bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysogen formation governs colonies while lytic infection is more prevalent in single cells of the bloom-forming cyanobacterium,Microcystis
Authors: Huang X. , Chase EE , Zepernick BN , Martin RM , Krausfeldt LE , Pound HL , Wu H. , Zheng Z. , Wilhelm SW 
Published: February 2025

AbstractWhile the bloom-forming cyanobacteriumMicrocystiscan exist as free-living single cells or within dense mucilaginous colonies, the drivers and consequences of colony formation remain unclear. Here, we integrated metatranscriptomic datasets from twoMicrocystisbloom events in Lake Taihu, China, to analyze and validate the functional differences between colonial and single-cellMicrocystis. Our results confirmed colony expression profiles were disproportionately enriched inMicrocystistranscripts (and functions) compared to other prokaryotic taxa. Concomitantly, viral infection strategies diverged byMicrocystiscommunity morphology: colony-associated cells expressed lysogeny-associated genes, while single cells exhibited increased signatures of lytic infection. These data are consistent with the hypothesis thatMicrocystiscolonies foster conditions favorable to lysogen formation—likely due to local high cell densities and the resulting advantage of superinfection immunity—whereas solitary cells experience stronger lytic pressure. On a broader scale, our findings refine the understanding of bloom dynamics by identifying how community morphological states coincide with distinct host–virus interactions. Cumulatively, this work underscores the importance of colony formation in shapingMicrocystisecology and highlights the need for mechanistic studies that disentangle the interplay between phage infection modes, colony formation, and microbial community structure.
Reversible lipid mediated pH-gating of connexin-46/50 by cryo-EM
Authors: Jarodsky Joshua M. , Myers Janette B. , Reichow Steve L. 
Published: February 2025

ABSTRACTGap junctions, formed by connexin proteins, establish direct electrical and metabolic coupling between cells, enabling coordinated tissue responses. These channels universally respond to intracellular pH changes, closing under acidic conditions to limit the spread of cytotoxic signals during cellular stress, such as ischemia. Using cryo-electron microscopy (cryo-EM), we uncover insights into the structural mechanism of pH-gating in native lens connexin-46/50 (Cx46/50) gap junctions. Mild acidification drives lipid infiltration into the channel pore, displacing the N-terminal (NT) domain and stabilizing pore closure. Lipid involvement is both essential and fully reversible, with structural transitions involving an ensemble of gated-states formed through non-cooperative NT domain movement as well as minor populations of a distinct destabilized open-state. These findings provide molecular insights into pH-gating dynamics, illustrating how structural changes may regulate gap junction function under cellular stress and linking Cx46/50 dysregulation to age-related cataract formation.
Modeling cerebral developmentin vitrowith L-MYC-immortalized human neural stem cell-derived organoids
Authors: Velazquez Ojeda Alejandra , Awabdeh Dina , Brewster Blake , Rockne Russell , O’Meally Denis , Yin Hongwei Holly , Carlesso Nadia , Brown Christine E. , Gutova Margarita , Barish Michael E. 
Published: February 2025

ABSTRACTA promising advance forex vivostudies of human brain development and formulation of therapeutic strategies has been the adoption of brain organoids that, to a greater extent than monolayer or spheroid cultures, recapitulate to varying extents the patterns of tissue development and cell differentiation of human brain. Previously, such studies been hampered by limited access to relevant human tissue, inadequate humanin vitromodels, and the necessity of using rodent models that imperfectly reproduce human brain physiology. Here we present a novel organoid-based research platform utilizing L-MYC-immortalized human fetal neural stem cells (LMNSC01) grown in a physiological 4% oxygen environment.We visualized developmental processes in LMNSC01 brain organoids for over 120 daysin vitroby immunofluorescence and NanoString gene expression profiling. Gene expression patterns revealed by NanoString profiling were quantitatively compared to those occurring during normal brain development (BrainSpan database) using theSingscoremethod. We observe similar developmental patterns in LMNSC01 organoids and developing cortex for genes characterizing neurons, astrocytes, and oligodendrocytes, and multiple pathways including those involved in apoptosis, neuronal cytoskeleton, neurotransmission, and metabolism. Notable properties of this LMNSC01 platform are its initiation with immortalized authentic human neural stem cells, growth in a physiological oxygen environment, the consistency of the organoids produced, and favorable comparison of their gene expression patterns with those reported for normal cortical development.SUMMARYEx vivostudies of human brain development has been advanced by adoption of organoids recapitulating to varying extentsin uteropatterns of tissue development and cell differentiation. We here present an organoid-based human cortical development platform employing immortalized fetal neural stem cells (LMNSC01) grown in a physiological (4% oxygen) environment. Characterizing LMNSC01 organoids for over 120 daysin vitroby immunofluorescence and expression profiling (using NanoString), and then comparing these profiles to those of normal cortical development (BrainSpan database), revealed similar developmental patterns for neurons, astrocytes and oligodendrocytes. Notable properties of this platform are its initiation with immortalized authentic human NSCs, growth at physiological oxygen concentration, and subsequent favorable comparison of their gene expression patterns with those observed during cortical development.
Synthetic community Hi-C benchmarking provides a baseline for virus-host inferences
Authors: Shatadru Rokaiya Nurani , Solonenko Natalie E. , Sun Christine L. , Sullivan Matthew B. 
Published: February 2025

AbstractMicrobiomes are now recognized as key influencers of diverse ecosystems, but it is increasingly evident that viruses impose significant constraints on these microbial communities. While viromics has expanded virus genomic catalogs, identifying hosts for these viruses remains a major challenge due to the limitations in scaling for cultivation and to the uncertain reliability ofin silicopredictions for understudied virosphere regions. A promising recent advance, Hi-C, a proximity ligation-based method, aims to infer virus-host linkages by analyzing sequences from cross-linked virus and host genomic fragments. This approach has been applied in at least seven studies, yet its accuracy has not been systematically assessed. Here we evaluate Hi-C performance in predicting virus-host interactions using a synthetic community consisting of four bacterial strains and nine phages with known, experimentally determined, quantitative interactions. Our analysis revealed that Hi-C linkage scores used in the literature perform poorly (13% specificity, 100% sensitivity). By converting linkage scores to Z-scores and applying filtering (Z-score ≥ 0.5), we dramatically increased prediction accuracy, though at reduced sensitivity (96% specificity, 57% sensitivity). These findings provide empirical data and establish guidelines for interpreting Hi-C inferred virus-host linkages, with the aim of improving its reliability across diverse ecosystems.
Neural dynamics of proactive and reactive cognitive control in medial and lateral prefrontal cortex
Authors: Khan Anas U. , Hoy Colin , Anderson Kristopher L. , Piai Vitoria , Stephens David King- , Laxer Kenneth D. , Weber Peter , Lin Jack J. , Knight Robert T. , Bentley J. Nicole 
Published: February 2025

AbstractGoal-directed behavior requires adjusting cognitive control to both react to and prepare for conflict. Previous work indicates theta oscillations and population activity in dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) are critical for reactive control. However, the neural mechanisms supporting proactive control are less clear. Here, we investigated the neural basis of behavioral adaptations when control is prepared in anticipation of conflict using intracranial EEG (iEEG) in dmPFC and dlPFC during a Stroop task where conflict frequency was manipulated across blocks. We observed canonical conflict-driven increases in dmPFC theta and in dmPFC and dlPFC local population activity, as indexed by high frequency activity (HFA). Conflict also suppressed theta power in both regions after the response, accentuated a pre-response beta desynchronization selectively in dlPFC, and increased a post-response beta rebound in both regions. Importantly, we identified a pre-trial marker of proactive control where dmPFC theta power increased before trials when conflict was expected, and theta, beta, and HFA conflict signals in both regions were enhanced when conflict was rare and diminished when conflict was common. These findings reveal shared HFA but dissociable oscillatory dynamics in dmPFC and dlPFC during reactive conflict processing, highlight pre-trial dmPFC theta as a potential substrate for proactive control, and refine the roles of dmPFC and dlPFC in control adaptations.
StackGlyEmbed: Prediction of N-linked Glycosylation sites using protein language models
Authors: Nafi Md Muhaiminul Islam , Rahman M Saifur 
Published: February 2025

AbstractN-linked glycosylation is one of the most basic post-translational modifications (PTMs) where oligosaccharides covalently bond with Asparagine (N). These are found in the conserved regions like N-X-S or N-X-T where X can be any residue except Proline (P). Prediction of N-linked glycosylation sites has great importance as these PTMs play a vital role in many biological processes and functionalities. Experimental methods, such as mass spectrometry, for detecting N-linked glycosylation sites are very expensive. Therefore, prediction of N-linked glycosylation sites has become an important research field. In this work, we propose StackGlyEmbed, a stacking ensemble machine learning model, to computationally predict N-linked glycosylation sites. We have explored embeddings from several protein language models and built the stacking ensemble using SVM, XGB and KNN learners in the base layer, with a second SVM model in the meta layer. StackGlyEmbed achieves 98.2% sensitivity, 92.5% balanced accuracy, 89.1% F1-score and 82.6% MCC in independent testing, outperforming the existing SOTA methods. StackGlyEmbed is freely available athttps://github.com/nafcoder/StackGlyEmbed.
Multi-omics-based analysis of the effect of longevity genes on the immune relevance of colorectal cancer
Authors: Huang Yichu , Min Guangtao , Wang Hongpeng , Jiang Lei 
Published: February 2025

AbstractBackgroundColorectal cancer (CRC) ranks as the third most prevalent cancer globally, with its incidence and recurrence rates steadily rising. To explore the relationship between CRC and longevity-associated genes, and to offer new therapeutic avenues for CRC treatment, we developed a prognostic model based on these genes to predict the outcomes for CRC patients. Additionally, we conducted an immune correlation analysis.MethodsWe conducted a comprehensive analysis of the effects of 81 longevity-associated genes in CRC by integrating multiple omics datasets. This analysis led to the identification of two distinct molecular subtypes and revealed that alterations in longevity-related genes across various layers were linked to clinicopathological features, prognosis, and cell infiltration characteristics within the tumor microenvironment (TME). The training and validation cohorts for the models were derived from the TCGA-COAD, TCGA-READ, and GSE35279 datasets. Subsequently, we developed a risk score model, and the Kaplan–Meier method was employed to estimate overall survival (OS). Ultimately, we established a prognostic model based on five longevity-associated genes: BEDN3, EXOC3L2, CDKN2A, IL-13, and CAPN9. Furthermore, we assessed the correlations between the risk score and factors such as immune cell infiltration, microsatellite instability, and the stem cell index.ResultsOur comprehensive bioinformatics analysis revealed a strong association between longevity genes and CRC. The risk score derived from the five newly identified longevity-associated genes was determined to be an independent prognostic factor for CRC. Patients categorized by this risk score demonstrated significant differences in immune status and microsatellite instability.ConclusionOur comprehensive multi-omic analysis of longevity-associated genes highlighted their potential roles in the tumor immune microenvironment, clinicopathological features, and prognosis, offering new insights for the treatment of CRC.
Identification of the immune-associated enhancer RNA SATB1-AS1 as a novel biomarker for thymic cancer prognosis
Authors: Wang Hongpeng , Huang Yichu , Min Guang-tao , Jiang Lei 
Published: February 2025

AbstractsObjectiveTo screen key enhancer RNAs (eRNAs) in thymoma (THYM) through The Cancer Genome Atlas (TCGA) database and explore their potential as prognostic molecules and therapeutic targets in THYM.MethodsGene expression RNA-seq profiles of 33 cancer types were retrieved and downloaded from the TCGA database, and Kaplan–Meier survival analysis and Spearman correlation analysis were applied to screen eRNAs and target genes associated with survival in THYM patients. The correlation of target eRNAs with clinical features was assessed. Gene set enrichment analysis was performed to investigate the potential biological functions of target eRNAs. Validation of the prognostic potential of target eRNAs across cancers in other cancer types.ResultsIn THYM, SATB1-AS1 and the target gene SATB1 were associated with poor patient prognosis, and SATB1-AS1 expression was correlated with patient stage (P<0.05). Gene and pathway enrichment analyses revealed that SATB1-AS1 was associated with leukocyte transendothelial migration, natural killer cell-mediated cytotoxicity, neutrophil extracellular trap formation, PD-L1 expression and the PD-1 checkpoint pathway in cancer.ConclusionSATB1-AS1 may be a key eRNA in THYM and has the potential to be a marker and therapeutic target for the early diagnosis and prognosis of THYM.
Chronic early-life obesity linked to childhood impulsivity predicts long-term psychosis trajectory through dose-dependent cerebellar dysmaturation in 22q11.2 Deletion Syndrome
Authors: Sandini Corrado , Reich Natacha , Delavari Farnaz , Pajic Lara , Escelsior Andrea , Forrer Silas , Imparato Andrea , Kojovic Nada , Latreche Caren , Parlatini Valeria , Cortese Samuele , Schneider Maude , Eliez Stephan 
Published: February 2025

AbstractBackgroundRecent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires: 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms.MethodsTo address these key issues, we investigated bidirectional pathways linking behavioral, BMI, and neurodevelopment trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 Deletion Syndrome (22q11DS), and 182 neurotypical controls, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association.ResultsChildhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories. In turn, pubertal BMI-increases were associated with concomitant worsening of depressive symptoms, while chronic BMI-increases emerging during childhood predicted the subsequent emergence of psychosis during late-adolescence/early-adulthood. The duration of increased BMI-status was associated with emergence of motor and cognitive disorganization, a key schizophrenia symptom domain, which was linked to progressive gray matter volume reductions in posterior-inferior cerebellum.ConclusionsThese findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS, by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.
OMKar: optical map based automated karyotyping of genomes to identify constitutional abnormalities
Authors: Dehkordi Siavash Raeisi , Jia Zhaoyang , Estabrook Joey , Hauenstein Jen , Miller Neil , Güleray-Lafci Naz , Neesen Jürgen , Hastie Alex , Chaubey Alka , Chun Pang Andy Wing , Dremsek Paul , Bafna Vineet 
Published: February 2025

AbstractThe whole genome karyotype refers to the sequence of large chromosomal segments that make up an individual’s genotype. karyotype analysis, which includes descriptions of aneuploidies and other rearrangements is crucial for understanding genetic risk factors, for diagnosis, treatment decisions, and genetic counseling linked to constitutional disorders. The current karyotyping standard is based on microscopic examination of chromosomes, a complex process that requires high expertise and offers Mb scale resolution.Optical Genome Mapping (OGM) technology can identify large DNA lesions in a cost-effective manner. In this paper, we developed OMKar, a method that uses OGM data to create a virtual karyotype. OMKar processes Structural (SV) and Copy Number (CN) Variants as inputs and encodes them into a compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming to maintain CN balance and then identifies constrained Eulerian paths representing entire donor chromosomes. In tests using 38 whole genome simulations of constitutional disorders, OMKar reconstructed the karyotype with 88% precision and 95% recall on SV concordance and 95% Jaccard score on CN concordance. We applied OMKar to 50 prenatal, 41 postnatal, and 63 parental samples from ten different sites. OMKar reconstructed the correct karyotype in 144 out of 154 samples, covering 25 of 25 aneuploidies, 32 of 32 balanced translocations, and 72 of 82 unbalanced variations. Detected constitutional disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, and Turner syndromes. Importantly, it identified a plausible genetic mechanism for five cases of constitutional disorder that were not detected by other technologies.Together, these results demonstrate the robustness of OMKar for OGM-based karyotyping. OMKar is publicly available athttps://github.com/siavashre/OMKar.
Development and psychometric testing of EPAT-16: A short and valid measure for patient-centeredness from the patient’s perspective
Authors: Christalle Eva , Kriston Levente , Zeh Stefan , Führes Hannah , Schellhorn Alica , Hahlweg Pola , Zill Jördis , Härter Martin , Scholl Isabelle 
Published: February 2025

ABSTRACTBackgroundWe previously developed the EPAT-64, a patient-reported experience measure designed to assess patient-centeredness (PC) across 16 dimensions of the validated integrative model of PC. While its modular structure makes it highly adaptable to examine certain dimensions of PC, generating an overall PC score requires assessing all 64 items. This is often challenging in routine settings with limited resources. Therefore, we developed and psychometrically tested a 16-item short form.MethodsWe conducted a cross-sectional study involving adult inpatients and outpatients receiving treatment for cardiovascular diseases, cancer, musculoskeletal disorders, and mental health conditions in Germany. To ensure comprehensive content coverage, we selected one item per dimension based on content relevance as well as item characteristics such as item difficulty and item-total correlation. We assessed the structural validity of a unidimensional model using confirmatory factor analysis (CFA), measured reliability with McDonald’s Omega, and evaluated construct validity by investigating the intercorrelation of the EPAT-16 sum score with measures of general health status and satisfaction with care.ResultsAll items of the final EPAT-16 showed high acceptability and good item-total correlations, with approximately two-thirds demonstrating appropriate item difficulty. CFA showed a slight misfit of the unidimensional model, but high average variance explained. McDonald’s Omega showed high reliability. All hypotheses about construct validity were confirmed.ConclusionsThe EPAT-16 demonstrated good psychometric properties, making it a feasible tool for assessing overall PC when resource constraints preclude using the full EPAT-64. In particular, it can be used in routine care for feedback and quality improvement, as well as in research to assess relationships with other relevant variables. Since its items were designed generically, it can be used for different medical conditions and settings, for example, for public reporting. Future research should evaluate the EPAT-16 in diverse, independent patient samples to confirm that its positive characteristics are consistent across different populations and cultures.Patient or Public ContributionPatients did not participate as active members of the research team. However, for the research proposal, several patient organizations provided positive feedback on the study aims and their relevance, signed a collaboration agreement, and later supported recruitment by distributing study information.
Predictive Capabilities of Polygenic Scores in an East-Asian Population-based Cohort: The Singapore Chinese Health Study
Authors: Chang Xuling , Shih Chih Chuan , Chen Jieqi , Lee Ai Shan , Tan Patrick , Wang Ling , Liu Jianjun , Li Jingmei , Yuan Jian-Min , Khor Chiea Chuen , Koh Woon-Puay , Dorajoo Rajkumar 
Published: February 2025

AbstractBackgroundExisting polygenic scores (PGS) are derived primarily from studies performed in European populations. It is still unclear how these perform in improving risk predictions in East-Asians.MethodsWe generated 2,173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study (SCHS), a prospective cohort of 23,622 middle-aged and older Chinese residing in Singapore. We used linear regression to evaluate PGS performances for quantitative traits by calculating the explained variance (r²). For dichotomized phenotypes, we employed logistic regression to estimate the area under the receiver operating characteristic curve (AUC) in predictive models.ResultsOverall, traits with higher heritability scores exhibited stronger associations with PGSs, while behavioural traits, for example sleep duration and hours spent watching TV, showed weaker associations. Height and type 2 diabetes (T2D) exhibited the largest SNP-based heritability estimates with the largest increments in explained variance and AUC, respectively, compared to phenotypic models. We explored the effect of T2D risk factors on the association between the T2D PGS (PGS003444) and incident T2D. The PGS association was significantly mediated and modified by hypertension (Pindirect=1.56×10−18,Pinteraction=1.11×10−6) and body mass index (BMI,Pindirect=1.25×10−36,Pinteraction=2.10×10−3). The prediction ability of PGS003444 for incident T2D was stronger was stronger among individuals who were non-overweight without hypertension (AUC=0.774) than in overweight individuals with hypertension (AUC=0.709).ConclusionsIn conclusion, our study demonstrated the divergent ability of PGSs in predictions of complex traits, and showed that for certain traits, such as T2D, PGSs may have the potential for improving risk prediction and personalized healthcare.