bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic and transcriptomic analyses reveal major differences between apple and pear scab nonhost resistance
Authors: Vergne Emilie , Chevreau Elisabeth , Ravon Elisa , Gaillard Sylvain , Pelletier Sandra , Bahut Muriel , Perchepied Laure
Published: June 2021

Abstract

Nonhost resistance is the outcome of most plant/pathogen interactions, but it has rarely been described in Rosaceous fruit species. Apple (Malus x domesticaBorkh.) have a nonhost resistance toVenturia pyrina, the scab species attacking European pear (Pyrus communisL.). Reciprocally,P. communishave a nonhost resistance toVenturia inaequalis, the scab species attacking apple. The major objective of our study was to compare the scab nonhost resistance in apple and in European pear, at the phenotypic and transcriptomic levels. Macro- and microscopic observations after reciprocal scab inoculations indicated that, after a similar germination step, nonhost apple/V. pyrinainteraction remained nearly symptomless, whereas more hypersensitive reactions were observed during nonhost pear/V. inaequalisinteraction. Comparative transcriptomic analyses of apple and pear nonhost interactions withV. pyrinaandV. inaequalis, respectively, revealed differences. Very few differentially expressed genes were detected during apple/V. pyrinainteraction, preventing the inferring of underlying molecular mechanisms. On the contrary, numerous genes were differentially expressed during pear/V. inaequalisinteraction, allowing a deep deciphering. Pre-invasive defense, such as stomatal closure, could be inferred, as well as several post-invasive defense mechanisms (apoplastic reactive oxygen species accumulation, phytoalexin production and alterations of the epidermis composition). In addition, a comparative analysis between pear scab host and nonhost interactions indicated that, although specificities were observed, two major defense lines seems to be shared in these resistances: cell wall and cuticle potential modifications and phenylpropanoid pathway induction. This first deciphering of the molecular mechanisms underlying a nonhost scab resistance in pear offers new possibilities for the genetic engineering of sustainable scab resistance in this species. Concerning nonhost scab resistance in apple, further analyses must be considered with the aid of tools adapted to this resistance with very few cells engaged.
Ciliated protozoa from industrial WWTP activated sludge: a biodiversity survey including trophic interactions and redescription ofBakuella subtropica(Spirotrichea, Hypotrichia) according to Next Generation Taxonomy
Authors: Liao Wanying , Serra Valentina , Gammuto Leandro , Spennati Francesco , Mori Gualtiero , Munz Giulio , Modeo Letizia , Petroni Giulio
Published: June 2021

Optimization of wastewater treatment with biological processes is a fundamental challenge of modern society. During past years new technologies have been developed for the purpose and prokaryotic organisms involved in the process extensively investigated. Nevertheless, relatively few studies so far analysed the protozoan community in these systems using modern integrative approaches, despite its obvious role in shaping ecological dynamics and, possibly, process efficiency. In the present study, we characterized the ciliate community in biological reactors of an Italian industrial (tannery) wastewater treatment plant (WWTP) applying modified Ludzack-Ettinger (MLE) process. This plant is characterized by moderate salinity, high solids retention time and high concentration of organic compounds, including a significant recalcitrant fraction. We performed the morphological and 18S rDNA characterizations of almost all the 21 ciliates retrieved along a one-year sampling period, and provided preliminary data on species occurrence, community dynamics, and trophic interactions. Only 16 species were observed on the sample collection day and most of them had an occurrence higher than 50%. The most frequently occurring and highly abundant organisms wereAspidiscacf.cicada,Euplotesspp.,Paramecium calkinsi, andPhialinasp.Cyclidiumcf.marinumwas only found on a single date and its presence was possibly related to a summer break-induced perturbation. All the species showed the capability to survive the short oxic/anoxic cycling typical of the studied WWTP process. Intriguingly, some of them (i.e.,Bakuella subtropicaandTrochiliopsis australis) turned out to be species isolated from brackish natural environment rich in organic load as well. As forB. subtropica, we provided an emended redescription according to the most recent taxonomy standards that include also mitogenomic sequencing.
SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets
Authors: Zheng Shuyu , Wang Wenyu , Aldahdooh Jehad , Malyutina Alina , Shadbahr Tolou , Tanoli Ziaurrehman , Pessia Alberto , Tang Jing
Published: June 2021

Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated SynergyFinder R package includes five main innovations. (1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. (2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. (3) We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. (4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. (5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.synergyfinderplus.org as a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.
Attention Networks and the Intrinsic Network Structure of the Human Brain
Authors: Markett Sebastian , Nothdurfter David , Focsa Antonia , Reuter Martin , Jawinski Philippe
Published: June 2021

Attention network theory states that attention is not a unified construct but consists of three independent systems that are supported by separable distributed networks: an alerting network to deploy attentional resources in anticipation of upcoming events, an orienting network to direct attention to a cued location, and a control network to select relevant information at the expense of concurrently available information. Ample behavioral and neuroimaging evidence supports the dissociation of the three attention domains. The strong assumption that each attentional system is realized through a separable network, however, raises the question how these networks relate to the intrinsic network structure of the brain.

Our understanding of brain networks has advanced majorly in the past years due to the increasing focus on brain connectivity. It is well established that the brain is intrinsically organized into several large-scale networks whose modular structure persists across task states. Existing proposals on how the presumed attention networks relate to intrinsic networks rely mostly on anecdotal and partly contradictory arguments. We addressed this issue by mapping different attention networks with highest spatial precision at the level of cifti-grayordinates. Resulting group maps were compared to the group-level topology of 23 intrinsic networks which we reconstructed from the same participants’ resting state fMRI data. We found that all attention domains recruited multiple and partly overlapping intrinsic networks and converged in the dorsal fronto-parietal and midcingulo-insular network. While we observed a preference of each attentional domain for its own set of intrinsic networks, implicated networks did not match well to those proposed in the literature. Our results indicate a necessary refinement of the attention network theory.
Song preferences predict the quality of vocal learning in zebra finches
Authors: Rodríguez-Saltos Carlos Antonio , Bhise Aditya , Karur Prasanna , Khan Ramsha Nabihah , Lee Sumin , Ramsay Gordon , Maney Donna L.
Published: June 2021

In songbirds, learning to sing is a highly social process that likely involves social reward. Here, we hypothesized that the degree to which a juvenile songbird learns a song depends on the degree to which it finds that song rewarding to hear during vocal development. We tested this hypothesis by measuring song preferences in young birds during song learning and then analyzing their adult songs. Song preferences were measured in an operant key-pressing assay. Juvenile male zebra finches (Taeniopygia guttata) had access to two keys, each of which was associated with a higher likelihood of playing the song of their father or that of another familiar adult (“neighbor”). To minimize the effects of exposure on learning, we implemented a reinforcement schedule that allowed us to detect preferences while balancing exposure to each song. On average, the juveniles significantly preferred the father’s song early during song learning, before they were themselves singing. At around post-hatch day 60, their preference shifted to the neighbor’s song. At the end of the song learning period, we recorded the juveniles’ songs and compared them to the father’s and the neighbor’s song. All of the birds copied father’s song. The accuracy with which the father’s song was imitated was positively correlated with the peak strength of the preference for the father’s song during the sensitive period. Our results show that preference for a social stimulus, in this case a vocalization, predicted social learning during development.
Genetic and biological hallmarks of colorectal cancer
Authors: Li Jiexi , Ma Xingdi , Chakravarti Deepavali , Shalapour Shabnam , DePinho Ronald A.
Published: June 2021

Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, and these insights have illuminated early detection, risk stratification, prevention, and treatment principles. Employing the hallmarks of cancer framework, we provide a conceptual framework to understand how genetic alterations in colorectal cancer drive cancer cell biology properties and shape the heterotypic interactions across cells in the tumor microenvironment. This review details research advances pertaining to the genetics and biology of colorectal cancer, emerging concepts gleaned from immune and single-cell profiling, and critical advances and remaining knowledge gaps influencing the development of effective therapies for this cancer that remains a major public health burden.
Winter fields antisense RNAs to kick off flowering
Authors: Jin Yu , Marquardt Sebastian
Published: June 2021

FLOWERING LOCUS C (FLC), a MADS-box transcription factor, plays a major role in determining flowering time in Arabidopsis. In this issue of Genes & Development, Zhao and colleagues (pp. 888–898) elucidate the role of COOLAIR antisense noncoding RNAs in FLC regulation through field trials and laboratory experiments. COOLAIR-mediated FLC silencing is induced by the first seasonal frost in the field and thus acts as a key molecular indicator during autumn for winter arrival.
Cloning Polymerase Chain Reaction (PCR) Products: Making T Vectors
Authors: Green Michael R. , Sambrook Joseph
Published: June 2021

During polymerase chain reaction (PCR), DNA polymerases such as Taq add a single, unpaired residue—preferentially an adenosyl residue—to each 3′ end of a double-stranded amplified product. The unpaired terminal (A) residues can pair with a linear T vector that carries an unpaired 3′-thymidyl residue at each end. T vectors can be prepared in the laboratory or they may be purchased ready-made from commercial suppliers. This protocol outlines two methods in common use to generate T vectors.
Simulations of applications using diaboloid mirrors
Authors: Sanchez del Rio Manuel , Goldberg Kenneth A. , Yashchuk Valeriy V. , Lacey Ian , Padmore Howard A.
Published: June 2021

The diaboloid is a reflecting surface that converts a spherical wave to a cylindrical wave. This complex surface may find application in new Advanced Light Source bending-magnet beamlines or in other beamlines that now use toroidal optics for astigmatic focusing. Here, the numerical implementation of diaboloid mirrors is described, and the benefit of this mirror in beamlines exploiting diffraction-limited storage rings is studied by ray tracing. The use of diaboloids becomes especially interesting for the new low-emittance storage rings because the reduction of aberration becomes essential for such small sources. The validity of the toroidal and other mirror surfaces approximating the diaboloid, and the effect of the mirror magnification, are discussed.
Structure of a dimer of the Sulfolobus solfataricus MCM N-terminal domain reveals a potential role in MCM ring opening
Authors: Meagher Martin , Spence Madison N. , Enemark Eric J.
Published: June 2021

Cells strongly regulate DNA replication to ensure genomic stability and prevent several diseases, including cancers. Eukaryotes and archaea strictly control DNA-replication initiation by the regulated loading of hexameric minichromosome maintenance (MCM) rings to encircle both strands of the DNA double helix followed by regulated activation of the loaded rings such that they then encircle one DNA strand while excluding the other. Both steps involve an open/closed ring transformation, allowing DNA strands to enter or exit. Here, the crystal structure of a dimer of the N-terminal domain of Sulfolobus solfataricus MCM with an intersubunit interface that is more extensive than in closed-ring structures, while including common interactions to enable facile interconversion, is presented. It is shown that the identified interface could stabilize open MCM rings by compensating for lost interactions at an open neighbor interface and that the prior open-ring cryo-EM structure of MCM loading has a similar extended interface adjacent to its open interface.
Well-being perception and lovemarks formation through experiential value in the context of the eco-friendly restaurant
Authors: Kim Seon Hee , Jeon Do Hyun , Jeon Hyeon Mo
Published: June 2021

Purpose

The purpose of this study is to provide useful data for setting up eco-friendly restaurant (EFR) marketing strategies by analyzing experiential value and well-being perception, lovemarks and behavior intention, before presenting practical proposals.

Design/methodology/approach

The data used in this study were based on a sample of 300 customers at “Seasonal Dining Table” in South Korea. Data were analyzed using confirmatory factor analysis and structural equation modeling.

Findings

As a result of the study, playfulness showed the greatest influence on well-being perception, followed by service excellent, aesthetics and efficiency. In addition, well-being perception was found to have a positive effect on brand love and brand respect. Finally, the role of experiential value, well-being perception and lovemarks as the determinants factors to increase the customer's behavioral intention toward EFR was confirmed.

Practical implications

The present research informed that effectively dealing with four constituents of experiential value (efficiency, service excellence, aesthetic and playfulness) are of utmost importance in building customers' well-being perception. In addition, customers' well-being perception and lovemarks should be improved to boost the level of behavior intention for EFR.

Originality/value

This is the first study to examine experiential value, well-being perception, lovemarks and behavior intention in the context of restaurants. In particular, it is differentiated from previous foodservice studies by examining the relationship between experiential value and well-being perception.
Polyfloral honey from urban beekeeping: two-year case study of polyphenols profile and antioxidant activity
Authors: Preti Raffaella , Tarola Anna Maria
Published: June 2021

Purpose

Urban beekeeping is spreading as an answer to promote bee conservation and to develop local economies. This study aims to highlight nutritional properties of polyfloral honeys produced in urban landscape and to compare them to the countryside counterparts.

Design/methodology/approach

This research has examined polyfloral urban honeys from a restricted area in Central Italy, for antioxidant capacity, total phenolic content and 15 polyphenols profile. Physicochemical parameters have been also determined to assess the overall quality of the samples. Results were compared with polyfloral honeys produced in surrounding countryside and monitored in two harvest years, 2018 and 2019. Principal component analysis was applied to the data to disclose significant differences among honeys and harvest years.

Findings

Urban honeys revealed up to threefold higher total amount of polyphenols with respect to rural honeys, and in the 2019 harvest, despite water scarcity that affected the national production, demonstrated 50% higher antioxidant capacity and total phenolic content. The majority of the 15 polyphenols studied resulted in more abundant urban honeys, in particular in the 2019 harvest. The multivariate analysis evidenced how honeys could be successfully separated according to their production area and harvest year by their different polyphenols profile.

Originality/value

Limited data are available on nutritional properties of urban honeys and on their content in antioxidants. The present results suggest that the cultivated urban environment, with its large floral biodiversity, can provide extra nutrition for bees, resulting in the production of a honey rich in nutraceutical compounds.
Advancing employability: applying training evaluation to employability development programs
Authors: Glerum David R. , Judge Timothy A.
Published: June 2021

Purpose

This paper aims to apply training evaluation to employability development, providing a systematic process to assess employability development programs' effectiveness under the framework of employability capital resources (Peeters et al., 2019).

Design/methodology/approach

The authors demonstrate the training evaluation process within an employability development program for US secondary school students. This process included providing validation evidence for measures of evaluation criteria across multiple samples of secondary school students and testing the effectiveness of the program utilizing a quasi-experimental design.

Findings

The authors systematically found support for the intervention's effects on training criteria (i.e. reactions, learning, behavior, results) and demonstrated the utility for training evaluation's application to employability development. The findings illustrate how a training evaluation approach can provide holistic evidence that an employability development program achieved its intended outcomes.

Originality/value

Employability is a new and burgeoning topic – however, employability development varies in how it is conceptualized, evaluated and assessed. By applying training evaluation approaches, employability development can be assessed within a unifying framework and better integrated within the Human Resource Management literature.
Forecasting mental health and emotions based on social media expressions during the COVID-19 pandemic
Authors: Tommasel Antonela , Diaz-Pace Andrés , Rodriguez Juan Manuel , Godoy Daniela
Published: June 2021

Purpose

The purpose of this paper is to present an approach for forecasting mental health conditions and emotions of a given population during the COVID-19 pandemic in Argentina based on social media contents.

Design/methodology/approach

Mental health conditions and emotions are captured via markers, which link social media contents with lexicons. First, the authors build time series models that describe the evolution of markers and their correlation with crisis events. Second, the authors use the time series for forecasting markers and identifying high prevalence points for the estimated markers.

Findings

The authors evaluated different forecasting strategies that yielded different performance and capabilities. In the best scenario, high prevalence periods of emotions and mental health issues can be satisfactorily predicted with a neural network strategy, even at early stages of a crisis (e.g. a training period of seven days).

Practical implications

This work contributes to a better understanding of how psychological processes related to crises manifest in social media, and this is a valuable asset for the design, implementation and monitoring of health prevention and communication policies.

Originality/value

Although there have been previous efforts to predict mental states of individuals, the analysis of mental health at the collective level has received scarce attention. The authors take a step forward by proposing a forecasting approach for analyzing the mental health of a given population at a larger scale.
Deconstructing the origins of Cressey’s Fraud Triangle
Authors: Tickner Peter , Button Mark
Published: June 2021

Purpose

Cressey’s Fraud Triangle has been referenced in 8,584 studies and academic papers [1] and is a stalwart of training courses for accounting and audit practitioners and fraud investigators. The Fraud Triangle has endured for three decades in the academic and practitioner worlds. This study aims to explore the origins of Cressey’s Fraud Triangle and challenge its practical value to a fraud investigator.

Design/methodology/approach

This study has developed from analysis of a targeted literature review carried out as part of a wider study into occupational fraud and corruption.

Findings

Cressey’s name is intrinsically linked to the Fraud Triangle, although he never used the expression during his lifetime. Two of the three motivational factors identified by Cressey (1953) were developed from the earlier work of Svend Riemer (1941), who it is suggested should have equal billing with Donald Cressey for the concepts that led to the creation of the Fraud Triangle.

Practical implications

The paper illustrates the limitations of Cressey’s Fraud Triangle for practitioners.

Originality/value

Many academics and researchers have either misunderstood Cressey’s role in the development of the Fraud Triangle or been unaware of its true origins. Although the pioneering work of Riemer is referenced in a 2014 study on the Fraud Triangle by Alexander Schuchter and Michael Levi, to the best of the authors’ knowledge, this paper is the first to identify the influence of Riemer on Cressey’s thinking and the development of the Fraud Triangle.
Effect of a community of practice on knowledge sharing across boundaries: the mediating role of learning goals
Authors: Matsuo Makoto , Aihara Motohiro
Published: June 2021

Purpose

A community of practice (CoP) is believed to be a driver for knowledge creation but it can hinder knowledge sharing across boundaries. Drawing on social cognitive theory, this study aims to investigate how a CoP within a single unit promotes knowledge sharing with other units by examining the mediating effect of the members’ learning goals (LG).

Design/methodology/approach

Structural equation modeling was conducted using a two-wave survey data on nurses from eight Japanese hospitals (n = 263).

Findings

The results indicated that LG fully and positively mediated the effect of a CoP on the knowledge-sharing intention of one unit toward other units and that LG fully and negatively mediated the effect of a CoP on knowledge withholding (KW) from other units.

Practical implications

Knowledge managers need to note that intellectual benefits from experienced CoP can play a key role in reducing the perceived risks associated with members’ knowledge sharing and in creating effective knowledge sharing with other units.

Originality/value

The main contribution is to identify the process by which CoP promotes knowledge sharing and prevents KW across boundaries mediated through LG. This study is the first to quantitatively show how LG cross inter-professional barriers caused by CoPs.
The creation and development of learning organizations: a review
Authors: Kumar Mohit , Paul Justin , Misra Madhvendra , Romanello Rubina
Published: June 2021

Purpose

In this paper, using the antecedents, decisions and outcomes (ADO) framework, the factors/key performance indicators (KPIs) most relevant for creating or building a learning organization (LO) are identified. This study aims to contribute to the field of knowledge management (KM) in terms of introducing KPIs to foster a business organization with a continuous learning process, mechanisms of knowledge creation and memorization.

Design/methodology/approach

In total, 57 papers were selected for this systematic literature review (SLR) from Web of Science and Scopus covering the period 1985–2019.

Findings

The 12 most relevant KPIs are identified based on the literature survey conducted in the field of LO.

Research limitations/implications

The managerial implications of this review paper will be an added advantage to the modern business organization worldwide that have adopted KM practices to foster knowledge management with information technology (IT) infrastructure. As IT infrastructure focuses on knowledge acquisition, dissemination and storage but the KPIs revealed through this review will help in transforming stored information as learning for the organization to improve its overall performance.

Originality/value

This review synthesizes prior studies and provides directions for future research.
Making personalised short breaks meaningful: a future research agenda to connect academia, policy and practice
Authors: Seddon Diane , Miller Emma , Prendergast Louise , Williamson Don , Cavaye Joyce Elizabeth
Published: June 2021

Purpose

There is a growing policy impetus to promote carer well-being through the provision of personalised short breaks. However, understanding of what makes for a successful personalised short break is limited. This paper aims to identify key evidence gaps and considers how these could be addressed.

Design/methodology/approach

A scoping review mapping the evidence base relevant to respite and short breaks for carers for older people, including those living with dementia, was completed. National and international literature published from 2000 onwards was reviewed. The scoping review focused on well-being outcomes, identified by previous research, as being important to carers.

Findings

Most studies investigating the outcomes of short breaks for carers supporting older people focus on traditional day and residential respite care. Although there have been developments in more personalised break options for carers, research exploring their impact is scarce. There is limited knowledge about how these personalised breaks might support carers to realise important outcomes, including carer health and well-being; a life alongside caring; positive caregiving relationships; choices in caring; and satisfaction in caring. Three priority lines of inquiry to shape a future research agenda are identified: understanding what matters – evidencing personalised short break needs and intended outcomes; capturing what matters – outcomes from personalised short breaks; and commissioning, delivering and scaling up personalised short breaks provision to reflect what matters.

Originality/value

This paper contributes to the development of an outcome-focused research agenda on personalised short breaks.
Investigation on selective laser sintering of PA12: dimensional accuracy and mechanical performance
Authors: Gazzerro Achille , Polini Wilma , Sorrentino Luca
Published: June 2021

Purpose

Selective laser sintering (SLS) has passed other techniques, thanks to its high print resolution, its ability to print microscale geometries without any additional support, its surface quality and its long-term thermal stability. However, despite the many advantages of SLS compared to fusion deposition modelling, there are still today some limitations on the materials to be printed. A limit critical from an industrial point of view is the aging of PA12 powder, i.e. the degradation of its physical and chemical performances, due to the high temperatures and the long printing cycles, thus involving a decrease of the mechanical properties of the printed parts. The purpose of this study was to charaterize mechanically and dimensionally specimens printed in PA12 through SLS by means of virgin or aged powder, i.e. powder just used for five printing cycles.

Design/methodology/approach

To achieve this aim, a set of specimens were designed, built, measured and mechanically tested; the obtained results were put into relationship with the values of the process parameters used to print them. Statistical tools to design the experiments and to analyse the obtained results were used.

Findings

The results show that the SLS process carried out through a Sintratec machine on PA12 powder has a good repeatability. To obtain the best dimensional and mechanical performances, it is needed to use virgin powder and place the part in the central zone of the printing area.

Originality/value

There are no scientific articles dealing with the influence of both the aging of the powder and the manufacturing parameters on the dimensional and mechanical characterization of specimens printed with SLS technique in PA12.
Psoriatic arthritis
Authors: Umezawa Yoshinori
Published: June 2021

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis. It is found in approximately 10% of psoriatic patients in Japan. PsA mainly affects the peripheral joints, spine, and/or sacroiliac joints. Left untreated, there is progressive, irreversible bone destruction leading to joint deformation and dysfunction. Before the era of biologic treatments, the diagnosis of PsA was difficult and available treatments were limited. Over time the pathology of PsA has become better understood, and many treatments now exist. Early detection and treatment of impending joint deformities are necessary to avoid impairment of PsA patients’ quality of life. Most patients develop the arthritis following the onset of the skin manifestations of psoriasis. The process of diagnosing PsA sometimes encounters difficulties because some patients may not show radiographic findings in the early stage, and may have normal levels of C‐reactive protein and matrix metalloproteinase‐3. For these cases, approaches such as magnetic resonance imaging or ultrasound imaging, as well as symptom questionnaires, are helpful. Currently, non‐steroidal anti‐inflammatory drugs, disease‐modifying antirheumatic drugs, and several biologics are the main treatments for PsA, which when used with an aggressive approach, will result in better patient outcomes.
Therapeutic potential of targeted‐gold nanospheres on collagen‐induced arthritis in rats
Authors: Shahen Samar M. , Mohamed Mohamed R. , Ali Moustafa R. K. , Samaka Rehab M. , Hamdy Germine M. , Talaat Roba M.
Published: June 2021

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti‐rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted‐nanoparticles) against collagen‐induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro‐inflammatory/anti‐inflammatory and angiogenic mediators’ expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres‐conjugated with nucleus localized peptide (nuclear membrane‐targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres‐conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators’ expression and induced anti‐inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane‐targeted AuNSs effectively attenuated arthritis progression without systemic side effects.
quickLD: An efficient software for linkage disequilibrium analyses
Authors: Theodoris Charalampos , Low Tze Meng , Pavlidis Pavlos , Alachiotis Nikolaos
Published: June 2021

Software tools for linkage disequilibrium (LD) analyses are designed to calculate LD among all genetic variants in a single region. Since compute and memory requirements grow quadratically with the distance between variants, using these tools for long‐range LD calculations leads to long execution times and increased allocation of memory resources. Furthermore, widely used tools do not fully utilize the computational resources of modern processors and/or graphics processing cards, limiting future large‐scale analyses on thousands of samples. We present quickLD, a stand‐alone and open‐source software that computes several LD‐related statistics, including the commonly used r2. quickLD calculates pairwise LD between genetic variants in a single region or in arbitrarily distant regions with negligible memory requirements. Moreover, quickLD achieves up to 95% and 97% of the theoretical peak performance of a CPU and a GPU, respectively, enabling 21.5× faster processing than current state‐of‐the‐art software on a multicore processor and 49.5× faster processing when the aggregate processing power of a multicore CPU and a GPU is harnessed. quickLD can also be used in studies of selection, recombination, genetic drift, inbreeding and gene flow. The software is available at https://github.com/pephco/quickLD.
Antagonism of Sigma‐1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice
Authors: Quadir Sema G. , Tanino Sean M. , Sami Yasmine N. , Minnig Margaret A. , Iyer Malliga R. , Rice Kenner C. , Cottone Pietro , Sabino Valentina
Published: June 2021

Background

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma‐1 receptors (Sig‐1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig‐1R hyperactivity may result in excessive alcohol drinking. Sig‐1R studies in mice are very scarce, and its potential role in alcohol‐induced hyperalgesia is also unknown.

Methods

In this study, we investigated the role of Sig‐1R in alcohol drinking and associated hyperalgesia in male mice, using an intermittent access 2‐bottle choice model of heavy drinking.

Results

The Sig‐1R antagonist BD‐1063 was found dose dependently to reduce both alcohol intake and preference, without affecting either water or sucrose intake, suggesting that the effects are specific for alcohol. Notably, the ability of BD‐1063 to suppress ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking animals. In addition, BD‐1063 reversed alcohol‐induced hyperalgesia during withdrawal, assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol‐naïve animals or locomotor activity in either group.

Conclusions

These data show that Sig‐1R antagonism dose‐dependently reduced ethanol consumption in heavy drinking mice as well as its efficacy in reducing alcohol‐induced hyperalgesia. These findings provide a foundation for the development of novel treatments for AUD and associated pain states.
Changes in alcohol‐related hospital visits during COVID‐19 in New York City
Authors: Schimmel Jonathan , Vargas‐Torres Carmen , Genes Nicholas , Probst Marc A. , Manini Alex F.
Published: June 2021

Background and Aims

Increased alcohol consumption has been proposed as a potential consequence of the coronavirus disease 2019 (COVID‐19) pandemic. There has been little scrutiny of alcohol use behaviors resulting in hospital visits, which is essential to guide pandemic public policy. We aimed to determine whether COVID‐19 peak restrictions were associated with increased hospital visits for alcohol use or withdrawal. Secondary objectives were to describe differences based on age, sex and race, and to examine alcohol‐related complication incidence.

Design

Multi‐center, retrospective, pre–post study.

Setting

New York City health system with five participating hospitals.

Participants

Adult emergency department encounters for alcohol use, alcoholic gastritis or pancreatitis or hepatitis, alcohol withdrawal syndrome, withdrawal seizure or delirium tremens.

Measurements

Age, sex, race, site and encounter diagnosis. Encounters were compared between 2019 and 2020 for 1 March to 31 May.

Findings

There were 2790 alcohol‐related visits during the 2019 study period and 1793 in 2020, with a decrease in total hospital visits. Of 4583 alcohol‐related visits, median age was 47 years, with 22.3% females. In 2020 there was an increase in percentage of visits for alcohol withdrawal [adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI) = 1.07–1.67] and withdrawal with complications (aOR = 1.40, 95% CI = 1.14–1.72), and a decline in percentage of hospital visits for alcohol use (aOR = 0.70, 95% CI = 0.59–0.85) and use with complications (aOR = 0.71, 95% CI = 0.58–0.88). It is unknown whether use visit changes mirror declines in other chief complaints. The age groups 18–29 and 60–69 years were associated with increased visits for use and decreased visits for withdrawal, as were non‐white race groups. Sex was not associated with alcohol‐related visit changes despite male predominance.

Conclusions

In New York City during the initial COVID‐19 peak (1 March to 31 May 2020), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.
A large‐scale genome‐wide association analysis reveals QTL and candidate genes for intramuscular fat content in Duroc pigs
Authors: Zhuang Z. , Ding R. , Qiu Y. , Wu J. , Zhou S. , Quan J. , Zheng E. , Li Z. , Wu Z. , Yang J.
Published: June 2021

This study aimed at identifying genomic regions and genes associated with intramuscular fat content (IMF) in Duroc pigs using a weighted single‐step GWAS. Data from 3912 pigs, of which 3770 animals were genotyped with GeneSeek Porcine 50K Bead chip, were used for the association analysis. We identified 19 genomic regions that each explained >1% of the additive genetic variance associated with IMF. Notably, a consistent QTL on SSC7 (117.42–117.92 Mb) was confirmed, explaining 3.70% of the additive genetic variance, and two genes, BDKRB2 and ATG2B, were highlighted as promising candidates for IMF. Two QTL (SSC7, 94.19–94.64 Mb; SSC14, 123.25–123.75 Mb), which harbored MED6 and MAP3K9 genes and TCF7L2 gene respectively, were newly identified as associated with IMF. In conclusion, we identified a consistent QTL and additional genomic regions and genes that contributed to the genetic variance of IMF using a large‐scale sample size of genotyped pigs and genealogical information.
Development of a core outcome set for interventions to prevent stillbirth
Authors: Kim Bobae V. , Aromataris Edoardo C. , Middleton Philippa , Townsend Rosemary , Thangaratinam Shakila , Duffy James M. N. , de Lint Willem , Coat Suzette , Flenady Vicki , Khalil Asma , Mol Ben W.
Published: June 2021

Aims

To develop a core outcome set for trials investigating interventions to prevent stillbirth.

Materials & Methods

Outcomes identified from a systematic literature review and semi‐structured interviews with parents in Australia and the UK were entered into a two‐round online Delphi survey and focus group/consensus meetings.

Results

A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher‐level neonatal care length of stay.

Conclusions

Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.
Clinical and histopathological features of myeloid neoplasms with concurrent Janus kinase 2 (JAK2) V617F and KIT proto‐oncogene, receptor tyrosine kinase (KIT) D816V mutations
Authors: Naumann Nicole , Lübke Johannes , Shomali William , Reiter Lukas , Horny Hans‐Peter , Jawhar Mohamad , Dangelo Vito , Fabarius Alice , Metzgeroth Georgia , Kreil Sebastian , Sotlar Karl , Oni Claire , Harrison Claire , Hofmann Wolf‐Karsten , Cross Nicholas C. P. , Valent Peter , Radia Deepti , Gotlib Jason , Reiter Andreas , Schwaab Juliana
Published: June 2021

We report on 45 patients with myeloid neoplasms and concurrent Janus kinase 2 (JAK2) V617F and KIT proto‐oncogene, receptor tyrosine kinase (KIT) D816V (JAK2pos./KITpos.) mutations, which are individually identified in >60% of patients with classical myeloproliferative neoplasms (MPN) and >90% of patients with systemic mastocytosis (SM) respectively. In SM, the concurrent presence of a clonal non‐mast cell neoplasm [SM with associated haematological neoplasm (SM‐AHN)] usually constitutes a distinct subtype associated with poor survival. All 45 patients presented with a heterogeneous combination of clinical/morphological features typical of the individual disorders (e.g. leuco‐/erythro‐/thrombocytosis and elevated lactate dehydrogenase for MPN; elevated serum tryptase and alkaline phosphatase for SM). Overlapping features identified in 70% of patients included splenomegaly, cytopenia(s), bone marrow fibrosis and additional somatic mutations. Molecular dissection revealed discordant development of variant allele frequency for both mutations and absence of concurrently positive single‐cell derived colonies, indicating disease evolution in two independent clones rather than monoclonal disease in >60% of patients examined. Overall survival of JAK2pos./KITpos. patients without additional somatic high‐risk mutations [HRM, e.g. in serine and arginine‐rich splicing factor 2 (SRSF2), additional sex combs like‐1 (ASXL1) or Runt‐related transcription factor 1 (RUNX1)] at 5 years was 77%, indicating that the mutual impact of JAK2 V617F and KIT D816V on prognosis is fundamentally different from the adverse impact of additional HRM in the individual disorders.
Interleukin-4 protects mice against lethal influenza and Streptococcus pneumoniae co-infected pneumonia
Authors: Peng Yang , Wang Xiaofang , Wang Hong , Xu Wenchun , Wu Kaifeng , Go Xuemei , Yin Yibing , Zhang Xuemei
Published: June 2021

Streptococcus pneumoniae co-infection post-influenza is a major cause of mortality characterized by uncontrolled bacteria burden and excessive immune response during influenza pandemics. Interleukin (IL)-4 is a canonical type II immune cytokine known for its wide range of biological activities on different cell types. It displays protective roles in numerous infectious diseases and immune-related diseases, but its role in influenza and S. pneumoniae (influenza/S. pneumoniae) co-infected pneumonia has not been reported. In our study, we used C57BL/6 wild-type (WT) and IL-4-deficient (IL-4−/−) mice to establish co-infection model with S. pneumoniae after influenza virus infection. Co-infected IL-4−/− mice showed increased mortality and weight loss compared with WT mice. IL-4 deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of IL-4 in decreasing post-influenza susceptibility to S. pneumoniae co-infection. Loss of IL-4 also resulted in aggravated lung damage together with massive proinflammatory cytokine production and immune cell infiltration during co-infection. Administration of recombinant IL-4 rescued the survival and weight loss of IL-4−/− mice in lethal co-infection. Additionally, IL-4 deficiency led to more immune cell death in co-infection. Gasdermin D (GSDMD) during co-infection was induced in IL-4−/− mice that subsequently activated cell pyroptosis. Treatment of recombinant IL-4 or inhibition of GSDMD activity by disulfiram decreased immune cell death and bacterial loads in lungs of IL-4−/− co-infected mice. These results suggest that IL-4 decreases post-influenza susceptibility to S. pneumoniae co-infection via suppressing GSDMD-induced pyroptosis. Collectively, this study demonstrates the protective role of IL-4 in influenza/S. pneumoniae co-infected pneumonia.
Comparison of the colour fading effects of sodium hypochlorite and ozone treatments
Authors: Yiğit İdil , Eren Semiha , Karalı Recep , Yıbar M. Fahri , Eren Hüseyin Aksel
Published: June 2021

Colour fading is a method that is used to achieve a vintage look in textile goods. It is desired by customers in the textile market. Additionally, customers demand that these types of products are produced by environmentally friendly methods. In this study, sodium hypochlorite and ozone were used as laboratory‐scale colour fading reagents on dyed cotton fabrics. Cotton fabrics were dyed with four different primary colours: red, yellow, blue and black. Dyed fabrics were subjected to ozone and sodium hypochlorite treatment under different treatment conditions. Ozone was chosen as an alternative for comparison and it was applied at fixed flow rate (5 L/min) and time (10 minutes). Colour differences, chemical oxygen demand, bursting strength and energy, water and chemical consumptions were measured. The surface morphology was characterised by scanning electron microscopy. We can conclude that ozonation is effective in discharging colour from dyed fabric samples, and the colour‐fading effect is uniform, like in sodium hypochlorite treatment. It was observed that both processes are similar in terms of strength and surface modification. Results showed a 90% cost reduction, 85% water conservation and a 26% chemical oxygen demand reduction.