bluuebunny/crossref_metadata_2025 huggingface dataset:
Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
Authors: Roberts Hannah E , Lopopolo Maria , Pagnamenta Alistair T , Sharma Eshita , Parkes Duncan , Lonie Lorne , Freeman Colin , Knight Samantha J L , Lunter Gerton , Dreau Helene , Lockstone Helen , Taylor Jenny C , Schuh Anna , Bowden Rory , Buck David
Published: March 2020

Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies (ONT) PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables genome-wide detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialized joint calling algorithms. We find the comparative performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6Mb deletion and a p.(Arg249Met) mutation involvingTP53are orientedin trans.
MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity
Authors: Lu Ya-Lin , Liu Yangjian , McCoy Matthew J. , Yoo Andrew S.
Published: March 2020

Neuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing anti-neurogenic genes. How these miRNAs function after the onset of the transcriptome switch to a neuronal fate remains unclear. Here, we identified direct targets of miRNAs by Argonaute (AGO) HITS-CLIP as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by a neuron-enriched RNA-binding protein, ELAVL3, that interacts with AGO and binds target transcripts, whereas the non-neuronal ELAVL1 counterpart fails to elevate the miRNA-target gene expression. Although existing literature indicate that miRNA-ELAVL1 interaction can result in either target gene upregulation or downregulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miRNA target gene upregulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the downregulation of genes involved in neuronal function and process outgrowth, and cellular phenotypes of reduced inward currents and neurite outgrowth. Results from our study support the role of miR-124 promoting neuronal function through positive regulation of its target genes.
Acute social isolation evokes midbrain craving responses similar to hunger
Authors: Tomova Livia , Wang Kimberly L. , Thompson Todd , Matthews Gillian A. , Takahashi Atsushi , Tye Kay M. , Saxe Rebecca
Published: March 2020

When people are forced to be isolated from one another, do they crave social interactions? To address this question, we used functional magnetic resonance imaging (fMRI) to measure neural responses evoked by food and social cues after participants (n=40) experienced ten hours of mandated fasting or total social isolation. After isolation, people felt lonely and craved social interaction. Midbrain regions showed selective activation to food cues after fasting and to social cues after isolation; these responses were correlated with self-reported craving. By contrast, striatal and cortical regions differentiated between craving food versus social interaction. Across deprivation sessions, we find that deprivation narrows and focuses the brain’s motivational responses to the deprived target. Our results support the intuitive idea that acute isolation causes social craving, similar to the way fasting causes hunger.
Metformin improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis
Authors: Zhu Xiaoqi , Shen Junyan , Feng Shengyu , Huang Ce , Liu Zhongmin , Sun Yi. Eve. , Liu Hailiang
Published: March 2020

The cerebral microvasculature is essential for preservation of normal cerebral function. Age-related decreases of neurogenesis and cognitive function are accompanied by reduced blood flow and a decline in neural stem cell (NSC) number. Here, we report that metformin administered by tail vein injection enhanced cognition in aged but not young mice in a dose-dependent manner. Further, metformin restored cerebral blood flow and brain vascular density and promoted neurogenic potential of the subependymal zone/subventricular zone both in vivo and in vitro. RNA-Seq result indicated that metformin could enhance glycolysis in blood, with an increase in relative mRNA expression of the enzyme in the glycolysis pathway from hippocampal tissue of metformin-treated mice. Mechanistically, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in the glycolysis pathway, may contribute to angiogenic and neurogenic potentials of NSCs. Interestingly, examination of peripheral blood mononuclear cells from people of various ages showed that mRNA expression of GAPDH gradually decreased with age, while its expression level positively correlated with cognitive levels. Our results indicate that metformin represents a candidate pharmacological approach for recruitment of NSCs in aged mouse brain by enhancing glycolysis and promoting neurovascular generation, a strategy that might be of therapeutic value for anti-aging in humans.

Graphical Abstract
Brainstem development requires galactosylceramidase and is critical for the pathogenesis of Krabbe Disease
Authors: Weinstock Nadav I. , Kreher Conlan , Favret Jacob , Bongarzone Ernesto , Wrabetz Lawrence , Feltri M. Laura , Shin Daesung
Published: March 2020

Krabbe disease (KD) is caused by a deficiency of galactosylceramidase (GALC), which induces demyelination and neurodegeneration due to accumulation of cytotoxic psychosine. Hematopoietic stem cell transplantation (HSCT) improves clinical outcomes in KD patients only if delivered pre-symptomatically. We hypothesized that the restricted temporal efficacy of HSCT reflects a requirement for GALC in early brain development. Using a novelGalcfloxed allele, we induced ubiquitous GALC ablation (Galc-iKO) at various postnatal timepoints and identified a critical period of vulnerability to GALC ablation between P4-6. EarlyGalc-iKO induction caused a worse KD phenotype, higher psychosine levels, and a significantly shorter life-span. Intriguingly, GALC expression peaks during this critical developmental period. Further analysis revealed a novel cell autonomous role for GALC in the development and maturation of immature T-box-brain-1 positive brainstem neurons. These data identify a perinatal developmental period, in which neuronal GALC expression influences brainstem development that is critical for KD pathogenesis.
The Effect of the Glossary on the Reliability and Performance of the Reading the Mind in the Eyes Test (RMET)
Authors: Toloza-Muñoz José , González-Mendoza Jean , Castillo Ramón D. , Morales-Bader Diego
Published: March 2020

The Reading the Mind in the Eyes Test (RMET) is used to measure high-level Theory of Mind. RMET consists of images of the regions surrounding the eyes and a glossary of terms that defines words associated with the gazes depicted in the images. People must identify the meaning associated with each gaze and can consult the glossary as they respond. The results indicate that typically developed adults perform better than adults with neurodevelopmental disorders. However, the evidence regarding the validity and reliability of the test is contradictory. This study evaluated the effect of the glossary on the performance, internal consistency, and temporal stability of the test. A total of 89 undergraduate students were randomly assigned to three conditions. The first group used the original glossary (Ori-G). The second group developed a self-generated glossary of gazes (Self-G). Finally, the third group developed a glossary that did not define gazes, but unrelated words instead (No-G). The test was administered before and after participants drew a randomly assigned image as a secondary task. The findings show that the number of correct answers was similar among the three conditions before and after the secondary task. However, the Self-G and No-G groups took less time to finish the test. The type of glossary affected the consistency and stability of the test. In our case, the Self-G condition made the responses faster, more consistent, and more stable. The results are discussed in terms of levels of processing and the detection of mental states based on gazes.
Analysis of p67 allelic sequences reveals a subtype of allele type 1 unique to buffalo-derivedTheileria parvaparasites from southern Africa
Authors: Mukolwe Lubembe D. , Odongo David O. , Byaruhanga Charles , Snyman Louwtjie P. , Sibeko-Matjila Kgomotso P.
Published: March 2020

East Coast fever (ECF) and Corridor disease (CD) caused by cattle- and buffalo-derivedT. parvarespectively are the most economically important tick-borne diseases of cattle in the affected African countries. The p67 gene has been evaluated as a recombinant subunit vaccine against East Coast fever (ECF), and for discrimination ofT. parvaparasites causing ECF and Corridor disease (CD). The p67 allele type 1 was first identified in cattle-derivedT. parvaparasites from east Africa, where parasites possessing this allele type have been associated with ECF. Subsequent characterization of buffalo-derivedT. parvaparasites from South Africa where ECF was eradicated, revealed the presence of a similar allele type, raising concerns as to whether or not allele type 1 from parasites from the two regions is identical. A 900 bp central fragment of the gene encoding p67 was PCR amplified fromT. parvaDNA extracted from blood collected from cattle and buffalo in South Africa, Mozambique, Kenya, Tanzania and Uganda, followed by DNA sequence analysis. Four p67 allele types previously described were identified. A subtype of p67 allele type 1 was identified in parasites from clinical cases of CD and buffalo from southern Africa. Notably, p67 allele type 1 sequences from parasites associated with ECF in East Africa and CD in Kenya were identical. Analysis of two p67 B-cell epitopes (TpM12 and AR22.7) revealed amino acid substitutions in allele type 1 from buffalo-derivedT. parvaparasites from southern Africa. However, both epitopes were conserved in allele type 1 from cattle- and buffalo-derivedT. parvaparasites from East Africa. These findings reveal detection of a subtype of p67 allele type 1 associated withT. parvaparasites transmissible from buffalo to cattle in southern Africa.
Third-generation dual-source computed tomography of the abdomen: comparison of radiation dose and image quality of 80kVp and 80/150kVp with tin filter
Authors: Choi Seung Joon , Park So Hyun , Park Seong Ho , Pak Seong Yong , Choi Jae Won , Ahn Su Joa , Shim Young Sup , Jeong Yu Mi , Kim Bohyun
Published: March 2020

Objective

To compare the radiation dose, objective and subjective image quality, and diagnostic performances of 80 kVp and 80/150 kVp with tin filter (80/Sn150 kVp) computed tomography (CT) in oncology patients.

Methods

One hundred forty-five consecutive oncology patients who underwent third-generation dual-source dual-energy CT of the abdomen for evaluation of malignant visceral, peritoneal, extraperitoneal, and bone tumor were retrospectively recruited. Two radiologists independently reviewed each observation in 80 kVp CT and 80/Sn150 kVp CT. Modified line-density profile of the tumor and contrast-to-noise ratio (CNR) were measured. Diagnostic confidence, lesion conspicuity, and subjective image quality were calculated and compared between image sets.

Results

Modified line-density profile analysis revealed higher attenuation differences between the tumor and the normal tissue in 80 kVp CT than in 80/Sn150 kVp CT (127 vs. 107, P = 0.05). The 80 kVp CT showed increased CNR in the liver (8.0 vs. 7.6) and the aorta (18.9 vs. 16.3) than the 80/Sn150 kVp CT. The 80 kVp CT yielded higher enhancement of organs (4.9 ± 0.2 vs. 4.7 ± 0.4, P < 0.001) and lesion conspicuity (4.9 ± 0.3 vs. 4.8 ± 0.5, P = 0.035) than the 80/Sn150 kVp CT; overall image quality and confidence index were comparable. The effective dose reduced by 45.2% with 80 kVp CT (2.3 mSv ± 0.9) compared to 80/Sn150 kVp CT (4.1 mSv ± 1.5).

Conclusions

The 80 kVp CT performed similar or better than 80/Sn150 kVp CT for abdominal tumor evaluation with 45.2% radiation dose reduction in oncology patients.
HumGut: A comprehensive Human Gut prokaryotic genomes collection filtered by metagenome data
Authors: Hiseni Pranvera , Rudi Knut , Wilson Robert C. , Hegge Finn Terje , Snipen Lars
Published: March 2020

Background

A major bottleneck in the use of metagenome sequencing for human gut microbiome studies has been the lack of a comprehensive genome collection to be used as a reference database. Several recent efforts have been made to re-construct genomes from human gut metagenome data, resulting in a huge increase in the number of relevant genomes. In this work, we aimed to create a collection of the most prevalent healthy human gut prokaryotic genomes, to be used as a reference database, including both MAGs from the human gut and ordinary RefSeq genomes.

Results

We screened > 5,700 healthy human gut metagenomes for the containment of > 490,000 publicly available prokaryotic genomes sourced from RefSeq and the recently announced UHGG collection. This resulted in a pool of > 379,000 genomes that were subsequently scored and ranked based on their prevalence in the healthy human metagenomes. The genomes were then clustered at subspecies resolution, and cluster representatives were retained to comprise the HumGut collection. Using the Kraken2 software for classification, we find superior performance in the assignment of metagenomic reads, classifying on average 94.5% of the reads in a metagenome, as opposed to 86% with UHGG and 44% when using standard Kraken2 database. HumGut, half the size of standard Kraken2 database and directly comparable to the UHGG size, outperforms them both.

Conclusions

The HumGut collection contains > 30,000 genomes clustered at subspecies resolution and ranked by human gut prevalence. We demonstrate how metagenomes from IBD-patients map equally well to this collection, indicating this reference is relevant also for studies well outside the metagenome reference set used to obtain HumGut. We believe this is a valuable resource in a field in dire need of method standardization. All data and metadata, as well as helpful code, are available athttp://arken.nmbu.no/~larssn/humgut/.
Self-cutting and integrating CRISPR plasmids (SCIPs) enable targeted genomic integration of genetic payloads for rapid cell engineering
Authors: Bloemberg Darin , Sosa-Miranda Daniela , Nguyen Tina , Weeratna Risini D. , McComb Scott
Published: March 2020

Since observations that CRISPR nucleases function in mammalian cells, many strategies have been devised to adapt them for genetic engineering. Here, we investigated self-cutting and integrating CRISPR-Cas9 plasmids (SCIPs) as easy-to-use gene editing tools that insert themselves at CRISPR-guided locations. SCIPs demonstrated similar expression kinetics and gene disruption efficiency in mouse (EL4) and human (Jurkat) cells, with stable integration in 3-6% of transfected cells. Clonal sequencing analysis indicated that integrants showed bi- or mono-allelic integration of entire CRISPR plasmids in predictable orientations and with limited indel formation. Interestingly, including longer homology arms (HAs) (500 bp) in varying orientations only modestly increased knock-in efficiency (∼2-fold). Using a SCIP-payload design (SCIPpay) which liberates a promoter-less sequence flanked by HAs thereby requiring perfect homology-directed repair (HDR) for transgene expression, longer HAs resulted in higher integration efficiency and precision of the payload but did not affect integration of the remaining plasmid sequence. As proofs-of-concept, we used SCIPpay to 1) insert a gene fragment encoding tdTomato into theCD69locus of Jurkat cells, thereby creating a cell line that reports T cell activation, and 2) insert a chimeric antigen receptor (CAR) gene into theTRAClocus. Here, we demonstrate that SCIPs function as simple, efficient, and programmable tools useful for generating gene knock-out/knock-in cell lines and suggest future utility in knock-in site screening/optimization, unbiased off-target site identification, and multiplexed, iterative, and/or library-scale automated genome engineering.
Structural influence of the conserved Hsp40 HPD tripeptide on Hsp70 chaperone function
Authors: Mallapre OO , Bascos NAD
Published: March 2020

The control of Hsp70 functions has been related to the modulation of ATP hydrolysis and substrate capture by Hsp40. Structural and biophysical analyses of Hsp40 variants and their interactions with Hsp70 have identified key residues for this functional control mechanism. Conserved residues in both Hsp40 and Hsp70 have revealed conserved interactions that link Hsp40 binding to the catalytic residues within Hsp70. The current work investigates the effect of documented J-domain dysfunctional mutations (i.e. D35N, H33Q) on the described interaction linkage. Molecular dynamics simulations were used to compare the persistence of individual bond types (i.e. H-bonds, salt bridges, hydrophobic interactions) between Hsp70 and the bound forms of functional and dysfunctional Hsp40 variants. The generated data suggests the involvement of both direct and allosteric effects for the tested mutations. The observed changes relate mutations in the conserved HPD tripeptide of Hsp40 to alterations in the interaction network that induces Hsp70 chaperone functions.

STATEMENT OF SIGNIFICANCE

The significance of the work may be summarized as follows. First, the interaction network for the simulated systems were observed to be different from one previously proposed for a disulfide linked complex (9). This may be attributed to altered residue movement and interactions without the restrictions set by the disulfide link. These results support the use ofin silicomethods to refine investigations of molecular contacts, particularly for systems, whose invitrostructural elucidation are difficult to achieve without modifications.

Second, key interactions for intermolecular and intramolecular contacts were observed within a short simulation time (0.1 ns) matched those from much longer runs (500 ns) (4). This result highlights the possibility of identifying key interactions with relatively low computational cost.
The cytosolicArabidopsis thalianacysteine desulfurase ABA3 delivers sulfur to the sulfurtransferase STR18
Authors: Selles Benjamin , Moseler Anna , Caubrière Damien , Sun Sheng-Kai , Ziesel Morgane , Dhalleine Tiphaine , Hériché Mathilde , Wirtz Markus , Rouhier Nicolas , Couturier Jérémy
Published: March 2020

The biosynthesis of many sulfur-containing molecules depends on cysteine as a sulfur source. Cysteine desulfurase (CD) and rhodanese (Rhd) domain-containing protein families participate in the trafficking of sulfur for various metabolic pathways in bacteria and human, but their connection is not yet described in plants. The existence of natural chimeric proteins, however, containing both CD and Rhd domains in specific bacterial genera suggests a general interaction between both proteins. We report here the biochemical relationships between two cytosolic proteins fromArabidopsis thaliana, a Rhd domain containing protein, the sulfurtransferase 18 (STR18), and a CD isoform referred to as ABA3, and compare these biochemical features to those of a natural CD-Rhd fusion protein from the bacteriumPseudorhodoferax sp.. We observed that the bacterial enzyme is bifunctional exhibiting both CD and STR activities using L-cysteine and thiosulfate as sulfur donors but preferentially uses L-cysteine to catalyze trans-persulfidation reactions.In vitroactivity assays and mass spectrometry analyses revealed that STR18 stimulates the CD activity of ABA3 by reducing the intermediate persulfide on its catalytic cysteine thereby accelerating the overall transfer reaction. Both proteins interactin plantaand form an efficient sulfur relay system whereby STR18 catalyzes trans-persulfidation reactions from ABA3 to the model acceptor protein roGFP2. In conclusion, the ABA3-STR18 couple likely represents an uncharacterized pathway of sulfur trafficking in the cytosol of plant cells, independent of ABA3 function in molybdenum cofactor maturation.
Incorporation of a nucleoside analog maps genome repair sites in post-mitotic human neurons
Authors: Reid Dylan A. , Reed Patrick J. , Schlachetzki Johannes C.M. , Chou Grace , Chandran Sahaana , Lu Ake T. , McClain Claire A. , Ooi Jean H. , Jones Jeffrey R. , Linker Sara B. , Tsui Enoch C. , Ricciardulli Anthony S. , Lau Shong , Schafer Simon T. , Horvath Steve , Dixon Jesse R. , Hah Nasun , Glass Christopher K. , Gage Fred H.
Published: March 2020

Neurons are the longest-living cells in our bodies, becoming post-mitotic in early development upon terminal differentiation. Their lack of DNA replication makes them reliant on DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, potentially giving rise to genomic dysfunction that may influence cognitive decline and neurodegenerative diseases. Despite this challenge, our knowledge of how genome instability emerges and what mechanisms neurons and other long-lived cells may have evolved to protect their genome integrity over the human life span is limited. Using a targeted sequencing approach, we demonstrate that neurons consolidate much of their DNA repair efforts into well-defined hotspots that protect genes that are essential for their identity and function. Our findings provide a basis to understand genome integrity as it relates to aging and disease in the nervous system.

One Sentence Summary

Recurrent DNA repair hotspots in neurons are linked to genes essential for identity and function.
In situdifferentiation of iridophore crystallotypes underlies zebrafish stripe patterning
Authors: Gur Dvir , Bain Emily , Johnson Kory , Aman Andy J. , Pasoili Amalia , Flynn Jessica D. , Allen Michael C. , Deheyn Dimitri D. , Lee Jennifer C. , Lippincott-Schwartz Jennifer , Parichy David
Published: March 2020

Skin color patterns are ubiquitous in nature, evolve rapidly, and impact social behavior1, predator avoidance2, and protection from ultraviolet irradiation3. A leading model system for vertebrate skin patterning is the zebrafish4-7; its alternating blue stripes and yellow interstripes depend on guanine crystal-containing cells called iridophores that reflect light. It was suggested that the zebrafish’s alternating color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes7-9. When we tracked iridophores, however, we found they did not migrate between stripes and interstripes but instead differentiated and proliferated in place based on their micro-environment. RNA seq analysis further revealed stripe and interstripe iridophores had different transcriptomic states, while cryogenic scanning electron microscopy and micro-X-ray diffraction showed they had different guanine crystal organizations and responsiveness to norepinephrine, all indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present a new model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, subcellular organelles arise in stripe and interstripe zones byin situdifferentiation. In this model, pattern phenotype depends not only on interactions among pigment cells that affect their arrangements, but also on factors that specify subcellular organization and physiological responsiveness of specialized organelles.
Measurement of the leakage flux in the vicinity of a transformer core
Authors: Duchesne Stéphane , Morganti Fabrice , Shulz Carl , Roger Daniel
Published: March 2020

Purpose

This study presents a new method for the detection of faults in large transformer cores. It is based on the analysis of leakage flux components in the vicinity of the sheet stack. The purpose of this study is to provide a nondestructive analysis tool for transformer cores during the assembly process to detect accidental defects such as inter-laminar short circuits.

Design/methodology/approach

The different components of the leakage flux allow localization of the fault in the stack and also permit to assess its severity. Out of the many kinds of defects which may appear in a transformer core, this method only detects those which actually cause an increase in the transformer’s global iron losses, which are thus the most detrimental.

Findings

The proposed method allows a more efficient control of the quality of the cores during their manufacturing process. Until now, it was only possible to know the quality of the core when the transformer was fully assembled.

Research limitations/implications

The accuracy of the method depends on the size of the defect and may request many measurements to give usable information.

Practical implications

Controlling iron losses in a core during its construction avoids heavy dismantling operations, both financially and temporally.

Originality/value

This method can help transformer manufacturers optimize their building process. In addition, the method remains effective regardless of the size of the core considered.
Employment and attitudes toward women among Syrian refugees
Authors: Baranik Lisa E.
Published: March 2020

Purpose

The current study examined employment rates and predictors of employment among Syrian refugees currently living in Lebanon and Jordan. This paper argues that men and women refugees have different experiences seeking out employment after resettlement due to patriarchal structures and attitudes toward women that are present in the Arab Middle East. The goals of this paper were a) to examine employment rates among Syrian refugees, b) to examine predictors of employment among male and female refugees, and c) to examine refugee status as a moderator of the relationship between attitudes toward women and employment status.

Design/methodology/approach

Nationally representative data from the Arab Barometer on 600 refugees and 1400 native-born individuals living in Lebanon and Jordan from 2016–2017 were used.

Findings

Native-born individuals living in Lebanon and Jordan were 2.16 times more likely to be employed than refugees. Men living in Lebanon and Jordan were 7.83 times more likely to be employed than women. Finally, refugee status moderated the relationship between attitudes toward women's rights and roles and employment. Among native-born women, a positive attitude toward women's rights and roles predicted employment status, whereas this positive relationship was not found for women refugees. Among refugee men, a positive attitude toward women's rights and roles was linked to a lower likelihood of holding a job.

Practical implications

These findings suggest that agencies supporting refugees should communicate realistic expectations about employment during resettlement and should address the challenges that women refugees face when seeking employment.

Originality/value

This study is the first study to identify attitudes toward women's rights and roles as a predictor of employment among refugee populations and highlights the unique struggles that refugee women face.
The adoption of electronic records management system (ERMS) in the Yemeni oil and gas sector
Authors: Hawash Burkan , Mokhtar Umi Asma’ , Yusof Zawiyah M. , Mukred Muaadh
Published: March 2020

Purpose

Identification of factors for electronic records management system (ERMS) adoption is important as it allows organizations to focus their efforts on these factors to ensure success. The purpose of this paper is to identify the factors that influence ERMS adoption in the Yemeni oil and gas (O&G) sector.

Design/methodology/approach

This paper conducts a systematic literature review (SLR) to extract the most common factors that could facilitate successful ERMS adoption. Information technology (IT) experts were asked to rank the extracted factors via an e-mail questionnaire and to recommend specific critical success factors that must be given extra attention to increasing the success of ERMS adoption. Essentially, the proposed methodology is technology-organization-environment (TOE) modeling to examine the important factors influencing decision-makers in the Yemeni O&G sector regarding ERMS adoption.

Findings

This paper identifies factors influencing ERMS adoption based on SLR and an expert-ranking survey. The data that were collected from IT experts were analyzed using the statistical package for the social sciences. The results showed that only 12 out of 20 factors were significant. The experts then added three new factors, resulting in 15 significant factors classified into the three dimensions as follows: technology, organization and environment.

Originality/value

Limited studies have been carried out in the context of the O&G sector, even among developed countries such as Canada, the UK and Australia. These studies have focused on a limited number of factors for ERMS adoption targeting better utilization of human resources, faster and more user-friendly system responses and suitability for organizational ease. This paper explores the factors that may prove useful in adopting of ERMS in the O&G sector of developing countries, similar to Yemen.
Phocine distemper virus uses phocine and other animal SLAMs as a receptor but not human SLAM
Authors: Seki Fumio , Ohishi Kazue , Maruyama Tadashi , Takeda Makoto
Published: March 2020

Morbilliviruses use the signaling lymphocyte activation molecule (SLAM) as a receptor to infect their hosts. Seals are almost the only animal species that show apparent infection with phocine distemper virus (PDV). Seal SLAM functioned as a PDV receptor. However, dolphin‐ and dog‐SLAM molecules, but not human SLAM, were also fully functional PDV receptors. These data suggest that the host range of PDV is not simply determined by its SLAM usage. However, human nonsusceptibility to PDV infection may be at least partly attributable to the inability of PDV to use human SLAM as a receptor.
Dexmedetomidine in the prevention of postoperative delirium in elderly patients following non‐cardiac surgery: A systematic review and meta‐analysis
Authors: Shen Qi‐hong , Li Hui‐fang , Zhou Xu‐yan , Yuan Xiao‐zhong
Published: March 2020

The efficacy of dexmedetomidine in the prevention of postoperative delirium (POD) remains ambiguous, however, it has been used to reduce the incidence of delirium in elderly patients. Here, we conducted a meta‐analysis study for assessing the effects of dexmedetomidine on POD among elderly patients following non‐cardiac surgery. A systematic literature search was performed against the PubMed, EMBASE, Cochrane Library, and Web of Science databases, and all relevant literature published till November 30, 2019, were considered. Our analysis included 16 randomised controlled trials conducted with 4534 patients for exploring the effects of dexmedetomidine on POD in elderly patients following non‐cardiac surgery. It was observed that the overall incidence of POD was significantly lower in the dexmedetomidine group than in the control group (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.43–0.61, P < .01). Similar results were obtained from subgroup analysis upon comparison of the placebo (RR 0.52, 95% CI 0.41–0.66, P < .01, moderate quality of evidence), propofol‐treated (RR 0.55, 95% CI 0.38–0.78, P < .01, low quality of evidence), and midazolam‐treated (RR 0.38, 95% CI 0.20–0.71, P < .01, low quality of evidence) groups. Trial sequential analysis revealed that the cumulative z‐value superseded the monitoring boundary and reached the required information size. However, patients who received dexmedetomidine had a higher incidence of bradycardia and hypotension. In conclusion, the meta‐analysis revealed that dexmedetomidine appears to decrease the risk of POD in elderly patients following non‐cardiac surgery. However, as some of the studies were heterogeneous and of low quality, high‐quality trials are necessary for drawing more definitive conclusions.
Hemodialysis patients with less extracellular water overload and smaller cardiac atrial chamber sizes are at greater risk of a fall in blood pressure during dialysis
Authors: Yoowannakul Suree , Vongsanim Surachet , Kotecha Tushar , Fontana Marianna , Davenport Andrew
Published: March 2020

Intradialytic hypotension is the most common complication of hemodialysis (HD) treatments. Excessive ultrafiltration results in reduced cardiac preload. We aimed to determine whether a fall in systolic blood pressure during HD was greater in patients starting HD with (a) less overhydration measured by extracellular water (ECW) and (b) lower cardiac preload by cardiac magnetic resonance imaging (MRI). Pre‐HD measurements of ECW and total body water (TBW) were performed using multifrequency bioimpedance (MFBIA). Cardiac chamber sizes and functions were determined by MRI. Twenty‐six patients, 18 males (69.2%), 11 (42.3%) with diabetes, mean age 63.9 ± 15.9 years were studied. Systolic blood pressure (SBP) fell in 15 (57.7%) patients, and either did not change or increased in 9. There was no difference in demographics between groups. Patients with a fall in SBP had lower pre‐HD ECW/TBW (0.400 ± 0.018 vs 0.418 ± 0.021), indexed right ventricular end‐diastolic volume (81.2 ± 37.6 vs 100.8 ± 33.7 mL/m2), and indexed left atrial size (13.7 ± 3.9 vs 18.3 ± 5.0 mL/m2), all P < .05, respectively. There were univariate correlations between the change in SBP and pre‐HD ECW/TBW for the trunk (r = .50, P = .009) and indexed left atrial volume (r = .54, P = .005). A fall in blood pressure occurred more commonly in patients starting HD with lower overhydration as measured by bioimpedance, and those with smaller cardiac chamber sizes. Patients with the lowest ECW/TBW and smallest cardiac chamber sizes had the greatest falls in SBP. This study reinforces the importance of determining physiological target weights and avoiding inappropriately low target weights for HD patients.
In vitro performance of trans‐valve left ventricular assist device installed at aortic valve position
Authors: Okamoto Eiji , Yano Tetsuya , Inoue Yusuke , Shiraishi Yasuyuki , Yambe Tomoyuki , Mitamura Yoshinori
Published: March 2020

In this study, we developed a trans‐valve left ventricular assist device (LVAD) that unites a rear‐impeller axial‐flow blood pump (AFBP) and a polymer membrane valve placed at the aortic valve position. The diameter and length of the rear impeller AFBP was 12 and 63 mm, respectively. The polymer membrane valve was similar to the jelly‐fish valve consisting of a valve leaflet made of silicone rubber (thickness 0.5 mm), valve ring (diameter: 25 mm), and valve spokes. The trans‐valve LVAD was examined in a mock circulation. An implantable pulsatile flow (PF) VAD was connected to an atrial reservoir to simulate the left ventricle (LV), and the Hall valve was worn in the inflow port, and the trans‐valve LVAD was placed in the outflow port as an outflow valve. When the motor rotational speed increased to 26 400 rpm, the mean aortic flow increased from 4.2 to 5.3 L/min, mean aortic pressure increased from 83.4 to 100 mm Hg, and mean motor current of the implantable PF VAD decreased from 1.18 to 0.94 A (unloading effect on LV −21%). The energy equivalent pressure increased from 85.2 to 102 mm Hg, and surplus hemodynamic energy (SHE) decreased by −15.4% from the baseline. In conclusion, the trans‐valve LVAD has an advantage of preserving pulsatility without any complicated mechanism and is a novel and promising LV support device.
Overprescribing and rational therapeutics: Barriers to change and opportunities to improve
Authors: Bennett Frances , Ferner Robin , Sofat Reecha
Published: March 2020

There is increasing national and international interest in overprescribing and polypharmacy, and the burden that the inappropriate use of multiple medicines can place on individual patients and on society as a whole. This paper explores the challenges faced by prescribers and pharmacists wishing to reduce polypharmacy, including the uncertainties about the risks and benefits of continuing or stopping individual drugs. We discuss the factors influencing us to prescribe—which may lead to overprescribing—including the increasing number of guidelines, perceived patient pressure and advertising. We offer a critical appraisal of the tools currently available to clinicians and pharmacists aiming to rationalise medicines, and finally a systems‐wide approach to improving overprescribing and problematic polypharmacy.
Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel
Authors: de Graaf Niels P. J. , Bontkes Hetty J. , Roffel Sanne , Kleverlaan Cornelis J. , Rustemeyer Thomas , Gibbs Sue , Feilzer Albert J.
Published: March 2020

Background

Skin patch testing is still seen as the gold standard for the diagnosis of allergic hypersensitivity. For several metals and for patients with a suspected adverse reaction to their medical device implant material, patch testing can be unreliable. The current alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LPT) using tritiated thymidine. This method is well‐established but requires handling of radioactive material, often uses heat‐inactivated allogenic human pooled serum and cannot determine T cell subsets.

Objective

To develop a radioactive free LPT by using carboxyfluorescein succinimidyl ester (CFSE) and to evaluate the influence of serum source (heat‐inactivated human pooled serum [HI HPS] vs autologous serum) on the sensitivity and specificity of the nickel‐specific LPT.

Methods

Peripheral blood mononuclear cells derived from nickel‐allergic patients and healthy controls were collected, labelled with CFSE and cultured in medium containing 10% HI HPS or 10% autologous serum with or without additional T cell skewing cytokine cocktails (Th1: IL‐7/IL‐12, Th2: IL‐7/IL‐4 or Th17: IL‐7/IL‐23/IL‐1β) in the absence or presence of NiSO4. The stimulation index (SI) was calculated as the ratio of divided cells, that is the percentage of CFSElow/neg CD3+CD4+ T‐lymphocytes upon nickel stimulation compared to the percentage of CFSElow/neg CD3+CD4+ T‐lymphocytes without antigen. These results were compared with the history of Ni allergy, patch test results and the MELISA test.

Results

Autologous serum positively influenced Ni‐specific proliferation while HI HPS negatively influenced Ni‐specific proliferation. The test protocol analysing CD4+ cells and autologous serum without skewing cytokines scored the best diagnostic values (sensitivity 95%; specificity 93%; and overall accuracy 94%) compared to the parallel test using HI HPS (accuracy 60%). Cytokine supplements did not further improve the test protocol which used autologous serum. The protocol using HI HPS could be further improved by addition of the cytokine skewing cocktails.

Conclusions

Here, we describe an optimized and highly accurate flow cytometric LPT which comprises of CFSE‐labelled cells cultured in autologous serum (not heat inactivated) and without the presence of T cell skewing cytokines.

Clinical relevance

The sensitivity and specificity of LPT is enhanced, compared to HI HPS, when autologous serum without skewing cytokines is used.
Assessing the Impact of the NIH CTSA Program on Clinical Trials Registered With ClinicalTrials.gov
Authors: Berg Arthur
Published: March 2020

Since 2006, the US Congress has appropriated ~ 7 billion dollars in total toward the (CTSA) program of the National Institutes of Health (NIH), representing ~ 1.5% of the NIH total budget. There is no doubt this investment has led to substantial improvements in clinical and translational research, but the impact of these large NIH‐sponsored awards to academic medical centers have largely been documented by anecdotal accomplishments. This paper provides a purely quantitative assessment of the impact of these awards on clinical trials registered on ClinicalTrials.gov. In particular, we find a dramatic increase in the number of registered clinical trials and clinical trial enrollment associated with the CTSA grant award. Additionally, the impact is shown to be magnified with the number of years of receiving CTSA funding.
Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin‐Induced Cutaneous Adverse Drug Reactions
Authors: Fohner Alison E. , Rettie Allan E. , Thai Khanh K. , Ranatunga Dilrini K. , Lawson Brian L. , Liu Vincent X. , Schaefer Catherine A.
Published: March 2020

The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin‐induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA‐B)*15:02 risk allele. In the multi‐ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self‐identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non‐Hispanic. We identified 264 (69%) CYP2C9*1/*1, 77 (20%) CYP2C9*1/*2, and 29 (8%) CYP2C9*1/*3. We also determined CYP2C19 genotypes, including 112 with the increased activity CYP2C19*17 allele. Using electronic clinical notes, we identified 32 participants (8%) with phenytoin‐induced cutaneous adverse events recorded within 100 days of first phenytoin dispensing. Adjusting for age, sex, daily dose, and race/ethnicity, participants with CYP2C9*1/*3 or CYP2C9*2/*2 genotypes were more likely to develop cutaneous adverse events compared with CYP2C9*1/*1 participants (odds ratio 4.47; 95% confidence interval 1.64–11.69; P < 0.01). Among participants with low‐intermediate and poor CYP2C9 metabolizer genotypes, eight (22%) who also had extensive and rapid CYP2C19 metabolizer genotypes experienced cutaneous adverse events, compared with none of those who also had intermediate CYP2C19 metabolizer genotypes (P = 0.17). Genetic variation reducing CYP2C9 metabolic activity may increase risk for phenytoin‐induced cutaneous adverse events in the absence of the HLA‐B*15:02 risk allele.
Tag‐less patency capsule for suspected small bowel stenosis: Nationwide multicenter prospective study in Japan
Authors: Nakamura Masanao , Watanabe Kenji , Ohmiya Naoki , Hirai Fumihito , Omori Teppei , Tokuhara Daisuke , Nakaji Konosuke , Nouda Sadaharu , Esaki Motohiro , Sameshima Yukinori , Goto Hidemi , Terano Akira , Tajiri Hisao , Matsui Toshiyuki ,   J‐POP study group
Published: March 2020

Study aims

The PillCam patency capsule (PPC) is an Agile tag‐less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention.

Methods

This prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively.

Results

Of 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn’s disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non‐confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels <4.0 g/dL, and previous small bowel obstruction (adjusted odds ratios: 4.21, 2.60, 2.47, 2.12, and 2.00; 95% confidence intervals: 2.62–6.78, 1.62–4.17, 1.43–4.27, 1.32–3.40, and 1.15–3.47, respectively).

Conclusions

The PillCam™ patency capsule helped preclude SBCE retention in most patients, but its accurate localization was essential for cases without excretion (Study registered the University Hospital Medical Information Network, #UMIN000010513).
Treatment of upper gastrointestinal bleeding in 2020: New techniques and outcomes
Authors: Lau Louis H. S. , Sung Joseph J. Y.
Published: March 2020

The clinical outcome of upper gastrointestinal bleeding has improved due to advances in endoscopic therapy and standardized peri‐endoscopy care. Apart from validating clinical scores, artificial intelligence‐assisted machine learning models may play an important role in risk stratification. While standard endoscopic treatments remain irreplaceable, novel endoscopic modalities have changed the landscape of management. Over‐the‐scope clips have high success rates as rescue or even first‐line treatments in difficult‐to‐treat cases. Hemostatic powder is safe and easy to use, which can be useful as temporary control with its high immediate hemostatic ability. After endoscopic hemostasis, Doppler endoscopic probe can offer an objective measure to guide the treatment endpoint. In refractory bleeding, angiographic embolization should be considered before salvage surgery. In variceal hemorrhage, banding ligation and glue injection are first‐line treatment options. Endoscopic ultrasound‐guided therapy is gaining popularity due to its capability of precise localization for treatment targets. A self‐expandable metal stent may be considered as an alternative option to balloon tamponade in refractory bleeding. Transjugular intrahepatic portosystemic shunting should be reserved as salvage therapy. In this article, we aim to provide an evidence‐based comprehensive review of the major advancements in endoscopic hemostatic techniques and clinical outcomes.