bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding a suitable library size to call variants in RNA-Seq
Authors: Quaglieri Anna , Flensburg Christoffer , Speed Terence P. , Majewski Ian J. 
Published: December 2020

AbstractBackgroundRNA sequencing allows the study of both gene expression changes and transcribed mutations, providing a highly effective way to gain insight into cancer biology. When planning the sequencing of a large cohort of samples, library size is a fundamental factor affecting both the overall cost and the quality of the results. Here we specifically address how overall library size influences the detection of somatic mutations in RNA-seq data in two acute myeloid leukaemia datasets.Results We simulated shallower sequencing depths by downsampling 45 acute myeloid leukaemia samples (100 bp PE) that are part of the Leucegene project, which were originally sequenced at high depth. We compared the sensitivity of six methods of recovering validated mutations on the same samples. The methods compared are a combination of three popular callers (MuTect, VarScan, and VarDict) and two filtering strategies. We observed an incremental loss in sensitivity when simulating libraries of 80M, 50M, 40M, 30M and 20M fragments, with the largest loss detected with less than 30M fragments (below 90%, average loss of 7%). The sensitivity in recovering insertions and deletions varied markedly between callers, with VarDict showing the highest sensitivity (60%). Single nucleotide variant sensitivity is relatively consistent across methods, apart from MuTect, whose default filters need adjustment when using RNA-Seq. We also analysed 136 RNA-Seq samples from the TCGA-LAML cohort (50 bp PE) and assessed the change in sensitivity between the initial libraries (average 59M fragments) and after downsampling to 40M fragments. When considering single nucleotide variants in recurrently mutated myeloid genes we found a comparable performance, with a 6% average loss in sensitivity using 40M fragments.ConclusionsBetween 30M and 40M 100 bp PE reads are needed to recover 90–95% of the initial variants on recurrently mutated myeloid genes. To extend this result to another cancer type, an exploration of the characteristics of its mutations and gene expression patterns is suggested.
A novel computational strategy for DNA methylation imputation using mixture regression model (MRM)
Authors: Yu Fangtang , Xu Chao , Deng Hong-Wen , Shen Hui 
Published: December 2020

AbstractBackgroundDNA methylation is an important heritable epigenetic mark that plays a crucial role in transcriptional regulation and the pathogenesis of various human disorders. The commonly used DNA methylation measurement approaches, e.g., Illumina Infinium HumanMethylation-27 and -450 BeadChip arrays (27 K and 450 K arrays) and reduced representation bisulfite sequencing (RRBS), only cover a small proportion of the total CpG sites in the human genome, which considerably limited the scope of the DNA methylation analysis in those studies.ResultsWe proposed a new computational strategy to impute the methylation value at the unmeasured CpG sites using the mixture of regression model (MRM) of radial basis functions, integrating information of neighboring CpGs and the similarities in local methylation patterns across subjects and across multiple genomic regions. Our method achieved a better imputation accuracy over a set of competing methods on both simulated and empirical data, particularly when the missing rate is high. By applying MRM to an RRBS dataset from subjects with low versus high bone mineral density (BMD), we recovered methylation values of ~ 300 K CpGs in the promoter regions of chromosome 17 and identified some novel differentially methylated CpGs that are significantly associated with BMD.ConclusionsOur method is well applicable to the numerous methylation studies. By expanding the coverage of the methylation dataset to unmeasured sites, it can significantly enhance the discovery of novel differential methylation signals and thus reveal the mechanisms underlying various human disorders/traits.
Stress-related changes in leukocyte profiles and telomere shortening in the shortest-lived tetrapod, Furcifer labordi
Authors: Eckhardt Falk , Pauliny Angela , Rollings Nicky , Mutschmann Frank , Olsson Mats , Kraus Cornelia , Kappeler Peter M. 
Published: December 2020

AbstractBackgroundLife history theory predicts that during the lifespan of an organism, resources are allocated to either growth, somatic maintenance or reproduction. Resource allocation trade-offs determine the evolution and ecology of different life history strategies and define an organisms’ position along a fast–slow continuum in interspecific comparisons. Labord’s chameleon (Furcifer labordi) from the seasonal dry forests of Madagascar is the tetrapod species with the shortest reported lifespan (4–9 months). Previous investigations revealed that their lifespan is to some degree dependent on environmental factors, such as the amount of rainfall and the length of the vegetation period. However, the intrinsic mechanisms shaping such a fast life history remain unknown. Environmental stressors are known to increase the secretion of glucocorticoids in other vertebrates, which, in turn, can shorten telomeres via oxidative stress. To investigate to what extent age-related changes in these molecular and cellular mechanisms contribute to the relatively short lifetime ofF. labordi, we assessed the effects of stressors indirectly via leukocyte profiles (H/L ratio) and quantified relative telomere length from blood samples in a wild population in Kirindy Forest. We compared our findings with the sympatric, but longer-lived sister speciesF.cf.nicosiai,which exhibit the same annual timing of reproductive events, and with wild-caughtF. labordithat were singly housed under ambient conditions.ResultsWe found that H/L ratios were consistently higher in wildF. labordicompared toF.cf.nicosiai. Moreover,F. labordialready exhibited relatively short telomeres during the mating season when they were 3–4 months old, and telomeres further shortened during their post-reproductive lives. At the beginning of their active season, telomere length was relatively longer inF.cf.nicosiai, but undergoing rapid shortening towards the southern winter, when both species gradually die off. CaptiveF. labordishowed comparatively longer lifespans and lower H/L ratios than their wild counterparts.ConclusionWe suggest that environmental stress and the corresponding accelerated telomere attrition have profound effects on the lifespan ofF. labordiin the wild, and identify physiological mechanisms potentially driving their relatively early senescence and mortality.
Intricate genetic variation networks control the adventitious root growth angle in apple
Authors: Zheng Caixia , Shen Fei , Wang Yi , Wu Ting , Xu Xuefeng , Zhang Xinzhong , Han Zhenhai 
Published: December 2020

AbstractBackgroundThe root growth angle (RGA) typically determines plant rooting depth, which is significant for plant anchorage and abiotic stress tolerance. Several quantitative trait loci (QTLs) for RGA have been identified in crops. However, the underlying mechanisms of the RGA remain poorly understood, especially in apple rootstocks. The objective of this study was to identify QTLs, validate genetic variation networks, and develop molecular markers for the RGA in apple rootstock.ResultsBulked segregant analysis by sequencing (BSA-seq) identified 25 QTLs for RGA using 1955 hybrids of the apple rootstock cultivars ‘Baleng Crab’ (Malus robustaRehd., large RGA) and ‘M9’ (M. pumilaMill., small RGA). With RNA sequencing (RNA-seq) and parental resequencing, six major functional genes were identified and constituted two genetic variation networks for the RGA. Two single nucleotide polymorphisms (SNPs) of theMdLAZY1promoter damaged the binding sites of MdDREB2A and MdHSFB3, while one SNP ofMdDREB2AandMdIAA1affected the interactions of MdDREB2A/MdHSFB3 and MdIAA1/MdLAZY1, respectively. A SNP within theMdNPR5promoter damaged the interaction betweenMdNPR5and MdLBD41, while one SNP ofMdLBD41interrupted the MdLBD41/MdbHLH48 interaction that affected the binding ability of MdLBD41 on theMdNPR5promoter. Twenty six SNP markers were designed on candidate genes in each QTL interval, and the marker effects varied from 0.22°-26.11°.ConclusionsSix diagnostic markers, SNP592, G122, b13, Z312, S1272, and S1288, were used to identify two intricate genetic variation networks that control the RGA and may provide new insights into the accuracy of the molecular markers. The QTLs and SNP markers can potentially be used to select deep-rooted apple rootstocks.
MALDI-TOF mass spectrometry for sub-typing of Streptococcus pneumoniae
Authors: Kann Sivkheng , Sao Sena , Phoeung Chanleakhena , By Youlet , Bryant Juliet , Komurian-Pradel Florence , Saphonn Vonthanak , Chou Monidarin , Turner Paul 
Published: December 2020

Abstract
Background
Serotyping of Streptococcus pneumoniae is important for monitoring of vaccine impact. Unfortunately, conventional and molecular serotyping is expensive and technically demanding. This study aimed to determine the ability of matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) mass spectrometry to discriminate between pneumococcal serotypes and genotypes (defined by global pneumococcal sequence cluster, GPSC). In this study, MALDI-TOF mass spectra were generated for a diverse panel of whole genome sequenced pneumococcal isolates using the bioMerieux VITEK MS in clinical diagnostic (IVD) mode. Discriminatory mass peaks were identified and hierarchical clustering was performed to visually assess discriminatory ability. Random forest and classification and regression tree (CART) algorithms were used to formally determine how well serotypes and genotypes were identified by MALDI-TOF mass spectrum.

Results
One hundred and ninety-nine pneumococci, comprising 16 serotypes and non-typeable isolates from 46 GPSC, were analysed. In the primary experiment, hierarchical clustering revealed poor congruence between MALDI-TOF mass spectrum and serotype. The correct serotype was identified from MALDI-TOF mass spectrum in just 14.6% (random forest) or 35.4% (CART) of 130 isolates. Restricting the dataset to the nine dominant GPSC (61 isolates / 13 serotypes), discriminatory ability improved slightly: the correct serotype was identified in 21.3% (random forest) and 41.0% (CART). Finally, analysis of 69 isolates of three dominant serotype-genotype pairs (6B-GPSC1, 19F-GPSC23, 23F-GPSC624) resulted in the correct serotype identification in 81.1% (random forest) and 94.2% (CART) of isolates.

Conclusions
This work suggests that MALDI-TOF is not a useful technique for determination of pneumococcal serotype. MALDI-TOF mass spectra appear more associated with isolate genotype, which may still have utility for future pneumococcal surveillance activities.
Elderly patients with atrial fibrillation in routine clinical practice—peri-procedural management of edoxaban oral anticoagulation therapy is associated with a low risk of bleeding and thromboembolic complications: a subset analysis of the prospective, observational, multinational EMIT-AF study
Authors: Unverdorben M. , von Heymann C. , Santamaria A. , Saxena M. , Vanassche T. , Jin J. , Laeis P.  , Wilkins R. , Chen C. , Colonna P. 
Published: December 2020

Abstract
Background
Annually > 10% of patients with atrial fibrillation on oral anticoagulation undergo invasive procedures. Optimal peri-procedural management of anticoagulation, as judged by major bleeding and thromboembolic events, especially in the elderly, is still debated.

Methods
Procedures from 1442 patients were evaluated. Peri-procedural edoxaban management was guided only by the experience of the attending physician. The primary safety outcome was the rate of major bleeding. Secondary outcomes included the peri-procedural administration of edoxaban, other bleeding events, and the main efficacy outcome, a composite of acute coronary syndrome, non-hemorrhagic stroke, transient ischemic attack, systemic embolic events, deep vein thrombosis, pulmonary embolism, and mortality.

Results
Of the 1442 patients, 280 (19%) were < 65, 550 (38%) were 65–74, 514 (36%) 75–84, and 98 (7%) were 85 years old or older. With increasing age, comorbidities and risk scores were higher. Any bleeding complications were uncommon across all ages, ranging from 3.9% in patients < 65 to 4.1% in those 85 years or older; major bleeding rates in any age group were ≤ 0.6%. Interruption rates and duration increased with advancing age. Thromboembolic events were more common in the elderly, with all nine events occurring in those > 65, and seven in patients aged > 75 years.

Conclusion
Despite increased bleeding risk factors in the elderly, bleeding rates were small and similar across all age groups. However, there was a trend toward more thromboembolic complications with advancing age. Further efforts to identify the optimal management to reduce ischemic complications are needed.
Trial registration: NCT# 02950168, October 31, 2016
Transcatheter closure for patent ductus arteriosus in patients with Eisenmenger syndrome: to do or not?
Authors: Xu Jing , Wang Liang , Shen Yunli , Geng Liang , Chen Fadong 
Published: December 2020

AbstractBackgroundPatent ductus arteriosus (PDA) complicated by Eisenmenger syndrome (ES) remains to be a major cause of morbidity and mortality worldwide. Giving increasing evidences of benefit from targeted therapies, ES patients once thought to be inoperable may have increasing options for management. This study aims to explore whether PDA in patients with ES can be treated with transcatheter closure (TCC).MethodsBetween August 2014 and July 2016, four of fifteen PDA-ES patients whose Qp/Qs improved significantly and Qp/Qs > 1.5 after acute vasodilator testing with 100% oxygen were selected to receive TCC and pulmonary vasodilator therapy. PAH-targeted drugs were prescribed before and after occlusion for all. Trial occlusion was performed before permanent closure.ResultsThe first TCC failed after initiation of PAH-targeted drugs for 6 months in four patients. After the medication was adjusted and extended to 12 months, TCC was performed for all without hemodynamic intolerances during perioperative period. Pulmonary artery systolic pressure (PASP) was significantly decreased (≥ 40%) immediately after TCC. During a mean follow-up of 48 ± 14.70 months, there were a further decrease of PASPs in two patients, the other two showed improved pulmonary vascular resistance, WHO functional class and six-minute walking distance despite deteriorated PASP.ConclusionSome selected PDA-ES patients might benefit from TCC and combined PAH-targeted drugs play a crucial role.
The diagnostic capability of electrocardiography on the cardiogenic shock in the patients with acute myocarditis
Authors: Yang Dan , Dai Qing , Wu Han , Chen Jianzhou , Zhang Jingmei , Wei Zhonghai 
Published: December 2020

Abstract
Background
The study was performed to assess the diagnostic capability of ECG on the cardiogenic shock (CS) in acute myocarditis. A new score was derived from the combination of the ECG parameters and the diagnostic value was also evaluated.

Methods
Total 103 consecutive patients with acute myocarditis admitted in Nanjing Drum Hospital were enrolled in the current study. The cohort was divided into fulminant myocarditis group (FM, n = 20) and non fulminant myocarditis group (NFM, n = 83). The demographic features, results of electrocardiography (ECG) and ultracardiography were compared. Logistic regression analysis was conducted to identify the relevant factors in ECG parameters. We created a new variable called “ECG score” by certain combination of ECG parameters. The diagnostic capability of ECG score for CS was compared with the existing diagnostic indices using regression model and receiver-operating characteristics (ROC) analysis.

Results
There were several changes on ECG significantly different between the two groups. Multivariate regression analysis demonstrated PR + QRS interval (P = 0.008), ventricular arrhythmia (P = 0.001) and pathological Q wave (P = 0.003) were the independent relevant factors of CS. The derived variable “ECG score” was identified as a significant relevant factor of CS by multivariate regression model. ROC analysis showed PR + QRS interval, ventricular arrhythmia and pathological Q wave all had equivalent diagnostic capability to left ventricular ejection fraction (LVEF) and shock index (SI). ECG score was equivalent to LVEF but superior to SI in diagnosing CS

Conclusions
ECG was valuable in diagnosing CS due to acute myocarditis. The ECG score was superior to the traditional diagnostic indices and could be used for an rapid recognition of CS.
Diversity in substance use behaviour among street children of Delhi under Bayesian paradigm
Authors: Verma Vivek , Mishra Ashwani Kumar , Dhawan Anju , Nath Dilip C. 
Published: December 2020

AbstractBackgroundShannon’s index is one of the measures of biodiversity, which is intended to quantify both richness and evenness of the species/individuals in the ecosystem or community. However, application of Shannon’s index in the field of substance use among the street children has not been done till date.MethodsThis paper is concerned with methods of estimating Shannon’s diversity index (SDI), which can be used to capture the variation in the population due to certain characteristics. Under the consideration that the probability of abundance, based on certain characteristics in the population, is a random phenomenon, we derive a Bayesian estimate in connection with Shannon’s information measure and their properties (mean and variance), by using a probability matching prior, through simulation and compared it with those of the classical estimates of Shannon. The theoretical framework has been applied to the primary survey data of substance use among the street children in Delhi, collected during 2015. The measure of diversity was estimated across different age profiles and districts.ResultsThe results unrevealing the diversity estimate for street children corresponding to each region of Delhi, under both the classical and Bayesian paradigms. Although the estimates were close to one another, a striking difference was noted in the age profile of children.ConclusionsThe Bayesian methodology provided evidence for a greater likelihood of finding substance-using street children, belonging to the lower age group (7-10, maximum Bayesian entropy-3.73), followed by the middle (11-14) and upper age group (15-18). Moreover, the estimated variance under the Bayesian paradigm was lesser than that of the classical estimate. There is ample scope for further refinement in these estimates, by considering more covariates that may have a possible role in initiating substance use among street children in developing countries like India.
Compositional and drug-resistance profiling of pathogens in patients with severe acute pancreatitis: a retrospective study
Authors: Fan Ning , Hu Yong , Shen Hong , Liu Shengjie , Zhao Guang , Sun Lanju , Li Chunyan , Zhao Xin , Li Yanning , Wang Jianhua , Cui Yunfeng 
Published: December 2020

Abstract
Background
Infection is one of the important causes of death in patients with severe acute pancreatitis (SAP), but the bacterial spectrum and antibiotic resistance are constantly changing. Making good use of antibiotics and controlling multi-drug-resistant (MDR) bacterial infections are of vital importance in improving the cure rate of SAP. We conducted a retrospective study in the hope of providing references for antibiotic selection and control of drug-resistant bacteria.

Methods
Retrospective analysis was performed on the data of patients hospitalized in our hospital due to acute pancreatitis (AP) in the past 5 years. General data were classified and statistically analyzed. Subsequently, the bacterial spectrum characteristics and the data related to drug-resistant bacterial infection of 569 AP patients were analyzed. Finally, unconditional logistic regression analysis was conducted to analyze the risk factors of MDR infection.

Results
A total of 398 patients were enrolled in this study and the hospitalization data and associated results were analyzed. A total of 461 strains of pathogenic bacteria were detected, including 223 (48.4%) gram-negative bacterial strains, 190 (41.2%) gram-positive bacterial strains and 48 (10.4%) fungal strains. The detection rates of resistance in gram-negative and gram-positive bacterial strains were 48.0% (107/223) and 25.3% (48/190), respectively. There were significant differences between the MDR group and the non-MDR group for the factors of precautionary antibiotic use, kinds of antibiotics used, receipt of carbapenem, tracheal intubation, hemofiltration and number of hospitalization days in the intensive care unit. Unconditional logistic regression revealed 2 risk factors for MDR bacterial infection.

Conclusions
Our results illustrate that gram-negative bacteria were the most common pathogens in SAP infection, and the proportion of gram-positive bacteria increased notably. The rate of antibiotic resistance was higher than previously reported. Unconditional logistic regression analysis showed that using more types of antibiotics and the number of hospitalization days in the ICU were the risk factors associated with MDR bacterial infection.
Anthropometric indicators as a discriminator of sarcopenia in community-dwelling older adults of the Amazon region: a cross-sectional study
Authors: Esteves Cássio Lima , Ohara Daniela Gonçalves , Matos Areolino Pena , Ferreira Vânia T. K. , Iosimuta Natalia C. R. , Pegorari Maycon Sousa 
Published: December 2020

Abstract
Background
Sarcopenia is a geriatric syndrome associated with negative health outcomes and the use of viable alternative screening tools may help in the diagnosis of this condition. This study aimed to analyze the association of sarcopenia with anthropometric indicators among community-dwelling older adults and to identify cut-off points for such indicators as a discriminant criterion for predicting sarcopenia.

Methods
This was a cross-sectional study conducted on community-dwelling older adults ≥60 years old (n = 411) of both sexes from Macapá, Amapá, Brazil. Socioeconomic, clinical and anthropometric data (arm circumference - AC, waist circumference - WC, calf circumference - CC and body mass index – BMI) were collected using a structured form. Sarcopenia was identified according to the EWGSOP 2 consensus. The association between anthropometric indicators and sarcopenia was performed using logistic regression and cut-off points established from the ROC Curve. Statistical significance was defined as p ≤ 0.05.

Results
Adjusted analysis indicated an independent and inverse association between sarcopenia and the anthropometric indicators: AC (odds ratio, OR: 0.63; 95% confidence interval, 95%CI: 0.53–0.76), CC (OR: 0.73; 95%CI: 0.62–0.85), WC (OR: 0.93; 95%CI: 0.90–0.97) and BMI (OR: 0.64; 95%CI: 0.53–0.76). The following cut-off points for older men and women represented the discriminant criterion for the presence of sarcopenia: WC (≤97 and ≤ 86 cm), CC (≤33 and ≤ 31 cm), AC (≤27 cm) and BMI (≤24.8 kg/m2 and ≤ 24.5 kg/m2) (area under the ROC curve superior to 0.70). BMI and AC were the indicators with the highest ability to discriminate older adults of both sexes with sarcopenia.

Conclusions
An increase of one unit of the indicators can reduce the probability of occurrence of sarcopenia. All indicators were considered to discriminate the occurrence of sarcopenia, with emphasis on BMI and AC, and could be used to screen for this condition among community-dwelling older adults.