bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-resolved evaluation of compound repositioning predictions on a text-mined knowledge network
Authors: Mayers Michael , Li Tong Shu , Queralt-Rosinach Núria , Su Andrew I. 
Published: December 2019

Abstract
Background
Computational compound repositioning has the potential for identifying new uses for existing drugs, and new algorithms and data source aggregation strategies provide ever-improving results via in silico metrics. However, even with these advances, the number of compounds successfully repositioned via computational screening remains low. New strategies for algorithm evaluation that more accurately reflect the repositioning potential of a compound could provide a better target for future optimizations.

Results
Using a text-mined database, we applied a previously described network-based computational repositioning algorithm, yielding strong results via cross-validation, averaging 0.95 AUROC on test-set indications. However, to better approximate a real-world scenario, we built a time-resolved evaluation framework. At various time points, we built networks corresponding to prior knowledge for use as a training set, and then predicted on a test set comprised of indications that were subsequently described. This framework showed a marked reduction in performance, peaking in performance metrics with the 1985 network at an AUROC of .797. Examining performance reductions due to removal of specific types of relationships highlighted the importance of drug-drug and disease-disease similarity metrics. Using data from future timepoints, we demonstrate that further acquisition of these kinds of data may help improve computational results.

Conclusions
Evaluating a repositioning algorithm using indications unknown to input network better tunes its ability to find emerging drug indications, rather than finding those which have been randomly withheld. Focusing efforts on improving algorithmic performance in a time-resolved paradigm may further improve computational repositioning predictions.
A pan-cancer somatic mutation embedding using autoencoders
Authors: Palazzo Martin , Beauseroy Pierre , Yankilevich Patricio 
Published: December 2019

Abstract
Background
Next generation sequencing instruments are providing new opportunities for comprehensive analyses of cancer genomes. The increasing availability of tumor data allows to research the complexity of cancer disease with machine learning methods. The large available repositories of high dimensional tumor samples characterised with germline and somatic mutation data requires advance computational modelling for data interpretation. In this work, we propose to analyze this complex data with neural network learning, a methodology that made impressive advances in image and natural language processing.

Results
Here we present a tumor mutation profile analysis pipeline based on an autoencoder model, which is used to discover better representations of lower dimensionality from large somatic mutation data of 40 different tumor types and subtypes. Kernel learning with hierarchical cluster analysis are used to assess the quality of the learned somatic mutation embedding, on which support vector machine models are used to accurately classify tumor subtypes.

Conclusions
The learned latent space maps the original samples in a much lower dimension while keeping the biological signals from the original tumor samples. This pipeline and the resulting embedding allows an easier exploration of the heterogeneity within and across tumor types and to perform an accurate classification of tumor samples in the pan-cancer somatic mutation landscape.
BaRTv1.0: an improved barley reference transcript dataset to determine accurate changes in the barley transcriptome using RNA-seq
Authors: Rapazote-Flores Paulo , Bayer Micha , Milne Linda , Mayer Claus-Dieter , Fuller John , Guo Wenbin , Hedley Pete E. , Morris Jenny , Halpin Claire , Kam Jason , McKim Sarah M. , Zwirek Monika , Casao M. Cristina , Barakate Abdellah , Schreiber Miriam , Stephen Gordon , Zhang Runxuan , Brown John W. S. , Waugh Robbie , Simpson Craig G. 
Published: December 2019

AbstractBackgroundThe time required to analyse RNA-seq data varies considerably, due to discrete steps for computational assembly, quantification of gene expression and splicing analysis. Recent fast non-alignment tools such as Kallisto and Salmon overcome these problems, but these tools require a high quality, comprehensive reference transcripts dataset (RTD), which are rarely available in plants.ResultsA high-quality, non-redundant barley gene RTD and database (Barley Reference Transcripts – BaRTv1.0) has been generated. BaRTv1.0, was constructed from a range of tissues, cultivars and abiotic treatments and transcripts assembled and aligned to the barley cv. Morex reference genome (Mascher et al. Nature; 544: 427–433, 2017). Full-length cDNAs from the barley variety Haruna nijo (Matsumoto et al. Plant Physiol; 156: 20–28, 2011) determined transcript coverage, and high-resolution RT-PCR validated alternatively spliced (AS) transcripts of 86 genes in five different organs and tissue. These methods were used as benchmarks to select an optimal barley RTD. BaRTv1.0-Quantification of Alternatively Spliced Isoforms (QUASI) was also made to overcome inaccurate quantification due to variation in 5′ and 3′ UTR ends of transcripts. BaRTv1.0-QUASI was used for accurate transcript quantification of RNA-seq data of five barley organs/tissues. This analysis identified 20,972 significant differentially expressed genes, 2791 differentially alternatively spliced genes and 2768 transcripts with differential transcript usage.ConclusionA high confidence barley reference transcript dataset consisting of 60,444 genes with 177,240 transcripts has been generated. Compared to current barley transcripts, BaRTv1.0 transcripts are generally longer, have less fragmentation and improved gene models that are well supported by splice junction reads. Precise transcript quantification using BaRTv1.0 allows routine analysis of gene expression and AS.
Transcriptomic analyses reveal physiological changes in sweet orange roots affected by citrus blight
Authors: Fu Shimin , Shao Jonathan , Roy Avijit , Brlansky Ronald H. , Zhou Changyong , Hartung John S. 
Published: December 2019

AbstractBackgroundCitrus blight is a very important progressive decline disease of commercial citrus. The etiology is unknown, although the disease can be transmitted by root grafts, suggesting a viral etiology. Diagnosis is made by demonstrating physical blockage of xylem cells that prevents the movement of water. This test was used to identify symptomatic trees from four commercial groves in Florida. Total RNA extracts of phloem-enriched scaffold root tissues were prepared from seven trees that failed to take up water and from one healthy tree. These RNA extracts were used for transcriptomic analyses using paired end RNA-Seq from an Illumina 2500 system. The expression of transcripts annotated as polyprotein of citrus endogenous pararetrovirus were estimated by both RT-qPCR and RNA-Seq.ResultsTranscripts from seven RNA-Seq libraries from trees affected by citrus blight were compared to a control tree. 129–148 million RNA fragments (two paired-end reads/fragment) were generated per library and were mapped to the sweet orange reference genome. In response to citrus blight stress, genes encoding aquaporins, proteins with water channel activity and several cellulose synthase genes were down-regulated, whereas genes involved in lignin and glucosinolate biosynthesis were up-regulated. Transcripts encoding proteins in pathways of carbohydrate metabolism, nucleotide synthesis, signaling, hormone metabolism, secondary metabolism, transport, and biotic stress pathways were overwhelmingly down regulated in all libraries.ConclusionReduced water intake and xylem plugging were observed in the trees tested and the changes in their transcriptome were analyzed. Plants adapted to reduced water flow by regulating primary and secondary metabolism, nuclear transport and hormone associated pathways. The patterns of energy generation, transcription, translation and protein degradation were consistent with irreversible decline. The down regulation of cellulose synthase transcripts and up regulation of transcripts related to lignin production likely lead to an imbalance in the pathways leading to wood formation, and may lead to the blockage of the xylem vessels seen as the cardinal symptom of citrus blight. Transcripts of a pararetrovirus were elevated in the transcriptome of roots used in this study.
Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana
Authors: Doucet Jennifer , Lee Hyun Kyung , Udugama Nethangi , Xu Jianfeng , Qi Baoxiu , Goring Daphne R. 
Published: December 2019

AbstractBackgroundIn the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown.ResultsA set of stigma-expressed pseudokinase genes, termedBRASSIKINs(BKNs), were identified and found to be present in only core Brassicaceae genomes. InArabidopsis thalianaCol-0,BKN1displayed stigma-specific expression while theBKN2gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linkedBKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on thebkn1/2mutant stigmas. In further analyses, the predominant transcript for the stigma-specificBKN1was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001Arabidopsisgenomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossingArabidopsisspecies,A. lyrataandA. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes.ConclusionIn this study, we have characterized the novel Brassicaceae-specific family ofBKNpseudokinase genes, and examined the function ofBKN1andBKN2in the context of pollen-stigma interactions inA. thalianaCol-0. Additionally, premature stop codons were identified in the predicted stigma specificBKN1gene in a number of the 1001A. thalianaecotype genomes, and this was in contrast to the out-crossingArabidopsisspecies which carried intact copies ofBKN1. Thus, understanding the function ofBKN1in other Brassicaceae species will be a key direction for future studies.
Recommendations to conduct and report systematic reviews in medical literature: a scoping review
Authors: Penedones Ana , Alves Carlos , Batel-Marques Francisco 
Published: December 2019

Abstract
Background
This scoping review aims to identify, review and characterize the published recommendations to conduct and/or to report a systematic review in medical interventions area.

Methods
A search was carried out in PubMed, EMBASE and Cochrane Library databases, using systematic reviews search filters. The search comprises all recommendations to conduct and/or report a systematic review. Data on methods were extracted from each recommendation. A descriptive analysis was performed.

Results
Eighty-three recommendations were identified. Approximately 60% of retrieved references were published in the last 6 years. Recommendations to both conduct and report a systematic review were issued in 47% studies. The guidance presented in each recommendation to conduct and/ or report a systematic review varied. Almost 96% of the recommendations offer guidance on systematic review methods section. The need and time for updating was only recommended in 29% of recommendations. Forty percent of recommendations endorsed their methods to any subject related to medical interventions. Half of the studies did not specify the design of studies to be included in a systematic review.

Conclusions
Several recommendations to conduct and/or report a systematic review were published and offered different guidance. Further research on the impact of such heterogeneity can improve systematic reviews quality.
Significance of serum Myostatin in hemodialysis patients
Authors: Esposito Pasquale , Battaglia Yuri , La Porta Edoardo , Grignano Maria Antonietta , Caramella Elena , Avella Alessando , Peressini Sabrina , Sessa Nicodemo , Albertini Riccardo , Di Natali Giuseppe , Lisi Claudio , Gregorini Marilena , Rampino Teresa 
Published: December 2019

Abstract
Background
Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of this condition. Previous studies have reported no conclusive results on the actual relationship between serum Mstn and wasting and malnutrition. So, in this study, we evaluated Mstn profile in a cohort of regular HD patients.

Methods
We performed a cross-sectional study, enrolling 37 patients undergoing bicarbonate-HD (BHD) or haemodiafiltration (HDF) at least for six months. 20 sex-matched healthy subjects comprised the control group. Mstn serum levels were evaluated by ELISA before and after HD. We collected clinical and biochemical data, evaluated insulin resistance, body composition, malnutrition [by Malnutrition Inflammation Score (MIS)] and tested muscle function (by hand-grip strength, six-minute walking test and a questionnaire on fatigue).

Results
Mstn levels were not significantly different between HD patients and controls (4.7 ± 2.8 vs 4.5 ± 1.3 ng/ml). In addition, while a decrease in Mstn was observed after HD treatment, there were no differences between BHD and HDF. In whole group of HD patients Mstn was positively correlated with muscle mass (r = 0.82, p < 0.001) and inversely correlated with age (r = − 0.63, p < 0.01) and MIS (r = − 0.39, p = 0.01). No correlations were found between Mstn and insulin resistance, such as between Mstn levels and parameters of muscle strength and fatigue. In multivariate analysis, Mstn resulted inversely correlated with fat body content (β = − 1.055, p = 0.002).

Conclusions
Circulating Mstn is related to muscle mass and nutritional status in HD patients, suggesting that it may have a role in the regulation of skeletal muscle and metabolic processes. However, also considering the lack of difference of serum Mstn between healthy controls and HD patients and the absence of correlations with muscle function tests, our findings do not support the use of circulating Mstn as a biomarker of muscle wasting and malnutrition in HD.
Propeller perforator flaps from the dorsal digital artery perforator chain for repairing soft tissue defects of the finger
Authors: Hu Haoliang , Chen Hong , Hong Jinjiong , Mao Weisheng , Tian Mintao , Wang Liping , Dong Jianghui , Li Xueyuan 
Published: December 2019

AbstractBackgroundWhen restoring the appearance and function of the fingers, hand surgeons face a challenge in choosing a suitable surgical method to repair finger skin defects.MethodsIn this study, we designed a long elliptical flap based on a propeller perforator flap and located slightly toward the dorsal lateral aspect of the finger. The flap with a pedicle consisting of the dorsal perforator of the distal digital artery and dorsal digital artery perforator chain is rotated to cover a large wound on the distal end. From December 2014 to December 2017, 10 patients with finger soft tissue defects were treated with the propeller perforator flap described in this study.ResultsAll flaps survived after surgery, and 2 had a transient venous congestion. After a follow-up period of 3 to 12 months, the static two-point discrimination of the flap was 8.06 ± 1.75 mm, and the range of motion was 149.4 ± 12.9°. This designed flap can span several angiosomes supplied by the perforators. Due to the inclusion of a vessel chain between the dorsal digital artery perforators, the length-to-width ratio of the flap can be up to 3:1.ConclusionsThis technique increases the size of flap that can be harvested safely while retaining a reliable blood supply. The present study describes a new method for repairing soft tissue defects of the finger by using the technique of propeller perforator flaps based on dorsal digital artery perforator chains.Trial registrationThe registration number of this study is ChiCTR1800014588; it has been retrospectively registered with Chinese Clinical Trial Registry (chictr.org.cn), 18/11/2019.
In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds
Authors: Abd Rani Nur Zahirah , Kumolosasi Endang , Jasamai Malina , Jamal Jamia Azdina , Lam Kok Wai , Husain Khairana 
Published: December 2019

Abstract
Background
Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds.

Method
M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release.

Results
Two new compounds; ethyl-(E)–undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), β-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate.

Conclusion
The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.
The content of patient counseling about interchangeable medicines and generic substitution in Finnish community pharmacies - a survey of dispensers
Authors: Rainio Riikka , Ahonen Riitta , Timonen Johanna 
Published: December 2019

Abstract
Background
Generic substitution aims to increase the use of more affordable generic preparations and restrain the growth of medicine expenditures. Pharmaceutical staff plays an important role in generic substitution by implementing substitution and counseling customers. The aim of this study was to explore how Finnish dispensers inform pharmacy customers about interchangeable medicines and generic substitution and what customers ask dispensers about generic substitution and the reference price system.

Methods
A questionnaire was sent to a random sample of dispensers (n = 1054) working in community pharmacies in spring 2018. The data was analyzed using frequencies, percentages and the Chi-square test and Fisher’s exact test. The open-ended questions were analyzed first using inductive content analysis and later with the quantitative methods mentioned above.

Results
The final study material consisted of 498 questionnaires (response rate 51%). The main topics dispensers always informed customers about were the physician’s record in the prescription not to substitute the medicine (69%) and that the prescribed or purchased interchangeable medicine did not belong in the reference price band (59%). Topics mentioned often by dispensers dealt with customer’s chance to choose their medicine from among several alternative products (68%) and the manufacturer of the interchangeable medicines (66%). Differences in appearance (33%) or in composition (28%) of interchangeable products were the most common topics mentioned only when the customer asked about them. Of the respondents 17.6% always and 51.4% often informed the customer about the least expensive interchangeable product at the point of dispensing. Customers’ questions about the generic substitution and reference price system most commonly (82.4%) concerned the similarity of interchangeable medicines.

Conclusions
Finnish dispensers provide customers with a wide range of information about different subjects when dispensing interchangeable medicines. Patient counseling generally meets the legislative requirements, except for price counseling. In future, information about generic substitution and interchangeable medicines should continuously be provided to customers both at pharmacies and elsewhere, e.g. through educational campaigns.
A comparative analysis of health surveillance strategies for administrative video display terminal employees
Authors: Gerassis Saki , Abad Alberto , Taboada Javier , Saavedra Ángeles , Giráldez Eduardo 
Published: December 2019

Abstract
Background
The objective of this study was to develop a strategy to optimize medical health surveillance protocols for administrative employees using video display terminals (VDTs). A total of 2453 medical examinations were analysed for VDT users in various sectors. From these data, using Bayesian statistics we inferred which factors were most relevant to medical diagnosis of the main disorders affecting VDT users. This information was used to build an influence diagram to evaluate the time and monetary costs associated with each diagnostic test and define an optimal protocol strategy based on occupational risks.

Results
Musculoskeletal and ophthalmological diseases were identified as the most frequent disorders among VDT users. The Bayesian network inferred age, sleep quality, activity level, smoking and the consumption of alcohol as risk factors. The blood count was the most costly test (5.23 USD/employee) and the second most costly test in time terms (4 min/employee), yet is a diagnostic test that has little influence on the medical decision regarding an employee’s capacity to perform their job.

Conclusions
Current occupational health surveillance protocols for VDT users may lead to expenditure that is 54% greater than necessary. For many employees and employers, failure to perform a wide range of medical tests for occupational health surveillance purposes is subjectively perceived as a threat to health. Awareness needs to be raised of the appropriate role of different health areas, so as to optimize diagnostic efficiency on the basis of greater flexibility.