bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Maternal IL-6 boosts glutamatergic synapses and disrupts hippocampal connectivity in the offspring
Authors: Mirabella Filippo , Desiato Genni , Mancinelli Sara , Fossati Giuliana , Rasile Marco , Morini Raffaella , Markicevic Marija , Grimm Christina , Amegandjin Clara , Termanini Alberto , Peano Clelia , Kunderfranco Paolo , di Cristo Graziella , Zerbi Valerio , Lodato Simona , Menna Elisabetta , Matteoli Michela , Pozzi Davide
Published: November 2020

Early prenatal inflammatory conditions are thought to represent a risk factor for different neurodevelopmental disorders, with long-term consequences on adult brain connectivity. Here we show that a transient IL-6 elevation, occurring at vulnerable stages of early neurodevelopment, directly impacts brain developmental trajectories through the aberrant enhancement of glutamatergic synapses and overall brain hyper-connectivity. The IL6-mediated boost of excitatory synapse density results from the neuron-autonomous, genomic effect of the transcription factor STAT3 and causally involves the activation of RGS4 gene as a candidate downstream target. The STAT3/RGS4 pathway is also activated in neonatal brains as a consequence of maternal immune activation protocols mimicking a viral infection during pregnancy. By demonstrating that prenatal IL-6 elevations result in aberrant synaptic and brain connectivity through the molecular players identified, we provide a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.
Emergence of a cephalosporin reduced susceptible Neisseria gonorrhoeae clone between 2014-2019 in Amsterdam, the Netherlands, revealed by a genomic population analysis
Authors: de Korne-Elenbaas Jolinda , Bruisten Sylvia M. , de Vries Henry J.C. , van Dam Alje P.
Published: November 2020

Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of reduced susceptible and resistant strains. For the purpose of epidemiological surveillance, a genomic population analysis was performed on Ng isolates from Amsterdam with a focus on ceftriaxone reduced susceptible isolates. Whole genome sequences were obtained from 318 isolates from 2014-2019 from Amsterdam, the Netherlands. Isolates were typed according to the Multi-Locus Sequence Typing (MLST) scheme and resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch- and global MLST7827 isolates. The majority of ceftriaxone reduced susceptible isolates belonged to MLST7363, MLST1901 and MLST7827. MLST7363 and MLST1901 were dominant reduced susceptible strains from 2014-2016 although MLST7827 emerged and became dominant during 2017-2019. MLST7827 reduced susceptible isolates carried a non-mosaic penA gene with A501V mutation and porB G121K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch- and other European MLST7827 isolates. Ceftriaxone reduced susceptible MLST7827 isolates emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB G121K/A121D mutations was strongly associated with ceftriaxone reduced susceptibility. Genetic clustering of Dutch- and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Therefore, close monitoring of the spread of this strain with an alarming susceptibility profile is needed.
Extensive MET alterations confer clinical response to MET inhibitors in gliomas
Authors: Zhao Zheng , Chen Jing , Bao Zhaoshi , Chai Ruichao , Zhang Ke-nan , Wu Lingxiang , Liu Hanjie , Mu Quanhua , Hu Huimin , Zeng Fan , Wang Zheng , Li Guanzhang , Chang Yuanhao , Wang Qiangwei , Wu Fan , Zhang Ying , Liu Yuqing , Zhang Wei , Kang Chunsheng , Wang Jiguang , Tao Rongjie , Wang Qianghu , Jiang Tao
Published: November 2020

Activating alterations of the MET gene are well-characterized oncogenic drivers, and MET inhibitors could successfully treat several tumor types with MET alterations, including gliomas with PTPRZ1-MET fusion. However, the full diversity and prevalence of MET alterations in gliomas are still lacking to accurately identify a subset of patients likely to benefit from MET inhibitor treatment. Here, we interrogated genomic profiles of 1,351 gliomas, and further identify 60 cases harboring MET alterations, including MET fusions and various MET exon skipping events. MET RNA alterations, but not MET amplification, are highly enriched in the secondary glioblastomas (sGBM) with significantly worse prognosis. Further molecular analysis has shown that MET RNA alterations acting an additive effects of MET overexpression are induced in the course of glioma evolution. In vitro and clinical studies indicate cells and patients harboring MET alterations have better response to MET inhibitors. Collectively, these data suggest that a subgroup of gliomas harboring MET alterations likely to have benefit from MET-targeted therapy.
Genetic and Epigenetic Features of Promoters with Ubiquitous Chromatin Accessibility Support Ubiquitous Transcription of Cell-essential Genes
Authors: Fan Kaili , Moore Jill E. , Zhang Xiao-ou , Weng Zhiping
Published: November 2020

Gene expression is controlled by regulatory elements with accessible chromatin. Although the majority of regulatory elements are cell type-specific, being in the open chromatin state in only one or a few cell types, approximately 16,000 regions in the human genome and 13,000 regions in the mouse genome are in the open chromatin state in nearly all of the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium, respectively. We performed a systematic analysis on the subset of 9,000 human and 8,000 mouse ubiquitously (ubi) open chromatin regions that were also classified as candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) by the ENCODE consortium, which we refer to as ubi-PLSs. We found that these ubi-PLSs had higher levels of CG dinucleotides and corresponded to the genes with ubiquitously high levels of transcriptional activities. Furthermore, the transcription start sites of a vast majority of cell-essential genes are located in ubi-PLSs. ubi-PLSs are enriched in the motifs of ubiquitously expressed transcription factors and preferentially bound by transcriptional cofactors that regulate ubiquitously expressed genes. Finally, ubi-PLSs are highly conserved between human and mouse at the synteny level, but not as conserved at the sequence level, with a high turnover of transcription factor motif sites. Thus, there is a distinct set of roughly 9,000 promoters in the mammalian genome that are actively maintained in the open chromatin state in nearly all cell types to ensure the transcriptional program of cell-essential genes.
IL-12 signaling promotes TET2-mediated DNA demethylation during CD8 T cell effector differentiation
Authors: Zebley Caitlin C. , Abdelsamed Hossam A. , Ghoneim Hazem E. , Alli Shanta , Haydar Dalia , Harris Tarsha , McGargill Maureen A. , Krenciute Giedre , Youngblood Ben
Published: November 2020

CD8 T cell memory differentiation endows T cells with an ability to rapidly induce effector functions upon pathogen re-encounter. While it is well established that substantial epigenetic remodeling occurs during the effector stage of the immune response, the signaling events that imprint CD8 T cells with these stable epigenetic programs are not well-defined. To gain insight into the signaling determinants of effector-associated epigenetic programming among CD8 T cells, we explored the role of IL-12 in the imprinting of IFNg expression during human CD8 T cell priming. We observed that TCR-mediated stimulation of human naïve CD8 T cells is not sufficient to induce substantial demethylation of the IFNg promotor. However, TCR stimulation in the presence of the inflammatory cytokine, IL-12, resulted in significant and stable demethylation of the IFNg locus that was commensurate with an increase in IFNg expression. We further show that IL-12-associated demethylation of the IFNg locus is coupled to cell division through TET2-dependent passive demethylation in anex vivohuman CAR T cell model system and anin vivoimmunologically competent murine system. Collectively, these data illustrate that IL-12 signaling promotes TET2-mediated effector epigenetic programming in CD8 T cells during the primary immune response and serve as proof of concept that signal 3 cytokines can be used to guide the induction of epigenetically regulated traits among T cells used for adoptive immunotherapies.
Expectations about motion direction affect perception and anticipatory smooth pursuit differently
Authors: Wu Xiuyun , Rothwell Austin C. , Spering Miriam , Montagnini Anna
Published: November 2020

Smooth pursuit eye movements and visual motion perception rely on the integration of current sensory signals with past experience. Experience shapes our expectation of current visual events and can drive eye movement responses made in anticipation of a target, such as anticipatory pursuit. Previous research revealed consistent effects of expectation on anticipatory pursuit—eye movements follow the expected target direction or speed—and contrasting effects on motion perception, but most studies considered either eye movement or perceptual responses. The current study directly compared effects of direction expectation on perception and anticipatory pursuit within the same direction discrimination task to investigate whether both types of responses are affected similarly or differently. Observers (n= 10) viewed high-coherence random-dot kinematograms (RDKs) moving rightward and leftward with a probability of 50, 70, or 90% in a given block of trials to build up an expectation of motion direction. They were asked to judge motion direction of interleaved low-coherence RDKs (0-15%). Perceptual judgements were compared to changes in anticipatory pursuit eye movements as a function of probability. Results show that anticipatory pursuit velocity scaled with probability and followed direction expectation (attraction bias), whereas perceptual judgments were biased opposite to direction expectation (repulsion bias). Control experiments suggest that the repulsion bias in perception was not caused by retinal slip induced by anticipatory pursuit, or by motion adaptation. We conclude that direction expectation can be processed differently for perception and anticipatory pursuit.
Pressure-induced Pb–Pb bonding and phase transition in Pb2SnO4
Authors: Spahr Dominik , Stękiel Michał , Zimmer Dominik , Bayarjargal Lkhamsuren , Bunk Katja , Morgenroth Wolfgang , Milman Victor , Refson Keith , Jochym Dominik , Byrne Peter J. P. , Winkler Björn
Published: November 2020

High-pressure single-crystal to 20 GPa and powder diffraction measurements to 50 GPa, show that the structure of Pb2SnO4strongly distorts on compression with an elongation of one axis. A structural phase transition occurs between 10 GPa and 12 GPa, with a change of space group fromPbamtoPnam. The resistivity decreases by more than six orders of magnitude when pressure is increased from ambient conditions to 50 GPa. This insulator-to-semiconductor transition is accompanied by a reversible appearance change from transparent to opaque. Density functional theory-based calculations show that at ambient conditions the channels in the structure host the stereochemically-active Pb 6s2lone electron pairs. On compression the lone electron pairs form bonds between Pb2+ions. Also provided is an assignment of irreducible representations to the experimentally observed Raman bands.
Robust error-based active disturbance rejection control of a quadrotor
Authors: Lechekhab Taki Eddine , Manojlovic Stojadin , Stankovic Momir , Madonski Rafal , Simic Slobodan
Published: November 2020

Purpose

The control of a quadrotor unmanned aerial vehicle (UAV) is a challenging problem because of its highly nonlinear dynamics, under-actuated nature and strong cross-couplings. To solve this problem, this paper aims to propose a robust control strategy, based on a concept of active disturbance rejection control (ADRC).

Design/methodology/approach

The altitude/attitude dynamics of a quadrotor is reformulated into the ADRC framework. Three distinct variations of the error-based ADRC algorithms, with different structures of generalized extended state observers (GESO), are derived for the altitude/attitude trajectory-following task. The convergence of the observation part is proved based on the singular perturbation theory. Through a frequency analysis and a quantitative comparison in a simulated environment, each design is shown to have certain advantages and disadvantages in terms of tracking accuracy and robustness. The digital prototypes of the proposed controllers for quadrotor altitude and attitude control channels are designed and validated through real-time hardware-in-the-loop (HIL) co-simulation, with field-programmable gate array (FPGA) hardware.

Findings

The effects of unavailable reference time-derivatives can be estimated by the ESO and rejected through the outer control loop. The higher order ESOs demonstrate better performances, but with reductions of stability margins. Time-domain simulation analysis reveals the benefits of the proposed control structure related to classical control approach. Real-time FPGA-based HIL co-simulations validated the performances of the considered digital controllers in typical quadrotor flight scenarios.

Practical implications

The conducted study forms a set of practical guidelines for end-users for selecting specific ADRC design for quadrotor control depending on the given control objective and work conditions. Furthermore, the paper presents detailed procedure for the design, simulation and validation of the embedded FPGA-based quadrotor control unit.

Originality/value

In light of the currently available literature on error-based ADRC, a comprehensive approach is applied here, which includes the design of error-based ADRC with different GESOs, its frequency-domain and time-domain analyses using different simulation of UAV flight scenarios, as well as its FPGA-based implementation and testing on the real hardware.
The impact of social support on job stress of shift working mothers: a study of casino employees in Macao
Authors: Liu Shuang
Published: November 2020

Purpose

The purpose of this paper is to provide an exploratory understanding of the impact of social support on job stress of shift working mothers in Macao casinos.

Design/methodology/approach

A qualitative research method was adopted in this study. A snowball sampling strategy was used to recruit participants, and in-depth semi-structured interviews were conducted on participants from different casinos of six Macao gaming operators.

Findings

The paper found out that emotional and instrumental supports from families and friends are the most important social support for shift working mothers to cope with their job stress in casinos.

Research limitations/implications

A qualitative method may lead to a misinterpretation or ignorance of key information due to the researcher bias. The snowball sampling strategy may lead to a biased sample which may not represent the entire population.

Originality/value

The understanding of what types of social support that shift working mothers appreciate and need the most may provide managerial implications for casino operators for a better support to their female employees.
Optimizing window size by integrating energy and lighting analyses considering occupants’ visual satisfaction
Authors: Montaser Koohsari Ayda , Heidari Shahin
Published: November 2020

Purpose

The purpose of this paper is to determine the approximate window-to-wall ratio (WWR), window width-to-height ratio (WHR) and sill level for a room in Rasht–Gilan province and to present an optimal window in each of the WWR ranges providing the minimum energy consumption by integrating artificial lighting and thermal analyses, whilst maintaining internal comfort conditions using dynamic evaluation.

Design/methodology/approach

The process of modelling has four main steps: 1 – defining the building's features and requirements, 2 – validating input weather file data by on-site measurement, 3 – determining input parameters for the lighting and thermal analysis and 4 – clarifying variable parameters and fitness function for the optimization algorithm. Also, the survey study is performed in a daylit office room, in which 30 employees are employed to answer the questions in three different times of a day. In this process, the impact of daylight on their visual comfort is surveyed in 1,350 different illuminance levels which are manually recorded.

Findings

The range of useful daylight illuminance (UDI) values is determined as 200–1,000 lux. The optimum range of WWRs in the case study is 15%–25%. Also, due to the appropriate window height, electric lighting could be decreased by 40%.

Originality/value

Thermal and lighting performance in buildings is the relation of facade characteristics to environmental sustainability. Recent studies focussed on optimizing WWR and window characteristics considering thermal comfort and energy analyses. However, architects need freedom for designing façade and making decisions in their first sketches. Thus a guideline for optimum window conditions in each WWR is required. Also, considering occupants' behaviour in practical buildings, the visual comfort investigation is a gap in WWR optimization.
Artificial intelligence in personnel management: the development of APM model
Authors: Chang Kirk
Published: November 2020

Purpose

Managers have mixed views of how artificial intelligence (AI) affects personnel management (PM). The purpose of this paper is to identify potential knowledge gap and bring new insights to the AI-personnel-management literature.

Design/methodology/approach

Both applicability and theoretical perspectives are adopted to critically discuss the constraint and opportunity of AI in PM. Tables and narrative analysis are used to clarify the role of AI in managerial practices.

Findings

Research findings have helped to develop a new model titled AI in Personnel Management (APM). The APM model unfolds itself in three levels, followed by potential outcome. The three levels comprise “organizational, managerial and individual job levels,” and the outcome comprises “organizational performance, employees’ well-being and staff turnover rate”.

Research limitations/implications

The APM model helps managers to understand the implication of AI in their workplace. With better understanding of AI’s implication, managers are more likely to develop appropriate AI-driven managerial policies, which in turn benefit employees and their organizations. The APM model acts as a reference guide, helping managers to evaluate the AI’s constraint and opportunity in their managerial practices.

Originality/value

The APM model is valuable and informative to the academic researchers, as it has first responded to Malik et al. (2019)’s call (re: the absence of AI and management literature), and, more importantly, it has advanced the knowledge of AI–management relationship, supporting scholars to further understand the role of AI in PM.
Who is the boss? Identifying key roles in telecom fraud network via centrality-guided deep random walk
Authors: Chang Yi-Chun , Lai Kuan-Ting , Chou Seng-Cho T. , Chiang Wei-Chuan , Lin Yuan-Chen
Published: November 2020

Purpose

Telecommunication (telecom) fraud is one of the most common crimes and causes the greatest financial losses. To effectively eradicate fraud groups, the key fraudsters must be identified and captured. One strategy is to analyze the fraud interaction network using social network analysis. However, the underlying structures of fraud networks are different from those of common social networks, which makes traditional indicators such as centrality not directly applicable. Recently, a new line of research called deep random walk has emerged. These methods utilize random walks to explore local information and then apply deep learning algorithms to learn the representative feature vectors. Although effective for many types of networks, random walk is used for discovering local structural equivalence and does not consider the global properties of nodes.

Design/methodology/approach

The authors proposed a new method to combine the merits of deep random walk and social network analysis, which is called centrality-guided deep random walk. By using the centrality of nodes as edge weights, the authors’ biased random walks implicitly consider the global importance of nodes and can thus find key fraudster roles more accurately. To evaluate the authors’ algorithm, a real telecom fraud data set with around 562 fraudsters was built, which is the largest telecom fraud network to date.

Findings

The authors’ proposed method achieved better results than traditional centrality indices and various deep random walk algorithms and successfully identified key roles in a fraud network.

Research limitations/implications

The study used co-offending and flight record to construct a criminal network, more interpersonal relationships of fraudsters, such as friendships and relatives, can be included in the future.

Originality/value

This paper proposed a novel algorithm, centrality-guided deep random walk, and applied it to a new telecom fraud data set. Experimental results show that the authors’ method can successfully identify the key roles in a fraud group and outperform other baseline methods. To the best of the authors’ knowledge, it is the largest analysis of telecom fraud network to date.
Effect of online hotel reviews on the relationship between defender and prospector strategies and management controls
Authors: Bortoluzzi Daiane Antonini , Lunkes Rogério João , Santos Edicreia Andrade dos , Mendes Alcindo Cipriano Argolo
Published: November 2020

Purpose

This study aims to analyze the effect of online hotel reviews on the relationship between defender and prospector strategies and management control system (MCS) design.

Design/methodology/approach

To conduct the study, this paper administered a questionnaire to large Brazilian hotels and analyzed data from 204 hotels using structural equation modeling and fuzzy logic.

Findings

The main results show that online hotel reviews have a positive and significant effect on the relationship between prospector strategy and personnel and action control. In contrast, online reviews have a negative effect on the relationship between defender strategy and personnel, action and results controls. Thus, it is confirmed that online reviews change the relationship between strategy and MCS design.

Practical implications

The results show that online reviews play an important role in the decisions of hotel managers regarding MCS design. Customer demand evaluations, which are regularly available online on analysis websites, help managers adapt the MCS design, ensuring that their actions are aligned with the adopted strategy. This study adds to previous studies by showing that hotel managers use the information from customer evaluations to improve their performance.

Originality/value

The management literature based on the contingency theory indicates that strategy is a variable that affects MCS design. This study extends this discussion by indicating that online reviews, specifically in the hotel industry, can also be a determining factor in defining management controls. In addition, this paper points out that OHR impacts differently, depending on the strategy used and the type of management control.
Two decades of international branch campus development, 2000–2020: a review
Authors: Wilkins Stephen
Published: November 2020

Purpose

The research aims to assess the achievements and challenges of international branch campuses (IBCs) to date and to consider how IBC development may progress in the future.

Design/methodology/approach

The article presents a review of the scholarly and grey literatures on IBCs. The commentary and discussion is structured around the objectives, perspectives and experiences of three key stakeholder groups, namely the institutions that own IBCs, students and host countries.

Findings

Some IBCs have failed to achieve their student recruitment and financial targets, while others have been successful, often expanding and moving into new, larger, purpose-built campuses. In the last few years, several countries have announced their intention to become a transnational education hub, or at least to allow the establishment of IBCs. It may be reasonable to assume that when there is demand for a product, supply will eventually follow. IBCs will survive and prosper as long as they provide benefits to each of their main stakeholder groups (i.e. students, institutions and governments), and as long as the local demand for higher education places exceeds the total supply.

Originality/value

The article provides a comprehensive and up-to-date review of IBC developments and research during the period 2000–2020. The findings and conclusions will be of interest to both researchers and practitioners.
Aphicidal activity of Bacillus thuringiensis strain AH‐2 against cotton aphid (Aphis gossypii)
Authors: Ajuna Henry B. , Kim Iksoo , Han Yeon Soo , Maung Chaw Ei Htwe , Kim Kil Yong
Published: November 2020

Bacillus thuringiensis (Bt) is the most commercialized entomopathogenic species. However, the low efficacy against notorious sap‐sucking Hemipteran pests and the high costs of production, reduce the applicability of Bt biopesticides. In this context, B. thuringiensis AH‐2 (Bt‐2) isolated from soil was found to release parasporal inclusions and aphicidal activity. Bt‐2 showed optimal growth at pH 8 and 30°C in tryptic soy broth (TSB) and maintained normal growth when cultured in cost‐effective test media, pink brown (PB), supplemented with either glucose (PBG) or sucrose (PBS). To study aphicidal activity against cotton aphid (Aphis gossypii), Bt‐2 and a commercial B. thuringiensis subspecies kurstaki (Btk) were used. Using third nymph (3 N) instars, treatment with Bt‐2 caused 70.2, 78.1 and 88.4% mortality at 10, 25 and 50% culture concentrations, respectively. Similarly, Btk resulted in 79.9, 80.4 and 92.9% mortality at 10, 25 and 50%, respectively. When cultured in TSB, PBG and PBS media, Bt‐2 culture (50%) resulted in 85.9, 82.9 and 82.2% 3 N mortality, respectively. Equally, Btk caused a mortality of 79.9, 78.9 and 78.9% in TSB, PBG and PBS, respectively. Bt‐2 exerted a notably higher aphicidal efficacy at 24 h after treatment compared to Btk, especially at low concentration. Moreover, both Bt strains significantly suppressed adult fecundity compared to control. At 50% culture concentration, Bt‐2 and Btk suppressed adult fecundity by 98.3 and 91.1%, respectively. Our result demonstrates a strong aphicidal efficacy of Bt‐2, and its potential production using cost‐effective PB medium.
Prognostic and clinicopathological roles of programmed death‐ligand 1 (PD‐L1) expression in thymic epithelial tumors: A meta‐analysis
Authors: Koh Hyun Min , Jang Bo Gun , Lee Hyun Ju , Hyun Chang Lim
Published: November 2020

Background

Programmed death‐ligand 1 (PD‐L1) is one of the immune checkpoint proteins, and plays an important role in the progression and microenvironment of cancer. PD‐L1 expression has been associated with poor survival in many cancers. Several studies have also shown an association between PD‐L1 expression and the prognosis of patients with thymic epithelial tumors (TETs). In this study, we systematically evaluated the prognostic and clinicopathological roles of PD‐L1 expression in TETs.

Methods

We searched the literature through PubMed, Embase and Cochrane library and chose the eligible studies, and subsequently performed a meta‐analysis to evaluate the prognostic and clinicopathological roles of PD‐L1 expression in TETs.

Results

Six of the 75 articles found in the literature were selected. PD‐L1 expression was significantly related to unfavorable overall survival (hazard ratio 1.52, 95% confidence interval [CI]: 1.01–2.30, P = 0.046) in TETs. PD‐L1 expression was significantly associated with male gender (odds ratio [OR] 1.55, 95% CI: 1.08–2.22, P = 0.017) and higher Masaoka stage (OR 3.93, 95% CI: 2.44–6.32, P < 0.001).

Conclusions

PD‐L1 expression was correlated with unfavorable prognosis in TETs, indicating PD‐L1 expression could help determine the prognosis of TET patients.
Clinical characteristics and risk factors for in‐hospital mortality of lung cancer patients with COVID‐19: A multicenter, retrospective, cohort study
Authors: Nie Lei , Dai Kai , Wu Jiang , Zhou Xia , Hu Junjun , Zhang Chao , Zhan Yan , Song Yu , Fan Wen , Hu Zhimin , Yang Hongshan , Yang Qiong , Wu Dongde , Li Fajiu , Li Daoyuan , Nie Rui
Published: November 2020

Background

Data on clinical, laboratory, and radiographic characteristics and risk factors for in‐hospital mortality of lung cancer patients with COVID‐19 are scarce. Here, we aimed to characterize the early clinical features of lung cancer patients with COVID‐19 and identify risk factors associated with in‐hospital mortality.

Methods

All consecutive lung cancer patients with laboratory‐confirmed COVID‐19 admitted to 12 hospitals in Hubei province, China, from 3 January to 6 May 2020 were included in the study. Patients without definite clinical outcomes during the period were excluded. Data on initial clinical, laboratory and radiographic findings were compared between survivors and nonsurvivors. Univariable and multivariable logistic regression analyses were used to explore the risk factors associated with in‐hospital mortality.

Results

Of the 45 lung cancer patients (median [interquartile range] age, 66 [58–74] years; 68.9% males) included, 34 (75.6%) discharged and 11 (24.4%) died. Fever (73.3%) and cough (53.3%) were the dominant initial symptoms, and respiratory symptoms were common. Lung cancer patients also presented atypical appearances of COVID‐19. In the multivariable analysis, prolonged prolongation prothrombin time (PT) (OR = 2.1, 95% CI: 1.00–4.41, P = 0.0497) and elevated high sensitivity cardiac troponin I (hs‐TNI) (OR = 7.65, 95% CI: 1.24–47.39, P = 0.0287) were associated with an increased risk of in‐hospital mortality.

Conclusions

Lung cancer patients with COVID‐19 have high in‐hospital mortality. Prolonged PT and elevated hs‐TNI are independent risk factors for in‐hospital mortality of lung cancer patients with COVID‐19.

Key points

Significant findings of the study

Lung cancer patients with COVID‐19 have atypical early symptoms and imaging features.

The prolonged prothrombin time and elevated high sensitivity cardiac troponin I are independent risk factors for in‐hospital mortality of lung cancer patients with COVID‐19.

What this study adds

This study characterizes the early clinical features of lung cancer patients with COVID‐19 in China, and identifies the risk factors associated with in‐hospital mortality of lung cancer patients with COVID‐19.
Sweet turning bitter: Carbohydrate sensing of complement in host defence and disease
Authors: Hevey Rachel , Pouw Richard B. , Harris Claire , Ricklin Daniel
Published: November 2020

The complement system plays a major role in threat recognition and in orchestrating responses to microbial intruders and accumulating debris. This immune surveillance is largely driven by lectins that sense carbohydrate signatures on foreign, diseased and healthy host cells and act as complement activators, regulators or receptors to shape appropriate immune responses. While carbohydrate sensing protects our bodies, misguided or impaired recognition can contribute to disease. Moreover, pathogenic microbes have evolved to evade complement by mimicking host signatures. While complement is recognized as a disease factor, we only slowly start to appreciate the role of carbohydrate interactions in the underlying processes. A better understanding of complement's sweet side will contribute to a better description of disease mechanisms and enhanced diagnostic and therapeutic options. This review introduces the key components in complement‐mediated carbohydrate sensing, discusses their role in health and disease, and touches on the potential effects of carbohydrate‐related disease intervention.

Linked Articles

This article is part of a themed issue on Canonical and non‐canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc
dUTPase inhibition confers susceptibility to a thymidylate synthase inhibitor in DNA‐repair‐defective human cancer cells
Authors: Yokogawa Tatsushi , Yano Wakako , Tsukioka Sayaka , Osada Akiko , Wakasa Takeshi , Ueno Hiroyuki , Hoshino Takuya , Yamamura Keisuke , Fujioka Akio , Fukuoka Masayoshi , Ohkubo Shuichi , Matsuo Kenichi
Published: November 2020

Deficiency in DNA repair proteins confers susceptibility to DNA damage, making cancer cells vulnerable to various cancer chemotherapies. 5‐Fluorouracil (5‐FU) is an anticancer nucleoside analog that both inhibits thymidylate synthase (TS) and causes DNA damage via the misincorporation of FdUTP and dUTP into DNA under the conditions of dTTP depletion. However, the role of the DNA damage response to its antitumor activity is still unclear. To determine which DNA repair pathway contributes to DNA damage caused by 5‐FU and uracil misincorporation, we examined cancer cells treated with 2ʹ‐deoxy‐5‐fluorouridine (FdUrd) in the presence of TAS‐114, a highly potent inhibitor of dUTPase that restricts aberrant base misincorporation. Addition of TAS‐114 increased FdUTP and dUTP levels in HeLa cells and facilitated 5‐FU and uracil misincorporation into DNA, but did not alter TS inhibition or 5‐FU incorporation into RNA. TAS‐114 showed synergistic potentiation of FdUrd cytotoxicity and caused aberrant base misincorporation, leading to DNA damage and induced cell death even after short‐term exposure to FdUrd. Base excision repair (BER) and homologous recombination (HR) were found to be involved in the DNA repair of 5‐FU and uracil misincorporation caused by dUTPase inhibition in genetically modified chicken DT40 cell lines and siRNA‐treated HeLa cells. These results suggested that BER and HR are major pathways that protect cells from the antitumor effects of massive incorporation of 5‐FU and uracil. Further, dUTPase inhibition has the potential to maximize the antitumor activity of fluoropyrimidines in cancers that are defective in BER or HR.
Is it really possible to compensate for colour blindness with a filter?
Authors: Valero Eva M. , Huertas Rafael , Martínez‐Domingo Miguel Ángel , Gómez‐Robledo Luis , Hernández‐Andrés Javier , Nieves Juan Luis , Romero Javier
Published: November 2020

In the last 2 decades, there has been a resurgence of the idea that passive aids such as colour filters can be an effective solution to compensate colour vision deficiency (CVD) or improve colour vision for subjects with CVD. We examine briefly the scientific evidence that has to date been gathered to study the reliability of these aids. In the light of our experience working in this field, we reflect on several related issues: why this question has not been elucidated before, how a filter would have to be designed for a specific task, and the importance of developing a personalised colour space for subjects with CVD to gain some insight into the effect of aids.
Assessment of Target Engagement in a First‐in‐Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders
Authors: Gehin Martine , Melchior Meggane , Welford Richard W.D. , Sidharta Patricia N. , Dingemanse Jasper
Published: November 2020

In this first‐in‐human study, the tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of sinbaglustat, a dual inhibitor of glucosylceramide synthase (GCS) and non‐lysosomal glucosyl ceramidase (GBA2), were investigated in healthy subjects. The single‐ascending dose (SAD) and multiple‐ascending dose (MAD) studies were randomized, double‐blind, and placebo‐controlled. Single doses from 10 to 2,000 mg in men and multiple doses from 30 to 1,000 mg twice daily for 7 days in male and female subjects were investigated. Tolerability, PK, and PD data were collected up to 3 days after (last) treatment administration and analyzed descriptively. Sinbaglustat was well‐tolerated in the SAD and MAD studies, however, at the highest dose of the MAD, three of the four female subjects presented a similar pattern of general symptoms. In all cohorts, sinbaglustat was rapidly absorbed. Thereafter, plasma concentrations decreased biphasically. In the MAD study, steady‐state conditions were reached on Day 2 without accumulation. During sinbaglustat treatment, plasma concentrations of glucosylceramide (GlcCer), lactosylceramide, and globotriaosylceramide decreased in a dose‐dependent manner, reflecting GCS inhibition. The more complex the glycosphingolipid, the more time was required to elicit PD changes. After treatment stop, GlcCer levels returned to baseline and increased above baseline at lowest doses, probably due to the higher potency of sinbaglustat on GBA2 compared to GCS. Overall, sinbaglustat was welltolerated up to the highest tested doses. The PK profile is compatible with b.i.d. dosing. Sinbaglustat demonstrated target engagement in the periphery for GCS and GBA2.
Diffuse Drivers of Modern Slavery: From Microfinance to Unfree Labour in Cambodia
Authors: Natarajan Nithya , Brickell Katherine , Parsons Laurie
Published: November 2020

Over the past two decades, the global issue of modern slavery has become increasingly prominent within development thinking and practice. Efforts to address it largely focus on criminal prosecutions of immediate ‘perpetrators’, for instance those who are direct employers or middlemen. This article adds to a growing call from critical scholars to look to the structural drivers of such highly exploitative labour relations. Drawing on an unfree labour approach that views debt bondage as embedded in and reproduced by capitalist accumulation, this analysis explores the diffuse drivers of unfree labour through the experiences of indebted farmers who have migrated from rural areas to work in and around Phnom Penh as debt‐bonded brick‐kiln labourers. The study demonstrates how debt discipline in the context of unregulated microfinance lending in rural Cambodia creates the conditions for unfree labour to emerge. Evidencing links between risky lending practices and unfree labour, the article strengthens calls to understand modern slavery as unfree labour and, in doing so, highlights the failures of the UN's Sustainable Development Goal 8 and other similar policies to make these crucial connections.
Inhibition of exosomal miR‐24‐3p in diabetes restores angiogenesis and facilitates wound repair via targeting PIK3R3
Authors: Xu Yan , Ouyang Liu , He Lei , Qu Yanzhen , Han Yu , Duan Deyu
Published: November 2020

Diabetic foot ulcer (DFU) is one of the common ailments of elderly people suffering from diabetes. Exosomes containing various active regulators have been found to play a significant role in apoptosis, cell proliferation and other biological processes. However, the effect and the underlying mechanism of action of diabetes patients derived from circulating exosomes (Dia‐Exos) on DFU remain unclear. Herein, we aim to explore the potential regulatory role of Dia‐Exos. First, we attempted to demonstrate the harmful effect of Dia‐Exos both in vivo and in vitro. miRNA‐24‐3p (miR‐24‐3p) was found enriched with Dia‐Exos. Hence, inhibition of this miRNA could partially reverse the negative effect of Dia‐Exos, thus, in ture, accelerates wound repair. Luciferase assay further verified the binding of miR‐24‐3p to the 3′‐UTR of phosphatidylinositol 3‐kinase regulatory subunit gamma (PIK3R3) mRNA and the PIK3R3 expression enhanced human umbilical vein endothelial cells functionality in vitro. Hence, the findings of this study reveal the regulatory role of Dia‐Exos in the process of wound healing and provide experimental evidence for the therapeutic effects of knocking down miR‐24‐3p in DFU treatment.
Potentials of AI in medical image analysis in Gastroenterology and Hepatology
Authors: Chen Hao , Sung Joseph J Y
Published: November 2020

With the advancement of artificial intelligence (AI) technology, it comes in a big wave carrying possibly huge impact in the field of medicine. Gastroenterology and hepatology, being a specialty relying much on diagnostic imaging, endoscopy, and histopathology, AI technology has promised improving the quality and consistency of care to the patients. In this review, we will elucidate the development of machine learning methods, especially the visual representation mechanism in deep learning on recognition tasks. Various AI‐image analysis applications in endoscopy, radiology, and pathology are covered in gastroenterology and hepatology and reveal the enormous potentials for AI in assisting diagnosis, prognosis, and treatment. We also discuss the promises as well as pitfalls for AI in medical image analysis and pointing out future research directions.
Comorbidities, anthropometric, demographic, and lifestyle risk factors for ulnar neuropathy at the elbow: A case control study
Authors: Mondelli Mauro , Mattioli Stefano , Vinciguerra Claudia , Ciaramitaro Palma , Aretini Alessandro , Greco Giuseppe , Sicurelli Francesco , Giorgi Stefano , Curti Stefania
Published: November 2020

We performed a prospective multicenter case‐control study to explore the association between ulnar neuropathy at elbow (UNE) and body and elbow anthropometric measures, demographic and lifestyle factors, and comorbidities. Cases and controls were consecutively enrolled among subjects admitted to four electromyography labs. UNE diagnosis was made on clinical and neurographic findings. The control group included all other subjects without signs/symptoms of ulnar neuropathy and with normal ulnar nerve neurography. Anthropometric measurements included weight, height, waist, hip circumferences, and external measures of elbow using a caliper. The participants filled in a self‐administered questionnaire on personal characteristics, lifestyle factors, and medical history. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by fitting unconditional logistic regression models adjusted by center and education level. We enrolled 220 cases (males 61.8%; mean age 51.7 years) and 460 controls (47.4% males; mean age 47.8 years). At multivariable analysis, UNE was associated to male gender (OR = 2.4, 95%CI = 1.6‐3.7), smoking habits (>25 pack‐years (OR = 2.3, 95%CI = 1.3‐4.1), body mass index (OR = 1.05, 95%CI 1.01‐1.10), polyneuropathies (OR = 4.1, 95%CI 1.5‐11.5), and leaning with flexed elbow on a table/desk (OR = 1.5, 95%CI 1.0‐2.2). Cubital groove width (CGW) turned out to be negatively associated with UNE (OR = 0.80, 95%CI = 0.74‐0.85). Our study suggests that some personal factors especially anthropometric measures of the elbow may play a role in UNE pathogenesis as the measures of wrist in CTS. We demonstrated that for each millimeter of smaller CGW the risk of idiopathic UNE increases of 25%.
Factors Associated with Caregiver Preferences for Children's Return to School during the COVID‐19 Pandemic
Authors: Limbers Christine A.
Published: November 2020

BACKGROUND

Amid the COVID‐19 pandemic, there is a need to understand caregiver preferences for their children's instructional format for the start of the 2020 to 2021 academic year. The purpose of the current study was to assess caregiver preferences for on‐campus versus virtual learning at home during the fall and factors associated with these preferences.

METHODS

Participants were caregivers of 4436 children and adolescents who were enrolled in pre‐kindergarten through high school at a large, public school district in Texas. Caregivers were asked to complete an anonymous, online survey about their initial preferences for their student's back to the school learning environment.

RESULTS

Caregivers of high‐ and middle‐school students were more likely to endorse a preference for an on‐campus/virtual hybrid instructional format and less likely to endorse a preference for a traditional, face‐to‐face instructional format compared to caregivers of elementary school students. Regardless of the school level, concerns about child health and safety were the factor most strongly associated with caregiver preferences for on‐campus versus virtual learning at home during the fall.

CONCLUSIONS

These data highlight the importance of school re‐opening plans offering virtual options and addressing caregiver concerns about children's health and safety amid the COVID‐19 pandemic.
Association of hepatitis C infection and risk of kidney cancer: A systematic review and meta‐analysis of observational studies
Authors: Wu Di , Hu Shiping , Chen Guozi , Chen Longjiao , Liu Jian , Chen Wenlin , Lv Youwen , Chen Xiaoni , Lin Shan , Wu Fenfang
Published: November 2020

Although some epidemiological studies have investigated the association between Hepatitis C virus (HCV) infection and the development of kidney cancer, the results are far from consistent. We conducted a systematic review and meta‐analysis of observational studies to determine the association. PubMed, EMBASE and Cochrane database were searched from 1 January 1975 to 7 January 2020. Study selection, data extraction and bias assessment (using the Newcastle‐Ottawa scale) were performed independently by 2 authors. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated using a random‐effects model. In all, 16 studies (11 cohort studies and 5 case‐control studies) involving a total of 391,071 HCV patients and 38,333,839 non‐HCV controls were included. The overall analysis showed a 47% higher risk to develop kidney cancer among the patients with HCV infection (pooled OR 1.47; 95% CI 1.14‐1.91), despite significant heterogeneity (I2 = 87.6%). The multivariable meta‐regression showed that study design, age, sample size and HIV co‐infection were significant sources of variance, and totally accounted for 82% of the I2. The risk of KC in HCV patients was further increased in studies without HCV/HBV‐ and HCV/HIV‐ co‐infection (pooled OR 1.66; 95%CI 1.23‐2.24). Multiple sensitivity analyses did not change the significant association. The present meta‐analysis indicated that HCV‐infected patients have a significantly higher risk of developing kidney cancer. Our results highlighted the rationale for improved renal surveillance in HCV patients for the early diagnosis of kidney cancer. Further investigations for the mechanisms underlying HCV‐induced kidney cancer are warranted.