bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CASP13-CAPRI targets as case studies to illustrate a novel scoring pipeline integrating CONSRANK with clustering and interface analyses
Authors: Barradas-Bautista Didier , Cao Zhen , Cavallo Luigi , Oliva Romina 
Published: September 2020

Abstract
Background
Properly scoring protein-protein docking models to single out the correct ones is an open challenge, also object of assessment in CAPRI (Critical Assessment of PRedicted Interactions), a community-wide blind docking experiment. We introduced in the field CONSRANK (CONSensus RANKing), the first pure consensus method. Also available as a web server, CONSRANK ranks docking models in an ensemble based on their ability to match the most frequent inter-residue contacts in it. We have been blindly testing CONSRANK in all the latest CAPRI rounds, where we showed it to perform competitively with the state-of-the-art energy and knowledge-based scoring functions. More recently, we developed Clust-CONSRANK, an algorithm introducing a contact-based clustering of the models as a preliminary step of the CONSRANK scoring process.
In the latest CASP13-CAPRI joint experiment, we participated as scorers with a novel pipeline, combining both our scoring tools, CONSRANK and Clust-CONSRANK, with our interface analysis tool COCOMAPS. Selection of the 10 models for submission was guided by the strength of the emerging consensus, and their final ranking was assisted by results of the interface analysis.

Results
As a result of the above approach, we were by far the first scorer in the CASP13-CAPRI top-1 ranking, having high/medium quality models ranked at the top-1 position for the majority of targets (11 out of the total 19). We were also the first scorer in the top-10 ranking, on a par with another group, and the second scorer in the top-5 ranking. Further, we topped the ranking relative to the prediction of binding interfaces, among all the scorers and predictors. Using the CASP13-CAPRI targets as case studies, we illustrate here in detail the approach we adopted.

Conclusions
Introducing some flexibility in the final model selection and ranking, as well as differentiating the adopted scoring approach depending on the targets were the key assets for our highly successful performance, as compared to previous CAPRI rounds. The approach we propose is entirely based on methods made available to the community and could thus be reproduced by any user.
A computational framework for modeling and studying pertussis epidemiology and vaccination
Authors: Castagno Paolo , Pernice Simone , Ghetti Gianni , Povero Massimiliano , Pradelli Lorenzo , Paolotti Daniela , Balbo Gianfranco , Sereno Matteo , Beccuti Marco 
Published: September 2020

Abstract
Background
Emerging and re-emerging infectious diseases such as Zika, SARS, ncovid19 and Pertussis, pose a compelling challenge for epidemiologists due to their significant impact on global public health. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to better understand the spreading characteristics of these diseases and to decide on vaccination policies, human interaction controls, and other social measures to counter, mitigate or simply delay the spread of the infectious diseases. Nevertheless, the construction of mathematical models for these diseases and their solutions remain a challenging tasks due to the fact that little effort has been devoted to the definition of a general framework easily accessible even by researchers without advanced modelling and mathematical skills.

Results
In this paper we describe a new general modeling framework to study epidemiological systems, whose novelties and strengths are: (1) the use of a graphical formalism to simplify the model creation phase; (2) the implementation of an R package providing a friendly interface to access the analysis techniques implemented in the framework; (3) a high level of portability and reproducibility granted by the containerization of all analysis techniques implemented in the framework; (4) a well-defined schema and related infrastructure to allow users to easily integrate their own analysis workflow in the framework. Then, the effectiveness of this framework is showed through a case of study in which we investigate the pertussis epidemiology in Italy.

Conclusions
We propose a new general modeling framework for the analysis of epidemiological systems, which exploits Petri Net graphical formalism, R environment, and Docker containerization to derive a tool easily accessible by any researcher even without advanced mathematical and computational skills. Moreover, the framework was implemented following the guidelines defined by Reproducible Bioinformatics Project so it guarantees reproducible analysis and makes simple the developed of new user-defined workflows.
EnClaSC: a novel ensemble approach for accurate and robust cell-type classification of single-cell transcriptomes
Authors: Chen Xiaoyang , Chen Shengquan , Jiang Rui 
Published: September 2020

Abstract
Background
In recent years, the rapid development of single-cell RNA-sequencing (scRNA-seq) techniques enables the quantitative characterization of cell types at a single-cell resolution. With the explosive growth of the number of cells profiled in individual scRNA-seq experiments, there is a demand for novel computational methods for classifying newly-generated scRNA-seq data onto annotated labels. Although several methods have recently been proposed for the cell-type classification of single-cell transcriptomic data, such limitations as inadequate accuracy, inferior robustness, and low stability greatly limit their wide applications.

Results
We propose a novel ensemble approach, named EnClaSC, for accurate and robust cell-type classification of single-cell transcriptomic data. Through comprehensive validation experiments, we demonstrate that EnClaSC can not only be applied to the self-projection within a specific dataset and the cell-type classification across different datasets, but also scale up well to various data dimensionality and different data sparsity. We further illustrate the ability of EnClaSC to effectively make cross-species classification, which may shed light on the studies in correlation of different species. EnClaSC is freely available at https://github.com/xy-chen16/EnClaSC.

Conclusions
EnClaSC enables highly accurate and robust cell-type classification of single-cell transcriptomic data via an ensemble learning method. We expect to see wide applications of our method to not only transcriptome studies, but also the classification of more general data.
MEIRLOP: improving score-based motif enrichment by incorporating sequence bias covariates
Authors: Delos Santos Nathaniel P. , Texari Lorane , Benner Christopher 
Published: September 2020

Abstract
Background
Motif enrichment analysis (MEA) identifies over-represented transcription factor binding (TF) motifs in the DNA sequence of regulatory regions, enabling researchers to infer which transcription factors can regulate transcriptional response to a stimulus, or identify sequence features found near a target protein in a ChIP-seq experiment. Score-based MEA determines motifs enriched in regions exhibiting extreme differences in regulatory activity, but existing methods do not control for biases in GC content or dinucleotide composition. This lack of control for sequence bias, such as those often found in CpG islands, can obscure the enrichment of biologically relevant motifs.

Results
We developed Motif Enrichment In Ranked Lists of Peaks (MEIRLOP), a novel MEA method that determines enrichment of TF binding motifs in a list of scored regulatory regions, while controlling for sequence bias. In this study, we compare MEIRLOP against other MEA methods in identifying binding motifs found enriched in differentially active regulatory regions after interferon-beta stimulus, finding that using logistic regression and covariates improves the ability to call enrichment of ISGF3 binding motifs from differential acetylation ChIP-seq data compared to other methods. Our method achieves similar or better performance compared to other methods when quantifying the enrichment of TF binding motifs from ENCODE TF ChIP-seq datasets. We also demonstrate how MEIRLOP is broadly applicable to the analysis of numerous types of NGS assays and experimental designs.

Conclusions
Our results demonstrate the importance of controlling for sequence bias when accurately identifying enriched DNA sequence motifs using score-based MEA. MEIRLOP is available for download from https://github.com/npdeloss/meirlop under the MIT license.
Long-read sequencing and de novo genome assembly of marine medaka (Oryzias melastigma)
Authors: Liang Pingping , Saqib Hafiz Sohaib Ahmed , Ni Xiaomin , Shen Yingjia 
Published: September 2020

Abstract
Background
Marine medaka (Oryzias melastigma) is considered as an important ecotoxicological indicator to study the biochemical, physiological and molecular responses of marine organisms towards increasing amount of pollutants in marine and estuarine waters.

Results
In this study, we reported a high-quality and accurate de novo genome assembly of marine medaka through the integration of single-molecule sequencing, Illumina paired-end sequencing, and 10X Genomics linked-reads. The 844.17 Mb assembly is estimated to cover more than 98% of the genome and is more continuous with fewer gaps and errors than the previous genome assembly. Comparison of O. melastigma with closely related species showed significant expansion of gene families associated with DNA repair and ATP-binding cassette (ABC) transporter pathways. We identified 274 genes that appear to be under significant positive selection and are involved in DNA repair, cellular transportation processes, conservation and stability of the genome. The positive selection of genes and the considerable expansion in gene numbers, especially related to stimulus responses provide strong supports for adaptations of O. melastigma under varying environmental stresses.

Conclusions
The highly contiguous marine medaka genome and comparative genomic analyses will increase our understanding of the underlying mechanisms related to its extraordinary adaptation capability, leading towards acceleration in the ongoing and future investigations in marine ecotoxicology.
Bacterial profile, antibiotic susceptibility pattern and associated risk factors of urinary tract infection among clinically suspected children attending at Felege-Hiwot comprehensive and specialized hospital, Northwest Ethiopia. A prospective study
Authors: Fenta Adugna , Dagnew Mulat , Eshetie Setegn , Belachew Teshome 
Published: September 2020

Abstract
Background
Urinary tract infection is one of the most common bacterial infections in children. Understanding the characteristics of uropathogens and their antimicrobial susceptibility pattern in a particular setting can provide evidence for the appropriate management of cases. This study aimed to assess the bacterial profile of urinary tract infection, their antimicrobial susceptibility pattern and associated factors among clinically suspected children attending at Felege-Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia.

Methods
A hospital-based cross-sectional study was conducted from February–April, 2019. A systematic sampling technique was employed. A mid-stream urine sample was inoculated on cystine lactose electrolyte deficient media and incubated for 24–48 h. Sub-culturing was done on Mac-Conkey and blood agar. Antimicrobial susceptibility test was done on Muller-Hinton agar. A binary logistic regression model was used to see the association between dependent and independent factors. A p-value< 0.05 at 95% CI was considered as statistically significant.

Results
The overall prevalence of urinary tract infection was 16.7% (95% CI 12.4–21.1). Both Gram-negative and Gram-positive bacterial isolates were recovered with a rate of 44/50 (88%) and 6/50 (12%) respectively. Among Gram-negative isolates, E. coli 28/44(63.6%) was predominant while S. saprophyticus 2/6(33.3%) was prevalent among Gram-positive bacterial isolates. Overall, a high level of resistance to ampicillin, augmentin, and tetracycline was shown by Gram-negative bacteria with a rate of 44/44(100%), 39/44(88.6%), and36/44 (81.8%) respectively. About 33/50(66%) of overall multidrug resistance was observed (95% CI 52–78). About six Gram-negative bacterial isolates were extended spectrum beta-lactamase (ESBL) producers. Having a history of urinary tract infection (P-0.003, AOR 1.86–22.15) and male uncircumcision (p-0.00, AOR 5.5–65.35) were the independent variables that associate for urinary tract infections.

Conclusion
In the present study, the prevalence of urinary tract infection among children was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection.
Blood lead concentration and its associated factors in preschool children in eastern Iran: a cross-sectional study
Authors: Zardast Mahmoud , Khorashadi-Zadeh Seyedeh Samira , Nakhaee Samaneh , Amirabadizadeh Alireza , Mehrpour Omid 
Published: September 2020

Abstract
Background
Lead is a toxic metal that affects almost every organ in the body. Children are more susceptible to lead toxicity because they ingest non-food items (pica), have oral exploratory habits, absorb more substantial amounts of ingested lead compared to adults, and have a developing central nervous system. This study describes venous blood lead concentrations (BLC) in young children living in Birjand, Iran.

Methods
A cross-sectional study was performed in 2016 on children 1–7 years of age who were referred to healthcare centers in Birjand City. Demographic information was obtained, and their BLC was tested using atomic absorption spectrometry (AAS).

Results
Four hundred children were tested. Their mean age was 52.37 ± 23.77 months; their mean BLC was 2.49 ± 2.64 μg/dL (median 1.85 μg/dL). Thirty-two (8%) children had a BLC > 5 μg/dL. A logistic regression model revealed that per one unit of increase in age, the chance of an elevated BLC decreased by 3% (OR (95%CI): 0.97 (0.96–0.99), p < 0.01). The risks of an elevated BLC was 61% lower in girls compared to boys (OR (95%CI): 0.39 (0.17–0.92), p = 0.03). Further, per one rate of increase in the BMI, the chance of an elevated BLC was higher (OR (95%CI): 1.13 (1.02–1.24), p = 0.01). Children whose fathers were laborers had higher BLC than those with employee fathers (p = 0.01).

Conclusion
Of 400 children aged 1–7 years old living in Birjand, Iran, 8% had elevated BLC. BLC correlated with the child ‘s age, gender, body mass index, and father’s occupation.
Impact of panelists’ experience on script concordance test scores of medical students
Authors: Peyrony Olivier , Hutin Alice , Truchot Jennifer , Borie Raphaël , Calvet David , Albaladejo Adrien , Baadj Yousrah , Cailleaux Pierre-Emmanuel , Flamant Martin , Martin Clémence , Messika Jonathan , Meunier Alexandre , Mirabel Mariana , Tea Victoria , Treton Xavier , Chevret Sylvie , Lebeaux David , Roux Damien 
Published: September 2020

Abstract
Background
The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel.

Methods
In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots.

Results
A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students’ SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students’ SCT scores, whatever the experience level of the expert panel.

Conclusions
Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.
A non-photosynthetic green alga illuminates the reductive evolution of plastid electron transport systems
Authors: Kayama Motoki , Chen Jun-Feng , Nakada Takashi , Nishimura Yoshiki , Shikanai Toshiharu , Azuma Tomonori , Miyashita Hideaki , Takaichi Shinichi , Kashiyama Yuichiro , Kamikawa Ryoma 
Published: September 2020

Abstract
Background
Plastid electron transport systems are essential not only for photosynthesis but also for dissipating excess reducing power and sinking excess electrons generated by various redox reactions. Although numerous organisms with plastids have lost their photoautotrophic lifestyles, there is a spectrum of known functions of remnant plastids in non-photosynthetic algal/plant lineages; some of non-photosynthetic plastids still retain diverse metabolic pathways involving redox reactions while others, such as apicoplasts of apicomplexan parasites, possess highly reduced sets of functions. However, little is known about underlying mechanisms for redox homeostasis in functionally versatile non-photosynthetic plastids and thus about the reductive evolution of plastid electron transport systems.

Results
Here we demonstrated that the central component for plastid electron transport systems, plastoquinone/plastoquinol pool, is still retained in a novel strain of an obligate heterotrophic green alga lacking the photosynthesis-related thylakoid membrane complexes. Microscopic and genome analyses revealed that the Volvocales green alga, chlamydomonad sp. strain NrCl902, has non-photosynthetic plastids and a plastid DNA that carries no genes for the photosynthetic electron transport system. Transcriptome-based in silico prediction of the metabolic map followed by liquid chromatography analyses demonstrated carotenoid and plastoquinol synthesis, but no trace of chlorophyll pigments in the non-photosynthetic green alga. Transient RNA interference knockdown leads to suppression of plastoquinone/plastoquinol synthesis. The alga appears to possess genes for an electron sink system mediated by plastid terminal oxidase, plastoquinone/plastoquinol, and type II NADH dehydrogenase. Other non-photosynthetic algae/land plants also possess key genes for this system, suggesting a broad distribution of an electron sink system in non-photosynthetic plastids.

Conclusion
The plastoquinone/plastoquinol pool and thus the involved electron transport systems reported herein might be retained for redox homeostasis and might represent an intermediate step towards a more reduced set of the electron transport system in many non-photosynthetic plastids. Our findings illuminate a broadly distributed but previously hidden step of reductive evolution of plastid electron transport systems after the loss of photosynthesis.
Altered brain-wide auditory networks in a zebrafish model of fragile X syndrome
Authors: Constantin Lena , Poulsen Rebecca E. , Scholz Leandro A. , Favre-Bulle Itia A. , Taylor Michael A. , Sun Biao , Goodhill Geoffrey J. , Vanwalleghem Gilles C. , Scott Ethan K. 
Published: September 2020

Abstract
Background
Loss or disrupted expression of the FMR1 gene causes fragile X syndrome (FXS), the most common monogenetic form of autism in humans. Although disruptions in sensory processing are core traits of FXS and autism, the neural underpinnings of these phenotypes are poorly understood. Using calcium imaging to record from the entire brain at cellular resolution, we investigated neuronal responses to visual and auditory stimuli in larval zebrafish, using fmr1 mutants to model FXS. The purpose of this study was to model the alterations of sensory networks, brain-wide and at cellular resolution, that underlie the sensory aspects of FXS and autism.

Results
Combining functional analyses with the neurons’ anatomical positions, we found that fmr1−/− animals have normal responses to visual motion. However, there were several alterations in the auditory processing of fmr1−/− animals. Auditory responses were more plentiful in hindbrain structures and in the thalamus. The thalamus, torus semicircularis, and tegmentum had clusters of neurons that responded more strongly to auditory stimuli in fmr1−/− animals. Functional connectivity networks showed more inter-regional connectivity at lower sound intensities (a − 3 to − 6 dB shift) in fmr1−/− larvae compared to wild type. Finally, the decoding capacities of specific components of the ascending auditory pathway were altered: the octavolateralis nucleus within the hindbrain had significantly stronger decoding of auditory amplitude while the telencephalon had weaker decoding in fmr1−/− mutants.

Conclusions
We demonstrated that fmr1−/− larvae are hypersensitive to sound, with a 3–6 dB shift in sensitivity, and identified four sub-cortical brain regions with more plentiful responses and/or greater response strengths to auditory stimuli. We also constructed an experimentally supported model of how auditory information may be processed brain-wide in fmr1−/− larvae. Our model suggests that the early ascending auditory pathway transmits more auditory information, with less filtering and modulation, in this model of FXS.
Individual, community and region level predictors of insecticide-treated net use among women in Uganda: a multilevel analysis
Authors: Ameyaw Edward Kwabena , Kareem Yusuf Olushola , Yaya Sanni 
Published: September 2020

Abstract
Background
Use of insecticide-treated net (ITN) has been identified by the World Health Organization as an effective approach for malaria prevention. The government of Uganda has instituted measures to enhance ITN supply over the past decade, however, the country ranks third towards the global malaria burden. As a result, this study investigated how individual, community and region level factors affect ITN use among women of reproductive age in Uganda.

Methods
The 2018–2019 Malaria Indicator Survey of Uganda involving 7798 women aged 15–49 was utilized. The descriptive summaries of ITN use were analysed by individual, community and region level factors. Based on the hierarchical nature of the data, four distinct binomial multilevel logistic regression models were fitted using the MLwiN 3.05 module in Stata. The parameters were estimated using the Markov Chain Monte Carlo (MCMC) estimation procedure and Bayesian Deviance Information Criterion was used to identify the model with a better fit.

Results
The proportion of women who use ITN was 78.2% (n = 6097). Poor household wealth status [aOR = 1.66, Crl = 1.55–1.80], knowing that sleeping under ITN prevents malaria [aOR = 1.11, Crl = 1.05–1.24] and that destroying mosquito breeding sites can prevent malaria [aOR = 1.85, Crl = 1.75–1.98] were associated with higher odds of ITN use. ITN use attributable to regional and community level random effects was 39.1% and 45.2%, respectively.

Conclusion
The study has illustrated that ITN policies and interventions in Uganda need to be sensitive to community and region level factors that affect usage. Also, strategies to enhance women’s knowledge on malaria prevention is indispensable in improving ITN use.