bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mining the Selective Remodeling of DNA Methylation in Promoter Regions to Identify Robust Gene-Level Associations with Phenotype
Authors: Quan Yuan , Liang Fengji , Zhu Yuexing , Chen Ying , Xu Ruifeng , Xiong Jianghui 
Published: January 2020

AbstractEpigenetics is an essential biological frontier linking genetics to the environment, where DNA methylation is one of the most studied epigenetic events. In recent years, through the epigenome-wide association study (EWAS), researchers have identified thousands of phenotype-related methylation sites. However, the overlap between identified phenotype-related DNA methylation sites are often quite small, and it might clue to methylation remodeling has a certain degree of randomness within the genome. Thus, the identification of robust gene-phenotype associations is crucial for interpreting pathogenesis. How to integrate the methylation values of different sites on the same gene and to mining the DNA methylation at the gene level remains a challenge. A recent study found that the DNA methylation difference of the gene body and promoter region has a strong correlation with gene expression. In this study, we proposed a Statistical difference of DNA Methylation between Promoter and Other Body Region (SIMPO) algorithm to extract DNA methylation values at the gene level. First, by choosing to smoke as an environmental exposure factor, our method led to significant improvements in gene overlaps (from 5% to 17%) between different datasets. In addition, the biological significance of these genes (∼23%) are significantly better than those identified by traditional probe-based methods (∼18%, P-value = 5.18e-03). Then, we selected two disease content (e.g., insulin resistance and Parkinson’s disease) to show that the biological efficiency of disease-related gene identification increased from 15.43% to 44.44% (P-value = 1.20e-28). Thus, our results declare that mining the selective remodeling of DNA methylation in promoter regions can identify robust gene-level associations with phenotype, and the characteristic remodeling of a given gene’s promoter region can reflect the essence of disease.
Loss of vacuolar acidity results in iron sulfur cluster defects and divergent homeostatic responses during aging inSaccharomyces cerevisiae
Authors: Chen Kenneth L. , Ven Toby N. , Crane Matthew M. , Brunner Matthew L.C. , Pun Adrian K. , Helget Kathleen L. , Brower Katherine , Chen Dexter E. , Doan Ha , Dillard-Telm Justin D. , Huynh Ellen , Feng Yen-Chi , Yan Zili , Golubeva Alexandra , Hsu Roy A. , Knight Raheem , Levin Jessie , Mobasher Vesal , Muir Michael , Omokehinde Victor , Screws Corey , Tunali Esin , Tran Rachael K. , Valdez Luz , Yang Edward , Kennedy Scott R. , Herr Alan J. , Kaeberlein Matt , Wasko Brian M. 
Published: January 2020

ABSTRACTThe loss of vacuolar/lysosomal acidity is an early event during aging that has been linked to mitochondrial dysfunction. However, it is unclear how loss of vacuolar acidity results in age-related dysfunction. Through unbiased genetic screens, we determined that increased iron uptake can suppress the mitochondrial respiratory deficiency phenotype of yeastvmamutants, which have lost vacuolar acidity due to genetic disruption of the vacuolar ATPase proton pump. Yeastvmamutants exhibited nuclear localization of Aft1, which turns on the iron regulon in response to iron sulfur cluster (ISC) deficiency. This led us to find that loss of vacuolar acidity with age in wildtype yeast causes ISC defects and a DNA damage response. Using microfluidics to investigate aging at the single cell level, we observe grossly divergent trajectories of iron homeostasis within an isogenic and environmentally homogeneous population. One subpopulation of cells fails to mount the expected compensatory iron regulon gene expression program, and suffers progressively severe ISC deficiency with little to no activation of the iron regulon. In contrast, other cells show robust iron regulon activity with limited ISC deficiency, which allows extended passage and survival through a period of genomic instability during aging. These divergent trajectories suggest that iron regulation and ISC homeostasis represent a possible target for aging interventions.
A probabilistic gene expression barcode for annotation of cell-types from single cell RNA-seq data
Authors: Grabski Isabella N. , Irizarry Rafael A. 
Published: January 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) quantifies gene expression for individual cells in a sample, which allows distinct cell-type populations to be identified and characterized. An important step in many scRNA-seq analysis pipelines is the annotation of cells into known cell-types. While this can be achieved using experimental techniques, such as fluorescence-activated cell sorting, these approaches are impractical for large numbers of cells. This motivates the development of data-driven cell-type annotation methods. We find limitations with current approaches due to the reliance on known marker genes or from overfitting because of systematic differences between studies or batch effects. Here, we present a statistical approach that leverages public datasets to combine information across thousands of genes, uses a latent variable model to define cell-type-specific barcodes and account for batch effect variation, and probabilistically annotates cell-type identity. The barcoding approach also provides a new way to discover marker genes. Using a range of datasets, including those generated to represent imperfect real-world reference data, we demonstrate that our approach substantially outperforms current reference-based methods, in particular when predicting across studies. Our approach also demonstrates that current approaches based on unsupervised clustering lead to false discoveries related to novel cell-types.
Low-cost microphysiological systems: Feasibility study of a tape-based barrier-on-chip system for small intestine modeling
Authors: Winkler Thomas E. , Feil Michael , Stronkman Eva F.G.J. , Matthiesen Isabelle , Herland Anna 
Published: January 2020

AbstractWe see affordability as a key challenge in making organs-on-chips accessible to a wider range of users, particularly outside the highest-resource environments. Here, we present an approach to barrier-on-a-chip fabrication based on double-sided pressure-sensitive adhesive tape and off-the-shelf polycarbonate. Besides a low materials cost, common also to PDMS or thermoplastics, it requires minimal (€ 100) investment in laboratory equipment, yet at the same time is suitable for upscaling to industrial roll-to-roll manufacture. We evaluate our microhpysiological system with an epithelial (C2BBe1) barrier model of the small intestine, studying the biological effects of permeable support pore size, as well as stimulation with a common food compound (chili pepper-derived capsaicinoids). The cells form tight and continuous barrier layers inside our systems, with comparable permeability but superior epithelial polarization compared to Transwell culture, in line with other perfused microphysiological models. Permeable support pore size is shown to weakly impact barrier layer integrity as well as the metabolic cell profile. Capsaicinoid response proves distinct between culture systems, but we show that impacted metabolic pathways are partly conserved, and that cytoskeletal changes align with previous studies. Overall, our tape-based microphysiolgical system proves to be a robust and reproducible approach to studying physiological barriers, in spite of its low cost.
Mutations in the tomato gibberellin receptors suppresses xylem proliferation and reduces water loss under water-deficit conditions
Authors: Illouz-Eliaz Natanella , Nissan Idan , Nir Ido , Ramon Uria , Shohat Hagai , Weiss David 
Published: January 2020

AbstractLow gibberellin (GA) activity in tomato (Solanum lycopersicum) inhibits leaf expansion and reduces stomatal conductance. These lead to lower transpiration and improve water status under transient drought conditions. Tomato has three GIBBERELLIN-INSENSITIVE DWARF1 (GID1) GA receptors with overlapping activities and high redundancy. We have tested whether mutation in a single GID1 reduces transpiration without affecting growth and productivity. CRISPR-Cas9gid1mutants were able to maintain higher leaf water content under water-deficit conditions. Moreover, whilegid1aexhibited normal growth, it showed reduced whole plant transpiration and better recovery from dehydration. Mutation inGID1ainhibited xylem vessels proliferation that led to lower hydraulic conductance. In stronger GA mutants, we also found reduced xylem vessel expansion. These results suggest that low GA activity affects transpiration by multiple mechanisms; it reduces leaf area, promotes stomatal closure and reduces xylem proliferation and expansion and as a result, xylem hydraulic conductance. We further examined ifgid1aperform better than the control M82 in the field. Under these conditions, the high redundancy of GID1s was lost andgid1aplants were semi-dwarf, but their productivity was not affected. Althoughgid1adid not perform better under drought conditions in the field, it exhibited higher harvest index.HighlightThe loss of the tomato gibberellin receptors GID1s reduced xylem proliferation and xylem hydraulic conductance. These contribute to the effect of low gibberellin activity on water loss under water-deficit condition.
Transfer of hepatocellular microRNA regulates cytochrome P450 2E1 in renal tubular cells
Authors: Matthews Olivia , Morrison Emma E , Tranter John D , Lewis Philip Starkey , Toor Iqbal S , Srivastava Abhishek , Sargeant Rebecca , Rollison Helen , Matchett Kylie P , Gray Gillian A , Goldring Chris , Park Kevin , Denby Laura , Dhaun Neeraj , Bailey Matthew A , Henderson Neil C , Williams Dominic , Dear James W 
Published: January 2020

AbstractExtracellular microRNAs have been demonstrated to have the ability to enter kidney tubular cells and modify gene expression. We have used a Dicer-hepatocyte-specific microRNA conditional knock-out (Dicer-CKO) mouse to investigate functional microRNA transfer from liver to kidney under physiological conditions and in the context of drug toxicity. Dicer-CKO mice demonstrated a time-dependent decrease in the hepatocyte-derived microRNA, miR-122, in the kidney in the absence of other microRNA changes. During hepatotoxicity, miR-122 increased in kidney tubular cells; this was abolished in Dicer-CKO mice. Depletion of hepatocyte microRNAs increased expression and activity of the miR-122 target - cytochrome (CYP) P450 2E1 - in the kidney. Serum extracellular vesicles (ECVs) from mice with hepatotoxicity increased proximal tubular cell miR-122 and prevented cisplatin proximal tubular cell toxicity. miR-122 also increased in urinary ECVs during hepatotoxicity in humans. Transfer of microRNA was not restricted to liver injury – we detected miR-499 release with murine cardiac injury, and this correlated with an increase in the kidney. In summary, a physiological transfer of microRNA to the kidney exists, which is increased by liver injury. Regulation of renal drug response due to signalling by microRNA of hepatic origin represents a new paradigm for understanding and preventing nephrotoxicity.
Collective cell sorting requires contractile cortical waves in germline cells
Authors: Chanet Soline , Huynh Jean-René 
Published: January 2020

ABSTRACTEncapsulation of germline cells by layers of somatic cells forms the basic unit of female reproduction called primordial follicles in mammals and egg chambers inDrosophila. How germline and somatic tissues are coordinated for the morphogenesis of each separated unit remains poorly understood. Here, using improved live-imaging ofDrosophilaovaries, we uncovered periodic actomyosin waves at the cortex of germ cells. These contractile waves are associated with pressure release blebs, which project from germ cells into somatic cells. We demonstrate that these cortical activities, together with cadherin-based adhesion, are required to sort each germline cyst as one collective unit. Genetic perturbations of cortical contractility, blebs protrusion or adhesion between germline and somatic cells induced failures to encapsulate any germ cells or the inclusion of too many germ cells or even the mechanical split of germline cysts. Our results reveal that germ cells play an active role in the physical coupling with somatic cells to produce the female gamete.
Loyalty formation toward Halal food
Authors: Suhartanto Dwi , Marwansyah Marwansyah , Muflih Muhammad , Najib Moh Farid , Faturohman Irgiana 
Published: January 2020

Purpose
The purpose of this paper is to integrate the Quality–Loyalty Model and the Religiosity–Loyalty Model to assess loyalty formation toward Halal food.

Design/methodology/approach
Data from 320 respondents were collected in Bandung Indonesia through a survey. A partial least-square modeling was employed to evaluate the association between food quality, religiosity, perceived value, satisfaction and loyalty.

Findings
This study discloses that the two integrated loyalty models are fit, indicating that incorporating these loyalty models provides a better comprehension of loyalty toward Halal food. Further, this study confirms the importance of both food quality and religiosity in determining loyalty.

Practical implications
This research offers an important finding for Halal food managers to develop customer loyalty through food quality and religiosity. This research recommends that Halal food managers, besides obtaining Halal certification, need to constantly innovate and adopt world food-quality standards to deal with customers’ constantly changing demands.

Originality/value
This research is the first that integrates the Quality–Loyalty Model and the Religiosity–Loyalty Model to get a better understanding of loyalty formation toward Halal food.
Does environmental concern drive Asian firms’ governance?
Authors: Mitra Aditi , Gaur Sanjaya Singh 
Published: January 2020

PurposeThe sustainability issues faced by Asian firms, such as environmental destruction and depletion of resources, require the existing corporate social responsibility (COSR) models to be carefully examined and re-conceptualized. Both researchers and practitioners have indicated how social equity and having a long-term business perspective are imperative to address environmental concerns alongside fulfilling the wealth maximization goals among firms. The purpose of this study is to contribute to the literature by examining the interrelationships between COSR parameters among firms, with social equity perspective.Design/methodology/approachThe data for this study comes from the Thomson Reuters Asset4 Index. The baseline sample of this study included 1,690 firms listed between 2011 and 2017. For hypothesis testing, fixed-effect panel analysis on 10,140 firm-year observations over seven years from 2011 to 2017 was conducted. These data points were drawn from four Asian countries (Malaysia, Thailand, Singapore and Hong Kong).FindingsThis study indicates that developed stock exchange markets among Asian markets such as Singapore and Hong Kong are transitioning from a strong focus on environmental issues to a more social equity-based economy, which is driving higher governance performance. This indicates the significance of the social dimension inherent in sustainable development and goes beyond just the ethical dimensions among the firms and the economy at large. The study also presents the challenges of re-modeling existing COSR framework among firms in Asia which do not have a clear road map on how to achieve environmental performance to achieve higher levels of human well-being, as well as the ethical considerations of achieving the wealth maximization goal.Originality/valueThis paper is unique in nature because it attempts to re-conceptualize the COSR models that support governance initiatives from an Asian market perspective by improving upon environmental performance, which in turn addresses critical issues around depleting resources and reducing wastage in the production process. The re-conceptualization model used in this study is based on the social exchange theory developed by George Homans in 1958. Accordingly, this study links the circular flow of resource procurement as well as production to the circular flow of resource replenishment seen in the chosen emerging Asian markets.
Sex counts: An examination of sexual service advertisements in a UK online directory
Authors: Kingston Sarah , Smith Nicola 
Published: January 2020

AbstractInternationally, sex work research, public opinion, policy, laws, and practice are predicated on the assumption that commercial sex is a priori sold by women and bought by men. Scarce attention has been devoted to lesbian, gay, bisexual, transgender, or queer/questioning (LGBTQ) sex working as well as women who pay for sex. This is as much an empirical absence as it is a theoretical one, for the ideological claim that women comprise the “vast majority” of sex workers is rarely, if ever, exposed to empirical scrutiny. Focusing on the UK, we address this major gap in evidence in order to challenge the gendered and heterosexist logics that underpin contemporary debates. We do so by presenting large‐scale data gained from the quantitative analysis of 25,511 registered member profiles of an online escort directory. Our findings point to heterogeneity rather than homogeneity in the contemporary sex industry including in terms of gender identity, sexual orientation, and advertised client base. For example, while two‐thirds of advertisements self‐identify as “Female,” one in four are listed as “Male;” less than half list their sexual orientation as “Straight;” and nearly two‐thirds advertise to women clients. Our study thus challenges prevailing heteronormative assumptions about commercial sex, which erase LGBTQ sex workers and other non‐normative identities and practices, and which we argue have important political, practical, and theoretical consequences.
A review of surgical and peri‐operative factors to consider in emergency laparotomy care
Authors: Boyd‐Carson H. , Gana T. , Lockwood S. , Murray D. , Tierney G. M. 
Published: January 2020

SummaryPatients undergoing emergency laparotomy are a heterogeneous group with regard to comorbidity, pre‐operative physiological state and surgical pathology. There are many factors to consider in the peri‐operative period for these patients. Surgical duration should be as short as possible for adequate completion of the procedure. This is of particular importance in the elderly and comorbid population. To date, there are limited data addressing the role of damage control surgery in emergency general surgery. Dual consultant‐led care in all stages of emergency laparotomy care is increasing, with increased presence out of hours and also for high‐risk patients. The role of the stoma care team should be actively encouraged in all patients who may require a stoma. Due to the emergent and unpredictable nature of surgical emergencies, healthcare teams may need to employ novel strategies to ensure early input from the stoma care team. It is important for all members of the medical teams to ensure that patients have given consent for both anaesthesia and surgery before emergency laparotomy. Small studies suggest that patients and their families are not aware of the high risk of morbidity and mortality following emergency laparotomy before operative intervention. Elderly patients should have early involvement from geriatric specialists and careful attention paid to assessment of frailty due to its association with mortality and morbidity. Additionally, the use of enhanced recovery programmes in emergency general surgery has been shown to have some impact in reducing length of stay in emergency surgical patients. However, the emergent nature of this surgery has been shown to be a detrimental factor in full implementation of enhanced recovery programmes. The use of a national database to collect data on patients undergoing emergency laparotomy and their processes of care has led to reduced mortality and length of stay in the UK. However, internationally, fewer data are available to draw conclusions.
Human factors and the safety of surgical and anaesthetic care
Authors: Marshall S. D. , Touzell A. 
Published: January 2020

SummarySafety of patients in the operating theatre relies on a cordial and efficient working relationship between all members of the theatre team. A team that communicates well, defines the roles of its members and is aware of their limitations will provide safe patient care. In this review, we will examine how human factors engineering – the science of how to design processes, equipment and environments to optimise the human contributions to performance – can be used to improve safety and efficiency of surgery. Although these are often dismissed as ‘common sense’, we will explain how these solutions emerge not from healthcare but from diverse disciplines such as psychology, design and engineering.
Advances in regional anaesthesia and acute pain management: a narrative review
Authors: Albrecht E. , Chin K. J. 
Published: January 2020

SummaryRegional anaesthesia has undergone several exciting advances in the past few decades. Ultrasound‐guided techniques of peripheral nerve blockade have become the gold standard thanks to the associated improvements in efficacy, ease of performance and safety. This has increased the accessibility and utilisation of regional anaesthesia in the anaesthesia community at large and is timely given the mounting evidence for its potential benefits on various patient‐centred outcomes, including major morbidity, cancer recurrence and persistent postoperative pain. Ultrasound guidance has also paved the way for refinement of the technical performance of existing blocks concerning simplicity and safety, as well as the development of new regional anaesthesia techniques. In particular, the emergence of fascial plane blocks has further broadened the application of regional anaesthesia in the management of painful conditions of the thorax and abdomen. The preliminary results of investigations into these fascial plane blocks are promising but require further research to establish their true value and role in clinical care. One of the challenges that remains is how best to prolong regional anaesthesia to maximise its benefits while avoiding undue harm. There is ongoing research into optimising continuous catheter techniques and their management, intravenous and perineural pharmacological adjuncts, and sustained‐release local anaesthetic molecules. Finally, there is a growing appreciation for the critical role that regional anaesthesia can play in an overall multimodal anaesthetic strategy. This is especially pertinent given the current focus on eliminating unnecessary peri‐operative opioid administration.
Postoperative recovery: the importance of the team
Authors: Nilsson U. , Gruen R. , Myles P. S. 
Published: January 2020

SummaryAn ageing population and rising healthcare costs are challenging cost‐efficient hospital systems wanting to adapt, employing novel organisational structures designed to merge diverse skill sets. This needs not only physician and nursing leadership but also new models of care. Anaesthetists have expanded their role into the broader multidisciplinary field of peri‐operative medicine, emphasising collaboration and safety in health teams. A greater focus on patient‐centred care and shared decision making, along with validated metrics to quantify quality improvement activities, have emphasised the importance of comfort, patient satisfaction and quality of life after surgery. Shared decision‐making is more likely to be manifest in a flat hierarchy in which each member of the team brings their own experience and skills to optimise patient care. Successful surgery is best achieved by a coordinated, multidisciplinary team, embedded in a culture of collaboration and safety.