bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity
Authors: Du Qian , Smith Grady C. , Luu Phuc Loi , Ferguson James M. , Armstrong Nicola J. , Caldon C. Elizabeth , Campbell Elyssa , Nair Shalima S. , Zotenko Elena , Gould Cathryn M. , Buckley Michael , Kaczorowski Dominik , Barton Kirston , Deveson Ira W. , Smith Martin A. , Powell Joseph E. , Skvortsova Ksenia , Stirzaker Clare , Achinger-Kawecka Joanna , Clark Susan J. 
Published: October 2020

AbstractDNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancerDNMT1andDNMT3BDNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.
Inhibition of SARS-CoV-2 viral entryin vitroupon blocking N- and O-glycan elaboration
Authors: Yang Qi , Hughes Thomas A. , Kelkar Anju , Yu Xinheng , Cheng Kai , Park Sheldon J. , Huang Wei-Chiao , Lovell Jonathan F. , Neelamegham Sriram 
Published: October 2020

ABSTRACTThe Spike protein of SARS-CoV-2, its receptor binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.
You-Gui-Wan ameliorates house dust mite-induced allergic asthma via modulating amino acid metabolic disorder and gut dysbiosis
Authors: Hsu Wei-Hsiang , Lin Li-Jen , Chao Yen-Ming , Lu Chung-Kuang , Kao Shung-Te , Lin Yun-Lian 
Published: October 2020

AbstractIntroductionAllergic asthma is a worldwide health problem, and its etiology remains incompletely understood. Besides, as current therapies for allergic asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. You-Gui-Wan (YGW), a traditional Chinese herbal remedy, has been used for boosting Yang, enhancing immunity and treating allergic asthma.ObjectivesThis study aims to explore the molecular changes during the development of allergic asthma and investigate the potential bio-signatures and the effect of YGW on house dust mite (HDM)-induced chronic allergic asthma in mice.MethodsDermatophagoides pteronyssinus (Der p), one of HDMs, was intratracheally administered once a week for a total of 7 treatments over 6 consecutive weeks to induce allergic asthma in mice. Serum metabolomics was analyzed by LC-QTOF-MS/MS. 16S rRNA-based microbiome profiling was used to analyze gut microbiota, and the correlation between metabolomic signatures and microbial community profiling was explored by Spearman correlation analysis.ResultsSerum metabolomic analysis revealed that 10 identified metabolites — acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine, were markedly elevated by Der p. These metabolites are mainly related to branch-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism. YGW administration reversed 7 of the 10 identified metabolites and chiefly affected BCAA metabolism. 16S DNA sequencing revealed that YGW profoundly changed Der p-induced gut microbiota composition. Multiple correlation analysis indicated 10 selected metabolites have a good correlation with gut microbiota.ConclusionDer p induced BCAA metabolic deviation in allergic asthma mice, and YGW administration effectively ameliorated the AA metabolic disorder, and improved gut dysbiosis. This study paves the way towards the interactions of Der-p on microbiome and gut microbiota, and the effects of YGW treatment as well as provides a support for YGW administration with potential benefits for allergic asthma.
GIANI: open-source software for automated analysis of 3D microscopy images
Authors: Barry David J. , Gerri Claudia , Bell Donald M. , D’Antuono Rocco , Niakan Kathy K. 
Published: October 2020

AbstractThe study of cellular and developmental processes in physiologically relevant three-dimensional (3D) systems facilitates an understanding of mechanisms underlying cell fate, disease and injury. While cutting-edge microscopy technologies permit the routine acquisition of 3D datasets, there is currently a limited number of open-source software packages to analyse such images. Here we describe GIANI (djpbarry.github.io/Giani), new software for the analysis of 3D images, implemented as a plugin for the popular FIJI platform. The design primarily facilitates segmentation of nuclei and cells, followed by quantification of morphology and protein expression. GIANI enables routine and reproducible batch-processing of large numbers of images and also comes with scripting and command line tools, allowing users to incorporate its functionality into their own scripts and also run GIANI on a high-performance computing cluster. We demonstrate the utility of GIANI by quantifying cell morphology and protein expression in confocal images of mouse early embryos and by segmenting nuclei from light sheet microscopy images of the flour beetle embryo. We also validate the performance of the software using simulated data. More generally, we anticipate that GIANI will be a useful tool for researchers in a variety of biomedical fields.
Androgen regulation of bowel function in mice and humans
Authors: Rastelli Daniella , Robinson Ariel , Matthews Lynley T. , Perez Kristina , Dan William , Yim Peter , Mixer Madison , Prochera Aleksandra , Hassan Rafla , Hall Kathryn , Ballou Sarah , Nee Judy , Lembo Anthony , Rao Meenakshi 
Published: October 2020

SummaryMany digestive disorders have prominent sex differences in incidence, symptomatology, and treatment response that are not well understood. Irritable bowel syndrome (IBS), for example, affects approximately 10% of the population worldwide and tends to have different manifestations in males and females. Androgens are steroid hormones present at much higher levels in post-pubertal males than females and could be involved in these sex differences, but their normal functions in the bowel are largely unknown. Here, we show that gonadal androgens are required for normal gastrointestinal motilityin vivo. In the healthy mouse gut, we detected androgen receptors in smooth muscle cells and a subset of enteric neurons. Surgical or genetic disruption of androgen signaling in adult mice selectively and reversibly altered colonic motility by affecting neurons rather than smooth muscle. To determine if androgens also influence human bowel function, we measured androgen levels in 208 adults with IBS. Free testosterone levels were lower in patients with IBS compared to healthy controls and inversely correlated with symptom severity. Taken together, these observations establish a role for androgens in the regulation of colonic motility and link altered androgen signaling with a common digestive disorder. These findings advance the fundamental understanding of gut motility, with implications for normal aging and disorders involving the gut-brain axis.
Inflight head stabilization associated with wingbeat cycle and sonar emissions in the Egyptian fruit bat
Authors: Rossborough Jackson , Salles Angeles , Stidsholt Laura , Madsen Peter , Moss Cynthia F. , Hoffman Larry F. 
Published: October 2020

AbstractSensory processing of environmental stimuli during locomotion is critical for the successful execution of goal-directed behaviors and navigating around obstacles. The outcome of these sensorimotor processes can be challenged by head movements that perturb the sensory coordinate frames directing behaviors. In the case of visually-guided behaviors, visual gaze stabilization results from the integrated activity of the vestibuloocular reflex and motor efference copy originating within circuits driving locomotor behavior. A recent videographic study showed that echolocating bats exhibit inflight head stabilization during a target identification and landing task, though compensatory timing of the bats’ sonar signals was not reported. In the present investigation we tested hypotheses that head stabilization is more broadly implemented during epochs of exploratory flight, and is temporally associated with emitted sonar signals, which would optimize acoustic gaze. This was achieved by measuring head and body kinematics with motion sensors secured to the head and body of free-flying Egyptian fruit bats. These devices were integrated with ultrasonic microphones to record the bat’s sonar emissions and elucidate their temporal association with periods of head stabilization. Head accelerations in the Earth-vertical axis were asymmetric with respect to wing downbeat and upbeat relative to body accelerations. This indicated that inflight head and body accelerations were uncoupled, outcomes consistent with the implementation of head movements that limit vertical acceleration during wing downbeat. Furthermore, sonar emissions during stable flight occurred most often during wing downbeat and head stabilization, supporting the conclusion that head stabilization behavior optimized sonar gaze and environmental interrogation via echolocation.Summary statementDirect measurements of head and body kinematics from affixed motion sensors revealed head stabilization behaviors during exploratory flights in bats. Most sonar emissions were temporally correlated with this behavior, thereby contributing to the optimization of acoustic gaze.
The impact of open-border organization culture and employees’ knowledge, attitudes, and rewards with regards to open innovation: an empirical study
Authors: Alassaf Deemah , Dabić Marina , Shifrer Dara , Daim Tugrul 
Published: October 2020

PurposeThe purpose of this paper is to fill a significant research gap in academic literature pertaining to open innovation (OI). To do so, this paper empirically tests the impact of organizational culture, employees’ knowledge, attitudes and rewards as antecedents and mediators of OI adoption in organizations, facilitating a more thorough understanding by using an empirical multi-level approach.Design/methodology/approachThis paper analyzes the results of the “Identification of Industrial Needs for Open Innovation Education in Europe” survey through a quantitative analysis using logistic regression models. This survey includes 528 employees working in 28 different industrial sectors in 37 countries, most of which are in Europe.FindingsThe results suggest a positive impact of organizational characteristics on the adoption of OI (i.e. including the adoption of outside-in and inside-out OI activities in participating organizations), showing that the openness of an organization’s culture increases its likelihood of adopting an OI paradigm. More importantly, the results highlight the positive mediating effect of employees’ knowledge and rewards on this relationship.Research limitations/implicationsThe data set that was the basis of this paper was generated in European countries, the results of the analysis are limited and appropriate for this region and may vary when applied to other regions of the world.Practical implicationsThe proposed multi-level approach offers new insight into organizational knowledge. It enables the improvement of OI and knowledge management practices in organizations by assisting practitioners and academics in recognizing the relationship between organizational culture; employees’ knowledge, attitudes and rewards; and the adoption of the OI paradigm.Social implicationsThis paper offers a possible explanation on why open-border cultures are more likely to have a successful OI adoption, by relating it to factors that advance in the presence of an open-border culture, such as active participation of OI relative departments in knowledge sourcing and knowledge exchange, and rewarding employees for OI activities.Originality/valueThis paper presents a new framework which links organizational culture to OI, moving on from merely examining culture in terms of its positive or negative impact on OI adoption. It contributes to research on the OI paradigm and knowledge management by highlighting the significance of antecedents and mediators from a multi-level perspective using multiple units of analysis. Most previous studies focus on a single unit of analysis.
Perceptions of wellness recovery action plan (WRAP) training: a systematic review and metasynthesis
Authors: Canacott Louise , Tickle Anna , Moghaddam Nima 
Published: October 2020

Purpose
The purpose of this systematic review was to address two questions: what is the qualitative evidence for the effects of the Wellness Recovery Action Plan (WRAP) training, as perceived by adults with mental health difficulties using it? What is the quality of qualitative literature evaluating WRAP?

Design/methodology/approach
Five electronic reference databases and the EThOS database for unpublished research were systematically searched, as well as two pertinent journals. Study quality was assessed using Critical Appraisal Skills Programme criteria and results analysed using thematic synthesis.

Findings
Of 73 studies, 12 qualitative papers met inclusion criteria and were generally good quality. Analyses demonstrated expected findings, such as increased understanding and active management of mental health in the context of group processes. Results also highlighted that WRAP training promoted acceptance and improved communication with professionals. Peer delivery of WRAP was highly valued, with contrasting perceptions of peers and professionals evident. Some cultural considerations were raised by participants from ethnic minorities.

Research limitations/implications
WRAP training participation has positive self-perceived effects beyond those captured by measures of recovery. Broader implications are suggested regarding earlier access to WRAP, professional support and communication between professionals and service users. Recommendations for further research include the relationship between social support and illness self-management and peer-delivered acceptance-based approaches. Multiple time-point qualitative studies could offer insights into WRAP training processes and whether changes are sustained.

Originality/value
As the first review of qualitative evidence regarding WRAP training, value is offered both through increased understanding of outcomes and also guidance for future research.
Inhibitory role of interleukin‐10 in the cutaneous reverse Arthus reaction
Authors: Ishiura Nobuko , Yanaba Koichi , Nashiro Kiyoko , Kudo Mari , Goto Taeko , Okochi Hitoshi , Sato Shinichi 
Published: October 2020

AbstractThe formation and deposition of immune complexes (IC) containing immunoglobulin (Ig)G antibodies induces an acute inflammatory response with tissue injury. One of the experimental models of IC‐related vasculitis is the cutaneous reverse passive Arthus reaction, in which IgG antibodies are injected i.d., followed immediately by the i.v. application of the corresponding antigen. This reaction is characterized by edema, hemorrhage and neutrophil infiltration. To assess the role of the anti‐inflammatory cytokine interleukin (IL)‐10 in IC‐related vasculitis, we investigated the cutaneous Arthus reaction using IL‐10 knockout (IL‐10KO) mice. Edema, which was quantified macroscopically by measuring the vascular leakage of Evans blue dye at 4 h after IC challenge, was significantly increased in IL‐10KO mice compared with wild‐type mice. In addition, hemorrhage, which was assessed by the average diameter of purpuric spots at 8 h after IC challenge, was enhanced significantly in IL‐10KO mice compared with wild‐type mice. Histological examination showed that the number of extravascular neutrophils was significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. Analysis of pro‐inflammatory cytokine mRNA expression showed that IL‐6 mRNA levels were significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. These results showed that IC‐induced inflammation and vascular damage were significantly enhanced in the absence of IL‐10. Thus, IL‐10 may limit tissue disruption by suppressing the excessive infiltration of neutrophils and cytokine expression in a mouse model of type III vasculitis.
Gray‐edged line sign of scabies burrow
Authors: Ueda Takashi , Katsura Yuri , Sasaki Azusa , Minagawa Daisuke , Amoh Yasuyuki , Shirai Kyoumi 
Published: October 2020

AbstractA scabies burrow is created by a mature female mite laying eggs through the stratum corneum, representing a kind of scabies eruption. We have noticed that the edges of the scabies burrow sometime appear as blackish‐gray lines. We named these lines the “gray‐edged line” sign, as a new feature of scabies burrows. The gray‐edged line sign has the following two tendencies: (i) it is rarely seen on the palm or sole; and (ii) when the burrow follows a curved course, the gray‐edged line often forms on the outer wall. Explaining the formation of this sign from clinical findings was difficult, so the aim of the present study was to elucidate the mechanisms underlying the gray‐edged line sign. This retrospective study involved collection of data from electronic medical records of patients treated for scabies in our department between April 2015 and February 2020. We treated 32 scabies patients, including 4 patients with the gray‐edged line sign. We analyzed clinical features, dermoscopy, histopathology and special stains. Fontana‐Masson staining showed melanin staining in three parts: feces; some keratinocytes around the scabies burrows; and the mouth and legs of the scabies mite. The gray‐edged line sign appears to represent mite feces containing melanin.
Interactions among global change pressures act in a non‐additive way on bumblebee individuals and colonies
Authors: Zaragoza‐Trello Carlos , Vilà Montserrat , Botías Cristina , Bartomeus Ignasi 
Published: October 2020

Abstract

Insect‐mediated pollination is fundamental for terrestrial ecosystems as well as for crop production. However, bee populations are declining as a consequence of different global change pressures. Even though these pressures do not act in isolation, their interactive effects have received less attention.

Through a cross‐treatment field experiment with Bombus terrestris colonies, we analysed the joint effect of climate warming, exposure to pesticides and landscape transformation on bumblebee development variables related to individual and colony fitness.

Our results show that an average increase of 1.62°C in the presence of high resource availability in the landscape increases the number of individuals of all colony castes. However, temperature increase is only favourable when foraging resources are not limiting. This is partly because under elevated temperatures, colonies can develop faster but also need to invest more in wax and silk material to protect the offspring and to cool the colony. We also found a decrease in the number of male production with exposure to pesticides.

At the individual level, colonies exposed to increased temperatures produced larger queens and workers, and at the same time, all castes presented less variability in body size. In addition, we observed a reduction in queen size with increasing resource availability.

Our experiment indicates that the interaction between global change pressures can be non‐additive and that colony‐level emergent properties of social species could buffer some of the individual impacts of these pressures. Hence, it is necessary to consider not only the joint effects of global change pressures but also the plasticity of the organisms' responses. This would help us to predict how populations will respond to these stressors in a complex real world and how species life‐history traits could modulate their adverse effects through complex phenotypic plastic responses.

A free Plain Language Summary can be found within the Supporting Information of this article.
Nalbuphine on postoperative gastrointestinal tract dysfunction after laparoscopic surgery for gynaecological malignancies: A randomized controlled trial
Authors: Chen Jia‐wei , Tian Lin , Zhang Le , Hu Jian‐ying , Huang Shao‐qiang , Jiao Jing 
Published: October 2020

AbstractThe aim of this study was to compare the effects of nalbuphine and sufentanil on the gastrointestinal (GI) tract after laparoscopic surgery for gynaecological malignancies. A total of 100 patients with American Society of Anesthesiologists (ASA) physical status I–II undergoing laparoscopic radical hysterectomy under general anaesthesia were enrolled. The patients were randomized to receive sufentanil (Group S) or nalbuphine (Group N) intraoperatively and postoperatively. The time to first passage of flatus, the time to first defaecation, the time to toleration of diet, the serum gastrin level, and the duration of hospital stay of the groups were compared. The Visual Analogue Scale (VAS) score for postoperative pain, the number of dispensed patient‐controlled analgaesics (PCAs), and the prevalence of postoperative nausea, vomiting, and dizziness of the groups were also compared. The time to first passage of flatus (P = .551), time to first defaecation (P = .310), time to toleration of diet (P = .182), serum gastrin level (P = .397), prevalence of postoperative nausea (P = .920) and vomiting (P = .334), number of dispensed PCAs (P = .167), and the duration of hospital stay (P = .482) of the two groups were not significantly different. The VAS scores at 6 hours (P = .008), 12 hours (P = .002), and 24 hours (P = .013) postoperatively were lower in Group N than in Group S. In conclusion, nalbuphine was not associated with improved postoperative GI dysfunction after laparoscopic surgery for gynaecological malignancies, but it was associated with reduced postoperative pain.