bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic nerve activity recovery from the skin recording using the modern optimal shrinkage technique
Authors: Su Pei-Chun , Chen Chao-Yi , Kuo Chia-Hao , Tsai Wei-Chung , Wu Hau-Tieng 
Published: January 2025

AbstractObjectiveThe widely used bandpass filter (BPF)-based algorithm for recovering sympathetic nerve activity (SNA) from the skin sympathetic nerve activity (SKNA-I) signal, recorded via electrocardiogram electrodes or subcutaneous sympathetic nerve activity (SCNA-I) in a lead I setup, has limitations. It excludes spectral information outside the BPF range and may retain artifacts, such as cardiac activity or pacemaker interference, in the recovered SNA (rSNA) signal. This study aims to develop an algorithm that recovers the full spectral SNA information as comprehensively as possible for evaluating the autonomic nervous system (ANS).MethodsWe propose a novel algorithm, S3 (SNA from Shrink and Subtraction), which integrates the optimal shrinkage algorithm (eOptShrink) with the template subtraction (TS) method. The performance of S3 was evaluated against other algorithms using semi-real simulated SKNA-I data, a human SKNA-I database including subjects with pacemakers or atrial fibrillation, and a mouse SCNA-I database.ResultsThe S3 algorithm demonstrated numerical efficiency and outperformed existing approaches, including traditional TS, BPF and other methods, in both time and frequency domains. Notably, in addition to the traditional 500-1000Hz spectral band, S3 effectively recovers spectral information across the 50-300Hz and 300-500Hz frequency bands, making it suitable for homecare ANS evaluation. All quantitative results are supported by the rSNA tracing for visual inspections.ConclusionS3 accurately recovers the full-spectrum SNA.SignificanceBy enabling the exploration of the entire SNA spectrum, S3 offers a promising tool for ANS evaluation and applications in homecare environments.
Specificity of a polygenic score for aggressive prostate cancer
Authors: Dornisch Anna M , Xu George J , Karunamuni Roshan , Brunette Charles A , Danowski Morgan E , Teerlink Craig C , Gaziano J. Michael , Garraway Isla P , Hauger Richard L , Kibel Adam S , Lynch Julie A , Maxwell Kara N , Rose Brent S , Andreassen Ole A , Dale Anders M , Donovan Jenny L , Hamdy Freddie , Lane Athene , Mills Ian G , Martin Richard M , Neal David E , Turner Emma L , Wolk Alicja ,   PRACTICAL Consortium,   VA Million Veteran Program, Vassy Jason L , Seibert Tyler 
Published: January 2025

AbstractTo address the concern that polygenic hazard scores for prostate cancer (PCa) might not distinguish between indolent and aggressive disease, we performedcase-onlyanalyses using a 601-variant polygenic score (PHS601). We hypothesized that among men who eventually developed PCa, those with higher PHS were more likely to develop aggressive disease.We analyzed genetic and phenotypic data from a diverse, national cohort of men diagnosed with PCa (Million Veteran Program, n = 69,901, 6413 metastatic). We used Cox proportional hazards models to examine the association of PHS601 with both age at onset of metastatic PCa (birth-to-met) and time from localized to metastatic diagnosis (localized-to-met). We performed an external validation of the case-only birth-to-met analysis in two population-based cohorts from the PRACTICAL Consortium.PHS601 was associated with both birth-to-met and localized-to-met within MVP. The HRs for men in the highest quintile of PHS601 vs. those in the lowest quintile (HR80/20) were 1.74 [1.65-1.84] and 1.41 [1.31-1.41] for birth-to-met and localized-to-met, respectively. These findings were validated in two external cohorts (COSM and ProtecT). PHS601 was also associated with earlier development of metastasis. Men with high PHS601 are diagnosed with prostate cancer at a younger age and are more likely to develop metastasis.
The effects of cryptic diversity on diversification dynamics analyses in Crocodylia
Authors: Darlim Gustavo , Höhna Sebastian 
Published: January 2025

AbstractIncomplete taxon sampling due to underestimation of present-day biodiversity biases diversification analysis by favouring slowdowns in speciation rates towards recent time. For instance, in diversification dynamics studies in Crocodylia, long-term low net-diversification rates and slowdowns in speciation rates have been suggested to characterise crocodylian evolution. However, crocodylian cryptic diversity has never been considered. Here, we explore the effects of incorporating cryptic diversity into a diversification dynamics analysis of extant crocodylians. We inferred a time-calibrated cryptic-species-level phylogeny using cytochromebsequences of 45 lineages compared with the formally recognized 26 crocodylian species. Diversification rate estimates using the cryptic-species-level phylogeny show increasing speciation and net-diversification rates towards the present time, which is contrasting to previous findings. Cryptic diversity should be considered in future macroevolutionary analyses, however representation of cryptic extinct taxa represents a major challenge. Additionally, further investigation of crocodylian diversification dynamics under different underlying genomic data is encouraged upon advances in population genetics. Our case study adds to diversification dynamics knowledge of extant taxa and demonstrates that cryptic species and robust taxonomic assessment are essential to study recent biodiversity dynamics with broad implications for evolutionary biology and ecology.
Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain
Authors: Han Xiangfei , Petrova Veselina , Song Yudong , Cheng Yu-Ting , Jiang Xingya , Zhou Hui , Hu Caleb , Chen Dean Shuailin , Yong Hyo Jeong , Kim Hyoung Woo , Zhang Biyao , Barkai Omer , Jain Aakanksha , Renthal William , Lirk Philipp , Woolf Clifford J. , Shi Jinjun 
Published: January 2025

AbstractSensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.
An improved gray whale assembly highlights how allospecific reference-genome choice can affect genomic diversity estimates
Authors: Brüniche-Olsen Anna , Black Andrew , Walden Kimberly K. O. , Fields Christopher , Bickham John W. , Dewoody J. Andrew 
Published: January 2025

AbstractGray whales (Eschrichtius robustus) are unique as bottom feeding baleen whales and they have long been a conservation concern on both sides of the Pacific, in part because they migrate and disperse farther than any other species on earth. They experienced drastic population size declines due to environmental changes and commercial whaling. Here, we present an improved genome assembly for the gray whale. This genome assembly covers 2.4 Gb divided across 2689 contigs with an N50 of 15Mb. From the new assembly, we identify 75Mb sex-linked contigs and a identify 94.6% of searched genes based on Benchmarking Universal Single-Copy Ortholog score. We use the gray whale assembly to explore the effects of mapping to conspecific vs allospecific reference genomes when estimating genome-wide heterozygosity (H) and runs of homozygosity (ROH). The use of allospecific genomes significantly underestimate bothHand ROH burden regardless of genomic distance and assembly quality. Our analyses highlight the importance of using contiguous conspecific assemblies in whale genomics and conservation.SignificanceGray whales are unique in their behavior, morphology and ecology. The novel and contiguous genome assembly presented here will serve as a valuable resource for studies of their population and comparative genomics, as well as for identifying key adaptations that have evolved in this clade. Finally, our results demonstrate that biases can arise when using allopatric assemblies to evaluate diversity metrics, so they should be used and interpreted with caution.
Sterile- or pathogen-induced endolysosomal damage activate the NLRP6 inflammasome in human intestinal epithelial cells
Authors: Boegli Alexandra , Bernard Elliott M. , Lacante Louise , Majeux Gaël , Mack Vanessa , Broz Petr 
Published: January 2025

AbstractNLRP6 controls host defense against bacteria and viruses in the gastrointestinal tract by a poorly understood mechanism. Here, we report that NLRP6 forms an inflammasome upon endolysosomal damage caused by sterile triggers or bacterial pathogens such asListeria monocytogenesin human intestinal epithelial cells (IECs). NLRP6 activation required Listeriolysin O-dependent cytosolic invasion ofL. monocytogenesand drove IEC pyroptosis via ASC/Caspase-1-mediated GSDMD cleavage. NLRP6 inflammasome formation was independent of bacterial PAMPs, such as lipoteichoic acid or dsRNA, which were previously reported to activate NLRP6.L. monocytogenesmutants deficient in cell-to-cell spread or escape from secondary vacuoles induced less cell death, linking bacteria-induced endolysosomal damage to NLRP6 activation. Finally, sterile endolysosomal damage recapitulated pathogen-induced NLRP6 activation and drove IEC pyroptosis. In summary, our study reveals that NLRP6 allows IECs to detect endolysosomal damage, thereby not only making it responsive to pathogens but more generally to wide-ranging sources of pathological endolysosomal damage.
FlashFold: a standalone command-line tool for accelerated protein structure prediction
Authors: Saha Chayan Kumar , Roghanian Mohammad , Häussler Susanne , Guy Lionel 
Published: January 2025

AbstractFlashFold is a fast, user-friendly tool for predicting protein structures and complexes. It can be installed locally on Linux or Mac operating systems, alleviating the computational needs, and eliminating reliance on third-party servers. FlashFold relies on a highly compact and adaptable built-in database to speed up the homology searching. Overall structure predictions are up to 3-fold faster than AlphaFold3 with sacrificing little or no accuracy. FlashFold is available athttps://github.com/chayan7/flashfold.
SOX9 plays an essential role in myofibroblast driven hepatic granuloma integrity and parenchymal repair during schistosomiasis-induced liver damage
Authors: Su Kim , Jokl Elliot , Costain Alice , Simpson Kara , Cheeseman Antonn , Phythian-Adams Alexander , Couper Kevin N , MacDonald Andrew S. , Piper Hanley Karen 
Published: January 2025

AbstractSchistosomiasis is a neglected, and potentially lethal, parasitic disease that affects hundreds of millions of people worldwide. As part of the schistosome lifecycle, parasite eggs accumulate within the liver where they evoke intense granulomatous pathology, typified by a dense extracellular matrix (ECM) barrier, which serves to contain toxic egg secretions. In severe cases, this progressive and irreversible egg-evoked ECM deposition can lead to pathological scarring, impaired liver function and lethality. Thus, identifying the core regulators that govern ECM deposition may aid discovery of new therapeutic targets for schistosomiasis. The transcription factor Sex determining region Y-box 9 (Sox9) is a known regulator of pathological scaring. We found that, followingSchistosoma mansoniinfection, SOX9 was ectopically expressed in myofibroblasts within the granuloma and in surrounding hepatocytes. In the absence of SOX9, granuloma size was significantly diminished, and mice failed to produce a robust ECM barrier around eggs, resulting in more diffuse liver injury and scattered distribution of immune cells. Immunologically, SOX9 loss in both naïve and infected mice led to an increase in hepatic neutrophil and monocyte proportions, with the expansion of Ly6clomonocyte populations in infected SOX9 deficient mice only. Infected SOX9–deficient mice also displayed exaggerated Type 2 inflammation, including pronounced eosinophilia. These data highlight the importance of SOX9 for intact hepatic granuloma formation during schistosomiasis and suggest SOX9 or its related factors may provide attractive future targets for meeting the clinical need to limit and/or reverse fibrotic disease.Author SummaryMammalian infection with schistosome worms results in the deposition of parasite eggs in the liver, where they secrete organ damaging toxins. In response, the liver generates a cellular granuloma barrier rich in extracellular matrix to limit these secretions and protect the overall organ. As in other liver injuries, SOX9 becomes progressively expressed in multiple cell types during the time course of schistosome infection. To understand the role of SOX9 in the liver response to schistosomes we utilised a global SOX9 deficient mouse model. These mice show reduced and disorganised granuloma formation during schistosome infection, with disrupted hepatic immune profiles. This suggests that SOX9 is required to form a robust and coordinated granuloma barrier that limits liver damage in this important but neglected parasitic disease.
Strain background interacts with chromosome 7 aneuploidy to determine commensal and virulence phenotypes inCandida albicans
Authors: Mishra Abhishek , Solis Norma V. , Dietz Siobhan M. , Crouch Audra L. , Filler Scott G. , Anderson Matthew Z. 
Published: January 2025

ABSTRACTThe human fungal pathobiontCandida albicansdisplays extensive genomic plasticity, including large-scale chromosomal changes such as aneuploidy. Chromosome trisomy appears frequently in natural and laboratory strains ofC. albicans. Trisomy of specific chromosomes has been linked to large phenotypic effects, such as increased murine gut colonization bystrainstrisomic for chromosome 7 (Chr7). However, studies of whole-chromosome aneuploidy are generally limited to the SC5314 genome reference strain, making it unclear whether the imparted phenotypes are conserved acrossC. albicansgenetic backgrounds. Here, we report the presence of a Chr7 trisomy in the “commensal-like” oral candidiasis strain, 529L, and dissect the contribution of Chr7 trisomy to colonization and virulence in 529L and SC5314. These experiments show that strain background and homolog identity (i.e., AAB vs ABB) interact with Chr7 trisomy to alter commensal and virulence phenotypes in multiple host niches.In vitrofilamentation was the only phenotype altered by Chr7 trisomy in similar ways across the two strain backgrounds. Oral colonization of mice was increased by the presence of a Chr7 trisomy in 529L but not SC5314; conversely, virulence during systemic infection was reduced by Chr7 trisomy in SC5314 but not 529L. Strikingly, the AAB Chr7 trisomy in the SC5314 background rendered this strain avirulent in murine systemic infection. Increased dosage ofNRG1failed to reproduce most of the Chr7 trisomy phenotypes. Our results demonstrate that aneuploidy interacts with background genetic variation to produce complex phenotypic patterns that deviate from our current understanding in the genome reference strain.AUTHOR SUMMARYCandida albicansis a clinically important fungus of humans that is also part of the microbiota that typically colonizes our bodies. Changes in the number of copies of chromosome 7 (Chr7) in the genome of the reference strain ofC. albicansenhances host colonization. We identified a third copy of Chr7 in a strain classified as a good colonizer of humans that doesn’t cause disease, mimicking the increased colonization of the reference strain. Here, we demonstrate that the number of copies of Chr7 alters phenotypes differently between these strains, and three copies of Chr7 does not universally produce a strain that is only a better commensal strain. Additionally, which copy of Chr7 in this diploid species exists as the third copy influences commensal and pathogen phenotypes. Therefore, trisomic changes of the same chromosome in differentC. albicansstrains have substantially different effects.
MutBERT: Probabilistic Genome Representation Improves Genomics Foundation Models
Authors: Long Weicai , Su Houcheng , Xiong Jiaqi , Zhang Yanlin 
Published: January 2025

AbstractMotivationUnderstanding the genomic foundation of human diversity and disease requires models that effectively capture sequence variation, such as single nucleotide polymorphisms (SNPs). While recent genomic foundation models have scaled to larger datasets and multi-species inputs, they often fail to account for the sparsity and redundancy inherent in human population data, such as those in the 1000 Genomes Project. SNPs are rare in humans, and current masked language models (MLMs) trained directly on whole-genome sequences may struggle to efficiently learn these variations. Additionally, training on the entire dataset without prioritizing regions of genetic variation results in inefficiencies and negligible gains in performance.ResultsWe present MutBERT, a probabilistic genome-based masked language model that efficiently utilizes SNP information from population-scale genomic data. By representing the entire genome as a probabilistic distribution over observed allele frequencies, MutBERT focuses on informative genomic variations while maintaining computational efficiency. We evaluated MutBERT against DNABERT-2, various versions of Nucleotide Transformer, and modified versions of MutBERT across multiple downstream prediction tasks. MutBERT consistently ranked as one of the top-performing models, demonstrating that this novel representation strategy enables better utilization of biobank-scale genomic data in building pretrained genomic foundation models.Availabilityhttps://github.com/ai4nucleome/mutBERTContactyanlinzhang@hkust-gz.edu.cn
Transcriptional Dynamics and Chromatin Accessibility in the Regulation of Shade-Responsive Genes in Arabidopsis
Authors: Paulisic Sandi , Boccaccini Alessandra , Dreos René , Ambrosini Giovanna , Guex Nicolas , Benstei Ruben Maximilian , Schmid Markus , Fankhauser Christian 
Published: January 2025

ABSTRACTOpen chromatin regions host DNA regulatory motifs that are accessible to transcription factors and the transcriptional machinery. In Arabidopsis, responses to light are heavily regulated at the transcriptional level. Shade, for example, can limit photosynthesis and is rapidly perceived by phytochromes as a reduction of red to far-red light ratio (LRFR). Under shade, phytochromes become inactive, enabling PHYTOCHROME INTERACTING FACTORs (PIFs), particularly PIF7, to promote genome-wide reprogramming essential for LRFR responses. An initial strong and fast regulation of shade-responsive genes is followed by attenuation of this response under prolonged shade. We wanted to determine whether the transcriptional response to shade depends on chromatin accessibility. For this, we used ATAC-seq to profile the chromatin of seedlings exposed to short (1h) and long (25h) simulated shade. We found that PIF7 binding sites were accessible for most early target genes before LRFR treatment. The transcription pattern of most acute shade-responsive genes correlated with a rapid increase in PIF levels and chromatin association at 1h, and its decrease at 25h of shade exposure. For a small subset of acutely responding genes, PIFs also modulate chromatin accessibility at their binding sites early and/or late in the response to shade. Our results suggest that in seedlings a state of open chromatin conformation allows PIFs to easily access and recognize their binding motifs, rapidly initiating gene expression triggered by shade. This transcriptional response primarily depends on a transient increase in PIF stability and gene occupancy, accompanied by changes in chromatin accessibility in a minority of genes.
Clinical and Genetic Determinants of Glioblastoma Multiforme Survival: A Retrospective Analysis
Authors: Gutiérrez-Arroyo Julia L. , Gallego-Porcar Pia , Carbonell-Martinez Elvira , González-Bonet Luis G. , Ibañez Maria Victoria , Díaz-Ruiz María , Caballero-Arzapalo Hugo , Soto Ariadna , Garcia-Oriola Guillermo , Borras-Moreno Jose Maria , Martinez-Cadenas Conrado , Marques-Torrejon Maria Angeles 
Published: January 2025

ABSTRACTGlioblastoma, the most aggressive primary brain tumour in adults, has a poor prognosis and limited survival despite advances in treatment. This study analysed 61 patients with glioblastoma multiforme treated at the General University Hospital of Castellon, Spain, focusing on clinical, tumour-specific and genetic factors influencing disease outcome. Variables included age, sex, BMI, extent of surgical resection, and use of radiotherapy or chemotherapy. Tumour characteristics assessed included location, size, proximity to the ventricular system and surgical approach. Genetic mutations in theIDH, EGFR, TP53andCDKN2Agenes were also analysed. Kaplan-Meier analysis was used to assess the impact of these factors on overall survival and progression-free survival. A significant finding was the strong association between surgical approach, tumour proximity to the ventricular system and survival: patients with tumours closer to the ventricles had significantly shorter survival, highlighting the critical role of spatial tumour characteristics in glioblastoma multiforme outcomes. These results suggest that integrating clinical, genetic and spatial tumour data into personalised treatment approaches could improve prognosis. Understanding these factors is critical to developing more effective strategies to meet the challenges of this aggressive and complex disease.
A rapidly closing window for coral persistence under global warming
Authors: Bozec Yves-Marie , Adam Arne A.S. , Nava Beatriz Arellano , Cresswell Anna K. , Haller-Bull Vanessa , Iwanaga Takuya , Lachs Liam , Matthews Samuel A. , McWhorter Jennifer K. , Anthony Kenneth R.N. , Condie Scott A. , Halloran Paul R. , Ortiz Juan-Carlos , Riginos Cynthia , Mumby Peter J. 
Published: January 2025

Summary paragraphCoral reefs around the world are threatened by recurrent marine heatwaves causing mass coral bleaching and mortality1. Mitigating future warming impacts requires strategic management2that adopts a long-term lens. Global analyses of projected heatwaves3,4are critical for decision-making but how disturbance refugia, coral life-histories and adaptation interact with warming is unknown. Here, we simulate coral eco-evolutionary dynamics across >3,800 individual reefs of Australia’s iconic Great Barrier Reef under the current suite of climate projections5. We forecast a rapid coral decline before mid-century regardless of emissions scenario. Under the most likely warming6, corals may continue to decline throughout the century. However, corals may recover after mid-century provided that warming is sufficiently slow, allowing thermal adaptation to keep pace with temperature changes – as projected if warming does not exceed 2°C. Higher emission scenarios would drive most reefs to a near collapse. Future resilient reefs were mostly found in bleaching refugia, which also possessed a greater diversity of thermal phenotypes. Although cool-adapted corals disperse to thermal hotspots, there was no evidence of ‘gene swamping’ undermining thermal adaptation. While opportunities exist to build management strategies that promote adaptation in thermal refugia and warm spots, curbing the rate of warming by 2050 is crucial for coral persistence.