bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLK4 inhibition as a strategy to enhance non-small cell lung cancer radiosensitivity
Authors: Dominguez-Vigil Irma G. , Banik Kishore , Baro Marta , Contessa Joseph N. , Hayman Thomas J. 
Published: February 2025

AbstractLung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and comprises 85% of cases. Despite treatment advances, local control after curative-intent chemoradiation for NSCLC remains suboptimal. Polo-like kinase 4 (PLK4) is a serine-threonine kinase that plays a critical role in the regulation of centrosome duplication and cell cycle progression and is overexpressed in NSCLC, thus, making it a potential therapeutic target. CFI-400945 is an orally available PLK4 inhibitor currently undergoing clinical trial evaluation. As radiation causes cell death primarily by mitotic catastrophe, a process enhanced by alterations in centrosome amplification, we hypothesized that disruption of the mitotic machinery by inhibition of PLK4 would enhance the effects of radiation in NSCLC. PLK4 inhibition by CFI-400945 resulted in radiosensitization of NSCLC cell lines. In contrast, CFI-400945 had no effect on the radiosensitivity of normal lung fibroblasts. PLK4 inhibition did not affect cell-cycle phase distribution prior to radiation, but rather the combination of CFI-400945 and radiation resulted in increased G2/M cell cycle arrest, increased centrosome amplification, and a concomitant increase in cell death through mitotic catastrophe. Lastly, CFI-400945 treatment enhanced the radiation-induced tumor growth delay of NSCLC tumor xenografts. These data indicate that targeting PLK4 is a novel approach to enhance the radiation sensitivity of NSCLCin vitroandin vivothrough potentiation of centrosome amplification and cell death through mitotic catastrophe.
‘SpikeNburst’ and ‘Nicespike’: Advanced Tools for Enhancing and AcceleratingIn VitroHigh-Density Electrophysiology Analysis
Authors: Wolff Robert , Polito Alessia , Buccino Alessio Paolo , Chiappalone Michela , Tucci Valter 
Published: February 2025

AbstractHigh-density multi-electrode arrays (HD-MEAs) have revolutionized electrophysiology by enabling the recording of neuronal activity with unprecedented spatial and temporal resolution. However, analysing these large-scale datasets poses significant challenges, including artefact removal, spike sorting, and accurate assessments of neuronal synchronization. Here, we present two Python-based tools, ‘spikeNburst’ and ‘nicespike’, designed to address these challenges and provide a scalable solution for the comprehensive analysis of HD-MEA recordings.ThespikeNbursttool integrates advanced methodologies for spike train filtering, burst and network burst detection, and synchronization analysis, and we implemented a full analysis pipeline in thenicespiketool, which includes GPU-accelerated spike sorting using template matching with Kilosort to accurately identify neuronal units spanning multiple electrodes. Together, these tools enable more precise analyses by mitigating redundancy and overestimation inherent in single-channel approaches. Their graphical user and command-line interfaces ensure accessibility for diverse user needs.We validated the tools on neuronal culture recordings, demonstrating their ability to identify somatic and dendritic features of neuronal units, characterize bursting behaviour, and quantify synchronization at both unit and network levels. By addressing critical limitations of existing methods,spikeNburstandnicespikeprovide a robust, scalable, and user-friendly framework for HD-MEA data analysis, advancing our ability to study neural network dynamics and single-cell activity in detail.
Precursor RNA structural patterns at SF3B1 mutation sensitive cryptic 3’ splice sites
Authors: Herbert Austin , Hatfield Abigail , Randazza Alexandra , Miyamoto Valeria , Palmer Katie , Lackey Lela 
Published: February 2025

AbstractSF3B1 is a core component of the spliceosome involved in branch point recognition and 3’ splice site selection. SF3B1 mutation is common in myelodysplastic syndrome and other blood disorders. The most common mutation in SF3B1 is K700E, a lysine to glutamic acid change within the pre-mRNA interacting heat repeat domain. A hallmark of SF3B1 mutation is an increased use of cryptic 3’ splice sites; however, the properties distinguishing SF3B1-sensitive splice junctions from other alternatively spliced junctions are unknown. We identify a subset of 192 core splice junctions that are mis-spliced with SF3B1 K700E mutation. We use our core set to test whether SF3B1-sensitive splice sites are different from control cryptic 3’ splice sites via RNA structural accessibility. As a comparison, we define a set of SF3B1-resistant splice junctions with cryptic splice site use that does not change with SF3B1 K700E mutation. We find sequence differences between SF3B1-sensitive and SF3B1-resistant junctions, particularly at the cryptic sites. SF3B1-sensitive cryptic 3’ splice sites are within an extended polypyrimidine tract and have lower splice site strength scores. We develop experimental RNA structure data for 83 SF3B1-sensitive junctions and 39 SF3B1-resistant junctions. We find that the pattern of structural accessibility at the NAG splicing motif in cryptic and canonical 3’ splice sites is similar. In addition, this pattern can be found in both SF3B1-resistant and SF3B1-sensitive junctions. However, SF3B1-sensitive junctions have cryptic splice sites that are less structurally distinct from the canonical splice sites. In addition, SF3B1-sensitive splice junctions are overall more flexible than SF3B1-resistant junctions. Our results suggest that the SF3B1-sensitive splice junctions have unique structure and sequence properties, containing poorly differentiated, weak splice sites that lead to altered 3’ splice site recognition in the presence of SF3B1 mutation.
Biplanar nulling coil system for OPM-MEG using printed circuit boards
Authors: Jas Mainak , Kamataris John , Matsubara Teppei , Dong Chunling , Motta Gabriel , Sohrabpour Abbas , Ahlfors Seppo P. , Hämäläinen Matti , Okada Yoshio , Sundaram Padmavathi 
Published: February 2025

AbstractOptically pumped magnetometers (OPMs) are a promising sensor technology for non-invasive measurement of human electrophysiological signals, in particular the magnetoencephalogram (MEG). OPMs do not need cryogenic cooling and can be placed conformal to the subject’s scalp, thus greatly reducing the sensor-to-source distance and improving signal sensitivity. OPMs, however, require near-zero background magnetic field to achieve linearity and minimize signal distortion. Prior work has proposed the use of biplanar field nulling coils to remove the uniform and gradient components of the background magnetic field. Biplanar coils have been expensive to construct, involving tedious error-prone manual winding of over 1000 m of copper wire. In this work, we designed and fabricated background field nulling coils (three uniform and three gradient components) on two-layer Printed Circuit Boards (PCBs). We used an open-source software (bfieldtools) to determine the current loops needed to produce the target magnetic field in a 50-cm-diameter spherical volume. We developed a software-based approach to connect the discrete current loops into a continuous conducting path traversing the two layers of the PCB. For ease of manufacture, the designed (1.5 × 1.5 m2) coils were cut along the symmetry axis and printed as pairs of 1.5 × 0.75 m2PCBs (2 oz Cu), soldered together and mounted on a sliding aluminum frame. The efficiency of the coils (1.3 - 7.1 nT/mA) was similar or higher than previously reported in the literature. We mapped the field inside the target region after field nulling inside our single-layer shielded room and were able to reduce the largest component of the background field from 21 to 2 nT. Using our nulling coil system, we were able to operate OPMs in a lightly shielded room (background field varying from 6.5 to 108 nT in the floor-to-ceiling direction) to record somatosensory evoked fields (SEFs) comparable to those measured using SQUID-based MEG in a 3-layer shielded room. We disseminate the software and hardware as an open-source packageopmcoils. This work will facilitate access to more affordable field nulling coils for OPM-MEG and help to realize the potential of OPM-MEG as an accessible sensor technology for use in human neuroscience.
Multiphase separation in postsynaptic density regulated by membrane geometry via interaction valency and volume
Authors: Yamada Risa , Brandani Giovanni B. , Takada Shoji 
Published: February 2025

AbstractBiomolecular condensates are found at various cellular locations, nucleus, cytoplasm, and membrane. These condensates often contain multiple components and can separate into multiple phases with various morphologies such as core-shell droplets, implicating functional roles. Demixing of condensates and their arrangements are determined by competitive interactions and by their locations. Recent studies reported a puzzling multiphase morphology of four components of postsynaptic density: AMPA-receptor, NMDA-receptor, PSD-95, and CaMKII. The multiphase morphology becomes apparently reversed as we move from the solubilized constructs to the membrane. In this study, using this system as a model, we study the multiphase behavior of condensates in solution (3D) and domain formation on and beneath the membrane (2D) and elucidate molecular mechanisms behind the puzzle. Our mesoscopic simulations reproduce that the CaMKII activation induces the core-shell multiphase separation found in 3Din vitroexperiment with AMPA-receptor/PSD-95 at the core and NMDA-receptor/CaMKII in the shell. Then, we obtain a reversed morphology on the postsynaptic membrane. The high valency and large volume of CaMKII appears to be a major factor in this reversal. Interestingly, we find that, while the CaMKII has dominant non-specific volume interaction in the 3D system, the specific multivalent interactions overcome the volume interaction for CaMKII beneath the membrane, reversing the morphology. On the membrane, the layered structures of receptors and CaMKIIs reduce the volume effects of CaMKII on receptors, making the multivalent interaction dominant. The membrane domain formation is distinct from the condensate formation in solution and modulated by their layered arrangement.SignificanceMany proteins form condensates in cells, which are often further separated into two or more phases, implicating functional roles. Recent experiments on postsynaptic density proteins provide an interesting puzzle on a multiphasic morphology; while they form core-shell droplets with AMPA-receptor at the core and NMDA receptor in the shell in soluble constructs, the multiphase morphology is reversed when they form nanodomains on the membrane. This study identifies the mechanism behind the puzzle by using computer simulations with a mesoscale model. While active CaMKII, an inducer of the multiphase morphology, has dominant non-specific volume interactions in solution, its specific domain-domain multivalent interaction overcomes the volume interaction under the membrane with their layered arrangement.
scWGBS-GPT: A Foundation Model for Capturing Long-Range CpG Dependencies in Single-Cell Whole-Genome Bisulfite Sequencing to Enhance Epigenetic Analysis
Authors: Liang Chaoqi , Ye Peng , Yan Hongliang , Zheng Peng , Sun Jianle , Wang Yanni , Li Yu , Ren Yuchen , Jiang Yuanpei , Xiang Junjia , Zhang Sizhe , Jiang Linle , Bai Weiqiang , Ma Xinzhu , Chen Tao , Zuo Wangmeng , Bai Lei , Ouyang Wanli , Li Jia 
Published: February 2025

ABSTRACTSingle-Cell Whole-Genome Bisulfite Sequencing (scWGBS) is a powerful technique for profiling DNA methylation at single-cell and single-nucleotide resolution, providing critical insights into epigenetic regulation in development, disease, and cellular heterogeneity. However, analyzing scWGBS data remains a significant challenge due to ultra-long genomic sequences with millions of CpG sites and sparse, stochastic coverage. Here, we introduce scWGBS-GPT, the first generative foundational language model specifically designed for high-resolution analysis of scWGBS data at the single-CpG level. By combining CpG special token design, Mamba backbone and Cross-Attention head, scWGBS-GPT efficiently processes ultra-long sequences while preserving both local CpG interactions and broader genomic context, enabling biologically meaningful interpretations. Pretrained on 1,000,000 single cells from 28 human and mouse tissues, scWGBS-GPT reconstructs sparse methylation landscapes, enhancing the resolution and accuracy of epigenetic analyses. It significantly outperforms existing methods in key biomedical applications—improving cell clustering to uncover previously unrecognized cellular heterogeneity, enhancing trajectory inference to map precise differentiation pathways, and automating the identification of critical epigenetic biomarkers relevant to disease progression and therapeutic targeting. These advancements establish scWGBS-GPT as a transformative tool in single-cell epigenomics, setting a new standard for DNA methylation analysis and unlocking novel insights into epigenetic mechanisms underlying health and disease. The code for scWGBS-GPT is available athttps://github.com/ChaoqiLiang/scWGBS-GPT.HighlightsscWGBS-GPT is the first foundation language model for scWGBS data analysis, trained on over 1,000,000 single cells from 28 human and mouse tissues, spanning 221 cell types.scWGBS-GPT combines CpG special token design, Mamba backbone, and Cross-Attention head for efficient processing of up to 2 million CpG sites per cell.scWGBS-GPT achieves State-of-the-Art Performance in Cell Clustering, Annotation, Pseudotime Inference.scWGBS-GPT is compatible with bulk WGBS data and excels in deconvoluting cell-free DNA methylation data, precisely inferring the tissue or organ of origin, enhancing non-invasive diagnostic capabilities.
Impact of Long Term Integrated Nutrient Management Practices on Soil Bacterial Diversity: A 16S rRNA-Based Metagenomic Approach
Authors: Ahlawat Vishal , Ahalawat Navjeet , Boora Nisha , Dadarwal R S , Dhanda Deepika , Sangwan Pooja , Kumar Vipin , Kumar Rajiv , Yadav Parmod Kumar 
Published: February 2025

AbstractThe growing world’s population, expected to surpass 9 billion by 2050, demands a 70–100% increase in farm productivity, posing significant challenges for sustainable agriculture. Conventional farming, reliant on chemical fertilizers and pesticides, negatively impacts environmental sustainability and food quality. Metagenomics, a culture-independent technique, has revolutionized the study of microbial communities by enabling comprehensive analysis of microbial diversity and function. This study evaluated the effects of combined nutrient management practices—including farmyard manure (FYM), wheat straw, green manure, and NPK fertilizers—on soil bacterial diversity using 16S rRNA-based metagenomic analysis. Key findings revealed the dominance of bacterial phyla such as Proteobacteria, Actinobacteria, and Firmicutes, which play critical roles in nutrient cycling, organic matter decomposition, and plant growth promotion. Distinct taxonomic distributions were observed across the samples, with Proteobacteria and Firmicutes dominating in control (T1), NPK (T2), and NPK_Green Manure (T5) treatments, while a shift in phyla composition was noted in NPK_FYM (T3) and NPK_WheatStraw (T4). Genus-level analysis revealed that Pseudomonas and Bacillus species were abundant in control (T1) and NPK (T2), while Sphingomonas species were dominant in NPK_FYM (T3). Further diversity analyses revealed significant variation across the samples, with T3 showing the highest richness and control (T1) showing the lowest richness. The rarefaction curve confirmed sufficient sampling for capturing microbial diversity, while beta diversity analysis, including Principal Coordinate Analysis (PCA) and Bray-Curtis clustering, indicated distinct microbial community structures across different treatments. The combined use of organic amendments with NPK fertilizer enhanced microbial diversity and population, indicating their potential to support resilient and productive soil ecosystems.
Demystifying The Myelingratio: Its Origin, Derivation and Interpretation
Authors: Gow Alexander 
Published: February 2025

AbstractMost studies involving myelingratios over the past 120 years assume this metric enumerates changes in myelin thickness (largergratio = thinner myelin) with axon or fiber diameter. And, moreover, such changes are directly correlated with internodal function (conduction velocity). However, such assumptions are warranted only in the absence of experimental errors and artifacts (i.e. under theoretical conditions). In reality,gratios easily under- or overestimate rates of change exceeding 10%, especially for small caliber fibers. Typical analyses of myelin internodes rely on an explicit mathematical model,, where DAis axon diameter and DFis fiber diameter (myelin plus axon). Shown recently and herein, this model approximates normal physiological conditions only when the axon-fiber diameter relation is directly proportional, whence it is concordant with the axomyelin unit model. However, in transient or non-steady states (development/aging, disease or myelin plasticity) with linear but not directly proportional relations,gratios poorly describe myelin structure. Acceptance of this counterintuitive assertion is predicated on a detailed understanding of thegratio – origins, properties and the biology represented – heretofore uncharted. In light of suchgratio limitations, more general and reliable metrics are proposed, the myelingcratio and theg’cline.
Heat-induced secondary dormancy contributes to local adaptation in Arabidopsis thaliana
Authors: Tran Nhu Loc Thuy , Ali Tahir , Schmitz Gregor , de Meaux Juliette 
Published: February 2025

AbstractSeeds should not germinate under conditions in which seedling development cannot be sustained. Dormancy, which allows seeds to remain inactive in an environment that would otherwise enable germination, helps optimize the timing of germination. The induction of a secondary type of dormancy after seed dispersal allows seeds to fine-tune germination to prevailing environmental conditions. In this study, we explore the relevance of secondary dormancy in response to heat for adaptation to local environments by characterizing natural variation in heat-induced secondary dormancy within a collection of 361Arabidopsis thalianaaccessions originating from across the European geographical range. We found that the acquisition of secondary dormancy varies with levels of primary dormancy and after-ripening. We found that both primary dormancy and heat-induced secondary dormancy formed an adaptive cline along temperature and precipitation gradients. The slope of this cline was steeper for secondary dormancy than for primary dormancy, indicating that secondary dormancy contributes most to local adaptation. Using species distribution models, we find that genotypes with high secondary dormancy are predicted to be more resilient to future climate change. We further identified several regions in the genome that specifically controlled the levels of secondary dormancy, one of which contained a novel candidate gene for secondary dormancy variation. Our findings show that secondary dormancy is a complex adaptive mechanism and a predominant contributor to the dormancy trait syndrome that favors plant survival in habitats exposed to harsh summers.Summary statementSecondary dormancy induced by heat exposure allows seed to adjust their germination strategies to the environment. This study shows that heat-induced secondary dormancy inArabidopsis thalianadepends on levels of primary dormancy. Its covariance with climatic parameter indicates that it can contribute to population resilience to climate change. This study further identifies the specific genetics underlying the ability to induce dormancy after dispersal.
The preclinical cardiac phenotype of the DE50-MD dog model of Duchenne muscular dystrophy
Authors: Sargent Julia , Fuentes Virginia Luis , Terry Rebecca , Riddell Dominique O. , Harron Rachel CM , Wells Dominic J. , Piercy Richard J. 
Published: February 2025

AbstractCardiomyopathy is the leading cause of death in the X-linked disorder, Duchenne Muscular Dystrophy (DMD) yet optimal management strategies remain undetermined. Advances in the search for novel DMD treatments, particularly at cell and molecular levels, rely heavily on the use of translational animal models. It is crucial that these models faithfully recapitulate the human clinical phenotype to best expedite the development of promising treatments.We sought comprehensively to describe the cardiac phenotype of DE50-MD dogs, a novel dystrophin-deficient model that harbours a mutation within the principal DMD mutational hotspot. Cardiac magnetic resonance imaging and echocardiographic studies were performed at approximately 12-week intervals in male, 3- to 18- month-old DE50-MD (n=17) and age-matched littermates, wild type (WT, n=14) dogs. Late gadolinium enhancement (LGE) imaging was performed in a subpopulation of DE50-MD (n=10) and WT (n=11) dogs aged 9 to 18 months. The DE50-MD dogs had smaller left ventricular (LV) mass and LV dimensions than WT dogs. While global ventricular systolic function was preserved, DE50-MD dogs showed early differences in strain and strain rate parameters. Only DE50-MD dogs demonstrated LGE (3/8 dogs studied at 18 months); the subepicardial to transmural, mid-to-basal LV LGE distribution resembling that of DMD patients and of other dystrophic dog models. Histopathological assessment confirmed that LGE corresponded to fibrofatty myocardial scarring, as described in DMD patients and other canine models of dystrophin-deficient cardiomyopathy. The DE50-MD early preclinical cardiac phenotype shares key features of DMD cardiomyopathy prior to onset of global LV systolic dysfunction. Their disproportionately low LV volume to mass supports possible combined physiological hypotrophy and tonic contraction in affected animals.