bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a Delphi survey to gain an international consensus on the challenges of conducting trials with adults with intellectual disabilities
Authors: Mulhall Peter , Taggart Laurence , Coates Vivien , McAloon Toni 
Published: December 2019

Background/aims People with intellectual disability experience higher rates of multi-morbidity and health inequalities, they are frequently prescribed medications and more likely to have an avoidable or premature death. There is a recognised lack of randomised controlled trials, and subsequently a lack of evidence base, for many of the interventions and treatments provided to people with intellectual disabilities. Very few disability-specific trials are conducted, and people with intellectual, and other cognitive, disabilities are routinely excluded from mainstream trials. There is an urgent need to facilitate more disability-specific trials or to encourage mainstream trialists to include people with disabilities in their studies. Obtaining a thorough understanding of the challenges inherent in these trials, and sharing this knowledge within the research community, may contribute significantly towards addressing this need. The aim of this study was to explore the practical and methodological challenges to conducting trials with adults with intellectual disabilities and to reach a consensus regarding which are the most important challenges for researchers for inclusion in a resource toolkit. Methods A three-round modified Delphi survey was conducted with a panel of international trials researchers within the intellectual disability field. Items were assessed in terms of the consensus level and stability of responses. Results A total of 64 challenges and barriers were agreed upon, across all aspects of the trial pathway, from planning through to reporting. Some challenges and barriers had been noted in the literature previously, but many previously uncited barriers (both systemic and attitudinal) were identified. Conclusion This is the first international survey exploring the experiences of researchers conducting randomised controlled trials with adults with intellectual disabilities. Many of the barriers and challenges reported can be overcome with creativity and some additional resources. Other challenges, including attitudes towards conducting trials with disabled populations, maybe harder to overcome. These findings have implications for conducting trials with other populations with cognitive or communication difficulties. Implications for disability researchers, funding bodies and ethical review panels are discussed.
Diagnostic and prognostic value of right ventricular eccentricity index in pulmonary artery hypertension
Authors: Wang Lili , Chen Xiaoling , Wan Ke , Gong Chao , Li Weihao , Xu Yuanwei , Wang Jie , He Juan , Wen Bi , Han Yuchi , Zeng Rui , Chen Yucheng 
Published: December 2019

The right ventricle experiences dynamic changes under pressure overload in pulmonary artery hypertension. This study aimed to evaluate the diagnostic and prognostic value of right ventricular eccentricity index (RVEI) in pulmonary artery hypertension. A total of 100 pulmonary artery hypertension patients (mean age, 36.85 (SD, 13.60) years; males, 30.0%) confirmed by right heart catheterization and 147 healthy volunteers (mean age 45.58 (SD, 17.58) years; males, 42.50%) were enrolled in this prospective study. All participants underwent cardiac magnetic resonance imaging (MRI) examination, and balanced steady‐state free precession (bSSFP) cine sequences were acquired. RVEI was measured on short‐axis cine images at the mid‐ventricular level of the right ventricle in end systole. The study found that RVEI was significantly lower in pulmonary artery hypertension patients than in healthy volunteers (1.84 (SD, 0.40) vs. 2.46 (SD, 0.40); p < 0.001). In pulmonary artery hypertension patients, RVEI was correlated with log(NT‐proBNP) (r = −0.388; p < 0.001), right ventricular end‐diastolic volume index (r = −0.452; p < 0.001), right ventricular end‐systolic volume index (r = −0.518; p < 0.001), and right ventricular ejection fraction (r = 0.552; p < 0.001). RVEI could discriminate pulmonary artery hypertension patients from healthy volunteers with 91.8% sensitivity and 68.0% specificity. Over median follow‐up of 14.8 months (interquartile range: 6.7–26.9 months), RVEI was demonstrated to be an independent predictor for adverse outcome (HR = 0.076; 95% CI, 0.013‐0.458; p = 0.005). In conclusion, MRI‐derived RVEI appears to be a useful diagnostic and prognostic value in pulmonary artery hypertension, and it provides incremental value to risk stratification strategy.
Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome
Authors: McCabe Kathryn L. , Popa Abbie M. , Durdle Courtney , Amato Michele , Cabaral Margarita H. , Cruz Joshua , Wong Ling M. , Harvey Danielle , Tartaglia Nicole , Simon Tony J. 
Published: December 2019

AbstractObjectivesOur ability to generate mental representation of magnitude from sensory information affects how we perceive and experience the world. Reduced resolution of the mental representations formed from sensory inputs may generate impairment in the proximal and distal information processes that utilize these representations. Impairment of spatial and temporal information processing likely underpins the non-verbal cognitive impairments observed in 22q11.2 deletion syndrome (22q11DS). The present study builds on prior research by seeking to quantify the resolution of spatial and temporal representation in children with 22q11DS, sex chromosome aneuploidy (SCA), and a typically developing (TD) control group.Participants and methodsChildren (22q11DS = 70, SCA = 49, TD = 46) responded to visual or auditory stimuli with varying difference ratios. The participant’s task was to identify which of two sequentially presented stimuli was of larger magnitude in terms of, size, duration, or auditory frequency. Detection threshold was calculated as the minimum difference ratio between the “standard” and the “target” stimuli required to achieve 75% accuracy in detecting that the two stimuli were different.ResultsChildren with 22q11DS required larger magnitude difference betweenspatialstimuli for accurate identification compared with both the SCA and TD groups (% difference from standard: 22q11DS = 14; SCA = 8; TD: 7;F = 8.42,p < 0.001).Temporaldetection threshold was also higher for the 22q11DS group to both visual (% difference from standard: 22q11DS = 14; SCA = 8; TD = 7;F = 8.33,p < 0.001) and auditory (% difference from standard: 22q11DS = 23; SCA = 12; TD: 8;F = 8.99,p < 0.001) stimuli compared with both the SCA and TD groups, while the SCA and TD groups displayed equivalent performance on these measures (p's > 0.05). Pitch detection threshold did not differ among the groups (p's > 0.05).ConclusionsThe observation of higher detection thresholds to spatial and temporal stimuli indicates further evidence for reduced resolution in both spatial and temporal magnitude representation in 22q11DS, that does not extend to frequency magnitude representation (pitch detection), and which is not explained by generalized cognitive impairment alone. These findings generate further support for the hypothesis that spatiotemporal hypergranularity of mental representations contributes to the non-verbal cognitive impairment seen in 22q11DS.
Stone-free rate after semirigid ureteroscopy with holmium laser lithotripsy versus laparoscopic ureterolithotomy for upper ureteral calculi: a multicenter study
Authors: Ali Ahmed Issam , Abdel-Karim Ali M. , Abd El Latif Ahmed A. , Eldakhakhny Amr , Galal Ehab M. , Anwar Ahmed Z. , El-Hawy Mamdouh M. , Fathelbab Tarek K. H. , Elbadry Mohamed S. , Elsharkawy Mostafa S. , Tawfiek Ehab R. 
Published: December 2019

Abstract
Background
Different treatment options were used to treat upper ureteral calculi. The aim of our study is to compare the stone-free rate and postoperative outcomes between semirigid ureteroscope with holmium laser lithotripsy and laparoscopic ureterolithotomy for the management of large solitary upper ureteral stones. Sixty-seven patients with a solitary upper ureteral stone who had LU or semirigid ureteroscopy in the period between January 2014 and March 2017 were included in our study. Out of the sixty-seven patients, 37 patients had semirigid ureteroscopy and holmium laser lithotripsy (Group A) and 30 patients had laparoscopic ureterolithotomy (Group B). Both groups were compared regarding operative time, intraoperative complications, need for auxiliary procedures, hospital stays, postoperative complications and stone-free rate.

Results
The mean stone size was 1.84 ± 0.12 cm in Group A and 1.79 ± 0.17 cm in Group B, P value = 0.2. The mean operative time was 61.5 ± 3.5 min in Group A and 63 ± 4.2 min in Group B, P value = 0.13. Stone migration was recorded in five cases (14%) in Group A while no cases in Group B had stone migration. Flexible ureteroscope was used as an auxiliary measure in five patients (14%) in Group A at the same session. No auxiliary measures were used in the LU group.

Conclusion
The stone-free rates after semirigid URS and laser lithotripsy are comparable to those following LU, especially when flexible URS is used to manage migrating stone fragments at the same session.
Colibri® insecticide induces male reproductive toxicity: alleviating effects of Lannea acida (Anacardiaceae) in rats
Authors: Tetsatsi Aimé Césaire Momo , Nkeng-Effouet Pepin Alango , Alumeti Désiré Munyali , Bonsou Georges Roméo Fozin , Kamanyi Albert , Watcho Pierre 
Published: December 2019

AbstractBackgroundImidacloprid, a neonicotinoid insecticide, has been associated to severe reproductive toxicity in mammals. Although some preventive measures have been reported, curative strategies are yet to be explored. The present study was designed to investigate the alleviating effects ofLannea acidaon the reproductive toxicity of colibri®, a commercial formulation of imidacloprid, in adult male rats.Materials and methodsSeventy rats were orally administered with colibri® (22.5 mg/kg, 10 mL/kg) for 14 days and treated for other 14 or 28 days with either aqueous or methanol extracts ofL. acida(170 or 340 mg/kg). Control animals were similarly treated with clomiphene citrate or vitamin E. Sexual organ weights, spermatozoa characteristics, sexual hormones, stress markers and testis histology were evaluated at the end of each treatment period.ResultsColibri® exposition induced reproductive toxicity marked by a decrease in sex organ weights, spermatozoa count, motility and viability. Colibri® also decreased testosterone, luteinizing hormone, follicle stimulating hormone concentrations and increased testicular oxidative stress. Spermatozoa morphology and testis histology were also severely altered. Similar to clomiphene citrate and vitamin E, treatment withL. acidaextracts significantly (p ≤ 0.05–0.001) reversed the above-mentioned damages, especially after 28 days of treatment with aqueous (340 mg/kg) and methanol (170 mg/kg) extracts.ConclusionPresent results indicate thatL. acidaexerts curative effects against colibri®-induced male reproductive toxicity. These results justify the use of this plant as fertility enhancer and suggest that it could be an alternative in the management of pesticide-derived male infertility.
Fully moderated t-statistic in linear modeling of mixed effects for differential expression analysis
Authors: Yu Lianbo , Zhang Jianying , Brock Guy , Fernandez Soledad 
Published: December 2019

Abstract
Background
Gene expression profiling experiments with few replicates lead to great variability in the estimates of gene variances. Toward this end, several moderated t-test methods have been developed to reduce this variability and to increase power for testing differential expression. Most of these moderated methods are based on linear models with fixed effects where residual variances are smoothed under a hierarchical Bayes framework. However, they are inadequate for designs with complex correlation structures, therefore application of moderated methods to linear models with mixed effects are needed for differential expression analysis.

Results
We demonstrated the implementation of the fully moderated t-statistic method for linear models with mixed effects, where both residual variances and variance estimates of random effects are smoothed under a hierarchical Bayes framework. We compared the proposed method with two current moderated methods and show that the proposed method can control the expected number of false positives at the nominal level, while the two current moderated methods fail.

Conclusions
We proposed an approach for testing differential expression under complex correlation structures while providing variance shrinkage. The proposed method is able to improve power by moderation and controls the expected number of false positives properly at the nominal level.
BISR-RNAseq: an efficient and scalable RNAseq analysis workflow with interactive report generation
Authors: Gadepalli Venkat Sundar , Ozer Hatice Gulcin , Yilmaz Ayse Selen , Pietrzak Maciej , Webb Amy 
Published: December 2019

Abstract
Background
RNA sequencing has become an increasingly affordable way to profile gene expression patterns. Here we introduce a workflow implementing several open-source softwares that can be run on a high performance computing environment.

Results
Developed as a tool by the Bioinformatics Shared Resource Group (BISR) at the Ohio State University, we have applied the pipeline to a few publicly available RNAseq datasets downloaded from GEO in order to demonstrate the feasibility of this workflow. Source code is available here: workflow: https://code.bmi.osumc.edu/gadepalli.3/BISR-RNAseq-ICIBM2019 and shiny: https://code.bmi.osumc.edu/gadepalli.3/BISR_RNASeq_ICIBM19. Example dataset is demonstrated here: https://dataportal.bmi.osumc.edu/RNA_Seq/.

Conclusion
The workflow allows for the analysis (alignment, QC, gene-wise counts generation) of raw RNAseq data and seamless integration of quality analysis and differential expression results into a configurable R shiny web application.
Prediction of novel mouse TLR9 agonists using a random forest approach
Authors: Khanna Varun , Li Lei , Fung Johnson , Ranganathan Shoba , Petrovsky Nikolai 
Published: December 2019

Abstract
Background
Toll-like receptor 9 is a key innate immune receptor involved in detecting infectious diseases and cancer. TLR9 activates the innate immune system following the recognition of single-stranded DNA oligonucleotides (ODN) containing unmethylated cytosine-guanine (CpG) motifs. Due to the considerable number of rotatable bonds in ODNs, high-throughput in silico screening for potential TLR9 activity via traditional structure-based virtual screening approaches of CpG ODNs is challenging. In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We employed an in-house experimentally validated dataset of 396 single-stranded synthetic ODNs, to compare the results of five machine learning algorithms. Since the dataset was highly imbalanced, we used an ensemble learning approach based on repeated random down-sampling.

Results
Using in-house experimental TLR9 activity data we found that random forest algorithm outperformed other algorithms for our dataset for TLR9 activity prediction. Therefore, we developed a cross-validated ensemble classifier of 20 random forest models. The average Matthews correlation coefficient and balanced accuracy of our ensemble classifier in test samples was 0.61 and 80.0%, respectively, with the maximum balanced accuracy and Matthews correlation coefficient of 87.0% and 0.75, respectively. We confirmed common sequence motifs including ‘CC’, ‘GG’,‘AG’, ‘CCCG’ and ‘CGGC’ were overrepresented in mTLR9 agonists. Predictions on 6000 randomly generated ODNs were ranked and the top 100 ODNs were synthesized and experimentally tested for activity in a mTLR9 reporter cell assay, with 91 of the 100 selected ODNs showing high activity, confirming the accuracy of the model in predicting mTLR9 activity.

Conclusion
We combined repeated random down-sampling with random forest to overcome the class imbalance problem and achieved promising results. Overall, we showed that the random forest algorithm outperformed other machine learning algorithms including support vector machines, shrinkage discriminant analysis, gradient boosting machine and neural networks. Due to its predictive performance and simplicity, the random forest technique is a useful method for prediction of mTLR9 ODN agonists.
A hybrid and scalable error correction algorithm for indel and substitution errors of long reads
Authors: Das Arghya Kusum , Goswami Sayan , Lee Kisung , Park Seung-Jong 
Published: December 2019

AbstractBackgroundLong-read sequencing has shown the promises to overcome the short length limitations of second-generation sequencing by providing more complete assembly. However, the computation of the long sequencing reads is challenged by their higher error rates (e.g., 13% vs. 1%) and higher cost ($0.3 vs. $0.03 per Mbp) compared to the short reads.MethodsIn this paper, we present a new hybrid error correction tool, called ParLECH (Parallel Long-read Error Correction using Hybrid methodology). The error correction algorithm of ParLECH is distributed in nature and efficiently utilizes thek-mer coverage information of high throughput Illumina short-read sequences to rectify the PacBio long-read sequences.ParLECH first constructs a de Bruijn graph from the short reads, and then replaces the indel error regions of the long reads with their corresponding widest path (or maximum min-coverage path) in the short read-based de Bruijn graph. ParLECH then utilizes thek-mer coverage information of the short reads to divide each long read into a sequence of low and high coverage regions, followed by a majority voting to rectify each substituted error base.ResultsParLECH outperforms latest state-of-the-art hybrid error correction methods on real PacBio datasets. Our experimental evaluation results demonstrate that ParLECH can correct large-scale real-world datasets in an accurate and scalable manner. ParLECH can correct the indel errors of human genome PacBio long reads (312 GB) with Illumina short reads (452 GB) in less than 29 h using 128 compute nodes. ParLECH can align more than 92% bases of anE. coliPacBio dataset with the reference genome, proving its accuracy.ConclusionParLECH can scale to over terabytes of sequencing data using hundreds of computing nodes. The proposed hybrid error correction methodology is novel and rectifies both indel and substitution errors present in the original long reads or newly introduced by the short reads.
Chondroitinase ABC reduces dopaminergic nigral cell death and striatal terminal loss in a 6-hydroxydopamine partial lesion mouse model of Parkinson’s disease
Authors: Fletcher Edward J. R. , Moon Lawrence D. F. , Duty Susan 
Published: December 2019

AbstractBackgroundParkinson’s disease (PD) is characterised by dopaminergic cell loss within the substantia nigra pars compacta (SNc) that leads to reduced striatal dopamine content and resulting motor deficits. Identifying new strategies to protect these cells from degeneration and retain striatal dopaminergic innervation is therefore of great importance. Chondroitin sulphate proteoglycans (CSPGs) are recognised contributors to the inhibitory extracellular milieu known to hinder tissue recovery following CNS damage. Digestion of these molecules by the bacterial lyase chondroitinase ABC (ChABC) has been shown to promote functional recovery in animal models of neurological injury. Although ChABC has been shown to promote sprouting of dopaminergic axons following transection of the nigrostriatal pathway, its ability to protect against nigrostriatal degeneration in a toxin-based module with better construct validity for PD has yet to be explored. Here we examined the neuroprotective efficacy of ChABC treatment in the full and partial 6-hydroxydopamine (6-OHDA) lesion mouse models of PD.ResultsIn mice bearing a full 6-OHDA lesion, ChABC treatment failed to protect against the loss of either nigral cells or striatal terminals. In contrast, in mice bearing a partial 6-OHDA lesion, ChABC treatment significantly protected cells of the rostral SNc, which remained at more than double the numbers seen in vehicle-treated animals. In the partial lesion model, ChABC treatment also significantly preserved dopaminergic fibres of the rostral dorsal striatum which increased from 15.3 ± 3.5% of the intact hemisphere in saline-treated animals to 36.3 ± 6.5% in the ChABC-treated group. These protective effects of ChABC treatment were not accompanied by improvements in either the cylinder or amphetamine-induced rotations tests of motor function.ConclusionsChABC treatment provided significant protection against a partial 6-OHDA lesion of the nigrostriatal tract although the degree of protection was not sufficient to improve motor outcomes. These results support further investigations into the benefits of ChABC treatment for providing neuroprotection in PD.
Analysis of factors influencing hospital-acquired infection in postoperative patients with intracranial aneurysm
Authors: Wang Jun , Ji Yuanyuan , Jiang Lidan , Zhao Xia , Guan Shaochen , Yang Piao , Yu Jie , Liu Yunyun , Zhang Hongqi 
Published: December 2019

Abstract
Background
Hospital-acquired infection (HAI) is a serious complication of neurosurgery. In recent years, the medical body has paid increasing attention to this issue.

Aim
We investigated the status of HAIs in patients who had undergone surgery for intracranial aneurysms and analysed their risk factors.

Methods
A retrospective analysis was carried out on the medical records of 542 patients with intracranial aneurysms after they were admitted for neurosurgery at Xuanwu Hospital of Capital Medical University between January and December 2016. Cases studied were divided into an infection group and a control group. Logistic regression analysis of the data was carried out.

Findings
Of the 542 patients with intracranial aneurysms who underwent surgery, 77 HAIs occurred in 64 patients, with an infection prevalence of 11.8% and prevalence of infection cases of 14.2%. Logistic regression showed that an admission Glasgow Coma Scale (GCS) score of less than 8 points (odds ratio = 4.261, 95% confidence interval 1.102–16.476), hyperglycaemia (2.759, 1.159–6.564), hypothermia treatment (6.557, 2.244–19.159), and central venous catheterisation (CVC) (8.853, 2.860–27.398) were independent risk factors for HAIs in patients with intracranial aneurysm who underwent surgery.

Conclusion
Being comatose upon hospital admission, having hyperglycaemia or hypothermia, and indwelling CVC are major risk factors for HAIs in patients undergoing surgery for intracranial aneurysms.