bluuebunny/crossref_metadata_2025_split huggingface dataset:
Costs of dispersal evolution under larval malnutrition
Authors: Vibishan B. , Malwade Akshay , Koner Anish , Khodake Vinayak , Dey Sutirth 
Published: November 2024

AbstractDispersal is a key eco-evolutionary process, and the causes and consequences of its evolution have been well-studied. However, although dispersal depends critically on the nutritional status of organisms, it is unclear how malnutrition affects the evolution of life history and the behavior of organisms under selection for increased dispersal. To address this issue, we used four replicate laboratory populations ofDrosophila melanogasterpreviously selected for increased dispersal for 66-67 generations on a protein-poor larval diet. Compared to the unselected controls, the selected populations had lower female body weight, fecundity, male desiccation resistance and mating propensity, but greater male locomotor activity and mating latency. There were no significant differences in aggression. We also compared our results qualitatively with those from a previous study on dispersal selection under a standard larval diet. Barring desiccation resistance, locomotor activity, and rest duration, all other traits investigated responded differently to dispersal selection between the poor and the standard larval nutritional regimes. These results show that the evolution of traits associated with dispersal can differ markedly depending on the nutrition available for the dispersing populations.
Interrelations of Serum Uric Acid, Beta-Cell Function, and Insulin Resistance in Indian Cohort: A Comprehensive Analysis
Authors: Thummala Sabitha , Kruthi Nithya , Fatima Sarah , Ghori Junaid Ahmed Khan , Saikia Katherine , Balamurali AR , Ranganathan Rahul 
Published: November 2024

AbstractBackgroundHyperuricemia, characterised by elevated levels of serum uric acid (SUA), has been linked to an increased risk of metabolic disorders, including type 2 diabetes. Understanding the relationship between SUA, beta-cell function, and insulin resistance is crucial for elucidating the pathophysiology of these conditions, especially in the Indian population, where such data is limited.ObjectiveThis study aimed to explore the interrelations between serum uric acid levels, beta-cell function, and insulin resistance in an Indian cohort.MethodsA cross-sectional study was conducted involving a representative sample of adults from an Indian population. Participants were stratified into sex-specific SUA quartiles. Key measurements included BMI, serum creatinine, lipid profiles, fasting insulin, HOMA1-B (beta-cell function), and HOMA1-IR (insulin resistance). Partial correlation coefficients were calculated to assess the associations between SUA and various metabolic parameters.ResultsSignificant differences were observed across SUA quartiles in terms of age, BMI, serum creatinine, HDL cholesterol, LDL cholesterol, triglycerides, total cholesterol, fasting insulin, HOMA1-B, and HOMA1-IR (all p-values < 0.05). Higher SUA levels were associated with increased BMI, serum creatinine, triglycerides, fasting insulin, HOMA1-B, and HOMA1-IR. Additionally, partial correlation analysis revealed positive correlations between SUA and BMI (r=0.065, p=0.026), fat mass (r=0.065, p=0.026), serum creatinine (r=0.277, p<0.001), triglycerides (r=0.084, p=0.004), fasting insulin (r=0.130, p<0.001), and HOMA1-B (r=0.078, p=0.008). Negative correlations were found between SUA and vitamin B12 (r=-0.117, p=0.000071), GFR (r=-0.113, p<0.001), total cholesterol (r=-0.068, p=0.021), LDL cholesterol (r=-0.080, p=0.006), HDL cholesterol (r=-0.071, p=0.016), and HbA1c (r=-0.170, p<0.001).ConclusionsElevated serum uric acid levels are significantly associated with increased beta-cell function and insulin resistance among Indian adults. These findings suggest that hyperuricemia could be an early marker for metabolic dysfunction, highlighting the need for early intervention strategies in this population. Further longitudinal studies are warranted to establish causal relationships and to explore the potential benefits of uric acid-lowering therapies in preventing metabolic diseases.Trial registrationNot applicable.
Publicly available continuously updated topic specific databases of randomised clinical trials: A scoping review
Authors: Boesen Kim , Hemkens Lars G , Janiaud Perrine , Hirt Julian 
Published: November 2024

AbstractConducting systematic reviews of clinical trials is arduous and resource consuming. One potential solution is to design databases that are continuously and automatically populated with clinical trial data from harmonised and structured datasets. We aimed to map publicly available, continuously updated, topic-specific databases of randomised clinical trials (RCTs). We systematically searched PubMed, Embase, the preprint servers medRxiv, ArXiv, and Open Science Framework, and Google. We described seven features (access model, database architecture, data input sources, retrieval methods, data extraction methods, trial presentation, and export options) and narratively summarised the results. We did not register a protocol for this review. We identified 14 continuously updated clinical trial databases, seven related to COVID-19 (first active in 2020) and seven non-COVID databases (first active in 2009). All databases, except one, were publicly funded and accessible without restrictions. They mainly employed methods similar to those from static article-based systematic reviews and retrieved data from journal publications and trial registries. The COVID-19 databases and some non-COVID databases implemented semi-automated features of data import, which combined automated and manual data curation, whereas the non-COVID databases mainly relied on manual workflows. Most reported information was metadata, such as author names, years of publication, and link to publication or trial registry. Two databases included trial appraisal information (risk of bias assessments). Six databases reported aggregate group level results, but only one database provided individual participant data on request. We identified few continuously updated trial databases, and existing initiatives mainly employ methods known from static article -based reviews. The main limitation to create truly live evidence synthesis is the access and import of machine-readable and harmonised clinical trial data.
Fractionated Potential-Guided Cryoablation Targeting Termination of Atrioventricular Nodal Reentrant Tachycardia While Avoiding the Compact Node Electrogram
Authors: Hirata Shu , Nagashima Koichi , Watanabe Ryuta , Wakamatsu Yuji , Hirata Moyuru , Kurokawa Sayaka , Otsuka Naoto , Sawada Masanaru , Okumura Yasuo 
Published: November 2024

AbstractBackgroundFractionated potential (FP) ablation during atrioventricular nodal reentrant tachycardia (AVNRT), is an effective strategy that minimizes redundant radiofrequency (RF) applications. This study aimed to evaluate the utility of cryoablation targeting FPs to effectively terminate AVNRT while further minimizing redundant cryoapplications. Moreover, we observed what appeared to be compact AVN (cAVN) or proximal His potentials—tiny, dull potentials (TDPs) with continuity to the His potential during sinus rhythm (SR) and AVNRT—in the anteroseptal area. The second aim of this study was to explore the significance of those potentials.MethodsAnalyzed were 53 slow-fast AVNRT patients who underwent ablation procedures. Ultra-high resolution activation maps in the triangle of Koch were obtained during SR (n=34) and AVNRT (n=46). TDPs during SR and AVNRT in the anteroseptal area were identified and annotated using the LUMIPOINT Activation Search tool.ResultsFP areas were observed in 19 patients (56%) during SR and in 46 (100%) during AVNRT. This area corresponded to the AVNRT termination and/or successful ablation site in all, with peak numbers of 8.8±1.4 during AVNRT and 5.3±1.3 during SR. The number of ablation points was 3.6±1.5 for the FP-guided cryoablation (n=32) (Bonferroni corrected P<0.05 vs. anatomical RF; and P<0.05 vs. FP-guided RF), 5.4±2.1 for the FP-guided RF ablation (n=11) (P=0.0825 vs. anatomical RF), and 8.2±3.2 for the conventional RF ablation (n=10). Transient AV block occurred in 11 patients (21%). All AV block sites overlapped with the TDP area in the phase just before the His potential during AVNRT and SR, with a confidence setting of ≥24% (35[24-60]%). Conversely, in 42 patients without AV block, no ablation was performed in this area.ConclusionThe FP-guided cryoablation strategy targeting AVNRT termination required fewer cryoapplications than RF ablation. The RF/cryo application in the TDP area during SR and AVNRT posed a risk of AV block.
Changes in monocyte subsets can predict the risk of AAA and are surrogate markers for AAA morphology in patients with late-stage disease
Authors: Hamann Bianca , Klimova Anna , Kapalla Marvin , Poitz David M. , Frank Frieda , Morawietz Henning , Reeps Christian , Hofmann Anja 
Published: November 2024

AbstractBackgroundMonocytes play a pivotal role in pathology of abdominal aortic aneurysm (AAA) and can display an immunophenotypic heterogeneity with functionally distinct subpopulations. Alterations in monocyte subsets have been described in CVD, and some are associated with cardiovascular risk, but their profile in AAA is poorly understood.AimWe aimed to comprehensively define associations of circulating monocyte phenotypes with AAA risk and AAA morphology.MethodsMonocyte subsets (CD14++CD16−; CD14++/CD16+; CD14+/CD16++) were analyzed in a prospective, observational study in patients with AAA (n=34) and varicose veins (n=34) by using flow cytometry.ResultsClassical monocytes were 1.6-fold lower (P=0.001) in AAA, while intermediate and non-classical monocytes were 1.8 (P=0.019) and 1.9-fold (P=0.025) higher in AAA, respectively. The differences remained significant after adjusting for age, sex and peripheral artery disease. A lower proportion of classical monocytes (HR: 0.73,P=0.002) and increases in intermediate (HR: 1.41,P=0.006) and non-classical monocytes (HR: 1.54,P=0.030) were associated with a higher risk of AAA. Non-classical monocytes showed an inverse correlation with AAA diameter (Pearson correlation =-0.64,P=0.001) and AAA volume (Pearson correlation =-0.50,P=0.003).ConclusionThe present study revealed age- and sex-independent shifts in monocytes, all of which were associated with risk of AAA disease. Non-classical monocytes were inversely correlated with AAA diameter and volume and thus may be surrogate markers for AAA morphology.What’s new?Classical monocytes are lower in patients with late-stage AAA.Non-classical monocytes showed the strongest increase in AAA disease.A reduction in classical monocytes is associated with increased risk of AAA.An increase in non-classical and intermediate monocytes is associated with an increased risk of AAA.Lowering in non-classical monocytes may be a surrogate marker for AAA morphology, particlarly AAA volume.Intermediate monocytes showed a positive correlation with the thickness of the intraluminal thrombus.What are the clinical implications?The increase in non-classical monocytes could be a novel surrogate marker for AAA volume, which could be useful when AAA diameter is insufficient or to monitor a saccular AAA, as there is a weaker correlation between diameter and risk of rupture in this type of AAA.The decrease in classical monocytes could be a useful surrogate marker for AAA volume and provide additional information on AAA diameter.Monocyte shifts and their association with AAA disease may be relevant for the diagnosis of AAA and should be verified in larger cohorts.The mechanisms behind the decrease in classical monocytes and the increase in intermediate and non-classical subsets should be investigated in furtherin vitrostudies as they offer therapeutic potential.Graphical Abstract
Decreased SNCA Expression in Whole-Blood RNA Analysis of Parkinson’s Disease Adjusting for Lymphocytes
Authors: Xu Kayla , Violich Ivo , Hutchins Elizabeth , Alsop Eric , Nalls Mike A. , Blauwendraat Cornelis , Gibbs J. Raphael , Cookson Mark R. , Moore Anni , Van Keuren-Jensen Kendall , Craig David W. 
Published: November 2024

AbstractBlood-based RNA transcriptomics offers a promising avenue for identifying biomarkers of Parkinson’s Disease (PD) progression and may provide mechanistic insights into the systemic biological processes underlying its pathogenesis beyond the well-defined neurodegenerative features. Previous studies have indicated an age-dependent increase in neutrophil-enriched gene expression, alongside a reduction in lymphocyte counts, in individuals with PD. These immune cell changes can obscure disease-relevant transcriptomic signals. In this study, we performed differential expression (DE) analysis of whole-blood RNA sequencing data from PD cohorts, incorporating a correction for immune cell-enriched gene expression, particularly neutrophil-related pathways, to improve the resolution of PD-associated molecular changes. Using 1,254 Parkinson’s Progression Markers Initiative (PPMI) samples with complete blood count (CBC) data, we developed a predictive model to estimate neutrophil percentages in a 6,987 PPMI and Parkinson’s Disease Biomarkers Program (PDBP) samples. We mitigated the confounding effects of immune cell-enriched gene expression by integrating predicted neutrophil percentages as a covariate in DE analysis. This approach revealed a consistent and significant downregulation of SNCA across all PD cohorts, a finding previously obscured by immune cell signatures. Lowered SNCA expression was found in individuals with known predisposition genes (e.g., SNCA, GBA, LRRK2) and in non-genetic PD cohorts lacking known pathogenic mutations, suggesting it may represent a key transcriptomic hallmark of the disease.
A quantitative approach to poxvirus infection reveals general correlates of antigen presentation and immunogenicity for viral CD8+T cell epitopes
Authors: Witney Matthew J , Croft Nathan P , Wong Yik Chun , Smith Stewart A , Flesch Inge EA , Keller Erica , La Gruta Nicole L , Purcell Anthony W , Tscharke David C. 
Published: November 2024

AbstractCD8+T cells are essential effectors in antiviral immunity that kill infected cells displaying viral peptide epitopes on MHC class I. The pathways underpinning antigen presentation on MHC I are well known but we lack a general understanding of the quantitative and kinetic relationships between source proteins and presented epitopes, and how these relate to immunogenicity. We used quantitative mass spectrometry to interrogate infection with vaccinia virus, the MPOX vaccine, measuring amounts of >40 viral epitopes and their source proteins multiple times after infection in four cell types. This revealed that up to 90% of the epitopes were presented as fast as their source proteins were made and that protein amounts failed to correlate with epitope levels. Further, a significant correlation between epitope levels and immunogenicity required presentation to be quantifiedex vivo, with each step away from a matched infection route and natural presenting cell eroding the association.
Mapping the Impact ofDUSP6in an ADHD iPSC derived-dopaminergic neuronal model
Authors: Namipashaki Atefeh , Hellyer Shane D. , Arnatkeviciute Aurina , Walsh Kevin , Nowell Cameron J , Polo Jose M. , Gregory Karen J , Bellgrove Mark A. , Hawi Ziarih 
Published: November 2024

AbstractAlthough the geneDUSP6has been implicated as a risk gene for ADHD in recent GWAS studies, its functional role in the aetiology of the condition remains poorly understood.DUSP6is reported to regulate dopaminergic neurotransmission by decreasing available synaptic dopamine, suggesting a potential mechanism by whichDUSP6may confer risk to ADHD. In this study, we employed CRISPR-Cas9 to knockoutDUSP6in induced pluripotent stem cells (iPSCs) derived from an individual with ADHD. These isogenic engineered cells were then differentiated into highly homogeneous dopaminergic neurons, including both heterozygous (Het) and homozygous (Hom) knockout lines, along with parental control lines, to assess changes in dopaminergic neurotransmission at both cellular and transcriptomic levels. Enzyme Linked Immunosorbent Assay (ELISA) analyses showed a dose-dependent trend of increasing dopamine levels, at extracellular level, in the knockout lines. RNA sequencing further supported this finding, showing that downregulation ofDUSP6lead to the upregulation of differentially expressed genes (DEGs) associated with the regulation of dopamine secretion and synaptic functions critical for dopamine signalling. These DEGs appear to encode components of the synaptic machinery essential for effective dopamine transmission or act as regulators of dopaminergic neurotransmission. Additionally, RNA sequencing uncovered other potential biological mechanisms through whichDUSP6may contribute to increase the risk for ADHD, including effects on neurogenesis, extracellular matrix-associated processes, lipid metabolism, and sex-specific gene expression. Furthermore, we identified overlaps betweenDUSP6knockout DEGs and those associated with other neuropsychiatric disorders, including major depression (MDD), bipolar disorder (BD), and schizophrenia (SCZ), suggesting shared genetic pathways potentially influenced byDUSP6. Together, this study provides deeper insights into the molecular underpinnings of the role played byDUSP6in the genetic aetiology of ADHD and its broader implications across related neuropsychiatric conditions.
Lrif1 modulates Trim28-mediated repression of theDuxlocus in mouse embryonic stem cells
Authors: Šikrová Darina , González-Prieto Román , Vertegaal Alfred C. O. , Balog Judit , Clemens-Daxinger Lucia , van der Maarel Silvère M. 
Published: November 2024

SUMMARYGermline mutations in SMCHD1, DNMT3B and LRIF1 can cause facioscapulohumeral muscular dystrophy type 2 (FSHD2). FSHD is an epigenetic skeletal muscle disorder in which partial failure in heterochromatinization of the D4Z4 macrosatellite repeat causes spurious expression of the repeat-embeddedDUX4gene in skeletal muscle, ultimately leading to muscle weakness and wasting. All three proteins play a role in chromatin organization and gene silencing; however, their functional relationship has not been fully elucidated. Here, we show that knockdown ofLrif1, but not of the other two FSHD2 genes, in mouse embryonic stem cells leads to modest upregulation of the 2-cell cleavage stage transcriptional program driven by the transcription factor Dux, which is the mouse functional homologue of human DUX4. Furthermore, we show that Lrif1 interacts with Trim28, a known Dux repressor and that this interaction is independent of Cbx proteins and Smchd1. We uncover that modestDuxupregulation inLrif1knockdown mESCs coincides with decreased Trim28 occupancy at theDuxlocus. Together, our results provide evidence for a conserved function of Lrif1 in repressing an early zygotic genome activator in mice and humans.
The infant brain rapidly entrains to visual statistical regularities during stimulus exposure
Authors: Capparini Chiara , Fourdin Lauréline , Wens Vincent , Dontaine Pauline , Aeby Alec , Bertels Julie 
Published: November 2024

AbstractStatistical learning (SL) has been studied quite extensively in infancy. Still, most evidence relies on post-exposure behavioural tasks whose directionality (familiarity vs. novel effects) may not be straightforward to predict nor to interpret. In addition, these tasks do not tell anything about the online learning dynamics and may be influenced by memory effects. In this work, we investigated online SL mechanisms by tracking neural entrainment to visual regularities in a group of 4- to 6-month-old infants exposed to a stream of shapes presented at 6 Hz. Shapes were either organized in doublets or presented randomly. Results revealed neural entrainment at the base frequency of 6 Hz and harmonics did not differ across conditions, confirming that infants attended to the stimuli similarly across conditions. On the other hand, entrainment at the doublet frequency of 3 Hz and harmonics varied across conditions and trials. Infants showed greater occipital entrainment to the doublet frequency in the deterministic condition than in the random one, especially over the first trials of exposure. This suggests that the brain can detect visual regularities from early infancy. Further, this sensitivity emerged early over the exposure period and did not show a learning curve. Hence, considering its time course and the brain regions involved, neural entrainment at the doublet frequency seems to reflect a bottom-up detection mechanism rather than a learning process. These findings are crucial to better understand how infants extract regularities during stimulus exposure and what neural entrainment can reveal in a visual SL task.
Reference-free Analysis of scRNA-seq Data Reveals Elevated rRNA and mtRNA Transcription during Neurogenesis in Axolotl
Authors: Zahan Ratul Md. Rownok , Karim Md. Redwanul , Hasan Samee Md. Abul , Rahman Atif 
Published: November 2024

AbstractAnalysis of single-cell RNA-seq data is typically performed on a gene expression matrix estimated by aligning reads to a reference transcriptome. However, this approach is difficult to apply to organisms with no or incomplete reference transcriptomes. In addition, events deviating from the reference remain undetected. Here we present a reference-free method to analyze single-cell RNA-seq data based onk-mers. We assess the performance of our method on a metastatic renal cell carcinoma dataset and find that it is largely able to capture differentially expressed genes. We then analyze a recently generated dataset to study neurogenesis in Axolotl and observe increased levels of transcription of rRNA and mtRNA during neurogenesis as well as a miRNA with previously predicted links to neuronal development. We also detect lncRNAs and intron retention in heart disease-related genes in diseased cardiomyocytes in an analysis of a congenital heart disease dataset.
Biofilm lifestyle as a common trait of ammonia-oxidizing archaea
Authors: Dreer Maximilian , Pribasnig Thomas , Hodgskiss Logan H. , Luo Zhen-Hao , Pozaric Fran , Schleper Christa 
Published: November 2024

AbstractAlthough widespread in nature, growth in biofilms has been relatively little explored in the globally distributed ammonia oxidizing archaea (AOA). Here we investigated six representatives of three different terrestrial and marine clades of AOA in a longitudinal and quantitative study for their ability to form biofilm and studied gene expression patterns of three representatives. While all strains grew on a solid surface, soil strains exhibited the highest capacity for biofilm formation. Based on microscopic and gene expression data, two different colonization strategies could be distinguished. S-layer containing AOA (from both soil and marine habitats) initialized attachment as single cells and subsequently formed denser layers and three-dimensional structures, while the S-layer free species of theNitrosocosmicusclade attached as suspended aggregates to the surface and henceforth showed fastest establishment of biofilm. Transcription profiles were significantly different between planktonic and biofilm growth in all strains and revealed individual reactions, often fulfilling shared functions. In particular the strong expression of different types of multicopper oxidases was observed in all strains indicating modifications of their cell coats. S-layer carrying AOA each additionally expressed a set of adhesion proteins supporting attachment. Detoxification of nitrous compounds, copper acquisition as well as the expression of transcription factor B were also shared reactions among biofilm producing strains. However, the majority of differentially expressed protein families was distinct among the three strains illustrating that individual solutions have evolved for the shared growth mode of biofilm formation in AOA, probably driven by the different ecological niches.