bluuebunny/crossref_metadata_2025 huggingface dataset:
EvoProDom: Evolutionary model of protein families by means of translocations of protein domains
Authors: Carmi Gon , Gorohovski Alessandro , Frenkel-Morgenstern Milana
Published: February 2020

Here, we developed a novel evolution of protein domains (EvoProDom) model for evolution of proteins, which was based on mix and merge of protein domains. We collected and integrated genomic and proteome data for 109 organisms. These data include protein domain content and orthologous protein families. In EvoProDom, we defined evolutionary events, such as translocations, as reciprocal exchanges of protein domains between orthologous proteins of different organisms. We found that protein domains, which frequently appear in translocation events, were enriched intrans-splicingevents,i.e., producing novel transcripts fused from two distinct genes. We presented in EvoProDom, a general method to obtain protein domain content and orthologous protein annotation, by predicting these data from protein sequences using the Pfam search tool and KoFamKOALA, respectively. This method can be implemented in other research such as proteomics, protein design and host-virus interactions.
Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling
Authors: Zhou Huijuan , Xue Chengbin , Gao Guannan , Lawless Lauren , Xie Linglin , Zhang Ke K.
Published: February 2020

The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.
Stress and behavioral correlates in the head-fixed method
Authors: Juczewski Konrad , Koussa Jonathan A. , Kesner Andrew J. , Lee Jeong O. , Lovinger David M.
Published: February 2020

Head-fixation of awake rodents is a method that allows for sophisticated investigation and manipulation of neural circuitsin vivo, that would otherwise be impossible in completely freely moving animals. However, while it is known that head-fixation induces stress, its scale and habituation dynamics remain unclear. Thus, interpretation of physiological and behavioral experiments would greatly benefit from the characterization of the stress response. In our study, we used the Mobile HomeCage system (Neurotar, Finland) where animals are head-fixed to an aluminum frame, but otherwise freely moving in an ultralight carbon container floating above an air-dispensing base. To better understand this experimental environment, we analyzed locomotion and stress during an extended habituation protocol. For 25 consecutive days, mice were prepared as they would be for recording experiments, i.e. head-fixed while standing on the air-lifted platform for 2 hours per day. Throughout 25 days, blood samples were taken periodically from the tail vein to measure variation in the stress-related hormone, corticosterone. These data were compared and contrasted with behavioral data including locomotion during the 2-hours head-fixed habituation sessions and several classical behavioral measurements known to be affected by chronic mild stress.
ToxoplasmaGRA15 limits parasite growth in IFNγ-activated fibroblasts through TRAF ubiquitin ligases
Authors: Mukhopadhyay Debanjan , Sangaré Lamba Omar , Braun Laurence , Hakimi Mohamed-Ali , Saeij Jeroen P.J.
Published: February 2020

The protozoan parasiteToxoplasma gondiilives inside a vacuole in the host cytoplasm where it is protected from host cytoplasmic innate immune responses. However, IFNγ-dependent cell-autonomous immunity can destroy the vacuole and the parasite inside.Toxoplasmastrain differences in susceptibility to human IFNγ exist but theToxoplasmaeffector(s) that determine these differences are unknown. We show that in human primary fibroblasts, the polymorphicToxoplasmasecreted effector GRA15 mediates the recruitment of ubiquitin ligases, including TRAF2 and TRAF6, to the vacuole membrane, which enhances recruitment of ubiquitin receptors (p62/NDP52) and ubiquitin-like molecules (LC3B, GABARAP). This ultimately leads to lysosomal degradation of the vacuole. In murine fibroblasts, GRA15-mediated TRAF6 recruitment mediates the recruitment of immunity-related GTPases and destruction of the vacuole. Thus, we have identified how theToxoplasmaeffector GRA15 affects cell-autonomous immunity in human and murine cells.
Mesoscopic-scale functional networks in the primate amygdala
Authors: Morrow Jeremiah K , Cohen Michael X , Gothard Katalin M
Published: February 2020

The primate amygdala performs multiple functions that may be related to the anatomical heterogeneity of its nuclei. At the level of single neurons, each function is reflected in stimulus- and task-specific responses. Given that neurons with a particular response profile are not clustered in any of the nuclei, single units may be too fine-grained to shed light on the mesoscale organization of the amygdala. We have extracted from local field potentials recorded simultaneously from multiple locations within the primate amygdala (Macaca mulatta) spatially defined and statistically separable responses to visual, tactile, and auditory stimuli. A generalized eigendecomposition-based method of source separation isolated coactivity patterns, or components, that in neurophysiological terms correspond to putative subnetworks. Some component spatial patterns mapped onto the anatomical organization of the amygdala, while other components reflected integration across nuclei. These components differentiated between visual, tactile, and auditory stimuli suggesting the presence of functionally distinct parallel subnetworks.
Genetic, cellular and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore
Authors: Trofimenko Evgeniya , Grasso Gianvito , Heulot Mathieu , Chevalier Nadja , Deriu Marco A. , Dubuis Gilles , Arribat Yoan , Serulla Marc , Michel Sébastien , Vantomme Gil , Ory Florine , Dam Linh Chi , Puyal Julien , Amati Francesca , Lüthi Anita , Danani Andrea , Widmann Christian
Published: February 2020

Cell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. They provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 potassium channels positively modulate cationic CPP direct translocation into cells by decreasing the transmembrane potential (Vm). These findings provide the first unbiased genetic validation of the role of Vm in CPP translocation in cells.In silicomodeling and live cell experiments indicate that CPPs, by bringing positive charges on the outer surface of the plasma membrane, decrease the Vmto very low values (−150 mV or less), a situation we have coined megapolarization that then triggers formation of water pores used by CPPs to enter cells. Megapolarization lowers the free energy barrier associated with CPP membrane translocation. Using dyes of varying sizes, we assessed the diameter of the water pores in living cells and found that they readily accommodated the passage of 2 nm-wide molecules, in accordance with the structural characteristics of the pores predicted byin silicomodeling. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular internalization in zebrafish and mouse models. Besides identifying the first proteins that regulate CPP translocation, this work characterized key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for strategies aimed at improving the ability of cells to capture CPP-linked cargosin vitroandin vivo.
A liquid biopsy platform for detecting gene-gene fusions as glioma diagnostic biomarkers and drug targets
Authors: Palande Vikrant , Detroja Rajesh , Gorohovski Alessandro , Glass Rainer , Flueh Charlotte , Kurtz Marina , Perez Shira , Shay Dorith Raviv , Siegal Tali , Frenkel-Morgenstern Milana
Published: February 2020

Gliomas account for about 80% of all malignant brain tumours. Diagnosis is achieved by radiographic imaging followed by tumour resection, to determine tumour cell type, grade and molecular characteristics. Glioblastoma multiforme (GBM) is the most common type of glioma, and is uniformly fatal. The median survival of treated GBM patients is 12-15 months. Standard modalities of therapy are unselective and include surgery, radiation therapy and chemotherapy, while precision medicine has yet to demonstrate improvements in disease outcome. We therefore selected GBM as a model to develop a precision medicine methodology for monitoring patients using blood plasma circulating cell-free DNA (cfDNA). Currently, tumour heterogeneity, clonal diversity and mutation acquisition are the major impedances for tailoring personalized therapy in gliomas in general, and particularly in GBM. Thus, a liquid biopsy diagnostics platform based on cfDNA sequencing may improve treatment outcome for GBM patients, by guiding therapy selection. In this study, we processed from 27 patients with glioma, 27 plasma samples for cfDNA isolation and 5 tissue biopsy samples for tumour DNA isolation. From a control group of 14 healthy individuals, 14 plasma samples were processed for cfDNA isolation. In glioma patients, cfDNA concentration was elevated compared to controls. Point mutations found in glioma tissue biopsies were also found in the cfDNA samples (95% identity). Finally, we identified novel chimeric genes (gene-gene fusions) in both tumour and cfDNA samples. These fusions are predicted to alter protein interaction networks, by removing tumour suppressors and adding oncoproteins. Indeed, several of these fusions are potential drug targets, particularly, NTRK or ROS1 fusions, specifically for crizotinib analogues (like entrectinib and larotrectinib) with enhanced penetration of the central nervous system. Taken together, our results demonstrate that novel druggable targets in gliomas can be identified by liquid biopsy using cfDNA in patient plasma. These results open new perspectives and abilities of precision medicine in GBM.
Exploring the impact of political regimes on biodiversity
Authors: Zizka Alexander , Rydén Oskar , Edler Daniel , Klein Johannes , Aronsson Heléne , Perrigo Allison , Silvestro Daniele , Jagers Sverker C. , Lindberg Staffan I. , Antonelli Alexandre
Published: February 2020

National governments are the main actors responsible for mapping and protecting their biodiversity, but countries differ in their capacity, willingness, and effectiveness to do so. We quantify the global biodiversity managed by different regime types and developed a tool to explore the links between level of democracy and other key socio-economic variables with the number of natural history specimens registered within country boundaries. Using this tool, distinct and previously unknown patterns emerge around the world, that urge for increased collaboration between the natural and social sciences to further explore these patterns and their underlying processes.
Customers' perceived value and dining choice through mobile apps in Indonesia
Authors: Shah Adnan Muhammad , Yan Xiangbin , Shah Syed Asad Ali , Ali Mudassar
Published: February 2020

Purpose

The latest mobile technology may shape consumers' motivations by allowing them to order a variety of foods using smartphone apps. Following the stimulus–organism–response (SOR) framework and using a mixed methods approach, this study investigates the impacts of different components of mobile dining on customers' perceived value, which leads to actual purchase intentions. Furthermore, this study examines the moderating effect of the restaurant type.

Design/methodology/approach

Data were collected via an online questionnaire survey from 351 individuals in the city of Jakarta (Indonesia) who actually used mobile apps to order food online. Data analysis was carried out using structural equation modeling.

Findings

The findings reveal that source credibility, review valence, the navigation system, food quality and service quality significantly impact customers' perceived value. Customers' perceived value, in turn, positively affects their purchase intentions. The findings also reveal that the impacts of review valence, the navigation system, food quality and service quality on customers' perceived value depend on the different levels of restaurants.

Originality/value

This study is among the first in the mobile commerce research that studies the impacts of mobile electronic word-of-mouth (eWOM), system quality and overall restaurant image on dining choices by considering actual mobile shoppers. Second, this study extends the SOR model to examine the impact of the mobile environment-based characteristics on the perceived value that leads to purchase intentions. Third, the current study examines whether the relationships that are discussed early on differ based on the restaurant type. The findings of this study could help practitioners achieve a deeper understanding of diners' behaviors due to the perceived benefits of mobile dining.
A study of grey literature in National Digital Library of India: analyses and trends
Authors: Moid Abdul , Raza M. Masoom , Jahan Keshwar
Published: February 2020

Purpose

This paper aims to examine the grey literature (GL) in National Digital Library of India (NDLI) with particular reference to synopsis, thesis, report and patent.

Design/methodology/approach

The National Digital Library of India (NDLI) was used to collect data from types of text content. After filtering text content, learning resource type was refined and four kinds of GL were randomly selected for further analysis in MS Excel.

Findings

As a primary source of information, a huge number of GL available in text form, in which the availability of reports are maximum, are selected. In NDLI, the majority of the selected grey resources, e.g. report, thesis, synopsis and patent, are open for access. It also discloses the significance of Education Resources Information Center (ERIC), from where majority of GL resources were extracted and the maximum number of resources is available in the English language.

Originality/value

GL is regarded as a valuable primary source of locally generated information. No such study was carried out specifically regarding NDLI. Besides, this study aids to understand the archiving method of GL. These findings also help the users to filtering or sorting out to access accurate information sources.
Role of virtual avatars in digitalized hotel service
Authors: Choi Youngjoon , Mehraliyev Fuad , Kim Seongseop (Sam)
Published: February 2020

Purpose

This study aim to attempt to conceptualize agency in a hospitality setting and examine the psychological effects of agency-related visual cues on user perception and intention to use to understand the role of agency in the digitalization of hotel services.

Design/methodology/approach

After developing demo videos of an express check-out application, two experiments were conducted to examine the effects of using an avatar and explain the psychological mechanism of how attributes of an avatar increase intention to use.

Findings

Study 1 found that the presence of an avatar had a positive influence on intention to use. Study 2 retested the findings of Study 1 and illustrated the psychological mechanism of how two attributes of an avatar (social position and gender) influenced perceived expertise and intention to use. A significant interaction effect between social position and gender was found on perceived expertise. Perceived expertise also mediated the effect of an avatar on intention to use in the male avatar conditions.

Originality/value

As the first attempt to investigate the role of avatars in human–computer interaction in a hotel setting, this study will serve as an example in testing the effects of agency-related technical features on user experience and behavioral intention, possibly broadening the current research scope of hospitality and tourism. This study also provides a useful guideline to develop and design a successful interface of digitalized hotel services.
A grounded theory study for digital academic entrepreneurship
Authors: Toniolo Korinzia , Masiero Eleonora , Massaro Maurizio , Bagnoli Carlo
Published: February 2020

Purpose

This research aims to investigate how digital academic entrepreneurship (AE) develops, exploring its evolution from a micro to a macro perspective and highlighting the role of intellectual capital along the process. This paper contributes to the Special Issue on digital AE, providing research and practical implications.

Design/methodology/approach

This study adopts a grounded theory approach which allows exploring the “How” question of digital AE. It focuses on the case of “Strategy Innovation,” the Ca' Foscari University of Venice (Italy) spin-off.

Findings

Digital AE develops and regenerates through a virtuous cycle that, while supported by digital technologies, starts from single individuals and their networks, reaches a broader ecosystem, and ends once back to individuals. This study offers insights about the social impact of academic venturing activities and provides practitioners with useful insights for the understanding of academic spin-offs activities and related opportunities.

Research limitations/implications

This study focuses on the specific research context of “Strategy Innovation,” Ca' Foscari University of Venice (Italy) spin-off. Future research should address in-depth analyses in the exploration of how digital AE emerges and evolves in different contexts and forms.

Originality/value

This study investigates digital AE's development over time, broadly illustrating the phenomenon from a micro to a macro perspective and presenting an explicative and analytical model.
Entrepreneurial orientation and firm performance in Italian firms
Authors: Galbreath Jeremy , Lucianetti Lorenzo , Thomas Ben , Tisch Daniel
Published: February 2020

Purpose

Considering that context is important and relying on a contingency perspective, the purpose of the study is to analyze the relationship between an entrepreneurial orientation (EO) and firm performance in one of the world's oldest economies: Italy. The contingency perspective relies on competitive strategy as a moderating variable.

Design/methodology/approach

Using a mix of primary and secondary data sources, relationships are explored in a sample of 229 Italian for-profit firms. Moderated regression analysis is used for the sample and additional tests are conducted by firm size groupings.

Findings

The analysis suggests that an EO is positively associated with firm performance in the sample firms. Further, competitive strategy acts as a moderating influence: a low-cost strategy negatively influences the relationship, while a differentiation strategy positively influences the relationship. The firm size groupings do not appear to affect the results.

Research limitations/implications

The study examines only for-profit firms in a single country, Italy; therefore, generalizability is limited. The results must be interpreted in light of these limitations.

Originality/value

This study contributes to the entrepreneurship literature by considering a relatively new international context in the EO–firm performance relationship. Further, a new contingency perspective is advanced by considering competitive strategy. In doing so, this study extends an understanding of the conditions under which an EO might be associated with firm performance.
A cross-firm analysis of corporate governance compliance and performance in Indonesia
Authors: Tanjung Miranda
Published: February 2020

Purpose

The study aims to construct a cross-firm corporate governance index to predict firm performance. The index consists of 15 governance elements from a large sample of the Indonesian firms covering the period from 2003 to 2013.

Design/methodology/approach

This study presents robust results as the findings are tested by applying the generalized method of moments (GMM) estimator to eliminate endogeneity problems and unobservable heterogeneity posed by the relationship between performance and firm-level governance practices.

Findings

The results indicate that the corporate governance index is associated with enhanced corporate financial performance. Likewise, the findings reported under the pooled ordinary least squares and GMM also indicate corporate governance sub-indexes (elements), which have significant effects on performance: whistleblower mechanism, audit quality, board of director size and blockholders.

Research limitations/implications

In the emerging market context, this study supports the notion that active and self-regulated governance practices are appreciated by the market and, in the end, can have a positive impact on financial performance. The analysis adds to the empirical literature by providing insights into how governance provisions are being actively implemented in the micro level. With regard to weak governance practices, this study is consistent with previous studies, according to which, firms have the opportunity to use corporate governance as a way of differentiating themselves from other players in countries with poorly regulated investor protection and institutional settings.

Originality/value

This study makes a positive contribution, as it looks at the impact of Indonesia’s corporate governance compliance on the basis of a set of 15 unique governance provisions, including the findings of the positive influence of corporate governance in family business.
Police cadet general and interactional knowledge of persons with autism spectrum disorders (ASDs)
Authors: Copenhaver Allen , Denney Andrew S. , Rapp Victoria
Published: February 2020

Purpose

The purpose of this study is to ascertain law enforcement cadet general knowledge of autism spectrum disorder (ASD) and practical knowledge in how to apply various aspects of their profession to persons with ASD.

Design/methodology/approach

In total, 341 law enforcement cadet surveys administered across ten individual law enforcement cadet classes were analyzed via two individual ordinary least squares (OLS) regression models. These regression models were designed to predict changes in cadet scores on their (1) general knowledge of autism scale (i.e., general knowledge regarding autism spectrum disorder itself) and (2) interactional law enforcement knowledge of autism scale (i.e., how to apply various aspects of their job to persons with ASD).

Findings

Findings show that cadets who had a stronger confidence in their ability to interact with persons who have ASD actually knew less than their counterparts with lower reported overall confidence. However, one's confidence in their ability to identify persons with ASD was associated with having better overall general knowledge of ASD itself. Similarly, the greater one's overall confidence in interacting with persons with ASD was associated with lower interactional knowledge. In each model, general autism knowledge and interactional knowledge were positively associated.

Practical implications

The results of this study have implications for cadet and officer training on ASD as each need to be trained in both general knowledge of autism and interactional autism knowledge skills related to the job functions of being a LEO. Policy implications and directions for future research are discussed.

Originality/value

The literature is sparse on law enforcement knowledge of and interaction with persons who have ASD. As such, this study has the potential to make a strong impact on the literature regarding law enforcement and their knowledge and/or interactions with persons who have ASD.
Application of a cascading filter implemented using morphological filtering and time–frequency peak filtering for seismic signal enhancement
Authors: Liu Yanping , Yan Zhengguo
Published: February 2020

Inspired by the idea of the iterative time–frequency peak filtering, which applies time–frequency peak filtering several times to improve the ability of random noise reduction, this article proposes a new cascading filter implemented using mathematic morphological filtering and the time–frequency peak filtering, which we call here morphological time–frequency peak filtering for convenience. This new method will be used mainly for seismic signal enhancement and random noise reduction in which the advantages of the morphological algorithm in processing nonlinear signals and the time–frequency peak filtering in processing nonstationary signals are utilized. Structurally, the scheme of the proposed method adopts mathematic morphological operation to first preprocess the signal and then applies the time–frequency peak filtering method to ultimately extract the valid signal. Through experiments on synthetic seismic signals and field seismic data, this paper demonstrates that the morphological time–frequency peak filtering method is superior to the time–frequency peak filtering method and its iterative form in terms of valid signal enhancement and random noise reduction.
Characteristics of diffuse large B‐cell lymphoma in patients with primary Sjögren's syndrome
Authors: Gorodetskiy Vadim Romanovich , Probatova Natalya Alexandrovna , Vasilyev Vladimir Ivanovich
Published: February 2020

Aim

Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing diffuse large B‐cell lymphoma (DLBCL), which is an aggressive and heterogeneous non‐Hodgkin lymphoma. This study aimed to characterize DLBCLs in patients with pSS.

Method

We identified 18 patients with DLBCL and pSS over a 22‐year period. Based on the 2016 WHO guidelines, we characterized DLBCL based on immunohistochemical tests using a broad panel of antibodies, and an Epstein‐Barr virus (EBV) test using in situ hybridization.

Results

The median time from initial pSS symptom onset to the DLBCL diagnosis was 20.5 years and the median time from the pSS diagnosis until the DLBCL diagnosis was 14 years. After the lymphoma diagnosis, the median overall survival was 3 months (range: 0‐212 months) and the 5‐year overall survival rate was 37.5%. Thirteen DLBCLs were re‐classified as DLBCL, not otherwise specified (NOS) in nine cases; EBV‐positive DLBCL, NOS in two cases; and T‐cell/histiocyte‐rich large B‐cell lymphoma in two cases. Five cases of DLBCLs were not re‐classified because their EBV status was unknown. The Hans algorithm, which uses a combination of staining for CD10, BCL6, and MUM1, was used to classify the DLBCLs into the germinal center B‐cell (GCB) subtype for three cases and the non‐GCB subtype for nine cases.

Conclusion

These results indicate that DLBCL tends to occur late in pSS cases and is mainly related to the non‐GCB subtype of DLBCL.
MiRNA‐96‐5p impacts the progression of breast cancer through targeting FOXO3
Authors: Yin Ziyi , Wang Wenyan , Qu Gengbao , Wang Lin , Wang Xiang , Pan Qin
Published: February 2020

Background

Breast cancer is the most common malignant tumor in women worldwide, with a high mortality rate. MicroRNAs are small non‐coding RNAs that negatively regulate the expression of target genes by interacting with the target gene 3'‐UTR, and participate in cell differentiation, proliferation, apoptosis and metabolism. The function of miRNA‐96‐5p in the progression of breast cancer has not been reported.

Methods

We used the StarBase database to investigate the expression of miRNA‐96‐5p in breast cancer and adjacent normal tissues. FOXO3 3'‐UTR construct and luciferase reporter assays was performed for the target gene. Expression levels of miRNAs including its target were analyzed by qRT‐PCR and western blot. Cell proliferation was detected by CCK8 and colony formation, EdU assay.

Results

Luciferase reporter assays showed miRNA‐96‐5p directly targeted FOXO3. Abrogation of miRNA‐96‐5p by transfection with its inhibitors in breast cancer cells significantly suppressed miRNA‐96‐5p expression and breast cancer cells proliferation. Western blot revealed that overexpression of miRNA‐96‐5p substantially reduced FOXO3 protein expression. We used the GEPIA, UALCAN and KM‐plotter databases to investigate the expression of FOXO3 in human breast cancer and adjacent normal tissues, and its correlation with survival. In addition, we found that FOXO3 spoiled miR‐96‐5p induced breast cancer cell proliferation block effecting.

Conclusions

miRNA‐96‐5p may exert a tumor promotion role through negatively regulating tumor suppressor gene FOXO3 and promoting cell proliferation.
China's Convergence with IFRS: Analysis of Dual‐listed Companies
Authors: Zhang Weiguo , Ye Jianfang
Published: February 2020

This study investigates China's convergence towards International Financial Reporting Standards (IFRS) using generally accepted accounting principles (GAAP) differences data disclosed in AH‐share companies’ annual reports from 2006 to 2017. We firstly find that 92% of AH‐share companies disclosed GAAP differences in 2006, immediately prior to implementation of converged Chinese accounting standards (CAS). This ratio decreased to 88% in 2007, 58% in 2010, and 38% in 2011, respectively. After 2011, less than one third of AH companies disclosed GAAP differences. Secondly, an increasing number of AH companies (35%) have published CAS‐based financial statements in Hong Kong from 2014. Thirdly, except for the first few years after 2007, the disclosed GAAP differences have dropped to a very low level; since 2010 the net profit and net assets GAAP differences ratios have been below 0.5%. Fourthly, reduction of the disclosed GAAP differences appears to be the result of efforts by Chinese standard setters and regulators, work related to the International Accounting Standards Board, or changes in China's special socio‐economic environment. Distinct from word‐by‐word comparison between CAS and IFRS, this research shows that China has achieved its original goal, namely an enterprise applying CAS should produce financial statements that are the same as those of an enterprise that applies IFRS. Our findings provide insights regarding China's institutional evolution in terms of the country's IFRS convergence effort, which are useful for further empirical study.
MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes
Authors: Wilczynski Milosz , Senderowska Daria , Krawczyk Tomasz , Szymanska Bozena , Malinowski Andrzej
Published: February 2020

Introduction

MicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets.

Material and methods

During the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in 50 tissue samples were performed.

Results

After the screening phase of the study, five miRNAs were selected (hsa‐miR‐18b, hsa‐miR‐148a‐5p, hsa‐miR‐204, hsa‐miR‐424, hsa‐miR‐129‐1‐3p). Validation revealed that miRNA‐204 and miRNA‐424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa‐miR‐204—P = .0008; hsa‐miR‐424—P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa‐miR‐204—.802 (96% confidence interval CI 0.676‐0.927), hsa‐miR‐424—.84 (95% CI 0.711‐0.969).

Conclusions

Compared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA‐204 and miRNA‐424.
Letter: increased risk of caesarean section for women with IBD—more questions than answers. Authors' reply
Authors: Tandon Parul , Huang Vivian
Published: February 2020

LINKED CONTENT

This article is linked to Tandon et al and Selinger papers. To view these articles, visit https://doi.org/10.1111/apt.15587 and https://doi.org/10.1111/apt.15649.
Western Australia Atropine for the Treatment of Myopia (WA‐ATOM) study: Rationale, methodology and participant baseline characteristics
Authors: Lee Samantha S.Y. , Mackey David A. , Lingham Gareth , Crewe Julie M. , Richards Michael D. , Chen Fred K. , Charng Jason , Ng Fletcher , Flitcroft Ian , Loughman James J. , Azuara‐Blanco Augusto , Logan Nicola S. , Hammond Christopher J. , Chia Audrey , Truong Tan Tai , Clark Antony
Published: February 2020

Importance

Atropine eyedrops are a promising treatment for slowing myopia progression in East Asian children. However, its effects on children in Australia, including those of non‐Asian background, have not been well‐studied.

Background

The Western Australia Atropine for the Treatment of Myopia (WA‐ATOM) study aims to determine the efficacy and long‐term effects of low‐dose atropine eyedrops in myopia control. This paper describes the study rationale, methodology and participant baseline characteristics.

Design

Single‐centre, double‐masked, randomized controlled trial.

Participants

Children (6‐16 years) with spherical equivalent ≤−1.50 D in each eye, astigmatism ≤1.50 D and myopia progression by ≥0.50 D/year.

Methods

Enrolled children were randomly assigned 2:1 to receive 0.01% atropine or placebo eyedrops. Participants are examined every 6 months during first 3 years of the study (2‐year treatment phase followed by a 1‐year washout phase), and then at a 5‐year follow‐up (2 years after the end of the washout phase).

Main Outcome Measures

Annual progression rate of myopia and axial length, tolerability to eyedrops and incidence and severity of unwanted effects.

Results

Out of 311 children who were referred, 242 were suitable for study participation, and 153 were subsequently enrolled. The baseline characteristics of enrolled participants are presented.

Conclusions and Relevance

Outcomes of the WA‐ATOM study will inform on the efficacy, tolerability, safety and long‐term effects of low‐dose atropine eyedrops in myopia control in Australian children. The impact of ocular sun exposure, iris colour and parental myopia on the efficacy of low‐dose atropine will also be assessed.
Health education decreases incidence of hand eczema in metal work apprentices: Results of a controlled intervention study
Authors: Reich Anna , Wilke Annika , Gediga Günther , Baurecht Hansjörg , Rodríguez Elke , Jakasa Ivone , Geier Johannes , Mempel Martin , Buhl Timo , Weidinger Stephan , Kezic Sanja , John Swen M. , Schön Michael P. , Brans Richard
Published: February 2020

Background

Metal work apprentices (MWAs) frequently develop work‐related hand eczema (HE).

Objectives

To evaluate the effect of health education on incidence of work‐related HE in MWAs and to assess confounding factors.

Materials/methods

In a prospective controlled intervention study, 131 MWAs received educational training on prevention of HE, whereas 172 MWAs and 118 office work apprentices served as controls. At baseline and during three yearly follow‐ups, questionnaires were completed and hands were examined. Saliva samples were collected for assessment of filaggrin (FLG) null mutations and an explorative genome‐wide association study (GWAS), and levels of various cytokines were assessed from stratum corneum samples.

Results

The 2‐year and 3‐year incidence of HE in the metalwork control group was 20.9% and 32.6%, respectively, which was significantly higher than in the intervention group (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.31 to 5.28, P < .01 and OR 3.47, 95% CI 1.88 to 6.40, P < .0001). The knowledge score was higher in unaffected MWAs (P < .05). Other factors significantly associated with developing HE in MWAs were smoking cigarettes (P < .01) and FLG mutations (P < .001). No significant associations were found regarding epidermal cytokine levels and GWAS.

Conclusions

Health education is effective in primary prevention of HE in MWAs. Individual factors should be considered in targeted counseling.
Ferroptosis: Final destination for cancer?
Authors: Ye Zeng , Liu Wensheng , Zhuo Qifeng , Hu Qiangsheng , Liu Mengqi , Sun Qiqing , Zhang Zheng , Fan Guixiong , Xu Wenyan , Ji Shunrong , Yu Xianjun , Qin Yi , Xu Xiaowu
Published: February 2020

Ferroptosis is a recently defined, non‐apoptotic, regulated cell death (RCD) process that comprises abnormal metabolism of cellular lipid oxides catalysed by iron ions or iron‐containing enzymes. In this process, a variety of inducers destroy the cell redox balance and produce a large number of lipid peroxidation products, eventually triggering cell death. However, in terms of morphology, biochemistry and genetics, ferroptosis is quite different from apoptosis, necrosis, autophagy‐dependent cell death and other RCD processes. A growing number of studies suggest that the relationship between ferroptosis and cancer is extremely complicated and that ferroptosis promises to be a novel approach for the cancer treatment. This article primarily focuses on the mechanism of ferroptosis and discusses the potential application of ferroptosis in cancer therapy.
Exposure–Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis
Authors: Paul Stéphane , Marotte Hubert , Kavanaugh Arthur , Goupille Philippe , Kvien Tore K. , de Longueville Marc , Mulleman Denis , Sandborn William J. , Vande Casteele Niels
Published: February 2020

Anti‐tumor necrosis factor (anti‐TNF) drugs are often prescribed for the treatment of rheumatoid arthritis (RA) and other immune‐mediated inflammatory diseases. Although this treatment has been shown to be effective in many patients, up to 40% of patients do not achieve disease control. Drug concentration in plasma may be a factor affecting the observed variability in therapeutic response. In this study, we aimed to identify the plasma concentrations of the anti‐TNF certolizumab pegol (CZP), associated with improvement in disease activity in patients with RA. Data were pooled from three randomized, controlled clinical trials with a combined total of 1,935 patients analyzed. Clinical outcomes of low disease activity (LDA) and remission were defined as Disease Activity Score in 28 joints with C‐reactive protein (DAS28(CRP)) ≤ 2.7 and < 2.3, respectively. Quartile analysis results indicated that there may be an exposure‒response relationship between CZP concentration and LDA/remission outcomes at weeks 12 and 24; the association was strongest for LDA (P < 0.05). Receiver operating characteristic (ROC) analysis showed that CZP concentrations ≥ 28.0 μg/ml at week 12, and ≥ 17.6 μg/ml at week 24, were associated with a greater likelihood of achieving LDA/remission outcomes. Although confirmatory studies are warranted to define the optimal CZP therapeutic range at weeks 12 and 24, these data indicate that CZP concentrations may be associated with improvement of disease activity.
Hydrazinocurcumin Induces Apoptosis of Hepatocellular Carcinoma Cells Through the p38 MAPK Pathway
Authors: He Hongtao , Qiao Kuangyuan , Wang Chao , Yang Wuhan , Xu Zhuo , Zhang Zhilei , Jia Yuming , Zhang Chong , Peng Li
Published: February 2020

Hydrazinocurcumin (HZC), a synthetic derivative of curcumin (CUR), has been documented to show anticancer potential in impeding tumor growth in several cancers, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms remain unclear. This study aimed to explore the function and underlying mechanisms of HZC on HCC cells, which may involve the p38 mitogen activated protein kinase (MAPK) pathway. HZC was first purified and identified. HepG2 cells were then subjected to treatment with HZC or CUR of different concentrations and p38 MAPK signaling inhibitor (SB203580) to verify their effects on HCC cell apoptosis and proliferation. Furthermore, the functional relevance between HZC and the p38 MAPK pathway in HCC was examined. It was observed that 40 μM HZC exhibited the best pro‐apoptosis effect in HCC cells. HZC was found to inhibit HCC cell proliferation and promote apoptosis, the effect of which was stronger than 5‐fluorouracil (5‐FU). More importantly, the anti‐oncogenic effect of HZC and 5‐FU was implicated with activation of the p38 MAPK pathway. In vivo experimental results showed that HZC inhibited tumor growth more effectively than 5‐FU through the p38 MAPK pathway. These results provide evidence that HZC exerted anti‐oncogenic and pro‐apoptosis effects in HCC cells through activation of the p38 MAPK pathway.
Safety of a compression stocking for patients with chronic venous insufficiency (CVI) and peripheral artery disease (PAD)
Authors: Stücker Markus , Danneil Olivia , Dörler Martin , Hoffmann Maren , Kröger Elena , Reich‐Schupke Stefanie
Published: February 2020

Background

With increasing age, it is increasingly common for patients to develop both chronic venous insufficiency (CVI) and peripheral artery disease (PAD). While there are special compression bandage systems commercially available for individuals thus affected, appropriate compression stockings have previously not been available. In the present study, we investigated the safety and effectiveness of a type of compression stocking specifically designed for this patient group (VenoTrain® angioflow, Bauerfeind Germany, German compression class 1 with high stiffness).

Patients and Methods

In a prospective case series, we included patients with both CVI (C3–C5 disease according to CEAP classification) and PAD (ankle‐brachial index of < 0.9 and > 0.5; absolute ankle systolic pressure of > 60 mmHg). Primary outcome measures consisted of 1) safety in terms of PAD, as determined by measuring acral pressure using acral photoplethysmography (APPG), and 2) effectiveness in terms of CVI symptoms, as assessed by using a suitable questionnaire (VVSymQ).

Results

Fifty patients were evaluated (mean age: 67.1; mean ankle‐brachial index: 0.75 ± 0.77). Fifteen patients had stage IIa PAD (according to Fontaine); 15, stage IIb; the remainder, stage I disease. Thirty‐one patients had stage C3 CVI (according to CEAP classification); 16 patients, stage C4; and three patients, stage C5 disease. Immediately after donning the medical compression stocking, systolic arterial pressure in the big toe increased significantly (from 83.3 mmHg ± 27.6 mmHg to 90.8 mmHg ± 24.1 mmHg) (p = 0.026). The VVSymQ score dropped significantly from 5.0 ± 4.95 points to 1.4 ± 2.26 points (p < 0.001), thus reflecting an improvement in CVI symptoms.

Conclusions

The compression stocking tested herein is safe for individuals with an ankle brachial index ≥ 0.5. Skin damage was not observed.
Adding Objectivity to Standard Setting: Evaluating Consequence Using the Conscious and Subconscious Weight Methods
Authors: Leventhal Brian C. , Grabovsky Irina
Published: February 2020

Standard setting is arguably one of the most subjective techniques in test development and psychometrics. The decisions when scores are compared to standards, however, are arguably the most consequential outcomes of testing. Providing licensure to practice in a profession has high stake consequences for the public. Denying graduation or forcing remediation has high‐impact consequences for students. Unfortunately, tests that classify individuals are subjected to false positive and false negative misclassifications. When determining a standard, standard setting panelists implicitly consider the negative consequences of the decisions made from test use. We propose the conscious weight method and subconscious weight method to bring more objectivity to the standard setting process. To do this, these methods quantify the relative harm of the negative consequences of false positive and false negative misclassification.
Performance Measures in Dose‐Finding Experiments
Authors: Flournoy Nancy , Moler José , Plo Fernando
Published: February 2020

In the first phase of pharmaceutical development, and assuming that the probability of positive response increases with dose, the main statistical goal is to estimate a percentile of the dose–response function for a given target value . We compare the Maximum Likelihood and centred isotonic regression estimators of the target dose and we discuss several performance criteria to assess inferential precision, the amount of toxicity exposure and the trade‐off between them for a set of some exemplary adaptive designs. We compare these designs using graphical tools. Several scenarios are considered using simulation, including the use of several start‐up rules, the change of slope of the dose‐toxicity function at the target dose and also different theoretical models, as logistic, normal or skew‐normal distribution functions.
Measuring the impact of a blended learning model on early literacy growth
Authors: Wilkes Shani , Kazakoff Elizabeth R. , Prescott Jen Elise , Bundschuh Kristine , Hook Pamela E. , Wolf Raffaela , Hurwitz Lisa B. , Macaruso Paul
Published: February 2020

In the context of trying to improve reading proficiency in elementary school students, this study investigated the use of digital technology as part of a blended learning program, Core5, in kindergarten and first grade classes. A quasi‐experimental design compared 283 treatment students instructed in schools using Core5 with 237 control students in schools using traditional instruction in an urban school district. At the beginning of the school year, all students were pretested with Dynamic Indicators of Basic Early Literacy Skills (DIBELS), a commonly used reading assessment. During the school year, the treatment schools implemented Core5, which includes the online component and offline teacher‐led lessons. The English Language Arts curriculum was evaluated and found to be similar across treatment and control schools. At the end of the school year, all students were post‐tested with DIBELS. Results from propensity score analyses showed that treatment students outperformed control students and that the discrepancy between treatment and control groups on post‐test scores was more pronounced when students had lower pretest scores. These outcomes point to the value of using Core5 for reading instruction in early elementary grades.