bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Out-of-Africa Migration of Human Herpes Simplex Viruses
Authors: Forni Diego , Pontremoli Chiara , Clerici Mario , Pozzoli Uberto , Cagliani Rachele , Sironi Manuela
Published: January 2020

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplex viruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called “worldwide” and “African” lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at ∼5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans but show that the worldwide distribution of circulating strains is the result of relatively recent events.
Characterization of a New Monopartite Begomovirus with a Betasatellite Associated with Leaf Curl, Yellow Vein, and Vein Enation inHibiscus rosa-sinensis
Authors: Huang Chih-Hung , Tai Chia-Hsing , Sharma Nabin , Chao Chia-Hung , Chang Chung-Jan , Jan Fuh-Jyh
Published: January 2020

A new begomovirus, tentatively named hibiscus yellow vein leaf curl virus (HYVLCV), was identified in Hibiscus rosa-sinensis plants showing symptoms of leaf curl, yellow vein, and vein enation on the undersides of the leaf in Taiwan. Sequence analysis of the full-length HYVLCV genome from the rolling cycle amplicon revealed a genome of 2,740 nucleotides that contains six open reading frames and a conserved sequence (5′-TAATATTAC-3′) commonly found in geminiviral genomes. HYVLCV shares the highest nucleotide identity (88.8%) with cotton leaf curl Multan virus (CLCuMuV) genome, which is lower than the criteria (91%) set for species demarcation in the genus Begomovirus. No begomoviral DNA-B was detected; however, a begomovirus-associated DNA betasatellite (DNA-β) was detected. The DNA-β (1,355 nucleotides) shares the highest nucleotide identity (78.6%) with malvastrum yellow vein betasatellite (MaYVB). Because the identity is slightly higher than the criteria (78%) set for the species demarcation threshold for a distinct DNA-β species, the DNA-β of HYVLCV reported in this study is considered the same species of MaYVB and tentatively named MaYVB-Hib. An expected 1,498-bp fragment was amplified with two HYVLCV-specific primers from 10 of 11 field-collected samples. Four independent amplicons were sequenced, revealing 100% nucleotide identity with the HYVLCV genome. Agroinoculation of a dimer of the infectious monopartite genome alone to Nicotiana benthamiana resulted in mild symptoms at 28 days postinoculation (dpi); coagroinoculation with the DNA-β satellite resulted in severe symptoms at 12 dpi. HYVLCV could be transmitted to healthy H. rosa-sinensis by grafting, resulting in yellow vein symptoms at 30 dpi.
Rubella Vaccine Persistence Within Cutaneous Granulomas in Common Variable Immunodeficiency Disorder
Authors: Bender Nicole R. , Cardwell Leah A. , Siegel Dawn , Sokumbi Olayemi
Published: January 2020

Common variable immunodeficiency disorder is a primary immunodeficiency disorder characterized by reduced levels of serum immunoglobulins and impaired antibody response. This condition may be associated with development of noninfectious granulomatous dermatitis of the skin which may be disfiguring and destructive. There are no published guidelines for the treatment of cutaneous granulomas in this patient population. In recent studies, rubella virus–positive cells in granulomas were localized to M2 macrophages which have an important role in wound healing and the secretion of immunoregulatory cytokines. We present a case of treatment-refractory, disfiguring common variable immunodeficiency disorder–associated granulomatous dermatitis. Immunofluorescence microscopy of the biopsy specimen confirmed the presence of rubella vaccine capsid proteins in M2 macrophages within the granuloma, a newly recognized phenomenon in this patient population. This knowledge may serve to identify future therapeutic targets or preventative strategies for granulomatous dermatitis in patients with primary immunodeficiency disorder.
Management of Wilson Disease Diagnosed in Infancy
Authors: Valentino Pamela L. , Roberts Eve A. , Beer Stacey , Miloh Tamir , Arnon Ronen , Vittorio Jennifer M. , Schilsky Michael L.
Published: January 2020

Increased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence‐based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence‐based approaches and best practice for managing treatment of infants with genetically diagnosed WD.
Open‐label Phase 3 Continuation Study of Cholic Acid in Patients With Inborn Errors of Bile Acid Synthesis
Authors: Heubi James E. , Setchell Kenneth D.R.
Published: January 2020

Background:

In patients with bile acid synthesis disorders (BASD), impairment in the primary bile acid synthetic pathway leads to reduced primary bile acids, upregulated synthesis of cholesterol, and production and accumulation of hepatotoxic atypical bile acids. Primary bile acid therapy downregulates bile acid synthesis, reduces the production of hepatotoxic intermediates, and produces a functional bile acid pool fostering normal liver function.

Methods:

This phase 3, open‐label, single‐arm study included patients with BASD who had received cholic acid (10–15 mg · kg−1 · day−1) as part of a previous study, or were newly diagnosed. Efficacy assessments included urinary atypical bile acids; serum liver chemistries; body weight and height. Efficacy analyses compared baseline with worst postbaseline response (primary) or best postbaseline response (sensitivity). Treatment‐emergent adverse events (TEAEs) were summarized.

Results:

Of 53 total patients (single enzyme defects, n = 41; Zellweger spectrum disorders, n = 12), 22 (42%) were treatment‐naïve, and 31 (58%) were on cholic acid from a previous study. Mean age at diagnosis was 55 months, and at present study, baseline was 9 years. Using baseline‐to‐best postbaseline analyses, statistically significant improvements in urinary bile acids (P = 0.003), height (P < 0.001), and body weight (P < 0.001) were observed. Serum alanine aminotransferase and aspartate aminotransferase levels tended to decrease from baseline in treatment‐naïve patients following cholic acid treatment and remained stable in previously treated patients. Treatment‐naïve patients improved in all baseline‐to‐best postbaseline analyses. The most common TEAE was upper respiratory tract infection (17%).

Conclusion:

Oral cholic acid provides a safe and efficacious short‐ and long‐term therapy for patients with BASD.
MetaConnect, a new platform for population viability modelling to assist decision makers in conservation and urban planning
Authors: Moulherat Sylvain , Bestion Elvire , Baguette Michel , Moulherat Matthieu , Palmer Stephen C.F. , Travis Justin M.J. , Clobert Jean
Published: January 2020

In a context of global change, scientists and policy-makers require tools to address the issue of biodiversity loss. Population viability analysis (PVA) has been the main tool to deal with this problem. However, the tools developed during the 90s poorly integrate recent scientific advances in landscape genetics and dispersal. We developed a flexible and modular modelling platform for PVA that addresses many of the limitations of existing software. MetaConnect is an individual-based, process-based and PVA-oriented modelling platform which could be used as a research or a decision-making tool. Here, we present the core base modelling of MetaConnect. We demonstrate its potential use through a case study illustrating the platform’s capability for performing integrated PVA including extinction probability estimation, genetic differentiation and landscape connectivity analysis. We used MetaConnect to assess the impact of infrastructure works on the natterjack toad metapopulation functioning.
FFselect: An improved linear mixed model for genome-wide association study in populations featuring shared environments confounded by relatedness
Authors: Schultz Nichol , Weigel Kent
Published: January 2020

Linear mixed models are effective tools to identify genetic loci contributing to phenotypic variation while handling confounding due to population structure and cryptic relatedness. Recent improvements of the linear mixed model for genome-wide association analysis have been directed at more accurately modeling loci of large effect. We describe FFselect (https://github.com/NicholSchultz/FFselect), a novel method that both builds upon recent advances and further extends the linear mixed model for genome-wide association analysis to allow modeling of shared environmental effects. FFselect improves power, controls false discovery rate, and simultaneously corrects for environmental confounding to improve the utility of GWAS.
Spatial Proximity Moderates Genotype Uncertainty in Genetic Tagging Studies
Authors: Augustine Ben C. , Royle J. Andrew , Linden Daniel W. , Fuller Angela K.
Published: January 2020

Accelerating declines of an increasing number of animal populations worldwide necessitate methods to reliably and efficiently estimate demographic parameters such as population density and trajectory. Standard methods for estimating demographic parameters from noninvasive genetic samples are inefficient because lower quality samples cannot be used, and they do not allow for errors in individual identification. We introduce the Genotype Spatial Partial Identity Model (SPIM), which integrates a genetic classification model with a spatial population model to combine both spatial and genetic information, thus reducing genotype uncertainty and increasing the precision of demographic parameter estimates. We apply this model to data from a study of fishers (Pekania pennanti) in which 37% of samples were originally discarded because of uncertainty in individual identity. The Genotype SPIM density estimate using all collected samples was 25% more precise than the original density estimate, and the model identified and corrected 3 errors in the original individual identity assignments. A simulation study demonstrated that our model increased the accuracy and precision of density estimates 63% and 42%, respectively, using 3 PCRs per genetic sample. Further, the simulations showed that the Genotype SPIM model parameters are identifiable with only one PCR per sample, and that accuracy and precision are relatively insensitive to the number of PCRs for high quality samples. Current genotyping protocols devote the majority of resources to replicating and confirming high quality samples, but when using the Genotype SPIM, genotyping protocols could be more efficient by devoting more resources to low quality samples.

Significance

We present a new statistical framework for the estimation of animal demographic parameters, such as abundance, density, and growth rate, from noninvasive genetic samples (e.g., hair, scat). By integrating a genetic classification model with a spatial population model, we show that accounting for spatial proximity of samples reduces genotype uncertainty and improves parameter estimation. Our method produces a fundamentally different approach to genetic capture-recapture by sharing information between the normally disjunct steps of assigning individual identities to genetic samples and modeling population processes. Further, it leads to more efficient protocols for processing genetic samples, which can lower project costs and expand opportunities for applying noninvasive genetics to conservation and management problems.
Overcoming Genetic Drop-outs in Variants-based Lineage Tracing from Single-cell RNA Sequencing Data
Authors: Lu Tianshi , Park Seongoh , Zhu James , Zhan Xiaowei , Wang Xinlei , Zhu Hao , Wang Tao
Published: January 2020

Lineage tracing provides key insights into the fates of individual cells in complex tissues. Recent works on lineage reconstruction based on the single-cell expression data are suitable for short time frames while tracing lineage based on more stable genetic markers is needed for studies that span time scales over months or years. However, variant calling from the single-cell RNA sequencing (scRNA-Seq) data suffers from “genetic drop-outs”, including low coverage and allelic bias, which presents significant obstacles for lineage reconstruction. Prior studies focused only on mitochondrial (chrM) variants and need to be expanded to the whole genome to capture more variants with clearer physiological meaning. However, non-chrM variants suffer even more severe drop-outs than chrM variants, although drop-outs affect all variants. We developed strategies to overcome genetic drop-outs in scRNA-Seq-derived whole genomic variants for accurate lineage tracing, and we developed SClineger, a Bayesian Hierarchical model, to implement our approach. Our validation analyses on a series of sequencing protocols demonstrated the necessity of correction for genetic drop-outs and consideration of variants in the whole genome, and also showed the improvement that our approach provided. We showed that genetic-based lineage tracing is applicable for single-cell studies of both tumors and non-tumor tissues using our approach, and can reveal novel biological insights not afforded by expressional analyses. Interestingly, we showed that cells of various lineages grew under the spatial constraints of their respective organs during the developmental process. Overall, our work provides a powerful tool that can be applied to the large amounts of already existing scRNA-Seq data to construct the lineage histories of cells and derive new knowledge.
Label-free three-dimensional observations and quantitative characterisation of on-chip vasculogenesis using optical diffraction tomography
Authors: Lee Chungha , Kim Seunggyu , Hugonnet Herve , Lee Moosung , Park Weisun , Jeon Jessie S. , Park YongKeun
Published: January 2020

Label-free, three-dimensional (3D) quantitative observations of on-chip vasculogenesis were achieved using optical diffraction tomography. Exploiting 3D refractive index maps as an intrinsic imaging contrast, the vascular structures, multicellular activities, and subcellular organelles of endothelial cells were imaged and analysed throughout vasculogenesis to characterise mature vascular networks without exogenous labelling.

Abstract Figure
LocusFocus: A web-based colocalization tool for the annotation and functional follow-up of GWAS
Authors: Panjwani Naim , Wang Fan , Wang Cheng , He Gengming , Mastromatteo Scott , Bao Allen , Gong Jiafen , Rommens Johanna M , Sun Lei , Strug Lisa J
Published: January 2020

Genome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP-level associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our establishedSimple Summethod to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. Full documentation and source code for LocusFocus are publicly available.
SMRT sequencing yields the chromosome-scale reference genome of tea tree,Camellia sinensisvar.sinensis
Authors: Zhang Qun-Jie , Li Wei , Li Kui , Nan Hong , Shi Cong , Zhang Yun , Dai Zhang-Yan , Lin Yang-Lei , Yang Xiao-Lan , Tong Yan , Zhang Dan , Lu Cui , Wang Chen-feng , Liu Xiao-xin , Jiang Wen-Kai , Wang Xing-Hua , Zhang Xing-Cai , Liu Zhong-Hua , Eichler Evan E. , Gao Li-Zhi
Published: January 2020

Tea is the oldest and most popular nonalcoholic beverage consumed in the world. It provides abundant secondary metabolites that account for its diverse flavors and health benefits. Here we present the first high-quality chromosome-length reference genome ofC. sinensisvar.sinensisusing long read single-molecule real time (SMRT) sequencing and Hi-C technologies to anchor the ∼2.85-Gb genome assembly into 15 pseudo-chromosomes with a scaffold N50 length of ∼195.68 Mb. We annotated at least 2.17 Gb (∼74.13%) of repetitive sequences and high-confidence prediction of 40,812 protein-coding genes in the ∼2.92-Gb genome assembly. This accurately assembled genome allows us to comprehensively annotate functionally important gene families such as those involved in the biosynthesis of catechins, theanine and caffeine. The contiguous genome assembly provides the first view of the repetitive landscape allowing us to accurately characterize retrotransposon diversity. The large tea tree genome is dominated by a handful of Ty3-gypsylong terminal repeat (LTR) retrotransposon families that recently expanded to high copy numbers. We uncover the latest bursts of numerous non-autonomous LTR retrotransposons that may interfere with the propagation of autonomous retroelements. This reference genome sequence will largely facilitate the improvement of agronomically important traits relevant to the tea quality and production.
Chamaeleo: a robust library for DNA storage coding schemes
Authors: Ping Zhi , Zhang Haoling , Chen Shihong , Zhuang Qianlong , Zhu Sha Joe , Shen Yue
Published: January 2020

Chamaeleo is currently the only collection library that focuses on adapting multiple well-established coding schemes for DNA storage. It provides a tool for researchers to study various coding schemes and apply them in practice. Chamaeleo adheres to the concept of high aggregation and low coupling for software design which will enhance the performance efficiency. Here, we describe the working pipeline of Chamaeleo, and demonstrate its advantages over the implementation of existing single coding schemes. The source code is available athttps://github.com/ntpz870817/Chamaeleo, it can be also installed by the command of pip.exe, “pip install chamaeleo”. Alternatively, the wheel file can be downloaded athttps://pypi.org/project/Chamaeleo/. Detailed documentation is available athttps://chamaeleo.readthedocs.io/en/latest/.

Author Summary

DNA is now considered to be a promising candidate media for future digital information storage in order to tackle the global issue of data explosion. Transcoding between binary digital data and quanternary DNA information is one of the most important steps in the whole process of DNA digital storage. Although several coding schemes have been reported, researchers are still investigating better strategies. Moreover, the scripts of these coding schemes use different programming languages, software architectures and optimization contents. Therefore, we here introduce Chamaeleo, a library in which several classical coding schemes are collected, to reconstruct and optimize them. One of the key features of this tool is that we modulize the functions and make it feasible for more customized way of usage. Meanwhile, developers can also incorporate their new algorithms according to the framework expediently. Based on the benchmark tests we conducted, Chamaeleo shows better flexibility and expandability compared to original packages and we hope that it will help the further study and applications in DNA digital storage.
Flattening of diurnal glucocorticoid oscillations causes Cd36 and insulin-mediated obesity
Authors: Tholen Stefan , Kovary Kyle M. , Rabiee Atefeh , Bielczyk-Maczyńska Ewa , Yang Wenting , Kraemer Fredric B. , Teruel Mary N.
Published: January 2020

Chronic stressors flatten diurnal glucocorticoid oscillations, resulting in obesity, insulin resistance, and diabetes. How such flattened diurnal glucocorticoid oscillations increase fat storage is unknown. Here we investigated the consequences in mice and found that flattening of glucocorticoid oscillations results not only in body weight gain, mainly due to increases in white fat depot mass, but also leads to hyperinsulinemia and fat accumulation in brown adipose tissue. A transcriptomic analysis of white and brown adipose tissues revealed that flattened glucocorticoid oscillations cause dysregulated lipid metabolism with a prominent role of the fatty acid transporter Cd36 and insulin-driven adipocyte hypertrophy. Indeed,Cd36knockout mice are partially protected against the adverse effects of flattened GC oscillations including body weight gain and lipid accumulation in the brown and visceral white fat depots. These results show the molecular mechanisms how flattened glucocorticoid oscillations can cause obesity and diabetes.
The Arabidopsis N-terminal Acetyltransferase NAA50 Regulates Plant Growth and Defense
Authors: Neubauer Matthew , Innes Roger W.
Published: January 2020

Stress signaling in plants is carefully regulated to ensure proper development and reproductive fitness. Overactive defense signaling can result in dwarfism as well as developmental defects. In addition to requiring a significant amount of energy, plant stress responses place a burden upon the cellular machinery, which can result in the accumulation of misfolded proteins and endoplasmic reticulum (ER) stress. Negative regulators of stress signaling, such asEDR1, ensure that stress responses are properly suspended when they are not needed. Here, we describe the role of an uncharacterized N-terminal acetyltransferase, NAA50, in the regulation of plant development and stress responses. Our results demonstrate that NAA50, an interactor of EDR1, plays an important role in regulating the tradeoff between plant growth and defense. Plants lackingNAA50display severe developmental defects as well as induced stress responses. Reduction ofNAA50expression results in arrested stem and root growth and senescence. Furthermore, our results demonstrate thatEDR1andNAA50are required for suppression of ER stress signaling. This work establishes thatNAA50is essential for plant development and the suppression of stress responses, likely through the regulation of ER stress. These experiments demonstrate a role for N-terminal acetylation in the suppression of ER stress, as well as the tradeoff between stress responses and development.

One Sentence Summary

Knockout in Arabidopsis of the broadly conserved N-terminal acetyl transferase NAA50 induces ER stress, leading to severe dwarfism and induction of defense responses.
Optimization of subsampling, decontamination, and DNA extraction of difficult peat and silt permafrost samples
Authors: Saidi-Mehrabad Alireza , Neuberger Patrick , Cavaco Maria , Froese Duane , Lanoil Brian
Published: January 2020

This study aims to act as a methodological guide for contamination monitoring, decontamination, and DNA extraction for peaty and silty permafrost samples with low biomass or difficult to extract DNA. We applied a biological tracer, either only in the field or both in the field and in the lab, via either spraying or painting. Spraying in the field followed by painting in the lab resulted in a uniform layer of the tracer on the core sections. A combination of bleaching, washing, and scraping resulted in complete removal of the tracer leaving sufficient material for DNA extraction, while other widely used decontamination methods did not remove all detectable tracer. In addition, of four widely used commercially available DNA extraction kits, only a modified ZymoBIOMICS™ DNA Microprep kit was able to acquire PCR amplifiable DNA. Permafrost chemical parameters, age, and soil texture did not have an effect on decontamination efficacy; however, the permafrost type did influence DNA extraction. Based on these findings, we developed recommendations for permafrost microbiologists to acquire contaminant-free DNA from permafrost with low biomass.

IMPORTANCE

Permafrost has the capacity to preserve microbial and non-microbial genomic material for millennia; however, major challenges are associated with permafrost samples, including decontamination of samples and acquiring pure DNA. Contamination of samples during coring and post coring handling and processing could affect downstream analyses and interpretations. Despite the use of multiple different decontamination and DNA extraction methods in studies of permafrost, the efficacy of these methods is not well known. We used a biological tracer to test the efficacy of previously published decontamination methods, as well as a bleach-based method we devised, on two chemically and structurally different permafrost core sections. Our method was the only one that removed all detectable tracer. In addition, we tested multiple DNA extraction kits and modified one that is able to acquire pure, PCR amplifiable DNA from silty, and to some extent from peaty, permafrost samples.
ERCC1-XPF Interacts with Topoisomerase IIβ to Facilitate the Repair of Activity-induced DNA Breaks
Authors: Chatzinikolaou Georgia , Stratigi Kalliopi , Agathangelou Kyriacos , Tsekrekou Maria , Goulielmaki Evi , Chatzidoukaki Ourania , Gkirtzimanaki Katerina , Aid-Pavlidis Tamara , Aivaliotis Michalis , Pavlidis Pavlos , Tsamardinos Ioannis , Topalis Pantelis , Bouwman Britta A. M. , Crosetto Nicola , Altmüller Janine , Garinis George A.
Published: January 2020

Type II DNA Topoisomerases (TOP II) generate transient double-strand DNA breaks (DSBs) to resolve topological constraints during transcription. Using genome-wide mapping of DSBs and functional genomics approaches, we show that, in the absence of exogenous genotoxic stress, transcription leads to DSB accumulation and to the recruitment of the structure-specific ERCC1-XPF endonuclease on active gene promoters. Instead, we find that the complex is released from regulatory or gene body elements in UV-irradiated cells. Abrogation of ERCC1 or re-ligation blockage of TOP II-mediated DSBs aggravates the accumulation of transcription-associated γH2Ax and 53BP1 foci, which dissolve when TOP II-mediated DNA cleavage is inhibited. Anin vivobiotinylation tagging strategy coupled to a high-throughput proteomics approach reveals that ERCC1-XPF interacts with TOP IIβ and the CTCF/cohesin complex, which co-localize with the heterodimer on DSBs. Together; our findings provide a rational explanation for the remarkable clinical heterogeneity seen in human disorders with ERCC1-XPF defects.
Using systems medicine to identify a therapeutic agent with potential for repurposing in Inflammatory Bowel Disease
Authors: Lloyd Katie , Papoutsopoulou Stamatia , Smith Emily , Stegmaier Philip , Bergey Francois , Morris Lorna , Kittner Madeleine , England Hazel , Spiller Dave , White Mike HR , Duckworth Carrie A , Campbell Barry J , Poroikov Vladimir , dos Santos Vitor AP Martins , Kel Alexander , Muller Werner , Pritchard D Mark , Probert Chris , Burkitt Michael D ,   the SysmedIBD consortium
Published: January 2020

Objective

Inflammatory bowel diseases cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs which alter NF-κB signalling and may be repositioned for use in inflammatory bowel disease.

Design

The SysmedIBD consortium established a novel drug-repurposing pipeline based on a combination of in-silico drug discovery and biological assays targeted at demonstrating an impact on NF-kappaB signalling, and a murine model of IBD.

Results

The drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic Clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions.

Clarithromycin’s effects were validated in several experiments: it influenced NF-κB mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to LPS, and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids.

Conclusions

These findings demonstrate that in-silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of inflammatory bowel disease; and that further clinical assessment of clarithromycin in the management of inflammatory bowel disease is required.
Benchmarking logistics facilities: a rating model to assess building quality and functionality
Authors: Baglio Martina , Perotti Sara , Dallari Fabrizio , Garagiola Elisabetta Rachele
Published: January 2020

Purpose

Logistics real estate has been experiencing a recent rebirth led by the growth of retailing and e-commerce. Although these sectors are looking for facilities matching their logistics needs, the identification of the most suitable building becomes a challenging task. To date, from both the practitioner’s and academic perspectives there is a lack of models for assessing the quality of logistics facilities together with functionality (i.e. whether a warehouse is suitable for hosting a given logistics activity). The purpose of this paper is to fill this gap by developing a rating model for assessing the quality and functionality of logistics facilities.

Design/methodology/approach

A three-pronged methodology was adopted. First, a Systematic Literature Network Analysis (SLNA) was carried out to identify the relevant features that must be taken into consideration when assessing logistics real estate. Second, a Delphi method involving experts in the field was used to fine-tune the list of features that emerged from the SLNA process and to evaluate the importance of each feature from a company perspective. The rating model was developed and validated through pilot tests on 27 logistics facilities.

Findings

The rating model is divided into four sections: location, technical specifications, external spaces and internal areas. As an output, the model determines the building quality and main functionality, together with a gap analysis to detect the weakest emerging elements.

Originality/value

This research fills an identified research gap in the logistics real estate literature. Specifically, it offers a quantitative and shared evaluation method, which can be used to estimate building quality and functionality, thus extending the scope of the previous assessment methods available.
How host-country nationals manage the demands of hosting expatriates
Authors: Fee Anthony
Published: January 2020

Purpose

Using job demands-resources (JD-R) theory as a conceptual apparatus, the purpose of this paper is to report an empirical exploration of the experiences of host-country national (HCN) employees when their organization hosts an expatriate assignment.

Design/methodology/approach

Semi-structured interviews were conducted with 23 Vietnamese HCNs who had vast experience hosting multiple self-initiated expatriates with organizational development objectives.

Findings

The study reveals previously hidden costs associated with locals’ support for expatriates, including a range of extra-role demands and more complex and stressful interpersonal interactions. These demands exceeded the current intercultural capabilities of many respondents, and while offset to some extent by their positive pre-arrival attitudes and culture-specific knowledge, led to sometimes counterproductive coping responses such as withdrawal behaviors.

Research limitations/implications

The study extends the JD-R framework by explicating which demands and resources are pertinent to HCNs, and how these activate particular coping strategies. The cultural context of Vietnam, as both a setting for the workplace interactions and imbued in the values and assumptions of respondents, limits the study’s transferability.

Practical implications

The findings provide guideposts for organizations in ways to offset HCNs’ hindrance demands (e.g. matching demands to current capabilities) and to encourage the use of productive coping strategies via, for instance, anticipating and mitigating potential challenges.

Originality/value

The study’s insights go some way toward articulating more fully the richness and complexity of HCNs’ experiences, and a more rounded perspective of the costs and benefits inherent in international work assignments.
Clinicians’ perceptions of telephone-delivered mental health services
Authors: Mercado Micaela , Little Virna
Published: January 2020

Purpose

The adoption of telephone-delivered mental health services (TDMHS) for scaling collaborative care or addressing access to mental health services in routine primary care practice is gradual despite the needs of the population. Although there are multi-level factors associated with efficient implementation of collaborative care, there is limited understanding of clinicians’ perceptions, experiences and acceptability providing mental health treatment exclusively over the telephone. The purpose of this paper is to explore behavioral health clinicians’ delivery of mental health services over the telephone within primary care settings.

Design/methodology/approach

This qualitative study explored behavioral health professionals’ perceptions and experiences providing remote, TDMHS. Convenience sampling was used to recruit 11 clinicians in New York, California and Arizona who provided collaborative care services to patients exclusively over the telephone. Semi-structured interviews were conducted, and analyzed using qualitative content analysis methods.

Findings

Three main themes and associated subthemes emerged from the analyses. The first theme was participants’ perceptions of TDMHS prior to implementation relating to patient characteristics, patient engagement and comparison to in-person therapy. The second main theme identified was participants’ experiences implementing TDMHS with subthemes relating to benefits, quality of care, gaps in care and concerns implementing TDMHS. The final theme that emerged from the analysis was participants’ perceived acceptability of TDMHS by patients.

Research limitations/implications

The small sample size limits the generalizability of these findings.

Practical implications

Mental health services delivered over the telephone are perceived as feasible and acceptable by behavioral health clinicians.

Originality/value

This study contributes to gaps in research about behavioral health clinicians’ beliefs, uptake and acceptability toward mental health services delivered exclusively over the telephone.
Analysis of the original influencing factors and secondary influencing factors of academic papers
Authors: Zhao Rongying , Bo Yu
Published: January 2020

Purpose

The influencing factors of academic papers have always been the focus of attention in the field of Scientometrics. Exploring the influencing factors of altmetrics indicators and traditional literature indicators on academic papers is beneficial to better explore the potential significance and value of academic papers in the evaluation of scientific research. The paper aims to discuss these issues.

Design/methodology/approach

Based on the latest JCR citation report, this paper selects 22 academic journals in the JIF Quartile Q1 journal of Information Science and Library Science, and then obtains the evaluation data of these journal papers from WOS database and Altmetric.com. This paper uses literature measurement, correlation analysis and regression analysis to explore the influencing factors of the paper.

Findings

The results show that the original influencing factors of academic papers have a significant impact on secondary influencing factors. What is more obvious is that the number of references (nr) presents a significant positive correlation with the total number of times (Z9), the number of uses (U1) and (U2).

Originality/value

This paper combines traditional literature indicators with Altmetrics indicators to study the influencing factors through primary influencing factors and secondary influencing factors. Through research, it denies the phenomenon that academic circles have published academic papers in the world in recent years to overemphasize certain factors to improve the influence of the paper.
Assessment of proteolysis in ultra‐high temperature milk using attenuated total reflectance–Fourier transform infrared spectroscopy
Authors: Ranvir Suvartan , Sharma Rajan , Gandhi Kamal , Upadhyay Neelam , Mann Bimlesh
Published: January 2020

This study investigated the suitability of attenuated total reflectance–Fourier transform infrared spectroscopy (ATR‐FTIR) as an alternative technique to assess proteolysis in ultra‐high temperature (UHT) milk. Commercial UHT milk samples were stored (5 and 30 °C) and analysed for four months. Milk samples were treated with acetic acid and trichloroacetic acid to obtain milk extracts containing peptides. The concentrated extracts were subjected to ATR‐FTIR, and the spectrum was obtained. Results were compared with techniques like high‐performance liquid chromatography, fluorescamine and 2,4,6‐trinitrobenzenesulphonic acid. The present study indicated that ATR‐FTIR‐based method can be used as an alternative method for assessing proteolysis in UHT milk.
Quantifying the spatial distribution and trends of supplementary feeding sites in South Africa and their potential contribution to vulture energetic requirements
Authors: Brink C. W. , Santangeli A. , Amar A. , Wolter K. , Tate G. , Krüger S. , Tucker A. S. , Thomson R. L.
Published: January 2020

Old world vultures are the most threatened group of raptors globally. Supplementary feeding sites (SFS) are a popular conservation tool, widely used to assist vulture populations. Despite their popularity, the impact of SFS on vultures remains largely unstudied. A lack of knowledge on the number, distribution and management of SFS is a key factor hindering such research. In this study, we compile records of SFS in South Africa and conduct questionnaires with SFS managers to characterize SFS. We identify 143 currently active SFS. Our data suggest that SFS numbers have been stable over the last decade. The average provisioning rate for all SFS was 64.6 kg day−1. Overall SFS provide an estimated 3301 tonnes of food to scavengers each year, the equivalent of 83% of the energetic needs of all vultures in the region. This contribution was highly skewed, however, with just 17% of active SFS sites providing 69% of all food. Furthermore, these resources were not equally distributed, with SFS in Limpopo, North West and Kwazulu‐Natal provinces providing 83% of the total meat provisioned. The three most common meat types provided at SFS were beef (39%), pork (33%) and game (19%). Worryingly, we found that 68% and 28% of SFS managers were unaware of the potential harmful effects of lead and veterinary drugs, respectively, which highlights potential poisoning risks associated with SFS. Examining exposure to SFS by different vulture species, we found that whilst SFS are accessible across the distribution range of vultures with large home ranges (e.g. African white‐backed and Cape vultures), those species with smaller home ranges have relatively poor accessibility. With this study, we demonstrate the potential importance, but also associated risks, of SFS to vultures in South Africa, and provide the information base to assess the impacts of this popular but as yet largely unassessed conservation tool.
Contesting the Hub‐and‐Spokes Model in Southeast Asia
Authors: Misalucha‐Willoughby Charmaine
Published: January 2020

The debate surrounding the United States’ hub‐and‐spokes alliance model in the Asia‐Pacific, that is, whether its endurance is a testament to its durability or whether its inability to face up to contemporary challenges reflects its failure—is best captured by recent norm research in International Relations. It can be argued that the U.S. hub‐and‐spokes model in Southeast Asia is not failing but is simply showing signs of contestation. The evolution of this network of regional security arrangements from U.S. alliances in Southeast Asia (with the Philippines and Thailand) to American security partnerships in that subregion (strategic partnership with Singapore and comprehensive partnership with Vietnam) reflects applicatory contestation. At the same time, the China factor and Washington’s evolving Asia strategy, which competes with the Middle East and with the “America First” instincts of the Trump administration, challenge the core of the San Francisco System’s validity. Hence, while the hub‐and‐spokes model is merely showing signs of contestation, the fact that it is undergoing validity contestation serves as a cautionary tale. Those U.S. policymakers supporting it will need to implement steps to avoid its complete erosion.
Long‐term safety and efficacy of psoas bladder hitch in infants aged <12 months with unilateral obstructive megaureter
Authors: Nakamura Shigeru , Hyuga Taiju , Tanabe Kazuya , Inoguchi Satoru , Kawai Shina , Nakai Hideo
Published: January 2020

Objective

To determine the long‐term safety and efficacy of ureteric reimplantation with psoas bladder hitch (PBH) in patients aged <12 months with unilateral obstructive megaureter (OM).

Patients and Methods

We retrospectively compared a group of patients aged <12 months (study group) with an group of patients aged ≥12 months (comparison group), who underwent PBH for OM between September 2007 and April 2017, in terms of preoperative patient characteristics, intra‐ and peri‐operative results, and postoperative results.

Results

The study group comprised seven infants, five boys and two girls. The median (range) age at the time of PBH was 3 (2–8) months; OM was detected by ultrasonography during the fetal period. The left side was affected in four infants and the right side in three. Four infants had primary OM (POM). In all three infants who had ectopic OM in the complete double renal pelvis and ureter, the OM involved the ureter from the upper half of the kidney. The median (range) follow‐up period after PBH was 45 (33–129) months. Comparison of the two groups showed no significant difference in terms of surgical time (P = 0.948) and length of hospital stay (P = 0.125). In both groups, hydroureteronephrosis improved postoperatively in all patients. There was no significant difference between the two groups in terms of postoperative complications, such as vesico‐ureteric reflux, febrile urinary tract infection and deterioration of ipsilateral renal function. Notably, no patient underwent reoperation in either group.

Conclusion

Psoas bladder hitch for unilateral OM including POM appears to be safe and effective in the long term for patients aged <12 months and for those aged ≥12 months. Although not routinely recommended, PBH appears to be a viable option for selected infants with POM.
Quality of life in adolescents with epilepsy, cerebral palsy, and population norms
Authors: Boldyreva Uliana , Streiner David L , Rosenbaum Peter L , Ronen Gabriel M
Published: January 2020

Aim

To compare: (1) self‐ and proxy‐reported quality of life (QoL) in adolescents with epilepsy, cerebral palsy (CP), both epilepsy and CP, and a representative general population sample; and (2) parental stress between parents of adolescents with epilepsy, CP, or both epilepsy and CP.

Method

This was a cross‐sectional observational study with 362 adolescents with epilepsy, 468 with CP, 192 with both CP and epilepsy, and 15 396 from the general population, assessed with the KIDSCREEN‐52 and Parenting Stress Index (PSI).

Results

All KIDSCREEN‐52 domains showed statistically significant differences across groups. The epilepsy population showed clinically better scores for ‘school environment’ than the general population (Cohen’s d=0.62). Parents scored adolescents with CP lower than adolescents with epilepsy or general populations on ‘physical health’ (d=0.57, d=0.55) and ‘social‐support and peers’ (d=0.82, d=0.91). Parents of adolescents with CP scored them lower than parents of the epilepsy group on ‘autonomy’ (d=0.62). Parents of adolescents with epilepsy scored them lower on ‘mood and emotions’ (d=0.52) and ‘social acceptance’ (d=0.66) than the general population. PSI scores were better for parents of adolescents with epilepsy than for parents of adolescents with CP (d=0.587) and with both CP and epilepsy (d=1.03,
d=0.613, d=0.528).

Interpretation

Adolescents with epilepsy or CP self‐report equal or better QoL than the general adolescent population, which should comfort families and allow clinicians to address parental concerns.

What this paper adds

Adolescents with epilepsy, with or without cerebral palsy (CP), self‐reported better school environment than adolescents in the general population.

Proxy quality of life (QoL) results showed clinically important differences across groups in 6 out of 10 domains of the KIDSCREEN‐52.

Proxy‐reported results showed poorer QoL scores for adolescents with epilepsy or CP than the general population.

Parental stress level was higher in parents of children with CP or both CP and epilepsy, than in those with only epilepsy.