bluuebunny/crossref_metadata_2025 huggingface dataset:
Translating Modern Slavery into Management Practice
Authors: Sarfaty Galit A.
Published: May 2020

This article examines how ill-defined legal norms around modern slavery are being outlined in supply chain legislation and then interpreted by management professionals. Building on an infrastructural analysis of supply chain governance, I uncover the set of practices that underlie recent regulations around modern slavery. I track the implementation of these laws by following the “chain of translation,” whereby information is transformed from on-the-ground raw data, to quantitative metrics of modern slavery risks, and, finally, to polished corporate statements. This analysis focuses on the critical role being played by the Supplier Ethical Data Exchange (Sedex), which is a platform for sharing responsible sourcing data. While Sedex is not an auditor and is not governed by lawyers, it is nonetheless serving an important function in interpreting legal norms around modern slavery and facilitating the implementation of supply chain laws. Yet there are potential costs to its expansive role. Sedex is translating modern slavery into a management problem largely based on quantitative metrics such as indicators and risk scorecards. While Sedex provides limited opportunities for public participation, it needs to be more transparent with respect to the methodology behind its metrics and provide further opportunities for comment by parties underrepresented in its governance.
Precarious Work, Unemployment Benefit Generosity and Universal Basic Income Preferences: A Multilevel Study on 21 European Countries
Authors: SHIN YOUNG-KYU , KEMPPAINEN TEEMU , KUITTO KATI
Published: May 2020

The idea of universal basic income (UBI) has been attracting increasing attention globally over recent years. However, research on the individual and institutional determinants of UBI support is scarce. The present study attempts to fills this gap by analysing workers’ attitudes towards UBI schemes in 21 European welfare states and focusing on the roles of precarious work (i.e. part-time work, temporary employment, low-skilled service employment, and solo self-employment) and unemployment benefit generosity (i.e. net replacement rate, payment duration, and qualifying period). We estimate fixed and random effects logistic models by merging country-level institutional data with the European Social Survey Round 8 data collected in 2016. The findings show that temporary employment is associated with positive attitudes towards UBI schemes, whereas other types of precarious work do not have significant influences. In addition, the results reveal that the more generous a country’s unemployment benefits, the less likely are workers in that country to support UBI schemes.
Gender, capital endowment and digital exclusion of older people in China
Authors: Yang Juhua , Du Peng
Published: May 2020

Amid rapid population ageing and the high-speed progress of information and communications technology, use of smart electronics can improve older people's quality of life by helping them to stay connected, active and independent, which may, in turn, increase their overall happiness and sense of social belonging. Taking a gender perspective, this paper aims to understand variations in digital exclusion among older people. Using data from the 2016 China Longitudinal Ageing Social Survey, it finds that digital exclusion seems to vary by gender, with rural female older people being most excluded, possibly because they have the lowest capital endowment. The gender difference in the digital divide is even more salient with all other things being equal. Digital exclusion in the information era may further exacerbate gender inequality, particularly for those who are already most vulnerable. Since digital inclusion is somewhat inherent in the concept of intelligent old-age support, it should be considered an urgent necessity to help older people, especially rural women, become familiar with smart electronic products.
Malnutrition and its associated factors among elderly Chinese with physical functional dependency
Authors: Ning Hongting , Du Yan , Ellis Donna , Deng Hong-Wen , Hu Hengyu , Zhao Yinan , Chen Huijing , Liao Lulu , Li Mengqi , Peng Linlin , Feng Hui
Published: May 2020

Objective:

To assess the prevalence and to identify the associated factors of malnutrition among elderly Chinese with physical functional dependency.

Design:

Face-to-face interviews using standardised questionnaires were conducted to collect demographic information, health-related issues and psychosocial status. Physical function was measured by the Barthel Index (BI), and nutrition status was assessed by the Mini Nutritional Assessment–Short Form. Multivariate binary logistic regression was used to assess associated factors of malnutrition.

Setting:

China.

Participants:

A total of 2323 participants (aged ≥ 60 years) with physical functional dependency in five provinces in China were enrolled using a multistage cluster sampling scheme.

Results:

The prevalence of malnutrition was 17·9 % (95 % CI 16·3, 19·4). Multivariable binary logistic regression revealed the independent risk factors of poor nutrition status were being female, older age, lower educational status, poor hearing, poor physical functional status, lack of hobbies, low religious participation, poor social support, lack of social participation and changes in social participation. The study found that the most significant independent risk factor for malnutrition was complete physical functional dependence (OR 4·46, 95 % CI 2·92, 6·82).

Conclusions:

The findings of the study confirm that malnutrition and the risk of malnutrition are prevalent in Chinese older adults with physical functional dependency. In addition to demographic and physical health-related factors, psychosocial factors, which are often overlooked, are independently associated with nutrition status in Chinese older adults with physical functional dependency. A holistic approach should be adopted to screen for malnutrition and develop health promotion interventions in this vulnerable population.
Phase Mapping in EBSD Using Convolutional Neural Networks
Authors: Kaufmann Kevin , Zhu Chaoyi , Rosengarten Alexander S. , Maryanovsky Daniel , Wang Haoren , Vecchio Kenneth S.
Published: May 2020

The emergence of commercial electron backscatter diffraction (EBSD) equipment ushered in an era of information rich maps produced by determining the orientation of user-selected crystal structures. Since then, a technological revolution has occurred in the quality, rate detection, and analysis of these diffractions patterns. The next revolution in EBSD is the ability to directly utilize the information rich diffraction patterns in a high-throughput manner. Aided by machine learning techniques, this new methodology is, as demonstrated herein, capable of accurately separating phases in a material by crystal symmetry, chemistry, and even lattice parameters with fewer human decisions. This work is the first demonstration of such capabilities and addresses many of the major challenges faced in modern EBSD. Diffraction patterns are collected from a variety of samples, and a convolutional neural network, a type of machine learning algorithm, is trained to autonomously recognize the subtle differences in the diffraction patterns and output phase maps of the material. This study offers a path to machine learning coupled phase mapping as databases of EBSD patterns encompass an increasing number of the possible space groups, chemistry changes, and lattice parameter variations.
Dosimetric impact of positron emission tomography-based gross tumour volume (GTV) delineation over conventional CT-based GTV delineation for carcinoma oesophagus
Authors: Kalyanasundaram Karthikeyan , Vellaiyan Subramani , Shanmugam Subramanian
Published: May 2020

Aim:

The aim of the study was to find the dosimetric impact of positron emission tomography (PET)-based gross tumour volume (GTV) delineation over computed tomography (CT)-based GTV delineation for carcinoma oesophagus.

Methods:

Fifteen patients with carcinoma oesophagus were retrospectively selected. Two sets of GTVs in CT plain images were generated, one with the help of intravenous and oral contrast (GTV CT) and the other with only using PET uptake with the standardised uptake value (simple way of determining the activity in PET) (SUV) > 2.5 (GTV PET). Corresponding PTVs were generated. For all patients, rapid arc plans were generated. Changes in target volumes and critical structure doses were evaluated. The Wilcoxon signed-rank test was used for statistical analysis, and p value < 0.05 was assumed as statistically significant.

Results:

Mean reduction in GTV was 5.76 ± 19.35 cc. Mean reduction in PTV 45 Gy was 42.40 ± 76.39 cc. Mean reduction in heart mean dose was 1.53 ± 2.16 Gy. Mean reductions in left lung V20% and V10% were 2.43 ± 4.28 and 3.25 ± 5.09 Gy, respectively. Mean reductions in right lung V20% and V10% were 3.11 ± 4.91 and 2.80 ± 4.51 Gy, respectively. Mean reduction in total lung mean dose was 1.00 ± 1.19 Gy.

Finding:

PET-based GTV contouring reduces the treatment volume and critical structure doses significantly over CT-based GTV contouring for carcinoma oesophagus.
Wolters Kluwer: 184 Years of Knowledge Innovation
Authors: Bartolone David
Published: May 2020

Wolters Kluwer is a global provider of professional information, software solutions, and services for customers in more than 180 countries. It employs approximately 19,000 people worldwide and has annual revenues of €4.6 billion of which 89% are derived from digital products and services. The company's roots can be traced back to the nineteenth century and to the merger of four entrepreneurial, family-run Dutch publishing houses: Wolters, Noordhoff, Samsom, and Kluwer. Throughout its 184-year history, Wolters Kluwer has adapted to a significant amount of environmental, cultural, and technological change, not the least of which was digitalization. It expanded internationally through numerous acquisitions and moved deeper into data and analytics. The company's four operational divisions - Health, Tax & Accounting, Governance Risk & Compliance and Legal & Regulatory - now aim together to achieve goals under a strategy entitled Accelerating Our Value. Those goals are three-fold: to grow expert solutions, to advance deep domain expertise and to drive operational agility. Today Wolters Kluwer is a data-driven, highly customer-experience-focused organization that continues to apply advanced technologies to complex problems. The author, David Bartolone, VP and General Manager, for the International Group within Wolters Kluwer's Legal and Regulatory, U.S. unit, describes Wolters Kluwer's history as well as the current organizational structure, and vision for the future. In addition, he draws upon his recent experience to describe Wolters Kluwer's international legal business.
Are User Surveys Fit for Purpose? A Case Study on the Use of a Contingent Valuation Survey at Middle Temple Library
Authors: Satterley Renae , Woellhaf Adam
Published: May 2020

In this article, based on a presentation at the BIALL Annual Conference in 2019, Renae Satterley and Adam Woellhaf discuss the methodology and potential effectiveness of using contingent valuation surveys in law libraries. Their approach is based on the Middle Temple Library's experience of running such a survey in 2018.
Use of Mobile Technologies by Law Students in the Law Library: a Detailed Investigation
Authors: Abbas Zaki , MacFarlane Andrew , Robinson Lyn
Published: May 2020

This paper follows up from a previous study on this topic and outlines the second part of a wider, two-part study on the information seeking behaviour (ISB) of law students. Exploratory work was outlined in a previous publication17 and there we found that although mobile technologies offered benefits to law students seeking information for their academic studies, there was concern from law librarians that the use of electronic resources via both non-mobile and mobile interfaces resulted in a loss of skills required for information retrieval due to the increasing capabilities of electronic resources’ search interfaces. To gain more insight into how law students were using mobile information resources, and better understand the advantages and disadvantages of such, we extended our study to a wider cohort and employed more research techniques including a focus group. This final phase of our study was conducted between 2015 to 2017. Here our cohort included another set of law librarians (13) and a further 54 law students. We expanded our research tools to include 2 thematic questionnaires and a focus group exercise. Our findings discovered that law librarians were concerned with the intangibility of digital formats. Law students remained indifferent to this aspect and valued the speed, multi-tasking and near-ubiquitous accessibility attributes that electronic format use via mobile technologies provided. These learnings and more, with conclusions, are reported in the course of this paper written by Zaki Abbas, Andrew MacFarlane and Lyn Robinson.
Measuring what matters – information systems for management of chronic disease in primary healthcare settings in low and middle-income countries: challenges and opportunities
Authors: Mayston R. , Ebhohimen K. , Jacob K.
Published: May 2020

Effective health information systems are essential to the delivery of high-quality community-based care for chronic disease which will be needed to address the changing healthcare needs of populations in low and middle-income country settings. Health management information systems (health service data collected at facility level) and electronic health records (data organised by individual patients) may support the measurement-based, collaborative approach that is central to the chronic care model, which has been adopted as the basis for task-shared models of care for mental health and non-communicable disease. We used the performance of routine information systems management to guide our commentary on the evidence-base about information systems to support chronic care. We found that, despite an appetite for using the information to support decision-making around service planning, this rarely happens in practice, reasons include that data is not perceived to be of good quality or fit for purpose. There is often a mismatch between technology design and the availability of specialised knowledge and infrastructure. However, when data collection is designed in collaboration with local stakeholders, there is some evidence of success, demonstrated by completion and accuracy of data forms. Whilst there are global targets for the development of health information systems and progress on these is undoubtedly being made, indicators for chronic disease are seldom prioritised by national governments and there is insufficient decentralisation to facilitate local data-driven decision-making. Our recommendations for future research and development, therefore, focus upon the need to integrate context into the design of information systems: through building strong multisectoral partnerships, ensuring newly developed indicators are well aligned to service models and using technology that is a good fit with local infrastructure. This approach will be necessary if information systems are to deliver on their potential to drive improvements in care for chronic disease.
The Filmmaker in Wartime: Sergei Eisenstein Inside and Out
Authors: Neuberger Joan
Published: May 2020

In 1941, Sergei Eisenstein had a decision to make. Iosif Stalin commissioned him to make a film about Ivan the Terrible, and in the months that followed he vacillated about how to depict the bloody tyrant. The Nazi invasion in June temporarily distracted him from work on the film, but by the time he was evacuated to Alma Ata in October, Eisenstein was committed to making the defiantly unorthodox, transgressive film that we have. What changed? The bombing of Moscow in July compelled Eisenstein to reflect on his public and private responsibilities and on individualism and collectivism in ways that complicated those categories and clarified his determination to make Ivan the Terrible a serious study of political power and violence. His diary from this period contributes a first-hand account of the bombing, and shows us Eisenstein's thinking about the political implications of interior and exterior at this critical stage in his life and work. This text, unpublished and unintended for publication, gives us a voice and a spectrum of positions that we have not heard before on this key set of discourses in Soviet history.
Sample-Selection Biases and the Historical Growth Pattern of Children
Authors: Schneider Eric B.
Published: May 2020

Bodenhorn et al. (2017) have sparked considerable controversy by arguing that the fall in adult stature observed in military samples in the United States and Britain during industrialization was a figment of selection on unobservables in the samples. While subsequent papers have questioned the extent of the bias (Komlos and A’Hearn 2019; Zimran 2019), there is renewed concern about selection bias in historical anthropometric datasets. Therefore, this article extends Bodenhorn et al.’s discussion of selection bias on unobservables to sources of children’s growth, specifically focusing on biases that could distort the age pattern of growth. Understanding how the growth pattern of children has changed is important because these changes underpinned the secular increase in adult stature and are related to child stunting observed in developing countries today. However, there are significant sources of unobserved selection in historical datasets containing children’s and adolescents’ height and weight. This article highlights, among others, three common sources of bias: (1) positive selection of children into secondary school in the late nineteenth and early twentieth centuries; (2) distorted height by age profiles created by age thresholds for enlistment in the military; and (3) changing institutional ecology that determines to which institutions children are sent. Accounting for these biases adjusts the literature in two ways: evidence of a strong pubertal growth spurt in the nineteenth century is weaker than formerly acknowledged and some long-run analyses of changes in children’s growth are too biased to be informative, especially for Japan.
Basalts From the Chukchi Borderland: 40Ar/39Ar Ages and Geochemistry of Submarine Intraplate Lavas Dredged From the Western Arctic Ocean
Authors: Mukasa Samuel B. , Andronikov Alexandre , Brumley Kelley , Mayer Larry A. , Armstrong Andrew
Published: May 2020

Submarine volcanism in the western Arctic Ocean, known as Amerasia Basin, is attributed to a mantle plume based on geophysics and meager geochemical evidence. Basaltic samples dredged from Chukchi Borderland within the basin have produced minimum 40Ar/39Ar ages for eruption at circa 118–112, circa 105–100, and circa 90–70 Ma, which we use to constrain tectonic models for basin opening. Major oxide and trace element concentrations and Sr, Nd, and Hf isotopic ratios of the lavas show that the circa 118–112 Ma samples from Northwind Ridge are tholeiites (low‐Ti tholeiite I) with low degrees of rare‐earth element (REE) fractionation, high overall heavy rare‐earth element (HREE), and Mg# (Mg‐number), which suggests magma derivation from a garnet‐free source followed by minor crystal fractionation. Strontium, Nd, and Hf isotope systematics for these lavas and ratios of highly incompatible trace elements point toward a lithospheric source. Eruptions at circa 105–100 and circa 90–70 Ma, both at Healy Spur, produced two types of lavas: low‐Ti tholeiite II—which are generally older than high‐Ti tholeiite—both common in continental flood basalt (CFB) provinces and both with trace element abundance patterns typifying a garnet‐free source and significant crystal fractionation for the high‐Ti tholeiite. The isotope characteristics for both groups are common features of asthenospheric sources. Composition‐time relationships for the lavas suggest inception of melting in the subcontinental lithospheric mantle (SCLM)—probably due to introduction of a heat source by a plume—followed later (at ca. 105–100 and ca. 90–70 Ma) by asthenospheric melting possibly triggered by plume rise.
Micro-light-emitting diodes with quantum dots in display technology
Authors: Liu Zhaojun , Lin Chun-Ho , Hyun Byung-Ryool , Sher Chin-Wei , Lv Zhijian , Luo Bingqing , Jiang Fulong , Wu Tom , Ho Chih-Hsiang , Kuo Hao-Chung , He Jr-Hau
Published: May 2020

Micro-light-emitting diodes (μ-LEDs) are regarded as the cornerstone of next-generation display technology to meet the personalised demands of advanced applications, such as mobile phones, wearable watches, virtual/augmented reality, micro-projectors and ultrahigh-definition TVs. However, as the LED chip size shrinks to below 20 μm, conventional phosphor colour conversion cannot present sufficient luminance and yield to support high-resolution displays due to the low absorption cross-section. The emergence of quantum dot (QD) materials is expected to fill this gap due to their remarkable photoluminescence, narrow bandwidth emission, colour tuneability, high quantum yield and nanoscale size, providing a powerful full-colour solution for μ-LED displays. Here, we comprehensively review the latest progress concerning the implementation of μ-LEDs and QDs in display technology, including μ-LED design and fabrication, large-scale μ-LED transfer and QD full-colour strategy. Outlooks on QD stability, patterning and deposition and challenges of μ-LED displays are also provided. Finally, we discuss the advanced applications of QD-based μ-LED displays, showing the bright future of this technology.
Micro-rocket robot with all-optic actuating and tracking in blood
Authors: Li Dengfeng , Liu Chao , Yang Yuanyuan , Wang Lidai , Shen Yajing
Published: May 2020

Micro/nanorobots have long been expected to reach all parts of the human body through blood vessels for medical treatment or surgery. However, in the current stage, it is still challenging to drive a microrobot in viscous media at high speed and difficult to observe the shape and position of a single microrobot once it enters the bloodstream. Here, we propose a new micro-rocket robot and an all-optic driving and imaging system that can actuate and track it in blood with microscale resolution. To achieve a high driving force, we engineer the microrobot to have a rocket-like triple-tube structure. Owing to the interface design, the 3D-printed micro-rocket can reach a moving speed of 2.8 mm/s (62 body lengths per second) under near-infrared light actuation in a blood-mimicking viscous glycerol solution. We also show that the micro-rocket robot is successfully tracked at a 3.2-µm resolution with an optical-resolution photoacoustic microscope in blood. This work paves the way for microrobot design, actuation, and tracking in the blood environment, which may broaden the scope of microrobotic applications in the biomedical field.
Genome diversification in globally distributed novel marine Proteobacteria is linked to environmental adaptation
Authors: Zhou Zhichao , Tran Patricia Q , Kieft Kristopher , Anantharaman Karthik
Published: May 2020

Proteobacteria constitute one of the most diverse and abundant groups of microbes on Earth. In productive marine environments like deep-sea hydrothermal systems, Proteobacteria are implicated in autotrophy coupled to sulfur, methane, and hydrogen oxidation, sulfate reduction, and denitrification. Beyond chemoautotrophy, little is known about the ecological significance of poorly studied Proteobacteria lineages that are globally distributed and active in hydrothermal systems. Here we apply multi-omics to characterize 51 metagenome-assembled genomes from three hydrothermal vent plumes in the Pacific and Atlantic Oceans that are affiliated with nine Proteobacteria lineages. Metabolic analyses revealed these organisms to contain a diverse functional repertoire including chemolithotrophic ability to utilize sulfur and C1 compounds, and chemoorganotrophic ability to utilize environment-derived fatty acids, aromatics, carbohydrates, and peptides. Comparative genomics with marine and terrestrial microbiomes suggests that lineage-associated functional traits could explain niche specificity. Our results shed light on the ecological functions and metabolic strategies of novel Proteobacteria in hydrothermal systems and beyond, and highlight the relationship between genome diversification and environmental adaptation.
“Direct to Drug” screening as a precision medicine tool in multiple myeloma
Authors: Bonolo de Campos Cecilia , Meurice Nathalie , Petit Joachim L. , Polito Alysia N. , Zhu Yuan Xiao , Wang Panwen , Bruins Laura A. , Wang Xuewei , Lopez Armenta Ilsel D. , Darvish Susie A. , Ahmann Greg J. , Henderson Kimberly J. , Tian Shulan , Kruse Jonas J. , Stewart William M. , Larsen Jeremy T. , Reeder Craig B. , Dingli David , Kapoor Prashant , Kumar Shaji K. , Fonseca Rafael , Bergsagel P. Leif , Braggio Esteban , Stewart A. Keith
Published: May 2020

Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin’s lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This “direct to drug” screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.
Role of pyruvate kinase M2-mediated metabolic reprogramming during podocyte differentiation
Authors: Yuan Qi , Miao Jiao , Yang Qianqian , Fang Li , Fang Yi , Ding Hao , Zhou Yang , Jiang Lei , Dai Chunsun , Zen Ke , Sun Qi , Yang Junwei
Published: May 2020

Podocytes, a type of highly specialized epithelial cells, require substantial levels of energy to maintain glomerular integrity and function, but little is known on the regulation of podocytes’ energetics. Lack of metabolic analysis during podocyte development led us to explore the distribution of mitochondrial oxidative phosphorylation and glycolysis, the two major pathways of cell metabolism, in cultured podocytes during in vitro differentiation. Unexpectedly, we observed a stronger glycolytic profile, accompanied by an increased mitochondrial complexity in differentiated podocytes, indicating that mature podocytes boost both glycolysis and mitochondrial metabolism to meet their augmented energy demands. In addition, we found a shift of predominant energy source from anaerobic glycolysis in immature podocyte to oxidative phosphorylation during the differentiation process. Furthermore, we identified a crucial metabolic regulator for podocyte development, pyruvate kinase M2. Pkm2-knockdown podocytes showed dramatic reduction of energy metabolism, resulting in defects of cell differentiation. Meanwhile, podocyte-specific Pkm2-knockout (KO) mice developed worse albuminuria and podocyte injury after adriamycin treatment. We identified mammalian target of rapamycin (mTOR) as a critical regulator of PKM2 during podocyte development. Pharmacological inhibition of mTOR potently abrogated PKM2 expression and disrupted cell differentiation, indicating the existence of metabolic checkpoint that need to be satisfied in order to allow podocyte differentiation.
miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis
Authors: Wu Binhua , Zhang Ligang , Yu Yunfei , Lu Tongyi , Zhang Yinmei , Zhu Wenhui , Song Qifang , Lv Chengding , Guo Jiaying , Tian Yiqiao , Deng Ning
Published: May 2020

miRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especially regarding to mechanism of tumor angiogenesis regulation. Based on the qRT-PCR and IHC analysis, we found that miR-6086 was maintained a very low level both in ovarian cancer cell lines and tissues. Further, we identified OC2 and EGFL6 as the direct targets of miR-6086 by luciferase assay and we observed an inverse relationship between the expression of miR-6086 and the OC2/VEGFA/EGFL6 axis. The Western blotting analysis suggested that OC2 could directly upregulate VEGFA and indirectly up-regulate EGFL6 through VEGFA. Moreover, miR-6086 could indirectly downregulate VEGFA through OC2. In addition, miR-6086, siOC2 and siEGFL6 could negatively regulate the tumor growth and angiogenesis of ovarian cancer (Skov3) in the animal studies, with the inhibition rates of 77.07%, 69.89%, and 73.62%, respectively (**p < 0.01). Moreover, the tumor cell proliferation, migration, and invasion of ovarian cancer cell lines (Caov3 and Skov3) and vascular formation (HUVECs) were significantly suppressed in vitro, by decreasing the AKT/MAPK pathways (*p < 0.05). Taken together, our results reveal that miR-6086 can suppress the angiogenesis networks in ovarian cancer by down-regulating the OC2/VEGFA/EGFL6 axis, directly or indirectly, which may provide potential targets for tumor therapeutics.
FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression
Authors: He Qihan , Yang Lin , Gao Kaiping , Ding Peikun , Chen Qianqian , Xiong Juan , Yang Wenhan , Song Yi , Wang Liang , Wang Yejun , Ling Lijuan , Wu Weiming , Yan Jisong , Zou Peng , Chen Yuchen , Zhai Rihong
Published: May 2020

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The mechanisms underlying NSCLC tumorigenesis are incompletely understood. Transfer RNA (tRNA) modification is emerging as a novel regulatory mechanism for carcinogenesis. However, the role of tRNA modification in NSCLC remains obscure. In this study, HPLC/MS assay was used to quantify tRNA modification levels in NSCLC tissues and cells. tRNA-modifying enzyme genes were identified by comparative genomics and validated by qRT-PCR analysis. The biological functions of tRNA-modifying gene in NSCLC were investigated in vitro and in vivo. The mechanisms of tRNA-modifying gene in NSCLC were explored by RNA-seq, qRT-PCR, and rescue assays. The results showed that a total of 18 types of tRNA modifications and up to seven tRNA-modifying genes were significantly downregulated in NSCLC tumor tissues compared with that in normal tissues, with the 2ʹ-O-methyladenosine (Am) modification displaying the lowest level in tumor tissues. Loss- and gain-of-function assays revealed that the amount of Am in tRNAs was significantly associated with expression levels of FTSJ1, which was also downregulated in NSCLC tissues and cells. Upregulation of FTSJ1 inhibited proliferation, migration, and promoted apoptosis of NSCLC cells in vitro. Silencing of FTSJ1 resulted in the opposite effects. In vivo assay confirmed that overexpression of FTSJ1 significantly suppressed the growth of NSCLC cells. Mechanistically, overexpression of FTSJ1 led to a decreased expression of DRAM1. Whereas knockdown of FTSJ1 resulted in an increased expression of DRAM1. Furthermore, silencing of DRAM1 substantially augmented the antitumor effect of FTSJ1 on NSCLC cells. Our findings suggested an important mechanism of tRNA modifications in NSCLC and demonstrated novel roles of FTSJ1 as both tRNA Am modifier and tumor suppressor in NSCLC.
Transgelin is a poor prognostic factor associated with advanced colorectal cancer (CRC) stage promoting tumor growth and migration in a TGFβ-dependent manner
Authors: Elsafadi Mona , Manikandan Muthurangan , Almalki Sami , Mahmood Amer , Shinwari Tasneem , Vishnubalaji Radhakrishnan , Mobarak Mohammad , Alfayez Musaad , Aldahmash Abdullah , Kassem Moustapha , Alajez Nehad M.
Published: May 2020

Colorectal cancer (CRC) is the fourth most common cancer type globally. Investigating the signaling pathways that maintain cancer cell phenotype can identify new biomarkers for targeted therapy. Aberrant transforming growth factor-β (TGFβ) signaling has been implicated in CRC progression, however, the exact mechanism by which TGFβ exerts its function is still being unraveled. Herein, we investigated TAGLN expression, prognostic value, and its regulation by TGFβ in CRC. While TAGLN was generally found to be downregulated in CRC, elevated expression of TAGLN was associated with advanced CRC stage and predicted poor overall survival (hazard ratio (HR) = 1.8, log-rank testP-value = 0.014) and disease-free survival (HR = 1.6, log-rank testP-value = 0.046), hence implicating TAGLN as poor prognostic factor in CRC. Forced expression of TAGLN was associated with enhanced CRC cell proliferation, clonogenic growth, cell migration and in vivo tumor formation in immunocompromised mice, while targeted depletion of TAGLN exhibited opposing biological effects. Global gene expression profiling of TAGLN-overexpressing or TAGLN-deficient CRC cell lines revealed deregulation of multiple cancer-related genes and signaling pathways. Transmission electron microscopy (TEM) revealed ultrastructural changes due to loss of TAGLN, including disruption of actin cytoskeleton organization and aberrant actin filament distribution. Hierarchical clustering, principle component, and ingenuity pathway analyses revealed distinct molecular profile associated with TAGLNhighCRC patients with remarkable activation of a number of mechanistic networks, including SMARCA4, TGFβ1, and P38 MAPK. The P38 MAPK was the top predicted upstream regulator network promoting cell movement through regulation of several intermediate molecules, including TGFβ1. Concordantly, functional categories associated with cellular movement and angiogenesis were also enriched in TAGLNhighCRC, supporting a model for the molecular mechanisms linking TGFβ-induced upregulation of TAGLN and CRC tumor progression and suggesting TAGLN as potential prognostic marker associated with advanced CRC pathological stage.
Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer
Authors: Yang Jian , Gong Yuhua , Lam Vincent K. , Shi Yan , Guan Yanfang , Zhang Yanyan , Ji Liyan , Chen Yongsheng , Zhao Yongliang , Qian Feng , Chen Jun , Li Pingang , Zhang Fan , Wang Jiayin , Zhang Xuanping , Yang Ling , Kopetz Scott , Futreal P. Andrew , Zhang Jianjun , Yi Xin , Xia Xuefeng , Yu Peiwu
Published: May 2020

Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916–21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.
The therapeutic potential of mesenchymal stem cells for cardiovascular diseases
Authors: Guo Yajun , Yu Yunsheng , Hu Shijun , Chen Yueqiu , Shen Zhenya
Published: May 2020

Mesenchymal stem cells (MSCs) are derived from a wide range of sources and easily isolated and cultured. MSCs have the capacity for in vitro amplification and self-renewal, low immunogenicity and immunomodulatory properties, and under certain conditions, MSCs can be differentiated into a variety of cells. In the cardiovascular system, MSCs can protect the myocardium by reducing the level of inflammation, promoting the differentiation of myocardial cells around infarct areas and angiogenesis, increasing apoptosis resistance, and inhibiting fibrosis, which are ideal qualities for cardiovascular repair. Preclinical studies have shown that MSCs can be transplanted and improve cardiac repair, but challenges, such as their low rate of migration to the ischemic myocardium, low tissue retention, and low survival rate after transplantation, remain. This article reviews the potential and methods of MSC transplantation in the treatment of cardiovascular diseases (CVDs) and the challenges of the clinical use of MSCs.
Evidence for a three-dimensional quantum spin liquid in PbCuTe2O6
Authors: Chillal Shravani , Iqbal Yasir , Jeschke Harald O. , Rodriguez-Rivera Jose A. , Bewley Robert , Manuel Pascal , Khalyavin Dmitry , Steffens Paul , Thomale Ronny , Islam A. T. M. Nazmul , Reuther Johannes , Lake Bella
Published: May 2020

The quantum spin liquid is a highly entangled magnetic state characterized by the absence of static magnetism in its ground state. Instead, the spins fluctuate in a highly correlated way down to the lowest temperatures. Quantum spin liquids are very rare and are confined to a few specific cases where the interactions between the magnetic ions cannot be simultaneously satisfied (known as frustration). Lattices with magnetic ions in triangular or tetrahedral arrangements, which interact via isotropic antiferromagnetic interactions, can generate such a frustration. Three-dimensional isotropic spin liquids have mostly been sought in materials where the magnetic ions form pyrochlore or hyperkagome lattices. Here we present a three-dimensional lattice called the hyper-hyperkagome that enables spin liquid behaviour and manifests in the compound PbCuTe2O6. Using a combination of experiment and theory, we show that this system exhibits signs of being a quantum spin liquid with no detectable static magnetism together with the presence of diffuse continua in the magnetic spectrum suggestive of fractional spinon excitations.
Probing the energy conversion process in piezoelectric-driven electrochemical self-charging supercapacitor power cell using piezoelectrochemical spectroscopy
Authors: Krishnamoorthy Karthikeyan , Pazhamalai Parthiban , Mariappan Vimal Kumar , Nardekar Swapnil Shital , Sahoo Surjit , Kim Sang-Jae
Published: May 2020

The design and development of self-charging supercapacitor power cells are rapidly gaining interest due to their ability to convert and store energy in an integrated device. Here, we have demonstrated the fabrication of a self-charging supercapacitor using siloxene sheets as electrodes and siloxene-based polymeric piezofiber separator immobilized with an ionogel electrolyte. The self-charging properties of the fabricated device subjected to various levels of compressive forces showed their ability to self-charge up to a maximum of 207 mV. The mechanism of self-charging process in the fabricated device is discussed via “piezoelectrochemical effect” with the aid of piezoelectrochemical spectroscopy measurements. These studies revealed the direct evidence of the piezoelectrochemical phenomenon involved in the energy conversion and storage process in the fabricated device. This study can provide insight towards understanding the energy conversion process in self-charging supercapacitors, which is of significance considering the state of the art of piezoelectric driven self-charging supercapacitors.
Control of electron-electron interaction in graphene by proximity screening
Authors: Kim M. , Xu S. G. , Berdyugin A. I. , Principi A. , Slizovskiy S. , Xin N. , Kumaravadivel P. , Kuang W. , Hamer M. , Krishna Kumar R. , Gorbachev R. V. , Watanabe K. , Taniguchi T. , Grigorieva I. V. , Fal’ko V. I. , Polini M. , Geim A. K.
Published: May 2020

Electron-electron interactions play a critical role in many condensed matter phenomena, and it is tempting to find a way to control them by changing the interactions’ strength. One possible approach is to place a studied system in proximity of a metal, which induces additional screening and hence suppresses electron interactions. Here, using devices with atomically-thin gate dielectrics and atomically-flat metallic gates, we measure the electron-electron scattering length in graphene and report qualitative deviations from the standard behavior. The changes induced by screening become important only at gate dielectric thicknesses of a few nm, much smaller than a typical separation between electrons. Our theoretical analysis agrees well with the scattering rates extracted from measurements of electron viscosity in monolayer graphene and of umklapp electron-electron scattering in graphene superlattices. The results provide a guidance for future attempts to achieve proximity screening of many-body phenomena in two-dimensional systems.
Protein-altering germline mutations implicate novel genes related to lung cancer development
Authors: Ji Xuemei , Mukherjee Semanti , Landi Maria Teresa , Bosse Yohan , Joubert Philippe , Zhu Dakai , Gorlov Ivan , Xiao Xiangjun , Han Younghun , Gorlova Olga , Hung Rayjean J. , Brhane Yonathan , Carreras-Torres Robert , Christiani David C. , Caporaso Neil , Johansson Mattias , Liu Geoffrey , Bojesen Stig E. , Le Marchand Loic , Albanes Demetrios , Bickeböller Heike , Aldrich Melinda C. , Bush William S. , Tardon Adonina , Rennert Gad , Chen Chu , Byun Jinyoung , Dragnev Konstantin H. , Field John K. , Kiemeney Lambertus FA. , Lazarus Philip , Zienolddiny Shan , Lam Stephen , Schabath Matthew B. , Andrew Angeline S. , Bertazzi Pier A. , Pesatori Angela C. , Diao Nancy , Su Li , Song Lei , Zhang Ruyang , Leighl Natasha , Johansen Jakob S. , Mellemgaard Anders , Saliba Walid , Haiman Christopher , Wilkens Lynne , Fernandez-Somoano Ana , Fernandez-Tardon Guillermo , Heijden Erik H. F. M. van der , Kim Jin Hee , Davies Michael P. A. , Marcus Michael W. , Brunnström Hans , Manjer Jonas , Melander Olle , Muller David C. , Overvad Kim , Trichopoulou Antonia , Tumino Rosario , Goodman Gary E. , Cox Angela , Taylor Fiona , Woll Penella , Wichmann Erich , Muley Thomas , Risch Angela , Rosenberger Albert , Grankvist Kjell , Johansson Mikael , Shepherd Frances , Tsao Ming-Sound , Arnold Susanne M. , Haura Eric B. , Bolca Ciprian , Holcatova Ivana , Janout Vladimir , Kontic Milica , Lissowska Jolanta , Mukeria Anush , Ognjanovic Simona , Orlowski Tadeusz M. , Scelo Ghislaine , Swiatkowska Beata , Zaridze David , Bakke Per , Skaug Vidar , Butler Lesley M. , Offit Kenneth , Srinivasan Preethi , Bandlamudi Chaitanya , Hellmann Matthew D. , Solit David B. , Robson Mark E. , Rudin Charles M. , Stadler Zsofia K. , Taylor Barry S. , Berger Michael F. , Houlston Richard , McLaughlin John , Stevens Victoria , Nickle David C. , Obeidat Ma’en , Timens Wim , Artigas María Soler , Shete Sanjay , Brenner Hermann , Chanock Stephen , Brennan Paul , McKay James D. , Amos Christopher I.
Published: May 2020

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.
Chaos-assisted two-octave-spanning microcombs
Authors: Chen Hao-Jing , Ji Qing-Xin , Wang Heming , Yang Qi-Fan , Cao Qi-Tao , Gong Qihuang , Yi Xu , Xiao Yun-Feng
Published: May 2020

Since its invention, optical frequency comb has revolutionized a broad range of subjects from metrology to spectroscopy. The recent development of microresonator-based frequency combs (microcombs) provides a unique pathway to create frequency comb systems on a chip. Indeed, microcomb-based spectroscopy, ranging, optical synthesizer, telecommunications and astronomical calibrations have been reported recently. Critical to many of the integrated comb systems is the broad coverage of comb spectra. Here, microcombs of more than two-octave span (450 nm to 2,008 nm) is demonstrated through χ(2) and χ(3) nonlinearities in a deformed silica microcavity. The deformation lifts the circular symmetry and creates chaotic tunneling channels that enable broadband collection of intracavity emission with a single waveguide. Our demonstration introduces a new degree of freedom, cavity deformation, to the microcomb studies, and our microcomb spectral range is useful for applications in optical clock, astronomical calibration and biological imaging.
Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line
Authors: Su Yapeng , Ko Melissa E. , Cheng Hanjun , Zhu Ronghui , Xue Min , Wang Jessica , Lee Jihoon W. , Frankiw Luke , Xu Alexander , Wong Stephanie , Robert Lidia , Takata Kaitlyn , Yuan Dan , Lu Yue , Huang Sui , Ribas Antoni , Levine Raphael , Nolan Garry P. , Wei Wei , Plevritis Sylvia K. , Li Guideng , Baltimore David , Heath James R.
Published: May 2020

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAFV600E mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to uncover a cell-state landscape with two paths connecting drug-naive and drug-tolerant states. The trajectory a given cell takes depends upon the drug-naive level of a lineage-restricted transcription factor. Each trajectory exhibits unique druggable susceptibilities, thus updating the paradigm of adaptive resistance development in an isogenic cell population.