bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential drug-drug interactions in patients with indication for prophylactic implantation of a cardioverter defibrillator: a cross-sectional analysis
Authors: Dornquast Christina , Dombrowski Mirja , Zabel Markus , Willich Stefan N. , Reinhold Thomas 
Published: March 2020

Abstract
Background
Due to demographic transition, multimorbidity and high numbers of medicinal products, polypharmacy rates will presumably further increase. This could lead to higher risks of potentially inappropriate medications with potential drug-drug interactions (PDDI). PDDI has already been investigated by several studies, but not for patients with indication for prophylactic implantation of a cardioverter defibrillator (ICD). Thus, the objective of this analysis was to examine the frequency of PDDI in that specific group of patients and compare patients with or without PDDI regarding potential underlying factors.

Methods
Cross-sectional data analyses were performed using data of the prospective EU-CERT-ICD study that primarily aimed to assess ICD effectiveness in Europe. Self-reported baseline medication data of patients from Germany and Switzerland were used. Patients who reported to take at least two drugs simultaneously for at least 80 days were defined as population at risk. By means of a publicly available interaction checker, we analyzed the medication data regarding occurrence and characteristics of PDDI categorized as minor, moderate, and major PDDI. The analyses were done using descriptive methods and chi square testing.

Results
The total population (n = 524) and the population at risk (n = 383) were rather similar with an average age of 64 years and about 80% male. PDDIs were found for 296 patients (in 57% of total population vs. 77% of population at risk). The moderate PDDI category was most frequently with 268 affected patients. Comparing patients with and without any PDDI, the proportion of patients with place of residence in Germany varied distinctly (93% vs. 78%). The frequency of any PDDI for the total population was twice as high in Germany as in Switzerland (p value < 0.001).

Conclusions
PDDIs were frequently observed in this selected patient population and differed markedly between German and Swiss patients. The results should lead to higher awareness of polypharmacy and PDDIs. Adequate cooperation between health care providers should be promoted and new technologies such as drug interaction information systems or digital patient files used.

Trial registration
The EU-CERT-ICD study is registered at www.clinicaltrials.gov (NCT02064192).
Transcriptome analysis of the response provided by Lasiopodomys mandarinus to severe hypoxia includes enhancing DNA repair and damage prevention
Authors: Dong Qianqian , Wang Zishi , Jiang Mengwan , Sun Hong , Wang Xuqin , Li Yangwei , Zhang Yifeng , Cheng Han , Chai Yurong , Shao Tian , Shi Luye , Wang Zhenlong 
Published: March 2020

Abstract
Background
Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O2 utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema. To investigate mechanisms underlying the responses of subterranean rodents to severe hypoxia, we performed a cross-species brain transcriptomic analysis using RNA sequencing and identified differentially expressed genes (DEGs) between the subterranean rodent Lasiopodomys mandarinus and its closely related aboveground species L. brandtii under severe hypoxia (5.0% O2, 6 h) and normoxia (20.9% O2, 6 h).

Results
We obtained 361 million clean reads, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. We identified 359 and 515 DEGs by comparing the hypoxic and normoxia groups of L. mandarinus and L. brandtii, respectively. Gene Ontology (GO) analysis showed that upregulated DEGs in both species displayed similar terms in response to severe hypoxia; the main difference is that GO terms of L. brandtii were enriched in the immune system. However, in the downregulated DEGs, GO terms of L. mandarinus were enriched in cell proliferation and protein transport and those of L. brandtii were enriched in nuclease and hydrolase activities, particularly in terms of developmental functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs in L. mandarinus were associated with DNA repair and damage prevention as well as angiogenesis and metastasis inhibition, whereas downregulated DEGs were associated with neuronal synaptic transmission and tumor-associated metabolic pathways. In L. brandtii, upregulated KEGG pathways were enriched in the immune, endocrine, and cardiovascular systems and particularly in cancer-related pathways, whereas downregulated DEGs were associated with environmental information processing and misregulation in cancers.

Conclusions
L. mandarinus has evolved hypoxia adaptation by enhancing DNA repair, damage prevention, and augmenting sensing, whereas L. brandtii showed a higher risk of tumorigenesis and promoted innate immunity toward severe hypoxia. These results reveal the hypoxic mechanisms of L. mandarinus to severe hypoxia, which may provide research clues for hypoxic diseases.
Investigation of the immunogenicity of Zika glycan loop
Authors: Henderson Elizabeth A. , Tam Christina C. , Cheng Luisa W. , Ngono Annie Elong , Nguyen Anh-Viet , Shresta Sujan , McGee Matt , Padgett Hal , Grill Laurence K. , Martchenko Shilman Mikhail 
Published: March 2020

Abstract
Background
Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus. Previous studies have identified neutralizing antibodies from Zika patients that bind to quaternary epitopes across neighboring envelope (E) proteins, called E dimer epitopes (EDE). An asparagine-linked glycan on the “glycan loop” (GL) of the ZIKV envelope protein protects the functionally important “fusion loop” on the opposite E subunit in the dimer, and EDE antibodies have been shown to bind to both of these loops. Human EDE antibodies have been divided into two subclasses based on how they bind to the glycan loop region: EDE1 antibodies do not require glycosylation for binding, while EDE2 antibodies strongly rely on the glycan for binding.

Methods
ZIKV GL was expressed on tobacco mosaic virus nanoparticles. Mice were immunized with GL or full-length monomeric E and the immune response was analyzed by testing the ability of sera and monoclonal antibodies to bind to GL and to neutralize ZIKV in in vitro cellular assay.

Results
We report here the existence of ZIKV moderately neutralizing antibodies that bind to E monomers through epitopes that include the glycan loop. We show that sera from human Zika patients contain antibodies capable of binding to the unglycosylated glycan loop in the absence of the rest of the envelope protein. Furthermore, mice were inoculated with recombinant E monomers and produced neutralizing antibodies that either recognize unglycosylated glycan loop or require glycan for their binding to monomeric E. We demonstrate that both types of antibodies neutralize ZIKV to some extent in a cellular virus neutralization assay.

Conclusions
Analogous to the existing EDE antibody nomenclature, we propose a new classification for antibodies that bind to E monomer epitopes (EME): EME1 and EME2 for those that do not require and those that do require glycan for binding to E, respectively.
Predictive QSAR model confirms flavonoids in Chinese medicine can activate voltage-gated calcium (CaV) channel in osteogenesis
Authors: Chan Ki , Leung Henry Chi Ming , Tsoi James Kit-Hon 
Published: March 2020

Abstract
Background
Flavonoids in Chinese Medicine have been proven in animal studies that could aid in osteogenesis and bone formation. However, there is no consented mechanism for how these phytochemicals action on the bone-forming osteoblasts, and henceforth the prediction model of chemical screening for this specific biochemical function has not been established. The purpose of this study was to develop a novel selection and effective approach of flavonoids on the prediction of bone-forming ability via osteoblastic voltage-gated calcium (CaV) activation and inhibition using molecular modelling technique.

Method
Quantitative structure–activity relationship (QSAR) in supervised maching-learning approach is applied in this study to predict the behavioral manifestations of flavonoids in the CaV channels, and developing statistical correlation between the biochemical features and the behavioral manifestations of 24 compounds (Training set: Kaempferol, Taxifolin, Daidzein, Morin, Scutellarein, Quercetin, Apigenin, Myricetin, Tamarixetin, Rutin, Genistein, 5,7,2′-Trihydroxyflavone, Baicalein, Luteolin, Galangin, Chrysin, Isorhamnetin, Naringin, 3-Methyl galangin, Resokaempferol; test set: 5-Hydroxyflavone, 3,6,4′-Trihydroxyflavone, 3,4′-Dihydroxyflavone and Naringenin). Based on statistical algorithm, QSAR provides a reasonable basis for establishing a predictive correlation model by a variety of molecular descriptors that are able to identify as well as analyse the biochemical features of flavonoids that engaged in activating or inhibiting the CaV channels for osteoblasts.

Results
The model has shown these flavonoids have high activating effects on CaV channel for osteogenesis. In addition, scutellarein was ranked the highest among the screened flavonoids, and other lower ranked compounds, such as daidzein, quercetin, genistein and naringin, have shown the same descending order as previous animal studies.

Conclusion
This predictive modelling study has confirmed and validated the biochemical activity of the flavonoids in the osteoblastic CaV activation.
Is it possible to substitute the monofilament test for the Ipswich Touch Test in screening for peripheral diabetic neuropathy?
Authors: Dutra Luz Marina Alfonso , Moura Mirian Conceição , do Prado Flaviene Alves , De Oliveira Lima Giselle , Melo Manuela Costa , Fernandez Rubens Nelson Morato , Novaes Maria Rita Carvalho Garbi 
Published: March 2020

Abstract
Background
This study aimed to assess the agreement and efficacy of the Ipswich Touch Test compared to the monofilament test in individuals with type 2 diabetes.

Materials and methods
A cross-sectional and analytical study was conducted. The inclusion criteria were patients with type II diabetes (n = 250) who did not present ulcers or amputation in either foot. The exclusion criteria were as follows: patients who presented sequelae of cerebrovascular disease or other neurological pathologies, as well as diagnoses of malignancy, alcohol abuse, liver cirrhosis, hepatitis B, AIDS, hypothyroidism, chronic kidney disease or lupus erythaematosus, as these clinical conditions could influence or bias the results (Won and Park in Endocrinol Metab 31:230–238, 2016). Sensitivity, specificity, predictive values, likelihood ratios, and Kappa index were calculated. Other factors assessed were glycated haemoglobin and body mass index.

Results
Most of the participants were female (71.2%), and glycated haemoglobin (HbA1c) was greater than 7% in 54.4% of the patients. The mean age was 59.43 years, and the mean time since diagnosis was 12.38 years. The Kappa index was 0.819 (p < 0.001), and the Ipswich Touch Test had a sensitivity of 83.33%, a specificity of 97.66%, a positive predictive value of 85.71%, a negative predictive value of 97.21%, a positive likelihood ratio of 30.19%, and a negative likelihood ratio of 0.17%. The level of significance was 5% in this study.

Conclusion
The Ipswich Touch Test resented good agreement and efficacy compared to the gold standard—the 10 g monofilament test.
The nonnegative weak solution of a degenerate parabolic equation with variable exponent growth order
Authors: Zhan Huashui 
Published: March 2020

AbstractA degenerate parabolic equation of the form $$\bigl( \vert v \vert ^{\beta-1}v\bigr)_{t}= \operatorname{div} \bigl(b(x,t) \vert \nabla v \vert ^{p(x,t)-2}\nabla v \bigr)+\nabla\vec{g}\cdot\nabla\vec{\gamma}(v) $$(|v|β−1v)t=div(b(x,t)|∇v|p(x,t)−2∇v)+∇g→⋅∇γ→(v) is considered, where $\vec{g}=\{g^{i}(x,t)\}$g→={gi(x,t)}, $\vec{\gamma}(v)=\{ \gamma_{i}(v)\}$γ→(v)={γi(v)}. If the diffusion coefficient $b(x,t)\geq0$b(x,t)≥0 is degenerate on the boundary, by adding some restrictions on $b(x,t)$b(x,t) and g⃗, the existence and uniqueness of weak solutions are proved. Based on the uniqueness, the stability of weak solutions can be proved without any boundary condition.
The geography of agriculture participation and food security in a small and a medium-sized city in Ghana
Authors: Ayerakwa Hayford Mensah , Dzanku Fred Mawunyo , Sarpong Daniel Bruce 
Published: March 2020

AbstractThe debate about the contribution of urban agriculture to urban household food security has not considered the possible differential effects by geography of production activities, focusing either on urban household’s participation in agriculture irrespective of where the activity takes place, or restricting participation to production within urban and peri-urban areas, or more narrowly, production within build-up urban spaces. Using a sample of 2004 households in a small and a medium-sized city in Ghana, this article contributes by disentangling urban household’s participation in agriculture by geography of production activities and the implications for the food security of urban households. We find no evidence from our sample that participation in agriculture in general matters for the food security of urban households. However, urbanites who produced food in both urban and rural areas had better food security in the medium-sized city.
Assessing the efficacy of CRISPR/Cas9 genome editing in the wheat pathogen Parastagonspora nodorum
Authors: Khan Haseena , McDonald Megan C. , Williams Simon J. , Solomon Peter S. 
Published: March 2020

Abstract
Background
The genome-editing tool CRISPR/Cas9 has revolutionized gene manipulation by providing an efficient method to generate targeted mutations. This technique deploys the Cas9 endonuclease and a guide RNA (sgRNA) which interact to form a Cas9-sgRNA complex that initiates gene editing through the introduction of double stranded DNA breaks. We tested the efficacy of the CRISPR/Cas9 approach as a means of facilitating a variety of reverse genetic approaches in the wheat pathogenic fungus Parastagonospora nodorum.

Results
Parastagonospora nodorum protoplasts were transformed with the Cas9 protein and sgRNA in the form of a preassembled ribonuclear protein (RNP) complex targeting the Tox3 effector gene. Subsequent screening of the P. nodorum transformants revealed 100% editing of those mutants screened. We further tested the efficacy of RNP complex when co-transformed with a Tox3-Homology Directed Repair cassette harbouring 1 kb of homologous flanking DNA. Subsequent screening of resulting transformants demonstrated homologous recombination efficiencies exceeding 70%. A further transformation with a Tox3-Homology Directed Repair cassette harbouring a selectable marker with 50 bp micro-homology flanks was also achieved with 25% homologous recombination efficiency. The success of these homology directed repair approaches demonstrate that CRISPR/Cas9 is amenable to other in vivo DNA manipulation approaches such as the insertion of DNA and generating point mutations.

Conclusion
These data highlight the significant potential that CRISPR/Cas9 has in expediting transgene-free gene knockouts in Parastagonospora nodorum and also in facilitating other gene manipulation approaches. Access to these tools will significantly decrease the time required to assess the requirement of gene for disease and to undertake functional studies to determine its role.
Diet composition and feeding strategy of John Dory, Zeus faber, in the coastal waters of Korea
Authors: Kim Han Ju , Kim Hyeong-Gi , Oh Chul-Woong 
Published: March 2020

Abstract
Background
Most fish undergo prey switch from juvenile to adult. It is thought that slightly different feeding habits occur among adult fishes due to growth, spawning, habitat change, and so on. Therefore, the diet of the John Dory Zeus faber (≥ 24 cm TL) was studied in the coastal waters of Korea by analysis of stomach contents, with comparison by season and size class of diet composition and prey diversity. Monthly samples were taken from February 2017 to January 2018.

Results
The results showed that the John Dory was a piscivorous predator, and pisces had occupied 82.3% of IRI%. Trichiurus lepturus and Trachurus japonicus were important preys in all size classes and seasons. Diet composition differed among the size classes and seasons (Chi-square test, P < 0.05). As body size of Z. faber increased, the occurrence of benthic fish (Glyptocephalus stelleri) tended to increase. The seasonal prey composition also changed depending on the abundant species of each season.

Conclusions
Z. faber is a piscivorous predator. The consumption habits of Z. faber appear to different results by their size and seasons. This study suggests that Z. faber could be considered an opportunistic predator.
Imaging of asbestos-related lung and pleural diseases as an endemic exposure in Egypt
Authors: Kolta Marian Fayek , Khairy Mostafa Ahmed , El Hinnawy Yasmine Hamdy 
Published: March 2020

Abstract
Background
Asbestos refers to a group of naturally occurring silicate minerals which have been traditionally used in building materials and household products. Inhalation of asbestos fibers, however, has been associated with adverse health outcomes, with the disease manifestations principally affecting the thorax. The aim of our study is to detect and evaluate the different radiological patterns of asbestos-related lung and pleural disease and its complications

Results
MDCT examination was able to assess and distinguish asbestosis as well as asbestos-related lung and pleural disease besides detection of any associated complications.

Conclusion
This study demonstrates that while reporting of malignant asbestos-related pleural disease is adequate, there is room for improvement in the reporting of more benign disease.
Integrated Informatics Analysis of Cancer-Related Variants
Authors: Pagel Kymberleigh A. , Kim Rick , Moad Kyle , Busby Ben , Zheng Lily , Tokheim Collin , Ryan Michael , Karchin Rachel 
Published: March 2020

PURPOSE The modern researcher is confronted with hundreds of published methods to interpret genetic variants. There are databases of genes and variants, phenotype-genotype relationships, algorithms that score and rank genes, and in silico variant effect prediction tools. Because variant prioritization is a multifactorial problem, a welcome development in the field has been the emergence of decision support frameworks, which make it easier to integrate multiple resources in an interactive environment. Current decision support frameworks are typically limited by closed proprietary architectures, access to a restricted set of tools, lack of customizability, Web dependencies that expose protected data, or limited scalability. METHODS We present the Open Custom Ranked Analysis of Variants Toolkit 1 (OpenCRAVAT) a new open-source, scalable decision support system for variant and gene prioritization. We have designed the resource catalog to be open and modular to maximize community and developer involvement, and as a result, the catalog is being actively developed and growing every month. Resources made available via the store are well suited for analysis of cancer, as well as Mendelian and complex diseases. RESULTS OpenCRAVAT offers both command-line utility and dynamic graphical user interface, allowing users to install with a single command, easily download tools from an extensive resource catalog, create customized pipelines, and explore results in a richly detailed viewing environment. We present several case studies to illustrate the design of custom workflows to prioritize genes and variants. CONCLUSION OpenCRAVAT is distinguished from similar tools by its capabilities to access and integrate an unprecedented amount of diverse data resources and computational prediction methods, which span germline, somatic, common, rare, coding, and noncoding variants.
Game Change from Reagent- to Substrate-Controlled Peptide Synthesis
Authors: Muramatsu Wataru , Hattori Tomohiro , Yamamoto Hisashi 
Published: March 2020

Abstract
An account of the development of Lewis-acid-catalyzed methods for racemization-free peptide synthesis is presented. These methods are based on the substrate control concept that has been exploited extensively in stereoselective reactions, but the concept has never previously been applied to peptide synthesis. The most important difference that has emerged between our methods and the conventional methods based on reagent control concept such as coupling-reagent-mediated and boronic-acid-catalyzed peptide bond-forming reactions is how to activate the reaction sites and racemization control. The reagent-controlled methods proceed by generating highly reactive esters in situ, leading to occasional racemization through the formation of oxazolone intermediates. On the other hand, our substrate-controlled methods do not go through the known racemization processes because the Lewis acids we use herein are designed to activate moderately as an anchor a specific carbonyl group that is located at a reasonable distance from the directing group. Based on the substrate control concept, we have developed six novel methodologies for peptide bond-forming reactions over the last five years.
Transarterial CT angiography for surgical planning of spinal dural arteriovenous fistula
Authors: Kular Saminderjit , Tse George , Budu Alexandru , Bacon Andrew , Choudhari Kishor , Nagaraja Sanjoy 
Published: March 2020

Objective:
We report a novel method to provide excellent anatomical depiction of a dural arteriovenous fistula (dAVF) for surgical planning.

Methods:
A 78-year-old female presented with progressive back pain, deteriorating mobility and urinary incontinence with a background of obesity and severe osteoarthritis. Initial MRI suspected dAVF and subsequent spinal angiography encountered an extremely tortuous and arteriosclerotic aorta, hence catheterisation of the segmental-intercostal and lumbar vessels proved challenging. Contrast injection into the aortic arch via a pigtail catheter for arterial-phase CT angiogram of the descending aorta was performed.

Results:
This modality of imaging delineated the dAVF showing extensive involvement of the whole spine accounting for the patient’s symptoms. Furthermore this allowed characterisation of bony anatomy in relation to the fistula facilitating precise surgical approach. The dAVF was successfully disconnected through a localised laminectomy centred over the lesion.

Conclusion:
This specific technique for dAVF characterisation has not been previously reported, although trans-venous angiography has been used to some effect. In view of diagnostic and therapeutic technical difficulties that are often faced in such patients, this technique may be a useful alternative that is not only helpful in accurate diagnosis but helps in providing an invaluable guide for the surgical approach.

Advances in knowledge:
This case highlights the difficulties that one may be faced within cases of tortuous vasculature and the obese patient population. With this in mind we demonstrate how a unique hybridised technique may provide valuable alternative to the neurosciences team should such a future scenario arise.