bluuebunny/crossref_metadata_2025 huggingface dataset:
Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology
Authors: Yu Eun Young , Zahid Syed S. , Aloe Sarah , Falck-Pedersen Erik , Zhou Xi Kathy , Cheung Nai-Kong V. , Lue Neal F.
Published: May 2021

Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblastoma malignancy. Their mechanistic connection is unclear. We analyzed neuroblastoma cell lines and morphologic subclones representing the adrenergic (ADRN) and mesenchymal (MES) differentiation states and uncovered sharp differences in their telomere protein and telomerase activity levels. Pharmacologic conversion of ADRN into MES cells elicited consistent and robust changes in the expression of telomere-related proteins. Conversely, stringent down-regulation of telomerase activity triggers the differentiation of ADRN into MES cells, which was reversible upon telomerase upregulation. Interestingly, the MES differentiation state is associated with elevated levels of innate immunity factors, including key components of the DNA-sensing pathway. Accordingly, MES but not ADRN cells can mount a robust response to viral infectionsin vitro. A gene expression signature based on telomere and cell lineage-related factors can cluster neuroblastoma tumor samples into predominantly ADRN or MES-like groups, with distinct clinical outcomes. Our findings establish a novel mechanistic connection between telomere and differentiation and suggest that manipulating telomeres may suppress malignancy not only by limiting the tumor growth potential but also by inducing tumor cell differentiation and altering its immunogenicity.
Synergistic and offset effects of fungal species combinations on plant performance
Authors: Hori Yoshie , Fujita Hiroaki , Hiruma Kei , Narisawa Kazuhiko , Toju Hirokazu
Published: May 2021

In natural and agricultural ecosystems, survival and growth of plants depend substantially on microbes in the endosphere and rhizosphere. Although numerous studies have reported the presence of plant-growth promoting bacteria and fungi in below-ground biomes, it remains a major challenge to understand how sets of microbial species positively or negatively affect plants’ performance. By conducting a series of single- and dual-inoculation experiments of 13 endophytic and soil fungi targeting a Brassicaceae plant species, we here evaluated how microbial effects on plants depend on presence/absence of co-occurring microbes. The comparison of single- and dual-inoculation experiments showed that combinations of the fungal isolates with the highest plant-growth promoting effects in single inoculations did not yield highly positive impacts on plant performance traits (e.g., shoot dry weight). In contrast, pairs of fungi including small/moderate contributions to plants in single-inoculation contexts showed the greatest effects on plants among the 78 fungal pairs examined. These results on the offset and synergistic effects of pairs of microbes suggest that inoculation experiments of single microbial species/isolates can result in the overestimation or underestimation of microbial functions in multi-species contexts. Because keeping single-microbe systems in outdoor conditions is impractical, designing sets of microbes that can maximize performance of crop plants is an important step for the use of microbial functions in sustainable agriculture.
A new role of low barrier hydrogen bond in mediating protein stability by small molecules
Authors: Yang Jianhong , Li Yong , Qiu Qiang , Wang Ruihan , Yan Wei , Yu Yamei , Niu Lu , Pei Heying , Wei Haoche , Ouyang Liang , Ye Haoyu , Xu Dingguo , Wei Yuquan , Chen Qiang , Chen Lijuan
Published: May 2021

Low barrier hydrogen bond (LBHB) is a special type of hydrogen bond which occurs where two heteroatoms with similar pKa values share a single proton resulting in an unusually strong and short hydrogen bond. LBHBs in protein play important roles in enzyme catalysis and maintaining protein structural integrity but its other biochemical roles are unknown. Here we report a novel function of LBHB in selectively inducing tubulin protein degradation. A tubulin inhibitor, 3-(3-Phenoxybenzyl) amino-β-carboline (PAC), promotes selective degradation of αβ-tubulin heterodimers by binding to the colchicine site of β-tubulin. Biochemical studies have revealed that PAC specifically destabilizes tubulin, making it prone to aggregation that then predisposes it to ubiquitinylation and then degradation. Structural activity analyses have indicated that the destabilization is mediated by a single hydrogen bond formed between the pyridine nitrogen of PAC and βGlu198, which is identified as a LBHB. In contrast, another two tubulin inhibitors only forming normal hydrogen bonds with βGlu198 exhibit no degradation effect. Thus, the LBHB accounts for the degradation. Most importantly, we screened for compounds capable of forming LBHB with βGlu198 and demonstrated that BML284, a Wnt signaling activator, also promotes tubulin heterodimers degradation in a PAC-like manner as expected. Our study has identified a novel approach for designing tubulin degraders, providing a unique example of LBHB function and suggests that designing small molecules to form LBHBs with protein residues resulting in the highly specific degradation of a target protein could be a new strategy for drug development.
Prowler: A novel trimming algorithm for Oxford Nanopore sequence data
Authors: Lee Simon , Nguyen Loan T , Hayes Ben J , Ross Elizabeth
Published: May 2021

Motivation

Quality control (QC) tools are critical in DNA sequencing analysis because they increase the accuracy of sequence alignments and thus the reliability of results. Oxford Nanopore Technologies (ONT) QC is currently rudimentary, generally based on whole read average quality. This results in discarding reads that contain regions of high quality sequence. Here we propose Prowler, a multi-window approach inspired by algorithms used to QC short read data. Importantly, we retain the phase and read length information by optionally replacing trimmed sections with Ns.

Results

Prowler was applied to mammalian and bacterial datasets, to assess effects on alignment and assembly respectively. Compared to Nanofilt, alignments of data QC’ed with Prowler had lower error rates and more mapped reads. Assemblies of Prowler QC’ed data had a lower error rate than Nanofilt QCed data however this came at some cost to assembly contiguity.

Availability and implementation

Prowler is implemented in Python and is available at: https://github.com/ProwlerForNanopore/ProwlerTrimmer

Contact

e.ross@uq.edu.au

Supplementary information

Supplementary data are available at Bioinformatics online.
Pyruvate kinase M1 suppresses development and progression of prostate adenocarcinoma
Authors: Davidson Shawn M. , Heyman Julia E. , O’Brien James P. , Liu Amy C. , Schmidt Daniel R. , Israelsen William J. , Dayton Talya L. , Sehgal Raghav , Bronson Roderick T. , Freinkman Elizaveta , Mak Howard , Malstrom Scott , Bellinger Gary , Carracedo Arkaitz , Pandolfi Pier P. , Courtney Kevin D. , Frangioni John , Jha Abhishek , DePinho Ronald A. , Horner James W. , Thomas Craig J. , Cantley Lewis C. , Loda Massimo , Vander Heiden Matthew G.
Published: May 2021

Most cancers, including prostate cancers, express the M2 splice isoform of pyruvate kinase (Pkm2). This isoform can promote anabolic metabolism to support cell proliferation; however, Pkm2 expression is dispensable for many cancers in vivo. Pyruvate kinase M1 (Pkm1) isoform expression is restricted to relatively few tissues and has been reported to promote growth of select tumors, but the role of PKM1 in cancer has been less studied. Pkm1 is expressed in normal prostate tissue; thus, to test how differential pyruvate kinase isoform expression affects cancer initiation and progression we generated mice harboring a conditional allele of Pkm1 and crossed this allele, as well as a Pkm2 conditional allele, to a Pten loss-driven prostate cancer model. We found that Pkm1 loss leads to Pkm2 expression and accelerates prostate cancer, while deletion of Pkm2 leads to increased Pkm1 expression and suppresses cancer. Consistent with these data, a small molecule pyruvate kinase activator that mimics a PKM1-like state suppresses progression of established prostate tumors. PKM2 expression is retained in most human prostate cancers, arguing that pharmacological PKM2 activation may be beneficial for some prostate cancer patients.
Structural basis for ligand recognition and G protein-coupling promiscuity of the cholecystokinin A receptor
Authors: Liu Qiufeng , Yang Dehua , Zhuang Youwen , Croll Tristan I. , Cai Xiaoqing , Dai Antao , He Xinheng , Duan Jia , Yin Wanchao , Ye Chenyu , Zhou Fulai , Wu Beili , Zhao Qiang , Eric Xu H. , Wang Ming-Wei , Jiang Yi
Published: May 2021

Cholecystokinin A receptor (CCKAR) belongs to family A G protein-coupled receptors (GPCRs) and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with sulfated ligand and to couple with divergent G protein subtypes, including Gs, Gi, and Gq. However, the basis for G protein coupling promiscuity and ligand recognition by CCKAR remain unknown. Here we present three cryo-electron microscopy (cryo-EM) structures of sulfated CCK-8 activated CCKAR in complex with Gs, Gi, and Gq heterotrimers, respectively. In these three structures, CCKAR presents a similar conformation, whereas conformational differences in “wavy hook” of Gα subunits and ICL3 of the receptor serve as determinants in G protein coupling selectivity. These structures together with mutagenesis data provide the framework for understanding the G protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.
A corpus for differential diagnosis: an eye diseases use case
Authors: Yepes Antonio Jimeno , Iraola David Martinez , Barnard Pieter , Joy Tinu Theckel
Published: May 2021

We have created a corpus for the extraction of information related to diagnosis from scientific literature focused on eye diseases. It was shown that the annotation of entities has a relatively large agreement among annotators, which translates into strong performance of the trained methods, mostly BioBERT. Furthermore it was observed that relation annotation in this domain has challenges, which might require additional exploration.

When using the trained models on MEDLINE, we could identify confirmed knowledge about the diagnosis of eye diseases and relevant new information, which supports the developments in this work. The corpus that we have developed is publicly available, thus the scientific community is able to reproduce our work and reuse the corpus in their work.
Regulation of Src tumor activity by its N-terminal intrinsically disordered region
Authors: Aponte Emilie , Lafitte Marie , Sirvent Audrey , Simon Valérie , Barbery Maud , Fourgous Elise , Maffei Mariano , Armand Florence , Hamelin Romain , Pannequin Julie , Fort Philippe , Pons Miquel , Roche Serge
Published: May 2021

The membrane anchored Src tyrosine kinase is involved in numerous pathways and its deregulation is involved in human cancer. Our knowledge on Src regulation relies on crystallography, which revealed intramolecular interactions to control active Src conformations. However, Src contains a N-terminal intrinsically disordered unique domain (UD) whose function remains unclear. Using NMR, we reported that UD forms an intramolecular fuzzy complex involving a conserved region with lipid-binding capacity named Unique Lipid Binding Region (ULBR), which could modulate Src membrane anchoring. Here we show that the ULBR is essential for Src’s oncogenic capacity. ULBR inactive mutations inhibited Src transforming activity in NIH3T3 cells and in human colon cancer cells. It also reduced Src-induced tumor development in nude mice. An intact ULBR was required for MAPK signaling without affecting Src kinase activity nor sub-cellular localization. Phospho-proteomic analyses revealed that, while not impacting on the global tyrosine phospho-proteome in colon cancer cells, this region modulates phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling, including EPHA2 and Fyn. Collectively, this study reveals an important role of this intrinsically disordered region in malignant cell transformation and suggests a novel layer of Src regulation by this unique region via membrane substrate phosphorylation.
Genome size evolution in the diverse insect order Trichoptera
Authors: Heckenhauer Jacqueline , Frandsen Paul B. , Sproul John S. , Li Zheng , Paule Juraj , Larracuente Amanda M. , Maughan Peter J. , Barker Michael S. , Schneider Julio V. , Stewart Russell J. , Pauls Steffen U.
Published: May 2021

Background

Genome size is implicated in form, function, and ecological success of a species. Two principally different mechanisms are proposed as major drivers of eukaryotic genome evolution and diversity: Polyploidy (i.e., whole genome duplication: WGD) or smaller duplication events and bursts in the activity of repetitive elements (RE). Here, we generated de novo genome assemblies of 17 caddisflies covering all major lineages of Trichoptera. Using these and previously sequenced genomes, we use caddisflies as a model for understanding genome size evolution in diverse insect lineages.

Results

We detect a ~14-fold variation in genome size across the order Trichoptera. We find strong evidence that repetitive element (RE) expansions, particularly those of transposable elements (TEs), are important drivers of large caddisfly genome sizes. Using an innovative method to examine TEs associated with universal single copy orthologs (i.e., BUSCO genes), we find that TE expansions have a major impact on protein-coding gene regions, with TE-gene associations showing a linear relationship with increasing genome size. Intriguingly, we find that expanded genomes preferentially evolved in caddisfly clades with a higher ecological diversity (i.e., various feeding modes, diversification in variable, less stable environments).

Conclusion

Our findings provide a platform to test hypotheses about the potential evolutionary roles of TE activity and TE-gene associations, particularly in groups with high species, ecological, and functional diversities.
Do socially responsible firms always disclose high-quality earnings? Evidence from an emerging socialist economy
Authors: Dang Hung Ngoc , Hoang Khanh , Vu Van Thuy , Nguyen Linh Van
Published: May 2021

Purpose

This paper aims to investigate the linkage between corporate social responsibility (CSR) and earnings quality (EQ) in the context of Vietnam, an Asian emerging economy characterized by high growth for decades and a socialist orientation. As CSR firms are expected to have high EQ, there arise concerns that corporate managers of CSR firms may use the reputation of the firm as a protection mechanism against the cost of earnings management.

Design/methodology/approach

The study uses a unique sample of Vietnamese CSR firms listed on Hanoi and Ho Chi Minh Stock Exchanges from 2015 to 2019. Several econometric tests are conducted to investigate whether corporate managers of CSR-active firms actively engage in earnings management and reduce the firms' EQ.

Findings

The empirical results show a negative impact of CSR on EQ, meaning that, in general, corporate managers of CSR firms in Vietnam opportunistically manage earnings. This confirms the paradox of the CSR–EQ relationship. In line with an emerging strand of research in the CSR literature, the finding suggests that the agency problem arises in CSR firms where corporate managers use their managerial discretion over accrual accounting to manipulate reported earnings.

Practical implications

The finding has practical implications for market participants and policymakers in improving monitoring mechanisms and enhancing the information environment in developing capital markets.

Originality/value

This is the first study in the literature that investigates and shows the paradox of the CSR–EQ relationship in the context of Vietnam, a new emerging economy that follows socialist orientation.
An integrated supply chain – human resource management approach for improved supply chain performance
Authors: Jena Sarat Kumar , Ghadge Abhijeet
Published: May 2021

Purpose

Human resource management (HRM) is struggling to cope with the increasingly volatile demand for skilled resources in the logistics and supply chain sector. Thus, this study discovers the possible integration of HRM and supply chain management (SCM) practices for improved supply chain performance. The purpose of this study is to explore the effect of intra HRM–SCM and joint HRM–SCM decisions on the performance of the supply chain.

Design/methodology/approach

An intra HRM–SCM and joint HRM–SCM model is developed following an empirical study. Survey data collected from 109 supply chain managers from Indian logistics firms are used to test the developed hypotheses. Structural equation modeling is used to analyze and validate the model.

Findings

The results suggest that supply chain performance is significantly influenced by joint HRM–SCM, compared to intra HRM–SCM practices, especially under volatile demand environments. Training and development, recruitment and selection, and performance management affect joint HRM–SCM significantly compared to the other three factors identified. Moreover, HRM and SCM show strong correlation and mutual support in identifying and fulfilling the demand of the logistics and supply chain sector.

Practical implications

With a growing trend toward globalization and digitalization, a joint HRM–SCM model will help businesses make robust and informed decisions for improved supply chain performance.

Originality/value

An empirical relationship between joint HRM–SCM, intra HRM–SCM, supply chain inhibitors and supply chain performance is established in this study. Although some part of this relationship may already exist, the study provides robust evidence to support this complex, collaborative relationship.
COVID-19 and cyber fraud: emerging threats during the pandemic
Authors: Ma Katelyn Wan Fei , McKinnon Tammy
Published: May 2021

Purpose

The emergence of the novel coronavirus (COVID-19) has threatened physical and mental health, and changed the behaviour and decision-making processes of individuals, organisations, and institutions worldwide. As many services move online due to the pandemic, COVID-19-themed cyber fraud is also growing. This article explores cyber fraud victimization and cyber security threats during COVID-19 using psychological and traditional criminological theories. It also provides a COVID-19-themed cyber fraud typology using empirical evidence from institutional and agency reports. Through organizing COVID-19-themed cyber fraud into four different categorizations, we aim to offer classification insights to researchers and industry professionals so that stakeholders can effectively manage emerging cyber fraud risks in our current pandemic.

Design/methodology/approach

The approach the study take for this conceptual paper is typology.
CIO reporting structure and firm strategic orientation – a content analysis approach
Authors: Karanja Erastus , Grant Donna , Zaveri Jigish S.
Published: May 2021

Purpose

Grounded in the principal-agent theory, this study aims to develop and test hypotheses too, investigate how the firm’s strategic orientations, namely, innovation, growth, differentiation and cost leadership impact the chief information officer (CIO) reporting relationship and structure.

Design/methodology/approach

The study uses content analysis to analyze a data set of press releases collected from the LexisNexis Academic wire index. The press releases were issued by firms when they hired CIOs between 2003 and 2007, yielding 128 firms, which had specific information about the CIO reporting relationship and structure.

Findings

The results reveal that firms seeking an innovation, growth or differentiation strategy have their CIOs reporting to the chief executive officer.

Research limitations/implications

The current study is motivated by the desire to replicate and extend the works of previous researchers who have assessed various CIO issues. Replication takes several forms such as the use of similar or different data sets, different research environments or reinvestigating research concepts through a different theoretical lens. This study makes use of a multi-firm data set spanning five years and the principal-agent theory as the theoretical framework to explore the CIO reporting relationship and structure. Although this study focuses on the hiring trends and the strategic orientations of the firms, future studies should explore other characteristics associated with the CIOs that might have an impact on the reporting relationship such as the years of experience, age, educational background of CIOs and information technology budgets.

Practical implications

The existing literature has not settled the debate as to whom the CIO should be reporting to and understanding the reporting relationships is important because, in many firms, the organizational structures and the reporting relationships are indicative of the power dynamics and how the organizational resources are controlled and shared.

Originality/value

Replication studies are important because they confirm, reinforce, extend and provide reliability to the paradigms and knowledge in the discipline, as well as offer reliability of the results upon which scientific progress is based.
Inexperienced decision-makers' use of positive heuristics for marketing decisions
Authors: Gilbert-Saad Antoine , McNaughton Rod B. , Siedlok Frank
Published: May 2021

Purpose

Research has reliably demonstrated that decision-makers, especially expert ones, use heuristics to make decisions under uncertainty. However, whether decision-makers with little or no experience also do, and if so, how? is unknown. This research addresses this issue in the marketing context by studying how a group of young and generally inexperienced entrepreneurs decide when asked to set a price and choose a distribution channel in a scenario involving a hypothetical firm.

Design/methodology/approach

The authors used think-aloud protocols to elicit data and then used inductive procedures to code the data for analysis.

Findings

The inexperienced entrepreneurs in the sample used three types of heuristics in their decision-making, forming a structured process that narrows in scope. First, metacognitive heuristics, which specify a decision-making approach, were used, followed by heuristics representing the criteria they considered, and finally, heuristics detailing the execution of a selected option. The authors also found that heuristics relating to a market orientation, especially customer-centric criteria, were the most common, but these were balanced with ones representing an internal orientation or growth.

Research limitations/implications

The generally inexperienced decision-makers the authors’ studied used heuristics in a structured way that helped them to select and balance several potentially conflicting decision-making criteria. As with most research using qualitative research designs, the generalizability of these findings is unclear. Further research on the mechanisms by which relatively inexperienced decision-makers learn the heuristics they use is recommended.

Originality/value

This research's novelty lies in its focus on heuristic use by nonexpert decision-makers under conditions of uncertainty and the findings about their scope and the order they are used. As the authors collected data from think-aloud protocols with relatively young entrepreneurs with limited experience, they also offer a description of the heuristics used by nascent entrepreneurs when making marketing decisions about pricing and channels. The most surprising conclusion is that even without relevant domain-specific knowledge, decision-makers can use heuristics in an ecologically rational way (i.e. structured to match the environment).
Interactions between below‐ground traits and rhizosheath fungal and bacterial communities for phosphorus acquisition
Authors: Honvault Nicolas , Houben David , Firmin Stéphane , Meglouli Hacène , Laruelle Frédéric , Fontaine Joël , Lounès‐Hadj Sahraoui Anissa , Coutu Arnaud , Lambers Hans , Faucon Michel‐Pierre
Published: May 2021

Plant–soil–microbe interactions play a central role in plant nutrient acquisition and thus ecosystem functioning and nutrient availability in agroecosystems. Adjustments in root morphology, root exudation and associations with micro‐organisms such as arbuscular mycorrhizal fungi are common for phosphorus acquisition. Yet how plant below‐ground functional traits interact with microbial communities for P acquisition remains largely unknown, limiting our understanding of phosphorus availability in agroecosystems.

Interactions between below‐ground functional traits and rhizosheath soil microbial communities for P acquisition were investigated across eight herbaceous species with contrasting root traits. Root morphological and physiological traits involved in P acquisition were quantified simultaneously with PLFA (phospholipid fatty acid) and NLFA (neutral lipid fatty acid) microbial bioindicators.

Multiple correlations were observed between root morphology, root exudates and rhizosheath fungal and bacterial communities. Root exudates and in particular release of malate and malonate were strongly linked with indicators of Gram‐negative bacteria, which were correlated with changes in rhizosheath soil P concentration and plant P content.

Our results suggest that root exudation of carboxylates may play an important role in plant–soil–microbe interactions for P acquisition, underlining their likely role in shaping microbial communities. Incorporating these interactions in biogeochemical models would lead to better predicting power and understanding of P cycling and ecosystem functioning.

A free Plain Language Summary can be found within the Supporting Information of this article.
The past, present, and future of herbivore impacts on savanna vegetation
Authors: Staver A. Carla , Abraham Joel O. , Hempson Gareth P. , Karp Allison T. , Faith J. Tyler
Published: May 2021

Herbivory is a key process structuring vegetation in savannas, especially in Africa where large mammal herbivore communities remain intact. Exclusion experiments consistently show that herbivores impact savanna vegetation, but effect size variation has resisted explanation, limiting our understanding of the past, present and future roles of herbivory in savanna ecosystems.

Synthesis of vegetation responses to herbivore exclusion shows that herbivory decreased grass abundance by 57.0% and tree abundance by 30.6% across African savannas.

The magnitude of herbivore exclusion effects scaled with herbivore abundance: more grazing herbivores resulted in larger grass responses and more browsing herbivores in larger tree responses. However, existing experiments are concentrated in semi‐arid savannas (400–800‐mm rainfall) and soils data are mostly lacking, which makes disentangling environmental constraints a challenge and priority for future research.

Observed herbivore impacts were ~2.1× larger than existing estimates modelled based on consumption. Wildlife metabolic rates may be higher than are usually used for estimating consumption, which offers one clear avenue for reconciling estimated herbivore consumption with observed herbivore impacts. Plant‐soil feedbacks, plant community composition, and the phenological or demographic timing of herbivory may also influence vegetation productivity, thereby magnifying herbivore impacts.

Because herbivore abundance so closely predicts vegetation impact, changes in herbivore abundance through time are likely predictive of the past and future of their impacts. Grazer diversity in Africa has declined from its peak 1 million years ago and wild grazer abundance has declined historically, suggesting that grazing likely had larger impacts in the past than it does today.

Current wildlife impacts are dominated by small‐bodied mixed feeders, which will likely continue into the future, but the magnitude of top‐down control may also depend on changing climate, fire and atmospheric CO2.

Synthesis. Herbivore biomass determines the magnitude of their impacts on savanna vegetation, with effect sizes based on direct observation that outstrip existing modelled estimates across African savannas. Findings suggest substantial ecosystem impacts of herbivory and allow us to generate evidence‐based hypotheses of the past and future impacts of herbivores on savanna vegetation.
From aims to actions: A critical analysis of government intervention in cultural drivers of domestic and family violence
Authors: Kuskoff Ella
Published: May 2021

Addressing the cultural drivers of domestic and family violence (DFV) has become a core policy priority for governments across Australia. Over the last five years, the Queensland Government has taken a particularly strong stance on the issue through its Domestic and Family Violence Prevention Strategy 2016–2026. This strategy identifies the Queensland Government's leading aim of changing the community culture that drives DFV. Although there is significant evidence to support this aim, there is equally important evidence suggesting that public policies often contain problematic assumptions and ideologies that limit their ability to achieve their aims. This article presents a critical discourse analysis of Queensland's Domestic and Family Violence Prevention Strategy 2016–2026 and related policy documents to examine the assumptions and ideologies underpinning Queensland's policy and their potential to impact on policy outcomes. The findings broadly identify three areas of concern, namely an assumed link between attitudes and behaviours; a disproportionate focus on general community members compared to DFV perpetrators; and an implicit reinforcement of the gender hierarchy. The article concludes with a discussion of the broader implications of these findings for future policy development in Australia.
Profile of the super rich in China: A social space analysis
Authors: Lu Peng , Fan Xiaoguang , Fu Fan
Published: May 2021

Various “rich lists” indicate that China now has one of the highest percentages of super rich people worldwide. However, very little is known about their sociopolitical profiles. Based on the annual Hurun China Rich Lists from 2000 to 2018, we created a new dataset of China's super rich that combines information from various sources. Using a multiple correspondent analysis, we reveal that the social spaces of China's super rich are derived from their political, cultural, and social capital. The Chinese super rich are mainly distinguished by their cultural and political capital, while their social capital is not fully independent from political capital. We also identify a division among the super‐rich who first appeared on the rich list during different periods. These divisions can inform the understanding of the emergence of the super‐rich in an economy that has only recently embraced capitalism and can help predict their evolution in an increasingly glocalized system.
From workers to capitalists in less than two generations: A study of Chinese urban top group transformation between 1988 and 2013
Authors: Yang Li , Novokmet Filip , Milanovic Branko
Published: May 2021

Economic and social transformation of China during the past 40 years is without precedent in human history. While the economic transformation was extensively studied, social transformation was not. In this paper, we use for the first time harmonized household surveys covering the period 1988–2013 to study the changes in the characteristics of the richest 5 percent of China's urban population. We find that it changed from being composed of high government officials, clerical staff, and workers in 1988 to professionals and small and large business owners in 2013. The educational level of the top group increased substantially. Membership in CCP has a positive (albeit small) effect on one's income but is particularly valuable to large business owners.
Survival and pretreatment prognostic factors for extensive‐stage small cell lung cancer: A comprehensive analysis of 358 patients
Authors: Huang Li‐Ling , Hu Xing‐Sheng , Wang Yan , Li Jun‐Ling , Wang Hong‐Yu , Liu Peng , Xu Jian‐Ping , He Xiao‐Hui , Hao Xue‐Zhi , Jiang Pei‐Di , Liu Yu‐Tao , Luo Jian , Zhou Sheng‐Yu , Wang Jin‐Wan , Yang Jian‐Liang , Qin Yan , Yuan Peng , Lin Lin , Shi Yuan‐Kai
Published: May 2021

Background

Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population.

Methods

We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis.

Results

The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression‐free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS.

Conclusions

This study provides real‐world evidence of the survival and prognosis of ES‐SCLC patients which will enable better evaluation and clinical decision‐making in the future.
Spermidine inhibits vascular calcification in chronic kidney disease through modulation of SIRT1 signaling pathway
Authors: Liu Xiaoyu , Chen An , Liang Qingchun , Yang Xiulin , Dong Qianqian , Fu Mingwei , Wang Siyi , Li Yining , Ye Yuanzhi , Lan Zirong , Chen Yanting , Ou Jing‐Song , Yang Pingzhen , Lu Lihe , Yan Jianyun
Published: May 2021

Vascular calcification is a common pathologic condition in patients with chronic kidney disease (CKD) and aging individuals. It has been established that vascular calcification is a gene‐regulated biological process resembling osteogenesis involving osteogenic differentiation. However, there is no efficient treatment available for vascular calcification so far. The natural polyamine spermidine has been demonstrated to increase life span and protect against cardiovascular disease. It is unclear whether spermidine supplementation inhibits vascular calcification in CKD. Alizarin red staining and quantification of calcium content showed that spermidine treatment markedly reduced mineral deposition in both rat and human vascular smooth muscle cells (VSMCs) under osteogenic conditions. Additionally, western blot analysis revealed that spermidine treatment inhibited osteogenic differentiation of rat and human VSMCs. Moreover, spermidine treatment remarkably attenuated calcification of rat and human arterial rings ex vivo and aortic calcification in rats with CKD. Furthermore, treatment with spermidine induced the upregulation of Sirtuin 1 (SIRT1) in VSMCs and resulted in the downregulation of endoplasmic reticulum (ER) stress signaling components, such as activating transcription factor 4 (ATF4) and CCAAT/enhancer‐binding protein homologous protein (CHOP). Both pharmacological inhibition of SIRT1 by SIRT1 inhibitor EX527 and knockdown of SIRT1 by siRNA markedly blocked the inhibitory effect of spermidine on VSMC calcification. Consistently, EX527 abrogated the inhibitory effect of spermidine on aortic calcification in CKD rats. We for the first time demonstrate that spermidine alleviates vascular calcification in CKD by upregulating SIRT1 and inhibiting ER stress, and this may develop a promising therapeutic treatment to ameliorate vascular calcification in CKD.
An exhausted phenotype of TH2 cells is primed by allergen exposure, but not reinforced by allergen‐specific immunotherapy
Authors: Wang Shu‐Hung , Zissler Ulrich M. , Buettner Maren , Heine Sonja , Heldner Alexander , Kotz Sebastian , Pechtold Lisa , Kau Josephine , Plaschke Mirjam , Ullmann Julia T. , Guerth Ferdinand , Oelsner Madlen , Alessandrini Francesca , Blank Simon , Chaker Adam M. , Schmidt‐Weber Carsten B. , Jakwerth Constanze A.
Published: May 2021

Background

Studies show that proallergic TH2 cells decrease after successful allergen‐specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to exhaustion due to chronic T‐cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergen exposure during AIT in mice and two independent patient cohorts.

Methods

OVA‐sensitized C57BL/6J mice were challenged and treated with OVA, and the development of exhaustion in local and systemic TH2 cells was analyzed. In patients, the expression of exhaustion‐associated surface markers on TH2 cells was evaluated using flow cytometry in a cross‐sectional grass pollen allergy cohort with and without AIT. The treatment effect was further studied in PBMC collected from a prospective long‐term AIT cohort.

Results

The exhaustion‐associated surface markers CTLA‐4 and PD‐1 were significantly upregulated on TH2 cells upon OVA aerosol exposure in OVA‐allergic compared to non‐allergic mice. CTLA‐4 and PD‐1 decreased after AIT, in particular on the surface of local lung TH2 cells. Similarly, CTLA‐4 and PD‐1 expression was enhanced on TH2 cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discovered a late‐differentiated TH2 population expressing both markers that decreased during up‐dosing but persisted long term during the maintenance phase.

Conclusions

This study shows that allergen exposure promotes CTLA‐4 and PD‐1 expression on TH2 cells and that the dynamic change in frequencies of exhausted TH2 cells exhibits a differential pattern during the up‐dosing versus the maintenance phases of AIT.
Integrating numerical cognition research and mathematics education to strengthen the teaching and learning of early number
Authors: Hawes Zachary , Merkley Rebecca , Stager Christine L. , Ansari Daniel
Published: May 2021

Background

Research into numerical cognition has contributed to a large body of knowledge on how children learn and perform mathematics. This knowledge has the potential to inform mathematics education. Unfortunately, numerical cognition research and mathematics education remain disconnected from one another, lacking the proper infrastructure to allow for productive and meaningful exchange between disciplines. The present study was designed to address this gap.

Aim

This study reports on the design, implementation, and effects of a 16‐week (25‐hour) mathematics Professional Development (PD) model for Kindergarten to Grade 3 educators and their students. A central goal of the PD was to better integrate numerical cognition research and mathematics education.

Sample

A total of 45 K‐3 educators and 180 of their students participated.

Methods

To test the reproducibility and replicability of the model, the study was carried out across two different sites, over a two‐year period, and involved a combination of two different study designs: a quasi‐experimental pre–post‐research design and a within‐group crossover intervention design.

Result

The results of the first implementation (Year 1), indicated that compared to a control group, both teachers and students benefited from the intervention. Teachers demonstrated gains on both a self‐report measure and a test of numerical cognition knowledge, while students demonstrated gains in number line estimation, arithmetic, and numeration. In Year 2, teachers in the intervention group demonstrated greater improvements than the control group on the self‐report measure, but not the test of numerical cognition knowledge. At the student level, there was some evidence of gains in numeration.

Conclusion

The current PD model is a promising approach to better integrate research and practice. However, more research is needed to determine in which school contexts the model is most effective.
An improved synthesis of indanocine and antiproliferative activity of 2‐benzylindanocine via microtubule destabilization
Authors: Khwaja Sadiya , Fatima Kaneez , Mishra Divya , Babu Vineet , Kumar Yogesh , Malik Sumera Banu , Tabassum Misbah , Luqman Suaib , Bawankule Dnyaneshwar U. , Chanda Debabrata , Khan Feroz , Mondhe Dilip M. , Negi Arvind S.
Published: May 2021

Indanocine, a potent anticancer investigational drug of National Cancer Institute‐USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2‐benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT‐116 and MIA PACA‐2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of β‐tubulin. It also exhibited anti‐inflammatory activity by down‐regulating IL‐6 and TNF‐α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti‐inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability.
Elucidating specificity of an allosteric inhibitor WNK476 among With‐No‐Lysine kinase isoforms using molecular dynamic simulations
Authors: Amarnath Jonniya Nisha , Sk Md Fulbabu , Kar Parimal
Published: May 2021

Specifically targeting the With‐No‐Lysine (WNK1) kinase, which is implicated in hypertension, renders a significant challenge in discovering competitive inhibitors due to the highly conserved ATP‐binding pocket. However, an allosteric inhibitor may impart high specificity against the WNK kinase isoforms since it targets the less conserved site and can provide greater efficacy even under high physiological ATP concentration. In the current study, we have investigated the structural and energetic basis of the specificity of the allosteric inhibitor WNK476 against WNK kinase isoforms by combining molecular dynamics simulations and free energy calculations using molecular mechanics Poisson–Boltzmann surface area. Our study reveals that the conformational stabilization of αC‐helix near the allosteric binding site, including conformational changes in activation and glycine‐rich loop regions, favors the specificity of WNK476 toward WNK1. The MM/PBSA calculations suggest that the non‐polar contribution from hydrophobic residues and polar solvation energy influences WNK/WNK476 complexation. Despite more favorable electrostatic and van der Waals interactions in WNK2/WNK476, WNK476 is more potent against WNK1 due to the lower contribution of disfavoring components—polar solvation and entropy. Further, we have identified that the hydrophobic residues of DLG, αC‐helix, β4, and β5 regions, and H‐bond network near the β4 strand play a critical role in the specificity of WNK476 against WNK1. Finally, our study reveals that residues Leu272, Val281, Phe283, and Leu369 of WNK1 actively contribute to the overall hydrophobic interactions for WNK1/WNK476. Overall, our study might help in the rational design of novel allosteric inhibitors against hypertension.
Tackling Scientific Misconceptions: The Element of Surprise
Authors: Theobald Maria , Brod Garvin
Published: May 2021

Misconceptions about scientific concepts often prevail even if learners are confronted with conflicting evidence. This study tested the facilitative role of surprise in children’s revision of misconceptions regarding water displacement in a sample of German children (N = 94, aged 6–9 years, 46% female). Surprise was measured via the pupil dilation response. It was induced by letting children generate predictions before presenting them with outcomes that conflicted with their misconception. Compared to a control condition, generating predictions boosted children’s surprise and led to a greater revision of misconceptions (d = 0.56). Surprise further predicted successful belief revision during the learning phase. These results suggest that surprise increases the salience of a cognitive conflict, thereby facilitating the revision of misconceptions.
The learning curve of transanal total mesorectal excision for rectal cancer is associated with local recurrence: results from a multicentre external audit
Authors: Van Oostendorp Stefan E. , Belgers H. J. (Eric) , Hol Jeroen C. , Doornebosch Pascal G. , Belt Eric J. Th. , Oosterling Steven J. , Kusters Miranda , Bonjer H. J. (Jaap) , Sietses Colin , Tuynman Jurriaan B.
Published: May 2021

Aim

Transanal total mesorectal excision (TaTME) has been suggested as a potential solution for the resection of challenging mid and low rectal cancer. This relatively complex procedure has been implemented in many centres over the last years, despite the absence of long‐term safety data. Recently, concern has arisen because of an increase in local recurrence in the implementation phase. The aim of this study was to assess the correlation between accumulated experience and local recurrences.

Method

An independent clinical researcher performed an external audit of consecutive series of all TaTME procedures in six centres in the Netherlands. Kaplan–Meier estimated local recurrence rates were calculated and multivariate Cox proportional hazards regression analysis performed to assess risk factors for local recurrence. Primary outcome was the local recurrence rate in the initial implementation (cases 1–10), continued adoption (cases 11‐40) and prolonged experience (case 41 onward).

Results

Six hundred and twenty‐four consecutive patients underwent TaTME for rectal cancer with a median follow‐up of 27 months (range 1–82 months). The estimated 2‐ and 3‐year local recurrence rates were 4.6% and 6.6%, respectively. Cox proportional hazards regression revealed procedural experience to be an independent factor in multivariate analysis next to advanced stage (ycMRF+, pT3‐4, pN+) and pelvic sepsis. Corrected analysis projected the 3‐year local recurrence rates to be 9.7%, 3.3% and 3.5% for the implementation, continued adoption and prolonged experience cohorts, respectively.

Conclusion

This multicentre study shows a high local recurrence rate (12.5%) after implementation of TaTME which lowers to an acceptable rate (3.4%) when experience increases. Therefore, intensified proctoring and further precautions must be implemented to reduce the unacceptably high risk of local recurrence at units starting this technique.