification accuracy while having the lightest computational complexities. Dilated InceptionV3 achieved better overall and per-class accuracy than any known methods on skin lesions classification to the best of our knowledge while experimenting with a complex open-source dataset with class imbalances.
Preliminary design of a box-wing VTOL UAV
Authors: Palaia Giuseppe , Cipolla Vittorio , Binante Vincenzo , Rizzo Emanuele
Published: December 2019

Purpose

This paper aims to present a preliminary study on a disruptive vertical take-off and landing (VTOL) configuration based on the best wing system concept by L. Prandtl.

Design/methodology/approach

A preliminary design has been addressed from several points of views: a conceptual design has been carried out thanks to in-house optimization tool; aerodynamic performances, propulsion design and mechanical design have been addressed to make the first prototype for preliminary vertical flight tests.

Findings

The study shows the feasibility of box-wing configuration for VTOL aircraft.

Practical implications

The work shows a general design procedure for box-wing unmanned air vehicle (UAV) configuration. The study of this configuration can be easily adopted in wider range, from UAV to general aviation. In the last category, it can be a promising configuration for the future of urban air mobility.

Originality/value

This work lays the foundation for studying and testing box-wing configuration for unmanned VTOL aircraft. The design procedure can be scaled to manned aircraft belonging to general aviation aircraft.
Sustainability disclosure through virtual community: the case of the wine sector
Authors: Fait Monica , Vrontis Demetris , Maizza Amedeo , Cavallo Federica
Published: December 2019

Purpose

The purpose of this paper is to observe how the motivational engagement system of the consumers should be established so that communities of practice became a driver to reducing the informative asymmetries of sustainability.

Design/methodology/approach

The paper proposes a conceptual framework called connection, discussion and influence (CDI), along which the motivational dimensions to disclose sustainability can be formed. The framework has been tested on 200 firms in the Italian wine industry. A correlation analysis proved to be suitable for identifying groups of representative variables representing the engagement motivations that characterize participation in sustainability-oriented virtual communities.

Findings

The findings of this paper suggest that the pro-social behavior represented by the exchange of knowledge oriented toward sustainability is enhanced by the engagement of online community members. This happens when the online community is structured so as to activate a virtuous circle between CDI.

Research limitations/implications

The main limitation of this study is the interviewees do not actually participate in a virtual community, but have only been asked if they would be potentially interested in participating in one, and about the importance they give to specific motivations.

Practical implications

The paper provides important reflections for companies operating in the wine industry that have been called to intervene in the disclosure of sustainability.

Originality/value

The virtuous circle described here is the main contribution of the paper, as it can serve as a driver for managers of virtual communities that choose to disclose their idea of sustainability to reduce informative asymmetries and to engage consumers.
Physical properties and organoleptic evaluation of gluten-free bread from proso millet
Authors: Woomer Joseph , Singh Manjot , Vijayakumar Paul Priyesh , Adedeji Akinbode
Published: December 2019

Purpose

Gluten-free (GF) foods have gained momentum among consumers due to an increase in incidence and awareness of gluten sensitivity and intolerance. Millet is a GF grain with nutritive qualities comparable to other cereals. However, it was not clear how millet-based GF products would be accepted, leading to the goal of this research. Therefore, the purpose of this paper is to evaluate the effect of formulation on physical properties and consumer preference of millet-based GF bread.

Design/methodology/approach

Three bread formulations were used: proso millet flour (100 percent), proso millet flour–corn starch (1:1), and proso millet flour–potato starch (1:1). Physical and sensory properties were statistically evaluated.

Findings

Starch addition to the bread formulation had a significant influence on bread volume, color and firmness. A consumer’s age, gluten intolerance and familiarity with millet products did influence the frequency of consumption of GF products. Gluten-intolerant panelists consumed GF products more often than others who are not. Older panelists reported consuming more GF products than younger panelists. Gender also had a significant effect on consumers’ preference for overall acceptability and crumb aroma. The formulation had a significant effect on consumers’ preference of crust color and crumb aroma.

Practical implications

The paper presents an understanding of how starch addition modulates bread properties for the GF market.

Originality/value

In this paper, the authors explored a novel approach to use different starches and proso millet for making GF bread and determined sensory responses based on demographics like age, celiac diagnosis and familiarity with GF foods. This vital information will help processors to determine the portion of the market to target and the formulation to explore further.
Balancing artistic and financial performance: is collaborative governance the answer?
Authors: Fanelli Simone , Donelli Chiara Carolina , Zangrandi Antonello , Mozzoni Isabella
Published: December 2019

Purpose

Opera houses have been traditionally publicly financed in many western countries. However, today many opera houses are facing serious financial troubles, due to the recent financial crisis. There is thus a widespread public debate on measures to ensure agency efficiency for performing arts organizations. Focusing on the reform implemented recently in Italy, which submitted opera houses that had severe financial difficulties to a recovery plan and encouraged forms of collaborative governance (CG), the purpose of this paper is to investigate the impact of CG on the performance of the arts sector.

Design/methodology/approach

Multiple case studies are used, on longitudinal data from multiple sources over a period of up to five years, in order to triangulate the narrative of financial and artistic performance and ensure trustworthiness. The study thus spans the period before the Bray Law came into force (2013) and covers the entire period in which recovery plans were implemented.

Findings

The analysis explores how opera houses are building sustainability for themselves and the community in terms of financial and artistic performance through CG. Various forms of CG adopted yielded positive results. Furthermore, more robust forms of CG generated better performance, especially from a financial point of view.

Originality/value

This paper adds to the limited knowledge of CG in the non-profit sector by bridging the fields of agency performance and CG. It discusses how the introduction of forms of CG can build up long-term sustainability, solving the dilemma of how to achieve financial equilibrium without compromising artistic quality, focusing on the case of opera houses, which are notably affected by Baumol’s cost disease.
What attracts vehicle consumers’ buying
Authors: Zhou Fuli , Lim Ming K. , He Yandong , Pratap Saurabh
Published: December 2019

Purpose

The increasingly booming e-commerce development has stimulated vehicle consumers to express individual reviews through online forum. The purpose of this paper is to probe into the vehicle consumer consumption behavior and make recommendations for potential consumers from textual comments viewpoint.

Design/methodology/approach

A big data analytic-based approach is designed to discover vehicle consumer consumption behavior from online perspective. To reduce subjectivity of expert-based approaches, a parallel Naïve Bayes approach is designed to analyze the sentiment analysis, and the Saaty scale-based (SSC) scoring rule is employed to obtain specific sentimental value of attribute class, contributing to the multi-grade sentiment classification. To achieve the intelligent recommendation for potential vehicle customers, a novel SSC-VIKOR approach is developed to prioritize vehicle brand candidates from a big data analytical viewpoint.

Findings

The big data analytics argue that “cost-effectiveness” characteristic is the most important factor that vehicle consumers care, and the data mining results enable automakers to better understand consumer consumption behavior.

Research limitations/implications

The case study illustrates the effectiveness of the integrated method, contributing to much more precise operations management on marketing strategy, quality improvement and intelligent recommendation.

Originality/value

Researches of consumer consumption behavior are usually based on survey-based methods, and mostly previous studies about comments analysis focus on binary analysis. The hybrid SSC-VIKOR approach is developed to fill the gap from the big data perspective.
What drives the impact of women directors on firm performance? Evidence from intellectual capital efficiency of US listed firms
Authors: Shahzad Faisal , Hussain Baig Mushahid , Rehman Ijaz Ur , Latif Fawad , Sergi Bruno S.
Published: December 2019

Purpose

The purpose of this paper is to study whether the presence of women directors on the corporate board influences financial performance (FP). To examine the underlying causal mechanism, the authors modeled firm-level intellectual capital efficiency (ICE) in the relationshipbetween board gender diversity (BGD) and FP.

Design/methodology/approach

Using a sample of 5,879 US firms, a structural model of BGD, IC and FP is conceptualized by accounting for the endogeneity issues and alternative measures of the key variables in the empirical framework. In the model, the percentage of women directors is taken as BGD measures and value-added intellectual coefficient as an IC performance measure, considering governance and corporate performance measures.

Findings

The authors find a significant impact of BGD on FP. In particular, the results suggest: BGD is linked to IC; the influence of board gender diversity on the FP is indirect; and ICE fully mediates the relationship between BGD and FP.

Originality/value

To the best of the author’s knowledge, no study has empirically investigated whether the firm-level IC performance explains the influence of BGD on FP. Drawing on the resource-based view and organizational learning theory of the firm, the authors empirically modeled the relationship between BGD and FP through a mediation mechanism of firm-level ICE to fill the void in the literature.
Service quality, religiosity, customer satisfaction, customer engagement and Islamic bank’s customer loyalty
Authors: Abror Abror , Patrisia Dina , Engriani Yunita , Evanita Susi , Yasri Yasri , Dastgir Shabbir
Published: December 2019

Purpose

The purpose of this study is to investigate the influential factors of customer loyalty to Islamic banks, namely, service quality, customer satisfaction, customer engagement and religiosity.

Design/methodology/approach

This study is a survey of 335 Islamic bank customers in West Sumatra, Indonesia. This research deployed purposive sampling and analyzed the data by using covariance-based structural equation modeling.

Findings

Service quality has a positive and significant impact on customer satisfaction. Religiosity has a significant and negative moderating impact on the service quality–customer satisfaction relationship. Service quality has no significant influence on customer loyalty. Customer satisfaction is a significant antecedent of customer engagement and loyalty. Finally, customer engagement has a significant and positive effect on customer loyalty.

Research limitations/implications

This study is a combination of cross-sectional and a single-country case. Accordingly, the results may not be representative of other countries. Similar studies in longitudinal data collection are conducted in other countries (e.g. ASEAN countries), which would therefore be worthwhile. Some antecedents of customer loyalty have been neglected in this study (e.g. customer value co-creation and customer commitment); hence, the future study may investigate those factors.

Practical implications

By considering these Islamic banks’ antecedents, the Islamic banks might enhance their customer loyalty. Also, this study has revealed the moderating role of religiosity in a loyalty relationship. Therefore, it will give insights for the Islamic bank managers in decision-making.

Originality/value

This study has revealed the moderating role of religiosity on the link between service quality and customer satisfaction in Islamic banks, which is, to the authors’ knowledge, neglected in the previous studies. The customers with high religiosity will have a higher standard of satisfaction and demand a better service quality than the customers with low religiosity. This study has also examined the relationships between service quality, religiosity, customer satisfaction, customer engagement and loyalty as a whole, which have been limited previously.
Annuities are not securities: the regulatory Island in Illinois
Authors: Schaff Michele L. , Schaff Jeffery E.
Published: December 2019

Purpose

Discusses the significance of the Illinois Supreme Court ruling in Van Dyke v. White, which clarified that annuities are not securities in the state of Illinois, with a particular focus on the ramifications to insurance, brokerage and investment advisory standards of care as well as causes of action for breaches thereof.

Design/methodology/approach

Describes the Court’s ruling as it relates to the industry going forward. Does not discuss the specifics of the plaintiff’s case or history.

Findings

The statutory language of Illinois’ securities laws specifically excludes annuities from the definition of securities. For this reason, the Illinois Department of Insurance has sole authority over regulating annuities, giving the Illinois Department of Securities no authority, except to the extent there is an investment advisor breach pursuant to §12(J) of the Illinois Securities Law of 1953. The industry has yet to react or adjust to the Court’s ruling, so there may be a future wave of reactions.

Originality/value

Assists the reader in understanding the unique regulatory environment of annuities in Illinois, the relevant standards of care related to annuity advice and transactions, and remedies for grievances after the Illinois Supreme Court ruling in Van Dyke v. White.
Resonanzfähigkeit: resonance capability in Luhmannian systems theory
Authors: Clark Carlton
Published: December 2019

Purpose

This paper aims to contribute to the sociological literature on moral communication and disciplinary apparatuses in a functionally differentiated society. It combines Luhmannian and Foucauldian theories to further the understanding of social system complexity.

Design/methodology/approach

The paper draws on the work of Niklas Luhmann, Michel Foucault and others to explore resonance capability, disciplinary apparatuses and the complexity–sustainability trade-off. The argument is illustrated with a discussion of the late-nineteenth- to early-twentieth-century anti-child labor movement.

Findings

The paper argues that organizations are better equipped than function systems to draw moral distinctions. Given the amorality of the function systems and the increasing secularization of modern society, a great deal of moral communication now occurs in non-religious organizations. These social systems increase their complexity in response to new problems, but the increased system complexity may become unsustainable.

Research limitations/implications

The paper contributes to the growing sociological literature that compares and sometimes attempts to synthesize the theories of Luhmann and Foucault. It also contributes to the literature on organizational theory.

Originality/value

The paper brings together the work of Luhmann, Foucault, Valentinov and others to advance the understanding of organizations and moral communication in a functionally differentiated society. It uses Google Books Ngrams, among other resources, to support the argument.
Imaging features of extramedullary plasmacytoma
Authors: Ryu Seung Wook , Cohen‐Hallaleh Violette
Published: December 2019

Extramedullary plasmacytomas are rare and can occur at any site. The imaging results are often nonspecific. This report highlights the radiographic, sonographic and cross‐sectional imaging features of extramedullary plasmacytomas.
Clinical application of photodynamic therapy for malignant airway tumors in China
Authors: Jin Faguang , Wang Hongwu , Li Qiang , Bai Chong , Zeng Yiming , Lai Guoxiang , Guo Shuliang , Gu Xing , Li Wangping , Zhang Haitao
Published: November 2019

With the development of interventional pulmonology, photodynamic therapy (PDT) is gradually being used in the treatment of respiratory malignant tumors because of its low level of trauma, high specificity, and compatibility with traditional or common therapies. However, at present, the data of clinical evidence‐based medicine for PDT applied in central airway tumors is very limited, and derives mainly from case reports or series of case studies which lack consensus on clinical diagnosis and treatment. In order to further disseminate China's experience, the Tumor Photodynamic Therapy Committee of China Anti‐Cancer Association and the World Endoscopy Association‐Respiratory Endoscopy Association invited experts from relevant fields to form an expert committee. After several rounds of discussion and revision by this committee, and following a vote, the consensus was formulated for reference by physicians in respiratory, oncology and other related disciplines to refer to the practice of tumor photodynamic therapy.
Prognostic impact of CD34 and SMA in cancer‐associated fibroblasts in stage I–III NSCLC
Authors: Schulze Arik Bernard , Schmidt Lars Henning , Heitkötter Birthe , Huss Sebastian , Mohr Michael , Marra Alessandro , Hillejan Ludger , Görlich Dennis , Barth Peter J. , Rehkämper Jan , Evers Georg
Published: November 2019

Background

Epithelial‐to‐mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer‐associated fibroblasts (CAFs) are reported to regulate this process.

Objectives

To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non‐small cell lung cancer (NSCLC).

Methods

Retrospectively, immunohistochemistry was performed to study stromal protein expression of both CD34 and SMA in 304 NSCLC patients with pTNM stage I‐III disease. All tissue samples were embedded on tissue microarrays (TMAs).

Results

Our analysis revealed an association for CD34+ CAFs with G1/2 tumors and adenocarcinoma histology. Moreover CD34+ CAFs were identified as an independent prognostic factor (both for progression free survival [PFS] and overall survival [OS] in stage I‐III NSCLC). Besides, SMA+ expression correlated with higher pTNM‐tumor stages and lymphatic spread (pN stage). In turn, SMA‐negativity was associated with improved PFS, but no prognostic impact was found on OS. Of interest, neither CD34+ CAFs nor SMA+ CAFs were associated with the primary tumor size, localization and depth of infiltration (pT stage).

Conclusions

CD34 was identified as an independent prognostic marker in pTNM stage I‐III NSCLC. Moreover, loss of CD34+ CAFs might influence the dedifferentiation of the NSCLC tumor from its cell origin. Finally, SMA+ CAFs are more prevalent in NSCLC tumors of higher stages and lymphonodal positive NSCLC.

Key points

Expression of CD34 on cancer associated fibroblasts (CAFs) is an independent prognostic factor in stage I‐III NSCLC.

SMA+ cancer associated fibroblasts are associated with higher tumor stages in NSCLC and might contribute to tumor progression in NSCLC.
Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts
Authors: Thesing C. S. , Lok A. , Milaneschi Y. , Assies J. , Bockting C. L. H. , Figueroa C. A. , Giltay E. J. , Penninx B. W. J. H. , Ruhé H. G. , Schene A. H. , Bot M. , Mocking R. J. T.
Published: December 2019

Objective

Omega‐3 (n‐3) and omega‐6 (n‐6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients.

Methods

Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8‐year follow‐up were analyzed using Cox regression analyses. Study‐specific estimates were pooled using mega‐ and meta‐analysis techniques.

Results

27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n‐3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98–1.41,P = 0.082; n‐6 PUFAs: HR = 1.08, 95% CI = 0.84–1.38,P = 0.55).

Conclusion

In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n‐3 PUFA ‘deficits’ through supplementation does not seem a promising option to prevent MDD recurrence.
Vitamin E acetate is not present in licit e‐cigarette products available on the UK market
Authors: Nyakutsikwa Blessing , Britton John , Bogdanovica Ilze , Langley Tessa
Published: December 2019

Aims

To determine whether nicotine‐containing vaping products submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) under the Tobacco and Related Products Regulations 2016 contain tetrahydrocannabinol or vitamin E acetate.

Methods

Analysis of data on ingredients for all products submitted for notification for the UK market by October 2017 to assess whether any were reported to contain vitamin E acetate or tetrahydrocannabinol (THC). The analysis was not pre‐registered and the results should therefore be considered exploratory.

Results

Vitamin E acetate and THC were not listed as an ingredient or emission in any of the 41 809 products that were submitted for notification.

Conclusions

In the United Kingdom, vapers and those considering switching from tobacco to vaping can be reassured that licit products available on the UK market do not contain tetrahydrocannabinol or vitamin E acetate.
FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence
Authors: Zhang Wei , Liu Huan , Deng Xiao‐Dong , Ma Ying , Liu Yun
Published: December 2019

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH‐dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2‐fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332–2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH‐dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171–2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404–2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444–2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.
Doxazosin down‐regulates sodium‐glucose cotransporter‐2 and exerts a renoprotective effect in rat models of acute renal injury
Authors: Rezq Samar , Nasr Ahmed M. , Shaheen Aya , Elshazly Shimaa M.
Published: December 2019

Sodium‐glucose cotransporter‐2 (SGLT2) is known to be involved in the progression of acute renal injury (ARI) and is regulated by different mediators in the kidneys including extracellular signal‐regulated kinase (ERK), hypoxia‐inducible factor 1 alpha (HIF1α) and prostaglandin E2 (PGE2). In the present study, we investigated the possible protective effect of doxazosin on renal ischaemia/reperfusion (IR) and glycerol‐induced ARI by determining its effect on SGLT2 via modifying ERK‐HIF1α pathway and/or PGE2. Rats were divided into control, sham or IR where the rats received the vehicle, doxazosin (8 mg/kg) or the SGLT2 inhibitor, dapagliflozin (10 mg/kg) for 3 days followed by 45 minutes bilateral renal ischaemia then 24 hours reperfusion. Another group of rats received the vehicle, doxazosin or dapagliflozin for three days followed by injection of 50% glycerol (8 mL/kg, IM) or saline. Kidney function tests, systolic blood pressure (SBP), oxidative stress markers (malondialdehyde [MDA] and NADPH oxidase), nitric oxide (NO), inducible nitric oxide synthase (iNOS), HIF1α, ERK phosphorylation and PGE2 levels were determined. Additionally, renal sections were used for immunological expression of SGLT2. ARI rats showed significantly increased SBP; worsened kidney function tests; increased oxidative stress, iNOS, NO, HIF1α levels; and decreased PGE2 and ERK phosphorylation along with up‐regulated SGLT2. Doxazosin treatment protected against the kidney damage and attenuated the associated biochemical changes. Doxazosin has a direct renoprotective effect possibly by down‐regulating SGLT2.
Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI‐1 study
Authors: Bang Yung‐Jue , Li Chung‐Pin , Lee Kyung‐Hun , Chiu Chang‐Fang , Park Joon Oh , Shan Yan‐Shen , Kim Jun Suk , Chen Jen‐Shi , Shim Hyun‐Jeong , Rau Kun‐Ming , Choi Hye Jin , Oh Do‐Youn , Belanger Bruce , Chen Li‐Tzong
Published: December 2019

The global, randomized NAPOLI‐1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (nal‐IRI+5‐FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine‐based therapy. Median overall survival (OS) with nal‐IRI+5‐FU/LV was 6.1 vs 4.2 months with 5‐FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post‐hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal‐IRI+5‐FU/LV (n = 34) had significantly longer median OS versus 5‐FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal‐IRI+5‐FU/LV versus 5‐FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal‐IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5‐FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal‐IRI+5‐FU/LV versus 5‐FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal‐IRI+5‐FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine‐based therapy, with a safety profile agreeing with previous findings. The nal‐IRI+5‐FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506)
A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity
Authors: Bayrak Nilüfer , Yıldırım Hatice , Yıldız Mahmut , Radwan Mohamed O. , Otsuka Masami , Fujita Mikako , Ciftci Halil I. , Tuyun Amaç Fatih
Published: December 2019

Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1–17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC50 values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 μM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11‐treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC50 value of 13.12 ± 1.71 μM, indicating that the moderate inhibition of ABL1 kinase is just an in‐part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP‐binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 μM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug‐like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.
Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma
Authors: Close H J , Stead L F , Nsengimana J , Reilly K A , Droop A , Wurdak H , Mathew R K , Corns R , Newton-Bishop J , Melcher A A , Short S C , Cook G P , Wilson E B
Published: December 2019

Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-β-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.