bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complete genome sequence of the nitrile biocatalyst Rhodococcus rhodochrous ATCC BAA-870
Authors: Frederick Joni , Hennessy Fritha , Horn Uli , de la Torre Cortés Pilar , van den Broek Marcel , Strych Ulrich , Willson Richard , Hefer Charles A. , Daran Jean-Marc G. , Sewell Trevor , Otten Linda G. , Brady Dean 
Published: January 2020

AbstractBackgroundRhodococci are industrially important soil-dwelling Gram-positive bacteria that are well known for both nitrile hydrolysis and oxidative metabolism of aromatics.Rhodococcus rhodochrousATCC BAA-870 is capable of metabolising a wide range of aliphatic and aromatic nitriles and amides. The genome of the organism was sequenced and analysed in order to better understand this whole cell biocatalyst.ResultsThe genome ofR. rhodochrousATCC BAA-870 is the firstRhodococcusgenome fully sequenced using Nanopore sequencing. The circular genome contains 5.9 megabase pairs (Mbp) and includes a 0.53 Mbp linear plasmid, that together encode 7548 predicted protein sequences according to BASys annotation, and 5535 predicted protein sequences according to RAST annotation. The genome contains numerous oxidoreductases, 15 identified antibiotic and secondary metabolite gene clusters, several terpene and nonribosomal peptide synthetase clusters, as well as 6 putative clusters of unknown type. The 0.53 Mbp plasmid encodes 677 predicted genes and contains the nitrile converting gene cluster, including a nitrilase, a low molecular weight nitrile hydratase, and an enantioselective amidase.Although there are fewer biotechnologically relevant enzymes compared to those found in rhodococci with larger genomes, such as the well-knownRhodococcus jostiiRHA1, the abundance of transporters in combination with the myriad of enzymes found in strain BAA-870 might make it more suitable for use in industrially relevant processes than other rhodococci.ConclusionsThe sequence and comprehensive description of theR. rhodochrousATCC BAA-870 genome will facilitate the additional exploitation of rhodococci for biotechnological applications, as well as enable further characterisation of this model organism. The genome encodes a wide range of enzymes, many with unknown substrate specificities supporting potential applications in biotechnology, including nitrilases, nitrile hydratase, monooxygenases, cytochrome P450s, reductases, proteases, lipases, and transaminases.
The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation
Authors: Chicco Davide , Jurman Giuseppe 
Published: January 2020

AbstractBackgroundTo evaluate binary classifications and their confusion matrices, scientific researchers can employ several statistical rates, accordingly to the goal of the experiment they are investigating. Despite being a crucial issue in machine learning, no widespread consensus has been reached on a unified elective chosen measure yet. Accuracy and F1score computed on confusion matrices have been (and still are) among the most popular adopted metrics in binary classification tasks. However, these statistical measures can dangerously show overoptimistic inflated results, especially on imbalanced datasets.ResultsThe Matthews correlation coefficient (MCC), instead, is a more reliable statistical rate which produces a high score only if the prediction obtained good results in all of the four confusion matrix categories (true positives, false negatives, true negatives, and false positives), proportionally both to the size of positive elements and the size of negative elements in the dataset.ConclusionsIn this article, we show how MCC produces a more informative and truthful score in evaluating binary classifications than accuracy and F1score, by first explaining the mathematical properties, and then the asset of MCC in six synthetic use cases and in a real genomics scenario. We believe that the Matthews correlation coefficient should be preferred to accuracy and F1score in evaluating binary classification tasks by all scientific communities.
A detailed in silico analysis of secondary metabolite biosynthesis clusters in the genome of the broad host range plant pathogenic fungus Sclerotinia sclerotiorum
Authors: Graham-Taylor Carolyn , Kamphuis Lars G. , Derbyshire Mark C. 
Published: January 2020

AbstractBackgroundThe broad host range pathogenSclerotinia sclerotioruminfects over 400 plant species and causes substantial yield losses in crops worldwide. Secondary metabolites are known to play important roles in the virulence of plant pathogens, but little is known about the secondary metabolite repertoire ofS. sclerotiorum. In this study, we predicted secondary metabolite biosynthetic gene clusters in the genome ofS. sclerotiorumand analysed their expression during infection ofBrassica napususing an existing transcriptome data set. We also investigated their sequence diversity among a panel of 25 previously publishedS. sclerotiorumisolate genomes.ResultsWe identified 80 putative secondary metabolite clusters. Over half of the clusters contained at least three transcriptionally coregulated genes. Comparative genomics revealed clusters homologous to clusters in the closely related plant pathogenBotrytis cinereafor production of carotenoids, hydroxamate siderophores, DHN melanin and botcinic acid. We also identified putative phytotoxin clusters that can potentially produce the polyketide sclerin and an epipolythiodioxopiperazine. Secondary metabolite clusters were enriched in subtelomeric genomic regions, and those containing paralogues showed a particularly strong association with repeats. The positional bias we identified was borne out by intraspecific comparisons that revealed putative secondary metabolite genes suffered more presence / absence polymorphisms and exhibited a significantly higher sequence diversity than other genes.ConclusionsThese data suggest thatS. sclerotiorumproduces numerous secondary metabolites during plant infection and that their gene clusters undergo enhanced rates of mutation, duplication and recombination in subtelomeric regions. The microevolutionary regimes leading toS. sclerotiorumsecondary metabolite diversity have yet to be elucidated. Several potential phytotoxins documented in this study provide the basis for future functional analyses.
A software package for immunologists to learn simulation modeling
Authors: Handel Andreas 
Published: January 2020

Abstract
Background
As immunology continues to become more quantitative, increasingly sophisticated computational tools are commonly used. One useful toolset are simulation models. Becoming familiar with such models and their uses generally requires writing computer code early in the learning process. This poses a barrier for individuals who do not have prior coding experience.

Results
To help reduce this barrier, I wrote software that teaches the use of mechanistic simulation models to study infection and immune response dynamics, without the need to read or write computer code. The software, called Dynamical Systems Approach to Immune Response Modeling (DSAIRM), is implemented as a freely available package for the R programming language. The target audience are immunologists and other scientists with no or little coding experience. DSAIRM provides a hands-on introduction to simulation models, teaches the basics of those models and what they can be used for. Here, I describe the DSAIRM R package, explain the different ways the package can be used, and provide a few introductory examples.

Conclusions
Working through DSAIRM will equip individuals with the knowledge needed to critically assess studies using simulation models in the published literature and will help them understand when such a modeling approach might be suitable for their own research. DSAIRM also provides users a potential starting point towards development and use of simulation models in their own research.
Method comparison for the direct enumeration of bacterial species using a chemostat model of the human colon
Authors: Moura Ines B. , Normington Charmaine , Ewin Duncan , Clark Emma , Wilcox Mark H. , Buckley Anthony M. , Chilton Caroline H. 
Published: January 2020

AbstractBackgroundClostridioides difficileinfection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Threein vitromodels were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria,Bacteroidesspp.,Lactobacillusspp.,Enterococcusspp.,Bifidobacteriumspp.,C. difficile,and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations ofPrevotellaspp.,Clostridium coccoidesgroup, andClostridium leptumgroup.ResultsBoth methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4 days) of the bacterial populations in the models that received the FMT.C. difficileproliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% forBacteroidesspp., to 62% for Enterobacteriaceae.ConclusionsGenerally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture.
Genome-wide association study identified candidate genes controlling continuous storage root formation and bulking in hexaploid sweetpotato
Authors: Bararyenya Astère , Olukolu Bode A. , Tukamuhabwa Phinehas , Grüneberg Wolfgang J. , Ekaya Wellington , Low Jan , Ochwo-Ssemakula Mildred , Odong Thomas L. , Talwana Herbert , Badji Arfang , Kyalo Martina , Nasser Yao , Gemenet Dorcus , Kitavi Mercy , Mwanga Robert O. M. 
Published: January 2020

Abstract
Background
Continuous storage root formation and bulking (CSRFAB) in sweetpotato is an important trait from agronomic and biological perspectives. Information about the molecular mechanisms underlying CSRFAB traits is lacking.

Results
Here, as a first step toward understanding the genetic basis of CSRFAB in sweetpotato, we performed a genome-wide association study (GWAS) using phenotypic data from four distinct developmental stages and 33,068 single nucleotide polymorphism (SNP) and insertion-deletion (indel) markers. Based on Bonferroni threshold (p-value < 5 × 10− 7), we identified 34 unique SNPs that were significantly associated with the complex trait of CSRFAB at 150 days after planting (DAP) and seven unique SNPs associated with discontinuous storage root formation and bulking (DCSRFAB) at 90 DAP. Importantly, most of the loci associated with these identified SNPs were located within genomic regions (using Ipomoea trifida reference genome) previously reported for quantitative trait loci (QTL) controlling similar traits. Based on these trait-associated SNPs, 12 and seven candidate genes were respectively annotated for CSRFAB and DCSRFAB traits. Congruent with the contrasting and inverse relationship between discontinuous and continuous storage root formation and bulking, a DCSRFAB-associated candidate gene regulates redox signaling, involved in auxin-mediated lateral root formation, while CSRFAB is enriched for genes controlling growth and senescence.

Conclusion
Candidate genes identified in this study have potential roles in cell wall remodeling, plant growth, senescence, stress, root development and redox signaling. These findings provide valuable insights into understanding the functional networks to develop strategies for sweetpotato yield improvement. The markers as well as candidate genes identified in this pioneering research for CSRFAB provide important genomic resources for sweetpotato and other root crops.
Comparison of ropivacaine combined with sufentanil for epidural anesthesia and spinal-epidural anesthesia in labor analgesia
Authors: Wang Yanshuang , Xu Mingjun 
Published: January 2020

Abstract
Background
To compare the application and efficacy of ropivacaine combined with sufentanil for continuous epidural anesthesia (CEA) and combined spinal-epidural anesthesia (CSEA) in labor analgesia.

Methods
Three hundred sixty pregnant women requesting labor analgesia from October 2017 to August 2018 were selected retrospectively. According to the anesthetic method, subjects were divided into CSEA group and CEA group. Ropivacaine combined with sufentanil were used in all subjects. The labor time, visual analogue scale (VAS), Apgar score of newborn, adverse pregnancy outcomes and adverse drug reactions were observed.

Results
There was no significant difference in pre-analgesia (T0) VAS scores between the two groups (P > 0.05). VAS scores of first stage of labor (T1), second stage of labor (T2) and third stage of labor (T3) in CSEA group were significantly lower than CEA group (P < 0.01). The onset time, T1 and total labor time in CSEA group were significantly shorter than CEA group (P < 0.01). There were no significant differences between T2 and T3 (P > 0.05). There were no significant differences in adverse pregnancy outcomes and Apgar scores at 1, 5 and 10 min after birth between the two groups (P > 0.05). The incidence of adverse drug outcomes in CSEA group was significantly lower than CEA group (P < 0.01). Maternal satisfaction in CSEA group was significantly higher than CEA group (P < 0.01).

Conclusion
Considering ropivacaine combined with sufentanil for CSEA achieved a shorter onset time and labor period, significant analgesic effect, lower adverse drug reactions rates and higher subject satisfaction than CEA, it may be worthy of clinical promotion and application.
Social support and depressive symptoms among family caregivers of older people with disabilities in four provinces of urban China: the mediating role of caregiver burden
Authors: Zhong Yaqin , Wang Jian , Nicholas Stephen 
Published: January 2020

Abstract
Background
To examine the relationship between social support and depressive symptoms of Chinese family caregivers of older people with disabilities, and to evaluate the role of caregiver burden as a potential mediator of that relationship.

Methods
A survey questionnaire was completed face-to-face by 567 primary family caregivers of older people with disabilities in four provinces in China. Covariates that may affect depressive symptoms, such as the characteristics of disabled people (socio-economic factors, functional and cognitive capacity) and caregivers (caregiver duration and self-rated health of caregivers) were collected. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS); depressive symptoms were assessed by the shortened 10 item version of Center for Epidemiological Studies Depression scale (CES-D); and the caregiver burden was assessed by the Zarit Burden Interview (ZBI).

Results
The prevalence of depressive symptoms among caregivers was 37.7%. Higher levels of social support was negatively associated with lower depressive symptoms. This relationship was partially mediated by the caregiver burden, where higher levels of the caregiver burden were negatively associated with depressive symptoms. Furthermore, caregivers who were women, spent extended time in caregiving and were in poor health, reported significantly higher depressive symptoms.

Conclusions
Our results indicated that social support was negatively associated with depressive symptoms in family caregivers and in the caregiver burden. The caregiver burden partially mediated the social support-depressive symptoms association. Interventions for family caregivers should include increasing social support, health monitoring and structured interventions to reduce the caregiver burden and attenuate family caregivers’ depressive symptoms.
Daytime napping and successful aging among older adults in China: a cross-sectional study
Authors: Xin Chunyu , Zhang Baiyang , Fang Shu , Zhou Junmin 
Published: January 2020

Abstract
Background
The study aimed to examine the association between daytime napping and successful aging (including its five dimensions, “low probability of disease,” “no disease-related disability,” “high cognitive functioning,” “high physical functioning,” and “active engagement with life”) among China’s older adults using data from the Chinese Health and Retirement Longitudinal Study conducted in 2015.

Methods
Cross-sectional data were used in the analysis. Multivariable logistic regressions were conducted to investigate the association between daytime napping and successful aging, and stratified analyses were performed to explore differences in nighttime sleep duration.

Results
A total of 7469 participants were included in the analysis. Daytime napping was prevalent in China’s older adults (59.3%). The proportion of study participants with “successful aging” was 13.7%. Additionally, 48.6, 91.7, 54.1, 78.5, and 49.1% participants achieved “low probability of disease,” “no disease-related disability,” “high cognitive functioning,” “high physical functioning,” and “active engagement with life,” respectively. Compared with the 0 min/day napping group, the > 60 min/day napping group was associated with a lower probability of achieving successful aging (OR, 0.762; 95% CI, 0.583–0.996). In the nighttime sleep duration stratification, the findings showed that in the ≥8 h/night group, napping > 60 min per day was associated with a lower likelihood of aging successfully (OR, 0.617; 95% CI, 0.387–0.984). Considering the five dimensions of successful aging, moderate and long daytime napping were negatively associated with “low probability of disease”; long daytime napping had negative associations with “no disease-related disability” and “high physical functioning”; moderate daytime napping had positive associations with “high cognitive functioning” and “active engagement with life.”

Conclusions
Long daytime napping showed a lower likelihood of successful aging among the elderly in China. Special attention is necessary for elderly people who sleep for longer duration both during day and night. Biological and social factors affecting the relationship between daytime napping and successful aging need to be explored in depth in the future.
HIV virological non-suppression and factors associated with non-suppression among adolescents and adults on antiretroviral therapy in northern Ethiopia: a retrospective study
Authors: Desta Abraham Aregay , Woldearegay Tewolde Wubayehu , Futwi Nesredin , Gebrehiwot Gebrecherkos Teame , Gebru Goyitom Gebremedhn , Berhe Asfawosen Aregay , Godefay Hagos 
Published: January 2020

AbstractBackgroundDespite the benefits of Antiretroviral Therapy (ART), there is a growing concern of treatment failure. This study aimed to assess viral non suppression rate and factors associated with HIV viral non suppression among adolescents and adults on ART in Northern Ethiopia.MethodsA retrospective cross sectional study was done on 19,525 study subjects. All the data in the database of Tigray Health Research Institute was exported to Microsoft excel 2010 and then data verification and filtration were done before exporting to STATA 14.0 for analysis. Generalized Estimating Equation (GEE) logistic regression was used for statistical modeling of viral non suppression.ResultsA total of 5153 (26.39%; 95%CI (25.77%, 27.02)) patients had no viral suppression despite being on ART. Being male (AOR = 1.27, 95% CI: 1.18, 1.37), 15–19 years of age (AOR = 4.86, 95%CI: 3.86, 6.12), patients from primary hospital (AOR = 1.26, 95%CI: 1.05, 1.52), WHO staging II (AOR = 1.31, 95%CI: 1.10, 1.54), poor ART adherence level (AOR = 2.56, 95%CI: 1.97, 3.33), fair ART adherence level (AOR = 1.61, 95%CI: 1.36, 1.90), baseline CD-4 count of < 200 cells/micro liter (AOR = 1.33, 95%CI: 1.14, 1.54), recent CD-4 count of < 200 cells/micro liter (AOR = 3.78, 95%CI: 3.34, 4.27), regimen types: 1c (AZT-3TC-NVP) (AOR = 1.32, 95%CI: 1.22, 1.44), 2 h (TDF-3TC-ATV/R) (AOR = 1.79, 95%CI: 1.27, 2.52) and declined immunological responses after ART initiation (AOR = 1.45, 95%CI: 1.30, 1.61) were significantly associated with viral non-suppression.ConclusionsThe virological non suppression was high which makes it less likely to achieve the third 90 UNAIDS target. Being male, patients with WHO staging II and poor ART adherence level were significantly associated with viral non suppression. Therefore, intensive adherence support and counseling should be provided. It is also a high time to determine the antiretroviral drugs resistance pattern given the fact that a large number of patients had virological non suppression.
Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling
Authors: Shahi Thakuri Pradip , Gupta Megha , Singh Sunil , Joshi Ramila , Glasgow Eric , Lekan Alexander , Agarwal Seema , Luker Gary D. , Tavana Hossein 
Published: January 2020

Abstract
Background
Cell migration and invasion are essential processes for metastatic dissemination of cancer cells. Significant progress has been made in developing new therapies against oncogenic signaling to eliminate cancer cells and shrink tumors. However, inherent heterogeneity and treatment-induced adaptation to drugs commonly enable subsets of cancer cells to survive therapy. In addition to local recurrence, these cells escape a primary tumor and migrate through the stroma to access the circulation and metastasize to different organs, leading to an incurable disease. As such, therapeutics that block migration and invasion of cancer cells may inhibit or reduce metastasis and significantly improve cancer therapy. This is particularly more important for cancers, such as triple negative breast cancer, that currently lack targeted drugs.

Methods
We used cell migration, 3D invasion, zebrafish metastasis model, and phosphorylation analysis of 43 protein kinases in nine triple negative breast cancer (TNBC) cell lines to study effects of fisetin and quercetin on inhibition of TNBC cell migration, invasion, and metastasis.

Results
Fisetin and quercetin were highly effective against migration of all nine TNBC cell lines with up to 76 and 74% inhibitory effects, respectively. In addition, treatments significantly reduced 3D invasion of highly motile TNBC cells from spheroids into a collagen matrix and their metastasis in vivo. Fisetin and quercetin commonly targeted different components and substrates of the oncogenic PI3K/AKT pathway and significantly reduced their activities. Additionally, both compounds disrupted activities of several protein kinases in MAPK and STAT pathways. We used molecular inhibitors specific to these signaling proteins to establish the migration-inhibitory role of the two phytochemicals against TNBC cells.

Conclusions
We established that fisetin and quercetin potently inhibit migration of metastatic TNBC cells by interfering with activities of oncogenic protein kinases in multiple pathways.