bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Microbubble Tracking for Super-Resolution Ultrasound Localization Microscopy using a Bi-Directional Long Short-term Memory Neural Network
Authors: Chen Xi , Lowerison Matthew R. , Shin YiRang , Wang Yike , Dong Zhijie , You Qi , Song Pengfei 
Published: February 2025

AbstractUltrasound localization microscopy (ULM) enabled high-accuracy measurements of microvessel flow beyond the resolution limit of conventional ultrasound imaging by utilizing contrast microbubbles (MBs) as point targets. Robust tracking of MBs is an essential task for fast and high-quality ULM image reconstruction. Existing MB tracking methods suffer from challenging imaging scenarios such as high-density MB distributions, fast blood flow, and complex flow dynamics. Here we present a deep learning-based MB pairing and tracking method based on a bi-directional long short-term memory neural network for ULM. The proposed method integrates multiparametric MB characteristics to facilitate more robust and accurate MB pairing and tracking. The method was validated on a simulation data set, a tissue-mimicking flow phantom, andin vivoon a mouse and rat brain.
SpaceBar enables clone tracing in spatial transcriptomic data
Authors: Kinsler Grant , Fagan Caitlin , Li Haiyin , Kaster Jessica , Dunne Maggie , Vander Velde Robert J. , Boe Ryan H. , Shaffer Sydney , Herlyn Meenhard , Raj Arjun , Heyman Yael 
Published: February 2025

ABSTRACTWe report a cellular barcoding strategy, SpaceBar, that enables simultaneous clone tracing and spatial transcriptomics profiling. Our approach uses a library of 96 synthetic barcode sequences that can be robustly detected by imaging based spatial transcriptomics (seqFISH), delivered such that each cell is labeled with a combination of barcodes. We used these barcodes to label melanoma cells in a tumor xenograft model and profiled both clone identity and spatial gene expressionin situ. We developed a gene scoring metric that quantifies how strongly gene expression is driven by intrinsic cellular cues or extrinsic environmental signals. Our framework distinguishes between clonal dynamics and environmentally-driven transcriptional regulation in complex tissue contexts.
Genetic Variants that Modulate Alzheimer’s Disease Risk Deregulate Protein-Protein Correlations in the Gyrus Temporalis Medius
Authors: Bouland Gerard A. , Tesi Niccolò , Zhang Meng , Ganz Andrea B. , Hulsman Marc , van der Lee Sven , Graat Marieke , Rozemuller Annemieke , Huisman Martijn , van Schoor Natasja M. , van der Flier Wiesje M. , Hoozemans Jeroen , Smit August B , Reinders Marcel J.T. , Holstege Henne 
Published: February 2025

AbstractWe conducted a comprehensive protein quantitative trait loci (pQTL) analysis on a unique set of Gyrus Temporalis Medius (GTM) samples obtained from 88 Alzheimer’s Disease (AD) patients, 53 non-demented individuals, and 49 cognitively healthy centenarians. This investigation revealed 8,081 genetic variants associated with the abundance of 227 proteins, including several novel variant-protein links not identified in a prior pQTL study of the prefrontal cortex or expression QTL (eQTL) analysis across 12 brain regions (GTEx). Among all the AD risk variants tested for possible pQTL effects, only rs429358-T (which encodes the APOE4 allele) was significantly linked to higher APOE levels in the GTM, potentially explaining why this region is particularly prone to AD pathology. Further, through differential correlation analysis we identified AD risk variants linked to altered protein-protein correlations, specifically rs9381040 in TREML2, rs34173062 in SHARPIN, and rs11218343 near SORL1. Notably, DDX17 appears to play a protective role in individuals with the rs9381040-T/T genotype by tightly regulating synuclein levels. Collectively, these findings demonstrate that AD risk variants disrupt protein–protein interactions, highlighting a genetic basis for the coordinated modulation of protein networks in AD.
Seroprevalence of Immunoglobulin G against measles and rubella over a 12-year period (2009 – 2021) in Kilifi, Kenya and the impact of the Measles-Rubella (MR) Vaccine campaign of 2016
Authors: Mburu CN , Ojal J , Selim R , Ombati R , Akech D , Karia B , Tuju J , Sigilai A , Smits G , van Gageldonk PGM , van der Klis FRM , Flasche S , Kagucia EW , Scott JAG , Adetifa IMO 
Published: February 2025

AbstractBackgroundMeasles and rubella have been targeted for elimination by the World Health Organization. Age-specific population immunity to measles and rubella is important to assess progress towards elimination but data are scarce. We conducted seroprevalence surveys to identify disease-specific population immunity profiles in children and adults in Kilifi.MethodsSera from cross-sectional surveys in the Kilifi Health Demographic Surveillance System (2009–2021) were analysed using a fluorescent bead-based multiplex immunoassay. Bayesian multilevel regression with post stratification was used to obtain seroprevalence estimates adjusted for the underlying population and assay performance. Associations between seropositivity and age, sex, location and ethnic group were assessed using a mixed effects logistic regression.ResultsMeasles-adjusted seroprevalence showed a significant increase from 88% in 2009 to 93% in 2021 (τ = 0.875, P = 0.01). Seropositivity was significantly higher in all age groups compared to those under 9 months. Seroprevalence among children ineligible for the first measles vaccine dose (MCV1) remained low (10–57%), whereas MCV1-eligible children (9–17 months) had higher seroprevalence (68–91%). Adult measles seroprevalence exceeded 96%. Rubella seroprevalence followed a similar pattern, with adults above 88%. Following the MR campaign, measles seroprevalence increased from 92% to 96% in eligible children, while rubella seroprevalence rose from 45% to 82%ConclusionPopulation immunity for measles significantly increased over the 12-year period suggesting improvement in immunisation program performance. To reduce reliance on frequent SIAs, efforts should focus on optimising both the timing and coverage of routine doses, particularly ensuring higher coverage of MCV2. The introduction of rubella vaccination has positively impacted immunity in children. Sustaining this immunity is essential to prevent potential gaps in older age groups, which could increase the risk of Congenital Rubella Syndrome (CRS) in infants
Characterization of transcriptomic changes acrossCoccidioidesmorphologies using RiboMarker®-enhanced RNA sequencing
Authors: Howard Jonathan M. , Manning Aidan C. , Clark Rachel C. , Williams Tahirah , Nobile Clarissa J. , Kazakov Sergei , Barberan-Soler Sergio 
Published: February 2025

ABSTRACTCoccidioidesis a dimorphic, pathogenic fungus responsible for transmission of the mammalian disease colloquially known as “Valley fever”. To better understand the molecular basis ofCoccidioidespathogenesis, previous studies have characterized transcriptomes that define transitions between the saprobic and pathogenic life stages of the two species that cause Valley fever -Coccidioides immitis and Coccidioides posadasii. However, none of these studies have focused on small RNA profiles, which have been shown in several pathogenic fungi to play crucial roles in host-pathogen communication, affecting virulence and infectivity. In this study, we analyzed changes in small RNA expression across three major morphologies ofC. posadasii: arthroconidia, mycelia, and spherules, from both intracellular and extracellular fractions. Utilizing RiboMarker® small RNA and RNA fragment library preparation, we show enhanced coverage across the transcriptome by increasing incorporation of normally incompatible RNAs into the sequencing pool. Using these data, we observed transcriptomic shifts during the transition of arthroconidia to either mycelia or spherules, marked largely by changes in both protein-coding, tRNA, and unannotated loci. As little is known regarding the mechanisms governing these life stage transitions, these data provide better insight into those small RNA- and fragment-producing genes and loci that may be required for progression betweenCoccidioidessaprobic and parasitic life cycles. Additionally, analysis of fragmentation patterns across all morphologies suggests unique patterns of RNA fragmentation across a cohort of RNA species that correlate with a given ecotype. Finally, we noted evidence of RNA export to the extracellular space, particularly regarding snRNA and tRNA-derived fragments as well as mRNA-derived transcripts, during the transition to either mycelia or spherules, which may play roles in cell-cell, and/or host-pathogen communication. Going forward, this newly established intra- and extracellularCoccidioidessRNA atlas will provide a foundation for potential biomarker discovery and contribute to our understanding of the molecular basis for virulence in Valley fever.
Expanding plant trait databases using large language model: A case study on flower color extraction
Authors: Bamba Masaru , Sato Shusei 
Published: February 2025

SummaryPlant trait databases play a crucial role in understanding ecological and evolutionary processes yet remain insufficient due to geographical and data availability limitations. To address this limitation, we developed a novel large-scale text extraction approach using a large language model (LLM) to transform descriptions of Floras into structured trait data, thereby expanding existing databases.We applied this approach to extract flower color information from theFlora of Chinaand integrate it into the TRY Plant Trait Database. After integration, the dataset expanded to 27,252 species, more than doubling the previously available flower color records. Additionally, we linked the dataset with occurrence records from GBIF and environmental data, including climate and soil properties, to disentangle ecological insight and flower color distribution.Our large-scale association analysis of flower colors and environments revealed that white, yellow, and red-type flowers exhibit distinct environments, suggesting that abiotic environment can play a role in flower color evolution.By transforming descriptions of Flora into structured data, our approach organizes traits across more plant species, creating new opportunities for ecological and evolutionary research. The present approach can be extended to other traits, enhancing our understanding of how plants adapt and respond to environmental changes on a global scale.
An antisense oligomer conjugate with unpredicted bactericidal activity againstFusobacterium nucleatum
Authors: Cosi Valentina , Jung Jakob , Popella Linda , Ponath Falk , Ghosh Chandradhish , Barquist Lars , Vogel Jörg 
Published: February 2025

ABSTRACTFusobacteria are commensal members of the oral microbiome that can spread from their primary niche and colonize distal sites in the human body. Their enrichment in colorectal and breast cancer tissue has been associated with tumor growth, metastasis, and chemotherapeutic resistance. The use of non-selective antibiotics to remove fusobacteria impairs tumor progression, but prolonged application risks side effects such as gastrointestinal problems and dysbiosis. Species-specific antisense antibiotics based on peptide nucleic acid (PNA) have shown efficacy in many Gram-negative species, suggesting that antisense PNAs may also enable a tailored depletion of fusobacteria. Here, we have investigated the antibacterial potential of cell-penetrating peptide (CPP)-PNA conjugates targeting the mRNA of putative essential genes inFusobacterium nucleatum. Unexpectedly, we observed no growth inhibition with any of the target-specific PNAs, but identified a non-targeting control CPP-PNA (FUS79, (RXR)4XB-GACATAATTGT) as a potent growth inhibitor ofF. nucleatum. Our data suggest that the CPP and specific sequence features of FUS79 are responsible for its activity, rather than an antisense effect. Interestingly, FUS79 also inhibits the growth of five additional fusobacterial strains but not ofF. nucleatumssp.vincentii(FNV). RNA-seq analysis indicates that FUS79 induces a membrane stress response in a vulnerableF. nucleatumstrain but not in FNV. Collectively, our attempt at developing antisense antibiotics for fusobacteria discovers a potent growth inhibitor, whose bactericidal effect appears independent of target-specific mRNA inhibition.IMPORTANCEEnrichment ofF. nucleatumat cancer sites is associated with increased tumor growth and metastasis. Antibiotic treatment to remove the bacteria was shown to change the course of cancer progression. Here we explore first steps to establish peptide nucleic acids (PNAs) as specific antisense antibiotics, thereby laying the foundation for further development of antisense technology in fusobacteria. While the CPP-PNA FUS79 was initially designed as a control, we observed that the compound was bactericidal for specific fusobacterial strains. Our results suggest that FUS79 might be able to selectively deplete fusobacterial strains from bacterial communities, offering a new perspective on fusobacterial removal at the tumor site.
Comparative Computational Docking Analysis of MPP+ and Dopamine Binding to Dopamine Transporter in Human and Zebrafish: Mechanistic Insights into MPTP Neurotoxicity
Authors: Razali Khairiah , Kumar Jaya , Mohamed Wael M. Y. 
Published: February 2025

Abstract1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces parkinsonism via its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP+), which structurally mimics dopamine and enters dopaminergic neurons via the dopamine transporter (DAT). To visually depict this mimicry, we performed ligand-protein docking analysis on two species: humans and zebrafish. Human DAT (PDB ID: Q01959) and zebrafish DAT (UniProt ID: Q90ZV1) proteins were prepared with AutoDock Tools. Meanwhile, MPP+ (PubChem ID: CID_39484) and dopamine (PubChem ID: CID_681) ligands were prepared and optimized using the General AMBER Force Field (GAFF) tool. Docking with AutoDock Vina used identical grid parameters of 40 x 40 x 40 Å, which allows blind docking. Binding affinities and interactions were analyzed and visualized using PyMol and LigPlot+. MPP+ exhibited comparable binding affinities to dopamine in both species (human: -7.2 vs -6.1 kcal/mol; zebrafish: -7.6 vs -6.4 kcal/mol), sharing seven out of nine binding residues in humans and nine out of twelve in zebrafish. Spatial overlap with dopamine binding site suggests MPP+ exploits DAT for neuronal entry. However, static docking limitations warrant dynamic validation. This study provides computational evidence for the dopamine-mimetic mechanism of MPP+ but underscores the need for molecular dynamics (MD) simulation and experimental confirmation.
Degradation of ribosomal RNA duringPlasmodium falciparumgametocytogenesis
Authors: Grünebast Janne , Singhal Ritwik , Bromley Robin , Kanatani Sachie , Watson Kaylee , Dumetz Franck , Pascini Tales Vicari , Tripathi Abhai , Dunning Hotopp Julie C , Sinnis Photini , Llinás Manuel , Serre David 
Published: February 2025

AbstractThe life cycle ofPlasmodium falciparumis characterized by complex regulatory changes that allow adaptation of the parasites to different environmental conditions, which are especially pronounced during transmission between the mammalian host and the insect vector. Previous studies have shown thatP. falciparumuses three types of ribosomal RNAs (rRNA A-, S1- and S2-types) at different stages of its life cycle. We used Oxford Nanopore Technologies (ONT) direct RNA sequencing to investigate the dynamics of rRNA usage throughout the parasite’s intraerythrocytic development, as well as in salivary gland sporozoites. Our study revealed a preponderance of A-type rRNAs during the intraerythrocytic cycle and gametocytogenesis, while S-type rRNAs slowly increase in abundance in mosquito stages starting three days post infection. Salivary gland sporozoites showed an even proportion of all rRNA types. By examining the length distributions of rRNA molecules, we detected an extensive and specific degradation of rRNAs during gametocytogenesis, starting in stage II gametocytes and continuing until the final stages of gametocyte development. We hypothesize that rRNA degradation may be linked to the global translational repression and metabolic quiescence described in stage V gametocytes, similar to mechanisms observed in bacterial and eukaryotic stress responses.
Annexin A1 as a key modulator of lung inflammation during coronavirus infections
Authors: Resende Filipe , Queiroz-Junior Celso Martins , Ascenção Fernando Roque , Chaves Ian de Meira , Lacerda Larisse de Souza Barbosa , Rocha Felipe , Teixeira Danielle , Galvão Izabela , Costa Victor , Fonseca Talita , Gualberto Arthur , Santos Ana Luiza de Castro , Martins Jenniffer , Lima Erick Bryan de Sousa , Monteiro Adelson Héric Alves , Zaidan Isabella , Grossi Laís C. , Costa Pedro Augusto Carvalho , Beltrami Vinicius Amorim , Sousa Lirlândia P. , Guimarães Pedro Pires Goulart , Campolina-Silva Gabriel , Teixeira Mauro M , Pinho Vanessa , Costa Vivian V 
Published: February 2025

AbstractExacerbated inflammation is a major contributor to tissue damage and mortality in infectious diseases, including SARS-CoV-2. The resolution phase of inflammation is critical for restoring tissue homeostasis following an injury. Annexin A1 (AnxA1) is a ubiquitous protein that plays a fundamental role in the resolution of inflammation, including in preclinical models of infectious disease. Here, we investigated the role of AnxA1 in coronavirus infection and its potential as a host-targeted therapeutic strategy against SARS-CoV-2. Wild-type (WT) and AnxA1 knockout (AnxA1KO) mice were intranasally infected with the murine betacoronavirus MHV-3 to study the endogenous role of AnxA1. Immunohistochemistry and Western blot analyses in the lungs of MHV-3-infected mice revealed increased AnxA1 expression and its cleavage, which was associated with neutrophilic infiltration (Ly6G+ cells) mainly in peribronchiolar and perivascular regions. AnxA1-deficient mice exhibited higher neutrophilic infiltration and lung damage, alongside increased CXCL1 production in the lungs, when compared to WT-infected mice. In a murine model of SARS-CoV-2 infection in K18-hACE2 mice, we found increased AnxA1 cleavage associated with lung inflammation. Treatment of SARS-CoV-2-infected K18-hACE2 mice with the AnxA1-mimetic peptide, Ac2-26, reduced lung damage and lethality, without altering the host ability to deal with viral replication. Notably, Ac2-26-treated mice exhibited similar levels of protection to that afforded by the nucleotide analogue Remdesivir, following SARS-CoV-2 infection. Our findings highlight the protective role of the endogenous AnxA1 in mitigating coronavirus-induced lung inflammation and underscore the therapeutic potential of AnxA1 mimetic Ac2-26as a host-targeted therapy against SARS-CoV-2.
Inspecting Consistency Between US and European Vitamin D Guidelines Using Physiologically-Based Pharmacokinetics Modelling
Authors: Tao You 
Published: February 2025

AbstractAccording to the US official guideline for vitamin D, serum 25-hydroxyvitamin D over 125 nmol/L is linked to potential toxicity. Using a physiologically-based pharmacokinetics model based on a randomised controlled trial in Cape Town, South Africa, we showed the 2000 IU daily dose, recommended by European Food Safety Agency as a safe dose, is expected to lead to serum concentration exceeding the 125 nmol/L threshold among some children and adolescents. This highlights inconsistency between different guidelines and the need to use modelling to bridge the gap between dose and pharmacokinetics.
Integrative Genome-Wide Association Studies of COVID-19 Susceptibility and Hospitalization Reveal Risk Loci for Long COVID
Authors: Cheng Zhongshan 
Published: February 2025

AbstractLong COVID presents a significant public health challenge, characterized by over 200 reported symptoms spanning multiple organ systems. Despite its complexity, genome-wide association studies (GWAS) offer a pathway to uncovering genetic risk factors, though progress has been hindered by the disorder’s symptom heterogeneity and the limited power of available datasets. Recent long COVID GWASs have highlighted key genetic associations, such as variants close toFOXP4,ABO, andHLA-DQA1, while underscoring the limitations posed by small sample sizes, restricted diversity, and misclassification biases. Here, an integrative analysis using COVID-19 GWAS data from the Host Genetics Initiative (HGI, release 7) was performed by leveraging proxy phenotypes to overcome the challenges of limited sample size or heterogeneity of long COVID cohorts, resulting in 62 independent single nucleotide polymorphisms (SNPs) prioritized as potentially associated with long COVID. These SNPs were categorized into three groups: (1) severe COVID-19-specific SNPs, such as SNPs mapped to two well-known loci involved in SARS-CoV2 entry (ACE2[rs190509934] andTMPRSS2[rs12329760]), as well as variants ofDPP9(rs7251000),FOXP4(rs12660421) andHLA-DQA1(rs17219281), exhibiting associations with severe COVID-19 but displaying weaker signals in non-hospitalized COVID-19 cases; (2) SNPs associated with both severe and mild COVID-19, including the SNP close toABO(rs505922), representing a catalog of SNPs predispose to both acute COVID-19 and chronic long COVID; and (3) non-hospitalization-specific SNPs, such as variants inKCTD16(rs62401842) andWASF3(rs56143829), highlighting genetic contributors specific to mild COVID-19 cases that might also contribute to long COVID. Further transcriptome-wide association studies (TWASs) across 48 GTEx tissues, leveraging GWAS data on COVID-19 hospitalization, susceptibility, and long COVID from the HGI consortium, revealed distinct tissue-specific patterns of association. Compared to the acute COVID-19 phenotypes, long COVID exhibited weaker association signals across heart, brain, and muscle-related tissues, as determined by correlations between gene expression of adjacent genes of candidate SNPs (43 out of 62 SNPs) and different COVID phenotypes. Notable TWAS hits includedDPP9(rs7251000),CCR1(rs17078348), andTHBS3(rs41264915). Phenome-wide TWASs also identified additional significant associations with long COVID related phenotypes, such asHLA-DQA1(rs17219281),HLA-A(rs9260038), andHLA-C(rs1634761) associated with immune-related diseases,GSDMB(rs9916158) associated with asthma,FOXP4(rs12660421) linked with sleep duration, highlighting their potential roles in long COVID pathophysiology. Therefore, current integrative approach offers a scalable framework for long COVID research by maximizing the statistical power of existing large-scale COVID-19 GWASs and provides novel insights into the genetic underpinnings of long COVID.