bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA TUG1 is down-regulated in Friedreich’s ataxia
Authors: Koka Mert , Li Hui , Akther Rumana , Perlman Susan , Wong Darice , Fogel Brent L , Lynch David R , Chandran Vijayendran 
Published: September 2023

AbstractFriedreich’s Ataxia (FRDA) is a neurodegenerative disorder caused by reduced frataxin (FXN) levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia with no cure, FRDA lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials. This study identifies long non-coding RNA Tug1 as a potential blood-based FRDA biomarker.In a previous study using a frataxin knockdown mouse model (FRDAkd), we observed several hallmark FRDA symptoms and abnormalities in various tissues. Building on this, we hypothesized that a dual-source approach—comparing the data from peripheral blood samples from FRDA patients with tissue samples from affected areas in FRDAkd mice, tissues usually unattainable from patients—would effectively identify robust biomarkers.A comprehensive reanalysis was conducted on gene expression data from 183 age- and sex-matched peripheral blood samples of FRDA patients, carriers, and controls, as well as 192 tissue datasets from FRDAkd mice. Blood and tissue samples underwent RNA isolation and qRT-PCR, and frataxin knockdown was confirmed through ELISA. Tug1 RNA interaction was explored via RNA pull-down assays. Validation was performed in serum and blood samples on an independent set of 45 healthy controls, 45 FRDA patients; 66 heterozygous carriers, and 72 FRDA patients. Tug1 and Slc40a1 emerged as potential blood-based biomarkers, confirmed in the FRDAkd mouse model (One-way ANOVA, p ≤ 0.05).Tug1 was consistently downregulated after Fxn knockdown and correlated strongly with Fxn levels (R2= 0.71 during depletion, R2= 0.74 during rescue). Slc40a1 showed a similar but tissue-specific pattern. Further validation of Tug1’s downstream targets strengthened its biomarker candidacy. In additional human samples, TUG1 levels were significantly downregulated in both whole blood and serum of FRDA patients compared to controls (Wilcoxon signed-rank test, p < 0.05). Regression analyses revealed a negative correlation between TUG1 levels and disease onset (p < 0.0037), and positive correlations with disease duration and Functional Disability Stage score (p < 0.04). This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases.In summary, this study highlights Tug1 as a crucial blood-based biomarker for FRDA. Tug1’s consistent expression variance across human and mouse tissues is closely associated to disease severity and key FRDA pathways. It also correlates strongly with Fxn levels, making it a promising early, non-invasive marker. TUG1 offers potential for FRDA monitoring and therapeutic development, warranting further clinical research.
The winner’s curse under dependence: repairing empirical Bayes using convoluted densities
Authors: Hawinkel Stijn , Thas Olivier , Maere Steven 
Published: September 2023

ABSTRACTThe winner’s curse is a form of selection bias that arises when estimates are obtained for a large number of features, but only a subset of most extreme estimates is reported. It occurs in large scale significance testing as well as in rank-based selection, and imperils reproducibility of findings and follow-up study design. Several methods correcting for this selection bias have been proposed, but questions remain on their susceptibility to dependence between features since theoretical analyses and comparative studies are few. We prove that estimation through Tweedie’s formula is biased in presence of strong dependence, and propose a convolution of its density estimator to restore its competitive performance, which also aids other empirical Bayes methods. Furthermore, we perform a comprehensive simulation study comparing different classes of winner’s curse correction methods for point estimates as well as confidence intervals under dependence. We find a bootstrap method by Tan et al. (2015) and empirical Bayes methods with density convolution to perform best at correcting the selection bias, although this correction generally does not improve the feature ranking. Finally, we apply the methods to a comparison of single-feature versus multi-feature prediction models in predictingBrassica napusphenotypes from gene expression data, demonstrating that the superiority of the best single-feature model may be illusory.
Life in a Central European warm-temperate to subtropical open forest: paleoecology of the rhinocerotids from Ulm-Westtangente (Aquitanian, early Miocene, Germany)
Authors: Hullot Manon , Martin Céline , Blondel Cécile , Rößner Gertrud 
Published: September 2023

AbstractThe locality of Ulm-Westtangente yielded the richest vertebrate fauna from the Aquitanian of Germany. Its dating to the Mammal Neogene Zone 2a, a turnover in Cenozoic climate, makes it a crucial source for the understanding of faunal, palaeoecological and palaeoenvironmental specifics of the European Aquitanian. However, if most taxa from Ulm-Westtangente have been studied, very little to nothing has been done on the large herbivores and notably on the two rhinocerotidsMesaceratherium paulhiacenseandProtaceratherium minutum. Here, we used a multi-proxy approach to investigate the paleoecology of these two species. The remains of the smaller speciesP. minutum(442 to 667 kg) are twice as abundant as those of the largerM. paulhiacense(1687 to 2576 kg), but both display a similar age structure (∼ 10 % of juveniles, 20 % of subadults and 70 % of adults), mortality curves, and mild prevalence of hypoplasia (∼ 17 %). Results from dental mesowear, microwear, and carbon isotopes indicate different feeding preferences: both were C3 feeders butM. paulhiacensehad a more abrasive diet and was probably a mixed feeder. Our study on rhinocerotids also yielded new paleoenvironmental insights, such as the mean annual temperature (15.8 °C) and precipitation (317 mm/year) suggesting rather warm and dry conditions.Statements and DeclarationsThe authors have no relevant financial or non-financial interests to disclose. This study was funded by a post doctoral fellowship of the Alexander von Humboldt Foundation (Germany).
Association of homelessness and diet on the gut microbiome: A United States-Veteran Microbiome Project (US-VMP) study
Authors: Hoisington Andrew J. , Stearns-Yoder Kelly A. , Stamper Christopher E. , Holliday Ryan , Brostow Diana P. , Penzenik Molly E. , Forster Jeri E. , Postolache Teodor T. , Lowry Christopher A. , Brenner Lisa A. 
Published: September 2023

AbstractMilitary Veterans account for 8% of homeless individuals living in the United States. To highlight associations between history of homelessness and the gut microbiome, we compared the gut microbiome of Veterans who reported having a previous experience of homelessness to those from individuals who reported never having experienced a period of homelessness. Moreover, we examined the impact of the cumulative exposure of prior and current homelessness to understand possible associations between these experiences and the gut microbiome. Microbiome samples underwent genomic sequencing and were analyzed based on alpha diversity, beta diversity, and taxonomic differences. Additionally, demographic information, dietary data, and mental health history were collected. A lifetime history of homelessness was found to be associated with alcohol use disorder, substance use disorder, and healthy eating index compared to those without such a history. In terms of differences in gut microbiota, beta diversity was significantly different between Veterans that had experienced homelessness and Veterans that had never been homeless (p= 0.047, Weighted UniFrac), while alpha diversity was similar. The microbial community differences were, in part, driven by a lower relative abundance ofAkkermansiain Veterans that had experienced homelessness (mean ± SD; 1.07 ± 3.85) compared to Veterans that had never been homeless (2.02 ± 5.36) (p= 0.014, ancom-bc2). Additional research is required to facilitate understanding regarding complex associations between homelessness, the gut microbiome, and mental and physical health conditions, with a focus on increasing understanding regarding the longitudinal impact of housing instability throughout the lifespan.ImportanceAlthough there are known stressors related to homelessness, as well as chronic health conditions experienced by those without stable housing, there has been limited work evaluating the associations between microbial community composition and homelessness. We analyzed, for the first time, bacterial gut microbiome associations among those with experiences of homelessness on alpha diversity, beta diversity, and taxonomic differences. Additionally, we characterized the influences of diet, demographic characteristics, military service history and mental health conditions on the microbiome of Veterans with and without any lifetime history of homelessness. Future longitudinal research to evaluate the complex relationships between homelessness, the gut microbiome, and mental health outcomes is recommended. Ultimately, differences in the gut microbiome of individuals experiencing and not experiencing homelessness could assist in identification of treatment targets to improve health outcomes.
Cardiac disease diagnosis based on GAN in case of missing data
Authors: Chen Xing , Zhang Na , Yang Xiaohui , Wang Chunyan , Qi Na , Luan Tianyun , Zhu Wendi , Zhang Chenjie , Yang Chao 
Published: September 2023

AbstractIn daily life, two common algorithms are used for collecting medical disease data: data integration of medical institutions and questionnaires. However, these statistical methods require collecting data from the entire research area, which consumes a significant amount of manpower and material resources. Additionally, data integration is difficult and poses privacy protection challenges, resulting in a large number of missing data in the dataset. The presence of incomplete data significantly reduces the quality of the published data, hindering the timely analysis of data and the generation of reliable knowledge by epidemiologists, public health authorities, and researchers.Consequently, this affects the downstream tasks that rely on this data. To address the issue of discrete missing data in cardiac disease, this paper proposes the AGAN (Attribute Generative Adversarial Nets) architecture for missing data filling, based on generative adversarial networks. This algorithm takes advantage of the strong learning ability of generative adversarial networks. Given the ambiguous meaning of filling data in other network structures, the attribute matrix is designed to directly convert it into the corresponding data type, making the actual meaning of the filling data more evident. Furthermore, the distribution deviation between the generated data and the real data is integrated into the loss function of the generative adversarial networks, improving their training stability and ensuring consistency between the generated data and the real data distribution. This approach establishes the missing data filling mechanism based on the generative adversarial networks, which ensures the rationality of the data distribution while filling the missing data samples. The experimental results demonstrate that compared to other filling algorithms, the data matrix filled by the proposed algorithm in this paper has more evident practical significance, fewer errors, and higher accuracy in downstream classification prediction.
BAllC and BAllCools: Efficient Formatting and Operating for Single-Cell DNA Methylation Data
Authors: Tian Wei , Ding Wubin , Shen Jiawei , Li Daofeng , Wang Ting , Ecker Joseph R. 
Published: September 2023

AbstractMotivationWith single-cell DNA methylation studies yielding vast datasets, existing data formats struggle with the unique challenges of storage and efficient operations, highlighting a need for improved solutions.ResultsBAllC (Binary All Cytosines) emerges as a tailored binary format for methylation data, addressing these challenges. BAllCools, its complementary software toolkit, enhances parsing, indexing, and querying capabilities, promising superior operational speeds and reduced storage needs.Availabilityhttps://github.com/jksr/ballcoolsContactecker@salk.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Estimation of Genetic Admixture Proportions via Haplotypes
Authors: Ko Seyoon , Sobel Eric M. , Zhou Hua , Lange Kenneth 
Published: September 2023

AbstractEstimation of ethnic admixture is essential for creating personal genealogies, studying human history, and conducting genome-wide association studies (GWAS). Three methods exist for estimating admixture coefficients. The frequentist approach directly maximizes the binomial loglikelihood. The Bayesian approach adds a reasonable prior and samples the posterior distribution. Finally, the nonparametric approach decomposes the genotype matrix algebraically. Each approach scales successfully to data sets with a million individuals and a million single nucleotide polymorphisms (SNPs). Despite their variety, all current approaches assume independence between SNPs. To achieve independence requires performing LD (linkage disequilibrium) filtering before analysis. Unfortunately, this tactic loses valuable information and usually retains many SNPs still in LD. The present paper explores the option of explicitly incorporating haplotypes in ancestry estimation. Our program, HaploADMIXTURE, operates on adjacent SNP pairs and jointly estimates their haplotype frequencies along with admixture coefficients. This more complex strategy takes advantage of the rich information available in haplotypes and ultimately yields better admixture estimates and better clustering of real populations in curated data sets.
SurvBal: Compositional Microbiome Balances for Survival Outcomes
Authors: Li Ying , Lee Teresa , Marin Kai , Hua Xing , Srinivasan Sujatha , Fredricks David N. , Lee John R. , Ling Wodan 
Published: September 2023

AbstractIdentification of balances of bacterial taxa in relation to continuous and dichotomous outcomes is an increasingly frequent analytic objective in microbiome profiling experiments. SurvBal enables the selection of balances in relation to censored survival or time-to-event outcomes which are of considerable interest in many biomedical studies. The most commonly used survival models – the Cox proportional hazards and parametric survival models are included in the package, which are used in combination with step-wise selection procedures to identify the optimal associated balance of microbiome, i.e., the ratio of the geometric means of two groups of taxa’s relative abundances.Availability and implementationSurvBal is available as an R package and a Shiny app:https://github.com/yinglia/SurvBal,https://yinglistats.shinyapps.io/shinyapp-survbal/.
Copy number variation introduced by a massive mobile element underpins global thermal adaptation in a fungal wheat pathogen
Authors: Moser Tralamazza Sabina , Gluck-Thaler Emile , Feurtey Alice , Croll Daniel 
Published: September 2023

AbstractCopy number variation (CNV) can drive rapid evolution in changing environments. In microbial pathogens, such adaptation is a key factor underpinning epidemics and colonization of new niches. However, the genomic determinants of such adaptation remain poorly understood. Here, we systematically investigate CNVs in one of the largest to date genome sequencing dataset spanning a worldwide collection of 1109 genomes from the major wheat pathogenZymoseptoria tritici. We found overall strong purifying selection acting on most CNVs. Genomic defense mechanisms likely accelerated gene loss over episodes of continental colonization. Local adaptation along climatic gradients was facilitated by CNVs affecting secondary metabolite production and gene loss in general. One of the strongest candidates for climatic adaptation is a highly conserved gene of the NAD-dependent Sirtuin family. The Sirtuin CNV locus localizes to an ∼68-kbStarshipmobile element unique to the species carrying genes highly expressed during plant infection. The element has likely lost the ability to transpose, demonstrating how the ongoing domestication of cargo-carrying selfish elements can contribute to selectable variation within populations. Our work highlights how standing variation in gene copy numbers at the global scale is a major factor driving climatic and metabolic adaptation in microbial species.
Genome-wide characterization of MLO family genes in bread wheat and Arabidopsis thaliana shed light on their role in growth and development, and resistance to powdery mildew, biotic and abiotic stresses
Authors: Hussain Babar , Ramzan Hamza , Raza Qasim , Atif Rana Muhammad , Budak Hikmet , Ghazy Abdel-Halim I. 
Published: September 2023

AbstractPowdery mildew (PM), caused by the fungus, Blumeria graminis tritici is a devastating and notorious disease that is prevalent across the globe and causes up to 62% of yield losses in wheat. The well-known 68 PM resistance loci (Pm1 -Pm68) are not long-lasting and break down when new races of pathogens interact with host plants. The editing of three known MLO genes through CRISPR/Cas9 has conferred resistance against PM. However, only seven MLO genes were known in wheat to date. Taking advantage of IWGSC Ref-seq v2.1 and using the gold-standard analysis pipeline that we have designed, we expanded this number to 47 and reported 40 additional potential CRISPR targets that can be used to develop PM resistance, disease resistance, and abiotic stress tolerance in wheat. We also performed phylogenetic, gene structure, and MOTIF analysis that indicated conserved evolutionary patterns, and the phylogenetic pattern was strongly supported by gene structure and MOTIF analysis. The gene duplication and evolution analysis showed that segmental duplications were prevalent and purifying selection operated during evolution. Comparative phylogenetic analysis with Arabidopsis thaliana and Brachypodium distachyon depicted that clade IV was exclusive for monocots. Finally, MLOs are expressed under powdery mildew, rusts, head blight, abiotic stresses, growth, and development thus TraesMLOs have a potential role in wheat under these conditions. Therefore, we hope that the MLO genes identified in this study will be edited through CRISPR/Cas9 or will be overexpressed to develop PM and disease-resistant and abiotic stress-tolerant wheat. Additionally, we performed most of the above-mentioned analyses for Arabidopsis thaliana, revised its numbers as compared to the TAIR database, and updated it outdated analysis performed in 2003.
CircWaveNet: A New Conventional Neural Network Based on Combination of Circlets and Wavelets for Macular OCT Classification
Authors: Arian Roya , Vard Alireza , Kafieh Rahele , Plonka Gerlind , Rabbani Hossein 
Published: September 2023

AbstractComputer-aided systems can help the ophthalmologists in early detection of most of ocular abnormalities using retinal OCT images. The need for more accurate diagnosis increases the need for modifications and innovations to current algorithms. In this paper, we investigate the effect of different X-lets on the classification of OCT B-scans of a dataset with one normal class and two abnormal classes. Different transforms of each B-scan have been fed to the designed 2D-Convolutional-Neural-Network (2D-CNN) to extract the best-suited features. We compare the performance of them with MSVM and MLP classifiers. Comparison with the accuracy of normal and abnormal classes reveals substantially better results for normal cases using 2D-Discrete-Wavelet-Transform (2D-DWT), since the structure of most normal B-scans follows a pattern with zero-degree lines, while for abnormalities with circles appearing in the retinal structure (due to the accumulation of fluid), the circlet transform performs much better. Therefore, we combine these two X-lets and propose a new transform named CircWave which uses all sub-bands of both transformations in the form of a multi-channel-matrix, with the aim to increase the classification accuracy of normal and abnormal cases, simultaneously. We show that the classification results obtained based on CircWave transform outperform those based on the original images and each individual transform. Furthermore, the Grad-CAM class activation visualization for B-scans reconstructed from half of the CircWave sub-bands indicates a greater focus on appearing circles in abnormal cases and straight lines in normal cases at the same time, while for original B-scans the focus of the heat-map is on some irrelevant regions. To investigate the generalizability of our proposed method we have applied it also to another dataset. Using the CircWave transform, we have obtained an accuracy of 94.5% and 90% for the first and second dataset, respectively, while these values were 88% and 83% using the original images. The proposed CNN based on CircWave provides not only superior evaluation parameter values but also better interpretable results with more focus on features that are important for ophthalmologists.
Comparisons of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9I) versus Ezetimibe on Major Adverse Cardiovascular Events Amongst Patients with Dyslipidaemia: A Population-Based Study
Authors: Chou Oscar Hou In , Li Lifang , Chung Cheuk To Skylar , Lu Lei , Lee Quinncy , Pui Hugo Hok Him , Leung Bosco Kwok Hei , Chang Carlin , Liu Tong , Wai Abraham Ka Chung , Lip Gregory , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong 
Published: September 2023

AbstractBackgroundProprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9I) have potential benefits against cardiovascular disease. The comparative risks of new-onset major adverse cardiovascular events (MACE) between PCSK9I and ezetimibe remain unknown.ObjectiveThis real-world study compared the risks of MACE upon exposure to PCSK9I and ezetimibe.MethodsThis was a retrospective population-based cohort study of patients with dyslipidaemia on either PCSK9I or ezetimibe between 1stJanuary 2015 and 30thOctober 2022 using a territory-wide database from Hong Kong. The primary outcome was new-onset MACE. The secondary outcomes were myocardial infarction, heart failure, stroke/transient ischaemic attack, and all-cause mortality. Propensity score matching (1:3 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations.ResultsThis cohort included 42450 dyslipidaemia patients (median age: 65.0 years old [SD: 11.1]; 64.54 % males). The PCSK9I and ezetimibe groups consisted of 1477 and 40973 patients, respectively. After matching, 67 and 235 patients suffered from MACE in the PCSK9I and ezetimibe groups, respectively, over a total of 14514.5 person-years. PCSK9I was associated with lower risks of MACE (Hazard ratio [HR]: 0.59; 95% Confidence Interval [CI]: 0.37-0.92) compared to ezetimibe use after adjusting for demographics, past comorbidities, other medications, and time-weighted means of lipid and glucose tests. Besides, while both alirocumab and evolocumab were associated with lower risks of MACE, evolocumab was associated with significantly lower risks of myocardial infarction, heart failure, and stroke/transient ischaemic attack. The results remained consistent in the competing risk and sensitivity analyses.ConclusionsPCSK9I use amongst dyslipidaemia patients was associated with lower risks of new-onset MACE and outcomes compared to ezetimibe after adjustments. Evolocumab might perform better than Alirocumab in reducing the risks of cardiovascular diseases.Illustrated Abstract