bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity of Rabies Virus G-Protein mRNA Formulated with Muscle Targeting Lipid Nanoparticles in Mice
Authors: Li Qin , Bai Huarong , Yu Xueliang , Liu Qiang , Hu Rongkuan 
Published: January 2025

AbstractRabies is a preventable zoonotic disease caused by the rabies virus (RABV) with a high mortality rate. Most vaccines on the market or under development have issues such as a low single-dose neutralization titer, complex processes, and high costs. During the COVID-19 pandemic, the successful development of mRNA vaccines has opened up a new avenue for preventive vaccines. As a new technology, mRNA has higher scalability. In this study, we designed an mRNA encoding the RV-G protein, encapsulated by our own muscle targeting lipid nanoparticles (LNP), and evaluated the expression of the RV-G protein in vitro, its immunogenicity, and its protection against virus infection in vivo. The results showed that RV-G mRNA was significantly expressed in vitro. High Virus-IgG binding titers and Virus-neutralizing antibody titers (VNT) were induced by immunization with RV-G mRNA-LNP. Additionally, our results show that the RV-G mRNA vaccine is better than commercially available vaccines in mice.
Deep Learning for Biomarker Discovery in Cancer Genomes
Authors: Unger Michaela , Loeffler Chiara M. L. , Žigutytė Laura , Sainath Srividhya , Lenz Tim , Vibert Julien , Mock Andreas , Fröhling Stefan , Graham Trevor A. , Carrero Zunamys I. , Kather Jakob Nikolas 
Published: January 2025

AbstractBackgroundGenomic data is essential for clinical decision-making in precision oncology. Bioinformatic algorithms are widely used to analyze next-generation sequencing (NGS) data, but they face two major challenges. First, these pipelines are highly complex, involving multiple steps and the integration of various tools. Second, they generate features that are human-interpretable but often result in information loss by focusing only on predefined genetic properties. This limitation restricts the full potential of NGS data in biomarker extraction and slows the discovery of new biomarkers in precision oncology.MethodsWe propose an end-to-end deep learning (DL) approach for analyzing NGS data. Specifically, we developed a multiple instance learning DL framework that integrates somatic mutation sequences to predict two compound biomarkers: microsatellite instability (MSI) and homologous recombination deficiency (HRD). To achieve this, we utilized data from 3,184 cancer patients obtained from two public databases: The Cancer Genome Atlas (TCGA) and the Clinical Proteome Tumor Analysis Consortium (CPTAC).ResultsOur proposed deep learning method demonstrated high accuracy in identifying clinically relevant biomarkers. For predicting MSI status, the model achieved an accuracy of 0.98, a sensitivity of 0.95, and a specificity of 1.00 on an external validation cohort. For predicting HRD status, the model achieved an accuracy of 0.80, a sensitivity of 0.75, and a specificity of 0.86. Furthermore, the deep learning approach significantly outperformed traditional machine learning methods in both tasks (MSI accuracy, p-value = 5.11×10−18; HRD accuracy, p-value = 1.07×10−10). Using explainability techniques, we demonstrated that the model’s predictions are based on biologically meaningful features, aligning with key DNA damage repair mutation signatures.ConclusionWe demonstrate that deep learning can identify patterns in unfiltered somatic mutations without the need for manual feature extraction. This approach enhances the detection of actionable targets and paves the way for developing NGS-based biomarkers using minimally processed data.
EASYstrata: a new workflow to infer evolutionary strata along sex chromosomes and other supergenes
Authors: Rougemont Quentin , Lucotte Elise , Boyer Loreleï , Jalaber Alexandra , Snirc Alodie , Giraud Tatiana , Rodríguez de la Vega Ricardo C. 
Published: January 2025

AbstractNew reference genomes and transcriptomes are becoming increasingly available across the whole tree of life, opening new avenues to tackle exciting evolutionary questions. However, there are still challenges associated with annotating genomes, aligning sequences, inferring evolutionary processes and a lack of methodological standardisation. Here, we propose a new workflow designed for evolutionary analyses to overcome these challenges, facilitating the detection of recombination suppression and its consequences in terms of rearrangements and transposable element accumulation. To do so, we assemble multiple bioinformatic steps in a single, reproducible and easy-to-use workflow. We combine state-of-the-art tools to quickly detect transposable elements, annotate newly assembled genomes, infer gene orthology relationships, compute divergence between sequences, infer evolutionary strata (i.e. stepwise extension of recombination suppression) and their structural rearrangements, and visualise the results at different steps in the process. This workflow was called EASYstrata and was applied to reannotate a set of 42 published genomes fromMicrobotryumfungi. We show in case examples that we recover the same strata as previously described. While this tool was mostly developed with the goal to infer divergence between sex or mating-type chromosomes, it can be applied to any pair of haplotypes whose pattern of divergence might be of interest, e.g. supergenes in autosomes. This workflow will facilitate the study of the numerous non-model species for which newly sequenced phased diploid genomes are becoming available.
Behavioral and neural sound classification: Insights from natural and synthetic sounds
Authors: Ogg Mattson 
Published: January 2025

ABSTRACTThroughout the course of a day, human listeners encounter an immense variety of sounds in their environment. These are quickly transformed into mental representations of objects and events that guide subsequent cognition and behavior in the world. Previous studies using behavioral and temporally resolved neuroimaging methods have demonstrated the importance of certain acoustic qualities for distinguishing among different classes of sounds during the early time period following sound onset (noisiness, spectral envelope, spectrotemporal change over time, and change in fundamental frequency over time). However, this evidence is largely based on correlational studies of natural sounds. Thus, two additional behavioral (Experiment 1) and EEG (Experiment 2) studies further tested these results using a set of synthesized stimuli (interspersed among a new set of natural sounds) that explicitly manipulated previously identified acoustic dimensions. In addition to finding similar correlational results as previous work (using new natural stimuli and tasks), classification results for the synthesized acoustic feature manipulations reinforced the importance of aperiodicity, spectral envelope, spectral variability and fundamental frequency change for representations of superordinate sound-categories. Analyses of the synthesized stimuli suggest that aperiodicity is a particularly robust cue in distinguishing some categories and that speech is difficult to characterize within this framework (i.e., using these acoustic dimensions and synthetic feature manipulations). These results provide a deeper understanding of the neural and perceptual dynamics that support the recognition of behaviorally important categories of sound in the time windows soon after sound onset.
Hybrid supramolecular-covalent bioresin promotes cell migration and self-assembly in light-based volumetric bioprinted constructs
Authors: Falandt Marc , Bernal Paulina Nunez , Longoni Alessia , Buchholz Maj-Britt , Quilis Pere Català , Widmann Klement , Barrera-Roman Mario , Malda Jos , Vermonden Tina , Rios Anne , Levato Riccardo 
Published: January 2025

AbstractThere is an increasing need for novel biomaterials compatible with advanced biofabrication technologies, which also permit cells to remodel their microenvironment. This remodelling is crucial for maturing tissue constructs into fully functional tissue replacements. Recent progress in supramolecular chemistries has allowed for the production of dynamic biomaterials. Their properties enable bonds to be reversibly broken by cells, facilitating processes requiring morphological changes or migration, crucial for tissue development and homeostasis. Here, we present a one-of-its-kind gelatin-based hybrid covalent/supramolecular biomaterial. We demonstrate the advantage of adding supramolecular-reactive moieties on covalent materials, over covalent bonds alone, in facilitating processes such as cell growth, migration, spreading and organoid proliferation. This is exemplified by enhanced MSC and T cell migration and improved vascular network formation in hybrid hydrogels over covalent-only materials. The combination of supramolecular and covalent bonds further enabled control over photocrosslinking, allowing the use of the material in volumetric bioprinting of complex structures with high shape fidelity. As a proof-of-concept we bioprinted complex breast-like structures from encapsulated normal breast cell lines with a tumor organoid core. We demonstrated that engineered T cells can migrate large distances into the breast tissue, specifically targeting tumor cells.Graphical abstract
Eye metrics are a marker of visual conscious awareness and neural processing in cerebral blindness
Authors: Kronemer Sharif I. , Gobo Victoria E. , Japee Shruti , Merriam Eli , Osborne Benjamin , Bandettini Peter A. , Liu Tina 
Published: January 2025

AbstractDamage to the primary visual pathway can cause vision loss. Some cerebrally blind people retain degraded vision or sensations and can perform visually guided behaviors. These cases motivate investigation and debate on blind field conscious awareness and linked residual neural processing. A key challenge in this research is that subjective measures of blind field visual conscious awareness can be misleading. Alternatively, eye metrics, including pupil size and eye movements are promising objective markers of conscious awareness and brain activity. In this study, we examined stimulus-evoked changes in pupil size, blinking, and microsaccades in the sighted and blind field of cerebrally blind participants. Using standard analysis and innovative machine learning methods, our findings support that eye metrics can infer blind field conscious awareness, even when behavioral performance on a visual perception task indicated otherwise. Furthermore, these eye metrics were linked to blind field visual stimulus-evoked occipital cortical field potentials. These findings support recording eye metrics in cerebral blindness and highlight potential clinical applications, including tracking the recovery of conscious vision and visual neural processing.
Modelling forest dynamics using integral projection models (IPMs) and repeat LiDAR
Authors: Rosen Alice , Battison Robin , Hernández Christina M. , Spacey Oliver , McLean Jessie , Prober Suzanne , Gascoigne Samuel , McMahon Sean , Jucker Tommaso , Salguero-Gómez Roberto 
Published: January 2025

ABSTRACTEstimating the life histories and population dynamics of trees is important for predicting how forests respond to climate change and disturbances. To do so, ecologist often use stage-structured population models, which explicitly account for individual heterogeneity. However, the data needed to parameterise these models is typically constrained by time- and labour-intensive field methods.Despite growing access to remote sensing imagery that could potentially ‘satiate’ these data-hungry population models, these data remain underutilised in population ecology. Here, we demonstrate a pipeline that integrates repeat-LiDAR data with a type of structured demographic model (Integral Projection Model, IPM) to examine forest-wide dynamics in response to environmental drivers. Using Australia’s Great Western Woodlands as a case study, we model the survival and growth of ∼40,000 eucalypt trees over a decade to estimate their life expectancy and characterise multiple stages of growth (height growth and crown expansion).Our results indicate distinct responses of small trees (where vital rates are predicted by height) and large trees (which invested predominantly in expanding crown area) to proxies for competition and soil moisture (local canopy density and topographic wetness index, respectively). Parameterising structured population models using LiDAR data therefore offers a step-change in perspective towards more ecologically meaningful forest dynamics.To broaden the application of this pipeline, we highlight three priorities: (1) Application to more complex systems such as mixed species stands and dense, multilayered canopies); (2) Incorporating complete life histories, including reproduction and early life stages; and (3) Using in long-term or comparative studies through improved availability of high-quality, comparable, repeat-LiDAR surveys. By combining remote sensing data with detailed insights from field- based studies, this pipeline represents a scalable framework for guiding forest management and conservation decisions.
Regulatory Analysis of Root Architectural and Anatomical Adaptation to Nitrate and Ammonium inBrachypodium distachyon
Authors: Rouina Hamid , Singh Dilkaran , Arlt Christopher , Malekian Babak , Schreiber Lukas , Stich Benjamin , Marshall-Colon Amy 
Published: January 2025

AbstractRoot system architecture plays an important role in nitrate and ammonium uptake, the two primary nitrogen (N) forms essential for plant growth. Plants deploy different strategies to optimize the N uptake by roots, based on a complicated regulatory network that controls root phenotype and physiology. Here, we studied the response of root architecture to varying N applications in the model speciesBrachypodium distachyon. Using a combination of phenotypic and transcriptomic analyses, we examined how different forms and concentrations of ammonium and nitrate affect root growth, biomass allocation, and N uptake. N concentrations significantly influence root traits such as root length, root hair development, and aerenchyma formation in response to nitrate and ammonium. Plants grown in ammonium conditions had thin but highly branched roots, whereas nitrate application resulted in shorter, thicker roots with denser root hair at higher nitrate concentrations. Furthermore, using advanced co-expression network analysis, we identified an Atypical Aspartic Protease (APs) gene encoding an aspartyl protease family protein and a phosphoenolpyruvate carboxylase 1 (PEPC1) gene in brachypodium, which potentially control the root architectural and anatomical adaptions to different N form. APs expression showed a positive correlation with total root length and lateral root development, along with a negative correlation with root hair density. In contrast, PEPC1 exhibited positive correlations with cortex, stele, root cross-sectional areas, and root hair density, while showing a negative correlation with total root length. These genes likely play an important role in the transcriptional regulatory networks involved in these adaptive responses, which highlight the complex interplay between root morphology, nitrogen metabolism, and environmental nutrient conditions.
Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity
Authors: Danzi Matt C. , Xu Isaac R. L. , Fazal Sarah , Dolzhenko Egor , Pellerin David , Weisburd Ben , Reuter Chloe , Sampson Jacinda , Folland Chiara , Wheeler Matthew , O’Donnell-Luria Anne , Wuchty Stefan , Ravenscroft Gianina , Eberle Michael A. ,   All of Us Research Program Long Read Working Group, Zuchner Stephan 
Published: January 2025

SummaryTandem repeats are a highly polymorphic class of genomic variation that play causal roles in rare diseases but are notoriously difficult to sequence using short-read techniques1,2. Most previous studies profiling tandem repeats genome-wide have reduced the description of each locus to the singular value of the length of the entire repetitive locus3,4. Here we introduce a comprehensive database of 3.6 billion tandem repeat allele sequences from over one thousand individuals using HiFi long-read sequencing. We show that the previously identified pathogenic loci are among the most variable tandem repeat loci in the genome, when incorporating nucleotide resolution sequence content to measure the longest pure motif segment. More broadly, we introduce a novel measure, ‘tandem repeat constraint’, that assists in distinguishing potentially pathogenic from benign loci. Our approach of measuring variation as ‘the length of the longest pure segment’ successfully prioritizes pathogenic repeats within their previously published linkage regions. We also present evidence for two novel pathogenic repeat expansion candidates. In summary, this analysis significantly clarifies the potential for short tandem repeat pathogenicity at over 1.7 million tandem repeat loci and will aid the identification of disease-causing repeat expansions.
Is early initiated physical rehabilitation exercise superior to no physical rehabilitation exercise following total hip arthroplasty? A systematic review and narrative synthesis
Authors: Madsen Merete Nørgaard , Mikkelsen Lone Ramer , Christiansen David Høyrup , Østergaard Helle Kvistgaard , Bandholm Thomas 
Published: January 2025

AbstractBackgroundPhysical rehabilitation exercise (PRE) is commonly prescribed in the early stage after total hip arthroplasty (THA). However, systematic reviews investigating the effectiveness of PRE have reported diverse results, and often included trials using PRE in both groups or initiated at a later stage after surgery, which does not reflect clinical practice. Therefore, the study objective was to investigate whether early initiated PRE following THA was superior to no PRE in terms of improving function, reducing pain and increasing quality of life at end of intervention and 12 months after surgery.MethodsA systematic review of randomized controlled trials (RCT) was conducted. Included studies were RCTs comparing PRE initiated within 3 months after primary THA due to osteoarthritis with no PRE. MEDLINE, Embase, Cinahl, Cochrane and Pedro were searched for published articles, while Scopus, Web of Science, ClinicalTrials.govand WHO International Clinical Trials Registry Platform were searched for conference papers and pre-registered trials. Study methodology was assessed by Cochrane Risk of Bias 2 (RoB2) tool and overall quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Incomplete outcome data and heterogeneity among studies precluded meta-analysis. Thus, data synthesis using vote counting was applied and tested by the binomial probability test. The results were narratively presented in text and tabular form distributed on pain, patient-reported function and performance-based function.ResultsA total of 10742 references were screened. Three trials (two published papers and one conference abstract) with a total of 151 participants were included in the narrative synthesis. Only outcomes at end of treatment (ranging from 3-18 weeks after surgery) were available. The observed direction of effect favored PRE in the single study reporting patient-reported function, in both studies reporting pain and in two out of three studies reporting performance-based function. However, the testing did not show significant evidence of effect of PRE. Overall, a high risk of bias was present, and quality of evidence was very low.DiscussionLimited and very low quality of evidence showed no clear benefits or harms of PRE. Hence, no conclusions on superiority of PRE to no PRE can be drawn. High quality randomized controlled trials are needed to determine the effectiveness of using PRE early after THA.OtherRegistration: PROSPERO, CRD42020203574
Perspectives on Cervical Cancer Prevention Strategies and a Combination Treatment for Cervical Precancer in South African Women Living with HIV and Male Partners
Authors: Teodoro Nicholas S. , Ngcobo Nkosinathi , Jean-Baptiste Milenka , Mulongo Masangu , Milford Cecilia , Beksinska Malgorzata , Burgess Jaqueline , Luvuno Sibusisiwe , Nkoana Jermina , Mayisela Nonkululeko , Rahangdale Lisa , Chibwesha Carla J. 
Published: January 2025

AbstractIntroductionCervical cancer remains the second most common cancer among women worldwide, with 85% of cases occurring in low-and middle-income countries (LMIC). Women living with HIV (WLWH) are at a particularly high risk of developing for high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical cancer, and the standard surgical treatment is far less effective in this population. Thus, research on medical therapies and combination treatment options remain a priority. In preparation for a clinical trial involving adjuvant intravaginal 5-fluorouracil (5FU) cream following surgical treatment for CIN2/3, we explored the acceptability of our proposed intervention among WLWH and male partners.MethodsWe conducted qualitative interviews with WLWH and male partners in Johannesburg, South Africa between April 2022 and September 2022. We invited WLWH to participate in semi-structured focus group discussions (FGDs), while male partners were invited to participate in semi-structured in-depth interviews (IDIs). The analysis utilized a rapid, deductive approach in which quotations were identified and categorized into relevant domains: factors affecting cervical cancer screening, the initiation of 5FU vaginal cream, and adherence to 5FU.ResultsWe conducted 9 FGDs comprising 48 WLWH and 18 IDIs with male partners. The mean age of participants was 43 years, and the majority (75%) had completed secondary education. Most women (75%) had also undergone Pap smear screening and 50% had a prior abnormal Pap smear. Qualitative analysis revealed that education on HPV and cervical cancer, prior experience with the health system, and social perceptions/stigma influenced cervical cancer screening uptake and were important factors in the initiation of and adherence to 5FU. Men’s knowledge about cervical cancer was extremely limited. Overall, participants’ perceptions of the proposed trial intervention were positive, with most participants expressing confidence that women would be able to use and adhere to the intravaginal 5FU cream. Concerns raised included possible effects of 5FU on fertility, contraceptive requirements, and the recommendation for brief periods of abstinence following cream use to prevent partner side effects.ConclusionsAlthough participants had some cervical cancer knowledge, misperceptions about HPV and cervical cancer were common and prevented follow-up for abnormal Pap results. Participants emphasized the need for thorough counseling about 5FU, citing this as integral for uptake. Utilizing stakeholder input to design the clinical trial is necessary to promote acceptability and adherence to the trial intervention.