bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study of hyperpolarization-activated currents in pulmonary vein cardiomyocytes isolated from rat, guinea pig, and rabbit
Authors: Takagi Daichi , Okamoto Yosuke , Ohba Takayoshi , Yamamoto Hiroshi , Ono Kyoichi 
Published: February 2020

AbstractPulmonary vein (PV) cardiomyocytes have the potential to generate spontaneous activity, in contrast to working myocytes of atria. Different electrophysiological properties underlie the potential automaticity of PV cardiomyocytes, one being the hyperpolarization-activated inward current (Ih), which facilitates the slow diastolic depolarization. In the present study, we examined pharmacological characteristics of the Ih of PV cardiomyocytes in rat, guinea pig and rabbit. The results showed that guinea pig and rat PV cardiomyocytes possessed sizeable amplitudes of the Ih, and the Ih of guinea pig was suppressed by Cs+, a blocker of the hyperpolarization-activated cation current. However, the Ih of rat was not suppressed by Cs+, but by Cd2+, a blocker of the Cl− current. The current density of the Ih of rabbit PV cardiomyocytes was significantly smaller than those of other species. This suggests that the ion channels that carry the Ih of PV cardiomyocytes differ among the animal species.
GARS: Genetic Algorithm for the identification of a Robust Subset of features in high-dimensional datasets
Authors: Chiesa Mattia , Maioli Giada , Colombo Gualtiero I. , Piacentini Luca 
Published: February 2020

Abstract
Background
Feature selection is a crucial step in machine learning analysis. Currently, many feature selection approaches do not ensure satisfying results, in terms of accuracy and computational time, when the amount of data is huge, such as in ‘Omics’ datasets.

Results
Here, we propose an innovative implementation of a genetic algorithm, called GARS, for fast and accurate identification of informative features in multi-class and high-dimensional datasets. In all simulations, GARS outperformed two standard filter-based and two ‘wrapper’ and one embedded’ selection methods, showing high classification accuracies in a reasonable computational time.

Conclusions
GARS proved to be a suitable tool for performing feature selection on high-dimensional data. Therefore, GARS could be adopted when standard feature selection approaches do not provide satisfactory results or when there is a huge amount of data to be analyzed.
Characterizing lineage-specific evolution and the processes driving genomic diversification in chordates
Authors: Northover David E. , Shank Stephen D. , Liberles David A. 
Published: February 2020

AbstractBackgroundUnderstanding the origins of genome content has long been a goal of molecular evolution and comparative genomics. By examining genome evolution through the guise of lineage-specific evolution, it is possible to make inferences about the evolutionary events that have given rise to species-specific diversification. Here we characterize the evolutionary trends found in chordate species using The Adaptive Evolution Database (TAED). TAED is a database of phylogenetically indexed gene families designed to detect episodes of directional or diversifying selection across chordates. Gene families within the database have been assessed for lineage-specific estimates of dN/dS and have been reconciled to the chordate species to identify retained duplicates. Gene families have also been mapped to the functional pathways and amino acid changes which occurred on high dN/dS lineages have been mapped to protein structures.ResultsAn analysis of this exhaustive database has enabled a characterization of the processes of lineage-specific diversification in chordates. A pathway level enrichment analysis of TAED determined that pathways most commonly found to have elevated rates of evolution included those involved in metabolism, immunity, and cell signaling. An analysis of protein fold presence on proteins, after normalizing for frequency in the database, found common folds such as Rossmann folds, Jelly Roll folds, and TIM barrels were overrepresented on proteins most likely to undergo directional selection. A set of gene families which experience increased numbers of duplications within short evolutionary times are associated with pathways involved in metabolism, olfactory reception, and signaling. An analysis of protein secondary structure indicated more relaxed constraint in β-sheets and stronger constraint on alpha Helices, amidst a general preference for substitutions at exposed sites. Lastly a detailed analysis of the ornithine decarboxylase gene family, a key enzyme in the pathway for polyamine synthesis, revealed lineage-specific evolution along the lineage leading to Cetacea through rapid sequence evolution in a duplicate gene with amino acid substitutions causing active site rearrangement.ConclusionEpisodes of lineage-specific evolution are frequent throughout chordate species. Both duplication and directional selection have played large roles in the evolution of the phylum. TAED is a powerful tool for facilitating this understanding of lineage-specific evolution.
Comparative population genomics reveals genetic divergence and selection in lotus, Nelumbo nucifera
Authors: Li Ye , Zhu Feng-Lin , Zheng Xing-Wen , Hu Man-Li , Dong Chen , Diao Ying , Wang You-Wei , Xie Ke-Qiang , Hu Zhong-Li 
Published: February 2020

Abstract
Background
Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous.

Results
In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively.

Conclusions
The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.
A fast-linear mixed model for genome-wide haplotype association analysis: application to agronomic traits in maize
Authors: Chen Heli , Hao Zhiyu , Zhao Yunfeng , Yang Runqing 
Published: February 2020

Abstract
Background
Haplotypes combine the effects of several single nucleotide polymorphisms (SNPs) with high linkage disequilibrium, which benefit the genome-wide association analysis (GWAS). In the haplotype association analysis, both haplotype alleles and blocks are tested. Haplotype alleles can be inferred with the same statistics as SNPs in the linear mixed model, while blocks require the formulation of unified statistics to fit different genetic units, such as SNPs, haplotypes, and copy number variations.

Results
Based on the FaST-LMM, the fastLmPure function in the R/RcppArmadillo package has been introduced to speed up genome-wide regression scans by a re-weighted least square estimation. When large or highly significant blocks are tested based on EMMAX, the genome-wide haplotype association analysis takes only one to two rounds of genome-wide regression scans. With a genomic dataset of 541,595 SNPs from 513 maize inbred lines, 90,770 haplotype blocks were constructed across the whole genome, and three types of markers (SNPs, haplotype alleles, and haplotype blocks) were genome-widely associated with 17 agronomic traits in maize using the software developed here.

Conclusions
Two SNPs were identified for LNAE, four haplotype alleles for TMAL, LNAE, CD, and DTH, and only three blocks reached the significant level for TMAL, CD, and KNPR. Compared to the R/lm function, the computational time was reduced by ~ 10–15 times.
Next-generation sequencing identified novel Desmoplakin frame-shift variant in patients with Arrhythmogenic cardiomyopathy
Authors: Lin Xiaoping , Ma Yuankun , Cai Zhejun , Wang Qiyuan , Wang Lihua , Huo Zhaoxia , Hu Dan , Wang Jian’an , Xiang Meixiang 
Published: February 2020

Abstract
Background
Arrhythmogenic cardiomyopathy (AC) is one of the leading causes for sudden cardiac death (SCD). Recent studies have identified mutations in cardiac desmosomes as key players in the pathogenesis of AC. However, the specific etiology in individual families remains largely unknown.

Methods
A 4-generation family presenting with syncope, lethal ventricular arrhythmia and SCD was recruited. Targeted next generation sequencing (NGS) was performed and validated by Sanger sequencing. Plasmids containing the mutation and wild type (WT) were constructed. Real-time PCR, western-blot and immunofluorescence were performed to detect the functional change due to the mutation.

Results
The proband, a 56-year-old female, presented with recurrent palpitations and syncope. An ICD was implanted due to her family history of SCD/ aborted SCD. NGS revealed a novel heterozygous frame-shift variant (c.832delG) in Desmoplakin (DSP) among 5 family members. The variant led to frame-shift and premature termination, producing a truncated protein. Cardiac magnetic resonance (CMR) of the family members carrying the same variant shown myocardium thinning and fatty infiltration in the right ventricular, positive bi-ventricular late gadolinium enhancement and severe RV dysfunction, fulfilling the diagnostic criteria of AC. HEK293T cells transfected with mutant plasmids expressed truncated DSP mRNA and protein, upregulation of nuclear junction plakoglobin (JUP) and downregulation of β-catenin, when compared with WT.

Conclusion
We infer that the novel c.832delG variant in DSP was associated with AC in this family, likely through Wnt/β-catenin signaling pathway.
The effect of preconditioning with high-intensity training on tissue levels of G-CSF, its receptor and C-kit after an acute myocardial infarction in male rats
Authors: Ghanimati Reza , Rajabi Hamid , Ramezani Fatemeh , Ramez Maral , Bapiran Mohsen , Nasirinezhad Farinaz 
Published: February 2020

AbstractBackgroundExercise training is known as a practical way to increase cardioprotection against stress, and it seems that stem cell recruitment is one of its mechanisms. The purpose of the present study was to investigate the effect of preconditioning with High-intensity interval training (HIIT) on tissue levels of G-CSF, its receptor and C-Kit following acute myocardial infarction in male rats.MethodsTwenty Male Wistar rats were randomly divided into 4 groups of control, MI, HIIT, and HIIT+MI. Training groups performed 2 weeks of high intensity interval training in 4 sections. The first section consisted training in 3 days and 2 sessions in each day (4 × 2 min with 35–40 m/min and 3 × 2 min with 25–30 m/min between high intervals. The second part included 2 days of training (4 × 2 min with 40 to 45 m/min and 3 × 2 min with 28 to 32 m /min). The third part was performed in 3 days with one more repetition. The fourth section consisted 2 days of training and with one more repetition compared to section 3. For induction of myocardial infarction, subcutaneous injection of isoprenaline was used. CK, total CK, LDH, and troponin T were measured in serum and G-CSF, G-CSFR and C-Kit proteins were measured by the Western Blot method in the heart tissue.ResultsThe results of this study showed that enzymes of CK, total CK, LDH, troponin T had a significant increase in both MI and HIIT+MI groups compared to the other two groups (P < 0.001) and these indices in the MI group were significantly higher than the HIIT+MI group. Also, the results demonstrated that G-CSF, G-CSFR and C-Kit protein expression in the heart tissue significantly increased after MI. As well as, 2 weeks of HIIT training significantly increased G-CSF and C-kit in the training group compared to the control group, but the training caused that these proteins does not increase in HIIT+MI group as much as MI group.ConclusionsAlong with other protective pathways, high intensity interval training can increase cardioprotection and decrease heart injuries through the increase in G-CSF, G-CSFR and C-kit level.
Outcome choice and definition in systematic reviews leads to few eligible studies included in meta-analyses: a case study
Authors: Saldanha Ian J. , Lindsley Kristina B. , Money Sarah , Kimmel Hannah J. , Smith Bryant T. , Dickersin Kay 
Published: February 2020

Abstract
Background
There is broad recognition of the importance of evidence in informing clinical decisions. When information from all studies included in a systematic review (“review”) does not contribute to a meta-analysis, decision-makers can be frustrated. Our objectives were to use the field of eyes and vision as a case study and examine the extent to which authors of Cochrane reviews conducted meta-analyses for their review’s pre-specified main outcome domain and the reasons that some otherwise eligible studies were not incorporated into meta-analyses.

Methods
We examined all completed systematic reviews published by Cochrane Eyes and Vision, as of August 11, 2017. We extracted information about each review’s outcomes and, using an algorithm, categorized one outcome as its “main” outcome. We calculated the percentage of included studies incorporated into meta-analyses for any outcome and for the main outcome. We examined reasons for non-inclusion of studies into the meta-analysis for the main outcome.

Results
We identified 175 completed reviews, of which 125 reviews included two or more studies. Across these 125 reviews, the median proportions of studies incorporated into at least one meta-analysis for any outcome and for the main outcome were 74% (interquartile range [IQR] 0–100%) and 28% (IQR 0–71%), respectively. Fifty-one reviews (41%) could not conduct a meta-analysis for the main outcome, mostly because fewer than two included studies measured the outcome (21/51 reviews) or the specific measurements for the outcome were inconsistent (16/51 reviews).

Conclusions
Outcome choice during systematic reviews can lead to few eligible studies included in meta-analyses. Core outcome sets and improved reporting of outcomes can help solve some of these problems.
Enterovirus D68 in a 6-year-old acute flaccid myelitis case in China, 2018: a case report
Authors: Wang Xiaoli , Zhang Pengfei , Li Jie , Chu Yanhui , Li Zheng , Yang Yang , Li Fu , Cui Shujuan , Huo Da , Wang Yu , Wang Quanyi 
Published: February 2020

Abstract
Background
Acute flaccid myelitis (AFM) are reported to be associated with enterovirus D68 infection. Though an increasing number of AFM cases were reported with EV-D68 infection in the US, few such cases have been found in China.

Case presentation
A 6-year-old boy presented with acute flaccid myelitis (AFM) involving left arm after fever and respiratory symptoms for 6 days. Computed Tomography (CT) revealed inflammation in both lungs and magnetic resonance imaging (MRI) of the brain and spine showed swelling in the left frontal lobe and brain stem. The patient was diagnosed with meningomyelitis. EV-D68 was detected from pharyngeal samples 36 days after the onset of the disease.

Conclusion
We report the first EV-D68 infection in case of AFM in mainland China. AFM surveillance systems is recommended to be established in China to guide diagnosis, case reporting, and specimen collection and testing for better understanding its etiologies.
The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains
Authors: Li Shengjia , Ouyang Jinming , Zhao Bin , An Minghui , Wang Lin , Ding Haibo , Zhang Min , Han Xiaoxu 
Published: February 2020

AbstractBackgroundThe rate of S68G mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase has increased and is closely related to the K65R mutation among CRF01_AE-infected patients who failed treatment. We aimed to explore the temporal association of S68G and K65R mutations and disclose the role of the former on susceptibility to nucleotide/nucleoside reverse transcriptase inhibitor (NRTI) and viral replication with the K65R double mutations among CRF01_AE-infected patients who failed treatment.MethodsThe occurrence of S68G and K65R mutations was evaluated among HIV-1 of various subtypes in the global HIV Drug Resistance Database. The temporal association of S68G and K65R mutations was analyzed through next-generation sequencing in four CRF01_AE-infected patients who failed treatment with tenofovir/lamivudine/efavirenz. The impact of the S68G mutation on susceptibility to NRTI and replication fitness was analyzed using pseudovirus phenotypic resistance assays and growth competition assays, respectively.ResultsThe frequency of the S68G mutation increased by 1.4–9.7% in almost all HIV subtypes and circulating recombinant forms in treatment-experienced patients, except subtype F. The S68G mutation often occurred in conjunction with the K65R mutation among RTI-treated patients, with frequencies ranging 21.1–61.7% in various subtypes. Next-generation sequencing revealed that the S68G mutation occurred following the K65R mutation in three of the four CRF01_AE-infected patients. In these three patients, there was no significant change detected in the half maximal inhibitory concentration for zidovudine, tenofovir, or lamivudine between the K65R and K65R/S68G mutations, as demonstrated by the phenotypic resistance assays. Virus stocks of the K65R and K65R/S68G mutations were mixed with 4:6, 1:1, and 9:1 and cultured for 13 days, the K65R/S68G mutants outgrew those of the K65R mutants irrespective of the input ratio.ConclusionsS68G may be a natural polymorphism and compensatory mutation of K65R selected by NRTIs in the CRF01_AE strain of HIV-1. This mutation does not affect susceptibility to NRTI; however, it improves the replication fitness of K65R mutants. This study deciphers the role of the S68G mutation in the HIV reverse transcriptase of the CRF01_AE strain and provides new evidence for the interpretation of drug-resistant mutations in non-B subtypes of HIV-1.
Prevalence of syphilis in female sex workers in three countryside cities of the state of Pará, Brazilian Amazon
Authors: de Souza Ronaldo Lopes , dos Santos Madeira Lucimar Di Paula , Pereira Marcelo Victor Serejo , da Silva Rachel Macedo , de Luna Sales João Bráullio , Azevedo Vania Nakauth , Feitosa Rosimar Neris Martins , Monteiro Jacqueline Cortinhas , de Oliveira Guimarães Ishak Marluisa , Ishak Ricardo , Ribeiro Andre Luis Ribeiro , Oliveira-Filho Aldemir B. , Machado Luiz Fernando Almeida 
Published: February 2020

Abstract
Background
Syphilis is a sexually transmitted infection (STI) transmitted from person to person mainly by sexual intercourse or through vertical transmission during pregnancy. Female sex workers (FSWs) are exposed especially to syphilis infection, and besides all the efforts to control the spread of STIs, syphilis prevalence is still rising, mainly occurring in low-income countries. This study aimed to investigate the syphilis prevalence, demographic characteristics and sexual habits among FSWs in the Amazon region of Brazil.

Methods
A cross-sectional study was carried out including 184 FSWs from 3 countryside cities of the state of Pará, Amazon region of Brazil. A venereal disease research laboratory test and an indirect immunoenzyme assay to test antibodies against Treponema pallidum were used for screening syphilis infection, while sexual habits and demographic data information were collected through a semi-structured questionnaire. Data was analyzed comparing groups with/without syphilis. Poisson regression models were used to estimate the reasons of prevalence (RP).

Results
The overall prevalence of syphilis was 14.1% (95% CI = 9.8–17.8). FSWs had between 15 and 56 years of age, most were unmarried (65.7%), had attended less than 8 years of formal education (64.1%), had between 10 and 20 partners per week (64.1%), and reported no previous history of STIs (76.1%) and regular use of condom (52.7%). Low level of education attending up to the primary school (RP adjusted = 3.8; 95% CI = 1.4–9.2) and high frequency of anal sex during the past year (RP adjusted = 9.3; 95% CI = 3.5–28.7) were associated with a higher prevalence of syphilis.

Conclusions
A high prevalence of syphilis among FSWs in the Brazilian Amazon region was identified, showing that syphilis is more likely to be transmitted in FSW working in low-income areas, which is attributed to the low level of education. Anal intercourse was found as a risk factor associated with syphilis. Health programs focused on risk populations appear as a rational way to control syphilis spread, which is a rising problem in Brazil and in other several countries.
The incidence of collagen-associated adverse events in pediatric population with the use of fluoroquinolones: a nationwide cohort study in Taiwan
Authors: Yu Pei-Han , Hu Chih-Fen , Liu Jen-Wei , Chung Chi-Hsiang , Chen Yong-Chen , Sun Chien-An , Chien Wu-Chien 
Published: February 2020

Abstract
Background
To evaluate the safety of using fluoroquinolones in pediatric population in Taiwan.

Methods
Patients aged 0~18 years old with fluoroquinolones prescriptions ≥5 consecutive days during year 2000 to 2013 were selected from the National Health Insurance Research Database, 4-time case number were selected as controls. We evaluated the patient’s outcome after the use of fluoroquinolones by reviewing a newly diagnosis of the following collagen-associated adverse events by International Classification of Diseases, Ninth Revision, Clinical Modification codes, covering tendons rupture, retinal detachments, gastrointestinal tract perforation, aortic aneurysm or dissection.

Results
Of the enrolled patients (n = 167,105), collagen-associated adverse effects developed in 85 cases (0.051%) in 6-month tracking, including 0.051% in the fluoroquinolones study cohort (17 in 33,421) and 0.051% (68 in 133,684) in the fluoroquinolones free comparison cohort. The crude hazard ratio for collagen-associated adverse events in the fluoroquinolones group was 0.997 (0.586–1.696; p = 0.990). After adjusting for age, sex, catastrophic illness, low-income household, seasons, levels of urbanization, and healthcare, the corrected hazard ratio in 6-month tracking with FQs was 1.330 (95% CI; 0.778–2.276; p = 0.255).

Conclusions
There is no significant difference of collagen-associated adverse effects between fluoroquinolones group and fluoroquinolones free group from our data. We propose that fluoroquinolones for pediatric population in clinical practice may be not so harmful as previous references reported.