bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligodendroglia vulnerability in the human dorsal striatum in Parkinson’s disease
Authors: Barba-Reyes Juan M. , Harder Lisbeth , Salas Sergio Marco , Jaisa-aad Methasit , Muñoz-Castro Clara , Rafati Nima , Nilsson Mats , Hyman Bradley T. , Serrano-Pozo Alberto , Muñoz-Manchado Ana B. 
Published: January 2025

AbstractOligodendroglia are the responsible cells for myelination in the central nervous system and their involvement in Parkinson’s disease (PD) is poorly understood. We performed snRNA-seq and image-based spatial transcriptomics of human caudate nucleus and putamen (dorsal striatum) from PD and Control brain donors to elucidate the diversity of oligodendroglia and how they are affected by the disease. We have defined fifteen subclasses, from precursor to mature cells, four of which are disease-associated. These PD-specific populations are characterized by the overexpression of heat shock proteins and distinct expression signatures, including immune responses and myelination alterations. We have also identified disruptions in cell communication and oligodendrocyte development, evidenced by changes in neurotransmitter receptors expression and cell adhesion molecules. These transcriptomic changes correlated with impaired myelin integrity and altered oligodendrocyte distribution in the striatum. Thus, we uncover oligodendroglia as a critical cell type in PD and a potential new therapeutic target.
Towards a Generative Paradigm for Large-scale Microbiome Analysis by Generative Language Model
Authors: Zhang Haohong , Kang Zixin , Zhang Yuli , Yang Ronghua , Ning Kang 
Published: January 2025

AbstractMicrobiome analysis has traditionally relied on taxonomic abundance tables, which, while effective, often constrain the exploration of deeper contextual relationships. In this study, we present MGM 2.0, a novel framework that applies advanced natural language processing (NLP) techniques to microbiome research. By reimagining microbiome samples as sentences and microbial species as words, MGM 2.0 enabled the extraction of nuanced patterns and relationships. The model demonstrated robust predictive performance in identifying exogenous species colonization (AUROC = 0.86). Additionally, through prompt-guided microbiome data generation, MGM 2.0 produced realistic microbial profiles conditioned on disease labels. The framework further revolutionized donor selection in fecal microbiota transplantation (FMT) by framing it as a sequence-to-sequence prediction task, enabling the prediction of post-transplantation community compositions and the identification of super donors for personalized treatments (average increase in C2R = 0.52). This innovative integration of NLP and microbiome science provides a versatile toolkit for predictive modeling, data generation, and personalized medicine.HighlightsIntroduced MGM 2.0, a generative language model utilizing sentence-like representation for microbiome analysis and generation.Demonstrated that sentence-like representation preserves sample distinctions, enabling accurate microbial sample classification tasks, such as colonization prediction.Generated realistic, disease-specific microbiome profiles using a prompt-guided approach, validated by a novel “Microbiome Turing Test.”Applied MGM 2.0 to fecal microbiota transplantation (FMT) donor selection, accurately predicting post-transplant community compositions and identifying potential “super donors” for personalized treatment strategies.
Metadata Harmonization from Biological Datasets with Language Models
Authors: Verbitsky Alexander , Boutet Patrick , Eslami Mohammed 
Published: January 2025

AbstractBiomedical research faces significant challenges in harmonizing metadata across diverse datasets due to inconsistent labeling and the lack of universally adopted ontologies. Conventional solutions, such as Common Data Elements, face adoption difficulties as they impede scientific progress by requiring researchers to navigate through thousands of standardized terms with subtle variations. Tools such as laboratory information management systems, while designed to enforce standardization, can hinder research progress when their rigid standards conflict with domain-specific documentation needs and evolving research practices. As a result of these challenges, researchers maintain their own annotation systems, leading to disconnected datasets that are difficult to integrate across studies.This study presents a novel approach using large language models to automatically standardize researcher annotations to standards within ontologies. The approach is applied to multiple domains such as oncology, alcohol research, and infectious disease. Data augmentation strategies are presented to align training data with the space of human representations. These strategies generate realistic variations of standard terms to simulate how researchers naturally document their work, especially valuable in domains lacking the extensive terminology mappings needed for training language models. Experiments with fine-tuned GPT-2 variants show up to 96% accuracy on in-dictionary tasks and 17% on out-of-dictionary tasks, outperforming traditional techniques and zero-shot GPT-4o applications. This implies that there can be up to a 96% reduction in metadata standardization labor if a term exists in an ontology. We also show a significant trade-off between domain-specific models versus those that aim to generalize across domains such as infectious disease or alcohol research. While larger models excel at generalization, fine-tuned models consistently outperform on domain-specific terminology. This approach enables more efficient and accurate research data integration across biomedical fields, though out-of-dictionary generalization remains a challenge across all model sizes.
Single cell resolved spatial immune repertoire unveils spatial heterogeneity of lymphoid aggregates in human immune disorders
Authors: Zhan Xiaojuan , Liu Yi , Guo Yanying , Zhou Wenwen , Yan Yixin , Zeng Hui , Dong Xuan , Chen Xiaoyu , Ma Rong , Liu Zhong , Zhu Fan , Zheng Xubin , Li Xinxing , Yin Jinwen , Chan Francis Ka-ming , Liu Chuanyu , Liu Longqi , Xu Xun , Hou Yong , Tao Haoran , Dong Yuliang , Zeng Tao , Li Young , Zhou Jingying , Zeng Zexian , Feng Yu 
Published: January 2025

AbstractAdaptive immunity, mediated by T and B cell responses, is essential for defending against infections and cancers while also being implicated in autoimmune diseases. Tracking T and B cell repertoiresin situat single-cell resolution is essential for understanding adaptive immune responses. To address the lack of tools forin situsingle-cell T/BCR (XCR) sequencing, we developed Stereo-XCR-seq, an efficient strategy for retrieving and sequencing TCR and BCR from Stereo-seq cDNA libraries at subcellular resolution. Stereo-XCR-seq provides unbiased full-length XCR reads alongside spatial transcriptomics, enabling the identification of heterogeneous lymphoid aggregates with distinct clonal activities in cancers and inflammatory bowel disease (IBD). We identified plasma cell aggregates that differ from tertiary lymphoid structures (TLSs) in both transcriptomic profiles and clonal activities, with spatial positioning potentially mediating unique immune responses. Collectively, Stereo-XCR-seq enablesin situsingle-cell profiling of T and B cell clonal activities within tissue microenvironments, providing insights into lymphocyte adaption to environmental stimuli. This technology provides potential for advancing our understanding of tissue immunity and the development of therapeutic strategies for immune disorders.
Phylogeny, ethnomedicinal use and the distribution of phytoestrogens in the Fabaceae
Authors: Thaweepanyaporn Kongkidakorn , Thompson Jamie B. , Vasudevan Nandini , Hawkins Julie A. 
Published: January 2025

AbstractAim of the studyEthnomedicinal knowledge is a critical resource for drug discovery, and when combined with phylogenetic analysis, it increases the precision of bioprospecting. Phytoestrogens, compounds from plants with estrogenic activity, are commonly found across the Fabaceae family and hold the potential for managing menopause-related symptoms. This study focuses on methods to identify novel sources of phytoestrogens from the Fabaceae.Materials and MethodsWe identified 183 Fabaceae species traditionally used as aphrodisiacs or with application to control fertility to create a cross-cultural dataset of ethnomedicinal use. Phylogenetic analysis revealed “hot nodes”—lineages with a higher-than-expected number of species with these traits. The known distribution of estrogenic flavonoids was used to test whether the frequency of phytoestrogen-containing species was higher in “hot nodes”. Additionally, we examined the overlap of aphrodisiac-fertility uses with neurological applications, hypothesising that such species may have bioactive compounds with estrogenic properties. Lastly, the “hot-node” lineages without previously known estrogenic flavonoids were identified.ResultsSpecies in hot nodes were more likely to contain estrogenic flavonoids (21% of species), a major group of phytoestrogens, compared to Fabaceae as a whole (7% of species). Moreover, aphrodisiac-fertility species with neurological applications showed even higher search efficiency, with 62% of such species confirmed to contain estrogenic flavonoids. Furthermore, we identified 43 high-priority hot nodes including several notable genera such asDelonixandIndigofera.These lineages might represent promising targets for future studies on phytoestrogens.ConclusionsThe results demonstrated the predictive power of combining phylogenetic and ethnomedicinal data to guide the discovery of novel drugs with therapeutic potential for menopause, fertility, and neurological health.
Plakophilin-2 Coordinates Energy Metabolism and Contractility in Cardiomyocytes, Revealing Its Roles beyond Desmosomes
Authors: Aycinena J. Alex , Tefera Anley E. , Perea-Gil Isaac , Holbrook-Smith Duncan , Williams Kevin , Shenwai Reva , Farshidfar Farshad , Ryback Brendan , Foppe Katelyn , Wu Iris , Zeng Aliya , Pell Melissa Van , Xu Emma , Woods Joseph , Jones Samantha , Hatter Yolanda , Dee-Hoskins Cristina , Madariaga Jessie , Robinson Kevin , Greer-Short Amara , Song Xiaomei , Ivey Kathryn N. , Priest James , Argast Gretchen , Hoey Timothy , Driggers Edward , Yang Zhihong Jane 
Published: January 2025

AbstractArrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Mutations in the desmosome genePlakophilin-2,PKP2, lead to reduction in PKP2 protein and collapse of desmosomes that is known to compromise contractility and electrical stability of cardiomyocytes. Our previous studies demonstrated the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model ofPkp2and revealed profound changes in mRNA signatures of metabolic enzymes that were reversed by the gene replacement approach. In this study, we used PKP2-deficient mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to identify changes in steady-state metabolite levels associated with impaired lipid homeostasis, glycolysis, and glucose oxidation. These metabolic phenotypes align with human ARVC metabolic data and reflect an intrinsic impairment of cellular energy metabolism. Here we showed for the first time that these intracellular metabolic defects were associated specifically with poor contractility of cardiomyocytes. AAV9:PKP2 restored contractility, improved electrophysiological properties and Ca2+transients. In contrast, we observed that treating PKP2-deficient cardiomyocytes pharmacologically with small molecule metabolic enhancers improved contractility but not electrophysiological properties and Ca2+transients, suggesting differential sensitivity of structure-mediated functions in response to metabolic perturbance. Our study modeled and revealed a direct intracellular connection between compromised PKP2 function and metabolic impairment. We proposed that an increased risk of decoupling energy-responsive contractility from less energy-responsive electrical activities can be a new arrhythmogenic mechanism, potentially responsible for exercise-triggered cardiac adversity in ARVC disease development and progression.
Histone deacetylase-1 is required for epigenome stability inNeurospora crassa
Authors: Ebot-Ojong Felicia , Ferraro Aileen R. , Kaddar Farh , Hull-Crew Clayton , Scadden Ashley W. , Klocko Andrew D. , Lewis Zachary A. 
Published: January 2025

AbstractPolycomb group (PcG) proteins form chromatin modifying complexes that stably repress lineage- or context-specific genes in animals, plants, and some fungi. Polycomb Repressive Complex 2 (PRC2) catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) to assemble repressive chromatin. In the model fungusNeurospora crassa,H3K27me3 deposition is controlled by the H3K36 methyltransferase ASH1 and components of constitutive heterochromatin including the H3K9me3-binding protein HETEROCHROMATIN PROTEIN 1 (HP1). Hypoacetylated histones are a defining feature of both constitutive heterochromatin and PcG-repressed chromatin, but how histone deacetylases (HDACs) contribute to normal H3K27me3 and transcriptional repression within PcG-repressed chromatin is poorly understood. We performed a genetic screen to identify HDACs required for repression of PRC2-methylated genes. In the absence of HISTONE DEACETYLASE-1 (HDA-1), PRC2-methylated genes were activated and H3K27me3 was depleted from typical PRC2-targeted regions. At constitutive heterochromatin, HDA-1 deficient cells displayed reduced H3K9me3, hyperacetylation, and aberrant enrichment of H3K27me3 and H3K36me3. CHROMODOMAIN PROTEIN-2 (CDP-2) is required to target HDA-1 to constitutive heterochromatin and was also required for normal H3K27me3 patterns. Patterns of aberrant H3K27me3 were distinct in isogenic Δhda-1strains, suggesting that loss of HDA-1 causes stochastic or progressive epigenome dysfunction. To test this, we constructed a newΔhda-1strain and performed a laboratory evolution experiment. Deletion ofhda-1led to progressive epigenome decay over hundreds of nuclear divisions. Together, our data indicate that HDA-1 is a critical regulator of epigenome stability inN. crassa.
Research advancements on the application of sterile insect technique for the control of lepidopteran pests over the past two decades: A Systematic Review
Authors: Karabo Bambo , Malinga LN 
Published: January 2025

AbstractMany lepidopterans’ species, such as fruit borer (Helicoverpa armigera) on tomato, apple mothCydia pomonella(codling moth), and orange mothThaumatotibia leucotreta(false codling moth), are among many lepidopterans that are crop pests. In the early 1930s, the concept of the sterile insect technique was conceived in response to the global threat of insect pests and the excessive use of insecticides, which were proven to pose a health risk to humans. This pest control tactic has gained and is currently gaining more traction in all regions where it is implemented on both small and large scales. This systematic review looks at the recent research advances in the application of sterile insect techniques for the control of lepidopteran pests. The paper analyses publications, focusing on the geographic distribution of studies, target species, irradiation source, and the year of publication. It highlights the growing interest in SIT as an environmentally friendly pest management strategy compared to insecticide use. The paper compiles and summarises information over the last two decades on the lepidopteran species studied, the study approach, the country where the study was performed, the source of irradiation, and the year of publication. It also analysed the suitability of each lepidopteran species as an SIT candidate and the effectiveness of this control strategy. The review resulted in 2 537, from which 24 publications matched the search criteria. From the results, 14 species were identified, and the most studied lepidopteran wasT. leucotreta. The review discusses the effectiveness of SIT in controlling various lepidopteran species and explores the potential for further development and implementation of SIT programmes globally.
Hsp70 chaperones, Ssa1 and Ssa2, limit poly(A) binding protein aggregation
Authors: Buchholz Hannah E. , Martin Sean A. , Dorweiler Jane E. , Radtke Claire M. , Knier Adam S. , Beans Natalia B. , Manogaran Anita L. 
Published: January 2025

ABSTRACTMolecular chaperones play a central role in maintaining protein homeostasis. The highly conserved Hsp70 family of chaperones have major functions in folding of nascent peptides, protein refolding, and protein aggregate disassembly. In yeast, loss of two Hsp70 proteins, Ssa1 and Ssa2, is associated with decreased cellular growth and shortened lifespan. While heterologous or mutant temperature sensitive proteins form anomalous large cytoplasmic inclusions inssa1Δssa2Δstrains, it is unclear how endogenous wildtype proteins behave and are regulated in the presence of limiting Hsp70s. Using the wildtype yeast Poly A binding protein (Pab1), which is involved in mRNA binding and forms stress granules (SGs) upon heat shock, Pab1 forms large inclusions in approximately half ofssa1Δssa2Δcells in the absence of stress. Overexpression of Ssa1, Hsp104, and Sis1 almost completely limits the formation of these large inclusions inssa1Δssa2Δ, suggesting that excess Ssa1, Hsp104 and Sis1 can each compensate for the lower levels of Ssa proteins. Upon heat shock, SGs also form in cells whether large Pab1 inclusions are present or not. Surprisingly, cells containing only SGs disassemble faster than wildtype, whereas cells with both large inclusions disassemble slower albeit completely. We suspect that disassembly of these large inclusions is linked to the elevated heat shock response and elevated Hsp104 and Sis1 levels inssa1Δssa2Δstrains. We also observed that wildtype cultures grown to saturation also form large Pab1-GFP inclusions. These inclusions can be partially rescued by overexpression of Ssa1. Taken together, our data suggests that Hsp70 not only plays a role in limiting unwanted protein aggregation in normal cells, but as cells age, the depletion of active Hsp70 possibly underlies the age-related aggregation of endogenous proteins.
A Novel COE-D8-Fosfomycin Conjugate Effectively Against First-line Antibiotic ResistantUropathogenic Escherichia coli
Authors: Ruan Lin , Fan Cun , Chen Jingjie , Wang Yingxia , Ren Yuji , Yuan Wenli , Xiong Xiaozhe , Guo Chunming 
Published: January 2025

AbstractRecurrent urinary tract infections (UTIs) are increasingly associated with antibiotic resistance, posing significant clinical challenges. This study evaluates the antimicrobial efficacy of the membrane-intercalating conjugated oligoelectrolyte COE-D8 against uropathogenic Escherichia coli (UPEC). Among 93 clinical UPEC isolates, over 50% demonstrated resistance to first-line antibiotics, with compound sulfamethoxazole showing the highest resistance (75% at a minimum inhibitory concentration (MIC) >512 μg/mL). COE-D8 significantly reduced resistance rates, achieving less than 50% at 32 μg/mL and below 5% at 512 μg/mL, while demonstrating at least fourfold faster bacterial elimination than standard antibiotics.Mechanistic studies revealed that COE-D8 disrupts bacterial membranes, inducing rapid lysis. However, its cytotoxicity in mammalian cells at 2 μg/mL limits clinical application. To address this, a combination therapy with fosfomycin was explored, significantly reducing COE-D8 toxicity by at least fourfold in vitro. In mouse models, fosfomycin co-administration mitigated COE-D8-induced toxicity and prevented mortality at higher doses without compromising antimicrobial efficacy.These findings highlight the potential of COE-D8, particularly in combination with fosfomycin, as a promising strategy to combat antibiotic-resistant UPEC while addressing toxicity challenges.
Shared and individual tuning curves for social vision
Authors: Varrier Rekha S. , Su Zishan , Liang Qi , Benson Tory , Jolly Eshin , Finn Emily S. 
Published: January 2025

AbstractA stimulus with light is clearly visual; a stimulus with sound is clearly auditory. But what makes a stimulus “social”, and how do judgments of socialness differ across people? Here, we characterize both group-level and individual thresholds for perceiving the presence and nature of a social interaction. We take advantage of the fact that humans are primed to see social interactions—e.g., chasing, playing, fighting—even in very un-lifelike stimuli such as animations of geometric shapes. Unlike prior work using these stimuli, we exploit their most advantageous property, which is that their visual features are fully parameterizable. We use this property to construct psychophysics-inspired “social tuning curves” for individual subjects. Social tuning curves are stable within individuals, unique across individuals, and show some relationship to socio-affective traits. Results support the view that social information processing begins early in the perceptual hierarchy. Further, our approach lays the foundation for a generative account of social perception in single subjects.
A simulation-based approach to optimizing resource allocation and logistics in construction projects: a case study
Authors: Nikoukar Shayan , Tavakolan Mehdi 
Published: January 2025

PurposeThis research aims to address the challenge of inefficient decision-making in site layout planning and resource allocation for construction projects. Existing approaches often rely on mathematical models that produce unrealistic results or encounter limitations confined to the site itself. To overcome these constraints, this study proposes a simulation-based approach with a focus on automatically optimizing tower crane placement, depot locations, and supplier selection. The primary objective is to minimize project costs while enhancing overall efficiency and productivity.Design/methodology/approachThe implementation integrates a genetic algorithm and a discrete event simulation model featuring a central control kernel. Key considerations include project boundaries, site layout features, depot locations, and manufacturing and transportation capabilities. The simulation process assesses each solution, encompassing critical stages like manufacturing, transfer to depot, site transportation, and installation. The proposed approach is tested using an actual steel structure project in Tehran, Iran.FindingsResults demonstrate substantial cost reductions compared to the contractor plan, showcasing the superiority of the proposed simulation-based optimization approach. The findings underscore the practical applicability of the research, providing valuable insights for industry professionals to make informed decisions and enhance project outcomes in real-world construction projects.Originality/valueThis integrated simulation-based optimization approach offers a robust framework for realistic and effective site layout planning and resource allocation in general steel construction projects. Its general simulation mechanism allows for easy expansion and application to similar projects, capable of assessing a large number of alternatives. The research contributes to the field by presenting a novel and effective method for addressing decision-making challenges in construction project planning and resource allocation.